Strengthening hospital nursing, Part III. Differences among professional groups in the hospital planning process. Interdisciplinary hospital planning processes are examined. Nurses, physicians, hospital administrators, and support and ancillary personnel from 75 hospitals participating in the national Strengthening Hospital Nursing Program indicate their perceptions of the project in relation to the centrality of the program in their hospitals, planning team development, and political issues. Differences and similarities among the professional groups are discussed. Additional articles on the Strengthening Hospital Nursing Program have appeared in the May and June 1992 issues of JONA. Part 1 explored the planning process in single and consortium hospital sites, and Part 2 examined the characteristics of effective planning processes.


Predictions of energy intake and energy allowance of patients with Duchenne muscular dystrophy and their validity. Patients with Duchenne muscular dystrophy are so malnourished that energy supplementation is crucial. Their degree of energy deficiency was assessed as difference between their energy intake and their energy allowance, which were deduced from easily measured parameters. A significant, negative relationship was found between the basal metabolic rate (BMR) (Y, %, BMR/standard BMR) and body weight (X, %, body weight/standard body weight) in the patients, from which the formula for the BMR was deduced to be Y = -1.116X + 174.5 (n = 202, r = -0.72, p less than 0.001). Thus, it is possible to estimate the energy allowance for individual patients by a factorial procedure from the presumed BMR and a factor for physical activity. In addition, their energy intake was calculated from a constant protein-energy % (14.6%) in their diet and nitrogen intake which was deduced from a significant positive correlation between their nitrogen intake (Y, mg/kg/day) and their nitrogen excretion in 24 h urine samples (X, mg/kg/day). This correlation conformed to the equation Y = 1.053X + 32.4 (n = 267, r = +0.76, p less than 0.001). The validities of the above predictions for energy intake and allowance were examined by plotting the degree of energy deficiency (% ratio of presumed intake/presumed allowance) against the concentrations of retinal binding protein, prealbumin and transferrin in the serum, because rapid turnover proteins are sensitive to energy deficiency. Significant positive correlations were obtained with both variables, suggesting that these predictions were valid.


Organizational change from the "mom and pop" perspective. Can hospitals successfully embark on large-scale organizational change without using outside consultants? Nursing administrators have an intense interest in the answer to this question. If change can be designed from inside the organization, the chances are greater that the change will fit better with the organization as a whole, and that buy-in by staff will be significant. The authors review the elements that need to be in place to conduct a successful change process internally, and support their concepts with a case study.


Liver microsomal mixed-function oxidases in response to dietary whole egg protein levels in rats. Relation between the activity of liver microsomal mixed-function oxidase system and dietary protein level was investigated in rats using purified whole egg protein, i.e. free from limiting amino acids. The animals were given either a diet containing 0, 5, 10, 20 or 40% of protein (experiment 1) or a diet containing 5, 10, 15 or 20% of protein (experiment 2) for 16 days. In experiment 2, half of the rats of each group were intraperitoneally injected sodium phenobarbital (PB) to induce the mixed-function oxidase system. The cytochrome P-450 content plateaued even at 5% level of dietary protein in experiment 1 and in the PB-untreated groups of experiment 2. However, it showed the highest value at 15% protein level in the PB-treated groups of experiment 2, indicating a shift of the response peak to a higher protein level due to an increase in protein requirement. Cytochrome P-450 reflected most specifically the dietary protein levels when the enzyme system was induced by PB. The 15% protein level, equivalent to 14.1 protein calories %, is a little higher than the optimal dietary level of whole egg protein ever obtained by usual nutritional indices.


Nutritional assessment of a group of Japanese elementary school children in Tokyo: with special emphasis on growth, anemia, and obesity. Anthropometric data, nutrient intake data, and blood biochemical parameters were analyzed for 66 elementary school children living in Tokyo, Japan, and their nutritional status was evaluated focusing on three problems: (1) zinc nutriture and growth, (2) anemia with iron deficiency, and (3) lipid nutriture and obesity. The subjects' mean energy and protein intakes met the recommended levels for Japanese children. However, their zinc intake levels were inadequate at 7.2, 8.3, and 8.5 mg in grades 2 (mean age: 8 yr), 4 (10 yr), and 6 (12 yr), respectively. Mean serum zinc concentration was 0.82 +/- 0.15 microgram/ml; the percentages of subjects who showed serum zinc concentration lower than 0.68 microgram/ml, the lower limit of the normal serum zinc concentration, were 28.6, 15.4, and 5.0% in grades 2, 4, and 6, respectively. These serum zinc concentrations indicated the existence of marginal zinc deficiency in some children, particularly in grade 2, though it was not severe enough to retard growth. Their iron intake levels (8.2, 10.2, and 10.2 mg for grades 2, 4, and 6, respectively) in combination with the proportion of iron intake from animal foods (37%) were judged to be adequate because no children showed serum ferritin, serum iron, or transferrin saturation levels lower than the criteria levels recommended for iron deficiency. Moreover, no definitely anemic children were found. Daily lipid intakes were 65.7, 74.5, and 78.3 g in grades 2, 4, and 6, respectively, and the mean percentage of energy intake from lipid to total energy intake, 32%, exceeded the level recommended. Mean serum total cholesterol concentrations and the percentage of subjects with elevated cholesterol levels (greater than or equal to 200 mg/dl) were high compared with the reported values. Means of the body mass index (BMI) and Rohrer Index (RI) for the subjects were slightly higher than Japanese standards. With these parameters for obesity, triglycerides and atherogenic index were positively correlated and HDL cholesterol and HDL cholesterol percentage to total cholesterol were negatively correlated.


The effect of milk and skim milk intake on serum lipids and apoproteins in postmenopausal females. The effects of milk and skim milk intake on serum lipids, apoprotein levels and fatty acid composition were investigated in postmenopausal females. After a 25-day intake of 200 ml/day of whole milk, the milk group had increased HDL and LDL cholesterol levels, with a slight decrease in the proportion of 18:0 fatty acids in the phospholipid fraction. The skim milk group, which had consumed 20 g/day of skim milk for 25 days, showed no changes. After intake of 400 ml/day of whole milk for 29 days, LDL, HDL and total cholesterol concentrations were even more increased and the VLDL-phospholipid concentration was decreased, with significant increases in apoA-I, apoA-II and apoB concentrations. In the skim milk group, consuming 40 g of skim milk per day for 29 days, total cholesterol, atherogenic index, HDL-triglyceride concentrations were decreased and HDL-phospholipid, apoA-I and apoA-II concentrations were increased. Daily skim milk consumption, which is effective in preventing osteoporosis, and careful selection of foods should be recommended for Japanese postmenopausal women who consume more than 200 ml/day of whole milk.


A pitfall in determining the globulin/albumin ratio in amaranth grains. In amaranth grains (Amaranthus hypochondriacus L. and Amaranthus cruentus L.), there were two albumin (Alb) fractions, Alb-1 and Alb-2; Alb-1 was extracted with water or 0.5 M NaCl, and Alb-2 was extracted with water after extracting Alb-1 and globulin. The amount of Alb-2 comprised about 30% of the total albumin and globulin content. Little or no measurable protein corresponding to the amaranth Alb-2 was extracted from seeds of buckwheat (Fagopyrum esculentum Moench), quinoa (Chenopodium quinoa L.), or barley (Hordeum vulgare L. cv Sekitorisai-1). That the globulin/albumin ratio (G/A) in amaranth grains has been conflicting among investigators probably accounts for the consideration of Alb-2 during extraction. We here report the revised G/A ratio of 0.3-0.4.


Effect of intraperitoneally administered nucleoside-nucleotide on the recovery from methicillin-resistant Staphylococcus aureus strain 8985N infection in mice. The effect of intraperitoneally administered nucleoside-nucleotide on the recovery from methicillin-resistant Staphylococcus aureus (MRSA) strain 8985N infection was studied in mice. Mice fed nucleic acid-free 20% casein diet were administered intraperitoneally with a nucleoside-nucleotide mixture or with saline (control group) daily for 30 days. On the tenth day on this treatment, mice were challenged with the bacteria. The survival rates were 25% and 72% for the control and nucleoside-nucleotide groups, respectively. The recovery of the survived mice from the infection was confirmed by the increment of body weight and the reduction of the bacteria in the organs. The results show the effectiveness of the intraperitoneal administration of the nucleoside-nucleotide mixture for the recovery from the MRSA strain 8985N infection in mice.


The impact of culture on psychotherapy: Korean clients' expectations in psychotherapy. The impact of culture on clients' expectations for psychotherapy has not been adequately studied. This is the first study to explore Korean clients' expectations in psychotherapy. A 120-item instrument was used to collect data on expectations for psychotherapy held by 25 Korean clients of the Asian Mental Health Clinic. Six hypotheses regarding expectations for therapist's discipline, characteristics, techniques, goals, and roles in psychotherapy were examined. The findings indicate that the model that Koreans have for a psychotherapeutic relationship is similar to the special teacher-disciple relationship in Korea. The study demonstrated that psychiatric nurses are held in high regard by Korean clients. Education of Koreans to Western psychotherapy concepts and procedures is essential. Recommendations were made for different treatment modalities integrating Western concepts of psychotherapy with Korean cultural concepts of mental health.


Guidelines for writing for publication.

Guidelines for writing for publication. Publishing is a worthwhile goal, achievable when separated into manageable steps and when the science and art of writing are addressed. The value of publishing is explored and several approaches to developing and publishing a manuscript are presented.


Health locus of control and safety restraint attitudes in a sample of motor vehicle accident victims. A study was undertaken to determine the health locus of control beliefs and the health promotion and safety restraint use attitudes of a sample of previously injured motor vehicle occupants. Health locus of control was not found to be related to more favorable attitudes toward safety restraint use and restraint use legislation.


Colon and stomach cancer mortality among automotive wood model makers. Automotive wood model makers have been reported to be at excess risk for colon and other cancers in recent epidemiologic studies. To further explore these risks, we conducted a retrospective cohort mortality study, with follow-up from 1940 through 1984, of 2294 white male wood model makers employed at any time until 1980 by three US auto makers. Using US mortality rates for comparison, we found elevated standardized mortality ratios of 1.2 (95% CI, 0.8-1.9) for colon cancer and 1.6 (95% CI, 0.9-2.6) for stomach cancer. We also conducted nested case-control studies for 20 colon and 17 stomach cancer cases and 543 age-matched controls. We found no trend of increased risk for colon or stomach cancer mortality with increased exposure to wood dust or to duration employed in wood model making.


Using a low-cost, prize-drawing incentive to improve recruitment rate at a work-site smoking cessation clinic. A major obstacle in promoting smoking cessation programs through work sites is recruiting adequate numbers of smokers. We used a quasi-experimental design to evaluate the effect of a low-cost incentive (a prize drawing) for attracting participants to a smoking cessation clinic offered at multiple work sites. Sixty-eight automobile dealerships were randomized to either a "prize" or control group. Smokers employed at work sites in the prize group were offered a chance to win a dinner for two for participating in a smoking cessation clinic. In November 1986, a questionnaire assessing tobacco use habits was sent to 3432 employees of the 68 work sites. A cohort of 844 smokers was identified from a total of 1986 employees who returned surveys. All smokers received registration materials to participate, free of charge, in one of three smoking cessation programs held in June 1987. The overall employee participation rate in the smoking cessation program was 6.6% (n = 56) with an overall work-site participation rate of 37.3% (n = 25). The rate was nearly identical in the "prize" and control groups (employee rate: 6.3% versus 6.7%; work-site rate: 39.4% versus 35.3%, respectively).


Freon injection injury to the hand. A report of four cases. During a 6-month period, the poison center was consulted on three occasions for advice regarding accidental injection of hexafluorethane (Freon) used in the manufacturing process of athletic shoes. A fourth case was later identified after consulting physicians near the manufacturing facility. Little information exists in the medical literature concerning injection of freon or other volatile substances. In each of these cases, workers inadvertently injected concentrated hexafluorethane into a finger while holding the shoe component and attempting to inject hexafluorethane. Each case presented with edema, limitation of motion, and crepitation. Hand roentgenogram revealed subcutaneous gas. Treatment was nonsurgical, consisting of splinting, tetanus immunization, and antibiotics. Rapid resolution of symptoms occurred in all four cases. Hexafluorethane is relatively inert when injected and has low toxicity. However, potential rapid expansion warrants observation for pressure injury.


Occupational wood dust exposures, lifestyle variables, and respiratory symptoms. The quantitative relationship of occupational exposure to airborne wood dust with nasal and pulmonary health problems is not clearly established, particularly for low to moderate exposures in the wooden furniture manufacturing industry. We examined the associations of pulmonary and nasal symptoms, wood dust exposure, and lifestyle variables (cigarette smoking, alcohol use, overweight, physical inactivity, and stress) in a sample of 168 woodworkers. Levels of wood dust exposure were not systematically associated with symptoms. Statistically significant associations were found for cigarette smoking; after controlling for the effects of smoking, heavy drinking was significantly associated with pulmonary symptoms, and perceived stress was associated with both pulmonary and nasal symptoms. These findings suggest that studies of the effects of low-level occupational wood dust exposures should control for the potential effects of lifestyle variables.


Preliminary evaluation of an employer-sponsored mammography screening program. Recognizing the importance of early detection of breast cancer, the Dow Chemical Company initiated a breast cancer awareness program in 1988. Evaluation of operational aspects of mammography screening component revealed that about half (53%) of 1186 eligible women in the evaluation cohort took part, although participation was three times higher for active than for retired employees. Eleven per cent of participants were considered to have "positive" screens, ie, had roentgenogram films with suspicious areas, and at least 82% of these women had follow-up medical services within 1 year of screening, as determined by a review of group insurance claims records. Two women with positive mammograms were subsequently diagnosed and treated for breast cancer within 2 months of screening. None of the women with negative mammograms developed breast cancer in the subsequent year. The suitability of group insurance data resources for responding to health care delivery questions is discussed.


Heart rate response of firefighters to actual emergencies. Implications for cardiorespiratory fitness. Heart rate (HR) and oxygen consumption (VO2) responses during actual fire-suppression emergencies were monitored in 10 male firefighters. These firefighters worked at 157 +/- 8 beats per minute (bpm) for 15 +/- 7 minutes. This was 88 +/- 6% of their previously determined HR max. Based on treadmill testing, the HR x VO2 relationship was established for each firefighter. The predicted VO2 derived from HR monitoring in actual emergencies was 25.6 +/- 8.7 mL.kg-1.min-1 or 63 +/- 14% of VO2 max (40.0 +/- 6.5 mL.kg-1.min-1). These values on the cardiorespiratory response to actual emergencies are very similar to results derived from studies employing fire-suppression simulations. Recommendations for the VO2 max of firefighters ranging from 33.5 to 42.0 mL.kg-1.min-1 that have been generated from simulation testing appear appropriate given the cardiorespiratory responses to actual emergencies.


Mortality of workers exposed to acrylonitrile. A retrospective cohort study was carried out in The Netherlands to investigate the potential carcinogenic effects in humans of occupational exposure to acrylonitrile (AN). The total study group consisted of 6803 workers "from eight chemical plants and one control plant" of whom 2842 had been exposed to AN between January 1, 1956 and July 1, 1979 for at least 6 months. All workers were employed by one of eight chemical companies. An extensive review of the available industrial hygiene data was conducted to assess the magnitude of past exposure to AN, occurrence of peak exposures, exposure to recognized potential human carcinogens, and respirator use. The total cohort was observed for mortality until January 1, 1988. In collaboration with the Central Bureau of Statistics, the causes of death were traced for the workers who died before 01-01-1988. In the exposed as well as in the nonexposed cohorts the total mortality was lower than expected, based on national mortality statistics. The observed cancer mortality in the exposed cohort was similar to the expected mortality. Specific analyses were carried out to investigate dose-response relationships and latency for total mortality and lung cancer mortality. Overall, no indications were found for a carcinogenic effect in this cohort of workers exposed to AN.


Health-risk behaviors of Army aircrew.

Health-risk behaviors of Army aircrew. Data from the US Army Health Risk Appraisal Program were used to compare health and fitness levels in flight and nonflight personnel. Survey data collected from an aviation brigade, consisting of 428 aircrew and 899 support personnel, were compared with US Army summary statistics. Flight personnel scored better on evaluation of hypertension, stress, weight standards, and seatbelt use. However, the prevalence of smokeless tobacco use, heavy alcohol consumption, and driving after drinking or riding with someone who consumed alcohol was significantly higher in flight personnel. This study suggests that although Army aircrew have better lifestyle habits overall, high-risk behaviors have been identified that warrant further evaluation.


Musculoskeletal discomfort in grocery express checkstand workers. An ergonomic intervention study. An intervention study of cashiers at a large grocery store was begun in response to employee symptoms of musculoskeletal discomfort, primarily shoulder, neck, and upper back pain, after introduction of a new express checkstand. The grocery company then instituted workplace changes directed at reducing stressful postures and the discomfort in the anatomical sites of primary concern. These changes were placement of a physical barrier to reduce trunk flexion from overreaching, installation of an adjustable keyboard to reduce static shoulder stress, and education of employees about good workplace practices to reduce musculoskeletal stress and fatigue. There was a statistically significant reduction in neck, upper back, or shoulder discomfort but not arm, forearm, or wrist discomfort. There was also a significant reduction in employee use of medication and days to recovery from discomfort but not in overall number of employees with symptoms or in hours able to operate the checkstand without discomfort. We found that ergonomic interventions, directed to the anatomical site of greatest employee concern, are likely to be effective, that employees were a good source of information on the ergonomic problems and solutions in their workplace, but that the overall approach must be iterative to achieve the maximum effect.


Acute cardiac ischemia in patients with syncope: importance of the initial electrocardiogram. To determine the prevalence of acute cardiac ischemia in emergency department (ED) syncope patients without chest pain and to determine which of these patients are at high risk for acute cardiac ischemia. Data were collected prospectively during a study of ED triage of patients who had had possible acute cardiac ischemia. Supplemental retrospective review of records was performed to differentiate syncope from dizziness. Six hospital EDs in New England (two primary teaching hospitals in urban locations, two medical-school-affiliated teaching hospitals, and two nonteaching hospitals in rural settings). 5,762 patients had presented to the ED with chief complaints consistent with acute cardiac ischemia, including chest pain, shortness of breath, dizziness, and syncope. The study sample consisted of 251 patients who had had syncope and no chest pain. The prevalence of acute cardiac ischemia among the syncope patients was 7% (18 of the 251 patients). Univariate analysis revealed the following to have significant association with acute cardiac ischemia: ischemic abnormalities on the electrocardiogram (ECG) obtained in the ED (p less than 0.001), arm or shoulder pain on presentation (p less than 0.05), rales (p less than 0.1), and prior history of exercise-induced angina (p less than 0.05) or myocardial infarction (p less than 0.1). All 18 patients with acute cardiac ischemia had ischemic abnormalities (pathologic Q waves, ST-segment elevation or depression, or T-wave abnormalities) on their presenting ECGs. For syncope patients who have no chest pain or ischemic abnormality on the presenting ECG in the ED, acute ischemia appears to be unlikely. Admission to the cardiac care unit for these patients for possible myocardial ischemia is probably unnecessary. However, patients who have syncope and ischemic abnormalities on the ECG are at risk for acute cardiac ischemia, even in the absence of chest pain. Hospital admission to rule out myocardial infarction for these patients is prudent.


Physician electrocardiogram reading in the emergency department--accuracy and effect on triage decisions: findings from a multicenter study. To determine how well physicians in emergency departments read electrocardiographic (ECG) ST-segment and T-wave changes and how this affects triage decisions. In the emergency departments of six teaching and nonteaching hospitals, the authors prospectively collected physicians' ECG readings and clinical data for 2,320 patients presenting with possible acute cardiac ischemia from 1979 to 1981. Compared with electrocardiographers, the study physicians misread as normal 41% of abnormal ST segments and 36% of abnormal T waves, and misread as abnormal 14% of normal ST segments and 17% of normal T waves. Trainees were significantly more sensitive readers of T-wave changes but less specific readers of both ST-segment and T-wave changes when compared with other physicians. Suboptimal triage was more likely when abnormal ST segments or T waves were misread as normal (22% vs. 11%, p less than 0.001, and 18% vs. 14%, p = 0.08, respectively). Conversely, coronary care unit (CCU) admission for patients without acute cardiac ischemia was more likely when normal ST segments were misread as abnormal (23% vs. 13%, p less than 0.0001). Physicians in emergency departments often misread the ST segments and T waves of patients with possible acute cardiac ischemia. Misreading is related to suboptimal triage and unnecessary CCU admission. Training emergency physicians to make these distinctions more accurately could improve medical care and hospital utilization.


Quitting smoking: reasons for quitting and predictors of cessation among medical patients. To describe why medical patients quit smoking and the methods they use. Cross-sectional and prospective cohort design. Patient smokers were enrolled in a study of physician counseling about smoking. One year later, 2,581 of the patients were asked about quit attempts and methods used. Of those, 245 former smokers whose quitting had been biologically validated were interviewed about why and how they had quit. Offices of internists and family practitioners in private practice and a health maintenance organization. Consecutive sample of ambulatory patients who smoked. Baseline questionnaires included demographic data, smoking history, and symptoms and diagnoses related to smoking. After one year, subjects were interviewed about smoking status and methods used in attempting to quit. Cessation was confirmed by biochemical testing. Those who had quit were asked about reasons for quitting. Seventy-seven percent of successful quitters gave health-related reasons for quitting and the quitters ranked "harmful to health" as the most important reason for quitting. In a multivariate analysis, those who had a college education, who had social pressures to quit, and who had greater confidence in being able to quit were more likely to have quit smoking one year later, while those who smoked their first cigarette within 15 minutes of awakening and who had more diagnoses related to smoking were less likely to have quit smoking one year later. Participation in a treatment program and having been counseled by a physician or nurse practitioner were positively related to successful quitting, while use of filters or mouthpieces was negatively related. Concerns about health are the most common reason patients give for quitting, and addiction is the most important barrier to quitting. Education, social pressure, provider advice, and formal programs, but not over-the-counter devices, appear to increase the chances that smokers will quit.


Yield of the screening review of systems: a study on a general medical service. To determine the usefulness of screening reviews of the cardiopulmonary and gastrointestinal systems during medical admissions. Case series. General internal medicine ward of a university hospital. 550 consecutive medical patients were initially screened at admission. The authors excluded 265 patients with life-limiting medical conditions, and they studied 98 patients with no known cardiopulmonary disease and 207 patients with no known gastrointestinal disease. Positive responses to screening systems review questions were evaluated using a standardized testing algorithm. Numbers of new diagnoses; potential for patient benefit. The authors made 26 new diagnoses for 25 patients (95% confidence limits, 16 to 37 patients), two of whom may have gained years of life as a result. The absolute yield of the screening cardiopulmonary and gastrointestinal reviews of systems of 550 patients admitted to an internal medicine service of a university hospital was a new diagnosis in about 5% of patients. An estimate of the cost-effectiveness compares favorably with those of other accepted screening practices.


The effects of a low-cost intervention program on hospital costs. To assess the impact of a low-cost education and feedback intervention designed to change physicians' utilization behavior on general medicine services. Prospective, nonequivalent control group study of 1,432 admissions on four general medicine services over 12 months. Two services were randomly selected to receive the intervention. The other two served as controls. Admissions alternated between control and intervention services each day. Results were casemix-adjusted using diagnosis-related groups (DRGs). Three internists blinded to patient study group assignment assessed quality of care using a structured implicit instrument. Four general medicine services at a university hospital. A brief orientation, a pamphlet of cost strategies and common charges, detailed interim bills, and information about projected length of stay and usual hospital reimbursement for each patient. Each service was staffed by a full-time internal medicine faculty member, one third-year and two first-year internal medicine houseofficers, three medical students, and a clinical pharmacist. Physicians were assigned to services for one-month periods by a physician unaware of the study design. To prevent crossover, houseofficers assigned to a service returned to the same service for all subsequent general medical inpatient assignments. Geometric mean length of stay was 0.44 days (7.8%) shorter for the intervention services than for the control services (p less than 0.01), and geometric mean charges were $341 (7.1%) less (p less than 0.01). Effects persisted despite using a more precise cost estimate or casemix adjustment. Intervention houseofficers demonstrated superior cost-related attitudes but no difference in knowledge of charges. Audits of quality of care detected no significant difference between groups. This low-intensity intervention reduced length of stay and charges, even under the cost-constrained context of the prospective payment system.


Call nights and patients care: effects on inpatients at one teaching hospital. To determine whether the timing and number of patients admitted by internal medicine housestaff under a traditional call schedule affect the resource utilization and outcome of care for those patients. Retrospective cohort study, using existing computerized records. University-affiliated 340-bed city/county teaching hospital. 22,112 patients discharged from the internal medicine service who had been admitted by an on-call first-year resident between January 1, 1980, and December 31, 1987. Admission after 5:00 PM was associated with decreased hospital length of stay (8.1%, p less than 0.0001), but increased total charges (3.1%, p = 0.007). The relative risk of inpatient mortality for patients admitted at night was 1.21 (p = 0.03). Patients of busier housestaff, as indicated by a larger number of on-call admissions, had lower total charges (1.7% decreased per admission) and no change in risk of inpatient mortality. While no linear relation was found between number of admissions and length of stay, analysis of nonlinear effects revealed that length of stay first rises, then falls as interns receive more on-call admissions. The number and timing of admissions by on-call internal medicine housestaff are significantly related to length of hospital stay, total charges, and likelihood of inpatient mortality at one teaching hospital. These variations should be considered in planning the reform of residency training programs.


Research, academic rank, and compensation of women and men faculty in academic general internal medicine. To evaluate the status of men and women faculty in academic general internal medicine, including their professional training, faculty responsibilities, research performance, academic rank, and compensation, to determine whether systematic differences exist by gender. The authors analyzed responses to a 55-part questionnaire sent to all full-time general internal medicine faculty at the major teaching hospitals in the United States. Unadjusted means were generated for men versus women faculty in demographics, training background, hours of work, professional time allocations, institutional support, professional self-assessment, research performance, academic rank, and compensation. Means were recalculated after adjusting for other variables using multivariate methods. The authors found no significant difference in the frequency of fellowship training between men and women faculty. Women and men perform similar professional activities, but even after multivariate adjustment, women devote less time to research and perceive less research skill and institutional support for their research, but have similar numbers of grants, abstracts, and publications in refereed journals and have similar academic ranks. Women faculty, however, receive lower compensation than do men faculty, even after adjustment. While the characteristics of men and women faculty are quite similar, including those defining their academic productivity, important differences exist in research time, perceived institutional support, and compensation. These differences cannot be explained by such obvious factors as age differentials, academic rank, or hours of work per week.


Patient expectations and satisfaction with medical care for upper respiratory infections. To describe the determinants of patient satisfaction with medical care, self-administered questionnaires were given to a consecutive sample of 237 patients coming to an ambulatory care practice for the treatment of upper respiratory infections (URIs). Patients' most important goal was to obtain a diagnosis (57%). They usually got more reassurance, medication, and personal interest than they had expected (p = 0.0001). In a multivariate model, patients' satisfaction was related to the degrees of personal interest and reassurance they had received and to whether they felt they had received the right medication (r2 = 0.45, p = 0.0001). The authors concluded that patients with URIs generally want a diagnosis but are primarily satisfied by the personal interest, the reassurance, and the medication they receive.


The heart of darkness: the impact of perceived mistakes on physicians. To describe how physicians think and feel about their perceived mistakes, to examine how physicians' prior beliefs and manners of coping with mistakes may influence their emotional responses, and to promote further discussion in the medical community about this sensitive issue. Audiotaped, in-depth interviews with physicians in which each physician discussed a previous mistake and its impact on his or her life. Transcripts of the interviews were analyzed qualitatively and the data organized into five topic areas: the nature of the mistake, the physician's beliefs about the mistake, the emotions experienced in the aftermath of the mistake, the physician's way of coping with the mistake, and changes in the physician's practice as a result of the mistake. Eleven general internists and medical subspecialists practicing at a community, university-affiliated hospital in Oregon. Themes emerging from analysis of the interviews were the ubiquity of mistakes in clinical practice; the infrequency of self-disclosure about mistakes to colleagues, family, and friends; the lack of support among colleagues; the degree of emotional impact on the physician, so that some mistakes were remembered in great detail even after several years; and the influence of the physician's professional locus of control on subsequent emotions. The perception of having made a mistake creates significant emotional distress for practicing physicians. The severity of this distress may be influenced by factors such as prior beliefs and perfectionism. The extent to which physicians share this distress with colleagues may be influenced by the degree of competitiveness engendered by medical training. Open discussion of mistakes should be more prominent in medical training and practice, and there should be continued research on this topic.


Sex and the teacher--learner relationship in medicine. As the numbers of women medical students, residents, and faculty increase, sexuality in teacher-learner relationships will present challenges for individuals and institutions. Ethical and legal guidelines regarding sexual harassment and contact already exist for many medical schools, hospitals, and professional organizations, as well as state and federal law. Individuals and institutions can begin to address these issues through policy development and educational sessions addressing human sexuality, communication skills, and the process of becoming a physician.


Integrating general medicine and rheumatology training in the outpatient setting: a practice model. The authors describe a primary care-based educational and practice model that integrates general medicine resident education in outpatient rheumatology with specialty fellowship training. Compared with the use of traditional specialty clinics, the model provides better access and service to patients and more appropriate training for residents. Revenues from clinical service delivered by faculty-supervised residents and fellows support 80% of the operating costs and educational activities of the model. The conceptual framework for the model reconciles the educational goals and practice philosophies of general medicine and specialty training and is applicable to training in other predominantly outpatient specialty areas.


Hyperparathyroidism and pregnancy: case report and review. In pregnant women with symptomatic hyperparathyroidism, parathyroidectomy should be undertaken during the second trimester. We feel that the woman who is initially diagnosed well into the third trimester should be treated medically unless the hypercalcemia worsens or other complications occur. Since the treatment of asymptomatic hyperparathyroidism itself is controversial, it is even more difficult to define the treatment plan for an asymptomatic pregnant patient who has primary hyperparathyroidism. However, a recent consensus panel recommended that young patients with asymptomatic hyperparathyroidism be treated surgically. Accordingly, we believe that the asymptomatic pregnant patient should also be treated surgically, preferably in the second trimester. Whether a patient is treated medically or surgically in these situations, the pregnancy should be considered high-risk. The neonate should be monitored carefully for signs of hypocalcemia or impending tetany. If the mother is treated medically to term (or if spontaneous or elective abortion occurs), the mother should be monitored for hyperparathyroid crisis postpartum. Sudden worsening of hypercalcemia can result from the loss of the placenta (active placental calcium transport may be somewhat protective) and dehydration. Finally, every effort should be made to make the definitive diagnosis early in pregnancy in order to initiate optimal management. The diagnosis should be suspected during pregnancy if the following conditions exist: appropriate clinical signs or symptoms (especially nephrolithiasis or pancreatitis), hyperemesis beyond the first trimester, history of recurrent spontaneous abortions/stillbirths or neonatal deaths, neonatal hypocalcemia or tetany, or a total serum calcium concentration greater than 10.1 mg/dL (2.52 mmol/L) or 8.8 mg/dL (2.2 mmol/L) during the second or third trimester, respectively.


Temporomandibular joint arthroscopy: a 6-year multicenter retrospective study of 4,831 joints. Four health outcomes (range of motion, pain, diet, and disability) were measured in six diagnostic categories (internal derangement with closed lock, internal derangement with painful click, osteoarthritis, hypermobility, fibrous ankylosis, and arthralgia) in a 6-year retrospective multicenter study of 4,831 temporomandibular joints having undergone arthroscopic surgery. After arthroscopic surgery, 91.6% of all patients had good or excellent motion; 91.3% had good or excellent pain reduction; 90.6% had good or excellent ability to maintain a normal diet; and 92% had a good or excellent reduction in disability. These health outcomes compare favorably with all other known treatments for these conditions. Also, the surgical technique was relatively free of complications (4.4%).


Holmium:YAG laser arthroscopy of the temporomandibular joint. A new pulsed midinfrared laser has become available for use in arthroscopic surgery of the temporomandibular joint (TMJ). This article reviews holmium:YAG (yttrium-aluminum-garnet) laser physics, its tissue effects, and reports initial experience with its use in TMJ arthroscopy. Because the Ho:YAG laser can precisely and rapidly resect cartilaginous tissues with only moderate necrosis, can function in a saline environment, and can be transmitted through conventional optical fibers, it has the potential of becoming a useful and adaptable system for TMJ arthroscopic surgery.


Early surgical intervention for orbital floor fractures: a clinical evaluation of lyophilized dura and cartilage reconstruction. Experience in the management of 77 isolated orbital floor fractures is presented. The transconjunctival approach was used exclusively to access the orbital floor and lyophilized dura and cartilage were used to reconstruct the floor, when indicated. Follow-up for an average of 36 months showed excellent cosmetic and functional results. A 20% complication rate was noted, which compares favorably with what is reported in the literature. There were no graft extrusions or infections and only one case of graft displacement. These findings support the concept of early treatment of orbital floor fractures, even in "minimally symptomatic" patients. Lyophilized dura and cartilage proved to be safe and effective materials for orbital reconstruction.


Erosion and heterotopic bone formation after alloplastic temporomandibular joint reconstruction. Twenty-three temporomandibular joint arthroplasties using metallic condylar prostheses were performed because of severe ankylosis (8 patients), segmental mandibular resections in tumor surgery (9 patients), and after extensive trauma (2 patients). A clinical and radiological follow-up study showed heterotopic bone formation in 52% of cases and glenoid fossa resorption in 43%. In one patient with rheumatoid arthritis the condyle eroded through the skull base 10 months after surgery. Seven prostheses (30%) were removed and/or exchanged during the average 27.6-month follow-up.


Simultaneous otoplasty and temporomandibular arthroplasty. By altering the standard postauricular incision for access to the temporomandibular joint (TMJ), a standard otoplasty can be performed simultaneously with TMJ arthroplasty. The procedure is described and results are presented. In six patients with at least a 2-year follow-up, the esthetic results have been stable. There has been no morbidity as a result of such simultaneous surgery.


The incidence of total hip replacement in orthognathic surgery patients receiving short-term steroid therapy. It is well known that long-term corticosteroid therapy can lead to avascular necrosis of the femoral head. There is suspicion among orthopedic surgeons that short-term, high-dose steroid use poses similar risks. The records of 2,773 patients (1,497 who had total hip replacement and 1,276 who had orthognathic surgery) were retrospectively reviewed. No hip replacements had been done in the orthognathic surgery group and none of the patients in the total hip replacement group had undergone orthognathic surgery. The use of short-course, systemic corticosteroids to reduce postoperative swelling in orthognathic surgery did not seem to cause avascular necrosis of the femoral head.


Treatment of mandibular angle fractures using two mini dynamic compression plates. Thirty patients with 31 fractures of the mandibular angle were treated by open reduction and internal fixation using two mini dynamic compression plates with self-threading screws placed through a transoral incision with transbuccal trochar instrumentation. None of the patients were placed into postsurgical maxillomandibular fixation (MMF) or training elastics. Complications requiring secondary surgical intervention occurred in nine fractures (29%). Three were early infections requiring incision and drainage, removal of the hardware, and postoperative MMF. One was a nonunion with malocclusion requiring application of a more rigid bone plate. Five fractures developed late chronic swelling and low-grade infection requiring plate removal. Osseous union had occurred in these cases and no MMF was necessary. The use of two mini dynamic compression plates in the manner done in this study was found to be a relatively easy but unpredictable treatment for fractures of the mandibular angle.


Histologic study of the fate of autogenous auricular cartilage grafts in the human temporomandibular joint. Biopsies of 30 autogenous auricular cartilage grafts previously placed in 21 patients with ankylosis and arthropathy of the temporomandibular joint were studied. These joints were reoperated because of persistent pain and limitation of motion. Histologically, all grafts showed viability of the cartilage. Eighteen cartilage grafts placed after Proplast (Vitek, Inc, Houston, TX) or Silastic (Dow Corning, Midland, MI) implants had been removed, all showed foreign-body granuloma with coexistent intact cartilage grafts. This indicated that the autogenous auricular cartilage was resistant to the foreign-body reaction. All cartilage grafts were encased by fibrous tissue. This overgrowth of fibrous tissue may be responsible for the ankylosis. Seven grafts showed cartilaginous proliferation grossly and all showed proliferation histologically. The cartilage proliferation also may contribute to the persistent symptoms and recurrent limitation of joint motion.


Temporalis muscle as a disc replacement in the temporomandibular joint of sheep. Temporalis muscle flaps were evaluated in sheep. Flaps placed following discectomy were examined at 2, 4, 12, and 24 weeks. Histologic evaluation showed avascular necrosis and subsequent displacement and loss of tissue from the joint resulting in close contact between the condyle and fossa. Muscle flaps placed lateral to the joint in operative controls were examined at 4, 12, and 24 weeks. This muscle remained viable while undergoing fibrous replacement. Although the surface layers of the condyle and fossa were initially lost, the tissues were reformed with time. This experiment showed that in the sheep, temporalis muscle does not withstand functional loading within the joint. However, despite the lack of interpositional material, the condyle and fossa can remodel.


A case of cheiloplasty--1864.

A case of cheiloplasty--1864. Six hundred twenty thousand American soldiers were killed in the Civil War--almost as many fatalities as in all wars from the American Revolution through Vietnam. Those soldiers who did not immediately succumb to their wounds often had injuries that taxed the skills and imagination of the surgeon. A case of extensive destruction of the lower face is presented.


Comparison of the use of bulk to micro culture of cell preparations for lymphokine-activated cytotoxicity assays. Different assay systems have been used to quantitate lymphokine-induced natural cytotoxic activity as a measure of immune status. This study compares the effects of inducing cytotoxicity in a bulk culture system, where effector cells are transferred to a micro culture well for assay, to a micro culture system where the effector cells are not transferred. The effector/target ratio for both the bulk and micro culture systems was calculated using the number of viable effector cells present at the time of target cell addition. After overnight incubation with interleukin-2 (IL-2), the lytic activity of murine spleen cells to targets using a micro culture system was increased two-fold over the bulk culture method. This increase was amplified further after 5 days of activation with IL-2, in that the micro culture system resulted in a four-fold increase in cytotoxic activity. The loss of some adherent cells in the bulk culture system did not explain the overall decrease in recovered cytotoxicity. The difference appeared to be related to cell loss during centrifugation. Therefore, the E/T ratios are different in the two systems if not corrected for the number of viable cells.


Reduced levels of free testosterone in four Catania-type alloalbuminemic males. We studied total testosterone, sex hormone binding globulin, and free testosterone in four males presenting an electrophoretically slow-moving genetic variant of albumin, the alloalbumin Catania. Free testosterone levels were lower in these cases, found in a year of observation, than those expected for the ages. This finding, which is not related to any disease and constantly not recognized in other males with various genetic variants, should induce consideration of a probable difference of the genetic variant in hormone binding.


An improved method for monitoring efficacy of anti-retroviral therapy in HIV-infected individuals: a highly sensitive HIV p24 antigen assay. Circulating human immunodeficiency virus (HIV) p24 antigen levels were measured by a highly sensitive HIV p24 antigen-capture enzyme-linked immunosorbent assay (ELISA) in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) otherwise negative for HIV p24 antigen measured by a commercial antigen-capture ELISA. The assays were performed at baseline and at several intervals during treatment with either zidovudine (ZDV) or dideoxyinosine (ddl). To further enhance the rate of antigen detection, serum was pretreated with hydrochloric acid to denature antibody in immune complexes. Utilizing this assay system, we monitored these patients for drug efficacy. HIV p24 antigen levels obtained by using this sensitive assay decreased in 3 of 8 patients receiving ZDV during 8 weeks of ZDV treatment. Similarly, ddl administration was associated with a decrease of HIV p24 antigen levels in 3 of 5 patients. Thus, the use of the highly sensitive HIV p24 antigen assay permitted the monitoring of surrogate HIV p24 antigen as a measure of efficacy of anti-retroviral therapy in all of these patients who were otherwise HIV p24 antigen-negative at the onset of anti-retroviral therapy.


Elevation of platelet-associated IgG in aplastic anemia. We determined platelet-associated IgG (PAIgG) levels in patients with aplastic anemia, idiopathic thrombocytopenic purpura (ITP), iron deficiency anemia, and systemic lupus erythematosus (SLE), as well as in normal healthy adults as a control group. To determine PAIgG levels, we used a competitive micro enzyme-linked immunosorbent assay, which had excellent reproducibility, recovery, and dilution. We confirmed its reliability by comparing it to the immunoradiometric assay. Both the aplastic anemia group (n = 27, mean +/- SD = 218.6 +/- 244.6 ng/10(7) platelets) and the ITP group (n = 82, mean +/- SD = 212.5 +/- 327.8 ng/10(7) platelets) had higher PAIgG levels than the SLE group (n = 4, mean +/- SD = 38.4 +/- 22.4 ng/10(7) platelets), iron deficiency anemia group (n = 10, mean +/- SD = 16.1 +/- 3.6 ng/10(7) platelets), and normal control group (n = 69, mean +/- SD = 16.1 +/- 3.6 ng/10(7) platelets. The higher platelet-associated IgG levels in aplastic anemia suggest that autoimmune mechanisms are involved.


An enzyme immunoassay for determining plasma concentrations of didemnin B. Didemnin A was conjugated at the amino terminus of the N-methylleucine residue, via the linkers N-succinimidyl-3-(2-pyridyldithio)-propionate and trans-1,4-maleimidomethyl-cyclohexane carboxylic acid, to keyhole limpet hemocyanin (KLH) and bovine serum albumin (BSA). The didemnin-KLH conjugates were used to hyperimmunize rabbits. The resulting high titer antisera were employed with didemnin-BSA conjugate-coated microtiter plate wells to develop an indirect competitive inhibition enzyme immunoassay (CIEIA) that was fully cross reactive with didemnin B. A CIEIA is described that is capable of detecting the drug in plasma from didemnin B-treated patients at concentrations down to 1-3 ng/ml. This simple, sensitive CIEIA has been employed to demonstrate plasma drug clearance profiles with samples from didemnin B-treated patients.


Enzyme immunoassay and immunochemical characterization of pancreatic stone protein in human serum. Monoclonal antibodies were raised against human pancreatic stone protein (PSP) and used for one-step enzyme immunoassay (EIA). PSP-S2-5 was employed as the standard in the assay. The assay's measurable range was 25-1,500 ng/ml and within run coefficient of variation was 3.7-6.4%. Analytical recovery of the assay was 101.5 +/- 5.65% (mean +/- SD). The results of experiments in which serum was fractionated by Mono S (cation exchange chromatography) suggested that most of immunoreactive material in human serum is PSP-S2-5. The EIA offers simple, rapid, and specific analysis of serum PSP level for clinical diagnosis.


Effect of heat inactivation and sheep erythrocyte adsorption on the titer of anticardiolipin antibodies in primary antiphospholipid syndrome and healthy blood donors' sera. The standard enzyme linked immunosorbent assay (ELISA) currently in use for detection of anticardiolipin antibodies (ACA) was used to evaluate the influence of heat inactivation and sheep erythrocyte adsorption on individual optical density (OD) of sera from healthy blood donors or patients with primary antiphospholipid syndrome. Each sample was tested after single or combined maneuvers as follows: adsorbed, adsorbed and inactivated, only inactivated, and compared to basal readings. A significant increase of ACA titers did occur after inactivation of normal sera, but adsorption had no effect. In contrast, neither inactivation nor adsorption changed ACA titer in primary antiphospholipid syndrome sera as a group, although in certain sera there were changes. This observation may suggest the presence in normal serum of a thermolabile factor which modulates ACA binding to its antigen and the reactivity of the anticardiolipin antibodies of the primary antiphospholipid syndrome with sheep erythrocyte membrane phospholipids.


Tumor markers CA 19-9 and CA 195 are also useful as markers for cystic fibrosis. When monoclonal kits are used we can no longer detect highly elevated serum concentrations of carcinoembryonic antigen in cystic fibrosis (CF) patients as we could earlier (Pediatr Res 10:223-236, 1975). Instead, we find increased concentrations of CA 19-9 or CA 195 in the CF sera. The serum levels of CA 19-9 not only reflect the pulmonary condition of CF patients but also respond well to antibiotic therapy. Several lines of evidence suggest that the elevated serum concentration of CA 19-9 is derived from sputum and corresponds with the amount of sputum in the lung. Correlations between CA 19-9 and CA 195 in random and serial specimens from both patients with CF and patients with pancreatic carcinoma suggest that all sera contain heterogeneous, Lewis blood group-related epitopes and the proportions of various epitopes are different among individual patients. When monitored on multiple tumor markers, the pattern of CF is different from that of pancreatic carcinoma although both usually show elevated CA 19-9. Our study indicates that both CA 19-9 and CA 195 can be used as sensitive markers for the early detection of exacerbation in CF patients.


Sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) for (antihuman T-cell leukemia virus type I) immunoglobulin G in serum using a synthetic peptide, Ala-Cys-Env gp46(237-262), as antigen. A sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) for (antihuman T-cell leukemia virus type I) IgG (anti-HTLV-I IgG) in serum using a synthetic peptide, Ala-Cys-env gp46(237-262), of HTLV-I is described. Anti-HTLV-I IgG in test serum, which had been incubated with excess of inactive beta-D-galactosidase to eliminate interference by anti-beta-D-galactosidase antibodies, was reacted simultaneously with 2,4-dinitrophenyl-bovine serum albumin-Ala-Cys-env gp46(237-262) conjugate and Ala-Cys-env gp46(237-262)-beta-D-galactosidase conjugate. The complex formed consisting of the three components was trapped onto polystyrene balls coated with affinity-purified (anti-2,4-dinitrophenyl group) IgG. After washing to eliminate nonspecific IgG in the test serum and excess of the beta-D-galactosidase conjugate, the complex was eluted from the polystyrene balls with epsilon N-2,4-dinitrophenyl-L-lysine and transferred to polystyrene balls coated with affinity-purified (anti-human IgG gamma-chain) IgG. beta-D-galactosidase activity bound to the (anti-human IgG gamma-chain) IgG-coated polystyrene balls was assayed by fluorometry. This assay was more sensitive than other methods using HTLV-I as antigen, and most negative and positive sera were discriminated. However, some results appeared to be false positive or false negative, and the peptide, Ala-Cys-env gp46(237-262), was suggested to be useful, in combination with other peptides, for improving the reliability of serodiagnosis by separately demonstrating antibodies against as many different epitopes of HTLV-I as possible.


Photosensitized oxidation of cholesterol in biological systems: reaction pathways, cytotoxic effects and defense mechanisms. Cholesterol resembles other unsaturated lipids in being susceptible to peroxidative degradation when exposed to a sensitizing agent, exciting light of suitable wavelength and molecular oxygen. Selected hydroperoxides of cholesterol can be used as relatively convenient and reliable indicators of primary photochemical mechanisms, allowing a distinction to be made between free radical-mediated and singlet oxygen-mediated reactions. When generated in cell membranes, hydroperoxides of cholesterol and other lipids can have deleterious effects on membrane structure and function. Such damage may be exacerbated if these photoproducts undergo one-electron reduction to oxyl radicals which in turn initiate chain peroxidation reactions. Cells can resist these effects by using a membrane-based glutathione peroxidase to catalyze the two-electron reduction and detoxification of lipid hydroperoxides. Recent advances in our understanding of cholesterol photo-oxidation from the standpoints of (a) mechanistic information, (b) cytotoxicity and (c) cytoprotection are discussed in this article.


Photodynamic inactivation of retroviruses by phthalocyanines: the effects of sulphonation, metal ligand and fluoride. The photodynamic inactivation of retroviruses was investigated using aluminium and zinc phthalocyanine (Pc) derivatives. The N2 retrovirus packaged in either of the two murine cell lines, Psi2 and PA317, was used as a model for enveloped viruses. AlPc derivatives were found to be more effective photodynamically for inactivation of the viruses than the corresponding ZnPc derivatives. Sulphonation of the Pc macrocycle reduced its photodynamic activity progressively for both AlPc and ZnPc. Fluoride at 5 mM during light exposure completely protected viruses against inactivation by AlPc. In the presence of F-, inactivation by the sulphonated derivatives AlPcS1 and AlPcS4 was reduced 2.5- and twofold respectively. In a biological membrane (erythrocyte ghosts), F- had no significant effect on AlPcS4-sensitized lipid peroxidation. Under similar conditions, cross-linking of spectrin monomers in ghosts is drastically inhibited (E. Ben-Hur and A. Orenstein, Int. J. Radiat. Biol., 60 (1991) 293-301). Since Pc derivatives do not inactivate non-enveloped viruses, it is hypothesized that inactivation occurs by photodynamic damage to envelope protein(s). Substitution of sulphonic acid residues reduces the binding of Pc derivatives to the envelope protein(s), thereby diminishing their photodynamic efficacy and the ability of F- to modify it.


Configuration of triporphyrin ethers probed by fluorescence measurements. The fluorescence spectra and lifetimes of triporphyrin ethers derived from hematoporphyrin, mesoporphyrin and protoporphyrin were examined, together with relative hydrophobicities estimated from reverse-phase high performance liquid chromatography (HPLC) elution times. The following data suggest a molecular arrangement with two of the three rings in a "folded configuration". The trimers display a greater fluorescence yield (phi f) than the corresponding diporphyrin ethers which contain only the two folded rings. The fluorescence lifetime data for the trimers are consistent with signals from both a folded ring pair (7-8 ns) and a free ring (14 ns). Reverse-phase HPLC studies indicate that the trimers are intermediate in hydrophobicity between the monomers and dimers. Preliminary data suggest that, for certain peripheral substitutions, the trimer configuration is superior to the dimer for photodynamic therapy.


Riboflavin-photosensitized anaerobic modification of rat lens proteins. A correlation with age-related changes. When rat lens homogenate or its soluble protein fractions are irradiated in the presence of riboflavin, a photo-adduct is obtained between this vitamin and the lens proteins. Irradiation of these proteins in the presence of riboflavin also leads to a modification in the chromatographic elution pattern with an increase in the high-molecular-weight fraction. In an aging study with rats, it was shown that the proportion of the high-molecular-weight protein fraction significantly increased with age, whereas the proportion of the low-molecular-weight protein fraction concomitantly decreased. It is postulated that aging produces an increase in the accessibility of the tryptophan residues of the lens proteins, as established by iodide fluorescence quenching experiments.


Fluorescence anisotropy studies of dibucaine.HCl in micelles and bacteriorhodopsin. Emission and excitation spectra for the local anesthetic drug, dibucaine.HCl in neutral and charged surfactant solutions and in bacteriorhodopsin (bR) have been investigated for lambda(ex) = 266 nm at room temperature. The total fluorescence and fluorescence anisotropy decays of the anesthetic in the same environments were also measured using a picosecond laser/streak camera system (lambda (ex = 266 nm)). The total fluorescence decay gave two components for dibucaine micellar and dibucaine bR solutions, one component in the range of 200-500 ps and the other in the range of 1200-3400 ps. Only the nanosecond timescale component was found for the dibucaine monomer surfactant solutions (1200-3000 ps), indicating that the anesthetic resides in the bulk solution. The fluorescence anisotropy decays of dibucaine in Triton X-100 and in lithium dodecyl sulfate (LDS) micelles are approximately 200 ps, which is attributed to dibucaine solubilized in the micellar environment. Dibucaine.HCl in anionic monomer solution exhibits an unusually large fluorescence anisotropy, r(t)max = 0.22 and a depolarization decay of less than 100 ps. This presumably results from a head-to-tail exciplex aggregation between the positively charged dibucaine and negatively charged dodecyl sulfate surfactant molecules. The anisotropy decay of dibucaine in bR is 300 ps. This solution was the only one which exhibited a residual fluorescence anisotropy, r(infinity) - 0.08. This implies that dibucaine is restricted in its rotational motion and suggests protein binding rather than lipid solubility.


Biological clocks: mechanisms and developments. Almost all organisms ranging from unicellular protists to mammals were found to show biological rhythms. Many workers have performed various kinds of experiment to understand the mechanism as well as to find the origin of the clock responsible for these rhythms. However, there is no doubt about the existence of a biologically controlled clock in almost all organisms; yet its origin and mechanism still remain a mystery. Many theories have been put forward to explain the mechanism of these biological clocks and it seems that the cell membrane may play a key role. The existence of a very high electric field of the order of 10(5) V cm-1 across the cell membrane may have some role in the mechanism of the biological clock. Of all the factors which have the effects on biological rhythms, light and temperature are found to be the most common. Also, the study of these biological clocks can help to solve the sleeping problems of international travellers and shift workers as well as to improve diagnosis, cure and prevention from diseases.


In vitro phototoxicity of nifedipine: sequential induction of toxic and non-toxic photoproducts with UVA radiation. Anecdotal reports suggest that the dihydropyridine calcium antagonist, nifedipine (NIF), may be phototoxic in human skin. We have studied NIF phototoxicity in vitro using UVA fluorescent tubes (Sylvania PUVA). NIF was phototoxic to Candida albicans and induced photohaemolysis both with NIF present during irradiation and with pre-irradiated drug. In V79 hamster fibroblasts, NIF (10 micrograms ml-1) was phototoxic MTT assay) 24 h after irradiation (0-112 kJ m-2); at 7.5 kJ m-2, about 70% of cells were damaged whilst at 37.5 kJ m-2, only about 45% of cells were damaged. A similar pattern was seen with pre-irradiated NIF. Absorption spectroscopy showed that the NIF absorption maximum (Amax approximately 340 nm) blue-shifted to 314 nm at low UVA doses (7.5 kJ m-2 or less) and red-shifted to 345 nm at higher doses (isosbestic point, 325 nm). Thin layer chromatography of irradiated NIF showed a single photoproduct (PP1; Amax approximately 314 nm) formed at 7.5 kJ m-2 or less which disappeared at higher UVA doses to give further photoproducts. PP1 was highly dark toxic to V79 cells (50% damage at about 5 micrograms ml-1) but PP1 pre-irradiated with UVA was non-toxic. Preliminary gas chromatography-mass spectroscopy studies suggest that PP1 is the nitroso derivative of NIF. These results indicate that NIF phototoxicity in vitro is partially mediated by initial formation of a toxic photoproduct (PP1) but, paradoxically, subsequent UVA irradiation may reduce phototoxicity. The NIF concentrations required to induce in vitro phototoxicity are much greater than therapeutic plasma levels. Unless there is skin accumulation of NIF or PP1, our in vitro results suggest that NIF may not be an important skin-photosensitizing agent in vivo.


Activation of mouse macrophages by in vivo and in vitro treatment with a cyanine dye, lumin. The cyanine photosensitizer, lumin, is a potent macrophage activating agent: 4 days after administration of small amounts of lumin to mice (20-40 ng mouse-1), peritoneal macrophages exhibited a greatly enhanced Fc-mediated ingestion activity; higher doses (more than 3000 ng mouse-1) did not have this effect. The in vitro photodynamic activation of macrophages in mouse peritoneal cells exposed to white fluorescent light (3 J m-2 s-1) was also studied in media containing various concentrations of lumin. A short light exposure (45 J m-2) with 10 ng lumin ml-1 produced a maximum ingestion activity of macrophages. Lumin has absorption peaks at 670 and 760 nm. Therefore we designed experiments in which peritoneal cells were exposed to a red fluorescent light (emission, 660 nm; 0.5 J m-2 s-1). In a medium containing 3 ng lumin ml-1 with 7.5 J m-2 of red light, a markedly enhanced ingestion activity of macrophages was observed. The photodynamic treatment of peritoneal macrophages alone did not stimulate phagocytic activity, but the photodynamic treatment of a mixture of non-adherent (B and T) cells and macrophages resulted in a greatly enhanced ingestion activity of macrophages. Thus non-adherent cells are required for the photodynamic activation of macrophages, implying that an activating factor is generated within the non-adherent cells and transmitted to the macrophages. This hypothesis was confirmed by the observation that co-cultivation of photodynamically treated non-adherent cells with untreated macrophages resulted in a greatly enhanced ingestion capacity.


Characterization of tumorous and normal tissue using a pH-sensitive fluorescence indicator (5,6-carboxyfluorescein) in vivo. The pH of the interstitial fluid of malignant tumours tends to be lower than that of normal tissue and is depressed by glucose administration. This study aimed to evaluate the effectiveness of dual-wavelength fluorometry using a pH-dependent indicator (5,6-carboxyfluorescein: 5,6-CF) for the detection of tumour areas in vivo. 5,6-CF has two main characteristics: it has two wavelengths of maximum absorbance (465 and 490 nm) and its fluorescence emission (maximum, 515 nm) increases as a function of pH in the physiological pH range of 6-7.4. The experimental study was performed on 28 CDF mice bearing lymphoid leukaemia P388 grafted subcutaneously. The tissue pH values were evaluated from the ratio of the fluorescence intensities (I490/I465) on the basis of a calibration curve linking pH measurements performed within the tissue using a microelectrode and values of the fluorescence intensity ratio. The fluorescence intensity reached its maximum value 60 min after 5,6-CF and glucose administration, followed by a plateau (90 min) when the ratios remained constant at 1.79 +/- 0.05 for normal tissue and 1.35 +/- 0.04 for tumour tissue (p less than 0.005). These results were correlated with the pH measurements in accordance with the calibration curve. This study validates the relevance of dual-wavelength fluorometry using a pH-dependent indicator to characterize in vivo normal and tumour tissues after glucose administration.


pH dependence of fluorescence and absorbance spectra of free sulphonated aluminium phthalocyanine and its conjugate with monoclonal antibodies. Water-soluble phthalocyanines and phthalocyanines linked to targeting monoclonal antibodies are considered to be one of the most promising photosensitizers in photodynamic therapy. Here the spectrum characteristics of sulphonated aluminium phthalocyanine and its protein conjugate in the pH range 1.8-12.0 in solution have been studied. The pK values are determined.


Affect regulation, nicotine addiction, and smoking cessation. Numerous investigators have examined the role of negative affective states and affect regulation in the initiation and development of cigarette smoking behavior, smoking cessation, and relapse prevention. Affect regulation refers to any attempt to alleviate negative mood states by means of pharmacologic-, cognitive-, behavioral- or environmental-change methods. The psychological construct/process of affect regulation is examined in relation to (1) the initiation, development, and maintenance of the cigarette smoking habit; (2) the process of quitting smoking; and (3) the long-term maintenance of smoking abstinence versus relapse. Various psychosocial factors and physiological mechanisms are explored that have been hypothesized to be links between negative mood states, nicotine addiction, and smoking cessation. Implications for smoking cessation treatment are discussed in the areas of (1) the use of pharmacologic agents, such as clonidine, in the reduction of nicotine withdrawal symptoms; (2) nicotine replacement therapy; and (3) skills-training approaches to smoking cessation and relapse prevention.


Preventing relapse in the treatment of nicotine addiction: current issues and future directions. Although smoking-cessation rates have continued to increase, the vast majority of smokers who quit eventually relapse. Between 1974 and 1985, over 1.3 million smokers quit during each of those years. However, 75% to 80% of those individuals resumed smoking within six months. This article describes the dynamic phenomenon of smoking relapse within the context of cyclical episodes of smoking and quitting during an individual's lifetime. Theories of the determinants of smoking relapse are reviewed and methods designed to prevent relapse are described. Smoking relapse is discussed in terms of three aspects of tobacco addiction: (1) biological-addiction mechanisms, (2) conditioning processes, and (3) cognitive-social learning factors. The major determinants of smoking relapse are reviewed, including nicotine withdrawal, stress, weight gain, social influences, conditioning factors, causal attributions, and environmental variables. A transtheoretical-developmental model is explored in the longitudinal investigation of the natural history of slips (lapses) and relapse episodes. Relapse prevention interventions are described that emphasize self-awareness, self-regulation, self-efficacy, affect regulation, social support, and lifestyle balance. Recent developments in pharmacological adjuncts to treatment are also examined. It is concluded that innovative relapse prevention methods need to be designed for hard-core smokers with histories of cessation failures, substance abuse and/or psychiatric impairment. These and other recommendations for future research on smoking relapse and relapse prevention are discussed.


Nicotine dependence and alcoholism epidemiology and treatment. Nicotine dependence in alcohol-involved adults is a long-ignored treatment problem. The absence of its discussion in the literature is difficult to defend in light of medical and epidemiological data on the cost and prevalence of this dual addition. Most descriptive studies of alcohol abusers published in the past 20 years have reported tobacco use rates of at least 90%. There is a crucial need to educate treatment professionals and their clients about the additional health risks associated with joint nicotine dependence and alcoholism. Historically, certain barriers to active intervention have existed in drug abuse treatment facilities, including (1) concerns that urging clients to quit smoking might have an adverse effect on their maintenance of sobriety, (2) a tendency to minimize the strength and severity of nicotine addition, (3) a lack of informative data on how best to treat smoking in recovering alcoholics, and (4) financial issues related to marketing and insurance compensation. Recent data obtained from recovering alcoholics who have tried to quit smoking and anecdotal reports from alcoholism treatment centers that have begun addressing nicotine addiction are now challenging these barriers. Education, role modeling, environmental control, and development of staff expertise can be incorporated into standard alcoholism treatment programs to jointly treat these paired addictions.


Marijuana and immunity.

Marijuana and immunity. Despite the fairly large literature that developed during the past 15 years or so, the effect of cannabinoids on the immune system is still unsettled. The evidence has been contradictory and is more supportive of some degree of immunosuppression only when one considers in vitro studies. These have been seriously flawed by the very high concentrations of drug used to produce immunosuppression and by the lack of comparisons with other membrane-active drugs. The closer that experimental studies have been to actual clinical situations, the less compelling has been the evidence. Although the topic was of great interest during the 1970's, as indicated by the preponderance of the references from that period, interest has waned during the present decade. This waning of interest suggests that perhaps most investigators feel that this line of inquiry will not be rewarding. The AIDS epidemic has also diverted the attention of immunologists to the far more serious problem of the truly devastating effects a retrovirus can have on a portion of the immune system. The relationship between the use of social drugs and the development of clinical manifestations of AIDS has been of some interest, however. Persons infected with the virus but not diagnosed as AIDS have been told to avoid the use of marijuana and/or alcohol. This advice may be reasonable as a general health measure, but direct evidence that heeding this warning will prevent the ultimate damage to the immune system is totally lacking.


Update on inborn errors of metabolism: primary lactic acidemia. Initially thought to be rare, primary lactic acidemia is diagnosed with increasing frequency. Elevations in lactate and pyruvate are markers for a variety of metabolic blocks. Although there have been great strides made in the diagnosis and treatment of lactic acidemia, much remains to be learned. As laboratory techniques improve, clinicians will be able to make an exact enzymatic diagnosis on an increasing percentage of patients. Specific enzymatic diagnosis also will help clinicians determine inheritance patterns, recurrence risks, and methods of prenatal diagnosis.


Treating crack cocaine dependence: the critical role of relapse prevention. In order to adequately address the treatment needs of crack cocaine dependent persons, a multidimensional approach to relapse prevention must be utilized. The value of a biopsychosocial model of crack addiction and the concept of phases of recovery in providing a rationale for the recommended approach to relapse prevention are emphasized. Research findings on the determinants of relapse for crack dependent patients and the psychosocial characteristics of the crack dependent individual justify the utility of certain relapse prevention strategies. Specifically, an approach to relapse is advocated that includes the provision of pharmacological adjuncts, psychoeducation on the multideterminants of relapse, and psychotherapy that attempts to remediate underlying psychological problems that are typically found in crack dependent patients.


The tobacco epidemic: lessons from history. Tobacco has caused the greatest epidemic of the twentieth century, which is beginning to wane in the United States, but is still growing in much of the world. The epidemic developed as a result of innovations in the tobacco industry and larger cultural changes over the 75 years prior to the introduction of Camel cigarettes in 1913. Factors that set the stage for the epidemic include the development of flue-cured and Burley tobaccos, the mechanization of cigarette production with its consequent concentration of capital in a few companies, the safety match, efficient transportation systems, and innovative advertising. Between 1913 and 1963, the cigarette industry experienced almost unbroken growth in the United States. However, since the early 1950s, increasing evidence that cigarettes cause lung cancer and other diseases has dictated that product innovation concentrate on the appearance of safety. In the late 1960s and for a sustained period since 1973, cigarette consumption has declined in the United States, but in the developing world the epidemic curve of cigarette use is still on the upswing. As tobacco use declines in the United States, it is crucial that the production of tobacco products as well as their consumption be reduced. Otherwise, attempting to control the problem in the United States will not result in a net reduction in mortality around the world.


Injury prevention: a survey of clinical practice. The purpose of this study was to determine what education and training pediatric nurse practitioners receive about injury prevention and control and what kinds of clinical activities PNPs perform with regard to injury prevention and control. Sixty-four members of the Greater New York Chapter of the National Association of Pediatric Nurse Associates and Practitioners were questioned. Data on demographic, professional, and practice characteristics and on education and training and clinical activities in injury prevention and control were collected. Results indicated that advice about child car restraints and automobile seat belts was routinely given by less than 30% of practitioners, information about smoke detectors was given by about 15%, and advice about firearms in the home was given by 7% or less. Implications for counseling to prevent injuries are discussed.


Counseling the high-risk adolescent.

Counseling the high-risk adolescent. Interviewing and counseling high-risk adolescents provides a challenge to nurse practitioners. The problems of poverty, substance abuse, mental illness, and low self-esteem overlay other characteristics of risk, making assessment and management of the adolescent's problems complex and difficult. Survey data, obtained in this study on adolescent risk-taking, suggest that violence, aggression, and thrill-seeking behaviors are increasingly common. The finding is supported by current national statistics on adolescents. A case study is used to show the process of gathering information on home and educational settings that can provide insight into family dysfunction and specific problem behaviors.


Child and adolescent obesity: the nurse practitioner's use of the SHAPEDOWN method. The prevalence of obesity in children and adolescents has increased approximately 50% in the last 20 years and now affects more than one in four young people. Although family-based approaches to the problem recently have shown weight losses maintained at 5-year and 10-year follow-up, this care is unavailable in many communities because of an insufficient availability of trained providers. Nurse practitioners are uniquely appropriate for providing child and adolescent obesity services yet appear to be underrepresented among pediatric obesity care providers. This article describes a method of preventive and therapeutic care that nurse practitioners can use in clinical practice.


Discouraging smoking: interventions for pediatric nurse practitioners. Smoking is the most preventable cause of death in this country, and it often begins in adolescence. By discouraging the use of cigarettes, pediatric nurse practitioner and other health care professionals can significantly reduce this current and future threat to the health of the nation's children and adolescents. This article describes factors associated with adolescent smoking and interventions to prevent the initiation of smoking.


Pediatric pain management (Part II).

Pediatric pain management (Part II). This article is the second in a two-part series on pediatric pain management. It primarily contains information about the use of narcotic analgesics for pediatric patients.


General design issues in efficacy, equivalency and superiority trials. Critical discussion is offered of design issues pertinent to three categories of clinical trials: efficacy trials, in which an experimental intervention is compared to an inert control, and equivalency and superiority trials, in which an experimental intervention is compared to an active control. The issues discussed are sample-size determination and power, problems in designing and analyzing multicenter trials, broad versus concentrated sampling of patients, the need (or not) for a placebo control group in an active control trial, the possible appropriateness of crossing patients over from one regimen to another, various methods of randomization, the intention-to-treat principle in repeated measurements studies, and possible logical conflicts between inferences from superiority trials and inferences from equivalency trials.


General issues in efficacy, equivalency, and superiority trials: clinical considerations. The design of clinical trials aimed at treating different types of periodontal diseases must take into account the prevalence of the disease in the population and the relationship of various descriptors, which may vary from disease to disease. For screening purposes, patients should be selected with disease in the high-severity range, in order to maximize the likelihood of detecting a therapeutic effect. Subsequent trials may be designed around a more representative group of subjects. Therapies must be evaluated on the basis of actual clinical changes, rather than their effect on presumed etiologic factors. The observed changes must be of clinical as well as statistical significance. The distribution of periodontal diseases within a dentition may affect as few as one or as many as over one hundred sites. Strategies are needed to correlate events observed at sites within the dentition, i.e. tooth surface-based measurements or scores, with events that are subject-based, e.g. concentration of blood or salivary components.


Logical and analytic issues in dental/oral product comparison research. Possible meanings of "superiority" and "equivalence" in comparative dental studies are considered. A proposed refinement of vocabulary is introduced to precisely distinguish between these meanings. Implications for data analysis of different interpretations of "superiority" and "equivalence" are explored, as are implications for study design where design and analytic considerations are inseparable. Conceptual problems of equivalence studies are stressed. Choice of analytic unit(s), scaling of dependent variables, use of surrogate variables, and validity checking are discussed as they pertain to comparative studies. Analytic methods for correlated responses and categorized responses are briefly surveyed, particularly with reference to periodontal research.


Toward strategies for the analysis of periodontal disease clinical trials. We consider design, analysis and regulatory issues relating to clinical trials in periodontal disease and identify complications commonly associated with such studies. Alternative statistical procedures that can be used for the analyses of data from periodontal research are reviewed and a case study of the analysis of a Phase II periodontal disease clinical trial is provided to illustrate the use of one of these procedures.


Biological and measurement issues critical to design of gingivitis trials. Chronic plaque-induced gingivitis is usually of little consequence, thus the concern about prevention and treatment must stem from the belief that preexisting gingivitis is necessary for periodontitis to develop. When clinical signs of gingivitis are present, an inflammatory infiltrate can be found upon histological evaluation. When clinical signs are absent, however, significant inflammation may still be present within the gingival tissues. Therefore, multiple clinical evaluations should be made, with special attention given to the visually inaccessible midinterdental area. The "gold standard" for evaluation of gingivitis is histological evaluation and other measurements should be evaluated against this standard. The significance of clinical severity measurements of gingivitis is not well-understood relative to onset of periodontitis; therefore, it is suggested that consideration be given to gingival evaluations based on the presence or absence of clinical signs of inflammation. Furthermore, equivalency and superiority of antigingivitis agents or devices should be predicated, at least in part, on their ability to prevent the onset of periodontitis.


Some thoughts on the measurement of gingivitis. The selection of a method for measurement is of critical importance in the planning of a study. Despite the great strides afforded by research of gingivitis, a "gold standard" for its measurement has yet to be clearly established. Traditional clinical indices continue to serve as "gold standards" in many investigations. There is a need for some caution and tentativity in interpreting the results of such studies. Additionally, those studies which yield data on an ordinal scale should make more use of statistical methodologies specifically geared toward the analysis of such data.


Specific statistical considerations relevant to the design and analysis of gingivitis trials demonstrating product superiority or equivalence. Simulation studies were conducted to address specific statistical issues which arise in the design and analysis of gingivitis studies whose principal aim is the demonstration of superiority or equivalence of one product to another. The effects of measurement scale, using differences or ratios of group means, particular statistical test produces and specific rules demonstrating superiority or equivalence were investigated. An alternative concept to equivalence--denoted "least as good"--was also defined and evaluated. For a wide class of possible distributions of gingivitis scores, characterized by specific gamma distributions, the student-t test applied to means of subject GI gingivitis scores proved to be the most powerful of the test produces considered, having statistical properties quite similar to the randomization or permutation test procedure. Transformations of subject GI mean gingivitis scores did not produce an advantage in demonstrating either superiority or equivalence, and in some cases made it more difficult. Little difference was observed in test results when using the difference in group means as compared with using the ratio of group means for demonstrating either equivalence or superiority. The clinically significant rule produced the lowest false-positive rates for products slightly better than the active control, and similar false-positive and -negative rates as the statistically significant rule for products clearly superior to the active control. Demonstration of product equivalence will require more subjects per group than demonstrating product superiority, the size of this difference being a function of the definition of superiority that is accepted. Showing that the 90% confidence interval for 100*R is completely contained within the [90%, 110%] interval is the preferred method of demonstrating equivalence today, although much more research needs to be done to improve methods for demonstrating product equivalence. The "least as good" alternative to "equivalence" makes it easier to demonstrate "equivalence" for products slightly better than the active control product, but both experience great difficulty in demonstrating equivalence for test products not quite as good as the active control.


Design issues specific to studies of periodontitis. Guidelines for clinical trials demonstrating equivalence or superiority for treatments for periodontitis are badly needed because of the great variety of drugs, agents, and devices now being developed. This paper focuses on three design issues. These are primary outcome variables and their measurement, disease-active vs disease-inactive sites and patients, and study duration. Determinants for selection of outcome variables include the biologic events to be observed, changes that are specific for periodontitis, and methods chosen to detect those changes. The primary outcome variables specific for periodontitis and appropriate for use in clinical trials are periodontal attachment level and alveolar bone status. Improved methods for measurement of both with excellent accuracy and reproducibility are now becoming available. Studies performed on untreated patients over the past decade demonstrate clearly that disease-active and disease-inactive pockets exist, at any given point in time most are inactive, disease progression is episodic and in most patients infrequent, and a rather small portion of the population--possibly around 5%--are unusually susceptible to rapid disease progression. These observations need to be taken into account in enrolling subjects into periodontitis clinical trials. Conducting a prestudy to identify actively diseased sites and susceptible subjects, or screening to enrich the proportion of active sites, is recommended. Determination of study duration is a very complex issue. It is related to the length of time required for maximal change and stabilization to occur in the biological events to be observed, the outcome variable(s) used to detect change, and the nature of the therapeutic interventions to be studied. No single duration is applicable to all periodontitis clinical trials. Large gaps in our knowledge about the design of periodontitis trials still exist, and additional research is needed.


Considerations for the interpretation of findings from single and multiple studies of periodontal conditions. This paper reviews considerations involved in the interpretation of results of individual periodontal clinical trials and the synthesis of findings of multiple studies. The purpose of each study must be considered, particularly whether it is an epidemiological investigation, prevention trial or therapeutic clinical trial. The definition of clear end-points, whether they be hygiene end-points associated with calculus and plaque or disease end-points that measure extent of gingivitis and periodontitis, is essential. Other statistical considerations include the following: adequate sample size, balanced design, use of covariates, issues of the appropriate sampling unit, and proper statistical analysis. Statistical issues that must be considered include the types of tests of hypotheses, use of multiple comparison procedures when more than two groups are involved, corrections for multiple testing and precise estimation of parameters with corresponding confidence intervals. When comparing across clinical trials, three sources of heterogeneity that must be considered are: treatments, diseases, and target populations. The technique of meta-analysis is described for the statistical interpretation of data arising from several trials. A meta-analysis is conducted for six dental clinical trials that evaluated a triclosan/copolymer formulation for the reduction of plaque, calculus or gingivitis. Results indicate that the first five studies, which were reported simultaneously, showed a common effect, i.e., that the formulation successfully reduced either plaque or calculus. When the sixth study, reported at a different time, was added to the analysis, the collection of studies did not satisfy the homogeneity assumption necessary for estimating a common effect size. This illustrates the importance of testing for homogeneity before pooling possibly dissimilar studies.


Issues in the evaluation of clinical trials of periodontitis: a clinical perspective. The goals of clinical trials designed to establish claims for equivalency or superiority of treatment for periodontitis must be clearly stated and defined in terms of measurable and meaningful response variables. It is suggested that these clinical trials use designs that compare new treatment methods to basic periodontal therapy which consists of thorough scaling and root planing, oral hygiene instruction, and regular maintenance care. The primary response variable should be clinical attachment level. It is important to document changes in probing depth since this is a meaningful measure to many clinicians. Gingival inflammation and bleeding should be used as secondary response variables because these are not necessarily indicative of progressive periodontal destruction. Radiographic measures of disease may be useful as primary response variables if safe, reproducible and valid methods of measuring change are utilized. Microbiological monitoring should be a secondary response variable because of numerous questions concerning sampling methodology, quantitative expression of data, and meaningful interpretation in terms of relevance to disease activity. The length of periodontitis trials should be set at a minimum of 9 months if claims of superiority or equivalency are made compared to basic periodontal therapy. Calibration trials should be included and measurement error should be expressed in terms that are meaningful to the clinician while retaining statistical validity. Statistical methods for determining change should take into account site and subject heterogeneity, bursts of change and gradual change over time. It is important that statistical techniques be used that detect change as early as possible and that appropriate consideration be given to the clinical implications of the type, magnitude and duration of change in outcome variables.


Effect of a social cognitive intervention on oral health status, behavior reports, and cognitions. An intervention designed to test the influence of cognitive restructuring on protective oral health behaviors was conducted with 108 patients with mild to moderate gingivitis. Subjects in the experimental group viewed slides of active, mobile bacteria taken from their mouths on 5 occasions: before and after prophylaxis and at 3 appointments, one month apart. A specially trained hygienist discussed with these participants the process of periodontal disease, the role of bacteria, and self-efficacy (self-control) for oral hygiene self-care. Both experimental and control group subjects received instruction in oral self-care procedures. Assessments of oral health using Löe and Silness' plaque and gingival indices (PI and GI) were taken throughout the study and at 3- and 6-month follow-up visits. Self-efficacy, oral hygiene intentions, attitudes, and values comprised the set of cognition variables. Plaque and gingival indices mean differences between groups approached significance at visit 6. Analyses were also performed using percent of gingival surfaces scored at "0" (no visible bleeding on probing). A trend occurred for group differences in percent "0" scores at visit 6, with the experimental group maintaining higher percent zeros (better health) at this 3-month follow-up. At visit 7 (9-month follow-up), PI and GI differences disappeared. No significant differences were found between groups for oral health cognitions or behavior reports over time. The data suggest that the cognitive-behavioral intervention produced a delayed relapse in protective oral self-care behaviors, and by extension, oral health status. Such a delay could be clinically relevant in promoting adherence to oral hygiene behavior between professional visits.


The effects of chlorhexidine on the attachment and growth of cultured human periodontal cells. The purpose of this investigation was to evaluate the effects of chlorhexidine (CHX) on the attachment and growth of human gingival fibroblasts and periodontal ligament cells using an in vitro system where periodontal cells were grown on root surfaces treated previously with CHX. Our results indicate that the attachment of periodontal cells onto root surfaces was not adversely affected when roots were treated for 15 minutes with up to 0.12% CHX. However, cell attachment and morphology were adversely altered with prior 0.2 to 2.0% CHX treatment. The cells appeared round and retracted from roots treated with 0.2% CHX. With 2% CHX treatment, the cells exhibited a foamy appearance in which most of the cytoplasm seemed to have been extracted from the cells. Although 0.12% CHX treatment did not adversely affect the attachment of periodontal cells onto roots, direct exposure to as little as 0.01% CHX caused a 90% reduction in 3H-thymidine incorporation by cultured gingival fibroblasts. We conclude that although 0.12% CHX did not inhibit the attachment of cultured periodontal cells to pretreated roots, direct exposure of cells to much lower concentrations of CHX (0.0025 to 0.01%) caused a dose-dependent inhibition of growth.