Thirst following water deprivation in dogs. Eight dogs were prepared with unilateral carotid loops, and trained to stand quietly in a modified Pavlov stand. They were deprived of water for 24 h, which significantly depleted both the cellular and extracellular fluid (ECF) compartments. When they were allowed access to water for 5 min, they promptly drank amounts sufficient to make up their fluid deficits. Infusion of water into the unilateral carotid loop to reduce the cerebral blood osmolality to normal did not consistently reduce drinking because of inadequate mixing in the Circle of Willis. The eight dogs were then prepared with bilateral loops and deprived of water. Infusion of water at 0.6 ml-kg-1-,min-1 reduced the jugular plasma osmolality to control levels but did not affect systemic osmolality and reduced the drinking by 72%. Intracarotid infusion of water at differing rates reduced drinking in a dose related fashion. Intravenous infusion of 0.15 M NaCl in an amount designed to expand the ECF volume to normal reduced drinking by 27%. Expansion of the ECF volume plus bilateral intracarotid infusion of water to remove the central osmotic stimulus completely inhibited drinking. It is concluded that drinking following water deprivation in dogs is controlled by both central osmotic and by extracellular fluid volume factors, and that the osmotic factor is the more important. The drinking stopped well before these fluid deficits, as judged by body fluid analysis, had been restored. Some other mechanisms, therefore, must be involved in satiety.


Psychiatric disturbances associated with Erhard Seminars Training: I. A report of cases. Erhard Seminars Training (est) is a large-group experience that is becoming widely available in this country. This is the first case report in the professional literature of psychiatric disturbance following est training. Five patients, only one of whom had a history of psychiatric disturbance, developed psychotic symptoms including grandiosity, paranoia, uncontrollable mood swings, and delusions. Further work is necessary to ascertain the factors that determine outcome in est.


The effects of National Health Insurance on Canadian Psychiatry: the Ontario experience. After studying psychiatric coverage under national health insurance in Ontario, the author concludes that psychiatric benefits can be provided on the same basis as other medical benefits and that a government system can maintain confidentiality. Costs have been reasonable and in line with the proportion of psychiartists to the total number of physicians, and psychiartists' incomes have increased substantially, even with comparatively low official fees. Despite the existence of NHI, the public mental health system has been maintained in Canada and has been expanded in regard to children's services. There appears to be a continued need for direct public funding of services for certain other groups such as the elderly, chronic patients, ans substance abusers.


The medical setting: is it beyond the psychiatrist? Recent events in medicine have afforded psychiatrists an opportunity to move beyond the traditional boundaries of their involvement in the medical setting. The growing preoccupation of the medically ill and their families with the psychosocial aspects of medical illness, their growing dissatisfaction with current patterns of patient care, and internists' increased awareness of the psychological needs of the nonpsychiartic medical patient have led to a rethinking of mind-body dualism and to increased involvement of the psychiatrist in general medical care.


Recent mental health litigation: a critical perspective. The author considers the effect of recent mental health litigation involving involuntary confinement, the right to refuse treatment, the least restrictive alternative, and the right to treatment on the role of the psychiatrist and the provision of mental health care. His thesis is that the implicit analogies between psychiatrists and agents of the criminal justice system and between patients and criminal defendants are misleading and that the recent changes in the law based on these analogies adversely affect the provision of mental health care.


Regulating psychiatric practice.

Regulating psychiatric practice. The trend toward increased regulation of psychiatry and medicine may alleviate some problems but increase others. Some models of practice may achieve monolithic dominance, and maldistribution of practitioners may increase. Covert fantasies about authority, leadership, and peer relations should be borne in mind in the attempt to create an informed, improved regulation of medical practice.


Tests of competency to consent to treatment. The authors describe the various tests of competency to consent to treatment used today, which include the following: 1)evidencing a choice, 2)"reasonable" outcome of choice, 3)choice based on "rational" reasons, 4)ability to understand, and 5)actual understanding. They analyze the applicability of these tests to patients' decisions to accept or refuse psychiatric treatment and illustrate the problems of ap-lying these tests by citing clinical case examples. They find that the circumstances in which competency becomes an issue determine which elements of which tests are stressed and which are underplayed.


Toward a model of the legal doctrine of informed consent. The authors draw together the disparate scholarly and judicial commentaries on consent to medical treatment to develop a model of the components in the decision-making process regarding consent to or refusal of psychiatric treatment. The components consist of the precondition of voluntariness, the provision of information, the patient's competency and understanding, and, finally, consent or refusal. They offer two models of valid consent: the objective model, which focuses on the congruence or lack of it between the patient and a "reasonable" person, and the subjective model, which focuses entirely on the patient's actual understanding.


Tarasoff: protective privilege versus public peril. The author reviews the decision made by the California Supreme Court in the case of Tarasoff v. the Regents of the University of California, et al., which stipulated that therapists must warn authorities specified by law as well as potential victims of possible dangerous actions of their patients. He states the basic points of the Northern California Psychiatric Society's amicus curiae brief on behalf of the university regents and discusses the issues raised by the Tarasoff decision vis--53a-vis the mental health profession and its dealings with potentially violent individuals.


Changing law and clinical dilemmas.

Changing law and clinical dilemmas. The author describes a case in which a severely depressed suicidal patient was treated with ECT despite her refusal to grant permission while involuntary commitment procedures were pending. He discusses the professional dilemmas caused by new, and sometimes conflicting, legal principles such as the right to treatment and the right to refuse treatment and suggests that psychiatrists work to clarify these principles while saftguarding themselves with the aid of appropriate legal counsel.


Retrospective audit: depressive neurosis. The charts of 100 patients with a primary diagnosis of depressive neurosis were subjected to retrospective audit using a format adapted from the American Psychiatric Association's Model Criteria Sets. Nineteen of the 33 unjustified variations from the audit criteria involved variations from the 8-28 day length of hospital stay. The author raises the question of whether the lower limit of 8 days is sufficiently flexible to permit hospitalization of acutely suicidal patients who can be discharged to outpatient care in less than 8 days.


Weight reduction in schizophrenics by molindone. The weight-reducing property of molindone, a recently introduced antipsychotic drug, was tested in 9 hospitalized chronic schizophrenic patients. There was an average weight loss of 7.6 kg after 3 months on molindone; most of the loss occurred during the first month. The mechanism producing this weight loss is uncertain, but a central anorexigenic effect may be an important factor.


Phenothiazine-induced bulbar palsy-like syndrome and sudden death. There have been periodic case reports of sudden death due to aspiration or asphyxiation in patients receiving phenothiazines. The mechanism of death is unknown. The author reports a case of a drug-induced bulbar palsy-like syndrome in a man receiving fluphenazine enanthate and reviews the literature on sudden respiratory death and phenothiazines. He postulates that phenothiazine-induced bulbar palsy may cause laryngeal and/or pharyngeal dysfunctions that are responsible for aspiration.


Angel's Trumpet psychosis: a central nervous system anticholinergic syndrome. The authors warn physicians that intoxication by Angel's Trumpet (Datura sauveolens) is becoming more frequent due to its use by adolescents and young adults as a legal, readily available hallucinogen. Ingestion of Angel's Trumpet flowers or a tea brewed from them results in an alkaloid-induced central nervous system anticholinergic syndrome characterized by symptoms such as fever, delirium, hallucinations, agitation, and persistent memory disturbances. Severe intoxication may cause flaccid paralysis, convulsions, and death. Treatment with intravenous physostigmine reverses the toxic effects of Angel's Trumpet.


Evaluation of the quality of psychiatric care for the aged. Older persons represent a high proportion of those receiving care in institutions because of behavioral problems; relatively few aged people are treated in mental health center and other outpatient settings. The author believes that the availability and accessibility of community services should be among the most important variables used in assessing quality of care for the aged. He encourages the establishment of new norms for the quality of services needed to restore and maintain maximum physical, psychological, and social integrity.


Substance abuse attitude changes in medical students. The authors describe a course in substance abuse given to sophomore medical students with the intention of positively influencing their attitudes toward substance-abusing patients and their treatment. Clinical problem solving and small group discussion were emphasized in addition to field trips. By pretest and posttest measures, significant positive changes were obtained in student attitudes: they reported feeling less upset when they encountered alcoholics, "hard" drug abusers, "soft" drug abusers, compulsive smokers, and obese overeaters as well as having a more positive view of the physician's role in the treatment of substance dependence. Personal experience with alcohol and other drugs was shown to have an influence on attitude changes.


Distinction between male and female invested partners in sexual disorders. Using the SCL-90, a self-administered symptom inventory, the authors evaluated 48 sexually asymptomatic male and female partners (invested partners) of sexually dysfunctional men and women. They found that the male invested partners showed significantly more psychological symptoms than the female invested partners but about the same symptom distress levels as sexually dysfunctional men. The authors hypothesize that the reason for this gender-specific difference in distress levels of invested partners is society's definition of the male's role as the responsibe partner regarding satisfaction in sexual relationships.


Attitudes toward parenting in dual-career families. The authors interviewed 28 dual-career families with young children and found that the wives and mothers in particular experience difficulties in respect to the proliferation of role demands in both home and job situations. The greatest strain was in the maternal role; guilt and anxiety were prominent. The literature is reviewed, techniques used by dual-career families to resolve role strain are discussed, and suggestions are made for the clinician's role as facilitator for reducing role strain among career mothers.


Group therapy with the terminally ill.

Group therapy with the terminally ill. The authors describe their four-year experience with a therapy group for patients with metastatic carcinoma. Patients in the group are helped by helping one another, by moving out of a morbid self-absorption, and by finding that they have much of value to share and to teach. The most important aspect of the group experience is the "presence" it offers; patients find support and the opportunity to express their needs and fears openly. The authors believe that group therapy is a valuable modality for the treatment of terminally ill patients and that much can be learned from such groups for the everyday therapy of the living.


Behavior therapy in a community mental health center. Behavioral principles offer an operational model for the services of a community mental health center. A demonstration and clinical research project adapted behavior analysis and therapy to the problems, patients, staff, and setting a typical comprehensive community mental health center. Innovations in the day hospital included a credit incentive system, educational workshops for community adaptation, and a goal-attainment method of planning and evaluating individual treatment. Behavior therapy was introduced for outpatients with anxiety and depression, marital conflict, and deficits in social skills. Consultation and education programs were established for parents, schools, and other community agencies. Experimental and evaluative research has documented the effectiveness of these programs.


Problems of Southeast Asian children in a refugee camp. The authors describe the efforts made to meet the mental health needs of Vietnamese children and their families in a large refugee camp. Many of the children received strong emotional support from the multigenerational Vietnamese families, and they adapted well to the new environment. However, children separated from their families demonstrated increased emotional vulnerability, and foster placement of children without families presented a serious problem. The authors suggest that our national commitment to these refugees may have ended when they left the confines of the refugee camp.


Boarding schools: effects on the mental health of Eskimo adolescents. Whether boarding schools undermine the mental health of Eskimo and Indian children has been a bitterly debated issue. The authors examined the effects of four representative boarding schools on 132 Alaskan Eskimo adolescents during their freshman and sophomore years. Forty-nine percent of the freshmen developed school-related social and emotional disturbances; 25% of these problems were judged serious. High levels of emotional disturbance were also found during the students' sophomore year. Although simple environmental changes may temporarily reduce the rate of disturbance among students, the long-term effects of boarding schools may still be deleterious.


Psychopathology and mental retardation: a statistical study of 100 mentally retarded children treated at a psychiatric clinic: II. hyperactivity. The authors studied 100 mentally retarded children referred to a psychiatric clinic and found that 39 were hyperactive. However, there was no significant relationship between hyperactivity and mental retardation (with or without psychosis) or brain damage. Comparison with a group of nonretarded children revealed no significant difference regarding hyperactivity, thus suggesting that the disorder is not an inevitable concomitant of mental retardation.


The ethics of practice in adolescent psychiatry. The author discusses ethical problems specific to practice with adolescents, a patient group which has special requirements in terms of their relations with authority figures and the kind and degree of external control they need. The psychiatrist who works with adolescents must be aware that his or her actions, attitudes, and personality can be crucial influences in the young person's development. Particular attention is needed in the areas of confidentiality, informed consent, and the impact of behavior control and other treatment techniques on adolescents.


Chromosome variants in children with psychiatric disorders. The authors studied the frequency of chromosome variants in 48 hospitalized children with psychiatric diagnoses (study group) in comparison with 10 hospitalized children with nonpsychiatric diagnoses (control group) and the results of three surveys of newborn children. They found that the frequency of variants in their study group was elevated in comparison with their control group and with the newborn surveys.


Postpsychotic depression and the need for personal significance. The author, who considers postpsychotic depression as a reaction to psychosis, illustrates some of the dynamics involved in the development and persistence of the state with letters from a patient. Among other dynamic and psychotherapeutic considerations, the need for self-realization and meaning in everyday life merits special emphasis in the treatment of those for whom escape from psychosis has meant not only  deliverance from terror, but also a loss of grandeur and significance.


Fatherhood and emotional illness.

Fatherhood and emotional illness. The authors describe four cases in which men developed emotional illnesses related to their wives' pregnancies. In all of the cases, the patients had experienced sibling rivalry at a significant time in their lives. This factor seemed to be more important dynamically in understanding their feelings about fatherhood than previously proposed factors, such as envy of the wife's childbearing capacity, dependence on the wife, and neurotic conflict with the oedipal father. The authors suggest that in men with neuroses, the issue of sibling rivalry is an important determinant of reactions to fatherhood.


Lawyers' use of psychiatry: II.

Lawyers' use of psychiatry: II. The authors surveyed 124 attorneys by mail questionnaires regarding their use of and attitudes toward psychiatric referrals. They found that, compared with a similar survey in 1965, fewer attorneys made referrals, but those who did made more. As in 1965, domestic problems were the usual reasons for referral in 1975; however, substantially more referrals of criminal defendants were made in 1975.


Genital exhibitionism in women.

Genital exhibitionism in women. Historically, genital exhibitionism has usually been regarded as an exclusively male phenomenon. The authors present a case study of a female exhibitionist which is at variance with that contention. They offer a formulation of the psychodymanics of female exhibitionism, focusing on its pregenital, attention-seeking purpose. The findings from this case justify a critical reexamination of the traditional definitions of exhibitionism.


The use of nicotine gum during cessation of smoking. The authors present three case studies which suggest that smoking withdrawal symptoms in certain individuals may be due to removal of nicotine per se, implying that smokers may develop a true physical dependence on cigarettes. Nicotine replacement by use of an experimental chewing gum containing nicotine in various dosages successfully prevented or alleviated the abstinence symptoms of the subjects studied.


Governmental peer review of training programs in child psychiatry. The authors present the results of a review of grant applications from 84 child psychiatry training programs that was conducted by the Psychiatry Education Branch of NIMH during fiscal year 1975. They found that training programs whose applications were approved were (among other things) university based and successful in filling training positions; they provided experiences in two or more treatment modalities in varied settings and with diverse types of patients, had active liaison with community organizations and with departments of pediatrics, and provided research opportunities for trainees.


Medical student education in psychiatry. The authors interpret data obtained from 99 medical schools which submitted grant applications for support of either undergraduate psychiatric education programs or human behavior programs. They tentatively conclude that high-quality programs for teaching medical students psychiatry are characterized by a well-rounded faculty, a psychodynamic orientation, a greater commitment to medical student education than to resident training, varied teaching methods, enthusiastic student response, and systematic evaluation that produces change in subsequent years.


Psychiatric education: state of the art, 1976. The authors describe an extraordinary review of 527 programs in 205 institutions conducted by the Psychiatry Education Branch of NIMH. Each institution was evaluated by 2 site visitors, whose findings were reviewed by a group of 12 special consultants. These consultants voted on approval of grant applications and assigned priorities to those which were approved. Direct results of the review included approval of 69% of the programs, increased support of programs in medical student education, consultation-liaison psychiatry, and psychiatric investigation, but a decrease in the total number of institutions supported. Indirect results were the encouragement of self-evaluation in each program reviewed, the valuable exchange of ideas among the educators involved in the review process, and implications for future reviews. The authors, who believe that psychiatric education is in good health, discuss the findings of this review in terms of the future of the field.


The educational challenge of consultation-liaison psychiatry. The authors examine issues related to quality of psychiatric consultation-liaison education programs on the basis of data from the fiscal year 1975 NIMH review of grant proposals for 71 such programs. This category received the lowest percentage of approval (31 approved, 40 disapproved), which is seen as a reflection of the state of development of the field. Although this is a difficult field in which to teach and practice, the authors feel that the numbers and quality of consultation-liaison programs will grow over the next 10 years and that the proliferation of training programs for primary care physicians and the return of psychiatry to the mainstream of medicine will facilitate this growth.


Research training in psychiatry.

Research training in psychiatry. The authors examined data on 13 requests for federal support for psychiatric research investigation that were evaluated as part of the NIMH review of psychiatric education grants in fiscal year 1975. Thirteen factors were found to be associated with quality of psychiatric research training, and the interaction and importance of these factors are illustrated in summaries of 5 programs. The ideal program is described as one in which there is a clearly stated concept, content that is broad and relevant enough to interest trainees in psychiatry, a continuing evaluation process, and superior research that can be documented. Adequate depth and breadth in terms of faculty and facilities are also essential. The authors believe that all psychiatrists should be encouraged to integrate scientific observation into their professional work and to evaluate systematically the effectiveness of their clinical interventions.


Characteristics of psychiatric residency programs and quality of education. As part of the fiscal year 1975 NIMH review of all psychiatric education grants, 144 basic residency training programs were thoroughly examined. In order to generate hypotheses about factors related to quality, the authors divided these grants into those given high priority rankings, those ranked in the middle, and those disapproved. Faculty and trainee characteristics, aspects of the service system, and organizational, educational, and evaluation factors were strongly related to quality. In general, good programs had a primary theoretical orientation with a tolerance for diversity, were not administratively responsible for community mental health centers but had strong community service ties, and tended to be in university settings. The authors point out the need to determine psychiatry's role vis-à-vis primary care and to develop a clear understanding of the place psychiatry will have in the health and mental health systems.


Relations between nutrition and cognition in rural Guatemala. The nutritional status of three and four year old children, as measured by height and head circumference, is related to cognitive performance in four rural Guatemalan villages. The relationships persist when social factors are taken into account. Families in two of the villages participate in a voluntary, high protein-calorie supplementation program. In the other two villages, the families receive a vitamin and mineral supplement with one-third of the calories. Although the longitudinal study still is ongoing there is some evidence that the children who receive the higher calorie supplement (or whose mothers received it during pregnancy and lactation) are most likely to score high in cognitive performance. The results support other animal and human studies that report an association between nutrition and cognitive development. The findings, while not diminishing social environmental explantions of differences in cognitive function, suggest the worth of nutrition intervention programs in rural areas of lesser-developed countries.


A computer-based record and clinical monitoring system for ambulatory care. The Regenstrief Medical Record system is a computer-based medical record system for ambulatory care which has been in operation since 1973. For each patient served, it contains a core medical record  including most objective data (treatment records, lab, x-ray and EKG, etc.) and selected items of subjective data. Its supports the care of patients by presenting the clinical data in clear and compact reports and by reminding the physician about clinical conditions that need corrective action. The generation of these computer reminders is totally controlled by physician authored protocols. Each protocol defines an important clinical condition and the content of the reminder to be triggered when that condition occurs. Physician compliance to the standards implicit in these protocols is improved by this feedback. Patient data are captured by computerized ancillary services, (laboratory and outpatient pharmacy) and by manual techniques. Much of these data are recorded by hand (as marks or numbers) on computer-tailored forms which can be optically read by machine. This system represents a different approach to the difficult problems of efficiently using and maintaining patient records.


Alcohol and motorcycle fatalities.

Alcohol and motorcycle fatalities. A series of 99 fatal motorcycle crashes in Maryland was studied retrospectively, using police and medical examiner records. Blood alcohol concentrations were determined for 62 motorcycle drivers; measurable amounts of alcohol were found in two-thirds (41), and one-half (31) had illegally high concentrations of 100 mg/100 ml or more. The police report mentioned alcohol in only 9 instances. High blood alcohol concentrations were found most commonly among drivers age 20-34.


The distribution of Naegleria fowleri in man-made thermal waters. The discharges of 16 thermal polluting factories were examined for the occurrence of Naegleria fowleri, the causative agent of primary amebic meningoencephalitis. Seven of these waters were shown to harbor this ameba. Of 22 N. fowleri isolates, 3 were highly virulent for mice when inoculated intranasally. The three pathogenic strains were isolated from three different places during summer. More N. fowleri were found during summer than in winter, which could be attributed to the lower temperature during winter. The distribution seems to be bound to the cooling waters of older factories and is not restricted to one type of factory. There are strong indications that the isolation of nonpathogenic seropositive strains from water is an indication for the occurrence of pathogenic N. fowleri.


Morbidity from Schistosoma mansoni in a Puerto Rican community: a population-based study. A population-based approach was used to investigate morbidity from Schistosoma mansoni in a rural community in eastern Puerto Rico that was representative of remaining endemic foci on the island. In 1974 the prevalence of infection 855 of 1,056 inhabitants was 32.7% and the geometric mean egg output was 17.6 eggs per gram. A standardized medical history was obtained, and physical and laboratory examinations were performed on 737 (70%) of the community residents. Quantitative S. mansoni egg counts were performed on 1 gram of feces with a modified Ritchie formol-ether concentration technique; other intestinal parasites were recorded on a semi-quantitative basis. Interviews and physical examinations were conducted "blind" to minimize observer bias, and statistical analysis was done on data from 149 infected subjects and 149 noninfected controls matched by age and sex. For subjects under 20 years of age the frequency of hookworm infection and trichuriasis and absolute eosinophilia was significantly higher in the infected group, but no difference was found in the frequency of signs and symptoms of schistosomiasis. For the subjects 20 years and over, the symptom "blood in the stool" was reported more frequently in the infected group, but hematocrit level did not differ between infected and noninfected controls. Although palpable livers were noted more frequently in infected (8) than in noninfected (1) subjects 20 years and over, further evaluation of these subjects cast doubt upon a causal role for S. mansoni. These data indicate that morbidity from S. mansoni infection in the community is low, a finding consistent with the apparent decline in S. mansoni morbidity in Puerto Rico during recent decades and the relatively low intensity of infection in this community. Nevertheless, because of the sporadic occurrence of S. mansoni-induced disease on the island, and because heavily infected subjects are clearly at greater risk of disease, we are recommending treatment for community residents with high egg output.


Mebendazole in the treatment of taeniasis solium and taeniasis saginata. A study was made of the effect on taeniasis of mebendazole, a drug known to be highly active against a variety of nematode species parasitic in humans. Thirty-seven patients infected with Taenia solium and four with Taenia saginata, some of whom had concomitant nematode infections, were treated with one of three dosages for 3 to 6 days. Within 48 hours of treatment most patients had eliminated long chains of intact, but apparently lifeless, proglottids. Assessment of results was made by monthly post-treatment observations for 4 to 5 months. The optimum effective dose of mebendazole appears to be 300 mg twice daily for 3 days.


Epidemiologic investigation of echinococcosis in American Indians living in Arizona and New Mexico. Ten cases of echinococcosis diagnosed in American Indians in Arizona and New Mexico between 1972 and 1975 were investigated as part of a regional epidemiologic study. Patients were visited at home to discover factors associated with local parasite transmission, to detect possible additional cases among family members, and to perform diagnostic tests on dogs. Six patients were Navajo, 2 Zuni, and 2 Santo Domingo Indians. An additional case in a Navajo man was detected by serologic testing of patients' family members; this was the 20th case diagnosed in the region since 1965. Dogs owned by three of the Navajo patients were infected with Echinococcus granulosus. Arecoline-purge testing of 110 dogs in the Zuni pueblo demonstrated echinococcosis in a single stray dog. The findings at slaughter of Navajo-owned sheep indicate that the infection is enzootic in this intermediate host. The epidemiologic findings suggest that humans were infected from dogs which contracted their infections from two sources. The first was sheep raised locally in rural areas of the Navajo Reservation where the infection is enzootic in the dog-sheep cycle; transmission was apparently facilitated by the widespread practice of home butchering. A second source of human infection was dogs which became infected by eating viscera of sheep of off-reservation origin; these sheep were purchased and butchered by individual families in urban areas of the Navajo Reservation and in the Zuni and Santo Domingo pueblos.


Acedapsone treatment of leprosy patients: response versus drug disposition. In 22 lepromatous Filipino patients receiving their first injection of 225 mg acedapsone (DADDS), dapsone (DDS), and monoacetyl DDS (MADDS) were present in plasma in approximately equal quantities. Peak levels of parent drug, DDS, and MADDS occurred between 22 and 35 days. The half-times of disappearance (T1/2) from plasma were 43 days for DDS and MADDS and 46 days for DADDS. Acetylator phenotyping with sulfamethazine (SMZ) and DDS showed that 17 patients were rapid and 5 patients were slow acetylators. Correlations between acetylation of SMZ and DDS after DDS and of acetylation of DDS after DDS and DADDS were highly significant. However, acetylation of DDS after DADDS did not differentiate the patients into acetylator phenotypes. The T1/2 of DDS after DDS in the patients was directly related to the minimum levels of DDS at 77 days after DADDS treatment. These minimum levels were 8-fold higher than the minimum inhibitory concentration (MIC) of DDS for Mycobacterium leprae in mice and rats, but not all patients responded satisfactorily. No relationship could be demonstrated between the bacteriologic response and any of the pharmacologic parameters examined in these Filipino patients. In a companion study, minimum levels of DADDS, MADDS, and DDS were determined in 447 leprosy patients of all disease types from the Karimui District of Papua New Guinea who had been receiving 225 mg DADDS every 70 to 80 days for the past 5 years. All patients exhibited DDS levels above the MIC of DDS for M. leprae, no significant differences in plasma sulfone levels were found among disease types, no relationship between rate of healing in paucibacillary patients and sulfone levels were found, and type of response in multibacillary patients and sulfone levels were unrelated. No substantial accumulation of the sulfones in the Karimui patients receiving continuous therapy with DADDS for 5 years was indicated from a comparison with the levels in the Filipino patients following a single injection of DADDS.


Occurrence of Histoplasma capsulatum Darling, 1906 in Israel, with a review of the current status of histoplasmosis in the Middle East. The isolation of Histoplasma capsulatum from a bat cave in the Galilee region of Israel is reported along with the discovery of a bat (Myotis myotis) infected by H. capsulatum. Soils collected in avian and chiropteran habitats throughout Israel also yielded the following fungi of medical interest: Arthroderma quadrifidum, A. tuberculatum, Candida parapsilosis, Chrysosporium indicum, C. keratinophilum, C. tropicum, Cryptococcus neoformans, Ctenomyces serratus, Microsporum gypseum, and Petriellidium boydii. All available reports concerning the occurrence of H. capsulatum and histoplasmosis in the Middle East are critically reviewed.


Rotaviruses in Venezuelan children with gastroenteritis. Rotaviruses were identified by electron microscopy in 19 of 26 (73%) Venezuelan children with gastroenteritis. Noncultivable adenoviruses and small (29-30 nm), spherical viruses were also observed in a few cases. Bacterial pathogens were isolated from five children (19%), all of whom were also carrying rotaviruses.


Analysis of the incidence of variola minor in an outbreak by use of a mathematical model. The incidence of variola minor during an outbreak was analyzed by use of mathematical model B proposed by Chelsky and Angulo. Several parameters were estimated. Among these, the propagating rate (ratio of receptor cases to source cases) seems to predict the outbreak decline better than inspection of the incidence curve. The estimated mean generation interval (18.6 days) supports the thesis that variola minor is not transmitted at onset of illness but, on the average, about 4 days later. The ratio of clinical to subclinical infections (about 1 to 1) approximates those ratios found in serological surveys of variola minor and variola major outbreaks.


Dientamoeba fragilis: a review with notes on its epidemiology, pathogenicity, mode of transmission, and diagnosis. Dientamoeba fragilis was found in 4.2% of approximately 43,000 individuals who submitted stools for parasitological examination during 1970 to 1974. The parasite was more frequently found in the younger age group (less than 20 years) than in older age groups, and more often in females than in males. Symptoms in 255 of patients in whom D. fragilis was the only parasite found and for whom detailed symptoms had been supplied, included: diarrhea, abdominal pains, anal pruritus, and loose stools. Analysis of mixed infections of D. fragilis with intestinal helminths suggests that such infections are random except for the combination of D. fragilis and Enterobius vermicularis. This combination occurred 9 times more often than theoretically expected. Daily periodicity and distribution of D. fragilis within stools of one patient were studied over a period of 6 months. More than twice as many organisms per ml of stool were present in the last than in the first portion evacuated. The total number of organisms excreted fluctuated markedly from day to day.


Search for subtype I strains of Venezuelan encephalitis virus among isolates from Trinidad, W.I., during 1960-1972. Twenty-one strains of Venezuelan encephalitis (VE) virus isolated from three habitats in Trinidad, W.I. during 1960 to 1972, were subtype III (Mucambo) VE virus by plaque-reduction neutralization tests. Like prototype Mucambo virus, each strain killed 8- to 15-week-old mice inoculated intraperitoneally. If the subtype I strain of VE virus that caused a major outbreak in Trinidad during 1943 to 1944 persisted on the island into the 1960s and early 1970s, it did not become the dominant VE virus in these three enzootic foci.


Prolonged western equine encephalitis viremia in the Texas tortoise (Gopherus berlandieri). Subcutaneous inoculation of 34 Texas tortoises (Gopherus berlandieri) with either of two strains of Western Equine Encephalitis (WEE) virus resulted in prolonged viremia of up to 105 days' duration. Peak viremia titers exceeded 10(6) suckling mouse intracranial lethal doses per milliliter. The length of the previremic period, the maximum viremia level attained, and the duration of viremia were markedly affected by environmental temperature. Higher temperatures (30 degrees C) shortened the previremic period and the duration of viremia and elevated the maximum viremia level. Lower temperatures had the opposite effect. Mechanisms are suggested whereby Texas tortoises could serve as an overwintering reservoir for WEE virus at any temperature. Neutralizing antibody was detectable following viremia in only 11 of 16 (69%) of surviving tortoises.


Difficult diagnosis of malaria.

Difficult diagnosis of malaria. Symptoms suggested malaria in a patient who had recently returned to the United States from Africa, but blood smears were persistently negative for malaria parasites. The diagnosis was established in an unusual way when a laboratory technician detected malaria parasites in a lupus erythematosus cell preparation.


Effect of Schistosoma mansoni infection on pentobarbital-induced sleeping-time in mice. The sleeping-time induced by sodium pentobarbital is greatly increased in mice experimentally infected with Schistosoma mansoni. The degree of hypnosis is affected by the female worm burden, probably because the hepatic lesions produced by schistosome eggs cause slow metabolisation of anesthetics.


Ultrastructure of the cyst of Giardia lamblia. An isolation technique involving filtration and discontinuous density gradient centrifugation was utilized for obtaining Giardia lamblia cysts from human feces. Highly concentrated preparations of cysts were examined by electron microscopy. The cyst of G. lamblia is surrounded by a moderately dense fibrous wall 0.3 mum thick. A thin layer of cytoplasm separates the cyst wall from electron lucid intracellular spaces located around the periphery of the cyst. Four nuclei are usually present. Basal bodies and axial filaments are located between the nuclei. Two sheets of microtubules are associated with the axial filaments. No mitochondria, endoplasmic reticulum, or Golgi apparatus is present. Parallel rows of microtubules with perpendicular ribbon-like structures are randomly distributed in the cytoplasm. Substructural units with a periodicity of 150 A are oriented perpendicularly to the longitudinal axis of the ribbons. The ribbon-like structures and associated microtubules represent disassembled portions of the sucking disc of the trophozoite form and apparently are reorganized into sucking disks upon division of the cyst organism.


Pulmonary capillariasis in a child in Iran. A 9-year-old boy in Teheran, Iran developed severe asthmatic symptoms, productive cough, and moderate eosinophilia. Lung biopsy demonstrated a helminth in a granulomatous lesion with foreign-body type cellular reaction leading to a tentative diagnosis of visceral larva migrans. Diethylcarbamazine, thiabendazole, and steroids were given, rapidly relieving the symptoms. In a subsequent review of the biopsy the helminth was identified as a Capillaria, probably Capillaria (Thominx) aerophila, a nematode parasite of dogs, cats, and other carnivores, apparently the ninth such infection to be reported in man.


Ocular angiostrongyliasis in Semarang, Central Java. A worm removed intact from the anterior chamber of the left eye of a 23-year-old woman from Central Java was identified as a mle Angiostrongylus cantonensis, 11.1 mm in length and 0.24 mm in maximum width. A useful degree of eye function was preserved. Five similar cases have been reported--three from Thailand, two from South Vietnam.


Post-prandial transportation and maintenance of Simulium ochraceum infected with Onchocerca volvulus. Simulium ochraceum females collected after feeding on subjects harboring Onchocerca volvulus were maintained and transported from Guatemala to California in small plastic tubes. Each tube had a perforated cap for entry of air, a wick as a reservoir for the nutrient solution (30% sucrose), a strip of filter paper for anchorage, and contained one fly. The tubes were kept in plastic boxes which, in turn, were maintained in portable coolers. Direct sunlight, heat and mechanical trauma easily killed the flies; moreover, loss of flies was also due to oversaturated wicks, high humidity in the plastic boxes, and loose tube caps. Approximately 70% of the captured flies could survive an 8-day period of captivity, and approximately 40% were still alive 11 days after capture.


Studies on schistosomal rectal and colonic polyposis. Anatomic and digestion studies were done on rectal and colonic schistosomal polyps from 30 patients. Results indicate that schistosomal colonic polyposis is principally due to high, localized egg burdens of Schistosoma mansoni or S. haematobium resulting in damage to the muscularis mucosa of the colon. Furthermore, atypically focal oviposition by S. mansoni is probably more important in genesis of rectocolonic polyposis than is schistosomiasis haematobium.


Schistosomal polyposis of the urinary bladder. Anatomic, clinical, and digestion analyses were done on 18 human urinary bladder polyps from patients with Schistosoma haematobium infections. Variations in histologic pattern conformed to stages in progression of the disease; most were from active cases with significant egg burdens. The data suggest that polypoid lesions of active schistosomiasis may persist as polyps in the inactive stage if antecedent active infection was heavy.


Schistosomal ulceration of the urinary bladder. Clinical, anatomic and digestion studies were done in 91 surgically treated cases of bladder ulceration in Egyptian patients with urinary schistosomiasis. Most patients were rural male farmers; their mean age was 29 years. Symptoms were similar to uncomplicated urinary schistosomiasis except for suprapubic or perineal pain. Two clinicopathologic entities were noted: 1) sloughing of polypoid patches in early active disease; and 2) chronic schistosomal ulceration of the bladder occurring at sites of very heavy Schistosoma haematobium egg burdens. The gross appearance, location, size and shape are described. The cost of treatment and duration of hospitalization are noted.


Surgical pathology of schistosomal obstructive uropathy: a clinicopathologic correlation. Schistosomal obstructive uropathy was studied by clinical, laboratory epidemiologic and pathologic analysis in 155 Egyptian patients treated surgically. Most patients were men; rural farmers or laborers. All had severe urinary schistosomiasis with heavy burdens of Schistosoma haematobium eggs in their urinary tracts. Schistosomal incomplete ureteral stenosis and schistosomal stenosis with ureterolithiasis were the most important obstructive lesions; these lesions were symmetrical and most frequent in the interstitial ureters decreasing proximally. The pathogenesis of these lesions is dependent upon focal destruction of ureteral muscle. The ureteral lesions proximal and consequent to schistosomal obstructive lesions are hydroureters resulting from active dilatation (due to increased hydrostatic pressure consequent to obstruction) and passive dilatation (due to loss of circular muscle action in sites of oviposition in the proximal ureter). Various combinations of these lesions with superimposed effects of bacterial infection and ureterolithiasis produce the spectrum of ureteral lesions attributable to urinary schistosomiasis.


[Multiple organic replacement in intensive care medicine seen from anaesthesiological view (author's transl)]. Additional effective methods have to be studied for in order to improve further the treatment of life threatening conditions which are accompanied by reversible breakdown of organic functions. The development and the recent state of different technical and biological replacement functions are presented and their advantages and disadvantages are described. Temporary multiple organic replacement (lung, kidney, liver) by way of peripheral vessels offers a therapeutic procedure capable of development. This procedure is based on the knowledge that in different endogenous and exogenous intoxications, and also after shock symptomatology generally, several vital functions are simultaneously disturbed or become acutely insufficient. This coincidental breakdown requires a simultaneous, effective, multilateral therapy. First partial successes by means of equipment for multiple organic replacement are critically analysed and conclusions for further improvement of its function are discussed.


[Effect of a preoperative separation of platelets on the postoperative blood loss subsequent to extracorporeal circulation in open heart surgery (author's transl)]. After operations with extracorporeal circulation there is a risk of clotting disorders, due to traumatisation of blood. The extent of cell damage are shown, in particular, by qualitative and quantitative impairment of platelet function. The clinical application of modern blood processors offer the possibility of selecting platelets from patients blood in the immediate preoperative period. Open heart operations were preceded by separation of platelets in 17 patients using a Haemonetics blood processor. After a postoperative retransfusion of the platelets an evident improvement in platelet function and a significant decrease in the predisposition to bleeding was demonstrated in the further postoperative period. During and after extracorporeal circulation the extent of microembolisation was registered by screen filtration pressure. In the clinical experiments, regularly, there is a significant increase of screen filtration pressure in the immediate postoperative period. These reactions were not seen in patients in whom preoperative separation of platelets was carried out. The most important clinical advantage of preoperative plateletpheresis consists in a significant decrease of postoperative blood loss. In particular the development of postperfusion lung will be prevented.


[Ophthalmodynamic findings during cardiac surgery with extracorporeal circulation (author's transl)]. Neurological disturbances were seen in patients who underwent open heart surgery with prolonged extracorporeal circulation. These were found mainly in patients older than 50 years and when episodes of hypotension lower than 50 mm Hg occurred during cardiopulmonary perfusion. A method of recognizing cerebral hypoperfusion would be most helpful to prevent brain damage. According to the experimental and clinical findings of Hager the method of ophthalmodynamography allows some conclusion of analogy in relation to the reaction of the brain vessels. The intraoperative ophthalmodynamogram was recorded in 8 patients undergoing surgery using extracorporeal circulation. The ophthalmodynamograms seen during surgery on the beating heart showed changes associated with surgical manipulation. When the arterial pressure fell the orbital pulsation was decreased. The orbital pulsation stopped when the spontaneous heat beat was replaced by extracorporeal circulation. There was no change attributable to the perfusion pressure produced by the roller pump. Cessation of the orbital oscilogram during extracorporeal circulation does not indicate a cerebral hypoperfusion. No neurological lesion was seen in our patients. We were able to show that amplitude of the ophthalmodynamogram is influenced more by the blood pressure amplitued than the mean arterial pressure.


[Changes of the blood gases following the application of naloxon (author's transl)]. 74 patients, undergoing gynaecological operations under neuroleptanesthesia were subdivided into 4 groups, each receiving Naloxone in different doses postoperatively. For a longer period of time tidal volume, respiratory rate, minute ventilation, blood gas volues and pain index were recorded. From the results one can conclude that 0.1-0.2 mg Naloxone i.v. seems to be the most effective dose to reverse opiate-induced respiratory depression. The initial i.v. dose should be followed by an i.m. dose of 0.2 mg, if required.


[Postoperative vomitting and gastroatonia following aorto-bifemoral bypass operations during halothane-combination anaesthesia and neuroleptanaesthesia (author's transl)]. 44 patients are analysed for the frequency of postoperative vomiting and the amount of gastroatonia following aorto-femoral bypass operations during neuroleptanaesthesia and halothane combination anasthesia. More than 60% of patients develop gastroatonia during both methods of anaesthesia. However it is less apparent on the first postoperative day after neuroleptanaesthesia and does not affect as many patients as after halothane combination anaesthesia. Postoperative vomiting is significantly more frequent after halothan combination anaesthesia than after neuroleptanaesthesia.


An index of cardiac output derived from the cardiopneumogram. The cardiopneumogram has been reinvestigated as an index of stroke volume and cardiac output in anaesthetized dogs. Using a water-filled oesophageal balloon to calibrate the system good correlations have been found between the values derived from dye dilution and the indices obtained from the cardiopneumogram.


Application of the new Australian standard for clinical lighting. A new Australian Standard "AS 1765-1975 Artificial Lighting for Clinical Observation" has recently been published. This specifies the quality of light necessary to accurately assess a patient's colour. The physical principles and terminology used in modern lighting are discussed, and the experimental work on which the new Standard is based is outlined. The only readily available fluorescent tubes which conform to the Standard are the imported Philips "TL40W/37" and the more efficient locally made "White Deluxe" tubes.


An evaluation of preoperative methods of preventing postoperative pulmonary complications. The effectiveness of three current regimes of preoperative respiratory care in reducing postoperative respiratory complications following herniorrhaphy was studied prospectively. No smoking for five days plus intensive physiotherapy, five days no smoking, and routine hospital admission two days preoperatively were the regimes. Clinical, bacteriological, chest X-ray, blood gas and respiratory function test data were the criteria for assessment. The same surgical and anaesthetic team performed each operation. No statistical difference between the groups for pulmonary complications was noted. A significant correlation was found between the preoperative vital capacity and arterial pO2; also between the preoperative forced expiratory volume in one second-vital capacity ratio with the postoperative arterial pO2.


Case report: anaesthesia in myotonic dystrophy. Pancuronium and a continuous infusion of althesin was used to produce muscular relaxation in a patient with myotonic dystrophy. Excellent muscle relaxation with absence of percussion or surgically induced myotonia was obtained but the EMG was not modified; an intracellular site of action of althesin is postulated. Cardiovascular stability was remarkable peroperatively; post-operatively an increased myocardial susceptibility to hypokalaemia was noticed.


Adsorption characteristics of volatile anesthetics on activated carbons and performance of carbon canisters. The adsorption characteristics, such as the adsorption capacity, the nature of the mass transfer zone, and heats of adsorption, are important for evaluating the performances of carbon canisters for removal of waste anesthetic vapors. The adsorption capacities and the natures of the mass transfer zones were measured for halothane, methoxyflurane, enflurane, isoflurane, and trichloroethylene on Witcarb 965 activated carbon. In addition, adsorption capacities and heats of adsorption for nitrous oxide, cyclopropane and oxygen were measured on the same carbon. The data indicate that high adsorption capacities of dilute anesthetic vapors on this activated carbon permit the use of carbon canisters for removal of these volatile anesthetics from mixtures with oxygen or nitrous oxide. In contrast, high concentrations of anesthetics such as nitrous oxide and cyclopropane cannot be removed economically by disposable canisters. A simplified procedure using the "characteristic curve" concept and "LUB/equilibrium section theory" for approximate prediction of the adsorption capacities and evaluation of the performance of a canister is outlined.


Urinary excretion of morphine during and after valvular and coronary-artery surgery. The urines of 34 patients anesthetized with morphine for mitral-valve or aortic-valve replacement operations or for coronary-artery disease revascularization procedures were analyzed for morphine and morphine-3-glucuronide before, during and for two hours after operation. Patients who had coronary-artery disease had higher urinary flow rates and excreted greater proportions of the administered morphine during induction of anesthesia, throughout operation, and for two hours postoperatively than patients with valvular heart disease. Correlation of total urinary output with total free morphine excreted after two hours in the recovery room was high, r = .84. Urinary morphine in the glucuronide form increased progressively from the time of induction of anesthesia to the postoperative period and was greater than 91 per cent for all patients after two hours in the recovery room. Patients who had coronary-artery disease required mechanical postoperative ventilation for significantly shorter periods than did those with valvular heart disease. The duration of postoperative ventilation was negatively correlated with total urinary output and total free morphine excreted in the urine from induction of anesthesia until two hours postoperatively (r = .80 and r = .77, respectively). The data demonstrate that urinary excretion of free morphine and morphine-3-glucuronide during and early after operation is greater in patients who have coronary-artery disease than in those with valvular heart disease. The findings also suggest that duration of mechanical ventilation after morphine anesthesia and operation is inversely related to urinary output and excretion of free morphine. (Key words: Analgesics, narcotic, morphine; Biotransformation (drug), morphine.)


Canine systemic and cerebral effects of hypotension induced by hemorrhage, trimethaphan, halothane, or nitroprusside. In 62 dogs, hypotension to a mean arterial pressure of either 40 or 50 torr (equivalent to a cerebral perfusion pressure of 30 or 40 torr, respectively) for one hour was induced by hemorrhage (oligemia), trimethaphan, halothane, or sodium nitroprusside. Before and during the period of hypotension, the following were measured: mean arterial blood pressure, cardiac output, whole-body O2 consumption, cerebral blood flow, cerebral O2 consumption, arterial blood gases, blood O2 content, and lactate, pyruvate, glucose, epinephrine, and norepinephrine concentrations. At the end of the period of hypotension, brain biopsies were taken for determination of adenosine triphosphate, phosphocreatine, lactate, and pyruvate concentrations. In an additional eight dogs following one hour of hypotension (at 40 torr) induced by one of the four techniques, the brains were perfused with carbon black, removed, and examined. In another ten dogs following hypotension (at 40 torr) induced with either halothane or trimethaphan, the animals were observed for three days and then killed for examination of the brain. Dogs maintained at a mean arterial pressure of 40 torr, despite differences in cerebral blood flow, demonstrated metabolic disturbances compatible with systemic and cerebral hypoxia. These were greatest in those dogs given nitroprusside in excess of 1.0 mg/kg, presumably due to cyanide toxicity. In dogs maintained at 50 torr, metabolic disturbances were minimal or absent in the halothane- and nitroprusside-treated dogs but were still apparent in the oligemic and trimethaphan-treated dogs. Carbon black infusions revealed no evidence of non-homogeneous flow. Three of the ten dogs observed for three days had persistent post-hypotension neurologic dysfunction. Two of these were given trimethaphan. The results suggest that the systemic and cerebral effects of halothane and nitroprusside (at doses less than 1.0 mg/kg) are similar and at a mean arterial pressure of 50 torr are of little consequence. By contrast, hypotension induced by trimethaphan or oligemia results in detectable metabolic alterations even at a pressure of 50 torr.


Cyanide release from sodium nitroprusside in the dog. Thirty-nine dogs (including eight from a previous study) were given during a one-hour infusion either low (less than 1.0 mg/kg) or high doses (greater than 1.0 mg/kg) of sodium nitroprusside in the presence or absence of circulating methemoglobin. In animals given low doses, the metabolic effects were relatively mild and consistent with those accounted for by a reduction in arterial pressure to 40 torr. In animals given high doses (with the same arterial pressure), metabolic alterations were significantly magnified and oxygen extraction was decreased. Animals pretreated with methemoglobin and given high doses of nitroprusside (again at the same arterial pressure) showed no toxic effect of nitroprusside. In separate studies, blood and tissue levels of cyanide were measured in dogs given high doses of nitroprusside (2.5-3.5 mg/kg) in the presence or absence of methemoglobin. In dogs given methemoglobin, 60 per cent of the administered cyanide (as nitroprusside) was recovered in the blood (as cyanmethemoglobin) after a one-hour infusion. Thereafter, blood cyanide levels declined over three hours to 25 per cent of peak levels, presumably by conversion to thiocyanate, since tissue levels of cyanide were negligible. In dogs not given methemoglobin, blood cyanide levels qualitatively followed a similar pattern but quantitatively were a fourth to a third those of pretreated dogs, and tissue levels of cyanide became elevated. It is concluded that in the dog nitroprusside, acutely administered, causes cyanide toxicity at doses exceeding 1.0-1.5 mg/kg, that the release of cyanide from nitroprusside in blood is rapid and in large quantities, that detoxification (presumably by conversion of cyanide to thiocyanate) is likewise fairly rapid but insufficient to prevent toxicity, and that protection is provided by methemoglobin.


Platelet function.

Platelet function. Basic knowledge regarding platelet physiology has been reviewed and related to clinical situations where platelet function is critically important. Platelet function tests such as aggregation and survival studies, which are research tools now, may soon be available to aid in the diagnosis and management of clinical bleeding problems. A growing understanding of drug-platelet interactions is allowing manipulation of platelets and the clotting system to improve the proganoses for patients who have thromboembolic diseases. Advances in platelet storage and transfusion techniques can save patients who previously might have bled to death. Proper application of the new developments in cardiopulmonary bypass and hemodilution, with attention to platelet and coagulation factor preservation, will contribute to securing hemostasis and conserving blood products.


Coronary vascular resistance during halothane anesthesia. To study the effect of halothane on the coronary circulation, the circumflex diastolic coronary vascular resistance was measured in the working heart and total mean coronary resistance (TCR) in the isolated nonworking heart of the dog during administration of 100 per cent oxygen and during administration of 2--3 per cent halothane in oxygen. In the working heart, when the diastolic aortic pressure was kept at a nearly control level, halothane induced decreases of 12 per cent in circumflex diastolic coronary vascular resistance and 18 per cent in left ventricular arteriovenous oxygen content difference and no significant change in diastolic coronary blood flow. This effect occurred in spite of the absence of any significant change of myocardial oxygen consumption. In the nonworking beating, arrested or fibrillating heart, halothane induced a decrease of 24 per cent in total mean coronary resistance. Since the decrease in circumflex diastolic coronary vascular resistance in the working heart connot be attributed to myocardial hypoxia and since the results in the isolated nonworking heart eliminate the influences of mechanical and neurohumoral factors on coronary resistance, it is concluded that the observed decrease in resistance is probably due to vasodilation produced by a direct action of halothane on the coronary vessels. This effect was not modified by beta-adrenergic blockade.


Pulmonary hemodynamics during induction of anesthesia. Changes in pulmonary hemodynamics and acid-base balance were recorded during induction of anesthesia using either intravenous administration of barbiturate (28 patients) or inhalation of N2O-O2-halothane (12 patients). The two types of induction resulted in equal elevations of pressures within the pulmonary circulation. The increase, proportional on the two sides of the heart, was most pronounced immediately before endotracheal intubation. Cardiac index decreased before and during intubation but subsequently increased to levels above control values. Systemic blood pressure increased more during barbiturate than during inhalation induction. Changes in acid-base balance were similar during the two types of induction: arterial blood PCO2 and PO2 increased, pH decreased, and standard bicarbonate remained unchanged. Changes in pulmonary arterial mean pressure and central venous pressure were correlated with changes in PACO2. Pulmonary capillary filtration pressure (i.e., pulmonary capillary wedge pressure minus plasma colloid osmotic pressure) was negative in every patient before anesthesia. During induction of anesthesia, filtration presures became positive in half the patients. Observed changes in circulation may have been caused by hypercapnia alone or by a combination of hypercapnia and vescular reflexes associated with instrumentation during intubation. The increased strain on the heart during induction of anesthesia may lead to cardiac failure in patients with diminished cardiac reserve.


Renal tubular site of action of fluoride in Fischer 344 rats. Methoxyflurane is capable of producing high-output renal failure in some patients and animal models, probably through metabolic liberation of free fluoride. The tubular site of action of fluoride was examined in Fischer 344 rats using clearance techniques. Free water reabsorption (TCH2O) and free water excretion (CH2O) were measured during mannitol or water diuresis in control rats and in rats given methoxyflurane or pretreated with sodium fluoride. Pretreatment produced statistically significant increases in urinary flow (from 10.5 +/- 1.4 to 20.1 +/- 1.9 mul/min/100 g b. wt.), in glomerular filtration rate (from 814 +/- 31 to 1,039 +/- 53 mul/min/100 g b. wt.), in per cent sodium excretion (from 0.107 +/- 0.008 to 0.155 +/- 0.015 per cent), and in per cent water excretion (from 1.27 +/- 0.15 to 2.00 +/- 0.20 per cent). Free water excretion remained relatively unaltered in rats pretreated with fluoride, perhaps due to elevated glomerular filtration rate and/or reduced proximal tubular reabsorption combined with inhibition of reabsorption in the ascending loop. Percentage free water reabsorption, on the other hand, was markedly reduced by the pretreatment, from 2.66 +/- 0.21 to 0.66 +/- 0.09 per cent. The observations are consistent with the hypothesis that fluoride inhibits tubular reabsorption primarily in the medullary portion of the ascending limb of Henle's loop, perhaps by inhibition of an active chloride pump located in this nephron segment.


Inorganic fluoride nephrotoxicity: prolonged enflurane and halothane anesthesia in volunteers. The effects of prolonged enflurane and halothane administration on urine-concentrating ability were determined in volunteers by examining their responses to vasopressin before anesthesia and on days 1 and 5 after anesthesia. A significant decrease in maximum urinary osmolality of 264 +/- 34 mOsm/kg (26 per cent of the preanesthetic value) was present on day 1 after enflurane anesthesia, whereas subjects anesthetized with halothane had a significant increase in maximum urinary osmolality of 120 +/- 44 mOsm/kg. Serum inorganic fluoride level peaked at 33.6 muM and remained above 20 muM for approximately 18 hours. Thus, the threshold level for inorganic fluoride nephrotoxicity is lower than previously suspected.


Contamination of medical gas and water pipelines in a new hospital building. Medical gases and water were sampled and tested for purity prior to the opening of a 176-bed addition to a 450-bed general hospital. Contamination was found. In delivered oxygen, compressed air, and nitrous oxide, this consisted of a volatile hydrocarbon at an initial concentration of 10 parts per million and a dust of fine gray particulate matter. In water from new taps bacterial contamination with as many 400,000 organisms per 100 ml was present. All these contaminants were considered potential hazards to patient safety. Studies were done to help delineate the nature and origin of these contaminants. Each contaminant was eventually largely eliminated by purging the respective pipeline systems with continuous flows. Planners, builders, and responsible medical personnel must be aware of the potential for such hazards in a new hospital building.


Hereditary complement defect and kinins involvement in asthma. Relationship between an inherited qualitative defect of the complement system and intrinsic asthma, and the direct participation of the kinin system in producing asthma, are reported. Qualitative complement impairment that produced hereditary angioedema in the son of an asthmatic father indicated that the kinin system was the vasoactive mediator in both cases.


Unreliability of maximum mid-expiratory flow rate as sole index of bronchodilator response in chronic asthma. Analysis of individual patterns of response to bronchodilation in asthmatics, rather than group averages, emphasizes the varying types of "asthma" as well as the need to examine all parameters of lung function when evaluating any new therapeutic agent. The often praised maximum mid-expiratory flow rate may be very misleading as a parameter of drug response.


A vascular test to detect iodide hypersensitivity (intolerance). Reliance upon conventional skin testing to detect hypersensitivity to iodides has proved unreliable. Present intravenous challenge methods often are inadequate and add an additional risk factor. This report describes an in vivo testing procedure that is safer because, other than for experimental corroboration of this method by direct iodide challenges, the use of non-iodide containing challenge material can be substituted to accurately detect possible iodide intolerance. Thus this procedure uses a parameter of measurement that does not require the eliciting of clinical symptoms by direct iodide challenge.


Value of delayed hypersensitivity index in patients with malignancy. A delayed hypersensitivity index can be obtained by standardized in vivo testing with available antigens. Recall antigens and DNCB to measure the afferent limb can be used to assess this important body function. The index is a valid indicator of cellular immunity, which is important as a dynamic indicator in many medical conditions and in treating patients with malignancy.


Hypersensitivity to tartrazine (FD&C Yellow No. 5) and other dyes and additives present in foods and pharmaceutical products. Tartrazine (FD&C Yellow No. 5) and other allowed certified color additives may have an exacerbating effect in chronic urticaria and asthma sufferers. In the individual patient the only way to determine their relevance is to administer test doses. By altering doses, timing and substances and by interspacing controls a battery of tests has been developed. Methods of testing for sensitization to food additives and analgesics are described.


Hageman complement and factor.

Hageman complement and factor. Complement components are activated by immunologic and non-immunologic mechanisms through various plasma protein systems such as immunoglobulins, properdin, plasmin, thrombin and Hageman factor. The activation of Hageman factor, followed by complement cleavage leading to liberation of various chemical mediators, can be initiated by exposure of negatively charged tissue components due to trauma and infection.


A search for species-specific antigens in the genus Penicillium. The immunological relationship between five different species of Penicillium was examined. Organisms included in the study were P. citrinum, P. chrysogenum, P. italicum, P. notatum and P. roqueforti. These species were selected because of their frequency in nature and their ability to grow on a wide variety of substrates. Antigen extracts were prepared by culturing each organism in synthetic media. Rabbit antisera tested against the various antigen extracts by immunodiffusion indicated a cross-reactivity between P. notatum and P. chrysogenum. No cross-reactivity between other species of Penicillium was detected.


RNA and protein components of maize streak and cassava latent viruses. Polyacrylamide gel electrophoresis indicated that maize streak (MSV) and cassava latent (CLV) viruses each contain one species of protein and two of RNA. The estimated protein mol. wt is 28000 for MSV and 34000 for CLV. The mol. wts obtained for the two RNA species using formamide-containing gels were the same for the two viruses: 1-7 X 10(6) and 1-3 X 10(6). It is suggested that the viruses have a two-part genome and that the tendency of their nucleoprotein particles to form pairs favours the delivery of complete genomes to sites of infection.


Autoanalysis of 14C-labelled amino acids: a simple flow cell technique. A description is given of a simple flow cell and modifications to an amino acid autoanalyser. These allow continuous monitoring of the 14C in effluent from chromatographic columns using a standard liquid scintillation counter.


Cell-mediated immune response to virulent and attenuated Anaplasma marginale administered to cattle in live and inactivated forms. The leukocyte migration-inhibition test (LMIT) and lymphocyte transformation of blood leukocytes from cattle exposed to virulent, attenuated, and inactivated preparations of Anaplasma marginale served as indices of cell-mediated immunity in bovine anaplasmosis. The LMIT response increased markedly in cattle vaccinated with attenuated A marginale or injected with virulent A marginale. Cattle inoculated with inactivated anaplasma developed a transient, low-level LMIT response. The response to antigenic stimulation recorded in the lymphocyte transformation test of leukocytes collected from cattle which were given live anaplasma was less than the response elicited from leukocytes collected from cattle vaccinated with inactivated anaplasma in adjuvant.


Effect of environmental temperature stress on intramammary infections of dairy cows and monitoring of body and intramammary temperatures by radiotelemetry. Four dairy cows were stressed by exposure to hot and cold environments in tests to determine the effect of environment on milk yield, somatic cell counts, and California mastitis test scores of milk from all mammary quarters and on bacterial counts of milk from infected quarters. Two cows were held in temperature-controlled rooms for successive 5-day periods at moderate (21 to 28 C), cold (-16 C), moderate, hot (36 to 37 C), and moderate environments. The cold and hot sequences were reversed for the other 2 cows. Temperature transmitters were surgically implanted in the skeletal muscles of the loin and gluteal regions; however, only one of these transmitters (gluteal region) functioned continuously throughout the experiment. At the end of this experiment, a transmitter was implanted in the gland cistern of a rear quarter of 1 cow, and the sequence of holding in the cold before the hot environment was used. Mean body temperature was approximately 1 degree higher (39.2 C) in the hot room (1 cow) and 3 to 4 degrees lower (35 C and 33 C), respectively, for 2 cows) in the cold room than that during the moderate temperature periods. A similar comparison showed that the mean intramammary temperature was 1 to 2 degrees higher (39.5 C) in the hot room and approximately 9 degrees lower (29.4 C) in the cold room. Exposure of the cows to hot and cold environments caused a greater loss in milk production in the 2 medium-yielding cows (23 to 28 kg/day) than in the 2 low-yielding cows (9 to 13 kg/day). The effect of the extreme temperatures on the somatic cell counts in uninfected quarters was limited to only a few quarters and was inconsistent (mean counts increased and decreased at both temperatures). The California mastitis test reactions showed no consistent changes during periods of heat and cold stress. Also, the effect of the environmental temperature on the intramammary infections also was inconsistent. The effect on bacterial counts appeared to vary with the type of organism. Some mean counts decreased in the heat and cold (Streptococcus agalactiae, Micrococcus sp), some increased (Pseudomonas sp), and another seemed independent (Streptococcus uberis) of the environmental temperature at which the cow was held.


Vaccination of dairy cattle against Q fever (Coxiella burneti): results of field trials. A phase I formalin-inactivated Q fever vaccine, using the Nine Mile strain of the organism, was tested for its ability to prevent dairy cows from shedding Coxiella burnetti in their milk. More than 1,400 Holstein-Friesian dairy calves and heifers from 5 dairies were used in field trials lasting over a 3-year period. Vaccination of 476 calves resulted in a geometric mean antibody titer of 1:123.3 compared with 1:2.4 for 486 nonvaccinated calves. The milk samples from 163 vaccinated calves were tested by mouse inoculation after the cows commenced lactation and were placed in their respective milking herds. Of these vaccinated animals, only 2 cows (1%) from 1 herd were suspected shedders, but on subsequent testing gave negative results. Among 164 nonvaccinated (control) cows, 39 (24%) were shedding C burnetii in their milk; this figure corresponded to the prevalence (23%) of shedders in the general population of dairy cows in California. The results of the current field trials indicated that vaccination greatly reduced the shedding of the Q fever organism in the milk of dairy cows.


Evaluation of xylazine and ketamine hydrochloride for anesthesia in horses. The cardiopulmonary effects resulting from the combination of xylazine and ketamine hydrochloride were evaluated in the adult horse. Xylazine (1.1 mg mg/kg) administered intravenously prior to or simultaneously with ketamine hydrochloride (2.2 mg/kg; intravenous) provided excellent analgesia and light anesthesia in all horses. Cardiac output, arterial blood pressure, pulmonary arterial pressure, central venous pressure, and pulmonary arterial wedge pressure remained within normal limits for the adult horse. Evidence of respiratory acidosis developed with time during the anesthetic period. Induction and recovery from anesthesia appeared smooth and excitement-free. In the horse, larger dosages of ketamine hydrochloride (6.6 mg/kg) following sedation with xylazine (1.1 mg/kg; intravenous) were accompanied by muscular tremor and rigidity, mydriasis, oculogyric movements, sweating, hypertension, tachycardia, and increased rectal temperature during recovery from anesthesia. Providing there is good sedation from xylazine, the combination of xylazine and ketamine hydrochloride as a short-term intravenous anesthetic technique in the horse appears safe and acceptable providing reasonably stable cardiopulmonary function. If the sedative properties of xylazine are not apparent or if excessive dosages of ketamine hydrochloride are used, the drug combination results in serious side effects precluding its use for anesthesia in the horse.


Functional aspects of blood platelets in irradiated burros. In irradiated burros (Equus asinus), a delayed clinical syndrome characterized by a depletion of megakaryocytes and platelets has been observed. To clarify the cause of this syndrome, the functional abilities of platelets in 7 irradiated and 3 control burros were studied in vitro. The irradiated burros were survivors (greater than 18 years) of total-body exposures to near-lethal doses of gamma-radiation. Burro platelet aggregability induced with adenosine diphosphate and thrombin, and with a complex stimulator from burro aortas, was determined by means of a self-calibrating aggregometer. Data indicate that the aggregation responsiveness to adenosine diphosphate and thrombin of platelets from surviving irradiated and unirradiated burros is not defective. An extractible collagen-like stimulator of platelet aggregation was discovered in the aorta of a burro that had survived greater than 24 years after exposure to a total-body dose of 545 roentgens (R) of tantalum-182 gamma-radiation. The platelet-aggregating ability of this stimulator from the vessel wall of the irradiated burro was nearly fourfold greater than that from the aorta of an unirradiated control. Perhaps a delayed radiation effect could be the cause of this vascular agent's high platelet-aggregating ability and could lead to a clinical syndrome marked by depletion of megakaryocytes and platelets.


Ultrastructural renal lesions in goats given a lethal dose of imidocarb diproprionate. Ultrastructural renal lesions were studied in 20 goats given one intramuscular injection of a lethal dose of imidocarb diproprionate (6.75 mg/kg). The lesions were limited to proximal convoluted tubular epithelial cells and at postinjection (PI) hour 3 included: plasma membrane disruption, smooth endoplasmic reticulum proliferation and dilatation, swelling and increased electron density of mitochondria, and cytoplasmic ground substance rarefaction. At PI hour 12, disruption of plasma membranes, with fragmentation of the microvilli, loss of junctional complexes, and cellular detachments from in tact basement membranes were observed in many tubular epithelial cells. Mitochondrial configurational alterations became more prominent at 6 and 12 hours, with the formation of large membrane-bounded structures containing fragmented cristae, clear vacuoles, and amorphous matrical material. The intramitochondrial foci of electron-dense amorphous flocculent material, which was first observed at 6 hours and increased in electron density and in number by 12 and 24 hours, were probably comprised of denatured, clumped matrical protein. The 2nd type of intramitochondrial and cytoplasmic electron-dense deposit was observed PI hour 24. The basement membranes remained intact in most proximal tubules to support regenerating epithelial cells on PI day 4 and thereafter.


Cyanide intoxication in sheep: therapeutic value of oxygen or cobalt. The combination of cobalt salts and oxygen with the traditional sodium nitrite-sodium thiosulfate antidote may have value as cyanide antidotes. Results reported previously in mice were extended to sheep in the present experiments. Cobaltous chloride (15 mg/kg of body weight) or oxygen with or without sodium nitrite and sodium thiosulfate were compared with respect to the median lethal dose of oral sodium cyanide. Although cobaltous chloride or oxygen used alone did result in a significant increase in the median lethal dose of sodium cyanide in sheep, the protection was minor compared with the overall protection provided by the classic antidotal combination of sodium nitrite and sodium thiosulfate. Cobaltous chloride combined with sodium nitrite and sodium thiosulfate did not provide any increase in protection more than that observed with sodium nitrite and sodium thiosulfate alone. Oxygen used in combination with sodium nitrite and sodium thiosulfate did significantly increase the protection. However, the increase in protection was not of sufficient magnitude to recommend it as a practicable addition to the present therapeutic regimen.


A genetic study of canine hip dysplasia. Using scores taken from pelvic radiographs of 1,186 German Shepherd Dogs, heritability estimates of canine hip dysplasia (CHD) were obtained. As measured by either of 2 scores defined, CHD was found to be 22.0% heritable. In this colony, CHD was a moderately heritable condition. To make progress in selecting against CHD, use of the progeny test to identify superior replacement breeders was stressed.


Development of microagglutination test for detecting Arizona hinshawii 7:1,7,8 infection in turkeys. A microagglutination antigen treated with tetrazolium dye was produced. The culture used was rendered nonmotile by growing in medium containing 1:1,000 concentration of phenol. A trial was conducted by infecting freshly hatched turkey poults with Arizona hinshawii 7:1,7,8. An equal number of poults were kept as negative controls. Starting with 4-week-old poults, blood samples, cloacal swabs, and environmental samples were obtained at 2-week intervals up to 16 weeks of age. The serum samples were tested by using tubeagglutination (TA), serum plate agglutination (SPA), and microagglutination (MA) tests for A hinshawii 7:1,7,8. A field trial was conducted, using known negative and infected turkey flocks, and serum samples were tested by MA, SPA, and TA tests. The results indicated that MA test was far more sensitive and superior to TA and SPA tests in detecting turkeys infected with A hinshawii 7:1,7,8. The field trial confirmed the laboratory trial observations.


Determination of total and ultrafilterable calcium and magnesium in normal equine serum. Total and ultrafilterable calcium (Ca) and magnesium (Mg) values were determined for Shetland pony stallions, stallions, and pregnant and diestrous mares, using a simple, inexpensive, quick procedure to obtain an ultrafiltrate of serum. There was no significant difference between horses and ponies, between stallions and mares, or between pregnant and nonpregnant mares. The percentage of total serum Ca that was ultrafilterable was 63.4+/-1.7 for horses and 64.8+/-2.2 for ponies. The percentage of total serum Mg that was ultrafilterable was 75.6+/-1.5 for horses and 77.0+/-1.7 for ponies. Total serum Ca was 12.56+/-0.26 mg/dl for horses and 12.43+/-0.32 mg/dl for ponies. Total serum Mg was 2.18+/-0.29 mg/dl for horses and 2.49+/-0.60 mg/dl for ponies. This technique can be coupled with specific assays for ionized forms of the cations or with ion electrodes to obtain values for protein-bound, ionized, or complexed and chelated Ca and Mg in equine serum.


Microembolization of the inner ear of the cat: a surgical technique. A surgical technique for the microembolization of the inner ear of the cat is described, and photomicrographs of representative central neural areas and end organ structures are presented.


A pharmacokinetic analysis of tylosin in the normal dog. Studies were conducted to determine certain kinetic variables for tylosin in the normal dog. These variables were determined by pharmacokinetic analysis, measuring the decrease in serum concentration of tylosin activity in 3 separate experiments. Tylosin, given as a single intravenous dose of 10 mg of tylosin activity/kg of body weight, was calculated to have an elimination half life (t1/2beta) of 54 minutes and was no longer detectable in the serum by assay methods at about 270 minutes. In addition, tylosin appeared to be highly distributed with an apparent volume of distribution of about 1.7 L/kg and a tissue-to-plasma ratio of about 0.7. The body clearance of tylosin was calculated to be about 22 ml/kg minute. A separate multiple-dose intravenous experiment with the same dose per injection was conducted and showed similar results. Also, single intramuscular injection of 10 mg of tylosin activity/kg showed tylosin to peak after injection in the serum at 30 minutes, attaining a concentration of approximately 1.5 mug/ml. This concentration was maintained through 60 minutes and decreased slowly through 540 minutes. Data generated through 17 clinical cases indicated that the minimum inhibitory concentration for tylosin in Pasteurella spp tested was about 6.25 mcs/ml and for hemolytic Staphylococcus spp tested greater than or equal to 0.4 mug/ml. Thus, it would appear that tylosin, given at the recommended dose (6.6 to 11.0 mg tylosin activity/kg of body weight once or twice per day), would produce serum levels insufficient to treat all Pasteurella spp and some hemolytic Staphylococcus spp tested since a serum level of tylosin at slightly higher than 1 mug/ml for about 30 minutes was achieved in this study.


Rat bioassay for estimating toxicity of plant material from larkspur (Delphinium sp). A technique was developed for estimating the toxicity for rats of an alcoholic extraction product from larkspur (Delphinium barbeyi Huth). The dried residue from alcohol extraction was reconstituted in buffered saline solution and subcutaneously injected into rats. Toxicity was expressed as miligrams of dry plant per gram of body weight. Samples from D barbeyi collected during prebloom and early flower bud stages of growth produced median lethal doses ranging from 5.0 to 6.7 mg/g of body weight. Difference in toxicity of the extract due to age of rats was not significant.


New method for determining eye anesthesia in an animal model. Some chemical which are injurious to the eye may also cause anesthesia. If the eye were unknowingly anesthetized, exposure to an irritant could go undected and cause injury. Techniques for determining whether the eye was anesthetized have been generally unreliable. Usually the technique consists of challenging the cornea with a probe and testing for a blink response. In a new method described herein, an indwelling subpalpebral lavage apparatus was surgically implanted in the dog. Through this apparatus, a test material was instilled into the eye without the animal's anticipation. Responses caused by the materials were monitored by electroencephalography. The normal response to an irritting material was increased frequency and decreased amplitude of the electroencephalogram tracing or a deflection of thepolygraph needle (blink response), or both. The method was evaluated with known eye anesthetic agents and appeared to be a useful way of detecting eye anesthesia.


En bloc thoracotomy in miniature swine.

En bloc thoracotomy in miniature swine. A radical thoractomy technique was developed and used in 4 miniature swine. It provided excellent exposure no postoperative complications.


Quantitative relationships between cigarette smoking and ventilatory function. In this study of a general population sample, highly significant quantitative relationships were noted between pack-years of smoking and functional impairment. Subjects with chronic productive cough showed steeper declines in the forced expired volume in 1 sec and forced expiratory flow after exhalation of 75 per cent of the forced vital capacity (Vmax 25), but a definite inverse relationship between ventilatory function and pack-years was demonstrated even among subjects who denied any cough or sputum production. Current smoking showed no relationship to 1-sec forced expiratory volume or Vmax 25 when total pack-years were taken into account. Age appeared to be an important independent determinant of per cent predicted values only in regard to the Vmax 25 in symptomatic nonsmoking women. A history of childhood respiratory trouble was associated with a lower ventilatory function regardless of smoking habits, and for this reason such subjects have been deleted from detailed analyses of dose-effect relationships. Allergy skin test reactivity in young to middle-aged adults showed a significant additive effect to pack-years as a determinant of forced expiratory flow toward the end of the forced vital capacity, but the effect was noted only among present smokers.


Trephine air drill, bronchial brush, and fiberoptic transbronchial lung biopsies in immunosuppressed patients. Seventy-nine nonthoracotomy lung and bronchial biopsy procedures were performed in 52 immunosuppressed patients: 22 renal transplants, 24 lymphoreticular malignancies, and 6 other disorders. The total diagnostic yield was 74 per cent (23 of 31) of the forcepts transbronchial biopsy procedures, 82 per cent (14 of 17) of the percutaneous trephine lung biopsies, and 28 per cent (9 of 31) of the bronchial brush biopsies. An etiologic diagnosis, including a variety of viral fungal, and parasitic diseases, was obtained in 42 per cent (13 of 31) of the transbronchial biopsy procedures and 65 per cent (11 of 17) of the percutaneous trephine lung biopsies. The etiologic diagnostic yield was increased to 48 per cent when bronchial brushing was combined with forceps transbronchial biopsy. Hemorrhage complicated 26 per cent of the transbronchial biopsy procedures and 17 per cent of the percutaneous trephine biopsies, whereas pneumothorax occurred in 19 per cent and 60 per cent, respectively. Hemorrhagic complications in patients undergoing transbronchial biopsy occurred 3 times as frequently among the uremic patients (5 of 11, 45 per cent) as among the nonazotemic patients (3 of 20, 15 per cent). Patients with thrombocytopenia, when corrected by platelet infusion, presented no increased risk. Of the 52 patients, 19 (36 per cent) died 2 to 60 days after biopsy, but no fatalities were related per se to the biopsy procedure.


Rifampim-combined chemotherapy in coal worker's pneumoconio-tuberculosis. Results of a retrospective study of rifampin-combined chemotherapy in 59 coal miners with pneumoconio-tuberculosis are reported. In 43 patients pneumoconiosis had attained the stage of progressive massive fibrosis. The follow-up period ranged from 24 to 78 months, except in 8 patients who died before the twenty-fourth month. Twenty-seven of the 59 patients were treated for the first time, and 32 were in retreatment. In none of them had rifampin been administered before. Although the objective was to administer rifampin in combination with one, 2, or even 3 companion drugs that had not been administered before and that had proved to be active on the patients' bacilli in vitro, this goal was fully reached only in the first treatment group; in 8 of the 32 retreated patients the drugs combined with rifampin were considered ineffective. The speed and rate of bacteriologic conversion were most impressive. Sputum conversion was obtained in 90 per cent of the patients; in the initial treatment group 100 per cent of the patients converted their sputum on culture at 5 months and in the retreatment group the corresponding figure was 84.4 per cent. These bacteriologic results are nearly as favorable as those obtained in cases of advanced pulmonary tuberculosis without pneumoconiosis treated with the same rifampin-containing drug regimens. It was concluded that rifampin-combined chemotherapy largely eliminates the handicap caused by the coexistence of tuberculosis and pneumoconiosis. Side effects due to rifampin were without practical significance. In 3 patients of 57 treated with ethambutol, visual impairment was observed. Mortality was high (27 per cent) but was caused by nontuberculous diseases, especially cardiorespiratory insufficiency. In 10 of the 16 patients who died, death occurred after bacteriologic conversion.


Pulmonary arteriovenous fistulas: increase in shunt at high lung volume. Intrapulmonary shunt measured in the sitting position by the oxygen breathing method increased at total lung capacity in 7 of 8 patients with pulmonary arteriovenous fistulas. This may explain the clinically noted increased murmur over a fistula on inspiration. The finding of an increased intrapulmonary shunt at total lung capacity might suggest the diagnosis in equivocal cases and provide a convenient test for follow-up after surgery.


Lipid composition of airway secretions from patients with asthma and patients with cystic fibrosis. Lipids from the particulate material obtained from pulmonary lavage of patients with asthma and cystic fibrosis were isolated and characterized. In both cases, lipids constituted 30 to 40 per cent of the dry insoluble material and phosphatidylcholine was the predominant lipid. Significant amounts of phosphatidylethanolamine and phosphatidyglycerol were present. Hexosyl ceramides, spingomyelin, phosphatidylinositol, phosphatidylserine, and lyso(bis)phosphatidic acid were present as minor lipid components. Appreciable quantities of neutral lipids were also found. Significant amounts of lysophosphatides and free fatty acids were present only in the lavage sediment from patients with asthma, and not in patients with cystic fibrosis. Phosphatidylcholine, lysophosphatidycholine, sphingomyelin, and phosphatidylglycerol of asthmatic lavage, but not cystic lavage, were highly saturated, containing mostly palmitic acid.


Study of the pulmonary circulation in a canine asthma model. Measurements of respiratory mechanics, gas exchange, and pulmonary hemodynamics were made before and serially for 2 hours after inhalation challenge with Ascaris suum extract in dogs with natural sensitivity to this antigen. Nine of 14 dogs randomly exposed to an inspired oxygen fraction of 0.21 or 0.60 to 0.70, responded to the challenge with bronchospasm reflected by a transient decrease of mean specific respiratory system conductance to 50 per cent of baseline after 5 to 15 min. This was accompanied by a decrease in alveolar ventilation in all and acidosis in some animals. No changes were observed in transmural pulmonary arterial pressure, cardiac output, pulmonary vascular resistance, and pulmonary blood volume in all 9 dogs who responded with bronchospasm, whether or not arterial hypoxemia was allowed to develop. In contrast, a significant increase in pulmonary vascular resistance occurred in control dogs in whom comparable degrees of arterial hypoxemia were produced by 10 per cent oxygen breathing or mechanical bronchial obstruction by placing beads in lobar and segmental airways. No changes in any parameter measured occurred in the 5 dogs who did not develop bronchospasm after antigen challenge. The results indicated that moderately severe, antigen-induced bronchospasm in anesthetized dogs has no effect on the pulmonary circulation even when associated with arterial hypoxemia. Because nonuniformity of alveolar hypoxia allowing redistribution of blood flow is probably not responsible for this failure to develop increases in pulmonary vascular resistance in induced asthma, it is suggested that the elaboration of chemical mediators may have interfered with the hypoxic pulmonary vasoconstrictor response.


Effect of influenza viral infection on the ingestion and killing of bacteria by alveolar macrophages. In experimental animals, influenza prediposes the lung to superinfection by reducing the antibacterial efficiency of the alveolar macrophage system. Because such defects may represent abnormalities in ingestion or inactivation of inhaled bacteria, these subcomponents of phagocytosis were tested in mice infected 5 days previously with influenza A virus (NWS or WSN). The mice were exposed to aerosols of Staphylococcus epidermidis and then the rates of bacterial inactivation and percentages of intracellularly located staphylococci were measured. Rates of bacterial inactivation were determined for the left lung by pour-plate enumeration methods. The percentage of ingested bacteria was determined in the in situ perfused right lung by histologically determining the intra- or extracellular location of 100 or more staphylococci. Rates of inactivation of S. epidermidis at 4 hours after bacterial challenge were: control, 90.1 per cent; WSN, 73.0 per cent; NWS, 68.6 per cent, P less than 0.01. The percentage of intracellular staphylococci at 4 hours were: control, 90.9 per cent; WSN, 69.9 per cent; and NWS, 73.8 per cent, P less than 0.01. Microcolonies of proliferating staphylococci were also observed within macrophages of mice infected with each strain of influenza. These experiments demonstrated that in this experimental model, influenzal infection impairs the inactivation of inhaled bacteria by retarding the ingestion of bacteria and by allowing bacteria to proliferate within macrophages.