Women's workload and its impact on their health and nutritional status. This paper highlights various issues in relation to the workload of women in developing countries and its impact on health and nutritional status. The determining factors in women's workload and work-time and the methods employed for assessment are described. The drawbacks of the methods used and the resulting inconsistencies in the data are reviewed. How women are subjected to different health stresses owing to their productive and reproductive roles has been examined under three categories of work: economic, domestic and agricultural. The interaction of women's workload and health is complex and multifactorial owing to variations in the environment and socio-economic conditions within developing countries. There is a critical need to re-examine the assumptions existing about women's workload in programmes aimed at reducing work-time and workload of women in developing countries.


Host-microflora correlations in infant nutrition. The intestinal microflora represents an enormous cell mass and has a high metabolic capacity. The symbiotic efficacy of these microbes in humans is still a matter of discussion. Of particular interest, from a biogenetic point of view, are potential symbiotic relations between the bifidobacterial microflora and the breast-fed infant. Our group has conducted studies related to this topic; they were aimed at determining the dimension of microbial assimilation by the host. Our studies with 15N-labeled bifidobacteria have shown that the bifidobacterial microflora is capable of upgrading nonessential nitrogen such as urea nitrogen for the synthesis of microbial protein. Oral single pulse labelings with 15N-labeled bifidobacteria were absorbed to approximately 90% and retained in the infant's protein pool to approximately 70%. These findings demonstrate the high intensity of the substrate flow from the microflora to the host. This might become important under conditions of marginal food protein intake or during periods of accelerated growth.


[Effectiveness of correcting radiation injuries of the thymic endocrine function by T-activin in conditions of reduced postradiation hypercorticism reaction]. T-activin administered to rats after exposure to whole-body 1.5 Gy neutron- and 6 Gy X-radiation increases considerably the thymosin-like serum activity, accelerates cellularity restoration in the thymus and spleen, but does not influence the survival rate. Ionol administered prior to X-irradiation reduces the postirradiation hypercorticism reaction and the indirect effect of radiation on lymphoid organs which it is responsible for. The combined injection of ionol and T-activin increases the thymosin-like serum activity and spleen cellularity to the highest possible level and increases the survival rate of rats from 24 to 64 per cent and the lifespan up to 6 days.


Selective changes in mouse behavioral development after prenatal benzodiazepine exposure: a progress report. 1. Animal studies of the effects of early exposure to CNS agents devoid of a major teratogenic potential must assess possible deviations from normal behavioral development in both a stage-specific and a behavior-specific fashion; several experiments on prenatal benzodiazepine (BDZ) exposure are reviewed, illustrating such an assessment strategy and discussing caveats on experimental designs and statistical analysis. 2. The offspring of mouse dams treated in late pregnancy with oxazepam (15 mg/kg p.o. twice daily on days 12-16) show a mild and reversible impairment in somatic and neurobehavioral development which is unlikely to be responsible for a series of other more specific changes. 3. The treatment produces a selective reduction of locomotor activity and amphetamine hyperactivity at the end of the second postnatal week, as well as a selective impairment of active avoidance at the young adult stage, in the absence of similar changes in scopolamine hyperactivity and passive avoidance. 4. The treatment also prevents the appearance at 28 days of morphine hyperactivity and of rebound hyperactivity after muscimol depression, without modifying the developmental profile of pain reactivity and of morphine and muscimol analgesia. 5. Young adult females previously exposed to oxazepam in utero show a marked enhancement of maternal aggression towards male intruders; mother-pup interactions are also modified, leading either to reduced or to exaggerated maternal care as a function of fostering procedures. 6. Overall, several effects of prenatal BDZ exposure appear to be amenable to modifications in monoaminergic system functions and/or to an accelerated development of GABAergic mechanisms; some of the changes in social and parental interactions, however, point to subtle modifications in the balance between different components of the fear-defensive repertoire, possibly due to an altered stimulus reactivity by mechanisms which are still poorly understood.


[State of cellular immunity effectors of the lung after inhalation of 239Pu polymer nitrate]. Wistar rats, who inhaled 239Pu (IV) at a dose that did not reduce the average life expectancy (the initial level in the lung was 0.77 kBq) did not exhibit any essential changes in the quality and functional activity of the alveolar macrophages. Revealed were the injuries to cells of bifurcation lymph nodes, the severity of which was a function of dose absorbed in the lung.


Do biochemical factors play a part in postnatal depression? 1. There are major changes in progesterone, oestrogen, cortisol and beta-endorphin level associated with parturition, and as all these can be psychoactive it is likely that they contribute to the mood changes that can occur at this time. However evidence for their involvement is, at present, indirect. 2. Postnatal depression itself appears to be a heterogeneous condition with different times of onset, and it is probable that various biological and social factors play a role to a differing degree in different individuals. 3. About half of postnatal depression appears to arise in the first two weeks after childbirth. Some cases follow a period of early euphoria. 4. A different subgroup is associated with thyroid dysfunction, which peaks two to five months postpartum. 5. The tyramine test does not predict vulnerability to postnatal depression. 6. It is suggested that in future research the time course of onset of the depression, and the nature of the mood changes that occur in the first postpartum week, are investigated as possibly relevant variables.


Neuroendocrine markers of serotonin responsivity in depression. 1. Studies of the biochemical mechanism of action of antidepressant drugs show that virtually all drugs, regardless of acute biochemical effects, result in the down regulation of CNS beta-1 adrenergic, serotonin-2 (5HT2), and perhaps 5HT1A receptors in rats in a time course which parallels the onset of antidepressant action in patients with major depressive disorder. 2. Recently, neuroendocrine techniques have been described which allow the study of 5HT receptor subtypes in man. These include fenfluramine-induced changes in ACTH, cortisol and prolactin secretion (perhaps for 5HT2 receptors) and ipsapirone-induced changes in ACTH and cortisol (for 5HT1A receptors). 3. Depressed subjects treated with antidepressants down regulate these markers of both 5HT2 and 5HT1A receptors in a time course consistent with their recovery from depression. 4. Studies in progress are attempting to demonstrate links between these receptor changes and clinical antidepressant responses.


Efficacy and tolerability of flupenthixol decanoate in the treatment of depression and psychosomatic disorders: a multicenter trial in general practice. 1. A number of controlled as well as uncontrolled studies indicate that flupenthixol in a low-dose regimen is effective in treating syndromes with depression, anxiety, and psychosomatic disorders. 2. In view of the low compliance rates among patients suffering from depressive syndromes, the author evaluated the efficacy and tolerability of flupenthixol decanoate i.m. in an unselected collective of such patients treated in general practices. 3. Flupenthixol decanoate i.m. induced remission in 25% of patients suffering from chronic pain, in 29% of patients with psychosomatic disorders. Patients with depression and anxiety remitted in 27% of the cases. Therapeutic benefit was seen in more than 90% of the patients. 4. The best results were observed in patients 1) who had not been treated with psychotropic drugs before, 2) whose disease had a duration of less than one year, 3) who were under 40 years of age, and 4) who were treated with a dose lower than 0.5 ml (10 mg flupenthixol decanoate).


Valproate treatment of mania.

Valproate treatment of mania. 1. Acute as well as prophylactic effects of the anticonvulsant valproate are described in patients with mania and bipolar affective psychoses. 2. In a long-term evaluation of valproate prophylaxis ranging up to 14 years, an average improvement of the phase chart of 12 patients was observed by a factor of 12. 3. The mode of action of this effect appears to be related to the GABAergic properties of the compound.


Neuropsychological indicators of the vulnerability to schizophrenia. Schizophrenia is associated with enduring deficits in neuropsychological functioning. It is widely undecided if the various aspects of neuropsychological impairment are a consequence of the disorder or if they are also present premorbidly and in populations at increased risk for schizophrenia (vulnerability markers). Neuropsychological deficits in healthy relatives of schizophrenic patients who are at an elevated risk for schizophrenia and who did not yet pass the period of risk would indicate that these deficits are vulnerability markers. This hypothesis was tested for three neuropsychological paradigms which have been proven to distinguish schizophrenic patients from controls. 33 siblings of drug-free schizophrenic probands revealed deficits has compared to 33 matched healthy controls in a blurred single target version of the Continuous Performance Test and in a multiple item version of the Span of Apprehension Test but not so in less difficult versions of both tests or in the time needed to react to stimuli with shifting modality.


Actions of oxaprotiline in the rat hippocampal slice. 1. Recordings were obtained from transverse slices of rat hippocampus, which were placed in a perfusion chamber and superfused with oxygenated artificial cerebrospinal fluid. 2. The effects of 10 microM (+)- or (-)-oxaprotiline applied by the bath were examined on the population spike, postsynaptic excitability in low Ca2+-high Mg2+ medium, the epileptiform discharge in Mg2+-free medium and long-term potentiation (LTP). Only the last paradigm (LTP) was significantly enhanced by (+)-oxaprotiline. 3. In rats chronically injected with (+)-oxaprotiline, neither LTP nor the actions of a variety of neurotransmitters in low Ca2+-high Mg2+ medium were significantly altered. 4. Intracellular recordings showed a small depolarization (3.5 +/- 1.6 mV) in response to 10 microM (+)- or (-)-oxaprotiline. Neither input resistance nor inward rectification, long-lasting afterhyperpolarization or accommodation were significantly altered. 5. Acute application, but not chronic treatment with (+)-oxaprotiline affects long-term potentiation in the hippocampal slice, presumably due to an effect on gabaergic inhibition.


Chronic clozapine treatment down-regulates serotonin 5-HT-1c receptors in rat brain. 1. The effects of chronic treatment with the atypical antipsychotic, clozapine, and classical antipsychotic, haloperidol, on serotonergic 5-HT-1c and dopamine D2 receptors in rat brain were studied with radioligand binding methods. 2. Two weeks' treatment with clozapine did not alter striatal D2 receptor characteristics measured with 3H-spiperone, but caused a 54% down-regulation of 3H-mesulergine binding to 5-HT-1c receptors in choroid plexus. 3. In contrast, two weeks' treatment with a classical neuroleptic, haloperidol increased significantly D2 receptor number in striatum, but had no effect on 5-HT-1c receptor binding. 4. In conclusion, alterations of 5-HT-1c receptor characteristics after chronic clozapine treatment may represent a mechanism that contributes to the unique clinical profile of this antipsychotic drug.


Effect of lithium on rod photoreceptor rhodopsin-coupled G-protein (transducin). 1. Lithium was known to inhibit both adrenergic and cholinergic agonist-induced activation of G-proteins in cerebral cortex. 2. Doly et al (1989) observed that lithium reduced the b-wave of the electroretinogram and suggested that the effect was due to inhibition of G-protein in photoreceptor cells. 3. This study was undertaken to test this hypothesis directly on photoreceptor cell membranes. Rod disk membranes containing the visual transduction machinery were isolated in the dark and the effect of lithium was tested on (a) activation by bright light of G-protein-mediated cyclic GMP hydrolysis, (b) light sensitivity of the activation, (c) the lifetime of the light-activated receptor, and (d) light activation of GTP-gamma-S binding to the membranes. 4. None of these processes were affected by lithium. It is therefore concluded that the effects of lithium on the b-wave of the electroretinogram should be due to influences on G-proteins in other parts of the retina.


Brain neuropeptides: changes by treatment with the convulsants pentylenetetrazole and bicuculline. 1. The effects of chemically induced convulsions, clinically similar to those elicited by electroconvulsive treatment (ECT), on brain regional distribution of neuropeptide Y-, neurokinin A-, substance P- and neurotensin-like immunoreactivities were studied in the rat. 2. Pentylenetetrazole (PTZ) and bicuculline (BIC) were used to induce grand mal seizures. Rats were divided into three groups receiving one of the following treatments: Saline, PTZ (45 mg/kg) or BIC (1.5 mg/kg). 3. After sacrifice by focused microwave irradiation, brains were dissected, peptides extracted and measured by specific radioimmunoassays. 4. Repeated grand mal convulsions induced by PTZ, in similarity to ECT, markedly increased NPY-LI concentrations in frontal cortex and hippocampus. In contrast to ECT, no changes in NKA- or SP-LI levels were seen. NT-LI was lowered in striatum. 5. Bicuculline effects were more circumscribed: some animals developed grand mal and died while convulsing (peptides not measured), others did not develop generalized seizures and were sacrificed after the fourth treatment. 6. The results demonstrate a similar effect of PTZ and ECT on regional NPY-LI concentrations and raise the possibility that grand mal, regardless of etiology, is necessary for effects on peptides.


Choice between delayed reinforcers in an adjusting-delay schedule: the effects of absolute reinforcer size and deprivation level. Choice between two reinforcers differing in magnitude and delay was investigated in rats using an adjusting-delay discrete-trials schedule in which the two reinforcers were associated with two levers (A and B). The delay to Reinforcer A (the smaller reinforcer) was always 2 sec, whereas the delay to Reinforcer B was varied in accordance with the distribution of choices in successive blocks of trials. In Experiment 1, the mean delay to the large reinforcer during the last 5 of 60 training sessions was greater when the rats were maintained at 80% than when they were maintained at 90% of their free-feeding body weights. In Experiment 2, the delay to the larger reinforcer was greater when the two reinforcers consisted of one and two 45-mg food pellets than when they consisted of three and six pellets. The results are consistent with a model of "self-control" which posits hyperbolic relations between reinforcer value and reinforcer magnitude, and between reinforcer value and delay of reinforcement.


Successive negative contrast in one-way avoidance learning in rats. In three experiments, successive negative contrast was examined in one-way avoidance learning. Reward magnitude in first (pre-shift) and second (post-shift) phases was manipulated by time spent in the safe compartment. Experiment 1 demonstrated that when time in the danger compartment was held constant, a group shifted from a large reward--30 sec spent in the safe compartment--to a small reward--1 sec--showed poor performance and longer response latency than a group conditioned with the small reward in both phases. Experiment 2 replicated this effect with a less intense shock and also demonstrated that a group shifted from large to small reward performed more poorly than a group exposed to large reward--30 sec--in both phases. Finally, Experiment 3 showed that changes in intertrial interval, defined as total time spent in the safe compartment and the danger compartment before the onset of the warning signal, were not responsible for this contrast effect. These results suggest that time spent in a safe place can act as appetitive incentive during one-way avoidance learning.


Delayed-matching-to-sample by marsh tits and great tits. The ability of two species of tits to remember the location and/or features of an object was tested in a delayed-matching-to-sample procedure. Three values of retention interval between presentation of the sample stimulus and the choice--30 sec, 5 min, and 15 min--were used. Both species performed at above-chance level at all retention intervals, and there was no significant decline in accuracy with increasing interval. A pool of 100 stimulus objects was used, but the results of control trials indicated that the birds responded primarily to location rather than stimulus features of the object itself. Although the food-storing marsh tit tended to perform at a higher level than the non-storing great tit, the only significant difference between the species was in the first 50 trials of the first treatment, when the birds were acquiring the task. The results are discussed in relation to the hypothesized special memory capacity of food-storing birds.


Reciprocal overshadowing between intra-maze and extra-maze cues. In three experiments, rats learned a maze discrimination where the location of food was defined either by reference to extra-maze cues alone, or by both extra- and intra-maze cues. Experiment 1 confirmed earlier results in showing that the presence of intra-maze cues failed to overshadow learning about extra-maze cues, in spite of the former's apparently greater salience. Experiment 2, however, suggested that this result was an artefactual consequence of differences between groups in the proportion of reinforced and unreinforced trials during the course of discriminative training. In Experiment 3, the discrimination was taught by a series of reinforced and unreinforced placement trials, and a significant overshadowing effect was observed. Intra-maze and extra-maze cues seem to compete for association with reinforcement in exactly the same way as any other cues.


The role of instrumental responses in memory retrieval in a T-maze. Retrieval of the memory of non-reward on a rewarded trial was investigated here employing rats in a T-maze. A forced choice procedure was used. The daily rewarded (R) and non-rewarded (N) trials always occurred in a fixed order, two R, four N, and finally two R, i.e. the series was R1-R2-N1-N2-N3-N4-R3-R4. In an original acquisition phase. Trial N4 of the series having occurred in a particular spatial alternative, e.g. left, it was followed by R3 either in the same alternative, Groups C and T, or in the opposite alternative, Group R. Group T, unlike Groups C and R, received a relatively long intertrial interval between N4 and R3. In a shift phase, groups were treated as in original acquisition except that the long intertrial interval (Group T) and the change in response (Group R) now occurred between R3 and R4 rather than N4 and R3. The major finding in original acquisition was slower running by Groups T and R than by Group C on Trials N2, N3, and N4. In shift, differences between the groups disappeared. These findings are consistent with the hypothesis that response-produced cues contribute to memory retrieval.


Inherent radiosensitivity and split-dose recovery in plateau-phase cultures of 10 human tumour cell lines. The radiation response of 10 human tumour cell lines, eight of them established in our Institute, was analysed. Single dose acute survival curves were constructed and fitted with the linear-quadratic (LQ) model. The mean inactivation dose (D) was also calculated, together with D(o) and n. In order to measure both split-dose recovery and delayed plating recovery of plateau-phase cells, confluent cultures were subjected to two doses of 2 Gy 24 h apart, and plated 24 h later, simulating clinical fractionation. Survival of these cells (S2 x 2) was compared to that following 4 Gy given to cells plated at low density and an overall recovery factor (RF) was derived, including both types of recovery. S2 x 2 and RF were compared to the intrinsic radiosensitivity parameters. The three melanoma cell lines differed in radiation response, and the three squamous cell carcinoma cell lines were rather radioresistant. The neuroblastoma cell line was highly sensitive, yet it expressed the highest beta and the highest RF. Using a non-parametric correlation test, S2 x 2 was found to be related to D, whereas RF was not related to the radiosensitivity parameters. However, the two cell lines with the lowest D and the lowest S2 expressed the highest RF. These results suggest that radiosensitive cell lines may have a considerable capacity to recover if confluent cultures are exposed to fractionated irradiation. The overall recovery factor (RF) used here is proposed as a useful measure of cellular recovery.


Digiplot: a PC programme for drawing tumour volumes for radiation therapy treatment planning using computed tomography images. Computed tomography (CT) provides explicit information for tumour localisation. However, CT data are displayed in the transverse plane, whereas on the Radiotherapy Simulation films, radiation portals are commonly directed into anteroposterior and lateral planes. Using present day radiotherapy planning computers, it is possible to read in the CT data to determine the tumour volume in anterior/posterior and lateral directions and to perform dosimetry calculations. In cases where the digital computer data cannot be used directly by the radiotherapy planning computer, (for example, owing to compatibility problems) the radiation oncologist must transfer information about tumour location from the CT hard copy images to the longitudinal planes of the simulation film by hand. This manual data transfer can now also be performed using the new personal computer programme, Digiplot, which we have developed and is described below. The application of Digiplot to the head and neck area has shown that it complies with the accuracy requirements laid down by the radiation oncologist. The clinical impact of Digiplot was tested on ten patients with a brain tumour. In two cases, Digiplot detected errors which had not been observed using the conservative (manual) method.


Low dose preoperative radiotherapy for carcinoma of the oesophagus: results of a randomized clinical trial. One-hundred-and-seventy-six patients with potentially operable squamous cell carcinoma or adenocarcinoma of the middle or lower thirds of the oesophagus were randomly assigned to preoperative radiotherapy or surgery alone. Patients assigned to the radiotherapy arm received 20 Gy in 10 treatments over 2 weeks, using parallel opposed 4 MV beams. The preoperative radiotherapy was not associated with any significant acute morbidity or any increase in operative complications. The median survival of the overall group of 176 patients was 8 months, and the 5-year survival was 13%. There was no significant difference in the survival of the 90 patients who received preoperative radiotherapy and the 86 who were managed by surgery alone. Proportional hazards analysis identified lymph node involvement, high tumour grade and male sex as significant adverse prognostic features, but the treatment option assigned had no prognostic significance. It was concluded that low dose preoperative radiotherapy offered no advantage over surgery alone.


Three-dimensional dose mapping from gamma knife treatment using a dosimeter gel and MR-imaging. A new method has been investigated for the mapping of dose distributions in three dimensions delivered by the Leksell gamma knife. The irradiation unit is used to selectively treat small volumes in the brain with single high doses of ionising radiation--a treatment procedure known as radiosurgery. The dosimetry method investigated utilises a dosimeter gel consisting of ferrous sulphate solution and agarose which is, prior to irradiation, loaded into a cavity in a spherical phantom. Chemical changes induced in the gel by the radiation are measured by means of an MR-scanner. This imaging method permits rapid evaluation of the dose distribution in an irradiated volume. It thus offers a potential verification of individual radiation intracranial target treatment regimes as well as quality assurance measurements, assuming that the precision and accuracy of the dose mapping are adequate. The dose and its distribution registered by the gel dosimeter, in this initial experiment, are in good agreement with corresponding computed data obtained with the KULA treatment planning system of the gamma knife. The gel has thus the potential of being an attractive alternative dose mapping method to those used at present in radiosurgery, i.e. radiographic film and small ionisation chambers. The precision of the dosimeter gel is, however, not yet sufficient high to be used as a basic dosimetry system for the gamma knife.


Incompletely resected advanced squamous cell carcinoma of the head and neck: the effectiveness of adjuvant vs. salvage radiotherapy. Between 1982 and 1988, 441 patients were treated at the Medical College of Virginia for AJC Stage III and IV squamous cell carcinoma of the head and neck. We report here on 84 patients whose tumors were incompletely resected based on histopathological margins of 1 mm or less. Of these 84 patients, 49 were treated with surgery alone and 35 received immediate postoperative irradiation to doses of 50-70 Gy. The two patient groups are comparable with respect to stage of disease, age, male/female and racial ratios. This retrospective analysis, based on follow-up of 24-110 months, gives actuarial locoregional tumor control and survival data. The local control and disease-free survival rates in the combined modality group are significantly superior at the p = 0.0006 and p = 0.0003 levels, respectively, relative to the group treated with surgery alone. Patients in the combined modality group also experienced a significantly improved adjusted and overall survival, p = 0.005 and p = 0.01, respectively. The administration of postoperative irradiation was not associated with an increased rate of complications. The benefit of radiotherapy on survival was only seen when given as postoperative treatment but was lost in patients treated for salvage after tumor recurrence.


Radiation therapy of stage I breast cancer: analysis of treatment technique accuracy using three-dimensional treatment planning tools. This paper presents the routine implementation of a method for use of three-dimensional (3-D) treatment planning for breast cancer patients with node negative disease, treated with breast conserving surgery. The patients were positioned on a device which fitted a CT aperture with a diameter of 70 cm. A patient reference system was defined by the mamillary plane and the sternum midline. Eight to twelve CT images per patient were taken. The target volume was defined in several CT slices. The treatment planning was made with a 3-D treatment planning system; the treatment technique was isocentric with tangential fields. The patient position was the same at the CT scanner and during the treatment. Four to six portal films per field per patient were routinely taken. The reproducibility of the set-up was investigated on 20 consecutive patients: the treatment-to-treatment variation results were related to the margin of the target. The comparison between treatment planning and portal films gave information about the isocenter displacement. No large discrepancy between measurements on simulator film and on portal films was found. Based on the presented results the described treatment technique has been introduced as part of a routine clinical practice at our institution.


Effects of position and mattress overlay on sacral and heel pressures in a clinical population. A comparison of pressure reducing properties of alternating air, static air, and water mattress overlays was conducted with 57 patients in a surgical intensive care unit. Sacral and heel pressures in both recumbent and semi-Fowler's positions were tested for each surface using a repeated measures design. Mean pressures for the alternating air mattress were significantly higher than pressures with other surfaces, regardless of position or site. There were significant main effects for position and site, with higher pressures in the semi-Fowler's position and at the sacral site. A significant interaction between surface, site, and position was found. Pressure sores developed in eight patients, but the incidence was not significantly different across groups. A pressure measuring device constructed from available clinical materials proved to be both sensitive and reliable. The findings suggest alternating air overlays should be avoided, and that positioning and periodic position change to reduce sacral pressures for patients requiring prolonged upper body elevation is important.


Preadmission self-instruction effects on postadmission and postoperative indicators in CABG patients: partial replication and extension. Fifty adult coronary artery bypass graft surgery patients were randomly assigned to preadmission self-instruction or posthospital admission instruction of therapeutic exercises (e.g., coughing). Self-instructed subjects reported higher positive mood scores, performed correctly significantly more exercise behaviors, and required less teaching time following hospital admission. Postoperatively, no group differences were found on mood states, physical activity, analgesic use, or length of hospital stay. Both groups, however, tended to use less pain medication than that reported by other researchers and experience shorter hospital stays than that assigned under the Diagnostic Related Groups prescription.


The stress response of mothers and fathers of preterm infants. Differences in neonatal intensive care unit (NICU) environmental stress, uncertainty, and anxiety of 23 mothers and fathers (couples) whose premature infants were hospitalized in an NICU were explored. Alterations in the parental role were found to be stressful for both mothers and fathers, with mothers reporting significantly greater stress in this area than did fathers. Stress and uncertainty decreased significantly over time. Mothers and fathers did not differ in level of anxiety. Findings suggest that both mothers and fathers are distressed by the admission of a premature to an NICU; however, mothers may be more distressed by certain aspects of the experience.


The organizational environments and services of VNAs and hospital-based home health care agencies. Visiting Nurse Associations (VNAs) and hospital-based home health care agencies (HBHHAs) were used to explore the impact of organizational environments on agency services. Disproportionate stratified random sampling, based on type and region of agency, was used to select the agencies. Seventy-three percent (120 HBHHAs and 156 VNAs) responded to the mail survey. Differences were found in the environments of the two types of agencies in funding and referral sources, amount of competition, accreditation by external bodies, and involvement in professional organizations. In terms of services, HBHHAs provided more types of high-tech services and were more likely to use external arrangements to provide services than VNAs. The organizational environment did have an impact on agency services. Medicare funding and referral sources, as environmental factors, had an impact on agency services.


Perceived risk of infection and attitudes toward risk groups: determinants of nurses' behavioral intentions regarding AIDS patients. The relationship of perceived occupational risk of AIDS and attitudes toward AIDS risk groups to behavioral intentions regarding the care of AIDS patients was examined among nurses (N = 496) residing in a selected area of New Jersey, a state with a relatively high number of reported AIDS cases. Hierarchical multiple regression analyses on anonymous mail survey responses revealed that, controlling for AIDS knowledge and years of education, nurses who perceived that caring for AIDS patients increased their risk of HIV infection scored higher on an index of intentions to avoid AIDS patient care. In addition, nurses who expressed more negative attitudes toward intravenous drug users or homosexuals were more likely to report similar intentions to avoid AIDS patient care. The implications of these findings for efforts to increase nurses' ability and willingness to provide quality care to persons with AIDS are discussed.


Divergent productive thinking factors and accuracy of nursing diagnoses. Theories of diagnosis in nursing (Carnevali, 1983; Gordon, 1982) and a model of intelligence (Guilford, 1979) were integrated to provide a theoretical basis for this study. In contrast to previous studies, accuracy of nursing diagnoses was measured as a continuous variable. It was hypothesized that three factors of divergent productive thinking, fluency, flexibility, and elaboration, would correlate positively with accuracy of nursing diagnoses. The sample consisted of 86 female nurses, graduates of generic baccalaureate programs with 1 to 5 years experience, who met the criterion of knowledge. Three written case studies (CS1, CS2, CS3) served as the criterion for accuracy. With CS1, none of the hypotheses were supported. With CS2, the three hypotheses were supported (p less than .05) and 10% of the variance was explained by one factor, fluency (p less than .01). With CS3, elaboration and accuracy were correlated (p less than .05). The findings provide beginning support for inclusion of exercises for divergent thinking in nursing education and practice.


Focus on psychometrics. Aggregating family data. Instruments to collect data about families are often administered to all or some individuals within the family. Researchers may wish to use these individual scores to describe the family. The purpose of this article is to describe the special issues with aggregation of data when only a small number of family members are used as respondents. A refinement of the definition of aggregation for family researchers is proposed to assist researchers to focus on specific issues when data are to reflect subgroups within the family. A few examples of changes in findings are reported to illustrate the effects of different aggregation schemes when two members of the family are used as respondents.


Sjögren's syndrome: historical overview and clinical spectrum of disease. Sjögren's syndrome is a chronic autoimmune and inflammatory disease characterized by lymphocyte proliferation that progressively destroys exocrine glands. The lymphocytes can infiltrate other and more vital organs and may at times become malignant. Another name for this disease is autoimmune exocrinopathy. It was first described over 100 years ago both as a benign syndrome of oral and ocular dryness and also as a lymphoid malignancy. Thus, Sjögren's syndrome is related to the autoimmune rheumatic diseases, as well as to lymphoid B-cell malignancies.


The immunogenetics of Sjögren's syndrome. The fact that patients with SS, either primary or associated with another connective tissue disease, show a striking tendency toward familial aggregation of SS, other autoimmune disease and autoantibodies suggest a role for genetic factors in the pathogenesis of this disease. What these factors are is as yet not known; however, it is clear that autoantibodies found in high frequency in SS, specifically anti-Ro and anti-La, are associated with HLA class II alleles, found at the HLA-DQA1 and DQB1 loci, which have in common the presence of specific amino acid residues that are found in the second hypervariable region of the first (outermost) domain. Additional roles for T-lymphocyte receptor and immunoglobulin genes are also suggested. Family studies, however, indicate the presence of an additional autosomal dominant gene(s), not linked to HLA or immunoglobulin heavy or light chain genes, in predisposition to SS. Identification of this additional genetic factor(s) should provide important clues in the pathogenesis of SS.


Antinuclear antibodies in Sjögren's syndrome. The definition and characterization of the reactivity of ANA in patients with SS are greatly improved with the current advances in cellular and molecular biology. Based on the characteristic autoantibody profiles in different systemic rheumatic diseases and the nature of the defined autoantigens, it has been proposed that the polyclonal autoimmune response is induced and maintained through an antigen-driven mechanism. The autoantigens are presented in the cell as components of large particles or structures composed of protein-protein or RNA-protein complexes; however, the role of these autoantibodies in the etiology and immunopathogenesis of SS remains to be determined.


Salivary and oral components of Sjögren's syndrome. The intraoral symptoms and signs of SS are not specific to SS, being shared with other conditions in which salivary function is diminished. The decrease in saliva causes chronic oral discomfort and functional problems and predisposes patients to dental caries and oral candidiasis. Many methods have been used to assess SGs in SS objectively, but at present a labial salivary gland biopsy specimen showing focal lymphocytic sialadenitis provides the best diagnostic criterion for the salivary component of SS, in terms of its disease specificity, convenience, availability, and low risk. The treatment of xerostomia in patients with SS consists of (1) preventing new and recurrent dental caries by frequent and regular application of topical fluoride, careful dental supervision, and avoidance of sucrose and other metabolizable carbohydrates between meals; (2) reducing oral symptoms by diagnosing and treating oral candidiasis (repeatedly if necessary); and (3) attempting to replace lost saliva by stimulating salivary secretion with physiologic sialogogues or pilocarpine, or if adequate amounts of saliva cannot be stimulated, using some form of saliva substitute, especially for patients wearing complete dentures.


Ocular manifestations of Sjögren's syndrome: keratoconjunctivitis sicca. As part of the triad of Sjögren's syndrome (SS), keratoconjunctivitis sicca (KCS) can be found in virtually all SS patients. This term emphasizes not only the reduced tear production but also the pathologic changes in the epithelial cells of the ocular surface. The symptoms of dry eye may vary from one patient to another depending on the severity of dryness, the ability of the diminished tear film to moisten the ocular surface, and the patient's tolerance for ocular discomfort. Treatment of the dry eyes is remarkably effective, and most patients benefit from moisturizing eyedrops to replace their own deficient tears. Major issues include the pathogenesis of decreased tear flow and ocular surface disturbances, as well as the roles of wound healing agents and anti-inflammatory medications in KCS therapy.


Cutaneous manifestations of Sjögren's syndrome. The major mucous membrane and cutaneous manifestation of Sjögren's syndrome (SS) is xerosis. Severe dryness of the eyes, mouth, nasal passage, and vagina produce many annoying symptoms, including photophobia, burning and itching of the eyes, alterations in taste and smell, recurring nonallergic bacterial sinusitis rhinitis, and dysparunia. SS patients frequently complain of dryness of lips and soreness and a burning sensation of the tongue and oral mucosa. SS patients also complain of dryness of their hair and note a decrease in luster, and severe dryness of the skin is frequently accompanied by pruritus.


Pulmonary and gastrointestinal manifestations of Sjögren's syndrome. The respiratory system is frequently involved in primary SS but this involvement is rarely clinically significant. Its manifestations are secondary to desiccation of the tracheobronchial tree and lymphocytic infiltration of the lung parenchyma. The desiccation of the tracheobronchial tree gives rise to the most important clinical manifestation, dry cough (xerotrachea), but is rarely a cause of infection and obstructive airways disease. The lymphocytic infiltration of the lung parenchyma starts as lymphocytic alveolitis in a very large number of SS patients but rarely evolves into frank lymphocytic interstitial pneumonitis and fibrosis. Even more rare is the evolution of pseudolymphoma into malignant lymphoma. Pleurisy with or without effusion is not a frequent manifestation of primary SS. It occurs often in secondary SS and is due to the underlying rheumatic disorder. In general, secondary SS rarely has significant pulmonary manifestations other than those of the disorder it accompanies. The manifestations from the gastrointestinal system in patients with SS include mucosal dryness, accelerated dental decay, and enlargement of the major salivary glands, as well as dysphagia, nausea, epigastric pain, and dyspepsia. The dysphagia is probably secondary to esophageal dysfunction, and the gastric symptoms might be attributable to chronic atrophic gastritis. Whether the small bowel is affected in SS patients is not clear. Pancreatic involvement usually is being expressed as subclinical acute or chronic pancreatitis. Finally, the liver could be involved in SS patients, and some studies indicate that the pathogenic process responsible for the hepatic damage and for the salivary gland destruction could be similar.


Central nervous system disease in Sjögren's syndrome. New insights into immunopathogenesis. Although peripheral nervous system disease is a well-established complication of primary Sjögren's syndrome (SS), until relatively recently little attention has been focused on the central nervous system (CNS) complications of this disorder. The observations discussed in this article pertain to patients with primary SS in whom the presence of a second connective tissue disorder and other etiologies for neurologic disease have been rigorously excluded. In this article, the growing clinical spectrum of CNS manifestations, neurodiagnostic techniques, serologic analyses, and immunogenetic markers associated with this disorder are reviewed.


Comparison of diagnosis and treatment of Sjögren's syndrome in Japan and United States. Today, as with western countries, diagnosis and treatment of Sjögren's syndrome (SS) patients in Japan are carried out by a team effort. The clinical manifestations of Japanese SS patients are quite similar also. There are, however, several minor modifications in the diagnosis and treatment of SS patients in Japan, which are presented in this article.


Diffuse infiltrative lymphocytosis syndrome: a disorder occurring in human immunodeficiency virus-1 infection that may present as a sicca syndrome. Certain adults and children infected with the human immunodeficiency virus(HIV)-1 developed a disorder termed diffuse infiltrative lymphocytosis syndrome (DILS) that, although having certain similarities to classic Sjögren's syndrome, manifests distinctive clinical, serologic, immunologic, and immunogenetic characteristics. DILS is characterized by circulating CD8 lymphocytosis and apparently antigen-driven CD8 T-cell infiltration of salivary and lacrimal gland, pulmonary, renal, gastrointestinal, and breast tissues. The disproportionately greater degree of salivary gland enlargement and extraglandular disease, as well as the low frequency of autoantibodies and differing HLA associations, serve to distinguish DILS from classic Sjögren's syndrome.


Treatment of the patient with Sjögren's syndrome. SS is a systemic autoimmune disease characterized by lymphocytic infiltrations of lacrimal and salivary glands. Extraglandular organs including skin, nerve, lung, and kidney may be involved. At the present time, there remains a great deal of confusion regarding the precise definition of SS. As a result, both patients and clinicians frequently have a difficult time in making a specific diagnosis and instituting a specific plan of therapy. Regardless of the diagnostic label, all patients with significant eye and mouth dryness should receive conservative therapy of tear replacement and intensive oral hygiene. Based on the presence or absence of clinical or laboratory features of systemic autoimmunity, additional therapies may prove beneficial in controlling the symptoms and progression of SS.


[General qualifying exams: a report of experience at the doctorate level]. This is a report of experience obtained on the occasion of General Qualifying Exams taken by candidates to the Doctoral degree in the Graduate Program of the School of Nursing at São Paulo and Ribeirão Preto, of the University of São Paulo. Documents concerning legal rules were consulted, along with relevant literature that permitted us to obtain in-depth information about the research lines, methods and activities used by nursing researcher, as a way of facilitating the collection of information about authors. We trust that this experience will help clarify the subject for colleagues who intend to take these exams.


[An instrument for the nursing consultation of patients with arterial hypertension under outpatient treatment]. The purpose of this article is to emphasize the nurse's role toward persons with arterial hypertension. Therefore it's introduced an application form that is used for nursing consultation to outpatients.


[The nursing consultation in geriatrics: the topics to be addressed in the physical examination--II]. The author approaches physical exam in elderly and other items that are essential to nurses consultation. This article completes the topic Nurses consultation on Geriatrics--part I.


[A descriptive study of the defining characteristics of nursing diagnosis: sexual dysfunction]. The defining characteristics of the nursing diagnosis "Sexual Dysfunction" were gathered from NAAM assessment records. From this population 96 records with the defining characteristics of Sexual Dysfunction were selected. The 9 defining characteristics proposed by The North American Nursing Diagnosis Association were used as a framework for the data collection tool. The 3 most frequently defining characteristics were absence of sexual desire (71.9%), vaginal discharge (64.5%), and pain (44.8%). The authors concluded that 6 defining characteristics have not appeared; absence of sexual desire and vaginal discharge can be considered as minor characteristics. The authors recommend the implementation of other studies to clarify the subjective defining characteristics.


[Occupational stress in the nurse of a central supply unit]. The goals of this study were to characterize the central supply nurses to verify the nursing activities that are involved in occupational stress, and to lessen the stressors. Eight nurses comprised the sample; they were 25 to 30 years old, worked in the unit less than 5 years and they were satisfied with their job. The administrative area were the most mentioned stressor. The recognition and valorization of central supply area is an important aspect to diminish the nurses stress.


[Leininger's transcultural theory].

[Leininger's transcultural theory]. The authors make a short review of the development of Transcultural Nursing, present several major concepts and definitions as well as some major assumptions of this theory. Some considerations are made on the "Sunrise" Theoretical Conceptual Model of Transcultural Care Diversity and Universality, developed and used by Leininger since 1965 to the present.


[The social and health policies in Brazil: a historical approach]. The author makes an historical approach of the brazilian social and health policies, trying to co-relate them to the changes of the mode of production of each historical cycle. She intends to clarify that social policies represent the state "administration" of conflicts between classes and that health policies express social inequalities, showed in a different access to health utilities.


[Transfusion risks and alternatives to transfusion]. The emergence of the acquired immunodeficiency syndrome (AIDS) has fueled concerns of both physicians and their patients about safety of blood transfusions. Although AIDS has generated the most fear, the risk today is extremely remote (1/60.000 units of blood). The risk of transmitting infectious disease by homologous transfusion is decreasing, as more donor screening and testing measures are implemented. The blood supply is safer that at any time, but small transfusion risks exist. The most common problems associated with transfusions are temporary: one in 100-300 recipients will experience fever or rash. The biggest problem is a mismatch of the well-known ABO blood groups and once in every 100-400.000 transfusions the hemolytic reaction is fatal. Viral hepatitis is another serious and important risk. At present hepatitis seems to strike between 1 and 3 percent of transfusion recipients. Most, if not all, of transfusion-associated hepatitis cases are caused by hepatitis C virus. Cytomegalovirus can cause primary infection, reactivation or reinfection by transfusion. Immunosuppressed patients are more likely to develop more severe disease. Epstein-Barr virus does not seem to cause significant post-transfusion disease. Bacterial or protozoal infections are an infrequently encountered adverse effect of transfusion. However, some clinical cases document the potential hazard of blood components as a vector for bacteria or protozoa. Homologous blood transfusion down-regulates some immune functions. Host defences against malignancy and infection may in some instances be severely compromised by transfusions of homologous blood.(ABSTRACT TRUNCATED AT 250 WORDS)


[Usefulness and limitations of vaccination against influenza]. Influenza viruses have caused major epidemics of respiratory disease and a high mortality in patients with advanced age and in those with underlying health conditions. It has been estimated in the USA that, during a moderate epidemic of influenza, there is an excess of 170,000 hospitalizations and approximately 20,000 to 40,000 influenza-associated deaths per years. Costs may exceed 1 billion dollars per year. Influenza viruses have been difficult to control because of a large animal reservoir and of the frequent change of the virus antigenic structure by major (shift) and minor (drift) variations. Current killed trivalent vaccines are made of two influenza A subtypes plus influenza B virus. Because of the antigenic variation, vaccine composition needs to be changed almost every year in order to contain the strains most likely to be effective. There are two types of vaccines--"whole" and "split". The latter has been treated to reduce pyrogenic components and is particularly indicated in children. Vaccine efficacy varies according to how closely the immunizing strains resemble the circulating wild strain. It also depends on the viral strains which had appeared in the preceding years (herd immunity), on the number of the doses administered and on the interval between the vaccination and the natural challenge. The antibody response to vaccine is short-lived. It is greatest in normal adults and lowest in aged and in immunosuppressed patients. Vaccination reduces clinical infections by 70-80% in children and adults, but only by 30% in elderly patients living in institutions.(ABSTRACT TRUNCATED AT 250 WORDS)


Herpes simplex pneumonia in a heart transplant recipient. An unusual case of Herpes simplex virus (HSV) pneumonia in a heart transplant recipient receiving chronic immunosuppressive therapy is reported. This infection presented an indolent course manifested by a chronic left pulmonary infiltrate unresponsive to antibiotic therapy and mild hypoxemia. Death eventually occurred as a consequence of an other infectious complication of the postoperative period. The HSV etiology of the necrotizing pneumonia observed at autopsy was established on the basis of histologic findings.


Serum albumin and others parameters in intravenous drug users HIV-infected. In 37 intravenous drug users (IVDUs) in the first stages of HIV-infection (17 in stage II and 20 in stage III according to CDC), compared with 32 IVDUs HIV-negatives, we found a significant decrease in circulating leucocytes (p less than 0.01), lymphocytes (p less than 0.005), platelets (p less than 0.005), serum albumin (p less than 0.005), and C3 (p less than 0.02) and significant increase in serum gammaglobulins (p less than 0.0005) and IgG (p less than 0.0005). On the other hand no difference was observed in hemoglobin and in IgA levels; nevertheless an inverse relationship between serum IgA and CD4+ lymphocytes was present in HIV-positive (HIV+) patients (r = -0.34; p = 0.04). This observation agrees with that is observed in the advanced stages of HIV-infection, which presents an increase in IgA serum levels. In these stages this fact could be due to a decrease of secretory IgA, with a deficient barrier effect; the consequent recirculation of intestinal antigens should enhance the antibody production, as well as serum IgA. In the IVDUs HIV-infected a reverse correlation between albumin serum levels and the length of HIV-positivity (r = -0.44; p = 0.008) and a direct correlation between albumin serum levels and circulating CD4+ lymphocytes (r = 0.37; p = 0.05) were present. There was no direct linear relationship between albumin serum levels and creatinine, on the contrary to what was observed in the control group. The decrease of albumin levels could have a prognostic value as in other clinical conditions, in which it is associated with a higher mortality risk. Many factors could act to decrease albumin levels, but the most important one is perhaps the malnutrition of HIV-infected patients that can also be present in the first stages of infection, negatively influencing the associated immunodeficiency.


[Presence and significance of anticardiolipin antibodies in infectious diseases]. IgG and IgM anti-cardiolipin antibodies were measured, by an ELISA technique, in the sera of patients with B hepatitis (28), infectious mononucleosis (10), chicken pox (12), HIV infection (20), acquired toxoplasmosis (41) and other infectious diseases [HBsAg+ chronic hepatitis (5), brucellosis (6), herpes zoster (4), boutonneuse fever (3), viral pneumonitis (4), rheumatic fever (2)]. Increased levels of anti-cardiolipin antibodies (aCL), at least in one immunoglobulin class, were detected in 37 out of 135 patients [27.4%; range: 7.3% (in the patients with toxoplasmosis) -80% (in the patients with HIV infection)]. Low or medium titer aCL were present in 28 patients, high titer in 9 (6 with HIV infection, 2 with chicken pox and I with lymphoadenopathic toxoplasmosis). None of the manifestations associated with aCL was present in the aCL-positive patients. Finally, positivity for aCL didn't seem to modify the clinical picture and the prognosis of the infectious disease.


[Iproniazid-induced acute hepatitis].

[Iproniazid-induced acute hepatitis]. Many drugs can cause an acute liver damage. The patient history is the guideline for diagnosis. Iproniazid, a monoamine-oxidase inhibitor not for sale in Italy, can frequently cause severe acute hepatitis. A case of acute iproniazid-induced, hepatitis in which the course was favourable, is reported.


[Use of 99mTc-HMPAO SPECT in the study of AIDS-correlated dementia]. AIDS dementia complex is a well-defined neurological manifestation of the HIV infection. Its anatomo-pathological pattern is cerebral atrophy, grey and white matter abnormalities and vascular changes, and the main symptom is progressive dementia. SPECT with Tc 99m HMPAO has proved to be an useful tool in studying Alzheimer and multi-infarct dementia, and its use has been recently proposed in AIDS-dementia. We studied with Tc 99m HMPAO 57 Pts (11 HIV+, 26 ARC, 17 AIDS) and control group of 7 drug-addicted seronegative Pts. We found positive results in 45% SPECT, 18% CT, 0% neurological tests of dementia in HIV+ phase, versus 52%, 41, 20% in ARC phase and 94%, 88% and 76% in AIDS phase, while all control Pts were negative. Control group is too small to exclude with all possibility of doubt cerebral blood flow impairment caused by drug damage but nevertheless we think that SPECT examination with 99 mTc HMPAO has an important role in assessing CBF changes in earlier stages of AIDS disease. These changes are probably forerunners of definitive cerebral damage and may be important markers of the advancement of disease.


[Monitoring of several hematological parameters of the erythroid series in patients with HIV infection treated with zidovudine]. Haematologic toxicity is the most common adverse effect related to long-term administration of zidovudine (AZT). We evaluated the kinetics of modifications of some haematologic parameters of erythroid series in 65 patients with HIV infection treated with AZT for a mean duration of 7.6 +/- 4.7 months (13 of them with a previous diagnosis of AIDS, 34 with ARC, 18 asymptomatic or with LAS/PGL), in order to correlate the observation and the evolution of these laboratory changes with the onset of severe anaemia. The development of macrocytosis occurs in a large majority of AZT-treated subjects, in spite of folate and vitamin B12 supplementation; the monitoring of erythrocytes distribution according to cellular volume and cellular haemoglobin concentration makes it possible to early recognize the occurrence of modification in erythropoiesis. There is no correlation between an elevated mean corpuscular volume and the development of severe anaemia (Hb less than or equal to 9 g/dl) in an individual patient; a fall in the reticulocyte count appears to be the earliest peripheral blood sign of the development of bone marrow toxicity.


Assessing response bias in random-digit dialling surveys: the telephone-prefix method. Knowledge of the characteristics of survey non-respondents is important to determine generalizability to the population of interest. In a recent random-digit dialling survey of health behaviours only 73 per cent of the households contacted provided any information about household composition, and only 74 per cent of those actually completed the extended interview, for an overall response rate of 54 per cent. To identify possible biases we grouped all attempted phone numbers by their prefix, and looked for the association between the response rate for that prefix and other summary variables known about the prefix. A simulation study showed that the method can identify non-response biases if certain assumptions are correct. The analysis suggested that our survey data under-represent older people and those with a college education. We found no significant biases in health behaviours, possibly because the basic assumptions did not hold. This method may assist in identification of non-response bias in other studies.


Discriminant analysis when all variables are ordered. Determination of the equation that relates an ordered dependent variable to ordered independent variables is sought. One solution, non-parametric discriminant analysis (NPD), involves obtaining the best monotonic step function by means of a computer search procedure. Although one can use alternative selection criteria in obtaining the equation, the illustrative examples use absolute distance. This paper compares the prediction procedures obtained from NPD with those from linear discriminant analysis, linear regression (with and without transformed variables), and logistic regression. We show that NPD is analogous to regression tree analysis with incorporation of ordered variables and monotonicity. We use various prediction functions to predict the example data, the data using the leave-one-out technique, and a verification set. Consistently, non-parametric discriminant analysis performs as good as or better than the tested alternatives.


Analysis of variance for repeated measures. Data: a generalized estimating equations approach. Various techniques are available for the analysis of repeated measures data, and the appropriate choice depends on distributional assumptions and study design features. A correct analysis must account for potential dependence between repeated observations on the same subject. Liang and Zeger proposed a more unified approach to the analysis of repeated measures data based on the application of generalized estimating equations. We examine the application of these methods to several types of data in which one estimates the mean response directly for each combination of discrete covariates, and uses an identity link. Computations for fitting this type of model are exceptionally simple. Numerical examples suggest that the proposed approach yields estimation and hypothesis testing results consistent with more specialized methods.


Analysis strategies for serial multivariate ultrasonographic data that are incomplete. Ultrasonographic measurement of intima-media thickness in the carotid artery has emerged as an important non-invasive means of assessing atherosclerosis, and has served to define primary outcome measures related to progression of arterial lesions in several large clinical trials and epidemiologic studies. It is characteristic that measurements often cannot be obtained from all sites during repeated examinations. This leads to incomplete multivariate serial data, for which the set and number of visualized sites may vary across time. We have contrasted several conditional and unconditional maximum likelihood analytical approaches, and have evaluated these with a simulation experiment based on characteristics of ultrasound measurements collected during the course of the Asymptomatic Carotid Artery Plaque Study. We examined analyses based on unweighted and generalized least squares regression in which we estimated cross-sectional summary statistics using raw means, unconditional maximum likelihood estimates and full maximum likelihood estimates. Since the genesis of missing data is not fully clear, and since the approaches we examined are based, to some degree, on the assumption that data are missing at random, we also examined the relative impact of deviations from such an assumption on each of the approaches considered. We found that maximum likelihood based approaches increased the expected efficiency of the analysis of serial ultrasound data over ignoring missing data by up to 21 per cent.


Comparisons between a new drug and active and placebo controls in an efficacy clinical trial. D'Agostino and Heeren (DH) discussed the multiple comparison issues that arise in evaluating both sensitivity and efficacy in over-the-counter drug trials. We propose a general definition of sensitivity that includes DH's definition as a special case. We also propose a test for sensitivity that coincides with the MIN test of Laska and Meisner at one extreme but has the advantage of identifying specific drugs satisfying the sensitivity criterion when some fail to do so. We suggest that the test of Dunnett as well as an extension of it may be useful for the efficacy comparisons.


A method of designing clinical trials for combination drugs. Many pharmaceutical companies are now exploring combination drug therapies as an alternative to monotherapy. Consequently, it is of interest to investigate the simultaneous dose response relationship of two active drugs to select the lowest effective combination. In this paper, we propose a method for designing clinical trials for drug combinations that seems to offer several advantages over the 4 x 3 or even larger factorial studies that have been used to date. In addition, our proposed method provides a convenient formula for calculating the required sample size.


Organization and analysis of safety data using a multivariate approach. The collection of safety data is an important part of clinical trials. These safety data are often described and reported in great detail with expenditure of substantial effort and energy. Because of the wide variety of data that require scrutiny from the safety perspective, however, statistical comparisons of the safety profiles of different treatments often lack focus and structure and result in situations where the comparisons for each individual item lack power and thus are inconclusive. In this paper, we propose to organize the safety data into a more manageable form by consolidating them into a number of K classes characterized by body systems and determined in conjunction with the underlying disease as well as the treatments involved. Within each class, we propose assignment to each patient of an overall intensity grade based on all relevant information. The consolidation of the safety data as proposed provides an informative summary for the safety profile of each treatment. The analysis of such organized data concentrates on comparison of the mean intensity grades for different treatments within the K classes simultaneously with use of scores that reflect the acceptability of the various intensity levels to an individual. Furthermore, we demonstrate that the proposed multivariate comparison has much higher power than the univariate one to detect differences in certain cases. We provide examples to illustrate the proposed procedure.


Comparing sample size formulae for trials with unbalanced allocation using the logrank test. This paper compares the sample size formulae given by Schoenfeld, Freedman, Hsieh and Shuster for unbalanced designs. Freedman's formula predicts the highest power for the logrank test when the sample size ratio of the two groups equals the reciprocal of the hazard ratio. The other three formulae predict highest powers when sample sizes in the two groups are equal. Results of Monte Carlo simulations performed for the power of the logrank test with various sample size ratios show that the power curve of the logrank test is almost flat between a sample size ratio of one and a sample size ratio close to the reciprocal of the hazard ratio. An equal sample-size allocation may not maximize the power of the logrank test. Monte Carlo simulations also show that, under an exponential model, when the sample size ratio is toward the reciprocal of the hazard ratio, Freedman's formula predicts more accurate powers. Schoenfeld's formula, however, seems best for predicting powers with equal sample size.


Sixteen S-squared over D-squared: a relation for crude sample size estimates. I suggest for memorization an equation for calculating approximate sample size requirements intended only for a specific set of values (80 per cent power for a two-tailed alpha = 0.05 test) which seems to occur often in biopharmaceutical research. After presenting the formula in terms of variance estimate s2 and effect size d, I derive a few alternative forms and then discuss the accuracy of the approximation and other properties as well as examples of its use.


Sample sizes for proportional hazards survival studies with arbitrary patient entry and loss to follow-up distributions. In proportional hazards survival studies, power depends on the observed number of deaths, d*. For a given choice of survival, loss, and patient entry distributions, sample sizes can be determined by equating d* to the expected number of deaths. Approximating the survival and loss distributions with piecewise exponential distributions, and patient entry with a piecewise linear distribution, significantly reduces the computational overhead, and the expected number of deaths can be evaluated routinely. The merits of this approach are illustrated by a clinical trial of chemotherapy for large bowel cancer.


The use of cusums and other techniques in modelling continuous covariates in logistic regression. The assessment of continuous covariates singly as possible predictors in a multivariable logistic regression model is an important first step in the analysis. An approach to plotting which uses a cusum (cumulative sum) of the binary response variable is described. Extreme-deviation statistics associated with the cusum may be used to detect monotonic and non-monotonic trends. Probability plots of the covariate in the two groups defined by the response variable may help to determine the appropriate scale (transformation) of the covariate and to anticipate possible problems with the logistic fit. The ratio of the variances in the response/non-response groups is informative about the need for a quadratic term in the logistic model. Smoothed scatterplots of the response are valuable in displaying the observed and fitted values. The techniques are illustrated with two data sets.


Empirical Bayes versus fully Bayesian analysis of geographical variation in disease risk. This paper reviews methods for mapping geographical variation in disease incidence and mortality. Recent results in Bayesian hierarchical modelling of relative risk are discussed. Two approaches to relative risk estimation, along with the related computational procedures, are described and compared. The first is an empirical Bayes approach that uses a technique of penalized log-likelihood maximization; the second approach is fully Bayesian, and uses an innovative stochastic simulation technique called the Gibbs sampler. We chose to map geographical variation in breast cancer and Hodgkin's disease mortality as observed in all the health care districts of Sardinia, to illustrate relevant problems, methods and techniques.


[Current pathogenetic principles in peptic ulcer]. New concepts in the pathophysiology of peptic ulcers must acknowledge 1. the close association of ulcers and Helicobacter pylori infection, 2. the protective role of endogenous prostaglandins, 3. the scarcity of new data on the importance of acidity (though presence of gastric acid remains indispensible for ulcer development). The different pathophysiologically relevant factors closely interact with each other. However, many not of actual concepts are still experimental and--apart from Helicobacter pylori--have not yet led to new therapeutical approaches.


[Therapeutic possibilities in therapy-resistant ulcers--surgical aspects]. Indications for surgery and choice of procedure in complicated or chronic gastroduodenal ulcer refractory to conservative treatment are presented. Operations in emergency states are undisputed although they carry a tenfold higher mortality rate than elective procedures. Therefore in spite of effective pharmacotherapy groups at risk have to be identified by interdisciplinary therapeutic concepts in order to enable elective operation on time. Next to patient and ulcer data the efficacy of various procedures has to be considered. The standardized operative techniques and their associated respective rates of complications and recurrence are compared with those of pharmacotherapy.


[Acute ulcer hemorrhage: when to operate--when to wait?]. The identification of prognostic factors in patients with bleeding peptic ulcer is an essential step for improving the outcome. Since recurrence of bleeding is associated with increased mortality, we therefore developed a new treatment policy based on prognostic information identified at emergency endoscopy. Patients with actively bleeding lesions or visible vessel and high risk of recurrent bleeding were operated upon within 6 h (duodenal ulcer) or 24 h (gastric ulcer) even after successful endoscopic control of bleeding. All other patients with oozing type of bleeding or with signs of recent bleeding during emergency endoscopy were primarily treated in a conservative manner. By using this strategy in a prospective trial the overall mortality rate could be markedly reduced from 14 to 5%.


[Therapeutic strategy in malignant polyps of the gastrointestinal tract]. Malignant polyps in the stomach are identical with early gastric carcinoma type I and IIa. Even if carcinomatous growth is restricted to the mucosa lymph node, metastases may occur; therefore, local measures like polypectomy or surgical excision are exceptional. Malignant gastric polyps should be treated according to classical tumour surgery. Things are different in malignant colonic polyps, i.e. adenomas with a carcinoma invading the submucosa. Unless one is dealing with a dedifferentiated carcinoma or invasion of lymph or blood vessels is seen a few millimetre of security are sufficient to save the patient from radical surgery.


[Chemotherapy in solid tumors of the gastrointestinal tract?]. Chemotherapy in disseminated stages of gastro-intestinal tumor only causes remission rates of 20 to 40% in a reproducible manner. Treatment is clearly palliative and does not influence median time of survival in these patients. In limited stages of esophageal or gastric cancer remission rates above 50% are achieved. However there is no evidence that chemotherapy in addition to surgery improves treatment results. Based on prospectively randomized studies, for stage-III colon carcinoma adjuvant chemotherapy using Fluorouracil and Levamisole is recommended. In resected carcinoma of rectum the adjuvant combination of chemotherapy and radiation improves local control of the tumor as well as survival of the patients. This modality of treatment is recommended.


[Tumor markers in the diagnosis and therapy of intestinal neoplasms]. Tumor-markers should only be used, if they could alter the management of the patient. Screening for hepatocellular cancer in patients with chronic liver disease and monitoring cancer therapy are established methods. In the future, benign and malignant diseases of the pancreas will become easier to differentiate by the determination of subgroups of Lewis A-antigens. During follow-up after curative surgery, markers are of limited value. Immunoscintigraphy is already in use, whereas therapy with monoclonal antibodies still remains investigational.


The biological significance of locoregional recurrence following breast conserving therapy. Although locoregional recurrence of breast cancer following mastectomy is usually a harbinger of systemic failure, patients experiencing locoregional disease recurrence after breast-conservation therapy enjoy a better prognosis. Tumor recrudescences after a breast-preserving surgical procedure represent both residual tumor and new primary breast carcinomas. Patient prognosis is dependent on the biological characteristics of both the original and recurrent neoplasms. At present, the best predictor of patient outcome is the extent of disease at the times of treatment. While many studies report no statistically significant adverse impact of locoregional recurrence on survival, small sample sizes may obscure such an effect.


Pathologic features related to local recurrence following lumpectomy and irradiation. Breast conservation (lumpectomy and irradiation) has grown increasingly popular as a primary therapy for breast cancer. For the majority of patients whose breast cancers are now being detected at T1N0, both the expected cosmetic result and the survival are excellent. For this reason the possibility of local recurrences in the breast has a disproportionally larger impact on treatment planning for these patients. Although the majority of local recurrences occur in the vicinity of the primary tumor site within the initial 5 years of irradiation, local recurrences can be expected to occur well into the second decade as follow-up is continued. The majority of these late recurrences will not be in the immediate vicinity of the prior excision but represent de novo breast cancers developing in a multicentric fashion in other quadrants. Factors which influence recurrence per se include the size, grade, and stage (nodal status) of the tumor. Such factors influence local, locoregional, and distant metastases. A number of pathologic factors appear to affect only local recurrences. These, including positive margins, gross multicentricity, extensive intraductal carcinoma, and invasive lobular carcinoma, all share a common feature of a greater likelihood of local residual tumor burden. The increased risk of local recurrences related to positive surgical margins and extensive intraductal carcinoma can largely be eliminated by increasing the volume of tissue excised or the radiation dose. In summary, there are no absolute contraindications based on pathologic features of the tumor or the state of the resection margins which should preclude consideration of breast conservation for an individual patient.


The pathologist's examination of the "lumpectomy"--the pathologists' view of surgical margins. Despite the widespread conservative management of breast cancer, the pathologists' examination of these specimens is far from uniform. Pathologists sample margins differently, and even disagree on what constitutes a positive margin. This variability in the pathologic examination of the lumpectomy creates tremendous problems in analyzing the existing literature on the importance of positive margins. Herein is a discussion of the available data on the significance of margin assessment. We furthermore suggest a practical approach to examining margins with an emphasis on a functional orientation of the specimen with respect to the nipple. Only by adopting a uniform system of margin assessment can we begin to critically evaluate the importance of positive margins in segmental resections of the breast.


Breast-conserving surgery: how much is enough? Breast-conserving operations for the treatment of small, apparently localized invasive breast cancer are now accepted by most surgeons. Still controversial are (1) the size of the primary tumor selected for breast conservation treatment, (2) how much breast tissue must be removed to provide an "adequate" margin to achieve local control, and (3) whether the entire breast needs to be treated by radiation therapy in all patients after adequate partial mastectomy. The results of breast-conserving operations at the Cleveland Clinic are presented and the case for selected, individualized therapy utilizing partial mastectomy without radiation therapy for selected patients with small invasive cancers is made.


Radiotherapy after breast-conservation surgery: how much is enough? The National Surgical Adjuvant Breast Project (NSABP) clinical trials have demonstrated that breast conservation surgery (lumpectomy), axillary dissection, and breast irradiation for women with Stage I and II invasive breast carcinoma provide disease-free survival and overall survival rates equivalent to modified radical mastectomy. Breast irradiation following lumpectomy decreases the incidence of in-breast tumor recurrence compared to lumpectomy alone. The addition of adjuvant systemic therapy appears to further decrease the incidence of in-breast tumor recurrence. Irradiation of the internal mammary and supraclavicular nodal regions is not indicated for patients with Stage I and II carcinoma. Similarly, irradiation of the axilla after axillary dissection is not indicated.


Multicentricity in early breast cancer.

Multicentricity in early breast cancer. Breast preservation has focused attention on the extent and distribution of cancer in the breast. Recent studies suggest that there is spread from the primary tumor rather than a random distribution of cancer throughout the breast. As a result the term multicentric has largely been replaced by multifocal. Evidence that there is a geographic relationship of secondary deposits to the primary lesions opens the way to wide excision as definative treatment for selected patients with both invasive and in situ breast cancer.


Radiation therapy and breast preservation: past achievements, current results, and future prospects. In this overview the historical development of breast-conserving therapy is sketched briefly from its origins in the second and third decades of this century, and current radiotherapeutic techniques are described. All randomized trials thus far conducted using modern radiotherapy indicate that total mastectomy provides no survival advantage compared with breast-conserving techniques. In patients suitable for such treatment, macroscopically complete local tumor excision followed by appropriate radiotherapy will lead to 90-96% local control in the breast at 5 years, and 81-93% at 10 years. It is likely that the strategy of reserving total mastectomy for treatment of intramammary failures will result in ultimate local control of disease on the chest wall which is superior to that provided by primary total mastectomy. Future prospects include the use of primary chemotherapeutic approaches for larger tumors, extending the possibilities of breast conservation to a majority of patients with tumors classically considered unsuitable for lumpectomy. In this context an increase in the use of radiotherapy in the primary treatment of breast cancer is anticipated.


[Immunotherapy of type 1 diabetes].

[Immunotherapy of type 1 diabetes]. Insulin-dependent diabetes mellitus is the late consequence of a chronic autoimmune disease directed to the B islet cell, that begins long before the hyperglycemic state. Experimental evidence suggests a central pathogenic role for autoreactive T lymphocytes. Immunointervention studies, particularly those using cyclosporin, have shown that it is possible to stop B cell destruction, even at the late stage of overt diabetes. New therapeutic approaches will be focused on the use of specific agents such as monoclonal antibodies and immunotoxins, and on earlier interventions allowed by the detection of genetic and immunological markers of prediabetes.


[Screening and prevention of type 1 diabetes]. Insulin-dependent diabetes mellitus is preceded by a prodromal phase during which insulin-secreting cells are progressively destroyed by immunological factors. Among genetically predisposed and high risk subjects, this phase of prediabetes can be identified by detection of immunological and metabolic markers. For these prediabetic subjects, specific immunomodulators, without adverse effect, will be available.


Breast tumor recurrence following lumpectomy with and without breast irradiation: an overview of recent NSABP findings. The latest findings from the NSABP B-06 trial on ipsilateral breast tumor recurrence (IBTR) continue to demonstrate that through 9 years of follow-up more patients treated with radiation remained IBTR free as compared to those receiving no radiation (P less than 0.001), regardless of age, nodal status, or tumor size. There is no significant difference in distant disease-free survival (DDFS) or survival between the two lumpectomy groups despite the highly significant difference in their probability of remaining IBTR free. A recent analysis shows that when a patient is diagnosed with an IBTR, the risk of distant metastatic disease increases, indicating that an IBTR is a marker for, not a cause of, distant metastatic disease. An IBTR indicates a greater risk for distant disease when the primary tumor was removed. Mastectomy or breast irradiation following lumpectomy eliminates or reduces the opportunity for identifying a marker of risk for distant disease, thus emphasizing the importance of an IBTR beyond the need for its removal. Since an IBTR is associated with a relative risk of 3.41 for the development of distant metastatic disease, systemic therapy subsequent to an IBTR should be considered. Evidence presented from recent NSABP studies indicates the value of systemic therapy for lowering the incidence of IBTR following lumpectomy and breast irradiation.


Ipsilateral breast tumor recurrence and survival following lumpectomy and irradiation: pathological findings from NSABP protocol B-06. Ipsilateral breast tumor recurrence (IBTR) occurred in 42 of 488 (9%) pathologically evaluable patients enrolled in NSABP protocol B-06 with a mean potential follow-up of 103 months (range 68-161 months) following treatment for Stage I and II invasive breast cancer by lumpectomy and local breast irradiation (LXRT). IBTR were observed at or close to the same quadrant as the index cancers and their histologic types and nuclear grades were similar if not identical in 95 and 93%, respectively. This information confirms our earlier findings which indicated that multicentricity is of little or no clinical significance in the treatment of breast cancer by LXRT; breast cancers rarely if ever change their biologic potential once clinically detected; and lastly, most if not all IBTR represent residual cancer. Cox regression analyses revealed only a patient age less than 35 years to be significantly related to IBTR. No relationship between IBTR and so-called extensive intraductal component (EIC) or 31 other pathologic features of the index cancers was found. Overall survival was significantly related to nodal status (P = 0.01), nuclear grade (P = less than 0.001) histologic tumor type (P = 0.01) and IBTR (P = less than 0.001). This latter was considered as an indicator rather than instigator of distant disease and reduced survival since the latter is no different in patients treated by LXRT, lumpectomy alone after which IBTR is much more frequent, or mastectomy, which precludes its expression. We conclude that there are as yet no viable markers which would contraindicate treating patients with breast cancer by LXRT.


[Administration of insulin in type 1 diabetes]. Insulin therapy by subcutaneous injection is not satisfactory: it rarely brings down glycaemia to its normal level, exposes to the risk of hypoglycaemia and hyperinsulinism, is difficult to endure for a long period and requires full patient's involvement. Improvements are being achieved in the route of insulin administration (intraperitoneal and nasal routes), the type of insulin (analogues) and the material used to administer the hormone (insulin pens and implantable pumps).


Breast-conserving surgery and selective adjuvant radiation therapy for stage I and II breast cancer. In this report we update our experience with selective adjuvant radiotherapy (XRT) following breast-conserving surgery (BCS) for early breast cancer. Of 150 evaluable private breast cancer patients treated by BCS since 1975, 83 were offered the option of foregoing adjuvant XRT because their primary disease met four pathological criteria: primary tumor less than or equal to 2.5 cm; adequate resection margins; no intramammary vascular, lymphatic, or perineural invasion by tumor; and minimal or no associated in situ cancer. Of the 67 patients who chose not to have XRT, four have developed local (breast) tumour recurrence at 80 months' median follow-up (5-year local recurrence rate 6.4% by Kaplan-Meier analysis). These findings are discussed in light of other series in which patients were carefully selected for BCS without XRT, and the observations of large randomized trials and unselected series of patients. We conclude that adjuvant XRT is not always necessary following BCS. The most valuable contribution of XRT to breast-conserving therapy is that a much larger proportion of breast cancer patients can be considered for conservative locoregional surgery than would otherwise be reasonable.


[Islets of Langerhans grafts and pancreas transplantation]. In theory, transplantation of the islets of Langerhans is the method of choice for the treatment of insulin-dependent diabetes. In actual fact, medical teams who have been working on this subject for about two decades have met with the problem of islet isolation, and for the time being this treatment cannot be considered effective. Pancreas transplantation gives satisfactory results in diabetics with renal impairment when it is coupled with kidney transplantation. However, it cannot yet be applied to all diabetics as its results are mediocre when performed alone, and it requires chronic immunosuppression. Pancreas transplantation not only increases the quality of life but also has the advantage of acting on degenerative complications: it may improve diabetic nephropathy, retinopathy and neuropathy. The results obtained are getting better year after year, and they are now close to those observed with other organ transplantations.


[Oral and dietary treatments of type 2 diabetes]. Non insulin-dependent diabetes mellitus requires a metabolic and vascular treatment in order to prevent macroangiopathy. Personal diet management, which is similar in diabetic and non diabetic comparable patients, is the basis of therapy. Any significant result cannot be expected without its observance. Sulfonylurea and biguanide drugs can enhance diet action and must be prescribed secondarily according to the level of hyperglycaemia. Blood pressure and lipid control is as important as glycaemic normalization. Early diet management of obese people should be the best approach to prevent type II diabetes.


[Prevalence of asthma. Survey of a school population in Villahermosa, Tabasco, Mexico]. In the state of Tabasco, Mexico, there apparently exists a great demand for medical care in children with asthma, yet the exact number of children with this illness is unknown. This motivated us to survey the parents of 5,625 school children with ages ranging from 6 to 12 years old (2,386 girls and 2,789 boys) living in the city of Villahermosa, Tabasco. The study included 11% of the school children in the vicinity. The survey showed that 22.3% of the population of school children refer chronic or repetitive respiratory symptoms; 8.7% referred a diagnosis of asthma; 6.8% bronchitis; 2.3% asthmatic form bronchitis; and 3.9% symptoms suggestive of repeated bronchial obstruction.


[Insulin in type 2 diabetes. Why, when, how?]. Non insulin-dependent diabetes is often associated with obesity and always with some degree of insulin resistance. First choice treatment consists of appropriate and sometimes hypocaloric diet and oral hypoglycemic agents. Using insulin becomes mandatory in patients with associated pathology or at risk of metabolic imbalance. Insulin administration must be discussed in each individual case when it aims at a long-term improvement of blood glucose control, taking into account the lack of consensus on this point and the potential drawbacks of insulin therapy, notably weight increase and risk of hypoglycaemia.


[Diabetes in elderly subjects].

[Diabetes in elderly subjects]. Problems raised by diabetes in subjects above 65 years of age are of three kinds: diagnostic, therapeutic and social. Passed the age of 40, there is a regular physiological increase of glycaemia, and this must be taken into account to diagnose diabetes and to set the threshold for therapeutic intervention. The treatment of elderly people has its specific imperatives, due to feeding habits and age-related changes in hepatic and renal functions. The presence of complications, sometimes multiple, explains that the patient often takes several drugs, which increases the risk of interaction between these drugs and oral antidiabetics. The therapeutic objectives must be adjusted to these imperatives, and neither the diabetic... nor his doctor must be afraid of insulin. The social status of elderly patients must not be neglected: the help of private nurses and the training in diabetology of the patient's entourage often permit to postpone the date of institutionalization.


[Treatments of diabetes in children].

[Treatments of diabetes in children]. The treatment of children with type I insulin dependent diabetes mellitus has been improved by the combination of multi-daily self blood glucose monitoring and insulin injections. Specific aspects of therapy in neonatal diabetes, as well as in infants, are discussed. Non insulin dependent diabetes is rarely observed in pediatric ages and is generally treated with simple diet control.


[Diabetes education].

[Diabetes education]. Diabetes is a chronic disease requiring a compelling and permanent treatment which has repercussions on the patient's daily activities, tempo of life, feeding habits and physical exercises. This treatment also carries a risk of acute metabolic complications dreaded by the patient, the main one being hypoglycaemia. These constraints and fears have important effects on the patient's state of mind and must be taken into consideration by all those who look after him. For a strict and global handling of the diabetics' medical problems, it has been found necessary to institute an educational approach aimed at informing the patient, teaching him practical actions, facilitating his autonomy and reducing his anxiety and isolation. This approach is called diabetes education. It requires special training, as well as time and means, and must be subjected to evaluation. It is now well established that diabetes education is able to reduce the constraints of the disease, the frequency of metabolic accidents and the cost of diabetes. It is usually developed in hospital structures, but it also concerns private diabetologists and other medical helpers. This should convince the State authorities to recognize this teaching activity as a genuine therapeutic activity.


Study on the prevalence of eccentric and concentric atherosclerotic plaques in various segments of the coronary arterial tree, in unselected and selected Bucharest population samples. A study was carried out on the prevalence and distribution of eccentric and concentric atherosclerotic plaques in the coronary arterial tree of 916 unselected apparently healthy subjects who died from accidents and of 150 selected patients who died from coronary heart disease. The results show that the percentages of eccentric and concentric plaques vary with age, sex, anatomical branching pattern and cause of death; there are also differences between major coronary arteries and main branch vessels. In addition to eccentric and concentric plaques, we revealed the existence of mixed (both eccentric and concentric) plaques, mainly located at branch points.


Incidence and evolutive tendency of intestinal metaplasia in chronic gastritis. The histologic examination of 556 gastric biopsies performed in patients with chronic gastritis, revealed the presence of intestinal metaplasia in 81 cases (14.5%). This was correlated with the evolutive stage of gastritis, the maximum incidence being observed in the case of gastric atrophy (24.7%). The iterative examination of the patients with intestinal metaplasia, allowed the determination of its evolutive tendency. After an average period of 5 years, the occurrence of gastric malignoma was observed in 5 cases (6.3%) thus confirming the oncogenic risk of intestinal metaplasia and justifying the careful "surveillance" of these cases.


Comparative study of the variations of the phagocytic capacity of polymorphonuclear leukocytes and of total plasma antioxidants in patients with pneumoconioses and lung cancer. A comparative, preliminary study of the phagocytic capacity of polymorphonuclear leukocytes, and of the total plasma antioxidants was carried out in a group of workers professionally exposed to mineral dusts and in a group of patients with lung cancer. Both groups exhibited advanced respiratory failure stages II and III. The phagocytic capacity of polymorphonuclear leukocytes was found significantly increased in workers with pneumoconioses and moderately increased in patients with lung cancer. On the other hand, the peroxides and total plasma antioxidants exhibited great individual variations. Thus in lung cancer it was observed that peroxides had a tendency to decrease and antioxidants to increase. The individual study of the variations of these three parameters might be able to differentiate the reversible from the irreversible stages of the respiratory changes.


Changes of circulating immune complexes in the serum and CSF of patients with multiple sclerosis. The level of circulating immune complexes (CIC) was studied before and after treatment in a group of 86 patients with multiple sclerosis (MS) (36 males and 50 females) ranging in age between 20 and 30 years and in 32 controls. CIC determinations were performed both in the serum and in the CSF, using the method of precipitation in polyethylene glycol (PEG). In 61.62% of the patients the mean serum CIC values (82.44 ODU; p = 0.01) exceeded those found in the controls (60.1 ODU) while the CSF mean CIC values (21.63 ODU; p = 0.05) exceeded those in the controls in 59.30% of the patients (12.8 ODU). The prevalence of patients with CIC values exceeding the control values presented variations according to the clinical stage of disease. Thus in the acute stage 83.33% of the patients presented the highest mean serum CIC values (110.5 ODU; p = 0.05) and 100% of the patients presented the highest mean CSF CIC values (27.9 ODU). After treatment it was observed that the prevalence of patients with high CIC values decreased. In conclusion it was observed that there is a correlation between the prevalence of patients with increased CIC values in the serum and CSF, and the clinical stage and treatment administered. This observation suggests that CIC determinations both in the serum and in the CSF may constitute an immunologic marker in MS.


Transesophageal determination of SNRT and SACT in paroxysmal supraventricular tachyarrhythmias. The paper tested the hypothesis that supraventricular tachyarrhythmias (SVT) could represent the first clinical manifestation of the sick sinus syndrome (SSS). Absolute sinus node recovery time (SNRT) and sinoatrial conduction time (SACT) were determined through transesophageal approach in 16 patients with paroxysmal SVT, but without bradycardic episodes between crises. The values considered normal were: SNRTa less than or equal to less than or equal to 1500 ms; SNRTc less than or equal to 525 ms; SACT less than or equal to 150 ms. SNRTa, SNRTc and SACT were normal in all subjects (SNRTa: 1077 ms; SNRTc: 400 ms; SACT: 111 ms) and suggest the absence of a notable sinusal disfunction in these patients. We concluded that SVT unassociated with bradycardia do not usually represent a manifestation of SSS. Consequently the administration of sinusal depressant drugs in such patients could be permitted without restrictions.