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One of the most intriguing aspects of the treatment of patients with affective disorders is the drug-induced sudden reversal of mood, from depression to mania or viceversa (1). Bunney reviewed 80 studies involving 3923 patients treated with tricyclic antidepressants or monoamineoxidase inhibitors and found that 9.6 per cent of these patients had switched from depression to mania or hypomania during the treatment (1). Recently it was reported that the frequency of drug-induced switches is much greater in bipolar than in unipolar patients (2).

This study was carried out in female Wistar-Münich rats with two-kidney, one-clip hypertension, using clipped normotensive rats as controls. Metabolic studies were performed in the first two weeks of pregnancy, consisting of daily measurement of systolic blood pressure (BP) (tail-cuff), body weight (BW), and salt and water balance. At the end of metabolic studies, glomerular dynamics were studied in the unclipped kidney by micropuncture. During pregnancy, urinary output of Na+ and water was greater in hypertensive than normotensive rats. The greater natriuresis accounted for a reduced Na+ retention and a lower increase in maternal BW. Micropuncture studies showed an impaired renal auto-regulation. These results show that hypertension in pregnancy causes a salt-losing tendency, that may be secondary to incomplete renal autoregulation.

The effects on hair growth by treatment with cimetidine have been studied. This drug has been given orally to 4 women with simple hirsutism and 3 women with peptic ulcer as controls for a period of 9 months. Hair growth slowed down in all of the treated women but the results were not statistically significant. A significant decrease in urine 17-ketosteroids has been observed, while plasma levels of testosterone, 17-beta estradiol, progesterone, FSH, LH and prolactin, did not change substantially. It is concluded that, on the whole, cimetidine doses not seem to induce such results on hair growth as to claim a role in the treatment of hirsutism in other current regimes.

The results are reported of a multidisciplinary diagnostic and therapeutic program applied to 381 patients with lung carcinoma from 1983 through 1985 at Mestre General Hospital. Cytologic and/or histologic diagnosis was established in 95% and staging accomplished in 96% of the patients. One-hundred-twenty-nine patients with non-small cell cancer were primarily treated by surgery (lobectomy or pneumonectomy); 3-year survival of this group was 48%. Of the 45 patients with pN1 or pN2 disease, 23 were treated with postoperative adjunctive mediastinal radiotherapy (50Gy/25 F/5Wk); however, survival showed no significant difference in the two groups. Ninety-seven inoperable patients were treated by radiotherapy alone; among those receiving doses of 50-60 Gy in 5 to 6 weeks, 3-year survival was 10%. Chemotherapy (CAMP), used in 23 cases (22 stage IV, 1 stage III), showed no improvement in survival, as compared with a similar series of patients submitted to symptomatic treatment alone. Of the 27 patients affected by small-cell carcinoma, 14 were treated with an aggressive radiochemotherapy protocol and 13 with palliative radiotherapy or low-dose chemotherapy: median survival in the two groups was respectively 45 and 60 weeks. Our study demonstrates the clinical feasibility of interdisciplinary programs routinely applied to a large population of lung cancer patients, and confirms its rationale in terms of early diagnosis, improved staging, and adequate treatment.

Generalized stochastic Petri nets (GSPNs) are presented and are applied to the performance evaluation of multiprocessor systems. GSPNs are derived from standard Petri nets by partitioning the set of transitions into two subsets comprising timed and immediate transitions. An exponentially distributed random firing time is associated with each timed transition, whereas immediate transitions fire in zero time. It is shown that GSPN are equivalent to continuous-time stochastic processes, and solution methods for the derivation of the steady state probability distribution are presented. Examples of application of gspn models to the performance evaluation of multiprocessor systems show the usefulness and the effectiveness of this modeling tool. 15 references.

Muzolimine (M) is a new Henle’s loop diuretic with no structural similarity to currently available diuretics. M is characterized by high-ceiling activity, long duration of action and absence of the ‘rebound phenomenon’ (1) and therefore may be more advantageous than the other diuretics in the treatment of renal, cardiac or epatic edema, generally associated with antidiuresis and hyponatremia. Several reports of life-threatening hyponatremia associated with thiazide administration have recently appeared in the literature (2, 3). The administration of Henle’s loop diuretic may, in fact, impair the capacity to excrete dilute urine by inhibiting NaCl reabsorption in the distal diluting segments. Yet, the effect of M on free-water excretion has not been investigated in edematous patients with hyponatremia.

From 1983 to 1987 we studied 30 patients with leukemia searching for chromosomal alterations. Cytogenetic studies of bone marrow showed an abnormal karyotype in 19 (67%). Seven out of 14 cases of acute leukemia presented different chromosomic alterations. The Philadelphia chromosome was found in 11 patients with chronic myeloid leukemia and 3 patients with chronic lymphatic leukemia; a Pseudo-Philadelphia chromosome was present in one patient, this being the first such finding in Chile. Thus, the karyotype is a valuable complementary study not only in chronic myeloid leukemia but also in chronic lymphatic leukemia and the acute lymphoblastic and non-lymphoblastic varieties.

A high-level Petri net model of the software architecture of an experimental MIMD multiprocessor system for Artificial Intelligence applications is derived by direct translation of the code corresponding to the assumed workload. Hardware architectural constraints are then easily added, and formal reduction rules are used to simplify the model, which is then further approximated to obtain a performance model of the system based on generalized stochastic Petri nets. From the latter model it is possible to estimate the optimal multiprogramming level of each processor so as to achieve the maximum performance in terms of overall throughput (number of tasks completed per unit time).

Since the controversy over the long term efficacy of lithium has been definitively overcome with the unequivocal demonstration that lithium is a valuable treatment for both the prevention and the attenuation of affective recurrences in a substantial portion of patients suffering from Major Affective Disorders (MAD) (1, 2, 3), studies with lithium have been focused more and more on attempts to predict which candidates might be expected to have good lithium responses (4, 5, 6, 7). Clinical and experimental needs both require this type of research. First of all, adequate recognition of patients who will respond differently to lithium, not only gives a rational basis for whether or not to undertake long term lithiumstabilization, it also influences investigations of new putative stabiliz-ing treatments (8), since the definition of the risk-benefit ratios of these alternative therapies will weigh differently if they are chiefly indicated for lithium responders or lithium non-responders. Furthermore, the differentiation of lithium responders from lithium non-responders could be of fundamental importance for proper understanding of the basic processes underlying the disease in the different subgroups of MAD.

– We investigated the renal function (urine volume, glomerular filtration rate, urinary osmolality and proteinuria) of 50 patients chronically treated with lithium carbonate for major affective disorder. No patient had any alteration in the parameters considered. No relationship was found between any of the parameters studied and duration of illness or lithium levels, both in serum and red blood cells. These results were confirmed by the administration of the DDAVP test to 10 patients of the original sample; no alteration of concentration ability was found. We suggest that the discrepancy between our findings and those of most authors was a result of the serum lithium level of our patient sample, which was lower than that usually used in other studies.

Experience in treating heroin addicts with a major neuroleptic, Chlothiapin (Entumin Sandoz) is described. Treatment was begun on 16 cases and completed on 12. Slight signs of asthenia appeared in three cases. All patients completing the treatment achieved a normal sleeping pattern and reduced anxiety. Thus after a 7 day course patients could be transferred to a specialist drug addiction centre.

In 1979-80, a cross-sectional study was carried out in 7118 Neapolitan school children aged 10-15 years. In 1980-81 and 1981-82 a longitudinal study was performed in a group of children with blood pressure above the mean + 1SD (in age and sex related peers) and in a group with blood pressure less than mean + 1SD. In the whole population blood pressure increased with age from 10 to 14 years. The major determinant of blood pressure was body weight, followed by heart rate. Three hundred and ninety-eight children (5.6%) were hypertensive having blood pressure greater than mean + 2SD. In children followed longitudinally, blood pressure was very labile; only 13 per cent of those originally having blood pressure mean + 1SD, in fact, remained in the same category. All of these, however, had blood pressure greater than mean + 2SD throughout the study.

In 25 patients with acute leukemia that presented chantes in liver function tests, 29 liver biopsies were done by percutaneous needle or peritoneoscopy and directed needle, to determine the nature of the lesion. In one case leukemic infiltration was found; 16 patients showed nonspecific lesions, one, granulomatous hepatitis, one, viral hepatitis; one showed no changes in the biopsy. In these twenty cases the treatment was not modified, the survival time was from 15 to 57 months (median 25 months), and 14 an still in remission. Five patients (20%) showed drug-induced hepatitis; in these it was necessary to modify to chemotherapy, the survival time in four cases was 2 to 9.6 months (median 4.8 months) and one is still in remission after 36 months of treatment. It is concluded that hepatic biopsy may be very useful in evaluating the undesirable effects of treatment of acute leukemia and in making therapeutic decisions. The risks of this procedure and the contraindications are similar in patients with acute leukemia and those with other diseases.

A case with evidence of acquired von Willebrand's syndrome associated with systemic lupus erythmatosus and Sjögren's syndrome is described. The patient, who had no family history of bleeding, presented a haemorrhagic diathesis of recent origin, the bleeding time was prolonged, procoagulant Factor-VIII and von Willebrand factor levels were low and platelet aggregation was decreased with different concentrations of Ristocetin. No improvement was seen after the tranfusion of cryoprecipitates, and there was no increase in procoagulant Factor-VIII. Clinical improvement resulted after treatment with corticosteroids, and later, the laboratory abnormalities characteristic of von Willebrand's disease became normal. The level of procoagulant factor-VIII reached the very high level of 810%.

The theme of the seasonal tendency of schizophrenic births certainly is not new for experimental psychiatry. The tendency was first noted about 60 years ago by Tramer (1), who noted an excess of schizophrenic births during the winter and early spring. Following this, a large number of studies were undertaken, taking thousands of cases into consideration (for references, see 2,3,4). Undoubtedly, some uncertainty still exists about the role each month plays in generating this asymmetrical distribution of schizophrenic births as well as about the exact dimensions of this phenomenon. Nonetheless, the association between the future condition of schizophrenia and birth in the period of the year between December and April (in the northern hemisphere) is no longer the subject of doubt.

In this study the effects of percutaneous transluminal renal angioplasty on blood pressure and renal function were studied in 9 hypertensive patients with stenosis of the main artery of a solitary functioning kidney. The outcome of the percutaneous dilatation of the renal artery stenosis, and the effects on blood pressure and renal function were evaluated for a mean period of 16.4 +/- 2.13 (SE) months (ranging from 3 to 65 months). A successful dilatation of the renal artery stenosis was shown in all the patients by the aortography performed 1 h after the procedure. At the discharge (7.8 +/- 0.9 days after dilatation), blood pressure was 'cured' in 2 patients and 'improved' in the remaining patients; renal function was improved in all patients who had reduced renal function. At the last follow-up, no restenosis was found in patients who repeated the follow-up angiography; blood pressure was 'cured' in 3 patients and 'improved' in 6 patients, and renal function appeared steadly improved. In contrast with other reports, our results demonstrate that percutaneous renal angioplasty is a safe and effective procedure and should be attempted before considering surgical intervention in patients with artery stenosis of a solitary functioning kidney.

The incidence of traumatic events during the first ten years of life was investigated in two groups of patients suffering from major affective disorder, as well as in mixed psychiatric patients and in healthy subjects. While there were no significant differences between the two groups of affective patients or between the two control groups, the incidence of subjects who underwent such trauma was significantly higher in depressives, compared with controls. These differences are small and are further reduced if events secondary to psychiatric disturbances of family members are excluded.

We evaluated the use of heparin in continuous flow centrifugation by continuous infusion. Doses were modified by assessment of the anticoagulant effect by the thrombin time dilution test (TTDT). Heparin is an efficient anticoagulant in continuous flow centrifugation and the TTDT is an effective and reliable method for control. The initial dose in leukapheresis is one unit per milliliter of blood during the first hour, then one-half the dose during the next hour, and then a one- quarter of the dose until the procedure is completed. A TTDT performed every 30 to 60 minutes will indicate whether the heparin dose should be modified. For plasmapheresis, it is necessary to determine the specific dose for each patient. There was no case of bleeding or extracorporeal coagulation of the blood.

This chapter describes a multiprocessor performance evaluation case study, and the modeling tools that were developed for this purpose. It is shown how the choice of the architecture of a multiprocessor system can be guided by analytical performance predictions in conjunction with implementation issues. The goal of the project of a multiprocessor system is the development of an efficient architecture which should not experience bottlenecks at the physical level due to contention for shared resources. A description is given of how the comparison among candidate architectures must be done using common assumptions and a similar workload model. Only after this preliminary work can an architecture be chosen and implemented as a good compromise between performance and implementation costs.