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Biomedical subjects

P Nussbaum

Publications and source records attributed to P Nussbaum.

11 recordsLinked to original sources

A schizophrenic patient with an arrhythmic circadian rest-activity cycle.

A haloperidol-treated patient with chronic schizophrenia had a near-arrhythmic circadian rest-activity cycle, whereas rhythms of 6-sulphatoxy-melatonin and core body temperature were of normal amplitude and phase-advanced. Sleep electroencephalography measured throughout a 31-h 'constant-bedrest' protocol revealed a phase-delayed sleep-wake propensity cycle, low sleep continuity (ultradian 'bouts'), and very little slow-wave sleep and slow-wave activity (0.75-4.5 Hz). Switching treatment to the atypical neuroleptic clozapine improved both the circadian organization of the rest-activity cycle and the patient's clinical state. This observation can be conceptualized in terms of the two-process model of sleep regulation. High-dose haloperidol treatment may have lowered the circadian alertness threshold, whereas clozapine augmented circadian amplitude (perhaps through its high affinity to dopamine D4 and serotonin 5HT7 receptors in the suprachiasmatic nuclei). Measurement of the circadian rest-activity cycle may be a useful non-invasive method to follow functional consequences of neuroleptic treatment.

Adult

High interleukin-10 serum levels are associated with fatal outcome in patients after bone marrow transplantation.

IL-10 plays an important role in the control of immune reactions during systemic infection. Here, IL-10 serum levels were investigated in patients after BMT. The IL-10 levels correlated with the clinical course of the patients and with serum levels of C-reactive protein (CRP) and neopterin (NP). A total of 26 patients with AML (7), ALL (12), CML (2), NHL (3) and multifocal Ewing's sarcoma (2) had received autologous (10) or allogeneic (16) BMT from related (9) or unrelated donors (7). Routine serum samples were obtained prior to BMT and at days 46 and 100 after BMT. However, in patients with severe complications additional samples were drawn at individual points in time. Prior to BMT, IL-10 serum levels were not detectable in 24/24 patients. Post-BMT, 11 patients developed elevated IL-10 levels, of these eight died of complications (DOC), whereas only one of 15 patients with undetectable IL-10 died of complications, indicating that high IL-10 levels were significantly correlated with severe life-threatening complications (chi2, P < 0.01). To determine the pathomechanism and role of the increased IL-10 levels, they were correlated to the respective NP and CRP serum concentrations. CRP and NP concentrations were found significantly elevated in patients with detectable IL-10, indicating a severe acute phase reaction associated with macrophage activation. In conclusion, high IL-10 serum levels in patients after BMT were significantly associated with fatal outcome. Since IL-10 is a strong suppressor of T cell immunity, high IL-10 production in patients with severe complications such as septic shock or GVHD > grade II after BMT might lead to functional immunodeficiency contributing to the poor prognosis of these patients.

Adolescent

Measurement of treatment response to sertraline in depressed multiple sclerosis patients using the Carroll scale.

We studied 11 patients with stable multiple sclerosis (MS) with major depression in terms of response to Sertraline at 100 mg q.d. in an open label trial. Patients were evaluated with self assessment measurements (Carroll scale) prior to and during treatment. Only one patient discontinued the drug during the three month treatment trial, and this was due to perceived lack of efficacy by the patient. The remainder of the patients completed at least three months of treatment and had significant improvement in depressive symptoms by self assessment measurements. No patients experienced side effects. Sertraline appears to be well tolerated and effective in treatment of major depression in MS. The Carroll scale is an easily administered means of assessing treatment response, and correlated highly with our clinical impressions.

1-Naphthylamine

Activation of protein kinase C induces de novo synthesis of the soluble interleukin-6 receptor in human B cells.

The mechanism of protein kinase C (PKC) induced release of the soluble interleukin-6 receptor (sIL-6R) from human B cells was investigated. Phorbol myristat acetat (PMA)-induced activation of PKC significantly enhanced the release of sIL-6R from the human B-cell line SKW 6.4. The PMA effect was completely blocked by cycloheximide, whereas different inhibitors of proteases had no effect. In contrast to the effect on sIL-6R release, FACS analysis did not reveal any effect of PMA on the expression of IL-6R on the surface of SKW 6.4 cells. After 6 h of stimulation with PMA, analysis of mRNA expression using a polymerase chain reaction-(PCR)-assisted mRNA amplification assay, showed increased expression of a spliced mRNA encoding for a soluble form of IL-6R. Comparable to the results in SKW 6.4 cells, activation of purified human B cells with PMA induced a significant augmentation of sIL-6R release which was also sensitive to cycloheximide. In conclusion, a novel mechanism of sIL-6R release is reported involving de novo synthesis. Thus, sIL-6R release from human B cells is completely different compared with that described in hepatocytes, which involved rapid, proteolytic cleavage of the membrane-bound receptor but not de novo synthesis. The results of this study may help to understand the molecular control of sIL-6R release from human B cells.

B-Lymphocytes

[A 10-year follow-up of cases with anorexia first hospitalized in the Canton of Zürich].

Out of all 38 anorexia nervosa patients hospitalized for the first time in a private or state hospital for pediatrics, internal medicine or psychiatry in the Canton of Zurich during the period 1973-1975, 28 cases could be assessed 10 years later using a semistructured interview. Catamnestic data were categorized according to Morgan and Russel (1975) in a general outcome score and an average outcome score. Regarding somatic and psychosocial dimensions, 11% of the patients examined can be considered symptom-free, 71% improved and 14% unchanged. One patient (4%) had died from the sequelae of anorexia. 64% increased in weight, nevertheless more than half of the patients had disturbed eating behavior at the time of this catamnestic study. An equally frequent finding was considerable impairment of psychologic well-being chiefly reflected in anxiety and depression. The time necessary to attain the normal weight range had varied between a few months and 11 years. Of 8 variables often claimed to be prognostic in the literature on the course of anorexia nervosa, only a short duration of illness before hospitalization was shown to be relevant. The patients with good or medium outcome most often consider psychotherapy or a partner relationship a decisive factor in the favorable course of their eating problem.

Adult

Effects of methyldopa on renal hemodynamics and tubular function.

To determine the effects of methyldopa on renal function, clearance studies were performed on hypertensive subjects during sustained steady-state water diuresis. The data reveal an acute fall in glomerular filtration rate and sodium clearance, whereas renal blood flow was unchanged. The antinatriuresis was the result of decreased filtration of sodium and possibly enhanced proximal tubular sodium reabsorption. These changes occurred before any demonstrable fall in systemic blood pressure; thus a direct effect of the drug on arteriolar resistance within the renal circulation is suggested. Chronic administration of methyldopa for 1 wk induced sustained reduction in blood pressure and resulted in the same changes in renal hemodynamics and sodium excretion noted after acute administration. These data suggest that methyldopa, like other antihypertensives, reduces glomerular filtration rate and increases sodium retention.

Adult

Differing effects of acid versus neutral phosphate therapy of hypercalciuria.

Studies were performed on 12 patients with idiopathic hypercalciuria to evaluate the hypothesis that the acid load accompanying potassium acid phosphate would adversely affect renal calcium reabsorption and citrate excretion compared to the neutral form of the phosphate salt. During acute clearance studies, neutral phosphate (NP) led to a fall in FECa (2.2 +/- 0.6% to 0.8 +/- 0.1%, P less than 0.02) and no change in titratable acidity (TA) or net acid excretion (NAE). Acid phosphate (AP) did not reduce FECa acutely, and led to a rise in TA (22 +/- 4 to 62 +/- 6 muEq/min, P less than 0.02) and NAE (46 +/- 6 to 6 89 +/- 7 muEq/min, P less than 0.02). During chronic administration, AP resulted in higher urinary calcium excretion in both absorptive (187 +/- 29 vs. 141 +/- 18 mg/day, P less than 0.02) and renal hypercalciuric patients (233 +/- 24 vs. 173 +/- 190.02 mg/day, P less than 0.02). Also, TA and NAE were higher following AP, whereas citrate excretion was lower (375.4 +/- 64.6 vs. 633.4 +/- 28.8 mg/day, P less than 0.01). These data suggest that the reported ineffectiveness of AP in the therapy of nephrolithiasis may be related to the deleterious effects of the acid load on calcium and citrate metabolism.

Acid-Base Equilibrium

The ocular pulse.

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Angiography