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Biomedical subjects

M Berger

Publications and source records attributed to M Berger.

At least 667 records · Page 37Linked to original sources

Home treatment of antibody-deficiency syndromes with intravenous immune globulin.

Immune globulin replacement is a safe and effective therapy for patients with antibody-deficiency syndromes. The need for frequent hospital visits for treatment and high cost remain significant problems. To surmount these problems, we developed a program of patient/family-performed home administration of intravenous immune globulin. Fourteen patients were selected with predetermined eligibility criteria. Nine patients chose to enter the study. Patients and/or relatives were taught the technique of intravenous administration. A signed agreement to perform the infusion under physician instructions was required. All patients successfully performed home treatment, with an average of 19 infusions completed per patient (range 10 to 24). Home treatment decreased absence from work and school. Another benefit noted was a better self-image for patients who require life-long therapy. Regular follow-up visits with the physician are important for adequate care of patients. We conclude that home self-administration of intravenous immune globulin is feasible, safe, and effective in selected patients.

Adolescent↗

Neuroendocrinological studies on depression with special reference to research at the Max-Planck-Institute of Psychiatry.

Hypercortisolism due to Cushing's syndrome or glucocorticoid therapy induces disturbances in several other endocrine systems and may also cause mental changes, predominantly depression of various degrees. On the other hand, it has repeatedly been shown that endogenous depression is often accompanied by hypercortisolemia, usually of a modest degree, and/or by changes in other hormonal systems similar to those observed in Cushing's syndrome and during treatment with glucocorticoids. Research performed at the MPIP on 327 psychiatric patients and 103 healthy subjects has demonstrated that, in contrast to Cushing's syndrome, the circadian rhythm in depression is usually well preserved, and that diurnal variation in mood is correlated with that rhythm. Furthermore, it was found that a modest hyperactivity of the HPA system, as indicated by enhanced UFC excretion and nonsuppression in the DST, is not specific for depression in general or its endogenous subtype. It can also be observed in many other psychiatric disorders and seems to mirror stress and the influence of other factors, such as weight loss due to anorexia, rather than a particular nosology. TSH blunting in the TRH test appears as a consequence of hypercortisolemia in psychiatric disorders as is the case in Cushing's syndrome and in the course of glucocorticoid therapy. Differences in the patterns of neuroendocrine abnormalities in depressives and other psychiatric patients probably reflect differences in the individual responsiveness of the various hormonal axes to stress rather than nosological subtypes of the disorder. A comparison of these results with the past and current literature reveals remarkable changes in the concepts of neuroendocrine dysfunctions in depression and leads to suggestions of new strategies for research on this subject.

Depressive Disorder↗

Serotonin reuptake inhibition vs. norepinephrine reuptake inhibition: a double-blind differential-therapeutic study with fluvoxamine and oxaprotiline in endogenous and neurotic depressives.

The antidepressive properties of the specific serotonin reuptake inhibitor fluvoxamine and the specific norepinephrine reuptake inhibitor oxaprotiline were investigated in a sequential design with the aim of evaluating the hypothesis that two distinct biochemical subtypes of depression exist. Responders were treated for 7 weeks with the compound to which they had responded. After 1 placebo week, the nonresponders were switched to the alternative compound. An evaluation of the data obtained during the 3-week treatment periods from 24 patients (37 trials) with major depression revealed a highly significant reduction of Hamilton Scores with both compounds, oxaprotiline and fluvoxamine. If the patients with major depression are subdivided into two groups, endogenous depressives and neurotic depressives, there is no significant difference between the therapeutic improvements (both compounds) achieved in the two groups. The data shows that only about 20% of the nonresponders on one compound responded to the alternative drug, whereas 90% of responders (within 3 weeks) were still responders after 7 weeks. The data are at variance with the concept of two distinct biochemical subtypes of depression (serotonergic vs. norepinephrinergic). Dexamethasone suppression tests, performed in 23 patients, gave no prognostic hint as to whether the patients reacted well to drug therapy or not.

Adult↗

Intensive insulin therapy justifies simplification of the diabetes diet: a prospective study in insulin-dependent diabetic patients.

Dietary and metabolic variables were investigated in 48 unselected, nonobese Type 1 (insulin-dependent) diabetic patients before and 3 mo after changing from (a) traditional insulin and diet therapy to (b) intensified insulin plus simplified diet therapy. HbA1c levels declined significantly from 9.04 +/- 0.25% with therapy (a) to 8.34 +/- 0.16% with therapy (b) (p less than 0.005). During (a), 58% of all patients used a personal diet plan, but only 15% of them performed food exchange according to the traditional diet prescription. Their eating habits remained unchanged during (b). Since improved metabolic control in this study could be obtained without adherence to traditional diet schedules, a simplification of the traditional diabetes diet prescription seems justified for nonobese Type 1 diabetic patients on intensified insulin therapy.

Adult↗

REM sleep and cortisol response to the cholinergic challenge with RS 86 in normals and depressives.

The influence of the muscarinic agonist RS 86 on rapid-eye-movement (REM) sleep and on hypothalamic-pituitary-adrenocortical (HPA) axis was studied in healthy subjects and in patients with a major depression. In both groups, RS 86 induced a shortening of REM latency and an increase in REM sleep; these effects were more pronounced in the depressives than in the controls. This finding supports the assumption that in depression the REM sleep regulating neurons are hypersensitive to cholinergic stimuli. However, neither in the healthy subjects nor in the depressed patients was an RS 86 induced increase in plasma cortisol seen. This observation does not agree with the assumption that, in humans, the HPA axis is stimulated by muscarinic neurons and that hypercortisolemia in depression is due to an overactivity of muscarinic neurons activating the HPA axis.

Adult↗

Effect of high calcium intake on pressor responsivity in hypertensive rats.

Some proposed mechanisms for the hypotensive effect of high calcium intake involve reduction in vascular responsivity. To assess the effect of dietary calcium on vascular responsivity, spontaneously hypertensive rats (SHR) were placed on normal (N-Ca; 0.4%) or high (H-Ca; 2.8%) casein-based synthetic diet for 4 wk. Intraarterial pressure, pressor response to graded intravenous infusion of norepinephrine (NE) and angiotensin II (ANG II), and in vitro vascular reactivity of tail artery segments to NE and transmural nerve stimulation (TNS) were studied. Urinary electrolyte excretion, plasma renin activity (PRA), aldosterone, NE, and epinephrine (EPI) were also determined. H-Ca SHR had a lower intraarterial systolic and diastolic pressure. However, H-Ca SHR had greater in vivo pressor response to both ANG II and NE. Maximal contractile force developed by tail artery segments in vitro in response to NE and TNS was slightly, but not significantly, higher in H-Ca SHR. In vitro dose-response curves to NE and TNS were not significantly different. Although H-Ca SHR had increased urinary excretion of sodium throughout the study period, PRA and aldosterone levels were similar in both groups. Plasma NE and EPI levels in the two groups were also not different. Despite lowered intra-arterial blood pressure, H-Ca SHR exhibited enhanced pressor response to ANG II and NE in vivo and a similar in vitro vascular reactivity to NE and TNS when compared with N-Ca SHR. Our results do not support a role for alterations in vascular reactivity to NE or ANG II in the hypotensive effect of high calcium intake in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

Sleep and dreams in eating disorders.

The results of several studies on sleep EEG and dreams in patients with eating disorders are presented and compared with the data obtained in patients with a major depression. The sleep pattern, which is characteristic of depression, could not be found in the eating disorder group. Regarding the cholinergic REM induction test, the depressive displayed a pronounced shortening of REM sleep latency. However, this biological marker, indicating a cholinergic hyperactivity in depression, could not be observed in patients with eating disorders. The content analysis of laboratory-recorded dreams yielded several differences between depression and eating disorders and also, more subtle, between anorexia and bulimia.

Anorexia Nervosa↗

Increased expression of complement decay-accelerating factor during activation of human neutrophils.

Decay-accelerating factor (DAF) is a membrane protein that protects blood cells from damage by autologous complement. Using monoclonal antibodies in both direct-binding studies and flow cytometry, we found that resting neutrophils (polymorphonuclear leukocytes [PMN]) expressed 10(4) DAF molecules on their surface, and that surface DAF expression more than doubled when the cells were activated. Upregulation of surface DAF occurred within minutes, paralleled the upregulation of complement receptor types 1 and 3 (CR1 and CR3), and was not dependent on new protein synthesis. It was unaffected by EDTA but was inhibited by 10 microM trifluoperazine, suggesting involvement of intracellular Ca2+ and calmodulin or protein kinase C. Upon activation, the affected PMN lacking surface DAF from patients with paroxysmal nocturnal hemoglobulinuria failed to increase DAF expression. In contrast, these cells increased CR1 and CR3 expression normally, suggesting that DAF deficiency in affected cells involves abnormal synthesis or packaging of DAF for intracellular storage. Translocation of DAF to the cell surface induced by chemoattractants may be important in allowing PMN to survive and function at inflammatory sites where there is rapid complement turnover.

CD55 Antigens↗

Impaired surface membrane expression of C3bi but not C3b receptors on neonatal neutrophils.

Because increased complement receptor expression is necessary for optimal function of adult neutrophils, we tested the hypothesis that the increased susceptibility of neonates to infection might be due to an impaired ability of neonatal neutrophils to increase expression of complement receptors in response to chemotactic stimuli. We used monoclonal antibodies and flow cytometry to compare surface expression of the receptors for the complement components C3b (CR1) and C3bi (CR3) on adult and neonatal cord blood neutrophils (PMNs). We also compared receptor expression on PMNs from infants delivered by cesarean section without labor versus infants delivered vaginally. Expression of both CR1 and CR3 was minimal on resting adult and neonatal PMNs maintained at 0 degrees C. There was a modest increase in expression of both receptors when PMNs were warmed to 37 degrees C. This increase was similar on adult and neonatal cells, both unfractionated in whole blood and after isolation with Percoll density centrifugation, with one exception. Expression of CR1 was greater on isolated PMNs from vaginally delivered infants versus adults when the cells were warmed to 37 degrees C. This difference was not observed with cells from infants delivered by cesarean section without labor, suggesting this modest increase in receptor expression may be due to factors associated with labor. When isolated cells were stimulated with either N-formyl-methionyl-leucyl-phenylalanine or zymosan-activated serum, expression of CR1 increased to the same extent in both neonatal and adult PMNs. In contrast, maximal CR3 expression on cord PMNs stimulated with N-formyl-methionyl-leucyl-phenylalanine or zymosan-activated serum was only 75% of the adult values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sex-related differences in renal size in mice: ontogeny and influence of neonatal androgens.

Kidneys of adult male mice are larger than those of females because of both cellular hyperplasia and hypertrophy. Administration of testosterone to adult female mice induced cellular hypertrophy but not hyperplasia, so that the weight of the kidney remained smaller than in male mice. The sexual dimorphism in kidney size is not congenital but programmed by neonatal endogenous androgens and expressed between 30 and 40 days of age. Treatment of newborn males with cyproterone acetate and of newborn females with testosterone induced female and male patterns of renal growth respectively. It appears that neonatal endogenous androgens are required to induce the characteristic cellular hyperplasia of the kidneys of male mice. Manipulation of androgen levels during neonatal and prepubertal life was found to affect the growth response of the kidney to androgens in adult male and female mice.

Androgen Antagonists↗

Mechanism of exercise-induced hypoglycemia during sulfonylurea treatment.

Exercise-induced hypoglycemia in diabetic patients on sulfonylurea treatment is not uncommon. However, its pathophysiology has not been examined. We studied 9 postabsorptive nondiabetic subjects after oral administration of 1.75 mg glyburide (glibenclamide) (protocol A), during 60 min of leg exercise on a bicycle ergometer at a work load of 80 +/- 10 W (protocol B), and during a combination of these conditions (protocol C). Serum glibenclamide levels rose to similar levels (160 ng/ml) with protocols A and C. Heart rate, blood pressure, and blood lactate levels increased immediately after onset of exercise and were comparable under conditions of protocols B and C. Serum insulin levels fell during protocol B from 6.1 +/- 0.6 to 4.0 +/- 0.3 microU/ml (P less than .001) but increased from 6.5 +/- 0.6 to 12.3 +/- 2.8 microU/ml during protocol A and from 6.6 +/- 0.6 to 12.7 +/- 4.3 microU/ml during protocol C, P less than .001. Maximal levels were reached at 80 min under both conditions. Comparable responses were seen for serum C-peptide concentrations. Blood glucose concentrations did not change during exercise alone. Glycemia decreased markedly after administration of the drug reaching a nadir of 49 +/- 3 mg/dl with protocol A and a nadir of 46 +/- 3 mg/dl under protocol C. However, the nadir was reached 80 min after oral ingestion of the drug when exercise and glyburide were combined, compared to 110 min (P less than .01) after ingestion of the drug alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Coats' disease in a renal transplant recipient.

We report the first case, to our knowledge, of Coats' disease, an idiopathic exudative retinopathy, in a renal transplant recipient. Due to certain similarities in clinical presentation and confounding factors present in patients who have received kidney allografts, our patient was originally misdiagnosed as having cytomegalovirus retinitis. We emphasise the significance of this diagnostic distinction and the association of this retinal syndrome with renal disease.

Adolescent↗

Characterization of a protein fatty acylesterase present in microsomal membranes of diverse origin.

A microsomal activity of baby hamster kidney cells which cleaves ester-type bound fatty acids from acyl proteins in vitro has been characterized. This activity is also present in microsomal membranes from pig liver, calf kidney, and human mucous cells. Cell free deacylation is described for the Semliki Forest virus acyl proteins E1 and E2 and the precursor of E2 designated p62. Acyl chain cleavage operates with both exogenous and endogenous viral acyl protein substrates. The in vitro cleavage requires microsomes solubilized by detergents of which various kinds are equally effective (Nonidet P-40, Tween 20, sodium deoxycholate, Triton X-100, or octyl-beta-D-glucoside). If microsomes are boiled for 15 min prior to the incubation, deacylation is abolished completely and no radioactivity is released from the palmitoylated acyl proteins during incubation with either detergents or microsomes alone. No changes in the molecular structure of the deacylated Semliki Forest virus proteins were detected, and the cleavage product was identified as free fatty acid. Deacylation is time- and temperature-dependent and can be enhanced by increasing the concentration of microsomal protein in the incubation mixture. It is completely inhibited under acidic conditions (pH 5) and at low temperature (4 degrees C). Deacylation also occurs in the presence of EDTA and bivalent cations such as Mg2+, Mn2+, and Ca2+ which influence the reaction marginally. On the other hand, fatty acid release is drastically reduced with a mixture of Co2+, Zn2+, and Hg2+ ions. The activity is not identical with protein fatty acyltransferase operating in the reverse direction, since a partially purified preparation of this acyltransferase failed to cleave fatty acids from fatty acylated substrate proteins. Taken together, these data lead us to postulate an enzymatic activity which cleaves fatty acids from ester-type fatty acylated proteins, and we propose to designate this enzyme a protein fatty acylesterase.

Animals↗