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Biomedical subjects

M Weiss

Publications and source records attributed to M Weiss.

At least 451 records · Page 25Linked to original sources

Spontaneous or experimentally induced formation of a special zone in the adrenal cortex of the adult brush-tailed possum (Trichosurus vulpecula).

The cytology and ultrastructure of the hypertrophied special zone, which is formed spontaneously in the adrenal cortex of adult female brush-tailed possums (Trichosurus vulpecula), was compared to the adrenocortical tissue in adult males in which the special zone, normally absent, was induced following castration alone or by additional treatment with follicle-stimulating hormone (FSH). The special zone in females was situated between the zona fasciculata and the zona reticularis, the latter being a rudimentary zone in this species. Special zone tissue extended as a broad band parallel to and on one side of the adrenal medulla. In the luteal phase of the reproductive cycle, the special zone cells showed ultrastructural features commonly associated with steroidogenic tissues, with many mitochondria and compact masses of smooth endoplasmic reticulum. Cytoplasmic lipid inclusions were rarely observed. In lactating females, however, the special zone cells exhibited cytological and ultrastructural features suggestive of a transformation in their morphology broadly divided into two types of cells: (1) cells at the periphery of the special zone (closest to the zona fasciculata) showed variable quantities of lipid inclusions, mitochondria with dispersed cristae, and segregation of the smooth endoplasmic reticulum into compact masses; (2) cells within the more central regions showed an increasing abundance of lipid inclusions which in many cells became the dominant feature of the cytoplasm. These special zone cells contained very little smooth endoplasmic reticulum and their mitochondria contained few cristae together with amorphous granular material within the matrix. In castrated males, special zone tissue developed between the zona fasciculata and the zona reticularis, appearing initially as focal islands of cells (8 months postcastration) and later (11 months postcastration) expanding into a single zone, probably via the proliferation and differentiation of adjacent cells of the zona fasciculata and longitudinal growth of the special zone. Similar focal aggregations of special zone cells were induced after 14 days of FSH treatment given to 2-month castrated males. In all castrated and FSH-treated castrated males, the ultrastructure of special zone cells was similar to that of special zone cells in luteal-phase female possums. The findings suggest that the formation and cellular composition of the special zone is associated with changes in the pituitary-gonadal axis and that FSH plays a primary role in the differentiation of this tissue.

Adrenal Cortex↗

Spiroergometric performance of children and adolescents with chronic renal failure.

Maximal physical performance (Wmax), maximal oxygen consumption (VO2max), maximal carbon dioxide production (VCO2max) and blood lactate (L) levels were measured in 34 paediatric patients with chronic renal failure (CRF) and 25 controls by spiroergometric testing on a bicycle ergometer. No patient was treated with erythropoietin. The workload was increased step-wise by 0.5 W/3 min up to a Wmax determined from the attainment of VO2max. In patients on conservative treatment (CT), on haemodialysis (HD) and after transplantation (TP) median Wmax per kilogram body weight was reduced to 76%, 73% and 73% of controls (C), respectively. In CT and HD patients VO2max and VCO2max were decreased to an even higher extent. The ventilatory anaerobic threshold, calculated from the levelling off of the respiratory equivalent (VE/VO2) during increasing workload, was only slightly higher in patients than in C when related to Wmax (NS). The physiological rise in L during exercise was blunted in CRF; 72% of patients on CT or HD did not exceed the expected threshold L level of 4 mmol/l; after TP the L changes normalized. The findings indicate that most children and adolescents with CRF are able to attain maximal physical performance but both the aerobic and the anaerobic capacity are often reduced. Preliminary findings indicate that treatment of renal anaemia with erythropoietin is able to considerably improve Wmax and VO2max in paediatric HD patients.

Adolescent↗

Methodological error and spatial variability of organ blood flow measurements using radiolabeled microspheres.

The quantitative analysis of the spatial variability of organ blood flow by means of radiolabeled microspheres (MS) requires that the methodological variability ("error") of the technique (RDmeth.) is known in each individual organ. Therefore, RDmeth. was quantified (eight to nine nuclides) in 6941 tissue samples from 13 organs of three anesthetized dogs, and the relative importance of errors originating from both the stochastic nature of MS distribution (RDtheo.) and the process of quantitation of MS radioactivity (RDcounting) was assessed under varying conditions (high/low specific MS activity (SAMS); inaccurate separation of gamma spectra; large sample size). At "minimized" methodological error (experiment 2), RDmeth. of samples trapping approximately 375 MS/nuclide was 5.8% and only slightly exceeded RDtheo. (5%). RDmeth. varied in the range 2.7-7.8% in individual organs and contributed little (3.5%) to the organs' observed spatial variability of flow. In contrast, RDmeth.--due to increased RDcounting--considerably exceeded RDtheo. when SAMS was low (experiment 3), overlap of two nuclides' main photopeaks was critical (experiment 1), or counting geometry was inappropriate (pulmonary tissue samples). At the same time, the contribution of RDmeth. to spatial flow variability rose to 7.9% (experiment 3), 26.9% (experiment 1), and 15-23% (lungs). Completely artifactual measurements, as indicated by an extremely high RDmeth. of sample flow, were rarely observed (less than 0.1%). In general, our data suggest that blood flow can be measured reproducibly and with low methodological error using up to 8 nuclides, RDmeth. does not essentially contribute to the observed spatial variability of organ blood flow, and, hence, organ flow variability may be accurately quantified using the MS technique. However, if sources of error as indicated above are present, the practice of using RDtheo. as a measure of RDmeth. (thereby neglecting RDcounting) may notably underestimate true MS error and result in an overestimation of spatial heterogeneity of organ blood flow. RDmeth., therefore, should be quantified separately in each region of interest prior to the onset of a new study.

Animals↗

[Anesthesia and intensive care for heart-lung transplantation].

Since Shumway carried out the first successful heart-lung transplant (HLT) in Stanford in 1981, HLT has become a new therapeutic means for patients with end-stage pulmonary disease or arterial hypertension. However, it is still rarely carried out because of a lack of donors and the complexity of the surgery and postoperative course. This review described the criteria for proper donor and recipient selection, as well as the anaesthetic and postoperative management of HLT patients at Marie Lannelongue Hospital. The lack of suitable organ grafts results, at least in part, from improper donor management. Pulmonary oedema by fluid overloading and excessive haemodilution should be carefully prevented. Low doses of catecholamines and vasopressin maintain circulatory stability and convenient organ function. The indications for HLT (primary pulmonary hypertension, Eisenmenger's complex, and end-stage bronchopulmonary disease) are all characterized by severe pulmonary hypertension, hypoxaemia and cardiac failure. Careful anaesthetic induction is required to avoid circulatory collapse. Cardiopulmonary bypass (CPB) should be started early, so that mediastinal dissection may be carried out in satisfactory haemodynamic conditions. After unclamping the aorta, circulatory support with fluid and catecholamine infusion is often required. High inspired oxygen fraction and end-expiratory positive pressure may be required because of reperfusion pulmonary oedema. Blood transfusion is often needed as there are major blood losses due to dissection of the posterior mediastinum during CPB. Postoperative catecholamine administration is prolonged over several days. Negative fluid balance is often necessary to reduce pulmonary oedema. Improvement in surgical technique, early extubation, and late prescription of steroids have reduced the incidence of tracheal complications. Acute renal failure often occurs as a result of prolonged CPB, hypovolaemia, drug nephrotoxicity and sepsis. Bacterial complications (pneumonia, mediastinitis) are the main causes of early death. After the 15th postoperative day, opportunistic infections and allograft rejection are the main complications. Since 1981, major advances in HLT recipient management resulted in improved survival rates (70-80% at 1 year, and 60-70% at 2 years for the best teams). Despite the complexity of management, and the longterm threat of obliterative bronchiolitis, HLT is, at present time, the only possibility for these young patients to recover a normal quality of life.

Anesthesia, General↗

Perfusion of the interventricular septum during ventilation with positive end-expiratory pressure.

OBJECTIVE: To determine whether regional hypoperfusion of the interventricular septum occurs during ventilation with positive end-expiratory pressure. DESIGN: Animal study. ANIMALS: Anesthetized, closed chest dogs (n = 8). INTERVENTIONS: Induction of experimental adult respiratory distress syndrome (ARDS) and then ventilation with 10, 15, and 20 cm H2O of positive end-expiratory pressure. MEASUREMENTS AND MAIN RESULTS: Cardiac output and regional interventricular septum blood flow were assessed at control, at induction of experimental ARDS, and at each level of positive end-expiratory pressure. Ventilation with 20 cm H2O of positive end-expiratory pressure decreased cardiac output (-32% vs. control, p less than .05), and did not change absolute, but increased relative (to cardiac output) interventricular septum blood flow. During experimental ARDS and ventilation at 20 cm H2O end-expiratory pressure, there was a redistribution of flow toward the right ventricular free wall (+93%, p less than .001) and the right ventricular part of the interventricular septum (+68%, p less than .01), while flow to the left ventricular interventricular septum and to the left ventricular free wall remained unchanged. Locally hypoperfused interventricular septum areas or findings indicative of interventricular septum ischemia were not observed during positive end-expiratory pressure. CONCLUSIONS: The decrease in cardiac output during positive end-expiratory pressure is not caused by impaired interventricular septum blood supply. The preferential perfusion of the right ventricular interventricular septum indicates increased local right ventricular interventricular septum oxygen-demand and suggests that during positive end-expiratory pressure, this part of the interventricular septum functionally dissociates from the left ventricular interventricular septum and the left ventricular free wall to support the stressed right ventricle.

Animals↗

Amine Accumulation in Acidic Vacuoles Protects the Halotolerant Alga Dunaliella salina Against Alkaline Stress.

Amines at alkaline pH induce in cells of the halotolerant alga Dunaliella a transient stress that is manifested by a drop in ATP and an increase of cytoplasmic pH. As much as 300 millimolar NH(4) (+) are taken up by the cells at pH 9. The uptake is not associated with gross changes in volume and is accompanied by K(+) efflux. Most of the amine is not metabolized, and can be released by external acidification. Recovery of the cells from the amine-induced stress occurs within 30 to 60 minutes and is accompanied by massive swelling of vacuoles and by release of the fluorescent dye atebrin from these vacuoles, suggesting that amines are compartmentalized into acidic vacuoles. The time course of ammonia uptake into Dunaliella cells is biphasic-a rapid influx, associated with cytoplasmic alkalinization, followed by a temperature-dependent slow uptake phase, which is correlated with recovery of cellular ATP and cytoplasmic pH. The dependence of amine uptake on external pH indicates that it diffuses into the cells in the free amine form. Studies with lysed cell preparations, in which vacuoles become exposed but retain their capacity to accumulate amines, indicate that the permeability of the vacuolar membrane to amines is much higher than that of the plasma membrane. The results can be retionalized by assuming that the initial amine accumulation, which leads to rapid vacuolar alkalinization, activates metabolic reactions that further increase the capacity of the vacuoles to sequester most of the amine from the cytoplasm. The results indicate that acidic vacuoles in Dunaliella serve as a high-capacity buffering system for amines, and as a safeguard against cytoplasmic alkalinization and uncoupling of photosynthesis.

Journal Article↗

Polyphosphate Hydrolysis within Acidic Vacuoles in Response to Amine-Induced Alkaline Stress in the Halotolerant Alga Dunaliella salina.

The location and mobilization of polyphosphates in response to an amine-induced alkaline stress were studied in the halotolerant alga Dunaliella salina. The following observations suggest that polyphosphates accumulate in acidic vacuoles: (a) Accumulation of large amounts of polyphosphates is manifested as intravacuolar dense osmiophilic bodies in electron micrographs. (b) Uptake of amines into the vacuoles induces massive hydrolysis of polyphosphates, demonstrated by in vivo(31)P-nuclear magnetic resonance, and by analysis of hydrolytic products on thin layer chromatograms. The analysis indicates that: (a) Polyphosphate hydrolysis is kinetically correlated with amine accumulation and with the recovery of cytoplasmic pH. (b) The major hydrolytic product is tripolyphosphate. (c) The peak position of the tripolyphosphate terminal phosphate in nuclear magnetic resonance spectra is progressively shifted as the cells recover, indicating that the pH inside the vacuoles increases while the pH in the cytoplasm decreases. (d) In lysed cell preparations, in which vacuoles become exposed to the external pH, mild alkalinization in the absence of amines induces polyphosphate hydrolysis to tripolyphosphates. It is suggested that amine accumulation within vacuoles activates a specific phosphatase, which hydrolyzes long-chain polyphosphates to tripolyphosphates. The hydrolysis increases the capacity of the vacuoles to sequester amines from the cytoplasm probably by releasing protons required to buffer the amine, and leads to recovery of cytoplasmic pH. Thus, polyphosphate hydrolysis provides a high-capacity buffering system that sustains amine compartmentation into vacuoles and protects cytoplasmic pH.

Journal Article↗

Hydrolysis of polyphosphates and permeability changes in response to osmotic shocks in cells of the halotolerant alga dunaliella.

The effects of osmotic shocks on polyphosphates and on the vacuolar fluorescent indicator atebrin have been investigated to test whether acidic vacuoles in the halotolerant alga Dunaliella salina have a role in osmoregulation. Upshocks and downshocks induce different patterns of polyphosphate hydrolysis. Upshocks induce rapid formation of new components, tentatively identified as 5 or 6 linear polyphosphates, formed only after upshocks with NaCl and not with glycerol, indicative of compartmentation of Na(+) into the vacuoles. Conversely, downshocks induce a slower transient accumulation of tripolyphosphates, indicating activation of a different hydrolytic process within the vacuoles. Osmotic shocks do not lead to release of atebrin from acidic vacuoles, indicating that they do not induce a major intravacuolar alkalinization. However, osmotic shocks induce transient permeability changes measured by amine-induced atebrin release from vacuoles. Hypoosmotic shocks transiently increase the permeability (up to 20-fold), whereas hyperosmotic shocks induce a rapid drop in permeability. Electron micrographs of osmotically shocked cells also reveal transient changes in the surface and internal organelles of D. salina cells. It is suggested that hyperosmotic and hypoosmotic shocks induce different changes within acidic vacuoles and in the organization and/or composition of the plasma membrane in Dunaliella.

Journal Article↗

Evaluation of effectiveness and tolerability of isosorbide mononitrate during a three-year period in patients with angina pectoris.

The antianginal effect and tolerability of isosorbide mononitrate (ISMN), 20 mg 2-3 times daily, orally were investigated in an open study in 28 patients, suffering from coronary heart disease and stable angina pectoris. Ergometric exercise tests were carried out before treatment and 2 h after drug intake, every 3 months during the first year and at 6-month intervals during the following 2 years. At the conclusion of the 3-year study the reduction of ST-segment depression, which had amounted to 58% after 1 year, could be improved to 78% (p less than 0.01). The frequency of angina was markedly reduced during the treatment with ISMN. While 14 of the patients had more than 3 episodes per day prior to the study, 16 patients were symptom-free at the end of the three years' therapy, and none of the patients had more than 1 or 2 attacks per day. The consumption of sublingual nitroglycerin diminished by 94% after one year and by 98% after 3 years of therapy (p less than 0.01). Headache was the only adverse effect observed in some of the patients (at the initiation of the treatment only). In conclusion this study demonstrated (1) the good tolerability of ISMN, at the doses used, and (2) the fact that the antianginal efficacy may be enhanced during the course of the therapy.

Adult↗

Hypocalciuria of preeclampsia is independent of parathyroid hormone level.

Hypocalciuria is a feature of preeclampsia. The roles of parathyroid hormone (PTH) and vitamin D 1,25(OH)2D3 (calcitriol) in its pathogenesis have not yet been determined. Fourteen preeclamptic women were compared with 12 women with chronic hypertension and 11 normotensives, all in the third trimester. Preeclamptics had the lowest urinary calcium excretion rate (62.1 +/- 32.8 mg/24 hours) compared with chronic hypertensive women (162.6 +/- 97.8 mg/24 hours) and normotensive controls (225.6 = 146.9 mg/24 hours) (P less than .05). Serum PTH was lowest in preeclamptics (9.8 +/- 5.5 pg/mL), in contrast to the chronic hypertensives (18.5 +/- 2.7 pg/mL) and normotensives (16.4 +/- 3.2 pg/mL) (P less than .005). Similarly, urinary cyclic adenosine monophosphate (cAMP) excretion was 2.9 +/- 1.4 mumol/24 hours in the preeclamptics, 5.1 +/- 1.7 mumol/24 hours in the chronic hypertensives, and 4.6 +/- 1.3 mumol/24 hours in the normotensive group (P less than .05). These data suggest that the mechanism of hypocalciuria in preeclampsia is independent of the PTH-calcitriol axis. Therefore, it is suggested that the hypocalciuria of preeclampsia is due to intrinsic renal tubular dysfunction.

Adult↗

Polyphosphate-hydrolysis--a protective mechanism against alkaline stress?

Different microorganisms, including yeast and algae, accumulate large amounts of polyphosphates. However, the physiological role of polyphosphates is largely unknown. In vivo 31P NMR studies, carried out in the unicellular alga, Dunaliella salina, demonstrate the cytoplasmic alkalization induces massive hydrolysis of polyphosphates, which is correlated kinetically with the recovery of cytoplasmic pH. Analysis of acid extracts of the cells indicates that long-chain polyphosphates are hydrolysed mainly to tripolyphosphate. It is suggested that the hydrolysis of polyphosphates provides a pH-stat mechanism to counterbalance alkaline stress.

Adenosine Triphosphate↗

[The prehospital phase of acute myocardial infarct and its significance for thrombolytic therapy].

Early thrombolytic therapy has become the treatment of choice for acute myocardial infarction (AMI). Of 189 patients admitted with AMI to the CCU of Berne University Hospital in 1988, only 17 (9%) underwent thrombolytic treatment. 101 patients (53%) were admitted within 4 hours after onset of symptoms. Early arrival (less than 4 hours) was significantly more frequent among patients admitted without prior medical consultation (76%, p less than 0.001), patients less than 65 years of age (67%, p less than 0.001), patients sustaining AMI outdoors (74%, p less than 0.005) and patients without a history of typical angina (71%, p less than 0.05). In all subgroups analyzed more than half of the prehospital delay (2.8 hours) was due to the patients' indecision whether to seek medical help; prehospital consultation by a general practitioner took 66 minutes and transportation arrangements 30 minutes; in-hospital delay from admission to intensive care treatment amounted to 72 minutes (39 minutes for arrival less than 4 hours; all median times). Overall in-hospital mortality was 16.6%. Mortality during a follow-up period of 4-16 months (overall 8.4%) was higher for patients with reinfarction (15.2%, p less than 0.05) and patients arriving with a delay greater than 4 hours (12.5%, p = 0.08). Combined mortality was 25% among 172 conservatively treated patients vs 0/17 among patients undergoing thrombolytic treatment (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗