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Biomedical subjects

W H Reinhart

Publications and source records attributed to W H Reinhart.

At least 19 recordsLinked to original sources

[Pseudotumor cerebri in minocyline treatment].

Pseudotumor cerebri or benign intracranial hypertension is a syndrome of raised intracranial pressure without obvious explanation. Most patients are obese women at childbearing age. Symptoms and signs usually include headache, nausea, vomiting, edema of the papilla, visual obscurations and rarely palsy of the nervus abducens. The prognosis is generally good, but progressive visual loss and eventual blindness are major risks. We report the case of a 21-year-old non-obese young woman who developed pseudotumor cerebri while taking minocycline for acne therapy. Identical symptoms occurred upon inadvert rechallenge with minocycline for the second time.

Acne Vulgaris↗

Effects of high-altitude exposure on vascular endothelial growth factor levels in man.

Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen and permeability factor that is inducible by hypoxia. Its contribution to high-altitude illness in man is unknown. We measured VEGF levels in 14 mountaineers at low altitude (490 m) and 24 h after their arrival at high altitude (4,559 m). At high altitude, VEGF increased from [mean (SEM)] 32.5 (9.2) to 60.9 (18.5) pg.ml(-1) (P < 0.004) in the arterial blood, and from 15.9 (2.9) to 49.3 (15.9) pg.ml(-1) (P= 0.0001) in the mixed venous blood. Whereas at low altitude venous and arterial VEGF levels were not statistically different from each other (P= 0.065), the VEGF concentration was significantly lower in venous than in arterial blood samples at high altitude (P=0.004). The pulmonary capillary VEGF concentration remained unchanged at high altitude [14.8 (2.5) vs 17.1 (5.4) pg.ml(-1), P=0.85]. VEGF levels in the nine mountaineers who developed symptoms of acute mountain sickness (AMS), and in the six subjects who had radiographic evidence of high-altitude pulmonary edema were similar to those in subjects without symptoms. VEGF was not correlated with either AMS scores, mean pulmonary arterial pressures, arterial partial pressure of O2, or alveolar-arterial O2 gradients. We conclude that VEGF release is stimulated at high altitude, but that VEGF is probably not related to high-altitude illness.

Adult↗

Commercial taxane formulations induce stomatocytosis and increase blood viscosity.

1. Taxanes are antineoplastic drugs which have cardiovascular side effects of unknown mechanism. We investigated their influence on blood viscosity and erythrocyte morphology. 2. Whole blood was incubated in vitro with increasing concentrations of Taxol, Taxotere, paclitaxel (0-100 microM) and the vehicles Cremophor-EL and Tween 80 (0-5% vol) for 1 h at 37 degrees C. Plasma and whole blood viscosity (Haematocrit 45%) were measured and erythrocyte morphology was assessed on glutaraldehyde-fixed cells. The same investigations were performed in seven patients before and after a Taxol-infusion. 3. Taxol and Taxotere induced a dose- and time-dependent stomatocytic shape transformation of erythrocytes. Paclitaxel alone had no effect, but the vehicles cremophor-EL and Tween 80, used in Taxol and Taxotere, respectively, induced a comparable degree of stomatocytosis. This suggests a preferential intercalation of these substances into the inner hemileaflet of the membrane lipid bilayer. Associated with this shape change a dose-dependent increase in plasma and whole blood viscosity was observed. Neither shape nor viscosity changes were reversible upon removal of the agents. After the infusion of 130-300 mg Taxol in patients a slight shift towards stomatocytosis and an increase in whole blood viscosity at high shear rate from 5.09+/-0.30 to 5.44+/-0.38 mPa.s (P<0.05) were confirmed. 4. Commercial taxane drug formulations induce stomatocytosis and increase blood viscosity, which is due to their formulation vehicles. These findings may contribute to the understanding of the cardiovascular side effects of these drugs.

Aged↗

Influence of D- and L-glucose on erythrocytes and blood viscosity.

BACKGROUND: Elevated blood glucose levels are associated with substantial morbidity and mortality. The pathomechanism behind it is not well understood. The aim of the present study was to investigate the effect of glucose on blood rheology. MATERIALS AND METHODS: Blood from healthy volunteers was incubated with various concentrations of D- and L-glucose for 1 h at 37 degrees C. Whole blood viscosity at haematocrit 45% was measured at high and low shear rate (94.5 and 0.1 s(-1)). Erythrocyte shape and volume were assessed. Haemoglobin solutions were incubated with D-glucose for up to 96 h and the viscosity was measured. RESULTS: D-glucose dissolved in H2O and diluted with isotonic NaCl, added to whole blood (additional D-glucose concentrations 0-80 mM), led to a red cell swelling and an increase in blood viscosity at low shear rate (0.1 s(-1)). This process was reversible upon removal of D-glucose. L-glucose, which is not transported into the red cell by the D-glucose-specific transport protein GLUT-1, had no effect. When D-glucose was dissolved and diluted in autologous plasma, haematocrit and viscosity remained unaffected, but L-glucose decreased both values. Incubation of a haemoglobin solution with D-glucose at 37 degrees C led to a time-dependent increase in glycosylated haemoglobin (HbA1C) up to 8%, but left the viscosity unchanged. CONCLUSION: Blood glucose tested in a wide range of concentrations did not affect blood viscosity and morphological or biophysical properties of erythrocytes.

Blood Viscosity↗

Drug-induced bronchospasm: analysis of 187 spontaneously reported cases.

BACKGROUND: The Swiss Drug Monitoring Center (SANZ) uses a systematic approach to the collection of spontaneously reported individual cases on suspected adverse drug reactions (ADRs). Spontaneous reporting schemes are designed to detect new, rare and unexpected ADRs and to act as an early warning system but there is a tendency to overreport severe reactions. OBJECTIVES: The aim of the study was to determine drug-induced episodes of bronchospasm, their seriousness and predisposing risk factors. An ADR is classified as serious if the reaction results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity. RESULTS: From 1986 to 1995 SANZ received 8,191 case reports of suspected ADRs. In 187 cases (2%) bronchospasm was reported. In 55% of these cases the reaction was regarded as serious. Analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) were reported most frequently and were involved in 24% of the cases of which 64.5% were classified as serious. In three cases a lethal outcome was reported after intravenous administration of metamizol. Anti-infectious agents were implicated in 18% (52% serious), cardiovascular drugs in 11% (50% serious), drug formulation agents in 9% (41% serious), vaccines and immunoglobulins in 5.5% (50% serious), and plasma volume expanders in 5.5% (80% serious). Other drug groups were involved in 27% of the cases. About 50% of patients experiencing bronchospasm after NSAIDs, pharmaceutical formulation agents, vaccines and immunoglobulins had predisposing risk factors such as asthma, atopy or drug allergy. In other drug groups a predisposing factor was identified in 27% or less. CONCLUSION: Drug-induced bronchospasm is frequently reported with NSAIDs, anti-infective agents, cardiovascular drugs and excipients with a high proportion of serious reactions.

Anti-Infective Agents↗

Gel-filtration of sickle erythrocytes: separation based on cell deformability.

UNLABELLED: Filtration of red blood cells (RBC) through columns of pre-swollen agarose-based beads has been evaluated using cells from subjects with sickle cell disease. Elution profiles from these gels showed elution times close to normal controls for a large fraction of sickle erythrocytes and a prolonged elution time for a sub-population of these cells. Analysis of red blood cell deformability using a computerized micropore filtration system (CTA) indicated that the deformability of sickle red blood cells in the first fraction was similar to controls but that the last fraction contained a sub-population of rigid RBC. We thus conclude that sickle red blood cell separation in columns of agarose-based beads is based upon cell deformability. Gel filtration therefore appears to be an interesting tool for the study of red blood cells in a variety of disorders with sub-populations of rigid, abnormal cells, and seems especially suited for studies in various sickle cell diseases. KEYWORDS: Deformability, gel filtration, sickle cell disease, erythrocyte

Anemia, Sickle Cell↗

Molecular biology and self-regulatory mechanisms of blood viscosity: a review.

Blood viscosity is determined by plasma viscosity, hematocrit, erythrocyte deformability and aggregation. Plasma viscosity and hematocrit are directly regulated by the organism. The molecular biology of the principal determinants of plasma viscosity, i.e., fibrinogen, immunoglobulins, albumin, and lipoproteins is outlined in this work. Hematocrit is regulated by erythropoietin, which is primarily induced by tissue hypoxia. Evidence begins to emerge that autoregulatory mechanisms may be involved in blood viscosity. Viscosity modulates gene transcription for albumin and apolipoproteins in cultured hepatocytes and the erythropoietin response to anemia in rats. Further investigations into these self-regulatory mechanisms in biorheology are, however, needed for a better understanding of blood viscosity regulation in health and disease.

Blood Viscosity↗

No influence of C-peptide, insulin, and glucagon on blood viscosity in vitro in healthy humans and patients with diabetes mellitus.

The influence of the hormones most involved in glucose homeostasis, C-peptide, insulin and glucagon on blood viscosity was tested in vitro. Whole blood (adjusted to haematocrit 45%) from healthy volunteers (n=24) and patients with diabetes mellitus (n=17) was incubated with 10(-7)-10(-10) M C-peptide, insulin or glucagon. None of these peptide hormones, neither at physiological nor at supraphysiological levels, had an influence on high (94.5 s(-1)) or low (0.1 s(-1)) shear rate viscosity. The small group of diabetic patients had a higher plasma viscosity and increased blood viscosity at 94.5 s(-1), which is in agreement with earlier studies, but decreased viscosity at low shear rate. We conclude that C-peptide, insulin and glucagon have no direct effect on blood viscosity in vitro. It is, therefore, unlikely that microvascular disturbances seen with either deficiency or excess of these hormones is due to haemorheological factors.

Adult↗

[Post-actinic jejunal lymphangiectasis: a rare case of malabsorption].

We report the case of a 63-year-old male hospitalised for chronic diarrhoea and weight loss of 11 kg within 2 years. The symptoms began after a trip to Thailand. Various investigations were negative and led to the assumption of tropical sprue, which was treated with tetracycline. Within 4 months the malabsorption deteriorated and the patient was readmitted with severe electrolyte imbalance. CT-scan of the abdomen revealed a thickened intestinal wall in the jejunum. Diagnostic laparotomy was performed and, surprisingly, revealed chylascites. Histology in a segment of the jejunum demonstrated intestinal lymphangiectasias as the cause of the malabsorption. These intestinal lymphangiectasias were most probably the sequela of radiotherapy 30 years earlier for testicular teratocarcinoma. Symptomatic therapy with middle chain triglycerides brought about substantially improvement.

Diarrhea↗

[Immediate hypersensitivity reactions to parenteral glucocorticoids? Analysis of 14 cases].

Immediate hypersensitivity reactions to parenteral glucocorticoids are rare but often serious and life-threatening. In the medical literature some hundred case reports of corticoid hypersensitivity after parenteral administration have been published. The pathomechanism may be immunological or non-immunological in nature and the reaction can be due to the steroid itself or to the excipients. We report on 14 suspected hypersensitivity reactions occurring in 13 patients immediately after parenteral glucocorticoid administration. These cases were reported to the Swiss Drug Monitoring Centre SANZ between 1981 and 1999. 5 out of 26 preparations available in Switzerland and 4 out of the 6 glucocorticoids used for parenteral administration were involved (beta-methasone, methylprednisolone, prednisolone, triamcinolone). 9 reactions were life-threatening: 3 patients experienced an acute asthma attack and 6 a serious anaphylactic reaction including shock. Risk factors were known in 10 patients: allergy was mentioned in 6 patients, and asthma and aspirin-sensitivity in 2 patients each. In 2 patients a clinically relevant cross-reaction with another glucocorticoid was known, while 6 patients tolerated another steroid without problems. Only in 6 cases were skin tests performed: 3 were positive for the preparation, and in one of these cases the skin test was positive for the steroid itself. In 2 cases the hypersensitivity reaction could be traced back to the additive carboxymethylcellulose. Practitioners should be aware of hypersensitivity reactions to glucocorticoids whenever there is a worsening of the clinical status in spite of maximal steroid therapy.

Adult↗

Pharmacological concentrations of arginine influence human whole blood viscosity independent of nitric oxide synthase activity in vitro.

l-Arginine, the natural precursor of NO, is infused in patients to restore endothelial function. Concentrations up to 7.5 mM l-arginine have been measured after parenteral administration. We investigated whether such high concentrations of amino acids influence blood viscosity in vitro. Incubation of whole blood from healthy volunteers with l-arginine, d-arginine, which has no effect on stereospecific NO synthases (NOS), the NOS substrate L-AME, the NOS inhibitor L-NNA, the amino acids l-lysine and l-glutamic acid, and finally NaCl dose-dependently decreased (up to 30% at 10(-2) M) low shear viscosity, which is primarily determined by erythrocyte aggregation. In contrast, the lipophilic NOS inhibitor L-NAME had no effect on low shear viscosity. All molecules failed to influence high shear viscosity, which is primarily determined by red cell deformability, and the erythrocyte shape remained unaltered. We conclude that high concentrations amino acids may decrease blood viscosity at low shear rate independent of NOS activity. This effect may contribute to the improved blood flow after intravascular administration of l-arginine.

Adult↗

[Potential drug interactions and number of prescription drugs with special instructions at hospital discharge].

OBJECTIVE: Up to 6% of all hospitalizations are due to adverse drug reactions and 20% of these are caused by drug-drug interactions. There is only little information on the prescription frequency of drug-combinations with the potential to induce dangerous drug-drug interactions and drugs with the need for special patient instruction (e.g. inhalers). The aim of our study was to investigate the frequency of such drug prescriptions at hospital discharge. PATIENTS AND METHODS: In a retrospective, descriptive study drug prescriptions of 100 patients discharged consecutively from the department of internal medicine of a 300 bed-hospital were analysed. Possible drug-drug interactions were detected using a special computer program. Furthermore, the number of prescriptions warranting patient instruction such as anticoagulants, antidiabetics, hormones, immunosuppressive drugs, chemotherapeutics, antituberculotic and antiepileptic drugs as well as inhalatives and injections was recorded. RESULTS: The mean age of the 100 patients (61 men, 39 women) was 61.7 years, the mean duration of the hospital stay was 9.2 days. At discharge, patients took an average of 3.5 different drugs. Half of the patients were given drug-combinations with the potential for drug-drug interactions, whereby 5% were at risk for the development of interactions of severe and 42% of intermediate degree. All drug-combinations with potentially severe interactions were prescribed deliberately. 31% of all patients took medications with the need for special education, with inhalatives being the most frequent. The prescription of drugs with potential interactions and the necessity for special patient instruction was more frequent in the elderly. CONCLUSIONS: Drug-combinations with the potential of harmful interactions and drugs with the requirement for special patient instruction are frequently prescribed at hospital discharge. The frequency of prescribing these drugs increases with age. Detection of potentially dangerous drug-drug interactions is simplified by special computer programs. Careful patient instruction about the use of certain drugs is a key issue to improve patient compliance and to guarantee an optimal treatment effect.

Aged↗

Influence of parathyroid hormone, calcitonin, 1,25(OH)2 cholecalciferol, calcium, and the calcium ionophore A23187 on erythrocyte morphology and blood viscosity.

Parathyroid hormone and calcitonin, both endocrine modulators of calcium homeostasis, may influence blood rheology. Parathyroid hormone is known to reduce erythrocyte survival, leading to anemia. Calcitonin has been found to have some vascular effects. We have analyzed the Influence of parathyroid hormone (10(-7) to 10(-10) mol/L), calcitonin (10(-6) to 10(-12) mol/L), 1,25(OH)2 cholecalciferol (10(-7) to 10(-10) mol/L), additional calcium in plasma (+1 and 2 mmol/L), and the calcium lonophore A23187 (50 micromol/L) on erythrocyte morphology and blood viscosity at high shear rate (94 s(-1)) and low shear rate (0.1 s(-1)) in vitro. The loading of erythrocytes with calcium by the ionophore A23187 produced a marked echinocytic shape transformation, an increased blood viscosity at high shear rate caused by decreased deformability of these cells, and a decreased viscosity at low shear rate caused by decreased aggregation of echinocytes. In contrast, increasing plasma calcium concentrations, parathyroid hormone, calcitonin, and 1,25(OH)2 vitamin D3 had no effect on erythrocyte morphology and blood viscosity. We conclude that an increase in intraerythrocytic calcium leads to severe echinocytosis and altered blood viscosity. The endocrine modulators of calcium homeostasis--namely, parathyroid hormone, calcitonin, and 1,25(OH)2 vitamin D3--apparently do not influence intraerythrocytic calcium to a significant degree and have, therefore, no influence on cell morphology and blood viscosity.

Blood Viscosity↗

Effects of leucocyte depletion on rheologic properties of human CPDA-1 blood.

BACKGROUND AND OBJECTIVES: Leucocyte depletion improves the quality of stored blood units. We have studied its role on blood viscosity. MATERIALS AND METHODS: Viscosity of CPDA-1 blood units was measured in a Couette viscometer at shear rates of 94.5 and 0.1 s(-1) prior to and following filtration with the Leukotrap((R)) A1 system on day 0 and after 21 days at +4 degrees C. RESULTS: On day 0, high but not low shear viscosity was significantly decreased. The red blood cell morphology was unaffected. On day 21, blood viscosity was increased similarly for unfiltered and filtered samples at both shear rates. The echinocytosis observed after storage correlated with the increase in viscosity. CONCLUSION: Leucocyte depletion is associated with a decrease in high shear viscosity. This effect is, however, completely lost after 21 days.

Adenine↗

C-reactive protein (CRP) in cerebro-vascular events.

BACKGROUND AND PURPOSE: C-reactive protein (CRP) is a useful prognostic factor in coronary heart disease. It has not been previously studied in acute cerebro-vascular events, which was the topic of the present study. METHODS: Patients admitted to the hospital for an acute cerebro-vascular event were prospectively investigated. C-reactive protein was determined nephelometrically. Infection or inflammation were excluded clinically and with an erythrocyte sedimentation rate <30 mm/h. Computed tomography or nuclear magnetic resonance imaging of the brain was performed. RESULTS: According to initial brain imaging and the clinical course the 138 patients were divided into five groups: 20 with transient ischemic attack, 20 with reversible neurological deficit lasting less than 2 weeks, 61 with completed stroke and restitution, 16 with stroke without restitution and 21 with cerebral hemorrhage. Median CRP values (range) were 3.2 (2.4-13.5), 3.3 (2.4-39.4), 4.2 (2.4-73. 4), 3.4 (3.2-44.0) and 3.5 (2.4-104.0 mg/l), respectively with no significant differences between groups in a non-parametric test (Kruskal-Wallis). Risk factors for vascular disease in general and stroke in particular had no visible influence on CRP levels. No relationship was found between time interval since onset of symptoms and CRP measurement, suggesting that an acute cerebro-vascular event has little influence on CRP values. CONCLUSION: CRP is not a useful marker to predict the outcome of an acute cerebro-vascular event on hospital admission. This is in contrast to acute coronary events.

Acute Disease↗

[Extensive eosinophilic pulmonary infiltrates in a depressive patient treated with maprotiline].

A 74 year old man developed progressive dyspnea under treatment with the tetracyclic antidepressant maprotiline for three months. A chest x-ray revealed extended pulmonary infiltrates. Marked eosinophilia of the periperal blood was found (up to 2300/microliter). Rapid clinical and radiological improvement was observed solely by withholding the drug. The eosinophil count retourned to normal within a few weeks. The possible pathogenesis is discussed and the literature reviewed.

Aged↗