[Insulin--the cause of hypertension?].
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Biomedical subjects
Publications and source records attributed to M Berger.
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High-performance liquid chromatography-thermospray mass spectrometry was applied to the analysis of various radiation-induced decomposition products of thymidine including N-(2-deoxy-beta-D-erythro-pentofuranosyl)formamide and the various diastereomers of 5,6-dihydroxy-5,6-dihydrothymidine, 5-hydroxy-5,6-dihydrothymidine and 5,6-dihydrothymidine. This method combines high sensitivity and product resolution, rendering it particularly useful for monitoring the formation of radiation-induced base damage within DNA.
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We describe a case of cerebellar neuroblastoma with histologic documentation of maturation into a ganglioglioma sixteen months later. Only chemotherapy was administered following the initial surgery and the child is well and disease-free three years following her final surgical procedure. The outcome of this patient supports previous hypotheses that the cerebellar neuroblastoma may be a less malignant tumor than its other primitive neuroectodermal posterior fossa counterparts. Furthermore, this case suggests a role for second-look surgery in the management of selected pediatric brain tumors.
The clinical and therapeutic features of 20 patients with medulloblastoma treated at Children's Hospital and Medical Center, Seattle, from 1980 to 1987, were retrospectively analyzed with regard to prognosis. The overall actuarial 5-year survival rate was 63%, with 57% of patients free from recurrence at 5 years. Residual contrast enhancement on CT scans taken immediately postoperatively was associated with a significantly decreased 5-year recurrence-free survival rate; the 5-year recurrence-free survival rate was 100% for those patients without post-operative residual enhancement compared to 41% for those patients with residual enhancement. A high risk group of patients with residual contrast enhancement persisting one year following diagnosis was identified. No patient in this group survived without disease progression. Other factors, including sex, age at diagnosis, evidence of tumor dissemination, or extent of surgical resection as reported by the neurosurgeon, did not significantly influence prognosis.
We have investigated the hypothesis that insulin is a causal and independent risk factor for blood pressure elevation in humans by comparing pre- and post-operative blood pressure values of 34 consecutive patients with histologically-confirmed diagnosis of insulinoma and 34 age- and sex-matched control patients. In patients with insulinoma hypoglycaemic symptoms were present for 18 (9-36) months. (Values are given as median and 95% confidence interval or mean and SD). After removal of insulinoma fasting plasma insulin levels decreased from 22 (16-28) mU/l to 11 (6-20) mU/l (p less than 0.003) and minimal fasting plasma glucose concentrations increased from 2.5 (2.0-3.0) to 4.4 (4.2-5.7) mmol/l (p less than 0.002) while blood pressure values remained unchanged. Body mass index before operation was comparable between the groups: 25.5 (5.4) kg/m2 in insulinoma patients and 24.8 (4.7) kg/m2 in control subjects. Pre-operative and post-operative blood pressure values did not differ between the groups, being (systolic/diastolic) 133 (18)/82 (9) mm Hg in insulinoma patients and 128 (15)/78 (10) mm Hg in control subjects before and 129 (19)/80 (10) mm Hg and 125 (11)/76 (7) after surgery. Chronic hyperinsulinaemia in patients with insulinoma is not associated with a detectable elevation of blood pressure values. Correction of hyperinsulinaemia after surgery for insulinoma does not result in blood pressure changes. These results argue against the hypothesis that insulin is an independent causal factor in the development of essential hypertension in humans.
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Using a mobile ambulance the quality of diabetes care was evaluated, according to the recommendations of the St. Vincent Declaration, in 95% of all known diabetic patients (n = 395) in a geographically defined rural area of Austria with 7871 inhabitants. Fourteen of the 395 patients had Type 1 (insulin-dependent) diabetes with age at onset of diabetes below 30 years. Of the 375 patients examined (women 61%, age 66 +/- 13 years, median diabetes duration 6 years) 16% were treated with insulin and 47% with oral agents; HbA1c levels were 7.3 +/- 1.7%. Prevalence of known hypertension was 54%; 68% of these patients had their blood pressure uncontrolled (systolic greater than or equal to 160 and/or diastolic greater than or equal to 95 mmHg); a further 15% of patients with previously unknown hypertension had blood pressure values of greater than or equal to 160 and/or greater than or equal to 95 mmHg. Urinary albumin concentrations of greater than 200 mg/l were found in 15% of patients, 2% had a serum creatinine level of greater than 177 mumol/l, no patient had renal replacement therapy. Six patients (1.5%) were blind. Screening for retinopathy identified six patients (out of 317 in whom the retina could be evaluated) for whom consultation with an ophthalmologist as soon as possible was recommended. Of the total patient group (n = 395) 20 patients (5%) had foot complications (amputations and/or ulcers): 14 patients had a total of 21 lower limb amputations (eight above knee, six below knee, seven below ankle); eight of these 14 patients lived in a nursing home; 11 patients had a total of 13 foot ulcers.(ABSTRACT TRUNCATED AT 250 WORDS)
The small heat shock protein (hsp) genes of Drosophila are expressed in cultured cells in response to the moulting hormone, ecdysterone. We show here that juvenile hormone (JHIII) and the juvenile hormone analogue, methoprene, inhibit that induction in a dose-dependent manner. Heat shock induction is not inhibited. In transient expression studies using S3 line cells transfected with EcRE-CAT constructs, methoprene inhibition was found to require a 2-hr pretreatment (before ecdysterone addition), and methoprene's continued presence was essential. Farnesol, farnesyl acetate, and retinoic acid did not cause inhibition. Several models of methoprene inhibition are discussed.
This study investigated sleep EEG during placebo and after cholinergic stimulation with RS 86 in 36 healthy subjects, 34 patients with major depression and 20 patients with anxiety disorders. Cholinergic stimulation with RS 86 led to a decrease of slow wave sleep and REM latency. RS 86 had a more profound impact on REM latency in patients with major depression than in healthy controls and patients with anxiety disorders. Six out of 36 healthy controls, three out of 20 patients with anxiety disorders and 24 of 34 patients with depression displayed sleep onset REM periods after cholinergic stimulation. Also effects on REM density and duration of the first REM period were more pronounced in major depression. Even in those patients with anxiety disorders and a secondary major depression no depression-like sleep abnormalities could be provoked. The results underline the usefulness of the cholinergic REM induction test to differentiate patients with major depression from those with other psychiatric disorders. The results can be interpreted as further evidence for the cholinergic-aminergic imbalance model of depression and for the reciprocal interaction model of nonREM-REM regulation.
1. Healthy volunteers and patients with a major depressive disorders were administered 1.5 mg RS 86 (a cholinergic agonist) and placebo in a randomized double-blind cross-over design at 10 p.m. prior to bedtime. 2. Polysomnographic recordings demonstrated a significantly more pronounced shortening of REM latency after cholinergic stimulation in depressed patients compared to healthy subjects. 3. Even those depressed patients displaying placebo REM latencies in the normal range showed sleep onset REM periods after cholinergic stimulation. 4. The results support the reciprocal interaction model of NonREM-REM sleep regulation and the cholinergic-aminergic imbalance model of depression.
We describe an unusual example of cellular immunodeficiency associated with interleukin-2 deficiency in an otherwise healthy 15-year-old boy who had isolated cryptococcal osteomyelitis of the scapula at 10 years of age. His previous medical history was remarkable only for prolonged, severe varicella infection at 6 years of age. He had persistent moderate lymphopenia, anergy, and absent lymphocyte blastogenic responses to mitogens, antigens, or monoclonal T cell antibodies. Subnormal blastogenic responses were seen after exposure to high concentrations of phorbol esters. Immunoglobulin levels and specific antibodies were normal. The patient has been in good health since treatment of his osteomyelitis. However, his lymphocyte blastogenic responses to mitogens have remained absent during 4 years of observation; investigation of the cause revealed a specific interleukin-2 deficiency resulting from defective generation of interleukin-2 messenger ribonucleic acid. Secretion of interleukin-1 by monocytes was normal, suggesting that the abnormal blastogenic response and interleukin-2 production were due to a problem intrinsic to T lymphocytes. The generation of messenger ribonucleic acid for interleukin-4 was not affected. Interferon-gamma was produced at subnormal levels. The addition of recombinant interleukin-2 restored lymphocyte blastogenic responses and increased the expression of interleukin-2 receptors. The clinical findings and immunologic abnormalities present in this patient differ from other primary and secondary immunodeficiencies associated with interleukin-2 deficiency. Thus our observations in this patient extend the spectrum of immunodeficiencies associated with abnormalities in the production of this important cytokine.
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Apart from the eminent changes in the neurotransmitter systems of the central nervous system, a disturbance of the calcium ion concentration may be of significance in the pathophysiology of affective psychoses. The present paper deals with the contribution of calcium ions in the generation of affective psychoses and discusses the calcium antagonism as a new strategy in the treatment of the disease. The following topics will be described: 1. Disturbances of calcium metabolism in affective psychoses, 2. a comparison of lithium and carbamazepine effects, 3. clinical studies with organic calcium channel blockers in affective psychoses and 4. the role of calcium ions in affective psychoses.
Dependent on the dosages used, digestion and absorption inhibitors or disaccharidase inhibitors, such as Acarbose, might cause malabsorption of nutrients, and hence, among other effects, affect caloric balances. This negative effect on caloric balance has actually been well documented in animal experimentation. However, in nondiabetic subjects with excessive degrees of obesity, no consistent weight reduction could be induced by disaccharidase inhibitors. Subsequently, Acarbose has been advocated for type 2 diabetic patients in dosages that might reduce postprandial hyperglycemia and insulinemia, whereas significant degrees of malabsorption should be excluded. At these dosages of the drug, there is no clinical perspective with regard to weight-reducing (side) effects of disaccharidase inhibitors. Whether a hypothetical diminution of serum insulin daily profiles during Acarbose treatment in obese type 2 diabetic patients might contribute to a normalization of the metabolic syndrome and to a facilitation of weight-reducing efforts remains speculative. At present, there does not seem to be much rationale in trying to exploit digestion and/or absorption inhibitors for weight-reduction therapies in obesity, unless they are used to enforce a negative caloric balance by malabsorption of nutrients.
Previous studies have shown that inhibition of the lipoxygenase pathway of arachidonic acid metabolism can prevent the development of elevated blood pressure in renin-dependent models of hypertension. Agents that inhibit the lipoxygenase pathway such as phenidone and the flavonoid baicalein can selectively attenuate contractile responses to angiotensin II in vivo as well as in isolated vascular tissue. In the present study, the effects of lipoxygenase inhibitors on pressor-induced changes in cytosolic calcium were examined in cultured rat vascular smooth muscle cells using the fluorescent dye fura-2. Two structurally unrelated lipoxygenase inhibitors, baicalein and 5,8,11-eicosatriynoic acid, attenuated angiotensin II-stimulated increases in cytosolic calcium in both normal and calcium-poor buffer. The addition of 5-, 12-, or 15(S)-hydroxyeicosatetraenoic acid alone to the cells had no acute effect on intracellular calcium concentration. However, the addition of 12(S)-hydroxyeicosatetraenoic acid but not 5- or 15(S)-hydroxyeicosatetraenoic acid restored the initial calcium response to angiotensin II in vascular smooth muscle cells pretreated with both inhibitors; 5,8,11-eicosatriynoic acid also reduced [Arg8]-vasopressin and endothelin-stimulated increases in intracellular calcium. The attenuation of vasopressor-induced calcium transients by agents that inhibit lipoxygenase may explain their observed hypotensive effects in vivo. Moreover, lipoxygenase products, in particular 12(S)-hydroxyeicosatetraenoic acid, may act as mediators for the intracellular actions of angiotensin II and possibly other pressor hormones in vascular tissue by regulation of intracellular calcium metabolism.
Angioedema is a problem that the otolaryngologist-head and neck surgeon is often asked to treat. This report concerns 17 patients admitted for care during a 5-year period. At their initial presentation, 94% of these patients manifested signs and symptoms of angioedema in the head and neck; three of them required urgent tracheotomy or intubation. As treatment of complement-mediated angioedema is distinct, an etiology-specific diagnostic and treatment protocol is presented. Of the patients, 35% had recent initiation of angiotensin-converting enzyme (ACE) inhibitor therapy for hypertension, and 6% demonstrated classic hereditary angioedema. However, the majority of them (59%) had unclear etiologies for their symptoms. Since angioedema is the final result of several possible abnormalities, a thorough knowledge of the differential diagnosis and clinical presentation is vital to patient management.