Biomedical subjects
Publications and source records attributed to T Lenz.
A 59-year-old white woman with temporal arteritis developed progressive renal failure. Renal biopsy results showed focal and segmental necrotizing glomerulonephritis; furthermore, giant cells were present in the destructed vessel walls. Immunosuppressive therapy did not prevent terminal renal failure. This case shows that renal involvement may be a feature of temporal arteritis.
BACKGROUND: The diagnosis of pheochromocytoma may be difficult because the clinical picture is variable. OBJECTIVE: The purpose of this paper is to report our experience and to review the published data on the diagnostic significance and risks of the clonidine suppression test in the diagnosis of pheochromocytoma. PATIENTS AND METHODS: 114 patients were evaluated for pheochromocytoma using the clonidine suppression test. RESULTS: The diagnosis was established in four patients. Overall accuracy of the test in our own series was 98% when the normal response to clonidine was defined as total plasma catecholamines of less than 500 ng/L, or less than 70% of the baseline value. No serious complication was noted. CONCLUSION: Our data and the published series demonstrate that the clonidine suppression test is accurate and safe in patients with suspected pheochromocytoma.
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BACKGROUND: Direct renal angiography is still the method of choice for identification of renal artery stenosis. Newer non-invasive diagnostic methods include color coded duplex sonography and also ambulatory 24-h blood pressure monitoring, since in a large proportion of patients with secondary forms of hypertension the usual blood pressure fall during nighttime disappears. PATIENTS AND METHODS: In a prospective in-hospital study we investigated 86 patients with suspected renovascular hypertension. Circadian blood pressure was measured oscillometrically and color coded duplex sonography was performed immediately before direct renal angiography. RESULTS: Angiography revealed renal artery stenosis (> or = 50%) in 42 patients. This compared to a sensitivity of 92.9% and specificity of 91.7% for the use of sonography in those patients (70.4%) who could be adequately examined. Mean 24-h pressure values as well as standard deviations of blood pressure means as an indicator for blood pressure variability were not different in the 2 groups of patients, when all the data were analysed together and also when the data for nighttime and daytime were examined separately. The percent of blood pressure fall during nighttime was also not different in the 2 groups. In both groups 4 hypertensive patients had a blood pressure increase during nighttime. In 11 patients without renal artery stenosis a blood pressure fall of < 10% was observed, compared to 12 patients with renal artery stenosis. The circadian pattern of pulse rate was similar in both groups. CONCLUSION: We conclude that ambulatory blood pressure monitoring has a considerably lower diagnostic value for renal artery stenosis compared to angiography and also to color duplex sonography. This method therefore does not appear to be an appropriate screening approach for this kind of secondary hypertension. The color coded duplex sonography, however, seems to be the best non-invasive diagnostic method in those patients, who can be adequately examined.
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Calcium entry in nonexcitable cells occurs through Ca(2+)-selective channels activated secondarily to store depletion and/or through receptor- or second messenger-operated channels. In amphibian liver, hormones that stimulate the production of adenosine 3',5'-cyclic monophosphate (cAMP) also regulate the opening of an ion gate in the plasma membrane, which allows a noncapacitative inflow of Ca2+. To characterize this Ca2+ channel, we studied the effects of inhibitors of voltage-dependent Ca2+ channels and of nonselective cation channels on 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP)-dependent Ca2+ entry in single axolotl hepatocytes. Ca2+ entry provoked by 8-BrcAMP in the presence of physiological Ca2+ followed first-order kinetics (apparent Michaelis constant = 43 microM at the cell surface). Maximal values of cytosolic Ca2+ (increment approximately 300%) were reached within 15 s, and the effect was transient (half time of 56 s). We report a strong inhibition of cAMP-dependent Ca2+ entry by nifedipine [half-maximal inhibitory concentration (IC50) = 0.8 microM], by verapamil (IC50 = 22 microM), and by SK&F-96365 (IC50 = 1.8 microM). Depolarizing concentrations of K+ were without effect. Gadolinium and the anti-inflammatory compound niflumate, both inhibitors of nonselective cation channels, suppressed Ca2+ influx. This "profile" indicates a novel mechanism of Ca2+ entry in nonexcitable cells.
SUBJECT: Prorenin, the biosynthetic precursor of renin, is present in organs of the human reproductive system. METHOD AND MATERIAL: In this study we tested whether the release of prorenin from superfused minced human chorion laeve tissue is related to that of other placental hormones. We also investigated whether intracellular second messenger systems are involved in the prorenin release from placental tissue. RESULTS: More than 95% of the total renin released was in the form of prorenin. The release pattern of human chorionic gonadotropin (hCG), estradiol and progesterone was similar to that of prorenin. Exogenous hCG, the estrogen receptor blocker tamoxifen and the progesterone receptor blocker RU 486, 8-bromo cyclic AMP, diltiazem and angiotensin II did not affect prorenin release. CONCLUSION: We conclude that prorenin, not active renin, is released from placental cytotrophoblastic tissue. This release occurs in parallel to that of other placental hormones but it is not regulated by steroid receptors, hCG, intracellular calcium or cyclic AMP.
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BACKGROUND: Renal angioplasty is an established therapy for treatment of renovascular hypertension. This study was performed to evaluate short- and long-term outcome of this procedure up until 3 years afterwards. PATIENTS AND METHODS: Altogether, 111 renal artery stenosis in 92 patients were dilated. Among these were 31 fibromuscular and 70 arteriosclerotic lesions, 4 transplant artery stenosis and 6 occlusions. RESULTS: The primary success rate for dilatation was approximately 90%. Serious complications occurred in 5 of the patients including 2 fatal myocardial infarctions about 2 weeks after the procedure. Restenosis (altogether 25%) almost exclusively occurred during the first few months after angioplasty (more often in arteriosclerotic lesions than in fibromuscular disease). Successful dilatation resulted in better blood pressure control. In several patients with preexisting chronic renal failure improvement of renal function was observed; in this group, however, restenosis occurred in about 1 third of the patients. CONCLUSIONS: Renal angioplasty is a suitable method for therapy of renovascular hypertension; in patients with preexisting renal failure improvement of renal function may ensue. The decision to treat with angioplasty must be weighted carefully against other established and also newer methods (surgery vs. antihypertensive medication vs. stent implantation) and should be reserved for specialized centers.
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Hypertension, which is attenuated by regular aerobic exercise, is associated with an increase in cytosolic platelet calcium [Ca+2]i. How aerobic exercise might lower blood pressure is unknown. We tested the hypothesis that exercise would influence the agonist-induced effect on platelet cytosolic calcium [Ca+2]i. Twenty, healthy normotensive men between 20 and 60 years of age (five per decade) were studied while resting supine for 30 min and after bicycle ergometry at a work load sufficient to achieve a heart rate of 200 beats per min minus age in years. On the next day, the protocol was repeated with the subjects exercising at 75% their maximum heart rate for 6 min. Venous blood was obtained from an indwelling cannula. Exercise had no effect on total or ionised serum calcium values. Adrenaline values increased from 0.2 +/- 0.03 to 0.55 +/- 0.1 (s.e.m.) nmol/l (P < 0.05), while noradrenaline increased from 1.46 +/- 0.18 to 4.72 +/- 0.44 nmol/l (P < 0.05). Resting platelet [Ca+2]i concentrations were 95.4 +/- 3.9 and 94.4 +/- 3.0 nmol/l on the two study days. The values were not correlated with age or level of fitness. The platelet [Ca+2]i was 99.2 +/- 4.2 nmol/l after exercise, not different from the resting values. Platelet activation with adrenaline and thrombin across a wide range of doses resulted in prompt increases in [Ca+2]i, which were 50% less in platelets after exercise than at rest (P < 0.05). Activation with angiotensin (Ang) II, on the other hand, was less pronounced and less clearly influenced by exercise. We conclude that exercise influences the platelet activation state and reactivity. The decreased [Ca+2]i responses to adrenaline and thrombin suggest that [Ca+2]i stores were in part depleted at exercise compared to rest, an effect not observed with Ang II perhaps because of the smaller number of Ang II-operative receptors on platelets.
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This 8-week, double-blind, multicentre study compared the efficacy and safety of the combination of quinapril and hydrochlorothiazide (HCTZ) with each drug as monotherapy. Outpatients with moderate to severe hypertension defined as supine diastolic blood pressure (DBP) > or = 105 mmHg and < or = 120 mmHg at the end of a 2 to 4-week placebo-baseline period were randomly assigned to one of the three treatments: once-daily 10 mg quinapril plus 12.5 mg HCTZ or monotherapy with these doses. After 4 weeks, the doses were to be doubled for the remaining 4 weeks. Three hundred and sixty-eight patients were randomized to double-blind medication; 346 completed the study. Seven patients withdrew due to lack of efficacy. Four patients withdrew due to side effects. In all three treatment groups, clinically significant reductions in DBP were achieved. Combination therapy was statistically more effective than each component taken as monotherapy. Adverse events were infrequent in all treatment groups. No patients experienced symptomatic hypotension or orthostatic hypotension.
A remarkably close correlation between platelet cytosolic calcium ([Ca2+i]) and arterial blood pressure has been identified in patients with essential hypertension. We tested the notion that a pharmacologically relevant infusion of angiotensin (Ang) II is associated with an increase in cytosolic calcium [Ca+2i]. Five normal volunteers received Ang II (5 ng/kg/min) for three hours or vehicle intravenously in random sequence respectively. The investigations were conducted at least 14 days apart. Plasma renin activity and blood pressure were measured every 20 minutes. [Ca+2i] was measured with the fluorescent indicator fura-2 before and at the end of the last hour of Ang II infusion. Mean arterial blood pressure increased by 10 mmHg during Ang II infusion (P < 0.05). Plasma renin activity decreased from 2.21 +/- 0.28 to 1.31 +/- 0.22 ng/ml/hour during the Ang II infusion (P < 0.05). On the other hand, [Ca+2i] was 131 +/- 13 nmol/l before and 129 +/- 13 nmol/l after the infusion (P = NS). The data suggest that agonists may increase blood pressure without an increase in platelet [Ca+2i]. Furthermore, Ang II may increase blood pressure independently of [Ca+2i].
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A 15-year-old girl had severe Raynaud's phenomenon and arthralgias. A high ANA-IF titer was found and undifferentiated connective tissue disease was diagnosed. After 7 years of moderately flaring disease the patient deteriorated and presented with congestive heart failure, pleuropericardial effusion, hemolytic uremic syndrome, proteinuria and moderate hypertension. Autoantibodies against DNA, Sm-protein, and very high titers against U1RNP were detected. Therapy with high steroid doses, a cyclophosphamide pulse and 4 weeks of plasmaphresis with plasma exchange improved the heart, but not the renal condition. Symptomatic pancreatitis became the dominant problem of a progressively consuming process that resulted in the death of the patient. Post-mortem examination revealed widespread vasculopathy with intima proliferation and only minimal fibrosis involving the kidneys, heart and other main organs, including the pancreas. Taken together, the clinical picture was of an overlap between scleroderma and systemic lupus erythemathosus; the serologic and histopathologic findings suggest a diagnosis of a severe form of mixed connective tissue disease (MCTD).