Biomedical subjects

M Ziegler

Publications and source records attributed to M Ziegler.

At least 19 recordsLinked to original sources

PubMed1992

Effects of sustained-release nicardipine on regression of left ventricular hypertrophy in systemic hypertension.

The effects of a sustained-release formulation of the calcium antagonist nicardipine on left ventricular (LV) mass, Doppler transmitral velocity profiles and plasma neurohumoral studies were analyzed in patients with mild to moderate systemic hypertension. A double-blind placebo control phase in 28 patients was carried out for 6 weeks with a subgroup of 13 subsequently entering an open-label long-term phase for 1 year. Nicardipine produced a significant decrease in systolic and diastolic pressure over the 6-week phase (158 +/- 15 to 142 +/- 9 mm Hg, and 100 +/- 5 to 89 +/- 9 mm Hg, respectively, both p less than 0.001). No significant differences in Doppler measures of mitral inflow or echocardiographic measures of LV function, wall thickness or mass were noted in the 6-week phase of the study. Although nicardipine increased both norepinephrine and renin values after the first dose, these levels had returned to baseline in most patients after 6 weeks. In addition, there was no evidence for stimulation of adrenomedullary activity because nicardipine had no effect on epinephrine or dopamine-B-hydroxylase levels at first dose or after 6 weeks. In the 13 patients treated for 1 year, systolic and diastolic pressure remained significantly decreased compared with pressure before therapy (135 +/- 9 vs 147 +/- 15 mm Hg, and 85 +/- 6 vs 97 +/- 9 mm Hg, both p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

PubMed1992

Renin-producing renal cell carcinomas--clinical and experimental investigations on a special form of renal hypertension.

The pathogenetic relationship between tumour and hypertension was investigated in 129 patients with renal cell carcinoma, of whom 41 (31.8%) were hypertensive. Of these 41 patients with renal tumours and hypertension, 6 (14.6%) were found to have primary reninism. In these patients the plasma renin activity in blood from the renal veins showed a tumour kidney to contralateral kidney ratio of between 4 and 7, and 2 patients also had secondary hyperaldosteronism. In the same 6 cases the renin content in the renal tumour tissue was significantly higher than that in tissue from the adjacent tumour-free renal cortex of the ipsilateral kidney. Immunohistochemical demonstration of renin in the tumour was only possible in these 6 cases. In 5 of these patients blood pressure returned to normal following nephrectomy; in the 6th case there was a drop in blood pressure after nephrectomy. In 3 renin-positive tumours examined, autonomous renin production was demonstrated in cell culture. Renin-producing renal cell carcinomas are an uncommon cause of renal hypertension. The differential diagnosis of hypertension should therefore also include renal tumour.

Captopril↗

PubMed1992

Monoclonal antibody-mediated cytotoxicity against rat beta cells detected in vitro does not cause beta-cell destruction in vivo.

Two monoclonal Beta-cell surface antibodies M10H6 und K14D10 were obtained by fusion of spleen cells of Balb/c mice with the myeloma cell line P(3)0. The monoclonal antibody M10H6 was induced by immunization with rat insulinoma cells finally boostered with disintegrated rat islets, whereas the K14D10 was generated after immunization with porcine proinsulin. Both monoclonals belong to the IgG2A isotype and were screened with insulin-producing rat insulinoma cells by an indirect immunofluorescence test as well as by a cellular enzyme linked immunosorbent assay. In addition to the cell surface binding on living Beta cells the monoclonals react with islets on cryostat sections of rat pancreas. The anti-islet cytotoxic potential of these monoclonals was measured by 51Chromium-release in the presence of complement or Fc-receptor bearing leucocytes using 51Chromium-labelled rat islet cells as target. Both antibody secreting hybridomas were propagated in syngeneic mice resulting in high levels of islet cell surface antibodies in ascites and sera from the recipient. High anti-islet cytotoxicity was mediated by ascites fluid, but no mouse developed hyperglycaemia. Furthermore, the repeated injections of the monoclonals into rats did not exert a diabetogenic action and failed to reduce the pancreatic insulin content although the attraction of the K14D10 to the pancreatic islets in vivo could be demonstrated. We conclude that islet cell surface antibody-mediated Beta-cell lysis in vitro may not be relevant to Beta-cell destruction in vivo.

Animals↗

PubMed1992

Activity and acceptability of piribedil in Parkinson's disease: a multicentre study.

Several controlled trials have shown that the dopamine agonist, Trivastal (piribedil), is active in the treatment of Parkinson's disease, particularly with regard to tremor. To determine its efficacy as monotherapy in patients previously untreated with levodopa, a 3-month multicentre study was conducted with Trivastal 50 mg LP in 113 patients with idiopathic Parkinson's disease. The study population consisted of 66 men and 47 women, aged 63.1, SD 0.6 (43-79) years with a 2.1, SD 0.2 (1-15) year history of Parkinson's disease. Mean disease stage was 1.82 (1-4) by the Hoehn and Yahr classification. Tremor was the predominant clinical feature in 42 patients; the remaining 71 patients displayed the full parkinsonian syndrom. Trivastal 50 mg LP was prescribed stepwise up to doses of 150-250 (207, SD 6.4) mg/day at the end of 3 months. No concomitant anti-parkinsonian medication was given. Patients were clinically assessed at 1, 2 and 3 months on the Webster scale, a specific tremor scale and the HARD depression scale. Mean results were as follows in the 90 patients completing the study. On the Webster scale, tremor fell from 1.7 to 1 (-41%, P less than 0.001), bradykinesia from 1.5 to 0.8 (-47%, P less than 0.001) and rigidity from 1.3 to 0.9 (-31%, P less than 0.001); on the specific scale, rest tremor decreased in daily duration and amplitude from 3.9 to 2.4 (-39%, P less than 0.001) and from 2.9 to 2.1 (-35%, P less than 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Arterial, portal or combined arterio-portal regional chemotherapy in experimental liver tumours?

The most appropriate route for regional administration of chemotherapeutic drugs to liver tumours was studied in a standardized rodent model: cells of Novikoff hepatoma were transplanted into the central liver lobe of Sprague-Dawley rats. From day 5 to day 12 after transplantation, the liver was continuously perfused with 420 mg/kg 5'-fluoro-2-deoxyuridine by subcutaneous osmotic micropumps via the hepatic artery (n = 20), the portal vein (n = 20) or both vessels together (n = 12). The tumour multiplication factor (TMF) and the vascularization of the tumour were evaluated. Arterial and combined infusion led to a highly significant reduction in TMF, but combined infusion was not more effective than arterial alone. Portal infusion had no significant effect. There was no correlation between vascularization and tumour response in arterial infusion, but a strong correlation in portal infusion. Thus chemotherapy via the portal route may be effective in selected tumours with considerable portal vascularisation.

Animals↗

PubMed1992

Chromogranin A correlates with norepinephrine release rate.

Chromogranin A (CgA) is an acidic protein co-released with catecholamines during exocytosis from sympathetic nerve terminals and chromaffin cells. Previous work has demonstrated that large scale perturbations in sympathetic nervous system (SNS) functioning result in corresponding changes in CgA levels in plasma. Little is known about the physiologic significance of CgA. We hypothesized that, since CgA and catecholamines are co-released from the same storage vesicles, and since CgA is not subject to reuptake or enzymatic metabolism, plasma CgA should reflect norepinephrine release from sympathetic terminals. We therefore measured venous CgA, norepinephrine levels, and norepinephrine release rate in 30 unmedicated subjects. Although the correlation of CgA with plasma norepinephrine was only modest (r = 0.37, p less than 0.05), its correlation with norepinephrine release rate was highly significant (r = 0.58, p less than 0.001). Thus, CgA may offer a novel perspective on peripheral sympathetic activity.

Adult↗

PubMed1992

Characterization of two porcine proinsulin reactive monoclonal antibodies by immunostaining of beta-cells in pancreatic sections of different species.

Murine monoclonal antibodies against porcine proinsulin were generated by somatic cell hybridization. As detected by radioimmunoassay, 2 monoclonal antibodies KSPI14D4 and KSPI13G10 showed a strong binding to 125I-labelled porcine proinsulin but not to insulin. The species specificity of these 2 monoclonals was found to be different as shown by indirect immunofluorescence using sections of Bouin-fixed pancreata of different species. The KSPI14D4 recognized the proinsulin of pig, mouse, man, cattle, rat, dog, and cat but not that of guinea pig, whereas the KSPI13G10 bound to porcine proinsulin only. From these results it is concluded that KSPI14D4 effectively recognizes a wide-spread epitope located in one of the insulin-C-peptide junctions of the proinsulin molecule, whereas KSPI13G10 is directed to a species-specific epitope of the porcine connecting peptide.

Animals↗

PubMed1992

[Malignant oncocytoma of the submandibular gland].

Case report on a malignant oncocytoma of the glandula submandibularis in a 56-year old female patient. Oncocytomas in otorhinolaryngology are very rare, mostly benign tumours appearing mainly in women between 60 and 90 years of age. They comprise oncocytes, which are epithelial cells with abnormally formed cytoplasm. Oncocytes have an acidophilic granular cytoplasm. Electron microscopy reveals a pronounced increase of hypertrophic mitochondria. Besides the benign variants there are also rare cases of malignant forms. Therapy consists of surgical resection.

Adenoma↗

PubMed1992

The effect of sodium iodate and melanin on the formation of glyoxylate.

Sodium iodate damages retinal pigment epithelium specifically, but the reason for this specificity is not well understood. The work reported here describes an effect of sodium iodate on melanin, a major component of the retinal pigment epithelium. Sodium iodate increases the ability of melanin to convert glycine to glyoxylate. Almost ten times as much glyoxylate is formed when sodium iodate is present compared to the amount formed with melanin alone, although iodate alone does not convert glycine to glyoxylate. A chemical reaction between sodium iodate and melanin is suggested as a partial explanation of the specificity of iodate toxicity towards retinal pigment epithelium.

Animals↗

PubMed1992

Sympathetic and immune interactions during dynamic exercise. Mediation via a beta 2-adrenergic-dependent mechanism.

BACKGROUND: The relation between the sympathetic nervous system and the immune system has not been fully defined. Recent investigations have suggested an adrenergically driven efflux of specific beta 2-receptor-rich lymphocyte subsets into the circulation with either exercise or infusion of exogenous catecholamines. METHODS AND RESULTS: To determine whether acute sympathetic stimulation mediates immunoregulatory cell traffic and function via a beta 2-receptor mechanism, we exercised 20 healthy volunteers before and after 1 week of treatment with either the nonselective beta-antagonist propranolol or the beta 1-selective antagonist metoprolol. Before treatment, exhaustive exercise according to the Bruce protocol led to a marked lymphocytosis. Tsuppressor/cytotoxic (Ts/c) and natural killer cells, subtypes with the largest density of beta-receptors, showed the most pronounced increases after exercise, with less impressive elevations in T(helper) and B cells. With respect to function, exhaustive exercise led to a decrease in concanavalin A-stimulated IL-2 receptor expression and [3H]thymidine incorporation while enhancing natural killer cell activity. One week of propranolol therapy blunted the exercise-induced increases in circulating Ts/c and natural killer subpopulations as well as the previously observed alterations in cellular immune function. Treatment with the beta 1-selective antagonist metoprolol, however, did not impair the influence of exercise on any of the above parameters. CONCLUSIONS: Acute sympathetic stimulation by exhaustive exercise leads to selective release of immunoregulatory cells into the circulation with subsequent alterations in cellular immune function, either secondary to subset changes or as a result of direct catecholamine effects on function. These changes are attenuated by propranolol but not metoprolol, suggesting a beta 2-mediated mechanism.

Adult↗

PubMed1992

Converting enzyme inhibition and blood pressure reactivity to psychological stressors.

There is considerable interest in blood pressure reactivity to psychological stressors. Because the sympathetic nervous system and the renin-angiotensin system are so responsive to stressors and are themselves the targets of many antihypertensive medications, many investigators have wondered if such medications decrease the blood pressure response to stressful stimuli. We studied 25 normotensive and 21 hypertensive men in a double-blind crossover study during which they received either placebo for 4 days or captopril (25 mg b.i.d.) for 4 days while they were hospitalized in a clinical research center. Patients were studied at resting baseline, while performing a mathematics task, and while reading out loud a disturbing newspaper article. Although captopril lowered the resting blood pressure levels, it had no effect on the amplitude of reactivity to stressors.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1992

[Varicocele in childhood. Treatment indications and value of sclerotherapy].

Varicocele is the most common surgically correctable cause of male subfertility. The incidence of varicocele is about the same in adolescents as in men (16.3%). Percutaneous transfemoral sclerotherapy has been performed in 42 of the authors' own cases; it is an alternative to surgical ligation of the varicocele and should be recommended whenever a varicocele is found, to prevent gonadotoxic damage.

Adolescent↗

PubMed1992

[Dopa-sensitive dystonia].

Dopa-sensitive dystonia has been recognised for twenty years. It may occur in the first years of life. It first affects the lower limbs, then generalized becomes, as in torsion dystonia. Eight clinical cases are presented in five boys and three girls. The absence of the disorder in the parents, but its presence in siblings in three cases suggests that it might be recessively inherited. The symptoms are severe enough to cause major functional disability. In some cases, the intensity of the motor disorder varies during the days being, less pronounced in the morning or after a nap and more marked in the evening. Nonetheless, this feature is not constant and thus cannot be considered as an essential diagnostic criterion. Treatment with levodopa gives remarkable and durable results, but it must be continued indefinitely. Abnormal movements accompany an overdose but regress when the dosage is decreased. Unlike Parkinson's disease, it is not necessary to increase or fragment doses to avoid fluctuations in the efficacy of treatment during the day. On the contrary, after several years of the illness a decrease in daily dosage sometimes to a single dose is possible. Discontinuing treatment leads to reappearance of dystonia after two or three days. There are no established biological criteria to aid diagnosis. However, a decrease in urine levels of homovanillic acid was observed in two cases. Dopa-sensitive dystonia should be regarded as distinct from juvenile Parkinson's disease, firstly because of its symptomatology and secondly, and more importantly, because of its particular course, since fluctuations in therapeutic efficacy are never observed. It is the only known example of dopaminergic insufficiency that is chronically almost completely controlled by a modest exogenous supply of levodopa.

Carbidopa↗

PubMed1992

Detection of antibodies against both isoforms of glutamate decarboxylase in BB/OK rats by western blotting and immuno trapping enzyme activity assay.

The GABA-producing enzyme glutamate decarboxylase (GAD) is a prominent autoantigen in insulin-dependent diabetes mellitus (IDDM). Autoantibodies against GAD were found with a high prevalence in IDDM patients and in animal models for IDDM. The aim of this study was to detect autoantibodies against both isoforms of GAD in diabetic and non-diabetic but diabetes-prone BB/OK rats by Western blotting and to test their specificity to GAD by an immuno-trapping enzyme activity assay. Eighteen diabetic and 18 non-diabetic BB/OK rats (age 121 +/- 20 days) were investigated. In 10/18 (56%) of the diabetic and 13/18 (72%) of the non-diabetic BB/OK rats autoantibodies against at least one GAD-isoform were detected by Western blotting. In the immunotrapping enzyme activity assay, the mean value of the diabetic (1151 +/- 552 cpm, n = 11) and nondiabetic BB/OK rats (1978 +/- 1213 cpm, n = 10) was significantly (p < 0.01) increased compared to the LEW. 1A control rats (581 +/- 274 cpm, n = 12). 7/10 (70%) individual sera of the non-diabetic and 5/11 (45%) of the diabetic BB/OK rats were positive in this test. In conclusion, the prevalence of GAD autoantibodies in BB/OK rat is connected with the genetic susceptibility to IDDM but is not a predictor for the onset of the disease in BB/OK rats.

Animals↗

PubMed1992

[Idiopathic left-sided varicocele. An ontogenetic abnormality?].

Phlebograms for sclerotherapy of varicoceles were performed in 659 patients. In 484 cases no valves of the left spermatic vein could be demonstrated. However, 172 patients showed sufficient valves or absent insertions of the spermatic veins at typical point with retrograde flow through collaterals (persistent intercardinal anastomoses). The value of nutcracker phenomena I and II is discussed. Ontogenetic disorders in the development of the secondary abdominal venous system are responsible for the occurrence of the idiopathic left-sided varicocele.

Adolescent↗

PubMed1992

Clinical application of intrauterine bone marrow transplantation for treatment of genetic diseases--feasibility studies.

Intrauterine bone marrow transplantation (BMT) may represent a new approach for correction of a large variety of genetic disorders in utero. The procedure may become feasible for more genetic disorders in the future, since a large majority of potentially correctible diseases can be diagnosed at an early stage of gestation in utero using molecular probes that permit analysis of small biologic samples and even few cells that may be obtained by chorionic villi biopsy and/or amniocentesis. Haploidentical paternal marrow (2 cases) and sibling bone marrow cells from a disease-free family members, were infused into the fetus. GVHD was avoided following in vitro T-lymphocyte depletion using monoclonal antilymphocyte (CDW52) antibodies (Campath-1) without affecting stem cell viability, similarly to the procedures in routine use in clinical BMT programs in man. Three women underwent intrauterine BMT at 34, 23 and 25 weeks of gestation for metachromatic leucodystrophy (Arylsulfatase A deficiency, 2 cases) and beta thalassemia major (1 case), respectively. A total of 33 x 10(8), 30 x 10(8) and 30 x 10(8) bone marrow cells were infused intraperitoneally (1 case), intraportally plus intraperitoneally (2 cases) with no fetal distress. Although the procedure was uneventful and no clinical evidence of GVHD was observed following delivery, correction of the basic disorders was not accomplished because of anticipated rejection of marrow allografts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

[Carcinoma of the kidney with production of renin. A special form of hypertension].

A correlation between the tumour and hypertension was investigated in 129 patients with renal cancer. Forty-one patients (31.8%) suffered from hypertension. Primary increased renin secretion was detected in 6 of these patients (14.6%). The renin activity quotient measured in the renal veins between the renal tumour and the contralateral kidney was between 4 and 7. Secondary hyperaldosteronism was detected in only 2 of the patients with a significantly different renin activity in the renal veins. The renin level detected in the tumour itself of these 6 patients was significantly higher than the level detected in the parenchyma of the same kidney. Renin was demonstrated immunohistochemically in the tumours of these patients. The blood pressure returned to normal after nephrectomy in 5 patients and a marked fall in blood pressure was observed in the 6th patient. Cell cultures of 3 tumours revealed autonomous renin production. Renin-secreting renal carcinomas represent a rare form of renal hypertension, which is why the possibility of renal cancer should also be considered when investigating a case of hypertension.

Aldosterone↗

PubMed1992

[Radioimmunoscintigraphy and magnetic resonance tomography in the diagnosis of urinary bladder cancer].

Magnetic resonance tomography is a method which is sufficiently precise to demonstrate morphological changes for tumor staging of carcinoma of the urinary bladder. The stage of the tumor was correct in 68 resp. 86% of the patients. The RIS shows organ and lymph node metastases and has the capability to differentiating between scar and tumor after transurethral resection. The local spread, especially the infiltration depth of the tumor, is not visible. In 90% of the patients a primary tumor was detected, only in 5 cases a false-negative and in 2 cases a false-positive finding was made.

Adult↗