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Biomedical subjects

M Ziegler

Publications and source records attributed to M Ziegler.

At least 145 records · Page 8Linked to original sources

Allelic loss on chromosome 17 in human ovarian cancer.

In order to identify a common region of deletion on chromosome 17 potentially containing a tumor-suppressor gene, 27 ovarian carcinomas and 3 ovarian tumors of low malignant potential (LMP) were examined for loss of heterozygosity (LOH) at 6 p arm and 10 q arm loci. Ninety percent of all tumors had deletions at one or more loci. On the p arm, there was a single near-common region of deletion on 17p13.3 (D17S30/pYNZ22.1; 86% LOH), an intervening locus with a low LOH rate, and a more proximal locus on 17p11.2 (D17S58/pEW301; 82% LOH) with a high LOH rate. In less aggressive tumors, LOH at D17S30 was not accompanied by LOH at p53. The q arm had a common region of deletion for high-stage carcinoma at D17S579 (Mfd188; 74% LOH) on q21, a locus tightly linked to the familial breast-ovarian-cancer syndrome (BRCAI) locus. D17S579 was lost in all informative high-stage carcinomas and retained in all low-stage carcinomas and tumors of LMP. There may be at least 2 tumor-suppressor genes, an early-acting gene on the p arm and a gene on the q arm involved in tumor progression and metastasis.

Adult↗

Characterization of monoclonal islet cell reactive autoantibodies from the diabetic biobreeding (BB/OK) rat.

Two fusion experiments using the heteromyeloma cell line CB-F7 and splenocytes from two diabetes-prone BB (BioBreeding) rats at the onset of diabetes resulted in 128 islet cell reactive autoantibodies primarily detected with permeabilized insulin-producing rat insulinoma cells (RIN) by a cellular enzyme-linked immunosorbent assay. Seventy-nine (62%) of 128 RIN cell reactive supernatants exhibited a cross-reactivity with rat splenic lymphocytes. Six stable hybridomas secreting monoclonal ICSA (islet cell surface antibodies) were established, but only one monoclonal antibody, R4B10, showed preferential beta-cell binding. Six monoclonal antibodies showed a dual reactivity as ICA (islet cell cytoplasmic antibodies) detected by immunostaining of pancreatic islet cryosections and as ICSA on the surface of viable islet cells, whereas two reacted only with an ICA-like pattern. One monoclonal ICSA was specifically displaced from the RIN cell surface by sera of type 1 diabetic patients.

Animals↗

Improved survival in biliary atresia patients in the present era of liver transplantation.

Therapy for patients with biliary atresia (BA) has become controversial, with orthotopic liver transplantation (OLTx) suggested in place of portoenterostomy. This is based on the unpredictable success of portoenterostomy, and the increased difficulty of the OLTx procedure following prior extensive liver surgery. The survival rate reported here for infants transplanted after unsuccessful portoenterostomy does not support this approach. OLTx was undertaken in 37 patients when end-stage liver failure followed primary portoenterostomy. Recipient age ranged from 6 months to 14 years (median, 13 months), and weight ranged from 5 to 45 kg (median, 8 kg) at the time of OLTx. Reduced-size allografts were used as the primary allograft in 25 patients (23 left lobe), and 12 received whole-organ allografts. Retransplantation was required in 5 patients, each received a reduced-size allograft. There was no increased incidence of vascular complications, primary nonfunction, irreversible rejection, intestinal perforation, biliary complications, sepsis, or lymphoma comparing the BA patients with all other non-BA patients who had undergone OLTx (all P = .16). There was no statistically significant difference in mean operative blood loss between BA patients (EBL = 1.99 BV) and non-BA patients (1.50 BV) (P = .14). Actuarial survival for the series of BA patients was 89% at 1 year, and 80% at 2 years. Following the introduction of reduced-size allografts, donor organs were selected for use with a priority on donor stability. The actuarial survival for BA patients during this time has improved to 96% at 1 year, and 91% at 2 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Kidney preserving surgery in renal cell tumors: indications, techniques and results in 152 patients.

Between 1975 and 1991, 142 patients with renal cell carcinoma and 10 with oncocytoma underwent a total of 164 kidney preserving operations. The indication for surgery was imperative (group 1, 47 patients) among those with a solitary kidney (9), renal insufficiency (17) or bilateral tumors (21). Of the patients with small or peripheral tumors and a healthy contralateral kidney 105 were selected for elective surgery (group 2). Most procedures were done either without ischemia (24%) or with warm ischemia (69%). In some patients from the imperative indication group hypothermia was achieved by in situ perfusion (5%) or ex vivo work bench surgery and autotransplantation (2%). Complication rates were 15% for group 1 and 9.5% for group 2. In group 1, 3 patients died of cancer, 5 lived with metastases and 2 had local tumor recurrence. No patient in group 2 had recurrences or metastases. The tumor-specific survival rate of patients with kidney preservation for renal cell carcinoma was comparable to that of a control group undergoing radical nephrectomy. Due to the high reliability and efficacy, kidney preserving surgery for renal cell carcinoma should be done more often, even in patients with a normally functioning contralateral kidney.

Adenoma↗

Ossifying renal tumor of infancy.

Ossifying renal tumor of infancy is a rare but distinctive tumor that presents as a mass in the pelvicaliceal system. It is usually suspected to be a calculus until surgical exploration reveals dense tumor attachment to the renal parenchyma. The histogenesis of this lesion has not been established. We present a case of this unusual neoplasm. A renal sparing procedure was performed on this biologically benign tumor. Followup after 20 months showed no evidence of recurrence.

Female↗

Induction of islet cell surface and insulin antibodies in Balb/c mice by application of porcine insulin and Freund's adjuvant is not associated with insulitis.

To investigate whether insulin antibody (IAB) formation is associated with the appearance of islet cell cytoplasmic antibodies (ICA), islet cell surface antibodies (ICSA) and insulitis Balb/c Bln mice were immunized with porcine insulin in combination with or without Freund's adjuvant. The animals received 8 i.p. injections and were followed up to 150 days for the development of antibodies and insulitis. Mice immunized with insulin in CFA developed IAB as well as ICSA. Mice only receiving Freund's adjuvant emulsified in saline also developed ICSA. ICA were not detectable. Inflammatory infiltrates were found in the exocrine pancreatic parenchyma but not in islets. The results show that nonspecific stimulation of the immune system and the application of insulin as antigen leads to both the formation of ICSA and IAB, while insulitis was not detectable.

Animals↗

Effect of daily oral vitamin D and calcium therapy, hypophosphatemia, and endogenous 1-25 dihydroxycholecalciferol on parathyroid hormone and phosphate wasting in renal transplant recipients.

Ten stable, normocalcemic renal transplant patients with good allograft function, hyperparathyroidism, and variable hypophosphatemia were treated for 2 to 9 months with oral calcium carbonate and replacement doses of vitamin D analogues. Parathyroid hormone levels (PTH) and renal phosphate wasting were not autonomous or fixed but decreased with therapy. Although serum 1-25(OH)2D3 levels could be shown to rise appropriately during oral vitamin D therapy and fall afterwards, a separate study in a larger group of patients showed no effect of elevated parathyroid hormone or hypophosphatemia to increase endogenous 1-25(OH)2D3 levels. Some 42% of patients with elevated carboxy-terminal PTH, had elevated N-terminal PTH, which was closely associated with more severe phosphate wasting. Aggressive oral calcium and vitamin D supplementation in certain normocalcemic renal transplant patients may decrease endogenous PTH levels, improve hypophosphatemia, and provide a physiologic increase in levels of 1-25(OH)2D3.

Administration, Oral↗

Vasopressin deficiency in primary nocturnal enuresis. Results of a controlled prospective study.

The lack of circadian rhythmicity of plasma arginine vasopressin (AVP) in primary nocturnal enuresis (PNE) in some children is known. The original test protocol is time-consuming and needs excellent compliance by children and parents. The goals of the presented study are the introduction of a simple screening test and the evaluation of the response of treatment using intranasal synthetic vasopressin. Fifty-five children (aged 8.2 +/- 3.1 years) with PNE and 15 children (aged 7.9 +/- 2.4 years) of a control group were investigated. Using a standardized protocol, AVP levels were measured by radioimmunoassay (RIA) under controlled water intake 3 times per day over a period of 72 h. Fourteen of 55 tested children (25.5%) with PNE had a significant decrease in nocturnal AVP when compared to the control group. We measured also an increased nocturnal urine volume and a lower urine osmolality in this enuretic group. Eight of 14 patients (57.1%) with plasma AVP deficiency (AVPD) also had bladder instability. Nine of 14 patients (64.3%) with AVPD with or without concomitant bladder instability were totally dry during desmopressin treatment, but only 2 (14.3%) remained dry after discontinuation of treatment. Our data suggest that nocturnal urine osmolality measurement may reflect AVPD and predict a positive treatment outcome.

Administration, Intranasal↗

[Renal oncocytoma. Diagnosis and its therapeutic consequences].

The angiographic findings (hypovascularity, spokewheel phenomenon, lucent rim, linear course of vessels) and CT features (central scar, hyperdense without contrast medium) of 20 patients with renal oncocytomas were analyzed. Simultaneously seven patients with renal cell carcinoma preoperatively misdiagnosed as oncocytoma were compared and critically discussed. Preoperatively, reliable differentiation of renal oncocytoma and renal carcinoma is not possible. Nevertheless, in the presence of features typical for oncocytoma the operative strategy should be "kidney-preserving surgery".

Adenoma, Oxyphilic↗

[Nuclear magnetic resonance tomography for improving the differential diagnosis of pathologic changes in the scrotal contents].

A total of 75 patients with scrotal pathology were examined using magnetic resonance imaging (MRI). The diagnostic results were compared with operative and histological findings and with the sonographic results available. Compared with sonography, MRI showed diagnostic advantages in the detection and characterization of malignant tumors and in the exclusion of non-tumorous testicular pathology (old torsions, periorchitis, old hematomas). No false-negative results were found by MRI. False-positive results were found in 2 out of 75 MRI examinations. The possibility of showing tunica albuginea, of imaging testes in various planes and its diagnostic accuracy of about 88% as well as the lack of ionizing irradiation make MRI the most reliable form of diagnostic imaging in the classification of scrotal pathology. Sonography (51/75) showed high sensitivity in detecting testicular disease (90%), but its specificity (55%) was disappointing and could not be quantified with regards to the differentiation of testicular cancer.

Adolescent↗

Mucolipidosis III presenting as a rheumatological disorder.

Genetic disorders of the osseous skeleton constitute a challenging area of differential diagnosis. Three patients, 2 girls and 1 boy, were referred to our pediatric rheumatology clinic because of progressive stiffness of their hands and flexion contractures of fingers, accompanied by additional musculoskeletal changes. One of the girls had been diagnosed in early childhood as having juvenile rheumatoid arthritis, the other was suspected to have scleroderma, and the boy had been labelled with "Hurler's syndrome." On evaluation, all 3 patients had the clinical and roentgenographic features of mucolipidosis III; the diagnosis of mucolipidosis III was confirmed by enzymatic assays. We call for an awareness of pediatricians, rheumatologists and orthopedic surgeons to the "rheumatological" presentation of mucolipidosis III. The establishment of a precise diagnosis will lead to adequate management and will allow appropriate genetic counseling.

Arthrography↗

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↗

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↗

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↗

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↗

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↗