Tumor debulking and IORT for recurrent gynecological carcinomas of the pelvic sidewall.
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Combined Modality Therapy↗
Biomedical subjects
H Schmid
Publications and source records attributed to H Schmid.
Specific catalytic activity of cathepsin S in comparison to cathepsins B and L along the rat nephron.
Assay conditions were elaborated to determine the catalytic activity of cathepsin S fluorometrically for direct comparison with the activities of cathepsins B + L(+S) and B along the nephron of the normal rat. These conditions include the use of 0.5 mM Z-Phe-Arg-AMC as substrate, which is saturating for the three enzymes. The stability of cathepsin S at pH 7.5 and the resistance of cathepsin B against inactivation by 0.5 microM Z-Phe-Phe-CHN2 permitted differentiation of these enzyme activities. The catalytic activity of cathepsin S in rat kidney homogenate (1.11 mumol/min x g protein) amounted to 2.1% of that of cathepsins B + L(+S) and to 3.2% of that of cathepsin B. It was ten-fold higher in the cortex (1.54 mumol/min x g protein) than in the medulla resembling the activity ratio of cathepsins B + L(+S) and B. In suspensions of isolated glomeruli and isolated proximal tubules the activities of cathepsin S were 0.76 and 3.21 mumol/min x g protein, respectively. The corresponding activities of cathepsins B + L(+S) amounted to 80.0 and 211.7 mumol/min x g protein consisting of 71% cathepsin B activity. In nephron segments microdissected from lyophilized renal sections, highest cathepsin S activity was found in the proximal convoluted tubules (4.21 mumol/min x g dry weight) followed by 0.83 mumol/min x g dry weight in proximal straight tubules of the superficial cortex. In the remaining segments cathepsin S activity was hardly detectable. Unlike cathepsin S activity, the activity of cathepsin B was distributed in parallel to that of cathepsins B + L(+S). The presence of relatively high cathepsin S activity in proximal convoluted tubules in co-localization with the activities of cathepsins B + L(+S) and B suggests a primary role of these enzymes in heterophagocytosis of proteins from the ultrafiltrate.
Animals↗
Standardization of a computerized method for calculating autonomic function test responses in healthy subjects and patients with diabetes mellitus.
The objectives of the present study were 1) to compare results obtained by the traditional manual method of measuring heart rate (HR) and heart rate response (HRR) to the Valsalva maneuver, standing and deep breathing, with those obtained using a computerized data analysis system attached to a standard electrocardiograph machine; 2) to standardize the responses of healthy subjects to cardiovascular tests, and 3) to evaluate the response to these tests in a group of patients with diabetes mellitus (DM). In all subjects (97 healthy and 143 with DM) we evaluated HRR to deep breathing. HRR to standing, HRR to the Valsalva maneuver, and blood pressure response (BPR) to standing up and to a sustained handgrip. Since there was a strong positive correlation between the results obtained with the computerized method and the traditional method, we conclude that the new method can replace the traditional manual method for evaluating cardiovascular responses with the advantages of speed and objectivity. HRR and BPR of men and women did not differ. A correlation between age and HRR was observed for standing (r = -0.48, P < 0.001) and deep breathing (r = -0.41; P < 0.002). Abnormal BPR to standing was usually observed only in diabetic patients with definite and severe degrees of autonomic neuropathy.
Adolescent↗
Time course of changes in heart rate and blood pressure variability in streptozotocin-induced diabetic rats treated with insulin.
Autonomic neuropathy is a frequent complication of diabetes associated with higher morbidity and mortality in symptomatic patients, possibly because it affects autonomic regulation of the sinus node, reducing heart rate (HR) variability which predisposes to fatal arrhythmias. We evaluated the time course of arterial pressure and HR and indirectly of autonomic function (by evaluation of mean arterial pressure (MAP) variability) in rats (164.5 +/- 1.7 g) 7, 14, 30 and 120 days after streptozotocin (STZ) injection, treated with insulin, using measurements of arterial pressure, HR and MAP variability. HR variability was evaluated by the standard deviation of RR intervals (SDNN) and root mean square of successive difference of RR intervals (RMSSD). MAP variability was evaluated by the standard deviation of the mean of MAP and by 4 indices (P1, P2, P3 and MN) derived from the three-dimensional return map constructed by plotting MAPn x [(MAPn + 1)-(MAPn)] x density. The indices represent the maximum concentration of points (P1), the longitudinal axis (P2), and the transversal axis (P3) and MN represents P1 x P2 x P3 x 10(-3). STZ induced increased urinary glucose in diabetic (D) rats compared to controls (C). Seven days after STZ, diabetes reduced resting HR from 380.6 +/- 12.9 to 319.2 +/- 19.8 bpm, increased HR variability, as demonstrated by increased SDNN, from 11.77 +/- 1.67 to 19.87 +/- 2.60 ms, did not change MAP, and reduced P1 from 61.0 +/- 5.3 to 51.5 +/- 1.8 arbitrary units (AU), P2 from 41.3 +/- 0.3 to 29.0 +/- 1.8 AU, and MN from 171.1 +/- 30.2 to 77.2 +/- 9.6 AU of MAP. These indices, as well as HR and MAP, were similar for D and C animals 14, 30 and 120 days after STZ. Seven-day rats showed a negative correlation of urinary glucose with resting HR (r = -0.76, P = 0.03) as well as the MN index (r = -0.83, P = 0.01). We conclude that rats with short-term diabetes mellitus induced by STZ presented modified autonomic control of HR and MAP which was reversible. The metabolic control may influence these results, suggesting that insulin treatment and a better metabolic control in this model may modify arterial pressure, HR and MAP variability.
Animals↗
Tumor-associated cysteine proteinase activities in human melanoma cells and fibroblasts of different origin.
Specific catalytic activities of cysteine proteinases including cathepsins B (EC 3.4.22.1) and L (EC 3.4.22.15) in human melanoma cell lines SK-MEL-28, SK-MEL-30, MEL-HO and in fibroblasts of different origin are reported. Cell line-specific pH profiles of these cysteine proteinases were determined fluorometrically with benzyloxycarbonyl-phenylalanyl-arginine-amidomethylcoumarine (Z-Phe-Arg-AMC) under saturated conditions. Single activities of cathepsins B and L were inactivated by urea and by benzyloxycarbonyl-phenylalanyl-phenylalanine-diazomethylketone (Z-Phe-Phe-CHN2) in order to describe the activities of these enzymes separately. The melanoma cell line MEL-HO, which originated from a primary lesion, showed highest activity of an unknown cysteine proteinase. This enzyme is not inactivated by urea and Z-Phe-Phe-CHN2 and has a Michaelis constant (K(M) value) of approximately 1 mM. The specific characteristics suggest that it is a tumor-associated cathepsin B. In addition, high invasive subpopulations of SK-MEL-28 and SK-MEL-30 cell lines isolated by an invasion assay showed higher proteinase activities than the low invasive subpopulations. Furthermore, in fibroblasts originating from melanoma tissue cysteine proteinase activities were increased compared to normal skin fibroblasts. In conclusion, these results indicate that these cysteine proteinases shown here are tumor-associated proteinases, possibly facilitating invasion and dissemination of melanoma cells.
Cell Line↗
[Paraneoplastic retinopathy in 2 patients with breast carcinoma].
Paraneoplastic retinopathies are rare paraneoplastic phenomena resulting in retinal degeneration. They occur in association with different tumor types, yet most frequently encountered in small cell carcinoma of the lung. Clinical symptoms may be present before the diagnosis of the underlying malignancy. They are characterized clinically by progressive visual loss with ring scotomas, photopsia and night-blindness. An autoimmune disorder is suggested. In the sera of patients antiretinal antibodies may be detected that are sometimes reactive with the 23 kD retinal antigen recoverin, a photoreceptorprotein. We report on two patients with breast cancer who developed paraneoplastic retinopathy during the course of disease. Immunologic tests showed antiretinal antibodies that were not reactive with the 23 kD retinal antigen recoverin.
Autoantibodies↗
[Trends in alcohol consumption in Switzerland from 1975-1992].
Based on four representative surveys independently conducted at 6-year intervals, the study presented here delineates the development of alcohol consumption in the general population of Switzerland between 1975 and 1992. A description of changes in the frequency and quantity of alcohol consumption by sex is presented, as well as specific changes by beverage type. Even though Switzerland remains one of the high consumption countries, a marked decline can be observed. Compared to 1975 when 28% of respondents reported daily alcohol consumption, this figure dropped to 20% in 1992. Although 10% consumed more than 60 grams of pure alcohol in the 1975 sample, this proportion fell to only 3% in 1992. This downward trend, which is also reflected in secondary statistics such as sales and mortality figures, can be mainly attributed to male consumers. In contrast to international trends, which in general demonstrate converging drinking patterns, reduced consumption in Switzerland, a wine-producing country, is mainly due to a decline in beer consumption and not in wine consumption.
Adolescent↗
Risk factors for sporadic salmonellosis in Switzerland.
A case-control study was conducted to identify determinants for the acquisition of sporadic Salmonella infection in Switzerland. Over a one-year period (1993), 223 case-control pairs were enrolled in the study and risk factors were assessed by means of self-administered questionnaires. Three-quarters of the isolates were identified as Salmonella enteritidis, most of which (80%) belonged to phage type 4. There were distinct differences in risk factors between infections with Salmonella enteritidis and those with other Salmonella serovars. In both groups recent travel abroad was positively associated with illness. This association was more pronounced for infections with non-enteritidis salmonellae [odds ratio (OR) 39.5; 95% confidence interval (CI) 6.6-236.8, compared to Salmonella enteritidis 4.0; 95% CI 1.8-9.1]. Among the presumably imported infections, Salmonella enteritidis was acquired mostly in other European countries, while other serovars were acquired mostly in countries outside of Europe. Eating food containing raw or undercooked eggs during the three days before the onset of illness increased the risk of infection with Salmonella enteritidis. Desserts made with raw eggs (OR 4.6; 95% CI 2.0-10.6) were more strongly associated with disease than consumption of soft-boiled eggs (OR 2.1; 95% CI 1.2-3.7), suggesting that the risk of infection was dependent on the extent to which eggs were cooked. Egg consumption was not associated with infections with serovars other than Salmonella enteritidis; however, the intake of medications other than antacids was found to be a risk factor (OR 3.5; 95% CI 1.1-11.4).
Adult↗
[Metastasis to the sternum or parasternal recurrence of breast carcinoma? Value of sonography].
Because of the high tendency of breast cancer to develop metastatic deposits in the skeleton, space-occupying processes in the sternal region are mostly attributed to osseous metastases and not to parasternal lymph node involvement, even in case of solitary lesions, primary tumor localizations in the inner quadrants, positive axillary nodes and negative X-ray or bone scan findings. The sonographic examinations of 115 patients with breast cancer and clinical and/or scintigraphic suspicion of sternal metastasis, however, revealed the typical bone metastases of the sternum with a small soft tissue tumors in only 27.8 %, whereas 59.1 % of the cases showed parasternal recurrences; 5.2 % had both. Non-tumorous changes were seen in 6.1 %, equivocal results in 1.7 %. Solitary osseous metastasis of the sternum was rare; multiple skeletal lesions were found in the majority of this group in contrast to the patients in the parasternal relapse group, which moreover showed strong overrepresentation of the primary tumor localization in the inner quadrants. X-rays of the chest or the sternum were often false-negative and not reliable, the bone scans positive only in cases of secondary sternal invasion or skeletal metastases. Concerning reliability and cost, sonography was the imaging method of first choice for diagnosis, therapy planning and follow-up for space-occupying processes in the sternal region, with CT or MRI as adjuncts in cases of extended tumors invading the mediastinum.
Adult↗
Magnesium metabolism: basic aspects and implications of ciclosporine toxicity in rats.
In rapidly growing male Sprague-Dawley rats with an initial body weight of 100 +/- 10 g, we investigated how alimentary magnesium (Mg) supply, Mg metabolism and ciclosporine (Ci)-associated nephrotoxicity are interrelated. Food with 100 ppm Mg (1Mg) or 1,000 ppm Mg (stMg) or 10,000 ppm Mg (rMg), Ci 20 mg/kg body weight daily or olive oil were applied for 3 months (n = 10/group). Mg concentrations in various compartments were measured by atomic absorption spectrophotometry. Creatinine clearance (Jaffe), urinary N-acetyl-beta-D-glucosaminidase (NAG) activity (fluorometrically), urinary sodium excretion (flame photometry) and osmolality were measured. Histomorphological examination was done and renal renin expression was studied by monoclonal antibodies. Ci reduced the Mg concentration of the femur under 1Mg (72.6 +/- 9.7 vs. 112.6 +/- 14.3 mmol/kg dry substance, p < 0.05) and under stMg (150.6 +/- 16.6 vs. 194.1 +/- 10.2 mmol/kg dry substance, p < 0.05), thus indicating Ci-related Mg deficiency. This was due to a significant increase in Mg excretion in Ci treatment compared to dietary controls. Under rMg, there was no difference between Ci-treated and control animals. Ci treatment lowered creatinine clearance in 1Mg (1.42 +/- 0.05 vs. 3.02 +/- 0.58 ml/min) and in stMg (1.04 +/- 0.45 vs. 2.18 +/- 0.51 ml/min), NAG/creatinine and urinary sodium excretion were negatively affected by Ci under 1Mg and stMg. Histomorphology showed macrocalcifications due to Mg deficiency and Ci-specific findings, which were markedly enhanced in 1Mg and stMg. Animals with plentiful Mg supply had no functional alterations due to Ci and no or weakly expressed histomorphological lesions. Renin-positive stained cells were higher in Ci-treated animals. This seems to be functionally relevant under 1Mg and stMg, since it was associated with sodium retention and elevated relative heart weight, indicating hypertension. Alimentary or drug-induced Mg deficiency plays a relevant role in the pathophysiology of chronic Ci nephrotoxicity. Our data suggest that Mg supplementation is helpful to reduce Ci toxicity, even if there is 'normal' alimentary Mg intake.
Animals↗
Transforming growth factor-beta in the development of rat diabetic nephropathy. A 10-month study with insulin-treated rats.
We investigated the intrarenal distribution of transforming growth factor-beta 1 (TGF-beta 1) protein and the TGF-beta 1 mRNA levels in the glomeruli and renal cortex of Wistar rats with streptozotocin-induced diabetes before and after the onset of diabetic nephropathy. Monthly urinary albumin excretion, glomerular filtration rate, glomerular volume, renal histology and immunohistochemical reaction for type-I collagen were also studied. The results showed progressively higher glomerular immunohistochemical TGF-beta 1 staining in rats with a diabetes duration of 24 and 40 weeks which was correlated with albuminuria (r = 0.905, p < 0.01) and was temporally associated with the appearance of glomerular deposition of total and type-I collagen. The glomerular content of TGF-beta 1 mRNA was higher in rats diabetic for 20 weeks while lower cortical RNA-TGF-beta 1 levels were found in rats with a diabetes duration of 1-40 weeks. These data suggest that this polypeptide may be an important mediator of diabetic glomerulosclerosis.
Animals↗
Determination of choline dehydrogenase activity along the rat nephron.
A radioenzymatic microassay was developed to quantitate choline dehydrogenase activity in single microdissected nephron segments. This enzyme is the rate limiting step in the biosynthesis of betaine, which serves as an intracellular osmoregulatory organic solute in mammalian kidney. The enzyme localized in renal mitochondrial inner membrane forms betaine aldehyde, which in the assay is converted to betaine by oxidative treatment. A histochemical procedure based on the formazan detection of tetranitroblue tetrazolium chloride was applied in parallel. The results show that activities in proximal convoluted and straight tubules are more than 5 times higher (21 to 25 pmol h-1 mm tubule-1) compared to distal nephron segments with no significant differences along the proximal tubule. Along the osmotic gradient from the outer medullary towards the papillary structures enzyme activities increased in ascending limbs of Henle's loop and collecting tubules. Collecting ducts showed two times higher activities than ascending loop segments when corrected for tubular cell volumes. The quantitative data were confirmed by the histochemical procedure. The results allow for the conclusion that betaine synthesis is sufficient to build up renal betaine, but cannot explain the distribution pattern of betaine along the corticopapillary axis. Additional mechanisms like intrarenal and tubular transport have to be postulated.
Alcohol Oxidoreductases↗
Allogeneic BMT vs. chemotherapy in late bone marrow relapsed childhood non-T/non-B ALL: results of BFM ALL relapse studies. BFM Relapse Study Group.
In first BM relapsed non-T/non-B ALL, the outcome is not significantly different after radio-chemotherapy compared with allogeneic BMT. Therefore, radio-chemotherapy is convenient af first late BM relapse and BMT may be performed not before a second BM relapse had occurred. Only a small subgroup of children with isolated BM relapse and peripheral blast cells > or = 10,000/microliter at diagnosis of first relapse has a dismal prognosis after radio-chemotherapy and might benefit from BMT.
Adolescent↗
[Prognostic significance of p53 autoantibodies in serum of patients with breast carcinoma].
Mutations in the p53 tumor suppressor gene are the most common genetic alterations associated with malignant tumors including breast and gynecologic carcinomas. Overexpression of p53 protein is a result of increased protein stability caused through conformationally alteration. Accumulation of mutant p53 in tumor cells may lead to a humoral immune response with development of p53 autoantibodies. In the present study we investigated the sera of 72 patients undergoing surgery for primary breast cancer and the relation between p53 antibody production, prognostic parameters and clinical outcome. Circulating p53 antibodies were detected in 15 of the 72 examined patients (21%). A correlation to conventional prognostic factors was not observed. Yet the overall survival was worse in patients with p53 antibodies (p < 0.04), suggesting a more aggressive tumor type.
Adult↗
[Response evaluation with mammography and ultrasound].
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Antineoplastic Combined Chemotherapy Protocols↗
[Principle and foundations of high dose therapy with stem cell transplantation].
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Antineoplastic Combined Chemotherapy Protocols↗
[Possibilities and limitations of drugs to protect the liver].
In this paper preventive liver protective agents for the prophylaxis of hepatopathies due to functional stress, and curative protective agents for therapy of existing liver damage are distinguished. Preventive liver protective agents are key substances in the metabolism of proteins, carbohydrates, lipids, and sulfur. For curative liver protective agents, inhibitors of RNA and protein synthesis, calcium antagonists and inhibitors of sulfhydryl (-SH) containing enzymes are proposed and substantiated.
Amino Acids↗
Autologous bone-marrow transplants compared with chemotherapy for children with acute lymphoblastic leukaemia in a second remission: a matched-pair analysis. The Berlin-Frankfurt-Münster Study Group.
It is unclear how best to treat children with acute lymphoblastic leukaemia (ALL) who are in a second remission. Treatment with bone-marrow transplants from HLA-identical siblings results in a statistically greater likelihood of leukaemia-free survival than does chemotherapy. Less than 25% of relapsed patients are able to benefit from this therapy due to a lack of matching donors; chemoradiotherapy or autologous BMT are considered for the rest. We compared treatment results for children who underwent autologous BMT with those who had chemotherapy. All patients were registered between 1983-94 in the multicentre trials. We selected groups of patients by matching variables associated with treatment outcome and duration of second remission. 52 matched-pairs were studied. The probability of event-free survival at 9 years was 0.32 (SD 0.07) for patients receiving chemotherapy versus 0.26 (SD 0.07) for patients who underwent autologous BMT. For two groups--children with prognostic factors indicating high risk of relapse and those with factors indicating lower risk--the outcome from transplantation did not differ significantly from that of chemotherapy: no advantage of autologous BMT over chemotherapy as post-induction treatment for children with ALL in a second remission could be detected with regard to event-free survival. Because autologous BMT has been used as the final step of treatment it is possible that its relative ineffectiveness has been due to the lack of continuation therapy after transplant. Attempts should be made to complement autologous BMT by subsequent immunotherapy, molecular biotherapy, chemotherapy, or a combination of these.
Adolescent↗