Search PubMed⌕ Search

Biomedical subjects

D Schmidt

Publications and source records attributed to D Schmidt.

At least 91 records · Page 5Linked to original sources
PubMed2001

Intakes of most nutrients remain at acceptable levels during a weight management program using the food exchange system.

OBJECTIVE: The purpose of this study was to determine if the food exchange system allows subjects' nutrient intake to remain at recommended levels during a weight-loss program. DESIGN: Subjects in an intervention were prescribed an energy-restriction diet and exercise program lasting 32 weeks, and nutrient intake was measured prestudy and after 12, 16, and 32 weeks. SUBJECTS/SETTING: Healthy but overweight and obese premenopausal women (n = 219) were recruited at 6 university sites into community-based weight loss programs. One hundred fifteen women completed all aspects of the study. INTERVENTION: Energy intake was set at 0.8 x resting metabolic rate (RMR) for weeks 1 through 12, 1.0 x RMR for weeks 13 through 20, and 1.2 x RMR for weeks 21 through 32. Energy intake was based on food exchange tables, with the number of food exchanges adjusted to encourage a distribution of 55% carbohydrate, 30% fat, and 15% protein. Subjects increased their daily walking distance to 3.2 km above prestudy levels. MAIN OUTCOME MEASURES: Nutrient intake was measured from four 3-day food records. STATISTICAL ANALYSES PERFORMED: Repeated measures analysis of variance, with specific time point changes assessed from paired t tests adjusted for multiple comparisons. RESULTS: Body mass decreased by a mean +/- SD of 6.7 +/- 3.2 kg at week 12 and 7.8 +/- 6.2 kg by week 32. Walking distance increased by an average of 17.2 +/- 10.0 km/week during the first 12 weeks, and 12.4 +/- 12.4 km/week during the last 20 weeks. Despite a 23% to 36% reduction in energy intake during the study, intake of most nutrients was maintained. Intake of vitamin E, calcium, iron, and zinc decreased significantly from prestudy levels during the first 16 weeks of the intervention, but not at week 32. APPLICATIONS/CONCLUSIONS: Intake of most nutrients can remain at recommended levels when overweight and obese women follow the American Diabetes Association/American Dietetic Association food exchange system during a community-based weight-loss program.

Adult↗
PubMed2001

Proof of principle trials: exploratory open studies.

The aims of the observational, early phase IIa studies are usually several in number and often competing, and therefore the priorities should be clearly defined. The preclinical data, particularly the mode(s) of action of the drug and the results on experimental models, can help to build hypotheses on the agent's potential efficacy for individual seizure types and syndromes. For ethical reasons, the population selected for the initial clinical trials of antiepileptic drugs (AEDs) should be patients with continuing seizures (e.g. no less than two to four partial seizures/month) in spite of several therapeutic attempts using other appropriate AEDs, taken in monotherapy and in various combinations. Although the inherent bias in open, observational studies has limited their use in comparing treatments in epilepsy, they have several advantages over controlled trials, including lower cost, greater timeliness and inclusion of a broader range of patients. Observational, open studies with well-chosen patients and an adequate design tailored to answer precise predefined questions (including go/no go criteria) are most valuable for experienced clinicians in determining the clinical benefit of the drug, and for the pharmaceutical company in assessing the commercial merit of proceeding with further clinical testing.

Anticonvulsants↗
PubMed2001

Levetiracetam, oxcarbazepine, remacemide and zonisamide for drug resistant localization-related epilepsy: a systematic review.

OBJECTIVE: To undertake a systematic review and meta-analysis of placebo controlled add-on trials of levetiracetam, oxcarbazepine, remacemide and zonisamide for patients with drug resistant localization related epilepsy. METHODS: We searched Medline, The Cochrane Library and contacted the relevant pharmaceutical companies. Outcomes were 50% or greater reduction in seizure frequency and treatment withdrawal for any reason. Data were synthesised in a meta-analysis. The effect of dose was explored in regression models for levetiracetam and remacemide. RESULTS: We found four trials (1023 patients) of levetiracetam, two (961) of oxcarbazepine, two (388) of remacemide and three (499) of zonisamide. Ignoring dose, the relative risks (95% CI) for a 50% response were 3.78 (2.62-5.44), 2.51 (1.88-3.33), 1.59 (0.91-2.97) and 2.46 (1.61-3.79), respectively. There was evidence for increasing effect with increasing dose for levetiracetam, oxcarbazepine and remacemide. The relative risks for treatment withdrawal were 1.21 (0.88-1.66), 1.72 (1.35-2.18), 1.90 (1.00-3.60) and 1.64 (1.02-2.62), respectively. CONCLUSIONS: These data suggest a useful effect for levetiracetam, oxcarbazepine and zonisamide. Levetiracetam has the more favourable 'responder-withdrawal ratio' followed by zonisamide and oxcarbazepine.

Acetamides↗
PubMed2001

Soluble Fas and Fas-ligand in bladder cancer in vitro and in vivo.

Circulating soluble Fas (sFas) and expression of Fas-ligand on cancer cells are mechanisms of immune escape. The aim of the present study was to investigate expression and production of Fas and Fas-ligand on bladder cancer cell lines of different grade as a basic mechanism of their secretion in vivo. sFas and sFas-ligand serum levels of patients with different stage of bladder cancer were examined to determine the possible clinical use of these molecules as tumor markers. Bladder cancer cell lines RT4 (G1), RT112 (G1), T24 (G3) and SUP (G4) were analyzed by flowcytometry for Fas and Fas-ligand expression. To determine if the Fas-ligand gene is transcribed in these bladder cancer cell lines, RT-PCR was performed on mRNA extracted from these cell lines. Production of sFas and sFas-ligand was examined in cell culture supernatants of the cancer cells as well as in the serum of 62 patients with bladder cancer by a specific ELISA test. We demonstrate that Fas is expressed in similar levels on all human bladder carcinoma cell lines. In T24 (G3) and SUP (G4) cell lines we were able to detect the Fas-ligand protein, whereas no Fas-ligand protein could be found in RT4 and RT112 (G1) cells. Fas-ligand mRNA was expressed in all bladder cancer cell lines. Furthermore, all bladder cancer cell lines produce sFas but no sFas-ligand in spite of mRNA expression. The range of sFas levels in the serum of all patients with bladder cancer was large and did not show a correlation to the histopathological stage of bladder cancer. Although there is in vitro evidence that sFas and Fas-ligand play a role in bladder cancer, no correlation between the sFas and s Fas-ligand serum levels and the histopathological stage of bladder cancer could be found. Therefore, serum sFas and sFas-ligand have to date limited clinical relevance.

Journal Article↗
PubMed2001

Clinical impact of histologic subtypes in localized non-anaplastic nephroblastoma treated according to the trial and study SIOP-9/GPOH.

BACKGROUND: Histologic subtypes of standard histology Wilms' tumor (WT) and the effect of preoperative therapy on their clinical and histologic features, deserve to be analysed in respect to outcome to find an adequate baseline for therapy. PATIENTS AND METHODS: The German Society of Paediatric Oncology & Haematology enrolled patients from January 1989 to March 1994 for therapy according the International Society of Paediatric Oncology trial & study 9. Standardised preoperative therapy with dactinomycin and vincristine for 4-8 weeks was generally applied in patients between 0.5 and 16 years with localized renal tumors and imaging typical for WT. In 99.5% of cases representative material was sent for review to the Kiel Paediatric Tumour Registry. For prospective subtyping of 329 WT (258 after preoperative therapy, 71 with immediate surgery) modified Beckwith & Palmer criteria were used. Reduction in volume measured by imaging prior to chemotherapy and surgery was used to assess response (poor response: reduction < 40%; good response: reduction > or = 40%). RESULTS: There were 39% of patients treated with immediate surgery and 12.4% of patients with preoperative therapy in the age group up to 12 months. The difference in age (P = 0.022) was linked with different amounts of epithelial WT (15.5% vs. 3.1%), median age: 0.58 and 0.93 years. Due to the effect of chemotherapy the amount of other WT changed: stromal 0% to 14%, mixed 45.1% to 29.4%, blastemal 39.4% to 9.3%). After preoperative therapy 37.6% of WT were predominantly regressive, 6.6% completely necrotic. Poor response was frequent in differentiated WT (86% of stromal, 75% of epithelial WT) but none relapsed. In the other WT with viable tumor left after preoperative therapy > 70% had good response, poor response was a risk factor (P = 0.0057). CONCLUSIONS: Subtyping according modified Beckwith & Palmer can be used in WT after preoperative therapy to stratify postoperative therapy in future. A milder therapy could be tested in differentiated WT at low stages and an intensified in the others with viable tumor left and poor response, i.e., mainly blastemal WT.

Adolescent↗
PubMed2001

Recommendations on the clinical use of oxcarbazepine in the treatment of epilepsy: a consensus view.

Extensive clinical use and a series of clinical trials have shown that oxcarbazepine is a valuable antiepileptic drug for the treatment of adults and children with partial onset seizures both in initial monotherapy, for conversion to monotherapy and as adjunctive therapy. The clinically recommended titration scheme for all forms of therapy in adults is to start with 150 mg/day at night and to increase by 150 mg/day every second day until a target dose of 900-1200 mg/day is reached. If necessary, one can go faster and start with up to 600 mg/day and titrate with weekly increments of up to 600 mg/day. In children, treatment can be initiated with 8-10 mg/kg/day body weight in two to three divided doses. Dosage can be increased by 8-10 mg/kg/day in weekly increments if necessary for seizure control. Hyponatremia (serum sodium <125 mmol/l) can develop gradually during the first months of oxcarbazepine therapy in approximately 3% of patients with a previously normal serum sodium. However, there is no need to measure baseline serum sodium concentrations unless the patient has renal disease, is taking medication which may lower serum sodium levels (such as diuretics, oral contraceptives or nonsteroidal anti-inflammatory drugs) or--in rare cases--has clinical symptoms of hyponatremia. During oxcarbazepine maintenance therapy measurement of serum sodium levels should also be considered if medications known to decrease sodium levels are added or symptoms of hyponatremia develop. Oxcarbazepine does not appear to have any clinically notable effects on other safety parameters such as renal and liver function or haematological test results. In summary, oxcarbazepine is a safe and well tolerated antiepileptic drug for partial epilepsy.

Anticonvulsants↗
PubMed2001

Increased production of IL-7 accompanies HIV-1-mediated T-cell depletion: implications for T-cell homeostasis.

We hypothesized that HIV-1-mediated T-cell loss might induce the production of factors that are capable of stimulating lymphocyte development and expansion. Here we perform cross-sectional (n = 168) and longitudinal (n = 11) analyses showing that increased circulating levels of interleukin (IL)-7 are strongly associated with CD4+ T lymphopenia in HIV-1 disease. Using immunohistochemistry with quantitative image analysis, we demonstrate that IL-7 is produced by dendritic-like cells within peripheral lymphoid tissues and that IL-7 production by these cells is greatly increased in lymphocyte-depleted tissues. We propose that IL-7 production increases as part of a homeostatic response to T-cell depletion.

Cohort Studies↗
PubMed2001

Glomerular cell number in normal subjects and in type 1 diabetic patients.

BACKGROUND: The number of cells in glomeruli has been a challenging measure, especially in human kidneys, with only a small amount of tissue obtained by biopsy. However, the number of cells and their function are important determinants of renal function in health and disease. METHODS: Modern morphometric techniques have now provided the means to determine the numerical density (Nv) and number (with a measure of glomerular volume) of endothelial cells, mesangial cells, and podocytes in plastic-embedded renal tissue biopsied from nondiabetic subjects (N = 36) and type 1 diabetic patients (N = 46) over an extended age range from childhood through late adult. RESULTS: Nv values for all glomerular cells varied only slightly with age and did not change within the range of glomerular lesions of diabetes studied. Thus, the increase in glomerular volume during childhood to a steady level thereafter was the primary determinant of total glomerular cell number. The number of mesangial cells and endothelial cells increased with age, reflecting the increase in all cells, while the podocytes remained unchanged in number over all ages studied (10 to 69 years). Numbers of total glomerular cells, mesangial cells, and endothelial cells were not changed with diabetes, while podocytes were fewer in number in diabetic patients of all ages, with reduced podocyte numbers even in diabetes of short duration. CONCLUSIONS: The essentially constant glomerular cell density in nondiabetic and diabetic subjects under different circumstances possibly indicates an underlying propensity for the glomerulus to regulate its architecture to maintain a constant number of cells per volume, no matter the size of the glomerulus or the severity of diabetic nephropathy studied in this set of patients. The reductions in podocyte numbers in both younger and older diabetic patients indicate a significant risk for functional abnormalities as diabetic nephropathy progresses. Moreover, these observations do not support the suggestion of marked increases in glomerular cell number (and especially mesangial cells) with the development and progression of diabetic nephropathy.

Adolescent↗
PubMed2001

[Ophthalmoscopic findings in 3 patients with panarteritis nodosa and review of the literature].

BACKGROUND: Ocular involvement in panarteritis nodosa (PAN) has been reported to occur in 10 to 20% of patients. In 3 patients with acute visual disturbance we point out unusual findings. PATIENTS: Case 1. A 40-year-old man initially presented with papilledema together with partial optic atrophy in both eyes, later polyneuropathy, gangrene of the toes and myalgic pains developed. Caliber changes in the small arteries in the liver were seen angiographically and recognized as signs of PAN. Under treatment with cyclophosphamide und prednisone no relapse occurred during a follow-up of 2 years. Case 2. In a 67-year-old man who suffered from arterial hypertension and coronary heart disease, central retinal artery occlusion occurred, at first in the left and then later in the right eye. The clinically suspected diagnosis of PAN (arterial hypertension, myalgia, polyneuropathy) was confirmed by a muscle biopsy. During a follow-up of 4 years--including treatment with prednisone and cyclophosphamide--no relapse occurred. Case 3. A 16-year-old adolescent with throbbing headaches and a thickened right temporal artery reported visual disturbances. These were due to an inflammation of choroidal vessels of the right eye appearing as an initial sign of PAN. Histology revealed a necrotising arteritis of the temporal artery. He presented with signs of Raynaud's disease, cachexia and arterial hypertension. Multiple vasculitic changes were detected by aorto-arteriography. Five months after the visual deterioration an anterior spinal artery syndrome with quadriplegia developed. After a follow-up of 2 years and treatment with prednisone und cyclophosphamide, he still had paralysis of both legs. The visual acuity was 1.0 in each eye. CONCLUSION: PAN should be considered in differential diagnosis in patients with acute inflammatory signs of the optic nerve head, the choroid and/or the retina together with general signs of the disease. If the disease is suspected, a muscle biopsy is indicated.

Adolescent↗
PubMed2001

Assessment of body composition change in a community-based weight management program.

OBJECTIVE: The purpose of this study was to validate the use of the leg-to-leg bioelectrical impedance analysis (BIA) system in assessing change in body composition over 32 weeks in overweight and obese women participating in a community weight management program. DESIGN: Intervention, with subjects prescribed an energy-restriction diet and exercise program for 32 weeks and body composition measured pre-study and after 12 and 32 weeks. SUBJECTS AND SETTING: Overweight and obese premenopausal women (n=201) with no overt disease were recruited at six sites into community-based weight loss programs. One hundred and twenty-four women completed all aspects of the study. INTERVENTION: Energy intake was set at 0.8 x resting metabolic rate (RMR) for weeks 1 through 12, 1.0 x RMR for weeks 13 through 20 and 1.2 x RMR for weeks 21 through 32. Energy intake was based on a food exchange table, with the number of food exchanges adjusted to encourage a percent distribution of 55% carbohydrate, 30% fat and 15% protein. Subjects increased their daily walking distance by 3.2 km above pre-study levels. MEASURES OF OUTCOME: Underwater weighing, seven skinfolds, and leg-to-leg BIA tests were used to assess body composition. RESULTS: A 3 x 3 repeated measures ANOVA revealed no significant difference in detecting change in FFM at 12 and 32 weeks among underwater weighing, BIA and skinfold, (F(4,492)=1.73, p=0.141) (decrease in FFM of 1.0+/-3.3 kg, 1.7+/-2.2 kg, and 1.4+/-3.3 kg respectively, 32 weeks). CONCLUSIONS: The leg-to-leg BIA system provides a valid measure of body composition change in overweight premenopausal women during a 32-week community-based weight loss program.

Adipose Tissue↗
PubMed2001

Biosynthesis of constitutive nitric oxide synthase-derived nitric oxide attenuates coronary vasoconstriction and myocardial depression in a model of septic heart failure induced by Staphylococcus aureus alpha-toxin.

OBJECTIVE: Myocardial depression, which frequently occurs in the course of septic shock, has been attributed to the cardiodepressant properties of nitric oxide (NO) generated by either the inducible NO synthase (iNOS) or the constitutive isoform (cNOS). We have previously demonstrated that alpha-toxin from Staphylococcus aureus induces thromboxane-mediated vasoconstriction accompanied by severe cardiodepression in isolated rat hearts. In the present study, we investigated the role of NO in the alpha-toxin-induced vascular and contractile abnormalities. DESIGN: Prospective, experimental study. SETTING: Research laboratory at a university hospital. SUBJECTS: Isolated hearts from male Wistar rats. INTERVENTIONS: Isolated hearts were perfused with purified staphylococcal alpha-toxin for 60 mins. MEASUREMENTS AND MAIN RESULTS: At a concentration of 0.25 and 0.5 microg/mL, alpha-toxin induced a rise in coronary perfusion pressure, depressed myocardial contractility, and caused edema formation. Simultaneously, a time- and dose-dependent rapid release of NO into the perfusate was noted as quantified by a chemiluminescence technique. L-NMMA, a nonselective inhibitor of NOS, but not PBITU, an iNOS-selective inhibitor, blocked NO synthesis, markedly increased the rise in coronary perfusion pressure and the loss in contractility, and enhanced edema formation in response to alpha-toxin. In contrast, zaprinast, a selective inhibitor of phosphodiesterase type V that is used for stabilization of cyclic guanosine monophosphate, attenuated the toxin-induced coronary vasoconstrictor response and the myocardial depression. L-arginine, the substrate of NOS, had similar, yet less potent, effects as zaprinast and slightly increased the release of NO caused by alpha-toxin. Immunohistochemical analysis of the myocardium at the end of the perfusion period demonstrated a positive staining for cNOS but not for iNOS. In addition, no up-regulation of iNOS mRNA was detected in the tissue of toxin-exposed hearts. CONCLUSIONS: Staphylococcal alpha-toxin provokes NO biosynthesis via activation of cNOS in rat hearts. NO partly antagonizes the deleterious effects of this pathogenicity factor on coronary vasoregulation and myocardial performance.

Animals↗
PubMed2001

Immunohistochemical expression analysis of inhibin-alpha and -beta subunits in partial and complete moles, trophoblastic tumors, and endometrial decidua.

The expression of inhibin-alpha subunit has been described in normal placentas, hydatidiform moles, and trophoblastic tumors. We performed a double immunohistochemical expression analysis of inhibin-alpha and inhibin-beta subunits in a cytogenetically well characterized series of 21 complete and 22 partial hydatidiform moles, 2 placental site trophoblastic tumors, and one choriocarcinoma. Syncytiotrophoblastic cells were consistently inhibin-alpha and inhibin-beta positive in all hydatidiform moles and in the one choriocarcinoma. Cytotrophoblast was negative for both subunits in all trophoblastic lesions studied. While villous intermediate trophoblastic cells were consistently inhibin-alpha negative in all hydatidiform moles, focal inhibin-beta immunoreactivity was detected in villous intermediate trophoblast in approximately one third of complete and partial hydatidiform moles. Decidual stromal cells in 40 hydatidiform moles were inhibin-alpha and inhibin-beta positive in approximately one third of cases. Both placental site trophoblastic tumors were inhibin-alpha positive but inhibin-beta negative. Our findings indicate that inhibin-alpha and -beta subunits are consistently coexpressed in syncytiotrophoblast in complete and partial moles. Immunohistochemical detection of inhibin subunits may be useful in the differential diagnosis of trophoblastic lesions.

Choriocarcinoma↗
PubMed2001

Malignant histiocytosis.

Until recently, malignant histiocytosis was a clearly defined clinical entity marked by fever, progressive wasting, lymphadenopathy, hepatosplenomegaly, and pancytopenia. However, for many years the morphologic findings in this disease continued to cause a great deal of controversy. Now it seems clear that most cases of malignant histiocytosis represent anaplastic large cell lymphoma (ALCL) with Ki 1 expression, and they are not related to the monocyte/macrophage system. This conclusion is based on histopathologic and immunohistochemical findings, and more recently, on results from genotypic studies. Thus, malignant histiocytosis is a "vanishing disease."

Histiocytic Sarcoma↗