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Biomedical subjects

M Schnitzler

Publications and source records attributed to M Schnitzler.

At least 19 recordsLinked to original sources
PubMed2006

Incompatible kidney donor candidates' willingness to participate in donor-exchange and non-directed donation.

Although paired donation, list donation and non-directed donation allow more recipients to receive living donor transplants, policy makers do not know how willing incompatible potential donors are to participate. We surveyed 174 potential donors ruled out for ABO-incompatibility or positive cross-match about their participation willingness. They were more willing to participate in paired donation as compared to list donation where the recipient receives the next deceased donor kidney (63.8% vs. 37.9%, p < 0.001) or non-directed donation (63.8% vs. 12.1%, p < 0.001). Their list donation willingness was greater when their intended recipients moved to the top versus the top 20% of the waiting list (37.9% vs. 19.0%, p < 0.001). Multivariate logistic regression modeling revealed that potential donors' empathy, education level, relationship with their intended recipient and the length of time their intended recipient was on dialysis also affected willingness. For paired donation, close family members of their intended recipient (odds ratio (OR) = 3.01, confidence intervals (CI) = 1.29, 7.02), with high levels of empathy (OR = 2.68, CI = 1.16, 6.21) and less than a college education (OR = 2.67, CI = 1.08, 6.61) were more willing to participate compared to other donors. Extrapolating these levels of willingness nationally, a 1-11% increase in living donation rates yearly (84-711 more transplants) may be possible if donor-exchange programs were available nationwide.

Adult↗
PubMed2001

Day-clinic treatment of late-life depression.

BACKGROUND: There are few studies evaluating treatment in gerontopsychiatric day-clinics. In this paper, data are presented on the outcome of day-clinic treatment in late-life depression. METHOD: Forty-four depressed elderly patients (mean Hamilton Depression Score: 17.6) were examined at admission and discharge for psychopathology, functioning in daily living, social situation, burden with medical disease and quality of life. RESULTS: At discharge, the patients showed a significant reduction in depressive symptoms, improvements in cognitive performance, social activities and contacts. However, a more detailed analysis revealed that only patients responding to treatment (n=20) improved in the respective parameters. Patients, who did not recover fully from depression (n=24), did not improve in any of these parameters. At admission, responders and nonresponders did not differ concerning quality of life. At discharge, responders were significantly more satisfied in 11 of 20 domains of life quality. A shorter life time duration of depressive disease and male sex were predictive for a remission of depression. Thus, it could be shown that a considerable number of patients suffering from late-life depression may be successfully treated in a gerontopsychiatric day-clinic and 45.5% fully recover from depression. CONCLUSIONS: The day-clinic setting meets the specific needs of patients suffering from late-life depression by maintaining them in the community, supporting their abilities for self-care and promoting social contacts. Treatment in a day-clinic may be recommended for many elderly depressed patients.

Activities of Daily Living↗
PubMed2000

Mutations associated with microsatellite unstable colorectal carcinomas exhibit widespread intratumoral heterogeneity.

Although microsatellite instability (MSI) has been shown to be present in 15% of sporadic colorectal carcinomas, the genetic events underlying the development of these tumors have not been well described. By investigating intratumoral heterogeneity, this study attempts to elucidate whether MSI-positive colorectal carcinomas develop as the result of a random accumulation of mutations or as an ordered, stepwise sequence of genetic alterations. Eighty-six regions from 16 MSI-positive sporadic colorectal carcinomas were examined for mutations in repeat nucleotide sequences of the tumour suppressor genes transforming growth factor beta type II receptor (TGFBRII), insulin-like growth factor II receptor (IGFIIR), and BAX, and the mismatch repair genes MSH3 and MSH6. At least 2 and up to 5 of these genes were mutated in each tumour, and widespread intratumoral heterogeneity was observed for each gene. Regions of tumour with TGFBRII mutations were correlated with a poorly differentiated histology. Unlike the situation in microsatellite stable colorectal carcinomas, the findings of the present study did not suggest that a particular sequence of tumour suppressor and mismatch repair genes are mutated during colorectal tumorigenesis. It seems likely that a random accumulation of mutations, as a result of a defect in the mismatch repair pathway, drives tumour progression in this type of colorectal carcinoma.

Colorectal Neoplasms↗
PubMed2000

Genetic analysis of multiple sporadic colon carcinomas from a single patient.

At least two separate genetic pathways of carcinogenesis in sporadic colon cancer involving the accumulation of mutations at various genetic loci have been described. About 15% of sporadic colorectal carcinomas arise via a mechanism associated with microsatellite instability (MSI) and mutations in transforming growth factor beta receptor II (TGFbetaRII), insulin-like growth factor II receptor (IGFIIR) and BAX, whilst the remaining 85% are associated with aneuploidy and gross chromosomal rearrangements. An 81-year-old woman had a sigmoid colon carcinoma resected and 18 months later developed two additional carcinomas of the caecum and transverse colon. To investigate whether there was a common genetic mechanism of carcinogenesis for the three lesions, MSI status was assessed, TGFbetaRII, IGFIIR and BAX were analysed for mutations and protein expression of transforming growth factor beta1 (TGFbeta1) and p53 were studied using immunohistochemistry. The caecal and transverse colonic carcinomas were both MSI positive but different mutations were identified in each lesion. No genetic abnormalities were identified in the sigmoid colonic carcinoma. This suggests that each carcinoma arose via a separate genetic mechanism of carcinogenesis.

Adenocarcinoma↗
PubMed2000

[Anxiety as a concomitant symptom of depression in the elderly].

Anxiety is a symptom frequently encountered in elderly depressed patients. It is supposed to have an unfavourable prognostic impact. We studied the frequency of psychic anxiety and its relationship to demographic, social and clinical variables in a group of 54 elderly depressed patients admitted to a gerontopsychiatric day-clinic. Severity of depression, cognitive performance, functional level, social situation and life satisfaction were studied by means of standardized instruments. In about half of the patients studied, we found significant psychic anxiety. Compared to the other depressed patients, patients with anxiety suffered more frequently from cognitive impairment and were more dissatisfied with the acceptance of their disease by other persons. They more frequently lived together with other persons in one household. When leaving psychic anxiety out of consideration as a depressive symptom, the severity of depression was not different in patients with and without anxiety. Anxious patients were equally responsive to day-clinic treatment as non-anxious patients. However, duration of treatment was considerably increased. Thus, elderly depressed patients with anxiety show particular psychosocial and clinical features and require special attention in diagnostics and treatment.

Activities of Daily Living↗
PubMed2000

[Outcome quality of gerontopsychiatric day-clinic treatment: changes in life-satisfaction:].

OBJECTIVE: The variety of institutional treatments in psychiatry, as well as financial aspects make it necessary to evaluate these institutions for the quality of their medical care. At the Central Institute of Mental Health in Mannheim, the quality of treatment at the geronto-psychiatric day-clinic is assessed on the level of outcome quality. METHOD: The patients are examined at admission, at discharge, half a year and one year after discharge. Psychopathology, activities of daily living, social situation and quality of life are assessed by means of standardized instruments. RESULTS: Preliminary results show that at discharge, patients are less depressed, have achieved a higher level of social activities and contacts and that their quality of life improved in most domains. In some domains of quality of life improvement is highly correlated with the amelioration of depressive symptoms, in others not. CONCLUSION: Whether these effects of treatment will last, has to be studied in follow-up examinations.

Activities of Daily Living↗
PubMed1998

Surgery for intestinal graft-versus-host disease: report of two cases.

PURPOSE: With allogeneic bone marrow transplantation becoming increasingly common, intestinal graft-versus-host disease often is seen within specialized transplant units. Surgeons are involved infrequently in the management of such patients, and yet occasionally are called upon to operate on critically ill patients with refractory disease. This article reviews the salient features of this condition and discusses possible indications for surgery. METHOD: Two cases of intestinal graft-versus-host disease that required laparotomy are presented. RESULTS: A 24-year-old male with severe, unremitting, acute intestinal graft-versus-host disease underwent small-bowel and large-bowel resections for massive bleeding. A 35-year-old male with recurrent symptoms of small-bowel obstruction after allogeneic bone marrow transplantation underwent small-bowel resection and multiple strictureplasties for chronic intestinal graft-versus-host disease. CONCLUSION: Surgery can be performed for complications of intestinal graft-versus-host disease not responding to medical therapy, with successful outcome.

Adult↗
PubMed1998

Cancer and inflammatory bowel disease: bias, epidemiology, surveillance, and treatment.

Individuals with chronic ulcerative colitis are at increased risk of developing colorectal carcinoma, particularly if there is long-standing disease or extensive colitis. It is generally accepted that the risk of colorectal cancer does not begin until 8 to 10 years after the time of diagnosis of ulcerative colitis. Thereafter it increases by approximately 0.5% to 1.0% per year. In patients with Crohn's disease, the risk of malignancy is smaller and less well defined. The most significant predictor of the risk of malignancy in patients with inflammatory bowel disease is the presence of dysplasia in colonic biopsies. There is considerable controversy in the literature regarding the efficacy of colonoscopic surveillance programs and the role of prophylactic surgery to prevent colorectal cancer. Surveillance certainly fails to detect carcinoma in some patients who are having regular colonoscopy. Concerns have also been raised as to the cost-benefit of colonoscopic surveillance in patients with colitis. Randomized controlled trials of surveillance programs are highly unlikely in view of the low prevalence of IBD in the population, the long period of observation required, and the probability of contamination of surveillance programs by colonoscopy for assessment of disease activity. Despite the lack of clear guidelines, surveillance colonoscopy and biopsy continues to be widely practiced. Research is proceeding to identify genetic and biochemical markers that may prove clinically useful for predicting cancer risk. At present, however, surveillance programs are likely to continue according to institutional practice. It is important for those participating in such programs to be aware of the limitations of colonoscopy and biopsy as a means of reducing the risk of cancer in inflammatory bowel disease.

Bias↗
PubMed1997

Clonality of dysplastic epithelium in colorectal adenomas from familial adenomatous polyposis patients.

Loss of function of both alleles of the APC gene results in colorectal adenoma formation in familial adenomatous polyposis, an autosomal dominant genetic disorder leading to multiple colorectal tumors at an early age. Previous molecular studies indicate that the mutant cells forming dysplastic epithelium within adenomas are clonally derived. We show, using immunostaining and molecular techniques, that the dysplastic epithelium of adenomas actually contains a mixture of cells derived from both mutant and normal stem cells. Well-differentiated mucous cells in the dysplastic epithelium, one of the indicators of severity of dysplasia, were derived from normal stem cells. Carcinomas in these patients, in contrast, contained only mutant cells, indicating that the subsequent mutations incurred by these cells have led to their isolation from the normal population.

Adenoma↗
PubMed1997

Chemotherapy for desmoid tumors in association with familial adenomatous polyposis.

PURPOSE: This study was designed to assess the effect of chemotherapy on complex desmoid tumors associated with familial adenomatous polyposis. METHODS: Five patients (3 males, 2 females; age range, 29-45 years) had symptomatic, unresectable intra-abdominal desmoid tumors in association with familial adenomatous polyposis that were unresponsive to conventional medical therapy. Each patient was treated with a cytotoxic chemotherapeutic regimen consisting of doxorubicin and dacarbazine followed by carboplatin and dacarbazine. Response to treatment was assessed by measurement of tumor size using computerized tomography. Follow-up has been for a mean of 22 (range, 10-30) months. RESULTS: One patient has had a complete response, and three patients have had a partial response, with a reduction in tumor volume of at least 50 percent. One patient had a minimum response to treatment and developed a rapid increase in tumor size on cessation of therapy. Complications of treatment included febrile neutropenia, severe epistaxis, and subclavian vein thrombosis. CONCLUSIONS: The cytotoxic chemotherapeutic regimen described is effective in the treatment of selected unresectable desmoid tumors associated with familial adenomatous polyposis and should be considered in symptomatic patients who do not respond to conventional medical therapy.

Adenomatous Polyposis Coli↗
PubMed1996

The identification of false positive responses to the pentagastrin stimulation test in RET mutation negative members of MEN 2A families.

OBJECTIVE: The pentagastrin stimulation test is the traditional test used for the identification of asymptomatic individuals in multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC). The identification of mutations in the RET proto-oncogene segregating with the disease phenotype in MEN 2A and FMTC families has made it possible to re-examine the validity of using this test for the identification of affected family members. DESIGN: Sequential and single pentagastrin stimulation test data were collected following the identification of RET mutation positive and RET mutation negative members of families with MEN 2A or FMTC. PATIENTS: RET mutations were identified in 16 Australian and New Zealand MEN 2A or FMTC families. An analysis of 39 individuals from these families was included in this study. Thirty-two individuals (14 males, 18 females) had previously been determined as RET mutation negative. Seven individuals (6 males, 1 female) had previously been determined as RET mutation positive. Two RET mutation negative males had thyroidectomy based on prior pentagastrin test results. MEASUREMENTS: Serum calcitonin levels in response to stimulation with pentagastrin were measured at 0, 1, 2, 5 and 10 minutes post injection. Mutation analysis of the RET proto-oncogene was performed in all individuals. In two RET mutation negative individuals from two MEN 2A families, thyroidectomy was performed and C-cells were quantitated in order to determine the diagnosis of C-cell hyperplasia. RESULTS: There was a statistically significant difference (P < 0.013) between RET mutation negative male and female mean peak calcitonin responses of 282 +/- 236 and 96 +/- 62 (mean +/- SD) ng/l respectively. False positive responses to pentagastrin stimulation were identified in seven individuals who were RET mutation negative in two of the 16 families. Histologic examination of the thyroid glands in the two RET mutation negative individuals who had thyroidectomy demonstrated C-cell hyperplasia in one but not in the other. CONCLUSIONS: There is considerable overlap between pentagastrin test results in individuals who are RET mutation positive and those who are RET mutation negative. These results indicate a need for routine performance of RET proto-oncogene analysis on all individuals at risk of developing MEN 2A or FMTC and a coupling of pentagastrin test results and RET proto-oncogene analysis in the decision to proceed with thyroidectomy.

Adolescent↗
PubMed1996

Sulindac increases the expression of APC mRNA in malignant colonic epithelial cells: an in vitro study.

BACKGROUND: Sulindac is a non-steroidal anti-inflammatory drug which induces regression of colonic polyps in patients with familial adenomatous polyposis. Animal and in vitro studies have shown that both the sulphide metabolite of sulindac, which is able to inhibit cyclo-oxygenase, and the sulphone metabolite, which lacks this ability, are able to inhibit the growth of colonic carcinoma cells. The exact mechanism by which these effects occurs is not known. AIMS: To examine the effect of sulindac sulphide and sulindac sulphone on the expression of APC messenger RNA (mRNA), and on the proliferation of colonic carcinoma cells in vitro. METHODS: The colonic carcinoma cell line LIM 1215 was treated with sulindac sulphide and sulindac sulphone (10 microM or 100 microM) for 24 hours. Total RNA was extracted and APC mRNA was quantitated using competitive reverse transcription polymerase chain reaction. Measurements of cell number, cell proliferation, and prostaglandin E2 concentrations were also made. RESULTS: A significant increase in APC mRNA was observed after treatment with 10 microM of both sulindac sulphide and sulindac sulphone (control: 37.2 (19.7); 10 microM sulindac sulphide: 129 (112.8); 10 microM sulindac sulphone: 207.7 (102.9) pg/(g total RNA) (p < 0.05). Prostaglandin E2 concentrations were significantly reduced after treatment with sulindac sulphide, but not after sulindac sulphone. Both agents produced a dose dependent reduction in cell numbers and cell proliferation, which was more noticeable after treatment with sulindac sulphide. CONCLUSIONS: Both sulindac sulphide and sulindac sulphone inhibit the growth of carcinoma cells in vitro and cause an increase in APC mRNA. The effect of these agents on colonic carcinogenesis is not mediated entirely by means of an inhibition of prostaglandin biosynthesis.

Adenomatous Polyposis Coli↗
PubMed1995

Quantitation of APC mRNA in human tissues.

The aim of this study was to develop a method for quantitation of APC mRNA and to measure APC mRNA levels in human tissues. This was done using a competitive reverse transcription PCR with a synthetic RNA control. APC mRNA (pg/microgram total RNA) was quantitated in the following tissues: normal colon 133.6 +/- 69.0; normal duodenum 16.6 +/- 15.7; normal thyroid 30.4 +/- 20.3; normal esophagus 65.2 +/- 58.8; colonic carcinoma 66.5 +/- 30.3; esophageal carcinoma 54.7 +/- 26.5; papillary thyroid carcinoma 55.8 +/- 32.9 and colonic adenomas from patients with familial adenomatous polyposis 46 +/- 15. APC mRNA levels were significantly lower in the duodenum and thyroid than in the colon and esophagus. The quantity of APC mRNA was lower in colonic adenomas from FAP patients than in normal colonic mucosa (p < 0.05).

Base Sequence↗
PubMed1994

A rapid screening method for the detection of mutations in the RET proto-oncogene in multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma families.

Multiple endocrine neoplasia type 2A (MEN2A) and familial medullary thyroid carcinoma (FMTC) are autosomal dominant inherited cancer syndromes with incomplete penetrance. Following the identification of mutations in the RET proto-oncogene that segregate with the disease phenotype in MEN2A, MEN2B, and FMTC, genetic screening of individuals with mutations in RET may be performed. We have employed restriction endonuclease digestion of polymerase chain reaction products as an alternative to sequence analysis for rapid identification of mutant gene carriers in families in which MEN2A and FMTC are segregating. Twenty-one Australasian MEN2A and FMTC families have been screened for mutations in a cysteine-rich region of the RET proto-oncogene. Seven independent mutations were identified in key individuals in 16 of these families. We have identified a mutation in codon 620, 2053 T-->C (Cys620Arg), and two mutations in codon 634 of exon 11 of RET, 2095 T-->C (Cys634Arg) and 2096 G-->A (Cys634Tyr), all three of which were present in both MEN2A and FMTC families.

Australia↗
PubMed1994

[Depression and sleep--the status of current research].

Abnormalities of REM sleep, i.e. shortening of REM latency, lengthening of the duration of the first REM period and heightening of REM density, which are frequently observed in patients with a Major Depressive Disorder (MDD), have attracted considerable interest. Initial hopes that these aberrant patterns of sleep constitute specific markers for the primary/endogenous subtype of depression have not been fulfilled. The specificity of REM sleep disinhibition for depression in comparison to other psychopathological groups is also challenged. Demographic variables like age and sex exert strong influences on sleep physiology and must be controlled when searching for specific markers of depressed sleep. It is still an open question whether abnormalities of sleep are state-markers or trait-markers of depression. Beyond baseline studies, the cholinergic REM induction test (CRIT) indicated a heightened responsitivity of the REM sleep system to cholinergic challenge in depression compared with healthy controls and other psychopathological groups, with the exception of schizophrenia. A special role for REM sleep in depression is supported by the well known REM sleep suppressing effect of most antidepressants. The antidepressant effect of selective REM deprivation by awakenings stresses the importance of mechanisms involved in REM sleep regulation for the understanding of the pathophysiology of depressive disorders. The positive effect of total sleep deprivation on depressive mood which can be reversed by daytime naps, furthermore emphasizes relationships between sleep and depression. Experimental evidence as described above instigated several theories like the REM deprivation hypothesis, the 2-process model and the reciprocal interaction model of nonREM-REM sleep regulation to explain the deviant sleep pattern of depression. The different models will be discussed with reference to empirical data gathered in the field.

Animals↗
PubMed1994

Bioequivalence of two commercially available levothyroxine-Na preparations in athyreotic patients.

The thyroid hormones levothyroxine and levotriiodothyronine are vital for normal growth and development and play an important role in energy metabolism. The bioequivalence of levothyroxine following administration of the test preparation (Eferox 100 tablets, Wyeth Pharma GmbH, Münster, Germany) and a reference preparation (each containing 100 micrograms levothyroxine-Na, the sodium salt of the natural thyroxine isomer) was investigated in 24 male and female patients with a lack of basal thyroid hormone secretion after an ablative thyroidectomy and postoperative radiotherapy. In a randomized, multicentric, open 3-factorial Latin-square (2 x 2 x 2) crossover study the subjects received two pharmaceutical units of the formulations once daily in the morning 30 min before breakfast during two periods of 35-42 consecutive days each. Serum concentrations of total thyroxine and total triiodothyronine were determined on screening day (basal concentrations), on the last 3 days of administration at predose to verify steady-state conditions, and on the last day of administration at 9 predetermined time points up to 24 h postadministration to obtain 24-h hormone profiles. The two formulations proved to be bioequivalent for levothyroxine regarding rate and extent of absorption. The bioequivalence decision was based on CSS,max and AUD0-24h.

Adult↗
PubMed1993

Comparison in acute myocardial infarction of anisoylated plasminogen streptokinase activator complex versus heparin evaluated by simultaneous thallium-201/technetium-99m pyrophosphate tomography.

In a subgroup of 45 patients with acute myocardial infarction (AMI) from the German multicenter trial of anisoylated plasminogen streptokinase activator complex (APSAC) (n = 20) versus heparin (n = 25), simultaneous thallium (TI)-201 technetium (Tc)-99m pyrophosphate (PYP) tomography was initiated to elucidate a possible benefit of APSAC over heparin. Findings in the 2 treatment groups were similar with respect to TI-201 defect score, relative scintigraphic infarct size, and in keeping with the main group coronary artery patency, global ejection fraction and maximal creatine kinase level. However, 2 different TI-201/Tc-99m PYP accumulation patterns within the area of infarction (homogeneous, group A; inhomogeneous, group B) were identified. Both treatment groups were similar with regard to the frequency of the homogeneous and inhomogeneous pattern. In comparing the 2 accumulation patterns, creatine kinase peaked earlier in group A than in group B, and global left ventricular ejection fraction was significantly higher in group A than in group B. In Group A, 30 of 31 patients and in group B 7 of 11 patients had a patent infarct-related vessel (p < 0.025). TI-201 defect score was lower in group A than in group B. Likewise, relative size of the infarction as determined from Tc-99m PYP images was significantly lower in group A than in group B. Fifteen patients experienced cardiogenic shock or severe heart failure. Patients in group B had a higher incidence of these in-hospital complications than patients in group A (92 vs 12%, p < 0.0005). Scintigraphic infarct size and TI-201 defect score were greater in patients with the aforementioned clinical events.(ABSTRACT TRUNCATED AT 250 WORDS)

Anistreplase↗