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Biomedical subjects

B Kremer

Publications and source records attributed to B Kremer.

At least 109 records · Page 6Linked to original sources
PubMed1996

[Economic considerations in critically ill intensive care patients].

Since 1992 the data for all patients referred to our ICU have been entered on computer and analyzed for parameters relevant to therapeutic effectiveness on the one hand and cost-containment on the other. The analysis of data for 5424 patients concerning APACHE II-score, age, number of ICU days, time of mechanical ventilation and/or hemodialysis, cardio-respiratory complications and insufficiency, ICU discharge date and hospital discharge date demonstrates a profile or our intensive care services using all resources efficiently. The data revealed no ethically acceptable parameter or necessity to include economic considerations in medical decisions which had to be taken for individual patients and situations.

Adult↗
PubMed1995

Somatic mosaicism in sperm is associated with intergenerational (CAG)n changes in Huntington disease.

We have analysed the CAG repeat in the Huntington disease (HD) gene in sperm and blood from 20 unrelated HD patients. Although the CAG repeat displayed significant mosaicism in sperm from all individuals, there were marked differences in the degree of repeat instability. Individuals who had either inherited or transmitted an expanded CAG repeat displayed the highest levels of repeat mosaicism, whereas individuals who had inherited or transmitted a contracted repeat had very limited CAG mosaicism in sperm. A strong association between intergenerational change in CAG allele size and the level of sperm repeat mosaicism was determined (P = 0.019). In contrast, neither blood CAG size nor repeat mosaicism in blood, were significantly associated with intergenerational CAG changes. These data suggest the presence of a cis-acting factor, separate from CAG size, that strongly influences the intergenerational behaviour of the CAG repeat. Additional studies are needed to determine whether analysis of CAG mosaicism in sperm is useful for assessing an individual's risk for transmitting large expansions or contractions to his offspring.

Adolescent↗
PubMed1995

Functional caudate imaging in symptomatic Huntington's disease: positron emission tomography versus single-photon emission computed tomography.

Functional neuroimaging with positron emission tomography previously demonstrated reduced caudate glucose metabolism in virtually all symptomatic patients with Huntington's disease (HD). Single-photon emission computed tomography studies of brain blood flow also have shown caudate abnormalities in patients with HD. The present study compared these two functional imaging modalities in 6 patients with HD who had been symptomatic for fewer than 5 years. All patients had significantly impaired caudate-thalamus and caudate-whole-slice glucose metabolism ratios as measured by positron emission tomography. However, only 3 had clearly abnormal caudate-thalamus activity ratios and 2 had clearly abnormal caudate-whole-slice ratios on single-photon emission computed tomography. These findings indicate that single-photon emission computed tomography imaging of caudate blood flow is a less sensitive indicator of caudate dysfunction in early HD than is positron emission tomography imaging of caudate glucose metabolism.

Anticonvulsants↗
PubMed1995

Hereditary late-onset chorea without significant dementia: genetic evidence for substantial phenotypic variation in Huntington's disease.

We examined five individuals and obtained information concerning six other members from two unrelated families, nearly all of whom developed chorea after age 50 (one patient developed chorea at age 40). The severity of chorea progressed in all patients and became disabling in some individuals approximately 15 years after onset. Cognitive impairment was absent or minimal. All five examined patients were cognitively normal, even 10 to 30 years following the onset of chorea. Formal neuropsychometric testing demonstrated mild cognitive impairment in two individuals. Nevertheless, all patients were able to maintain employment or carry on with their usual household tasks until chorea was severe. One individual first became demented 30 years after the onset of chorea. Neuroimaging (with CT or MRI) in four patients failed to demonstrate significant caudate or putaminal atrophy 8 to 15 years following the onset of chorea. Three other family members (who were not available for examination) were said to have suffered chorea (without any mental decline) beginning after age 50, with subsequent survival of 20 years (in one) and 30 years (in two). Given this constellation of history and findings, three experienced neurologists and two medical geneticists concluded that these patients had a familial chorea syndrome distinct from Huntington's disease (HD). However, genetic analysis of the trinucleotide (CAG) repeat length associated with HD (in 4p16.3) determined repeat lengths of 44 and 46 in four patients tested (within the HD range). We conclude that these patients have HD and that such families represent further convincing examples of significant phenotypic variation for HD.

Age of Onset↗
PubMed1995

Sex-dependent mechanisms for expansions and contractions of the CAG repeat on affected Huntington disease chromosomes.

A total of 254 affected parent-child pairs with Huntington disease (HD) and 440 parent-child pairs with CAG size in the normal range were assessed to determine the nature and frequency of intergenerational CAG changes in the HD gene. Intergenerational CAG changes are extremely rare (3/440 [0.68%]) on normal chromosomes. In contrast, on HD chromosomes, changes in CAG size occur in approximately 70% of meioses on HD chromosomes, with expansions accounting for 73% of these changes. These intergenerational CAG changes make a significant but minor contribution to changes in age at onset (r2 = .19). The size of the CAG repeat influenced larger intergenerational expansions (> 7 CAG repeats), but the likelihood of smaller expansions or contractions was not influenced by CAG size. Large expansions (> 7 CAG repeats) occur almost exclusively through paternal transmission (0.96%; P < 10(-7)), while offspring of affected mothers are more likely to show no change (P = .01) or contractions in CAG size (P = .002). This study demonstrates that sex of the transmitting parent is the major determinant for CAG intergenerational changes in the HD gene. Similar paternal sex effects are seen in the evolution of new mutations for HD from intermediate alleles and for large expansions on affected chromosomes. Affected mothers almost never transmit a significantly expanded CAG repeat, despite the fact that many have similar large-sized alleles, compared with affected fathers. The sex-dependent effects of major expansion and contractions of the CAG repeat in the HD gene implicate different effects of gametogenesis, in males versus females, on intergenerational CAG repeat stability.

Adolescent↗
PubMed1995

[Immunocytologic detection of micro-metastatic cells in patients with gastrointestinal tumors].

The success of surgical treatment of gastric-, colorectal- and pancreatic cancer is often limited due to local recurrence, the development of metastases or peritoneal carcinosis by cells which have been seeded already at the time of operation. Immunocytological methods enable the detection of disseminated cancer cells before their clinical manifestation as demonstrated by this study. Lavage samples from the peritoneal cavity and bone marrow samples from 147 patients with an adenocarcinoma of the stomach, colon and pancreas were investigated with a panel of six different monoclonal antibodies against tumor-associated antigens (CEA, CA-19-9, 19-1A, C-54-0, Ra96) and cytokeratin, respectively. Additionally, 43 patients with benign diseases were investigated as a control group. Micrometastatic cells were detected either in the bone marrow or the peritoneal cavity in 51% of the cancer patients (gastric cancer: 51%, colorectal cancer: 40%, pancreatic cancer: 72%). The occurrence of stained cells in the peritoneal cavity and bone marrow samples correlated with the tumor stage and showed even in about 30% of patients with a stage I tumor positive bone marrow and/or peritoneal cavity samples. No unspecific reactions were found in the control group. The 2-year follow up shows a significant correlation between tumor cell detection and the survival. Our study strongly indicates a clinical benefit of this method in adjuvant therapy concepts.

Adenocarcinoma↗
PubMed1995

[Preoperative locoregional staging of stomach carcinoma with endosonography].

From January 1987 till February 1992, a total of 203 consecutive patients with gastric carcinoma were evaluated with endosonography before operation. Endosonographic findings were categorized according to the TNM classification and compared with the histology of the resected specimen (n = 165). The overall accuracy rate of EUS in the assessment of the depth of tumor infiltration was 78%. The sensitivity and specificity of EUS in the detection of regional involved nodes were 82% and 84% respectively. Microscopic tumor invasion and indistinguishable inflammatory changes were the most frequent causes of misinterpretation by EUS. Tumor stenosis was a clear limitation for endosonography in 14% of the cases.

Female↗
PubMed1995

[Results of liver resection in 113 patients with metastases of colorectal carcinomas].

Between 1985-1991 and 1991-1994 118 liver resections in 113 patients with colorectal liver metastases were performed by our group at the University hospitals of Hamburg and Kiel. The data of 106 patients were analysed regarding the prognostic factors: age, sex, localisation--stage--grading of the primary tumor, localisation--number--size--synchronous/metachronous appearance of metastases, extent and radicality of the liver resection. The results showed, that a significant prognostic influence regarding the long-term survival rate could only be achieved in patients, in which a R0-resection with a histologically proven tumor free margin of more than 1 cm was performed. In these cases (n = 46) a median survival time of 38 months was observed. In patients with histologically proven tumor free resection margins < 1 cm (n = 38) the median survival time was 24 months, in patients with R1-resections (n = 7) 26 months and in patients with R2-resections (n = 15) 20 months respectively.

Adult↗
PubMed1995

[Unilateral recurrent nerve paralysis in suspected Lyme borreliosis].

Cranial nerve palsy can often be observed in Borrelia burgdorferi infection. A dysphonic patient with a long lasting left-sided recurrent nerve palsy was treated with ceftriaxone, an antibiotic drug for the therapy of Lyme borreliosis. On the 7th day of application the paretic vocal fold showed recovering movements up to regular vocal fold function and normal stroboscopic results. Clinical and serologic constellations and their therapeutical implications are discussed.

Adult↗
PubMed1994

A worldwide study of the Huntington's disease mutation. The sensitivity and specificity of measuring CAG repeats.

BACKGROUND: Huntington's disease is associated with an expanded sequence of CAG repeats in a gene on chromosome 4p16.3. However, neither the sensitivity of expanded CAG repeats in affected persons of different ethnic origins nor the specificity of such repeats for Huntington's disease as compared with other neuropsychiatric disorders has been determined. METHODS: We studied 1007 patients with diagnosed Huntington's disease from 565 families and 43 national and ethnic groups. In addition, the length of the CAG repeat was determined in 113 control subjects with a family history of Alzheimer's disease (44 patients), schizophrenia (39), major depression (16), senile chorea (5), benign hereditary chorea (5), neuroacanthocytosis (2), and dentatorubropallidoluysian atrophy (2). The number of CAG repeats was also assessed in 1595 control chromosomes, with the size of adjacent polymorphic CCG trinucleotide repeats taken into account. RESULTS: Of 1007 patients with signs and symptoms compatible with a diagnosis of Huntington's disease, 995 had an expanded CAG repeat that included from 36 to 121 repeats (median, 44) (sensitivity, 98.8 percent; 95 percent confidence interval, 97.7 to 99.4 percent). There were no significant differences among national and ethnic groups in the number of repeats. No CAG expansion was found in the 110 control subjects with other neuropsychiatric disorders (specificity, 100 percent; 95 percent confidence interval, 95.2 to 100 percent). In 1581 of the 1595 control chromosomes (99.1 percent), the number of CAG repeats ranged from 10 to 29 (median, 18). In 12 control chromosomes (0.75 percent), intermediate-sized CAG sequences with 30 to 35 repeats were found, and 2 normal chromosomes unexpectedly had expanded CAG sequences, of 39 and 37 repeats. CONCLUSIONS: CAG trinucleotide expansion is the molecular basis of Huntington's disease worldwide and is a highly sensitive and specific marker for inheritance of the disease mutation.

Adult↗
PubMed1994

Immunocytological detection of micrometastatic cells: comparative evaluation of findings in the peritoneal cavity and the bone marrow of gastric, colorectal and pancreatic cancer patients.

The prognosis of digestive cancers is poor mainly due to intraperitoneal relapse by cells which may have already been seeded at the time of surgery. Using immunocytology we investigated the peritoneal cavity and, as a comparison, the bone marrow of 147 patients with gastric, colorectal and pancreatic cancer for micrometastatic cells. Cytological samples from peritoneal cavity lavages and bone marrow aspirates were analyzed using monoclonal antibodies (MAbs) against tumor-associated antigens (TAA) (CEA, CA-19-9, 17-1-A, C-54-0, Ra96) and compared to a MAb staining cytokeratins (KL-1). Patients with benign diseases served as controls. Intraperitoneal micrometastatic cells were detected in 27% of colorectal, 43% of gastric and 58% of pancreatic cancer patients. In the bone marrow, the corresponding data were 29% for colorectal, 25% for gastric and 58% for pancreatic cancer patients. Combined evaluation of both compartments increased the detection rate significantly (colorectal cancer: 40%, gastric cancer: 52%, pancreatic cancer: 72%). No unwarranted reactions were found in the control group. Combining 3 antibodies (CA-19-9, Ra96, C-54-0) enabled good detection for peritoneal cavity samples. In the bone marrow, the use of 2 antibodies (KL-1 and CA-19-9) detected 94% of all positive samples, whereas KL-1 and CA-19-9 stained approx. 70% of all positive samples in each case. The occurrence of stained cells in the peritoneal cavity correlated with classical prognostic factors (TNM classification).

Antibodies↗
PubMed1994

Detection of the anti-p53 antibody response in malignant and benign pancreatic disease.

Genomic alterations in the p53 tumour-suppressor gene and overexpression of p53 protein, resulting from gene mutations, are frequently found in pancreatic cancer. In this study we analysed the sera of 160 patients with malignant and benign pancreatic diseases for the presence of circulating antibodies to the p53 protein. The analysis of the sera was performed using two different enzyme-linked immunosorbent assay (ELISA) systems. To further substantiate the results, all sera were analysed by the Western blot technique using a cell lysate of PancTu-1 cells (p53 mutation at codon 176) as antigen source. Additionally, all positive sera were analysed by the Western blot technique using recombinant p53 as the antigen source. Although the rate of p53 mutations in pancreatic tumours is of the same order as in other adenocarcinomas (> or = 50%), an antibody response was found in only 5/78 (6.4%) sera from patients with pancreatic cancer. Two out of 82 (2.4%) sera of patients with benign pancreatic diseases were clearly positive for p53 antibodies. One additional specimen was weakly positive, i.e. only in one ELISA and Western blot system.

Adult↗
PubMed1994

Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm.

Huntington disease is associated with an unstable and expanded (CAG) trinucleotide repeat. We have analysed the CAG expansion in different tissues from 12 affected individuals. All tissues examined were found to display some repeat mosaicism, with the greatest levels detected in brain and sperm. Regions within the brain showing most obvious neuropathology, such as the basal ganglia and the cerebral cortex, displayed the greatest mosaicism, whereas the cerebellar cortex, which is seldom involved, displayed the lowest degree of CAG instability. In two cases of childhood onset disease we detected differences of 8 and 13 trinucleotides between the cerebellum and other regions of the brain. Our results provide evidence for tissue specific instability of the CAG repeat, with the largest CAG repeat lengths in affected regions of the brain.

Adult↗
PubMed1994

DNA haplotype analysis of Huntington disease reveals clues to the origins and mechanisms of CAG expansion and reasons for geographic variations of prevalence.

This study of allelic association using three intra- and two extragenic markers within 150 kb of the Huntington disease (HD) mutation has provided evidence for linkage disequilibrium for four of five markers. Haplotype analysis of 67 HD families using markers in strong linkage disequilibrium with HD identified two haplotypes underlying 77.6% of HD chromosomes. Normal chromosomes with these two haplotypes had a mean number of CAG repeats significantly larger than and an altered distribution of CAG repeats compared with other normal chromosomes. Furthermore, haplotype analysis of five new mutation families reveals that HD has arisen on these same two chromosomal haplotypes. These findings suggest that HD arises more frequently on chromosomes with specific DNA haplotypes and higher CAG repeat lengths. We then studied CAG and CCG repeat lengths in the HD gene on 896 control chromosomes from different ancestries to determine whether the markedly reduced frequency of HD in Finland, Japan, China and African Blacks is associated with an altered frequency of DNA haplotypes and subsequently lower CAG lengths on control chromosomes compared to populations of Western European descent. The results show a highly significant inverse relationship between CAG and CCG repeat lengths. In populations with lowered prevalence rates of HD, CAG repeat lengths are smaller and the distribution of CCG alleles is markedly different from Western European populations. These findings suggest that, in addition to European emigration, new mutations make a contribution to geographical variation of prevalence rates and is consistent with a multistep model of HD developing from normal chromosomes with higher CAG repeat lengths.

Africa↗
PubMed1994

Normal CAG repeat length in the Huntington's disease gene in senile chorea.

There is a widely held belief that most patients presenting with senile chorea have late-onset Huntington's disease (HD) with an unknown family history. We measured CAG trinucleotide repeat expansion in the HD gene in four patients with a clinical presentation of senile chorea and found that CAG repetition lengths were normal. These findings support senile chorea as being a distinct clinical entity that is nosologically separate from late-onset HD.

Aged↗
PubMed1994

[Immunocytologic detection of disseminated tumor cells in the peritoneal cavity and bone marrow in patients with pancreatic carcinoma].

Despite radical surgical treatment, the prognosis of patients with pancreatic cancer is poor. The success of surgical treatment is often limited due to local recurrence and especially the development of metastases and peritoneal carcinosis by cells which have been seeded already at the time of operation. Immunocytological methods enabled the detection of disseminated cancer cells before their clinical manifestation as demonstrated by this study. Lavage samples from the peritoneal cavity and bone marrow samples from 34 patients with an adenocarcinoma of the pancreas were investigated with a panel of six different monoclonal antibodies against tumor-associated antigens (CEA, CA-19-9, 17-1A, C-54-0, Ra96) and cytokeratin, respectively. Additionally, 43 patients with benign diseases were investigated as a control group. By this method, micrometastases were detected either in the bone marrow or the peritoneal cavity in 76% of pancreatic cancer patients. The occurrence of stained cells in the peritoneal cavity and bone marrow samples correlated with the tumor stage and showed even in early stages (I and II) a detection rate of 43% (bone marrow) and 33% (peritoneal cavity), respectively. No unspecific reactions were found in the control group. The 1-year follow-up shows a significant correlation between tumor cell detection and the survival (p = 0.03). Our study demonstrates that in most patients pancreatic cancer is a disseminated disease at time of diagnosis. It underlines the need for adjuvant postoperative therapy concepts.

Adenocarcinoma↗