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T Neumann

Publications and source records attributed to T Neumann.

At least 73 records · Page 4Linked to original sources
PubMed1995

Relevance of carbohydrate-deficient transferrin as a predictor of alcoholism in intensive care patients following trauma.

Every second traumatized patient is a chronic alcoholic. Chronic alcoholics are at risk due to an increased morbidity and mortality. Reliable and precise diagnostic methods for detecting alcoholism are mandatory to prevent posttraumatic complications by adequate prophylaxis. The patient's history, however, is often not reliable, and conventional laboratory markers are not sensitive or specific enough. The aim of this study was to investigate whether carbohydrate-deficient transferrin (CDT) is a sensitive and specific marker to detect alcoholism in traumatized patients. One hundred and five male traumatized patients or their relatives gave their written informed consent to participate in this institutionally approved study. All patients were transferred to the intensive care unit after admission to the emergency room, followed by surgical treatment. Diagnostics included an alcoholism-related questionnaire, conventional laboratory markers (mean corpuscular volume, gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase), and CDT sampling (microanion-exchange chromatography, turbidimetry, and radioimmunoassay, respectively). Only patients in whom a reliable history could be obtained were included. Alcoholism was diagnosed if the patients met the Diagnostic and Statistical Manual of Mental Disorders criteria for chronic alcohol abuse or dependence. The administration of fluids before CDT sampling was carefully documented. Patients did not differ significantly regarding age, Trauma and Injury Severity Score, and Acute Physiology and Chronic Health Evaluation score. The sensitivity of the CDT research kit was 70% and of the commercially available kit CDTect was 65%. Early sampling in the emergency room and before administration of large volumes of fluid increased the sensitivity to 83% for the CDT research kit and 74% for CDTect, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Treatment of burned mice with hyperbaric oxygen reduces mesenteric bacteria but not pulmonary neutrophil deposition.

OBJECTIVE: Hyperbaric oxygen (HBO) is used but unproven for many conditions, including burns. We hypothesized that HBO therapy might increase oxygen delivery to intestine during burn shock and decrease mucosal injury. SETTING: University research laboratory. DESIGN AND STUDY PARTICIPANTS: We studied the effects of HBO therapy (100% oxygen at 2.4 atm absolute) on mesenteric bacterial colonies (MBCs) in mice following 32% total body surface area burns. MBCs were counted 24 or 48 hours postburn by culturing mesenteric tissue. Intestinal histologic features were examined, acid-base balance was measured, and pulmonary neutrophil deposition was estimated by lung myeloperoxidase content. INTERVENTIONS: HBO delivered in a compression chamber. MAIN OUTCOME MEASURE: Numbers of mice with MBCs. RESULTS: With twice-daily HBO treatments, each treatment lasting 1.5 or 2 hours, fewer burned mice had MBCs. Three HBO treatments within 24 hours produced seizures, death, and increased numbers of mice with MBCs. Numbers of mice with MBCs were not influenced when compressed air (2.4 atm absolute) or 100% oxygen (1 atm absolute) was used. Villus histologic findings showed less damage in burned mice that received HBO therapy than in controls. Metabolic acidosis was not affected by HBO therapy, nor were lung myeloperoxidase levels. CONCLUSION: HBO therapy was associated with reduced numbers of mice with MBCs after burn injury and reduced histologic evidence of mucosal damage, but lung myeloperoxidase levels and metabolic acidosis were not affected. HBO therapy may increase oxygen delivery to ischemic intestine and improve cellular metabolism; alternatively, increased tissue oxygen may augment killing of translocated bacteria by phagocytic cells. HBO deserves further investigation for burn treatment, but because of the narrow therapeutic window and continued neutrophil sequestration in the lungs, we should proceed cautiously.

Acid-Base Equilibrium↗
PubMed1994

Detection of more than 50 different CFTR mutations in a large group of German cystic fibrosis patients.

We have conducted a comprehensive study of the molecular basis of cystic fibrosis (CF) in 350 German CF patients. A screening approach based on single-strand conformation analysis and direct sequencing of genomic polymerase chain reaction products has allowed us to detect the molecular defects on 95.4% of the CF chromosomes within the coding region and splice sites of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The spectrum of sequence changes comprises 54 different mutations, including 17 missense mutations, 14 nonsense mutations, 11 frameshift mutations, 10 splice site variants and two amino acid deletions. Eleven of these mutations have not previously been described. Our results reflect the marked mutational heterogeneity of CF in a large sample of patients from a non-isolated population.

Adult↗
PubMed1994

Exon 9 of the CFTR gene: splice site haplotypes and cystic fibrosis mutations.

The alternatively spliced exon 9 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene codes for the initial part of the amino-terminal nucleotide-binding fold of CFTR. A unique feature of the acceptor splice site preceding this exon is a variable length polymorphism within the polypyrimidine tract influencing the extent of exon 9 skipping in CFTR mRNA. We investigated this repeat for its relationship to CFTR mutations and intragenic markers on 200 chromosomes from German patients with cystic fibrosis (CF). Four frequent length variations were strongly associated with the four predominant haplotypes previously defined by intragenic marker dimorphisms. One of these alleles displayed absolute linkage disequilibrium to the major CF mutation delta F508. Other frequent CFTR mutations were linked to one particular splice site haplotype indicating that differential exon 9 skipping contributes little to the clinical heterogeneity among CF patients with an identical mutation. We also identified a novel missense mutation (V456F) and a novel nonsense mutation (Q414X) within the coding region of exon 9. The missense mutation V456F adjacent to Walker motif A was present in a pancreas-sufficient CF patient. In contrast, the pancreas-insufficient Q414X/delta F508 compound heterozygote suffered from a severe form of the disease, indicating that alternative splicing of exon 9 does not overcome the deleterious effect of a stop codon with this exon.

Alleles↗
PubMed1994

[The relevance of CDT (carbohydrate-deficient transferrin). Preoperative diagnosis of chronic alcohol abuse in intensive care patients following elective tumor resection].

The increase of alcoholism-related problems is associated with vital postoperative clinical complications in chronic alcohol abusers. In particular, the alcohol withdrawal syndrome (AWS) may provoke potentially life-threatening complications in alcohol-dependent patients. Hence, a precise diagnosis of alcohol dependence is mandatory preoperatively, requiring an extensive case history using alcoholism-associated questionnaires. Additional new biological markers for detecting alcoholism could improve the accuracy of preoperative diagnosis. Carbohydrate-deficient transferrin (CDT) reflects increased alcohol consumption. The aim of our interdisciplinary study was to investigate whether the validity of the preoperative diagnosis of chronic alcohol abuse might be improved by measuring CDT. METHODS. A total of 45 patients from the departments of Otorhinolaryngology, Maxillofacial Surgery, and Abdominal and Thoracic Surgery were included in our prospective clinical study. Patients underwent resection of malignant oral, pharyngeal, laryngeal, or oesophageal tumours and were transferred to the intensive care unit for postoperative management. Routine preoperative history, examinations, and laboratory tests including GGT, MCV, ASAT, and ALAT, were supplemented by a specific alcohol-related questionnaire and CDT measurement. The patients were categorised in four groups based on history and the questionnaire: continuously abstinent subjects; sober subjects for at least 7 days; chronic abusers; and dependent subjects. CDT was separated by isocratic anion exchange chromatography and quantified by turbidimetric determination. Statistical analysis was performed by the Kruskal-Wallis test. RESULTS. Preoperatively, 21 patients were at major risk for alcoholism-related complications: 12 were chronic abusers and 9 were diagnosed as dependent. CDT was significantly increased in both groups, and was pathologically elevated in 16 of the 21 patients. Sampling occurred significantly long after the last alcohol intake in the 5 patients with normal CDT values (median: 6.0 days; range: 2-12 days) compared with the 16 with pathologically elevated CDT levels (median: 1.0 day; range: 0-4 days; P = 0.002). The sensitivity of CDT elevation was 16 out of 24 (76%), the specificity 16 out of 16 (100%). Sixteen patients had no previous history of alcohol consumption (sober for at least 7 days) and 8 were definitely abstinent. Both of these groups had normal CDT values. CONCLUSIONS. CDT was a sensitive and specific marker for chronic alcohol consumption in our patient population. Since CDT is a state marker, repeated determinations might be useful to estimate a patient's drinking habits. The combination of CDT and an alcohol-related questionnaire was reliable for detecting alcohol-dependent patients preoperatively.

Adult↗
PubMed1994

[Hysteroscopic study in patients with abnormal uterine bleeding].

The experience of hysteroscopy performed in our Service in Abnormal Uterine Bleeding (AUB) is presented in order to show the utility of this procedure as a diagnostic method and compare these results with Dilatation and Curettage (DC). Eighty five patients underwent diagnostic hysteroscopy procedure, followed by DC; 54 were postmenopausal (63.6%) and 31 were premenopausal (36.4%). The distention media used was liquid. In 47 patients (55.2%) the hysteroscopic diagnostic was normal or atrophic endometrium, in 16 patients (18.8%) was hyperplasia, in 17 patients (20%) was endometrial polyp, 4 cases (4.7%) were described as cancer and in 1 case (1.3%) the diagnostic was bone metaplasia. We compared the results with the histology of DC obtaining a correlation of 93%. These results confirm the high accuracy of this procedure as a diagnostic method in uterine bleeding regarding its specificity and sensibility.

Adult↗
PubMed1993

Cystic fibrosis: the impact of analytical technology for genotype-phenotype studies.

The generalized exocrinopathy cystic fibrosis (CF) is the most common severe genetic disease in Caucasian populations. A panel of more than 700 chromosomes from German and Turkish CF patients was screened for disease-causing mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene by chemical cleavage of mismatch, single strand conformation polymorphism, restriction analysis and direct sequencing of genomic DNA amplified by polymerase chain reaction. Besides the major 3-bp deletion, delta F508 that was found on 73% of German CF chromosomes, more than 50 other missense, nonsense, frame-shift, and splice-site mutations have already been identified. In general, a CFTR mutation is linked with a single 10-marker haplotype which indicates that in most cases a particular mutation spread from a common ancestor. The comparison of mutation genotypes with the disease phenotype emphasized the causative role of the type and localization of the CFTR mutation for clinical course and prognosis. Pancreatic status and the risk of colonization of airways with opportunistic pathogens are genetically determined. Most patients who are harbouring mutations in the nucleotide binding folds were suffering from severe CF disease. Mild or even aberrant forms of CF were observed for many missense mutations located in the putative transmembrane domains or for mutations that are expected to result in a truncated protein of half of wild-type CFTR.

Cystic Fibrosis↗
PubMed1993

Genetic determinants of airways' colonisation with Pseudomonas aeruginosa in cystic fibrosis.

Exocrine pancreatic insufficiency and lung infection with Pseudomonas aeruginosa are major features of cystic fibrosis (CF). This monogenic disease is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. 267 children and adolescents with CF who were regularly seen at the same centre were assessed for an association of the CFTR mutation genotype with exocrine pancreatic function and the age of onset of chronic colonisation with P aeruginosa. The major mutation delta F508 accounted for 74% of CF alleles; 33 further CFTR mutations had been detected on the CF chromosomes of the study population by June, 1992. With the exception of delta F508/R347P compound heterozygotes, patients of the same mutation genotype were either pancreas insufficient (PI) or pancreas sufficient (PS). The age-specific colonisation rates with P aeruginosa were significantly lower in PS than in PI patients. The missense and splice site mutations that are "mild" CF alleles with respect to exocrine pancreatic function were also "low risk" alleles for the acquisition of P aeruginosa. On the other hand, the proportion of P aeruginosa-positive patients increased most rapidly in the PI delta F508 compound heterozygotes who were carrying a termination mutation in the nucleotide binding fold-encoding exons. Pancreatic status and the risk of chronic airways' colonisation with P aeruginosa are predisposed by the CFTR mutation genotype and can be differentiated by the type and location of the mutations in the CFTR gene.

Adolescent↗
PubMed1993

Antibacterial activities of OPC-17116, ofloxacin, and ciprofloxacin against 200 isolates of Neisseria gonorrhoeae.

OPC-17116 is a new fluoroquinolone with potent activity against aerobic and anaerobic organisms. We evaluated the susceptibilities of 200 clinical gonococcal isolates including organisms with plasmid and chromosomally mediated resistance to beta-lactams and tetracycline. The antibiotics studied included OPC-17116, ofloxacin, ciprofloxacin, penicillin, tetracycline, erythromycin, azithromycin, and ceftriaxone. All isolates tested were susceptible to the quinolone class of antibiotics. The MICs of ciprofloxacin, ofloxacin, and OPC-17116 for 90% of isolates tested were 0.004, 0.03, and 0.004 micrograms/ml, respectively. For organisms with chromosomally mediated resistance to penicillin and tetracycline, geometric mean MICs of all antibiotics including the quinolones were increased.

Anti-Infective Agents↗
PubMed1993

[Diagnosis of diseases of the large salivary glands of the head by ultrasound, sialography and CT-sialography. A comparison of methods].

In the present study 162 patients with clinically suspected diseases of the major salivary glands were examined via sonography (n = 162), sialography (n = 111) and CT-sialography (n = 49). The reliability of the three radiological procedures was assessed in diagnosing sialoadenitis, sialolithiasis and glandular and extraglandular tumors. Forty-seven patients were examined with all three methods, 64 patients with sonography and sialography, 2 patients with sonography and CT-sialography and 49 patients with only sonography. The results were compared retrospectively with histologically (70%), cytologically (26%) and clinically proven diagnoses. A sialoadenitis was diagnosed via sonography at a sensitivity of 58%. Sialography frequently produced a false diagnosis of "glandular tumor", which resulted in a comparatively lower sensitivity of 54%. This finding contrasted with the experiences of other authors. A glandular tumor was correctly diagnosed by all three methods and had approximately the same sensitivity (sonography 89%, sialograph 91% and CT-sialography 92%). The correct diagnosis of salivary gland tumors was found by sonography and CT-sialography in 76% of cases and by sialography in 83% of cases. CT-sialography was clearly the superior diagnostic method for detecting extraglandular tumors. Sonography proved its worth as the fundamental procedure for special diagnostic testings of the salivary glands. Sialography is necessary for obtaining important additional information, especially in cases with suspect glandular tumors. CT-sialography is indispensable in the diagnosis of tumors, especially if a malignant, extraglandular or medially localized process is suspected.

Diagnostic Imaging↗
PubMed1992

Intra- and extragenic marker haplotypes of CFTR mutations in cystic fibrosis families.

In order to facilitate the screening for the less common mutations in the cystic fibrosis (CF) gene viz., the CF transmembrane conductance regulator gene (CFTR), marker haplotypes were determined for German non-CF (N) and CF chromosomes by polymerase chain reaction analysis of four polymorphisms upstream of the CF gene (XV-2c, KM.19, MP6-D9, J44) and six intragenic polymorphisms (GATT, TUB9, M470V, T854T, TUB18, TUB20) that span the CFTR gene from exon 6 through exon 21. Novel informative sequence variants of CFTR were detected in front of exons 10 (1525-61 A or G), 19 (3601-65 C or A), and 21 (4006-200 A or G). The CF locus exhibits strong long-range marker-marker linkage disequilibrium with breakpoints of recombination between XV-2c and KM.19, and between exons 10 and 19 of CFTR. Marker alleles of GATT-TUB9 and TUB18-TUB20 were found to be in absolute linkage disequilibrium. Four major haplotypes encompass more than 90% of German N and CF chromosomes. Fifteen CFTR mutations detected on 421 out of 500 CF chromosomes were each identified on one of these four predominant 7-marker haplotypes. Whereas all analysed delta F508 chromosomes carried the same KM.19-D9-J44-GATT-TUB9-M470V-T854T haplotype, another frequent mutation in Germany, R553X, was identified on two different major haplotypes. Hence, a priori haplotyping cannot exclude a particular CF mutation, but in combination with population genetic data, enables mutations to be ranked by decreasing probability.

Alleles↗
PubMed1991

Cystic fibrosis with three mutations in the cystic fibrosis transmembrane conductance regulator gene.

Three mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene were discovered in a pancreas-insufficient patient with cystic fibrosis (CF) who displayed an uncommon combination of almost normal chloride concentration in sweat tests and typical symptoms of gastrointestinal and pulmonary disease. The R553Q mutation was found on the maternal delta F508-CFTR gene. Codon 553 is located within a consensus motif of the ATP-binding cassette transport proteins at a less conserved position. Other members of this protein superfamily contain a glutamine instead of arginine at the homologous position, suggesting a modulating rather than disease-causing role of the R553Q mutation in CFTR. The amplification refractory mutation system did not detect the R553Q mutation in a further 65 normal, 113 delta F508, and 91 non-delta F508 CF chromosomes. The index case carried the R553X nonsense mutation on the paternal chromosome. The R553X mutation was present on a further 9 out of 86 German non-delta F508 CF chromosomes linked with the XV2c-KM19-Mp6d9-J44-GATT haplotypes 2-2-2-1-1 and 1-1-2-1-2. The location of R553X on separate haplotypes including both alleles of the intragenic GATT repeat suggests an ancient and/or multiple origins of the R553X mutations. The association of the genotype of the CFTR mutation and the clinical phenotype was assessed for the patients carrying the related genotypes delta F508/delta F508 (n = 80), delta F508/R553X (n = 9) and delta F508-R553Q/R553X (n = 1). In compound heterozygotes, the median chloride concentration in pilocarpine iontophoresis sweat tests was significantly lower than in the delta F508 homozygotes (P less than 0.01). The patient groups were significantly different with respect to the distributions of the centiles for height (P less than 0.001) and weight (P less than 0.01) as the most sensitive predictors of the course and prognosis in CF. Growth retardation was more pronounced in the compound heterozygotes.

Amino Acid Sequence↗