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Biomedical subjects

G Schumacher

Publications and source records attributed to G Schumacher.

At least 19 recordsLinked to original sources
PubMed1997

Liver transplantation: treatment of choice for hepatic and neurological manifestation of Wilson's disease.

Liver transplantation (LTX) is an approved method to treat patients with end-stage liver cirrhosis and acute liver failure due to Wilson's disease. Initially, there was some consideration about the indication for LTX in the case of Wilson's disease with severe neurological impairment but normal liver function. From 1988 until 1995, 13 out of 700 LTX (1.9%) were performed for Wilson's disease. Indications for LTX were (I) intractable neurological impairment with normal liver function (n = 4; including one patient with Child A cirrhosis), (II) fulminant hepatic failure (n = 3), and (III) end-stage liver cirrhosis (n = 6) (Child B, n = 1; Child C, n = 5). There were 8 females and 5 males with a mean age of 27 yr (range 15-34 yr). All patients of group I required continuous nursing care before LTX, in spite of pretreatment with d-penicillamine and zinc. The most frequent symptoms in these patients were dysphagia (n = 4), dysarthria (n = 4), tremor (n = 4), sialorrhea (n = 3), ataxia (n = 3), dystonia (n = 3) and handwriting difficulties (n = 3). All patients of group II presented with hemolytic anemia. The survival rate was 100%, and all patients were doing well after a mean follow-up period of 32.8 months (range 8-68 months). The postoperative course was without severe infectious and other complications. All patients of group I revealed the first signs of improvement for all types of neurological symptoms 4-6 wk after LTX. One patient has been without any symptoms from 18 months until 5.5 yr after LTX. Two patients with short-term follow-up also had noticeable improvement of neurological impairment, but residual symptoms are still present. One patient showed only slight improvement. We conclude that Wilson's disease may be a good indication for LTX for both neurological manifestation with stable liver function and hepatic manifestation with cirrhosis or acute liver failure.

Adolescent↗
PubMed1996

Liver tumors: comparison of MR imaging with Gd-EOB-DTPA and Gd-DTPA.

PURPOSE: To compare the usefulness of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) and gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) in the diagnosis of focal liver lesions. MATERIALS AND METHODS: Thirty-one patients with focal liver lesions underwent T2- and T1-weighted spin-echo magnetic resonance (MR) imaging and fast low-angle shot two-dimensional MR imaging before, during, and after intravenous administration of three different doses of Gd-EOB-DTPA (12.5, 25, and 50 mumol per kilogram body weight). Gd-DTPA-enhanced imaging (dose, 0.1 mmol per kilogram body weight) was performed in the same patients within 1 week of Gd-EOB-DTPA imaging. RESULTS: During the perfusion phase (the 3 minutes after injection of contrast material), the dynamic enhancement characteristics seen after injection of 25 and 50 mumol of Gd-EOB-DTPA were similar to those seen with Gd-DTPA. At the lowest dose of Gd-EOB-DTPA (12.5 mumol), the dynamic enhancement characteristics were not comparable to those seen with Gd-DTPA. During the hepatobiliary phase (1.5 minutes to 4 hours after injection), Gd-EOB-DTPA-enhanced images yielded a dose-independent, statistically significant improvement in the detection rate of additional metastases, hepatocellular carcinomas, and hemangiomas compared with unenhanced and Gd-DTPA-enhanced images (P < .05). CONCLUSION: Gd-EOB-DTPA-enhanced MR imaging enables improved detection of hepatic lesions over Gd-DTPA-enhanced MR imaging while providing comparable differential diagnostic information.

Adult↗
PubMed1996

[Cholecystoduodenal fistula with subsequent gallstone ileus: case report of an unusual course].

Gallstone ileus is a rare complication of cholecystolithiasis with a high mortality because of the advanced age of the patients and the often delayed diagnosis. Signs of a cholecystoduodenal fistula are often absent in conventional ultrasonic and radiological methods. Treatment options are: 1. Enterolithotomy, 2. One stage procedure or 3. Two stage procedure consisting of enterolithotomy and the surgery of the biliary tract. In the case of our patient we performed a conventional cholecystectomy and the closure of the cholecystoduodenal fistula, which was found accidentally. When the gallstone ileus appeared 6 days later the enterolithotomy was performed. Thus in case of accidentally found cholecystoduodenal fistula an exploration of the abdominal cavity and the small intestine to find the gallstone should be performed on principle. Gallstones with a diameter of more than 2-3 cm should be removed by enterolithotomy to prevent the gallstone ileus.

Aged↗
PubMed1995

Circulating granulocyte antibodies in first attacks of colitis.

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) have recently been demonstrated in the sera of patients with inflammatory bowel disease (IBD). METHODS: The presence of ANCA was studied in 107 sera obtained during 1 year from 48 patients with a first attack of IBD and in 33 such sera from 19 patients with infectious or infectious-type colitis (non-relapsing colitis (NRC)). RESULTS: In 65% (31 of 48) of the IBD patients positive immunofluorescence reactivity against granulocytes was observed, compared with in 5% of the NRC patients. No significant difference in granulocyte reactivity was found either between patients with colonic Crohn's disease and those with ulcerative colitis or between active and inactive phases of the disease. Most of the sera showed a perinuclear immunofluorescence staining pattern (68%), in contrast to the classical cytoplasmic staining pattern seen in Wegener's granulomatosis. In sera obtained at the first visit from the 31 IBD patients with positive granulocyte reactivity a hitherto unknown antibody against beta-glucuronidase was found in 42%, whereas in 45% the specificity was not identified. Other antibodies, rarely seen, were directed against myeloperoxidase, lactoferrin, elastase, and cathepsin G. No antibody directed against lysozyme was detected. CONCLUSIONS: Positive granulocyte reactivity practically excluded NRC and was seen in more than half of IBD patients. Antibodies against beta-glucuronidase were common, but still almost half of the antibodies remained unknown.

Adult↗
PubMed1995

Health status measures in allied health curricula: results of a national survey.

Multidimensional health status measures can be used as vehicles to improve communications between patients and clinicians and to monitor, measure, and manage clinical progress. However, earlier work indicated that few multidimensional health status instruments were used as outcome measures in allied health research. To determine if these instruments were included in physical therapy (PT), occupational therapy (OT), respiratory therapy (RT), communication sciences and disorders (CSD) and health information management (HIM) career entry curricula, we surveyed the directors of all PT, OT, RT-BS, CSD and HIM programs in the United States. Based on responses from 130 (100%) of PT programs, 79 of 80 (99%) of OT programs, 31 of 32 (97%) of RT-BS programs, 144 of 199 (72%) CSD programs and 44 of 53 (83%) of HIM programs, we conclude that few allied health students are introduced to multidimensional health status instruments in their professional programs. We suggest that (1) the inclusion of multidimensional quality of life measures could be used as a mechanism to introduce allied health students to a broader definition of health; (2) the use of these instruments in clinical practice will assist therapists to communicate better with patients and address issues of their concern; and (3) their use will provide common clinical assessment instruments and vocabularies to facilitate the interdisciplinary management of patients.

Allied Health Occupations↗
PubMed1994

The refined structures of a stabilized mutant and of wild-type pyruvate oxidase from Lactobacillus plantarum.

The crystal structure of pyruvate oxidase (EC 1.2.3.3) from Lactobacillus plantarum stabilized by three point mutations has been refined at 2.1 A resolution using the simulated annealing method. Based on 87,775 independent reflections in the resolution range 10 to 2.1 A, a final R-factor of 16.2% was obtained at good model geometry. The wild-type enzyme crystallizes isomorphously with the stabilized enzyme and has been analyzed at 2.5 A resolution. Pyruvate oxidase is a homotetramer with point group symmetry D2. One 2-fold axis is crystallographic, the others are local. The crystallographic asymmetric unit contains two subunits, and the model consists of the two polypeptide chains (residues 9 through 593), two FAD, two ThDP*Mg2+ and 739 water molecules. Each subunit has three domains; the CORE domain, the FAD domain and the ThDP domain. The FAD-binding chain fold is different from those of other known flavoproteins, whereas the ThDP-binding chain fold resembles the corresponding folds of the two other ThDP enzymes whose structure is known, transketolase and pyruvate decarboxylase. The peptide environment most likely forces the pyrimidine ring of ThDP into an unusual tautomeric form, which is required for catalysis. The structural differences between the wild-type and the stabilized enzyme are small. All three point mutations are at or near to the subunit interfaces, indicating that they stabilize the quarternary structure as had been deduced from reconstitution experiments.

Amino Acid Sequence↗
PubMed1994

A prospective study of first attacks of inflammatory bowel disease and infectious colitis. Clinical findings and early diagnosis.

In 105 patients with a first attack of colitis, clinical, microbiologic, laboratory, and histologic features were studied prospectively with the aim of differentiating inflammatory bowel disease (IBD) from infectious colitis as early as possible. Of the patients who proved to have IBD the mode of onset of diarrhoeal symptoms was insidious in 56% and non-insidious in 44%, whereas in 81% of those who proved to have infectious colitis the onset was acute. Most patients with infectious colitis presented within 1 week, had early fever, and did not show histologic features characteristic of IBD. Most IBD patients with a more acute onset had clinical warning signs of IBD such as slight previous bowel symptoms, a late presentation time (> 1 week), and absence of early fever or had histologic features characteristic of IBD. These features were basal plasmacytosis, crypt distortion, more than two vertical crypt branches, villous mucosa, mucosal atrophy, epithelioid granuloma, and Paneth cell metaplasia. Moreover, 61% of the IBD patients with a non-insidious onset fell ill in connection with travelling abroad, gastrointestinal infection, or treatment with antibiotics. Knowledge of the above clinical and histologic factors will facilitate differentiation of IBD from infectious-type colitis.

Adolescent↗
PubMed1994

A prospective study of first attacks of inflammatory bowel disease and infectious colitis. Histologic course during the 1st year after presentation.

To investigate the possibilities of differentiating between inflammatory bowel disease (IBD) and infectious colitis on histologic grounds, a prospective histologic study of 105 patients with a first attack of colitis was undertaken. Rectal biopsies were performed on four occasions during 1 year. The strongest predictor of IBD was basal plasmacytosis, followed by more than two vertical crypt branches per medium-power field, crypt distortion, villous mucosa, and mucosal atrophy. These signs were rarely found among patients with infectious colitis. Their frequency increased with the interval between initial symptoms and the first biopsy. To study the development of histologic features in the absence of treatment, the IBD patients were divided into groups depending on this interval. Focal or diffuse basal plasmacytosis increased from 38% in the group with an interval of 1-15 days to 89% in those who presented in 121-300 days, and crypt distortion from 0% to 78%, whereas absence of signs indicating IBD decreased from 62% to 11%. The presence of focal basal plasmacytosis seems to be the earliest sign of IBD. The frequency of histologic signs indicating IBD was maximal (88%) at the 1-week biopsy. After recovery, the basal plasmacytosis and villous mucosa decreased, whereas crypt distortion and mucosal atrophy remained unchanged. Early treatment did not prevent the appearance of any feature.

Adult↗
PubMed1993

Stabilization of creatinase from Pseudomonas putida by random mutagenesis.

Creatinase (creatine amidinohydrolase, EC 3.5.3.3) from Pseudomonas putida is a homodimer of 45 kDa subunit molecular mass, the three-dimensional structure of which is known at 1.9 A resolution. Three point mutants, A109V, V355M, and V182I, as well as one double mutant combining A109V and V355M, and the triple mutant with all three replacements, were compared with wild-type creatinase regarding their physical and enzymological properties. High-resolution crystal data for wild-type creatinase and the first two mutants suggest isomorphism at least for these three proteins (R. Huber, pers. comm.). Physicochemical measurements confirm this prediction, showing that the mutations have no effect either on the quaternary structure and gross conformation or the catalytic properties as compared to wild-type creatinase. The replacement of V182 (at the solvent-exposed end of the first helix of the C-terminal domain) does not cause significant differences in comparison with the wild-type enzyme. The other point mutations stabilize the first step in the biphasic denaturation transition without affecting the second one. In sum, the enhanced stability seems to reflect slight improvements in the local packing without creating new well-defined bonds. The increase in hydrophobicity generated by the introduction of additional methyl groups (A109V, V182I) must be compensated by minor readjustments of the global structure. Secondary or quaternary interactions are not affected. In going from single to double and triple mutants, to a first approximation, the increments of stabilization are additive.

Cloning, Molecular↗
PubMed1993

A prospective study of first attacks of inflammatory bowel disease and non-relapsing colitis. Microbiologic findings.

In 105 patients with a first attack of colitis, thorough microbiologic investigations of rectal biopsy, faecal, and serum samples were performed with the aims of identifying the colitis-causing agents and shedding light on factors that may precipitate or aggravate the onset of inflammatory bowel disease. Sixty-one patients were found to have inflammatory bowel disease. In 13 (21%) of these patients microbial findings were positive. Eight of the 61 patients fell ill during or immediately after antibiotic treatment, and 10 while travelling abroad. Forty-one of the 105 patients had non-relapsing colitis. In 32 (78%) of these the microbial findings were positive. Six of these 41 patients fell ill during or immediately after antibiotic treatment, and 14 while travelling abroad. Alteration of the intestinal microflora on travelling, gastrointestinal infection, or treatment with antibiotics seems to precipitate or aggravate the symptoms in latent inflammatory bowel disease. In such patients the mode of onset is often changed from insidious to more acute, which may cause difficulty in differentiation from non-relapsing colitis.

Acute Disease↗
PubMed1993

First attack of inflammatory bowel disease and infectious colitis. A clinical, histological and microbiological study with special reference to early diagnosis.

To investigate the possibilities of differentiating between inflammatory bowel disease (IBD) and infectious colitis on clinical, microbiological, laboratory and histological grounds, a prospective study of 105 patients with a first attack of colitis was undertaken. Rectal biopsy was performed on four occasions during 1 year. In 56% of the patients who proved to have IBD, the mode of onset of diarrhoeal symptoms was insidious and in 44% it was more acute, while in 81% of those who proved to have infectious colitis the onset was acute. Most patients with infectious colitis presented within 1 week, had early fever, and did not show any histological features characteristic of IBD. In most IBD patients with a non-insidious onset there were clinical warning signs of IBD, such as slight previous bowel symptoms, a late presentation time (> 1 week) and absence of early fever, or histological features characteristic of IBD. Moreover, 62% of the IBD patients with a non-insidious onset fell ill in connection with travelling abroad, gastrointestinal infection or treatment with antibiotics. Travel abroad seemed to be associated with an increased risk of developing IBD. The strongest histological predictor of IBD was basal plasmocytosis, followed by more than two vertical crypt branches/MPF, crypt distortion, villous mucosa, mucosal atrophy, epithelioid granulomas and Paneth cell metaplasia. These signs were rarely or never found among patients with infectious colitis. Their frequency increased with the interval between the initial symptoms and the first biopsy. The presence of focal basal plasmocytosis seems to be the earliest sign of IBD. The frequency of histological signs indicating IBD was maximal (88%) at the 1-week biopsy. During treatment the basal plasmocytosis and villous mucosa decreased, while crypt distortion and mucosal atrophy remained unchanged. Early treatment did not prevent the appearance of any feature. Nor did it prevent relapse. In 21% of the IBD patients microbial findings were positive. The findings consisted in known colitis-causing agents in 14% and other agents, such as viruses, in another 7%. In 78% of the patients with non-relapsing colitis (NRC), colitis-causing agents were found. Haemolytic strains of E. coli were detected more often in IBD. Among the IBD patients, 65% showed positive immunofluorescence reactivity to neutrophil granulocytes, indicating the presence of antineutrophil antibodies (ANCA). The corresponding figure for NRC patients was 5%. Antibodies against beta-glucuronidase were found in 42% of the patients with granulocyte reactivity.

Acute Disease↗
PubMed1993

Engineering enzymes for clinical diagnosis.

The enzyme creatine amidinohydrolase (creatinase, EC 3.5.3.3.) is a major limiting factor in the enzymatic creatinine determination because of its comparatively poor catalytic activity and stability in the native form. The gene from Pseudomonas putida coding for creatinase was cloned and used for overexpression of the protein in E coli and Pseudomonas. In addition, it was possible by means of 'random' mutagenesis in vivo and subsequent screening using an activity plate assay to isolate creatinase derivatives that are more stable towards detergents and elevated temperature under test kit conditions. This example shows that enzymes can be optimized for use in given assay conditions by mutagenesis of cloned DNA and suitable screening methods.

Cloning, Molecular↗