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Biomedical subjects

J Otto

Publications and source records attributed to J Otto.

At least 37 records · Page 2Linked to original sources

Secretin-pancreozymin test (SPT) and endoscopic retrograde cholangiopancreatography (ERCP): both are necessary for diagnosing or excluding chronic pancreatitis.

Results of the SPT and the ERCP staged for their severity were compared in 202 patients. The correlation between both investigations was significant (p < 0.001); however, ERCP showed significantly more severe changes (p = 0.04). Furthermore, we found that 129 (64%) patients had parallel SPT and ERCP results, matching in all four gradings of severity. Forty-three (21%) patients had abnormal results for both SPT and ERCP, but the severity gradings did not parallel. Finally, 30 (15%) patients showed totally nonparallel results, a normal SPT and abnormal ERCP, or vice versa. Abnormal ERCP but normal SPT results were found in 23 of these 30 patients (group 1), and normal ERCP but abnormal SPT results in the seven remaining cases (group 2). In the first group, more patients had a history of acute pancreatitis compared to the second group (19 vs. one, p < 0.005). Based on medical history, laboratory and functional test results, and other morphological tests, chronic pancreatitis was diagnosed in two of 23 patients in group 1 and in all seven patients in group 2. Follow-up interviews (86 +/- 54 months) were possible in 20 of the remaining 21 patients in group 1 and showed definite chronic pancreatitis in one and probable chronic pancreatitis in another two of them, whereas in the other 17 patients no symptoms of acute pancreatitis or abdominal pain suggestive of chronic pancreatitis had occurred. In conclusion, both SPT and ERCP should be used to complement each other when chronic pancreatitis is suspected. ERCP seems to over-diagnose the disease since duct changes may only reflect scars after severe acute pancreatitis, or old age, and are not necessarily a sign of chronic pancreatitis. SPT seems to diagnose chronic pancreatitis with more reliability.

Adult↗

Cloning and expression of a murine fascin homolog from mouse brain.

The fascins are a widely distributed family of proteins that organize filamentous actin into bundles. We have cloned, sequenced, and expressed the murine homolog. Fascin is most abundant in brain and is found in other tissues including uterus and spleen. The deduced open reading frame encodes a protein of 493 amino acids with a molecular mass of 54,412 Da. Previous solubility problems with bacterially expressed fascins were overcome by producing the mouse protein as a fusion with Escherichia coli thioredoxin. A method for cleaving the fusion protein and for purifying active recombinant fascin is described. The N-terminal sequence and molecular mass estimated on SDS gels indicate that recombinant fascin is full-length. Two-dimensional gel electrophoresis suggests that recombinant fascin is post-translationally modified in a manner similar to that observed in mouse brain. Recombinant fascin and the fusion protein are recognized by monoclonal anti-fascin antibodies and will bundle rabbit skeletal muscle F-actin in vitro at a stoichiometry of 4.1:1 actin to fascin. Electron cryomicroscopy images show that the reconstituted bundles are highly ordered. However, their fine structure differs from that of echinoid fascin-actin bundles. This structural difference can be attributed to fascin.

Acetylation↗

Lovastatin inhibits diet induced atherosclerosis in F1B golden Syrian hamsters.

3-Hydroxy-3-methylglutaryl-CoA (HMG CoA) reductase inhibitors are the drugs most commonly prescribed in the US to lower blood cholesterol. Previous studies have shown their efficacy in reducing plasma low density lipoprotein (LDL) cholesterol. However, little is known about their effects on preventing diet induced atherosclerosis. We have investigated the changes in lipoprotein profiles and extent of atherogenesis in hamsters (F1B strain) consuming an atherogenic diet with and without lovastatin. Thirty-six animals were randomized into 3 groups of 12 animals each, with similar plasma cholesterol levels. One group of animals received a basal chow diet, and the other two groups a basal diet plus 10% (w/w) coconut oil and 0.05% cholesterol. After 2.5 weeks, one of the groups received the latter diet supplemented with lovastatin (25 mg/kg/day). A second study was carried out in which animals received the same diets, but lovastatin was given during the 10 week period at a dose of 12.5 mg/kg/day. At the end of the experimental period, animals were sacrificed and lipoprotein cholesterol, liver enzymes, and aortic foam cell development were determined. Animals fed the high fat diet plus lovastatin had significantly lower levels of non-high density lipoprotein (HDL) cholesterol than those fed the unsupplemented high fat diet. No differences were observed in mean levels of this parameter between animals fed the low fat diet and those receiving lovastatin. The amount of aortic lipid staining was significantly less in the lovastatin and low fat groups when compared to the unsupplemented high fat groups. These results indicate that lovastatin can prevent diet induced aortic lipid deposition in this animal model.

Analysis of Variance↗

[Therapy of rheumatic disease with a hydroxyethylsalicylate gel. Results of 2 clinical studies of effectiveness and bioavailability].

Two clinical studies were carried out to investigate the efficacy and safety as well as the local and systemic availability of a hydroxyethylsalicyclate gel. A double blind, multicenter trial, involving 113 patients with nonarticular rheumatic back pain, revealed statistically significant relief of pain as compared with placebo. Local and systemic tolerance was excellent. An open study of bioavailability after local application in 16 patients showed a mean salicylate concentration of 0.93 +/- 0.5 microgram/ml in the synovial fluid and 0.40 +/- 0.23 microgram/ml in the synovial membrane, compared with 0.14 +/- 0.04 microgram/ml in the serum. Genetisinic acid was not detected, while OH-hippuric acid was detected only in the serum and synovial fluid.

Administration, Topical↗

Recovery of the pancreas after acute pancreatitis is not necessarily complete.

In 38 patients, exocrine pancreatic function was tested by means of the secretin-pancreozymin test (SPT) and pancreatic duct system with endoscopic retrograde cholangiopancreatography (ERCP) 34 +/- 36 mo (mean +/- SD, range 1-156 mo) following acute pancreatitis. SPT and ERCP results were both normal in 19 (50%). They were both abnormal in four (11%) patients (group 1). Fourteen (37%) patients with normal SPT had abnormal ERCP test results (group 2), and one (3%) patient with normal ERCP had abnormal SPT (group 3). All patients except one of group 2 could be followed up within a mean observation time of 105 +/- 46 mo (range 24-168 mo): Chronic pancreatitis developed in all four patients of group 1, in one patient of group 2, and in the single patient of group 3, and suspected chronic pancreatitis in another patient of group 2. Eleven of the remaining 12 patients with abnormal ERCP results, but normal exocrine pancreatic function (group 2), showed no signs or symptoms of acute or chronic pancreatitis. It is concluded that (1) recovery to normal does not necessarily occur after acute pancreatitis, (2) progression to chronic pancreatitis is possible at a considerable percentage, and (3) duct changes demonstrated by ERCP may persist without any later signs and symptoms of acute or chronic pancreatitis.

Acute Disease↗

A nested PCR method for the detection of Bacillus anthracis in environmental samples collected from former tannery sites.

A nested PCR has been developed to detect Bacillus anthracis spores in natural soil and waste samples which may be heavily contaminated by organic and inorganic compounds as is the case at former tannery sites. Outer and inner pairs of primers were designed from the protective antigen gene of the plasmid pX01 as well as from the genes B and C of the capsule region of the plasmid pX02. The DNA was prepared from an enrichment broth after killing the vegetative cells by H2O2 treatment. The method allows the detection of less than 10 spores per 100 g of the original soil sample. This is between 10(4)-fold and 10(7)-fold more sensitive than the conventional culture diagnosis.

Bacillus anthracis↗

The course of pain is the same in alcohol- and nonalcohol-induced chronic pancreatitis.

The natural course of pain in chronic pancreatitis was followed up in 318 patients over 10.6 +/- 8.0 years (median, 9.0 years). By the end of our follow-up, a significant decline in pain in alcoholics (n = 228) and nonalcoholics (n = 90) (p < 0.001 and p < 0.03) was marred by the fact that, even after more than 10 years, 50% of alcoholics and 62% of nonalcoholics still reported pain attacks (difference insignificant). Only alcoholics had pain relief with increasing exocrine pancreatic insufficiency (p < 0.02), but 54% of alcoholics and 73% of nonalcoholics still had pain attacks despite severe, enzyme substitution-requiring exocrine pancreatic insufficiency. The development of severe endocrine pancreatic insufficiency did not significantly influence the course of pain. It is concluded that no clinically relevant differences exist in the course of pain in alcoholic and nonalcoholic chronic pancreatitis.

Alcoholism↗

Phase II trial of cisplatin, fluorouracil, and pure folinic acid for locally advanced head and neck cancer: a pharmacokinetic and clinical survey.

PURPOSE: To analyze clinical and pharmacokinetic data of cisplatin (CP)/fluorouracil (FU)/l folinic acid (l FA) chemotherapy administered as first-line treatment to locally advanced head and neck cancer patients. PATIENTS AND METHODS: Thirty-nine patients (35 men and four women; median age, 60 years; six stage III and 33 stage IV) received CP on day 1 (100 mg/m2) followed by l FA (200 mg/m2/d x 5) plus FU (500 mg/m2/d x 5) administered by continuous venous infusion (three cycles planned). Mean plasma concentrations of FU, l FA, and 5-methyltetrahydrofolate (5MTHF) over the cycle were computed. RESULTS: Clinical response was assessable for 33 patients. Response rates on the primary tumor site (n = 33) were 63.7% complete responses (CRs), 24.2% partial responses (PRs), and 12.1% treatment failures. Response rates on lymph nodes (n = 27) were 40.7% CRs, 37.1% PRs, and 22.2% treatment failures. The most frequent toxicity was mucositis (36.2% of cycles grade 3 to 4). Grade 3 to 4 nausea-vomiting, diarrhea, neutropenia, and thrombocytopenia occurred in 6.7%, 1.9%, 13.3%, and 1% of cycles, respectively. Pharmacokinetic analysis showed a wide interpatient variability for both FU (mean, 1.01 mumol/L; range, 0.16 to 2.09), l FA (mean, 1.89, mumol/L; range, 0.52 to 7.88) and 5MTHF plasma concentrations (mean, 3.85 mumol/L; range, 1.30 to 8.11). A significant correlation was demonstrated between FU concentration and hematologic toxicity grade, mucositis grade, and nausea-vomiting/diarrhea grade. Regarding tumor response, patients who failed to respond significantly exhibited lower FU and total folate concentrations than patients with a CR or PR. CONCLUSION: This study highlights the efficacy of CP/FU/l FA in head and neck carcinoma and establishes the clinical importance of coupled FU/FA pharmacokinetics to predict pharmacodynamic variability.

Adult↗

Anaphylactic reactions to bee-sting challenges in allergic children are not modified by endogenous catecholamines.

To investigate the role of basal catecholamine levels and the response of the adrenergic system to expected bee stings, plasma catecholamines were measured before and 1 and 2 min after bee-sting challenges. Twenty-one children (aged 4-15 y) with bee-sting allergies were selected for sequential challenges to establish the need for venom immunotherapy. The time interval between the challenges varied from 2 to 6 wk. Epinephrine, norepinephrine, and dopamine plasma levels were measured using a simultaneous single-isotope radioenzymatic assay. On the first challenge, 33% of the children experienced a normal local reaction, 29% a large local reaction, and 38% a systemic reaction. On the second challenge in 18 out of 21 subjects, 67% experienced a normal normal local reaction, 22% a large local reaction, and 11% a systemic reaction. Epinephrine and norepinephrine plasma levels increased significantly on the first and second challenges. Dopamine plasma levels showed a significant increase on the first challenge only. Plasma catecholamine levels after the second challenge revealed a significant positive correlation between epinephrine increases measured 1 and 2 min after the challenge and the concomitant sting reaction. Basal epinephrine, norepinephrine, and dopamine plasma levels did not differ significantly between patients who experienced different types of sting reactions. Based on our data, we conclude that clinical reactions to in-hospital insect-sting challenges are not affected by early increases in plasma catecholamine levels produced by the expected stress situation.

Adolescent↗

[The natural course of chronic pancreatitis--pain, exocrine and endocrine pancreatic insufficiency and prognosis of the disease].

The natural course of the classical symptoms of chronic pancreatitis, i.e. pain, exocrine and endocrine pancreatic insufficiency, was followed up in 335 patients over a median of 9.8 years (mean 11.3 +/- 8.3 years). Pain relief was not obtained in the majority of patients, even after a longterm observation of > 10 years, and severe exocrine and/or endocrine insufficiency, severe duct abnormalities and pancreatic calcifications developed. Alcohol abstinence failed to have a significant beneficial effect on pain. Pancreatic surgery led to pain relief immediately after operation, but later on the pain course between operated and nonoperated patients was not significantly different. Repeated exocrine pancreatic function tests in 143 patients showed that functional exocrine impairment came to a standstill (46%), or improved (11%). At the end of the observation, 22% of 335 patients still had normal endocrine function and only 40% required insulin treatment. Alcohol abstinence had a significant beneficial effect on endocrine, but not on exocrine pancreatic insufficiency. Chronic pancreatitis led to a sharp increase in unemployment and retirement. Pancreatic carcinoma occurred in 3% and extrapancreatic carcinoma in 4%. The mortality rate within the observation period was 22%, pancreatitis-induced complications accounted for 13% of these deaths.

Adult↗

Renal tolerance of cisplatin in patients more than 80 years old.

PURPOSE: Assessment of cisplatin (CDDP) tolerance in patients more than 80 years old in good general condition who may benefit from CDDP-based treatment. PATIENTS AND METHODS: Data on 35 patients older than 80 years who received one to six chemotherapy cycles (median, three cycles; total number of cycles, 98) including CDDP (60 to 100 mg/m2) were analyzed retrospectively. Before treatment, all patients had normal renal function as defined by serum creatinine (SC) levels below 132 mumol/L. Renal function was evaluated by measurement of SC and creatinine clearance (CC) before and after each course of chemotherapy. CC was calculated according to the Cockroft and Gault formula, where CC = (140 - age) x weight kg/0.814 x SC mumol/L. Renal toxicity was evaluated by the difference between prechemotherapy SC and the maximum SC level observed (delta SC) and by the difference between prechemotherapy CC and the minimal CC observed after treatment with CDDP (delta CC). The evolution of SC and CC during repeated courses of CDDP was analyzed, as were any extrarenal toxicities. RESULTS: Renal function remained stable in 19 patients (54%) with delta SC less than 18 mumol/L and 18 of 35 patients (51%) with delta CC less than 9 mL/min. A slight deterioration in renal function was observed in 13 patients (37%) with delta SC greater than 18 mumol/L and less than 60 mumol/L, and with a delta CC greater than 11 mL/min and less than 21 mL/min. In three patients (9%), delta SC was greater than 60 mumol/L (71, 73, 115 mumol/L) and delta CC was greater than 21 mL/min (25, 26, 36 mL/min). There were no cases of severe renal insufficiency, clinical ototoxicity, or neurotoxicity > or = grade 2. Treatment was terminated after one or two courses in three patients because of grade 2 or 3 hematologic toxicity and in two patients for grade 3 nausea or vomiting. CONCLUSION: CDDP at moderate doses can reasonably be administered to patients older than 80 years who may benefit from antineoplastic chemotherapy.

Aged↗

Fascin, an echinoid actin-bundling protein, is a homolog of the Drosophila singed gene product.

A cDNA for fascin, an actin-bundling protein in echinoderms, has been cloned, sequenced, and expressed. The predicted mass of the protein is approximately 55 kDa, similar to that observed for fascin purified from sea urchin eggs. Bacterially expressed fascin reacts with antibodies prepared against sea urchin egg fascin. Fascin has a strong sequence similarity to the singed gene (sn) product in Drosophila and has similarities with a 55-kDa human actin-bundling protein. No extensive similarities were found with other known actin-binding/bundling proteins, indicating that this is a separate gene family.

Amino Acid Sequence↗

Natural course in chronic pancreatitis. Pain, exocrine and endocrine pancreatic insufficiency and prognosis of the disease.

The natural course of the classical symptoms of chronic pancreatitis, i.e. pain, exocrine and endocrine pancreatic insufficiency, was followed up in 335 patients over a median of 9.8 years (mean 11.3 +/- 8.3 years). Pain relief was not obtained in the majority of patients, even after a long-term observation of > 10 years, and severe exocrine/endocrine insufficiency, severe duct abnormalities and pancreatic calcifications developed. Alcohol abstinence failed to have a significant beneficial effect on pain. Pancreatic surgery led to pain relief immediately after operation, but later on the pain course between operated and nonoperated patients was not significantly different. Repeated exocrine pancreatic function tests in 143 patients showed that functional exocrine impairment came to a standstill (46%), or improved (11%). At the end of observation, 22% of 335 patients still had normal endocrine function and only 40% required insulin treatment. Alcohol abstinence had a significant beneficial effect on endocrine, but not on exocrine pancreatic insufficiency. Chronic pancreatitis led to a sharp increase in unemployment and retirement. Pancreatic carcinoma occurred in 3% and extrapancreatic carcinoma in 4%. The mortality rate within the observation period was 22%, pancreatitis-induced complications accounted for 13% of these deaths.

Adult↗

[Population screening on a population level in Leipzig within the scope of the Bavarian cholesterol project].

Cholesterol determinations of 15.391 inhabitants of Leipzig were carried out in November 1990 within the Bavarian Cholesterol-Screening-Project. The aim of this screening on population basis was to identify individuals with elevated blood cholesterol levels as one of the risk factors of atherosclerosis. Capillary blood cholesterol was measured by means of the Reflotron dry-chemistry system (Boehringer, Mannheim). 27% of the inhabitants of Leipzig show cholesterol levels lower than 5.2 mmol/l as recommended by the European Society of Atherosclerosis Research. Furthermore the characteristic age dependence is seen. In comparison with the town Nürnberg lower mean cholesterol values were found in Leipzig.

Adult↗

[Neurodermatitis in childhood. Differential diagnosis--complications-- therapy].

The incidence of atopic dermatitis of 2-5% makes it one of the most common chronic diseases of childhood. In 80% of the patients, the skin symptoms first appear within one year of birth. In the differential diagnosis in infants, consideration must be given to candidiasis, seborrhoeic eczema and scabies; bacterial and viral superinfections are common complications. Approximately 80% of the victims have a disposition for atopy; in 50-80%, allergic rhinoconjunctivitis and/or bronchial asthma develops in addition. Despite recent progress in the understanding of the etiopathogenesis of atopic dermatitis, causal treatment is not yet in sight. For this reason, rational symptomatic treatment combined with exhaustive informative talks with and supervision of the children and their parents are of major importance for the management of this disease.

Child↗

Beta-2-adrenoceptors of polymorphonuclear leukocytes in children with atopic dermatitis. Their number and affinity to the radioligand [125I]-cyanopindolol.

[125I]-cyanopindolol (ICYP) was used in a binding assay to compare the number and affinity of beta 2-adrenoceptor binding sites on circulating polymorphonuclear leukocytes (PMN) of 21 children with atopic dermatitis (AD) and 23 age-matched controls. We found no correlation between the beta 2-adrenoceptor density and the age of the children in either collective. Furthermore, the number and affinity of beta 2-adrenoceptor binding sites on PMN was neither influenced by sex nor severity of disease, serum IgE level or percentage of eosinophils in the differential blood count. There was a tendency towards a lower number of beta 2-adrenoceptors in AD subjects (1,429 +/- 587 receptors/PMN) compared to controls (1,753 +/- 596 receptors/PMN), but this difference was statistically not significant.

Adolescent↗