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Biomedical subjects

M Manns

Publications and source records attributed to M Manns.

187 records · Page 11Linked to original sources

Two different subtypes of antimitochondrial antibodies are associated with primary biliary cirrhosis: identification and characterization by radioimmunoassay and immunoblotting.

Antimitochondrial antibodies from patients with primary biliary cirrhosis react with different mitochondrial polypeptides as demonstrated by Western blots. The IgG fractions of a patient with primary biliary cirrhosis Stage I reacting exclusively with a pair of polypeptides at 48,000 daltons (p 48) on Western blot and from a patient with Stage III primary biliary cirrhosis reacting exclusively with a single 62,000 dalton polypeptide (p 62) were labeled with 125I; two radioimmunoassays were established detecting antimitochondrial antibodies against p 62 and p 48, respectively. Autologous sera blocked the assay, but the two reference sera did not block each other. Fourteen of 40 patients with primary biliary cirrhosis reacted with p 62, 6/40 with p 48 and 20 sera with both antigens. Sera from 200 patients with various hepatic and nonhepatic diseases were negative for anti-p 62 and anti-p 48. This collection of sera included 5 patients with nonhepatic autoimmune disorders, 3 with drug-induced pseudolupus syndrome and 2 with syphilis II, which were positive for antimitochondrial antibodies by immunofluorescence. Mitochondrial autoantigens p 62 and p 48 were both localized on mitoplasts, presumably inner mitochondrial membranes; they were thermolabile, trypsin- and chymotrypsin-sensitive, but resistant to DNAase, RNAase and neuraminidase treatments. In cesium chloride density gradients, p 62 floated at 1.28 gm per cm3 and p 48 at 1.30 gm per cm3. Thus, radioimmunoassays have been developed that specifically detect two distinct primary biliary cirrhosis-specific subtypes of antimitochondrial antibodies: anti-p 62 and anti-p 48. All primary biliary cirrhosis sera were positive for at least one of these antimitochondrial antibodies subtypes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Thermal energy balance during in vitro continuous veno-venous hemofiltration.

Hypothermia has been recognized as a potential side effect of continuous hemofiltration, but the thermal energy loss within the extracorporeal circuit has not yet been quantified. The authors measured temperature decrease and thermal energy balance in vitro at different points within the extracorporeal circuit of the Acu-men (Fresenius Medical Care, Bad Homburg, Germany), a new device for continuous hemofiltration. The device employs a disposable cartridge with a pneumatic blood pump as the driving force for the blood. Furthermore, a volumetric balancing chamber is used to balance filtrate with replacement fluid. At a blood flow of 120 ml/min, a filtrate volume of 1.4 L/hr, and a replacement fluid temperature of 20 degrees C, temperature decreased from the beginning to the end of the extracorporeal circuit from 37.0 degrees C to 32.4 degrees C. This corresponds to a calculated in vitro thermal energy loss of 3,300 kJ/d. The in vivo thermal energy loss might be significantly less because of baroreceptor induced peripheral vasoconstriction, with reduced heat loss through the skin. The blood tubing contributed 26%, the hemofilter 31%, and the produced filtrate 43% to the negative thermal energy balance. Heat transmission within the volumetric balancing system of the Acu-men reduced the heat loss by 15%. Heating of replacement fluid to 30 degrees C, 37 degrees C, or 42 degrees C reduced the thermal energy loss by 22%, 48%, and 72%, respectively.

Equipment Design↗

Phase II study of systemic gemcitabine chemotherapy for advanced unresectable hepatobiliary carcinomas.

BACKGROUND/AIMS: Patients with advanced unresectable hepatobiliary carcinomas have a dismal prognosis. The efficacy of systemic chemotherapy in these patients is negligible and often, in particular in patients with hepatocellular carcinomas, the toxicity of chemotherapy outweighs the potential palliative effect of antineoplastic agents. Gemcitabine is a new anticancer agent with a mild toxicity profile, which has demonstrated antineoplastic activity in many solid tumors. Therefore we investigated the effect of gemcitabine in patients with advanced nonresectable hepatocellular and cholangiocellular carcinomas in a phase II study. METHODOLOGY: Twenty-three patients with cholangiocellular carcinoma and 20 patients with hepatocellular carcinoma were enrolled into the study. Eighteen of the 20 patients with hepatocellular carcinomas had liver cirrhosis. Gemcitabine was administered once weekly over 30 min for 3 consecutive weeks out of every 4 weeks. Patients with cholangiocellular carcinomas received gemcitabine also in the forth week of the first cycle with no rest to the following cycle. Disease status was assessed every 4 weeks. RESULTS: Overall the regimen was well tolerated. The median number of gemcitabine administration was 15 (range, 3-37) in the group of patients with cholangiocellular carcinomas and 7.6 (range, 3-21) in the group of patients with hepatocellular carcinomas. In the group of patients with hepatocellular carcinomas thrombocytopenia was the most frequent side effect (30% grade 3/4). Among the patients with cholangiocellular carcinomas nausea and neutropenia were the most commonly observed side effects. The overall response rate of hepatocellular carcinomas was only 5% and chemotherapy generally did not improve the tumor symptoms of the patients in this group. In contrast, in the group of cholangiocellular carcinomas, seven patients achieved a partial response (overall response rate 30%). Eleven patients with cholangiocellular carcinomas revealed tumor symptoms before the onset of gemcitabine treatment. Seven of these patients developed a treatment related clinical benefit as defined as a relief of tumor symptoms or gain of weight. CONCLUSIONS: Our results indicate that the treatment of cholangiocarcinomas with gemcitabine is effective and should be further evaluated in phase III studies. In contrast, palliative chemotherapy with gemcitabine cannot be recommended in patients with hepatocellular carcinoma and liver cirrhosis.

Adult↗

[Therapy of Helicobacter pylori infection: current status].

H. pylori is closely associated with gastritis, peptic ulcer disease and gastric cancer. A causative role of H. pylori is now established in type B gastritis, its role in non ulcer dyspepsia is unresolved. Eradication of H. pylori results in a marked decrease of peptic ulcer relapse rates. Gastric cancer risk is 2- to 8-fold increased if gastric mucosa is colonized by H. pylori. Treatment of H. pylori infection is difficult although the organism is highly sensitive to several antibiotics in vitro. Monotherapy with bismuth suppresses bacterial growth, but hardly ever eradicates the organism. Combination of amoxicillin with omeprazole may eradicate H. pylori in about 60-80% of patients and is well tolerated. Triple therapy (bismuth, amoxicillin, metronidazole) is the most effective treatment modality and results in eradication rates of 80% to 90%, however, side effects are noticed in 20%-30% of patients. Eradication of H. pylori should be considered under the following conditions: relapsing peptic ulcer, resistant peptic ulcer, break-through ulcer on maintenance treatment with H2-blockers, complicated ulcer. There is no indication for eradicating treatment in patients with simple H. pylori positive gastritis and NSAID-associated ulcer.

Anti-Bacterial Agents↗