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Biomedical subjects

M Franke

Publications and source records attributed to M Franke.

At least 37 records · Page 2Linked to original sources

Treatment of diarrhoea in human immunodeficiency virus-infected patients with immunoglobulins from bovine colostrum.

Diarrhoea and weight loss are found in more than 50% of patients with the acquired immunodeficiency syndrome (AIDS). In some patients the symptoms can be very severe, leading to death even in the absence of opportunistic infections. In 30% of these patients, enteric pathogens cannot be identified, and approximately only half of the identifiable aetiologic agents of diarrhoea in patients infected with the human immunodeficiency virus (HIV) were treatable with antibiotics. Immunoglobulins from bovine colostrum (Lactobin, Biotest, Dreieich, FRG) contain high titers of antibodies against a wide range of bacterial, viral and protozoal pathogens as well as against various bacterial toxins. Lactobin (LIG) is quite resistant to 24-h incubation with gastric juice. In a multi-center pilot study 37 immunodeficiency patients with chronic diarrhoea [29 HIV-infected patients, 2 patients with common variable immunodeficiency (CVID), one unidentified immunodeficiency, five patients with graft versus host disease (GvHD) following bone marrow transplantation] were treated with oral LIG (10 g/day for 10 days). Good therapeutic effects were observed. Out of 31 treatment periods in 29 HIV-infected patients 21 gave good results leading to transient (10 days) or long-lasting (more than 4 weeks) normalisation of the stool frequency. The mean daily stool frequency decreased from 7.4 to 2.2 at the end of the treatment. Eight HIV-infected patients showed no response. The diarrhoea recurred in 12 patients within 4 weeks (32.4%), while 19 patients were free of diarrhoea for at least 4 weeks (51.3%). In 5 patients intestinal cryptosporidiosis disappeared following oral LIG treatment. LIG treatment was also beneficial in 4 out of 5 GvHD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

[Discrepant results with immunohistochemical detection TDx/ADx?].

In the last 2 years we had some problems to confirm the thin-layer results (amphetamines, opiates, benzodiazepines, barbiturates and cocaine) with the immunoassay system TDx/ADx. Between January 1989 and December 1990 we did 883 screenings in urine samples (pre- and postmortal) and had 157 discrepancies (20%). In regard of the high level of discrepancies, we had to test the compatibility of TDx and ADx, their detection limits and compared the results with a second method, thin-layer chromatography. Determining the correlation coefficients to prove our results statistically, we found that both systems, TDx and ADx, work reproducible.

Chromatography, Thin Layer↗

Effective natural interferon-alpha therapy in recombinant interferon-alpha-resistant patients with hairy cell leukemia.

To explore the relationship between anti-interferon-alpha (anti-IFN-alpha) antibodies and loss of clinical responsiveness to IFN-alpha treatment, we examined sera from 59 patients with hairy cell leukemia who responded to therapy with recombinant IFN-alpha-2a (rIFN-alpha-2a). During the first 2 years of therapy, 10 patients developed rIFN-alpha-2a-neutralizing and 15 rIFN-alpha-2a-binding antibodies. Nine of the 59 initially responding patients became resistant to rIFN-alpha-2a and suffered a relapse of the disease at 7 to 24 months of treatment. All nine relapsing patients tested positive for both neutralizing and binding antibodies with titers above 400 INU/mL, while none of the antibody-negative patients relapsed. Six patients with detectable binding antibody titers below 400 INU/mL continued to respond to treatment. By measuring the IFN kinetics and the levels of the IFN-induced Mx-homologous protein in mononuclear cells after a single injection each of rIFN-alpha-2a and nIFN-alpha the IFN antibodies of eight of the nine resistant rIFN-alpha patients were found to be highly specific for rIFN-alpha-2a. Therefore, these eight patients were switched to natural IFN-alpha (nIFN-alpha) therapy at doses of 3 million IU, three times a week. All eight patients responded to treatment with nIFN-alpha, achieving durable objective responses similar to those obtained previously with rIFN-alpha-2a. These data clearly demonstrate that rIFN-alpha antibody-positive patients can effectively be treated with nIFN-alpha.

Adult↗

Comparative therapy with cefpirome alone and in combination with rifampin and/or gentamicin against a disseminated Pseudomonas aeruginosa infection in leukopenic mice.

Treatment of disseminated Pseudomonas aeruginosa infection in leukopenic mice was evaluated using cefpirome alone and in combination with gentamicin and/or rifampin. Mice were made leukopenic with cyclophosphamide and infected through a skin incision with an inoculum of 1250 organisms (13 LD50). Antibiotics were administered subcutaneously for 48 h. Although the addition of cefpirome to gentamicin and/or rifampin improved survival significantly at 48 h compared with untreated controls (84.6%-100% vs. 38.5%), therapy with these combinations did not improve survival significantly from that achieved with cefpirome alone. Quantitative blood and tissue (liver, spleen, kidney, lung) cultures in mice treated with cefpirome alone or including rifampin were lower than in infected controls or groups receiving therapy that excluded cefpirome. Highest counts were observed in mice receiving cefpirome plus gentamicin. Except for the cefpirome plus gentamicin group, which demonstrated areas of acute tubular necrosis, the cefpirome group had less tissue pathology than infected controls.

Animals↗

Transjugular intrahepatic portacaval stent shunt: preliminary clinical results.

A percutaneous transjugular, intrahepatic portacaval shunt was created by means of a combined jugular and transhepatic approach. In the hepatic tissue track joining the portal and hepatic veins balloon-expandable stents were placed. Two of three patients with life-threatening variceal bleeding and Child C liver cirrhosis benefited from the procedure. One patient in severe hepatorenal failure prior to the procedure died 11 days after the shunt procedure of pulmonary complications. This procedure may be a promising alternative to current therapy in high-risk patients with esophageal bleeding.

Adult↗

[Randomized comparative study of secondary prevention of Pneumocystis carinii pneumonia in patients with acquired immunologic deficiency syndrome].

Pneumocystis carinii pneumonia is one of the most frequent infectious complications in patients with the acquired immunodeficiency syndrome (AIDS). A prospective trial was initiated to compare azidothymidine alone with azidothymidine plus aerosolized pentamidine as a secondary prophylaxis for pneumocystis carinii pneumonia. 27 patients (24 male, three female, average age 39 years) were enrolled, 14 patients receiving azidothymidine and pentamidine aerosol and 13 azidothymidine alone. After 166 days of follow-up, this trial had to be terminated prematurely, since the efficacy of pentamidine aerosol in the prevention of pneumocystis carinii pneumonia was clearly demonstrated in two recently published studies. Two patients died during the study period, one in either group, but neither due to pneumocystis carinii pneumonia. Two patients developed histologically proven pneumocystis carinii pneumonia; both patients were allocated to the azidothymidine arm. Pneumocystis carinii pneumonia was suspected clinically but not proven in four patients, three were randomized in the azidothymidine arm. Pentamidine was well tolerated and produced no severe side effects. The sample size is too small to draw definitive conclusions concerning the efficacy of pentamidine aerosol in AIDS patients.

Acquired Immunodeficiency Syndrome↗

Bone marrow investigation with technetium-99m microcolloid and magnetic resonance imaging in patients with malignant myelolympho-proliferative diseases.

In 63 patients with primary extramedullary malignant lymphoma or plasmacytoma, a study was performed in order to evaluate bone marrow involvement. All patients underwent a 99mTc microcolloid bone marrow whole body imaging (scintigraphy), using a gamma camera interfaced with a computer, followed by nuclear magnetic resonance bone marrow imaging (MRI), (1.5 Tesla). MR images were made of the lumbosacral region, the pelvic region, both femoral and other parts of the skeleton, according to focal lesions in the scintigraphy. A posterior iliac crest bone marrow biopsy was used as a standard reference. In the present study, both scintigraphy and MRI showed a dissiminated or focal involvement or a combination of both. In 53 of the 63 patients (84%) the results were in accordance. Pathological MR signals or pathological findings in scintigraphy did not always correspond to tumorous bone marrow involvement, and were shown to reflect reactive changes in the central part of the skeleton in combination with a periphery radionuclide extention interpreted as a periphery compensatory hematopoietic proliferation. The negative predictive value of scintigraphy and MRI was 92% and 100%, respectively. When combining the results of both examinations, the positive predictive value increased from 49% to 58%, if the bone marrow biopsy is accepted as gold standard. The results indicate that bone marrow investigation performed simultaneously using scintigraphy and MRI is superior both to the use of either of the methods alone and to the traditional iliac crest bone marrow biopsy.

Adolescent↗

[The transjugular intrahepatic portosystemic stent-shunt. A new nonsurgical percutaneous method].

In a 49-year-old male patient suffering from severe symptoms of end-stage portal hypertension and Child's stage C metabolic status, an intrahepatic stent-assisted portosystemic shunt was established for the first time exclusively by means of interventional radiology. Via transjugular access, a modified Brockenbrough needle was used to puncture the right branch of the portal vein via the right liver vein. As a target, a Dormia-basket was used that had previously been exposed in the right main portal branch. After successful puncture and balloon dilation of the artificial tract, two Palmaz stents were implanted to keep the tract permanently open. The portosystemic pressure gradient dropped from 38 to 18 mm Hg. The clinical status of the patient improved substantially during the following days. However, the patient died on day 11 after the procedure because of sudden onset of acute respiratory distress arising from acute nosocomial fungus and cytomegalovirus infection worsened by his primary immunoincompetence. Autopsy demonstrated a totally patent shunt without superficial thrombus. Microscopically, a thin endothelial layer on the inner shunt surface was found to be present.

Humans↗

Results of a multicenter placebo-controlled double-blind randomized phase III clinical study of treatment of rheumatoid arthritis with recombinant interferon-gamma.

In a multicenter placebo-controlled double-blind randomized clinical study, 91 patients with rheumatoid arthritis were given 28 days' treatment with recombinant interferon-gamma (50 micrograms daily for 20 days, then 50 micrograms each second day up to day 28, given by subcutaneous injection). The aim of the study was to provide a methodologically clear demonstration of the efficacy of treatment with interferon-gamma, using criteria that could be handled by statistical tests. Evaluatable documentation was available for 79 patients, of whom 40 were treated with the active compound. The principal criterion for the statistical evaluation of the therapeutic success was improvement of the Ritchie "joint pain index" or Lansbury "joint pain index" by at least 30% within 28 days. The chi-square test showed superiority of the interferon arm over the placebo arm with an error probability of alpha less than 1%. In addition, efficacy of interferon-gamma was demonstrated in respect of practically all parameters investigated. The frequency of side-effects, including febrile reactions, was the same for the active compound and the placebo. During interferon treatment the daily maximum body temperature was raised by 0.3 degrees C on average, but was below 37.2 degrees C at all times.

Adolescent↗

Induction of antinuclear antibodies in patients with rheumatoid arthritis receiving treatment with human recombinant interferon gamma.

Of six patients with rheumatoid arthritis (RA) treated with human recombinant interferon gamma for two to eight months, three developed antinuclear antibodies (ANAs). This was accompanied by a simultaneous clinical exacerbation of the disease activity. In this study both anti-inflammatory and immunostimulatory effects of human recombinant interferon gamma in patients with RA were observed.

Adult↗

Follicle-stimulating hormone (FSH) immunoactivity in porcine follicular fluid is not pituitary FSH.

Two inhibitors of FSH binding to receptor have been isolated from porcine follicular fluid and shown to have in vitro biological activity. These inhibitors were distinct separable entities with opposite biological effects (agonist and antagonist) on cultured FSH-responsive Sertoli cells. In light of the fact that the agonist-containing fraction (P4) inhibited [125I]human (h) FSH binding to anti-hFSH antiserum as well as to receptor, characterization of this factor was undertaken to determine its relationship to pituitary FSH. The P4 fraction was further purified by affinity chromatography, which removed a major protein from immunoreactive components. Western blotting of sodium dodecyl sulfate-polyacrylamide gels using polyclonal (anti-hFSH) and monoclonal (anti-hFSH beta) antibodies revealed a major immunoreactive band at 55,000 mol wt (Mr). When electrophoresed under reducing conditions, major immunoreactive proteins at 58,000 and 45,000 Mr were identified. These bands were also observed in extracts from bovine testes and raw porcine follicular fluid after electrophoresis and Western blotting. Whereas the monoclonal antibody used to characterize this inhibitor does not recognize porcine pituitary FSH, the Mr of the immunoreactive proteins are greater than that of pituitary FSH, and the immunoreactive bands do not reduce to subunits, as observed for pituitary FSH under reducing conditions, we conclude that gonadal extracts contain FSH-immunoreactive proteins that are immunologically and biochemically distinguishable from pituitary FSH. While the physiological role of these proteins remains to be determined, their presence in gonadal extracts or fluids vitiates assessment of FSH within the gonad by RIA using antiserum against hFSH.

Animals↗

Multiple phosphorylation of human SS-B/LA autoantigen and its effect on poly(U) and autoantibody binding.

The metabolic turnover rates and the effect of in vitro phosphorylation on poly(U) and autoantibody binding of human SS-B/La ribonucleoprotein, an autoantigen expressed in various autoimmune disorders, were studied. The determination of the metabolic turnover rates of SS-B/La protein, SS-B/La protein phosphorylation and RNA binding yielded values of 12.1 h, 3.6 h and 3.7 h, respectively, indicating a possible functional correlation of RNA-binding and phosphorylation. This assumption was confirmed by studies of in vitro phosphorylation using purified SS-B/La protein and purified casein kinase type II as a model system. A high degree of phosphorylation of the SS-B/La protein (molecular mass 49 kDa) substantially diminished its binding capacity for poly[3H]U. However, binding of human autoantibodies against SS-B/La antigen increases 2-fold with increased SS-B/La phosphorylation. Complete phosphorylation in vitro led to partial molecular transformation, yielding an antigenically cross-reacting component with an apparent molecular mass of 51 kDa which could not be detected during in vivo phosphorylation.

Autoantibodies↗