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Biomedical subjects

S Hoffmann

Publications and source records attributed to S Hoffmann.

At least 145 records · Page 8Linked to original sources

[Caries in the permanent teeth of 7- to 15-year-old Hamburg pupils].

The dental health status of 2193 seven- to fifteen-year old pupils was evaluated in Hamburg. A total of 20.6% of these school children hat caries-free dentitions. Among the seven-year-old children this figure was 43.4% and it dropped down to 4.8% among the fifteen-year old ones. DMFS values increased from 1.0% to 13.8% between the same groups. Obviously, caries prevalence was increasing to a statistically significant degree with the lower social classes.

Adolescent↗

[Hematopoietic growth factors].

Hematopoietic growth factors represent a subgroup of the cytokines and are also called colony-stimulating factors (CSFs) because of their effects in bone marrow culture. These glycoproteins are produced by a large number of cells and serve to transmit signals within the hematopoietic and the immune system either by themselves or by inducing the production and the release of other cytokines. As their genes have been cloned by molecular biology in the last year, these "recombinant" factors can be produced in large amounts for clinical trials. Cytokines make possible completely new therapy concepts by enabling medicine both to intervene in and modulate the body's own physiological processes. Therapy studies conducted with hematopoietic growth factors to date are encouraging and mostly demonstrate only tolerable dose-dependent side effects. In contrast to the maximal tolerable dose usually applied for cytotoxic therapy regimens, this "biological therapy" aims to a minimal effective dose, known e.g. from interferon. The following article will attempt to provide an insight into the first results of clinical trials and in future possibilities in the clinical application of these factors.

Animals↗

Pseudallescheria boydii infection of the central nervous system.

Pseudallescheria boydii is a rare cause of central nervous system infection characteristically presenting as a neutrophilic meningitis or multiple brain abscesses. Factors predisposing to central nervous system infection with this fungus include immunosuppression and near drowning. The organism is infrequently cultured from fluid obtained by lumbar puncture, delaying clinical recognition and appropriate antifungal therapy. All untreated patients with P boydii infection of the central nervous system died. We describe a patient who developed a persistent neutrophilic meningitis with focal neurologic deficits due to P boydii 6 months after a freshwater aspiration pneumonia. We also review the characteristic clinical and pathologic features of previously reported cases and emphasize the importance of early detection and treatment in the management of this frequently intractable disease.

Adult↗

Phase I-II study on weekly administration of pirarubicin in patients with metastatic breast cancer.

A phase I-II study of weekly low-dose pirarubicin was performed in 19 patients with advanced breast cancer. The goal was to establish the optimal dose intensity, i.e., the maximal dose applicable at tolerable toxicity within the intended schedule. Each of the four different dose groups used (20, 24, 25, and 27 mg/m2) comprised 4-5 patients. In over 47% of patients, objective remissions were obtained (confidence interval 26%; 71%) including one complete and eight partial remissions; the median duration of remission was 41 weeks (range 16-72), and the median time to reach remission was 12 weeks (range 6-36). Efficacy of treatment was more dependent on prior chemotherapy than on pirarubicin dosage. The weekly i.v. push injection of the drug was easily applicable at an outpatient clinic and well tolerated. WHO grade 3 was the highest toxicity observed for leukopenia (3/19), leukopenia associated with infection (1/19), nausea/vomiting (2/19) and alopecia (6/19). More severe myelosuppression was avoided by interrupting the weekly application until recovery of leukocytes to greater than or equal to 3.5 x 10(3)/mm3. No clinical signs of cardiotoxicity were observed. Generally, mild to moderate signs of cardiac dysfunction acquired during therapy were detected by special cardiac monitoring. Only in 3 of 19 patients was a cumulative dose of more than 550 mg/m2 surpassed. This was accepted as the upper limit for conventional anthracycline therapy. The median cumulative dose applied was 325 mg/m2/week (range 58.2-800.0). Because of maldistribution of prognostic factors, no dose-response relationship could be established. With respect to the total time for which each patient was studied, the dose group of 27 mg/m2 achieved the highest dose intensity with a median of 17.4 mg/m2/week (range 13.5-22.4). Therefore, the dosage of 27 mg/m2/week is recommended to be used in further phase II-III trials of weekly applied pirarubicin.

Adult↗

Intraincisional antibiotic in addition to systemic antibiotic treatment fails to reduce wound infection rates in contaminated abdominal surgery. A controlled clinical trial.

One hundred ninety patients with peritonitis at the time of abdominal surgery were allocated at random to systemic antibiotic treatment alone or systemic antibiotic treatment combined with topical application of antibiotics in the wound at the time of wound closure. The overall wound infection rate was 17 percent without significant difference between the two treatment groups (P greater than 0.80).

Abdomen↗

Serum- and oncoprotein-mediated induction of a gene with sequence similarity to the gene encoding carcinoembryonic antigen.

We describe the molecular identification of a gene, designated T1, whose expression in mouse NIH 3T3 cells is strongly induced by the Ha-ras(EJ) and v-mos oncogenes and by serum. The T1 gene encodes a 38.5-kDa protein, as predicted from its primary sequence and shown by in vitro translation. The protein was processed at its amino terminus and extensively modified by N-linked glycosylation in vitro in the presence of microsomal vesicles. Sequence comparison of T1 with the MIPSX data base (Max-Planck-Institut für Biochemie, Martinsried/Munich) revealed similarity to the human carcinoembryonic antigen, a tumor marker which is overexpressed in colon adenocarcinomas and in fetal tissues. Considerable sequence similarity has also been observed to the short conserved region of other proteins which, like carcinoembryonic antigen, are encoded by members of the immunoglobulin gene superfamily.

Amino Acid Sequence↗

Induction of a mitogen-responsive gene after expression of the Ha-ras oncogene in NIH 3T3 fibroblasts.

A cDNA clone, T1, has been isolated whose corresponding mRNA was transiently expressed at highly elevated levels after conditional expression of the Ha-ras(EJ) gene and after mitogenic activation of quiescent NIH 3T3 cells. Glucocorticoid hormone stimulated substantial T1 expression as well but only in proliferating cells. At least two different signaling pathways participate in the regulation of the T1 gene: a protein kinase C-dependent signal is involved in the response of proliferating NIH 3T3 cells to glucocorticoid in the absence but not the presence of p21ras, whereas a protein kinase C-independent mechanism mediates the response to serum factors. Treatment of cells with the protein kinase inhibitor 2-aminopurine blocked induction of expression of the T1 gene. T1 mRNA accumulation is regulated at the transcriptional level.

2-Aminopurine↗

The v-mos and c-Ha-ras oncoproteins exert similar effects on the pattern of protein synthesis.

The effects of the ras and the mos oncogene products on the pattern of newly synthesized proteins was investigated in NIH3T3 cell lines. A conditional expression system which allowed hormonal induction of the oncogenes was utilized to detect effects on the accumulation of oncoproteins by two dimensional gel electrophoresis of crude cell extracts. Strong and reproducible changes of protein synthesis following the expression of the ras and mos oncogenes were detected. Transiently induced synthesis of four proteins with a molecular mass of 23 kDa, 32 kDa, 35 kDa, and 47 kDa was observed. These changes were qualitatively indistinguishable in both, ras and mos oncogene expressing cells. This is in agreement with the notion that the two oncogene products act on a common signal transduction pathway. Serum mediated growth induction of quiescent NIH3T3 cells led to a different pattern of altered protein synthesis. We observed the transient alteration in the synthesis rates of three proteins with a molecular mass of 27 kDa, 47 kDa and 52 kDa. Only the 47 kDa protein was also subject to regulation by the oncoproteins. One of the proteins whose synthesis was strongly induced by the ras and mos oncogene products is also expressed by heat shock.

Animals↗

Successful fibrin seal closure of a contaminated fistula. Case report.

In a 43-year-old woman, a large, contaminated fistula, initially with vesicointestinal communication, was successfully closed by application of fibrin seal. The course of three sealing attempts indicated that local pretreatment with antibiotics may have been important for the final result. At 4-year follow-up examination there was no recurrence of the fistula.

Adult↗

Induction of stable chimerism and elimination of graft-versus-host disease by depletion of T lymphocytes from bone marrow using immunomagnetic beads.

The goal of transplantation is the induction of immunologic tolerance. At present, nonspecific immunosuppression is used to prevent graft rejection and, commonly, graft-versus-host disease (GVHD). Nevertheless, nonspecific immunosuppressive therapy is frequently complicated by infection, malignant tumors, and drug toxicity. In order to examine whether hematopoietic chimerism can be used to induce specific allograft tolerance, we have reconstituted lethally irradiated Lewis rats with ACI bone marrow that has been depleted of T cells with use of immunomagnetic beads. This technique consists of binding OX-19, a mouse anti-rat pan-T lymphocyte monoclonal antibody, to magnetic polymer beads. Mixing of bone marrow or splenocytes with the bead/OX-19 complexes, followed by magnetic separation, results in significant depletion of T cells with minimal nonspecific cell loss. Immunomagnetic T-cell depletion of bone marrow, followed by reconstitution of a lethally irradiated host, allows for the development of stable, mixed hematopoietic chimerae without evidence of GVHD. These hosts are immunocompetent by clinical criteria. Recipients of untreated donor bone marrow that did or did not receive nonspecific immunosuppression demonstrated varying degrees of GVHD and reduced survival. The ability to rapidly and simply deplete T lymphocytes from bone marrow and produce stable, immunocompetent hematopoietic chimerae without GVHD may be an important method for tolerance induction to vascularized allografts.

Animals↗

[Experimental studies of in vitro IFN induction by different polynucleotides in human cell culture systems].

Several polynucleotides were tested for interferon induction in comparison with the standard Poly (IC) in human diploid fibroblasts and in human leukocyte suspensions. We received high IFN-titre following superinduction of the polynucleotides in human fibroblasts. These results show that under superinduction conditions partly 3 times more interferon is induced in comparison with the standard inductor Poly (IC). The tested concentration of 10 micrograms/ml polynucleotides did not result in any IFN yields or only in very low ones in human leukocytes, which were only within the range of detectability.

Cells, Cultured↗

Incidence and diagnosis of acute rheumatic fever in Denmark, 1980 and 1983. A retrospective analysis of the fulfillment of the revised Jones criteria in hospitalized patients.

A review of 1547 official hospital record summaries concerning discharges during the period 1980 through 1983 of patients whose diagnoses had been coded as acute rheumatic fever revealed that in only 61% of the cases had this illness been diagnosed or suspected. A substantial proportion of the remaining patients had had acute non-rheumatic pericarditis diagnosed. The medical records were analyzed for 141 patients diagnosed in 1980 or 1983 by hospital departments as having acute rheumatic fever with regard to the revised Jones criteria. They were fulfilled in 47 patients, 23 of whom were considered unlikely cases of rheumatic fever. Eight patients were considered possible cases, although they did not fulfill the revised Jones criteria. The current annual incidence of acute rheumatic fever was estimated to be at most 0.3 per 100,000 inhabitants.

Acute Disease↗

Bacterial lysis of fibrin seal in vitro.

We performed an in vitro study to determine whether certain bacteria may lyse a commercially available fibrin seal (Beriplast, Behringwerke, Marburg, FRG). Fibrinogen solution was mixed with actively growing bacterial cultures, and thrombin was added. During 20 days of incubation at 37 degrees C complete lysis was observed with a number of different bacteria, however, at different rates. Complete lysis within 1-5 days was observed for the following species (number of strains in parentheses): Streptococcus faecalis (3), Pseudomonas aeruginosa (2), Serratia marcescens (2), and Serratia liquefaciens (1). Lysis was observed after 6-10 days for Enterobacter cloacae (2), Morganella morganii (2), Escherichia coli (2), S. marcescens (1), and Klebsiella pneumoniae (2). Lysis after 11-16 days was observed for Streptococcus pyogenes (2), S. faecalis (2), and Staphylococcus aureus (2). Rapid lysis was associated with the ability of the strain to liquefy gelatin, i.e. the production of a protease.

Aprotinin↗