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Biomedical subjects

U Goebel

Publications and source records attributed to U Goebel.

At least 19 recordsLinked to original sources

Smoking habits in patients diagnosed with ANCA associated small vessel vasculitis.

OBJECTIVES: To study the prevalence of smoking at onset of symptoms in patients with small vessel vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA). METHODS: A retrospective study, in 197 patients with ANCA associated vasculitis, of the history of cigarette smoking at onset of symptoms. Prevalence of smoking in patients with ANCA associated vasculitis was compared with age-specific values for the general population in Germany. RESULTS: 27 (14%) patients were smokers at the time of first disease manifestation (p < 0.001, compared with the entire population); 54 (27%) had smoked previously with 1-110 pack-years (median 18) but had stopped > or = 2 years before onset of vasculitis; 116 (59%) patients were lifelong non-smokers. At onset of symptoms, active smokers were younger (median age 42 years) than patients with vasculitis (median 54 years, p < 0.01, Mann-Whitney U test) with a lower percentage of women (15%, p < 0.005, Fisher's exact test) than in the entire group (47%). Smokers, non-smokers, or ex-smokers did not differ in organ manifestation, mortality, and development of end stage renal disease and relapse rate. CONCLUSIONS: The proportion of active smokers in the group of patients with ANCA associated vasculitis is significantly lower than in the entire population. Cigarette smoking may be associated with a reduced risk of ANCA associated vasculitis.

Adolescent↗

Necrotizing small-vessel vasculitis confined to the uterine cervix.

OBJECTIVES: To report our experience with five cases of apparently isolated small-vessel vasculitis of the uterine cervix. METHODS: Case study of five patients with necrotizing vasculitis discovered incidentally in surgical specimens of the female genital tract, and a review of the pertinent literature on this subject. RESULTS: All patients lacked clinical and serological features of the well-delineated vasculitic syndromes. Comprehensive workup failed to yield any evidence of an underlying disorder. All patients were managed expectantly and did not develop systemic vasculitis during follow-up ranging from 6 months to 5 years. CONCLUSIONS: Isolated vasculitis of the female genital tract can be encountered as an innocuous finding in otherwise healthy individuals. The cause and pathogenesis of this disorder remain obscure. Rheumatologists should be familiar with this rare and vexing form of vasculitis and with its benign prognosis.

Adult↗

Turkish pepper (extra hot).

A 38 year old female office worker was admitted with a newly discovered blood pressure of 250/110 mm Hg. Evaluation for secondary forms of hypertension was negative and treatment was begun. Sodium excretion was markedly reduced, plasma aldosterone was normal, and plasma renin activity was low. Therefore, presence of an aldosterone-like activity was suspected. Eventually, the patient confessed to abusing "Turkish Pepper", a brand of Scandinavian liquorice candies and "Fisherman's Friend", another brand of liquorice candies, concurrently. After eliminating liquorice from her diet, the hypertension disappeared thus allowing her antihypertensive treatment to be stopped.

Adult↗

Hypercalcemia due to talc granulomatosis.

Pulmonary disease due to talc, a group of hydrous magnesium silicates, is almost exclusively encountered after occupational exposure. One form of this rare disorder is talc granulomatosis. In varying degrees, hypercalcemia is typical of granulomatous disease but has not yet been reported in talcosis. We report the case of a former mold maker who presented with hypercalcemia. Laboratory findings indicated extra-renal 1-alpha-hydroxylation of 25-hydroxyvitamin D. Pulmonary infiltrates prompted a lung biopsy that disclosed talc granulomatosis. We suggest that talc granulomatosis should be added to the list of granulomatous disorders capable of causing hypercalcemia due to increased extra-renal 1-alpha-hydroxylation of 25-hydroxyvitamin D.

Aged↗

High ethanol tolerance in young adults is associated with the low-activity variant of the promoter of the human serotonin transporter gene.

Central serotonergic neurotransmission has been implicated in the aetiology of ethanol tolerance and dependence. Cellular expression of the serotonin transporter and serotonin reuptake is modulated via a polymorphic, repetitive element in the 5'-flanking regulatory region of the serotonin transporter gene (5-HTTLPR). We report the association of the low-activity, short variant of the 5-HTTLPR with high ethanol tolerance among young adults in a case-control association study (n = 713). The low-activity 5-HTTLPR showed a significantly increased allele frequency (chi2 = 7.30; df = 2; P = 0.007) and genotype frequency among young adults (< or =26 years) with high ethanol tolerance homozygous for the short allele (chi2 = 7.58; df = 1; P = 0.02). The estimated odds ratio for the homozygous short variant compared to the homozygous long variant was 2.82 (95% CI 1.30-6.11). This indicates that the low-activity 5-HTTLPR may be involved in the neuronal mechanisms responsible for ethanol tolerance and dependence.

Adult↗

Therapeutic management of rare malignant pancreatic tumors in children.

Malignant pancreatic tumors in children are rare. The major problem for the clinician is a lack of experience and of accepted therapeutic strategies. Malignant pancreatic tumors in children show a pattern different from that in adults. In infants, especially pancreatoblastomas, solid cystic tumors of females, and endocrine carcinomas of the pancreas must be expected. We report our experience in three patients with malignant pancreatic tumors (one pancreatoblastoma and two malignant endocrine pancreatic carcinomas) and review the present literature with a focus on the typical clinical and biologic features and the presently recommended therapeutic strategies. Pancreatoblastomas and solid cystic tumors are mainly found in the head of the pancreas. Fibrotic capsules with rare, late metastases are characteristics of these tumors, indicating total resection to be an important therapeutic procedure. Pancreatoblastomas should additionally be treated with chemotherapy (ADM, IFO, cis-PL, VP16). Endocrine carcinomas of the pancreas (malignant gastrinomas and malignant insulinomas) should also primarily be treated with radical surgery, including extensive lymph node dissection. In case of distant metastases, local resection (liver) or somatostatin in combination with chemotherapy (streptozocin in the case of malignant insulinomas) may be used.

Adolescent↗

Randomized comparison of rotational chemotherapy in high-risk acute lymphoblastic leukaemia of childhood--follow up after 9 years. Coall Study Group.

UNLABELLED: A frequent change of drug combinations may circumvent drug resistance in the treatment of patients with acute lymphoblastic leukaemia (ALL). In study COALL 85/89 201 children with high-risk ALL were randomized to receive over a period of 8 months rotational chemotherapy with six drug combinations given either in slow rotation (SR) (each combination given twice in succession) or in rapid rotation (RR) (each combination given once with a repetition of the drug combinations). Treatment of central nervous system leukaemia consisted of cranial irradiation and intrathecal methotrexate. Both SR and RR treatment groups were then given continuation chemotherapy of oral 6-mercaptopurine and methotrexate until 2 years after the date of diagnosis. The 9-year event-free survival (EFS) rate for the whole group is 69% +/- 3%, and the survival rate 75% +/- 3% at a median follow up of 5.8 years. Failure to achieve remission at day 28 was the most important prognostic factor (EFS 12% +/- 7% vs. 75% +/- 3% in the remission group). In the RR group, 11/100 patients were not in remission at day 28 opposed to 7/101 patients in the SR group. Children aged < 1 year (6/6 relapses) or aged > or = 10 years had a worse prognosis (EFS 64% +/- 5% vs. 77% +/- 4% in patients 1-10 years old). After 5 years EFS was inferior in the RR group attributable to a significantly higher relapse rate in children with a WBC > or = 100/nl. The EFS at 9 years for all patients, however, is similar in both groups (SR 72% +/- 5% vs. RR 67 +/- 5%). CONCLUSION: The COALL 85/89 treatment protocol with early intensive therapy and rotation of different drug combinations offers longterm disease-free survival for children with high-risk ALL. a continuous 4-week exposure to one drug combination may be necessary to achieve optimal results, especially in children with a high leukaemic cell burden.

Antineoplastic Combined Chemotherapy Protocols↗

Mixed haematopoietic colony formation via immature blast cell clusters on foetal mesenchymal cell layers distinguishes stem cells from peripheral blood, cord blood, bone marrow and blood stem cells mobilized by granulocyte-macrophage colony-stimulating factor.

Multilineage colony formation was evaluated from healthy donors' bone marrow (BM), peripheral blood (PB) and cord blood (CB) and compared with blood stem cell (BSC) harvests of sarcoma patients mobilized with granulocyte-macrophage colony-stimulating factor (GM-CSF). The test was a modified CFU-blast assay performed with and without an irradiated foetal mesenchymal cell layer (HFFF). These non-transformed mesenchymal cells served as a good source of haematopoietically active stroma cells in that cytokine expression patterns (interleukin (IL)-6, granulocyte (G)-CSF, GM-CSF) and adhesion molecules on HFFF cells were qualitatively identical to BM-derived fibroblasts, but the expression density of adhesion receptors was significantly higher. This HFFF layer stimulated blood stem cells of GM-CSF-treated patients significantly more than a cocktail of exogenous growth factors with IL-1, IL-6, and stem cell factor (SCF). The reverse was true for multilineage colonies from healthy donors' PB, BM, and CB. According to these results, stem cells of GM-CSF-treated patients are functionally distinct due to their dependence on stroma-derived factors and/or matrix-adhesion interactions and can be reproducibly evaluated on these mesenchymal cells.

Blood Cells↗

Chemical and immunological characteristics of four different L-asparaginase preparations.

We studied the differences in protein composition and immunologic reactivity of two E. coli-derived L-asparaginase (l-Asp) preparations (I and II), Erwinia-Asp (III) and PEG-modified E. coli l-Asp (IV). On gel filtration, each of preparations I-III showed three major peaks at 100, 270 and 460 KD, all with enzyme activity, whereas PEG-Asp showed peaks at 35 and 220 KD. On SDS-PAGE one major subunit could be identified at 32 KD (I and II) or 40 KD (III), whereas PEG-modified l-Asp could only be detected by lowering the polyacrylamide concentration and gave a single band above 200 KD. Using a polyclonal rabbit antibody generated against preparation I, only the E. coli l-Asp preparations (I and II) formed precipitin lines on Ouchterlony double diffusion. After freezing and thawing, preparation IV also reacted with this antibody. In sera from patients treated with preparation I, antibodies (detected by ELISA) reacted with preparations I and II but not with preparations III and IV. These results indicate that Erwinia-Asp (III) and PEG-Asp (IV) are distinct from E. coli preparations (I and II) by molecular weight and immunological behavior. They also provide an experimental rationale for the use of Erwinia-Asp as well as PEG-Asp in E. coli Asp-sensitized patients.

Asparaginase↗

Elimination of l-asparaginase in children treated for acute lymphoblastic leukemia.

The elimination of l-asparaginase (l-Asp) was studied in 8 children treated for acute lymphoblastic leukemia according to the CoALL 82 protocol. The patients received four doses of l-Asp as a single agent during induction chemotherapy. We studied the elimination of l-Asp during the first infusion in 1 child, during the second in 3, during the third in 2 and during the forth in 2 children. Using Western blot technique and an experimental rabbit antibody to l-Asp, we were able to detect a single band at 32 kilodaltons (KD) in the serum of all patients between 4 and 36 h after infusion. The molecular weight remained unchanged and no other bands occurred during the time of observation. The detection limit of this method was calculated to 5 micrograms/ml using radial immunodiffusion. Incubation of l-Asp with pooled normal human serum caused no degradation of the enzyme during 48 h at 37 degrees C. Neither the total enzyme nor fragments were detectable in the urine of the patients collected during 8 h after l-Asp infusion. From these results we conclude that l-Asp is not cleaved by proteases in humans. The enzyme is most probably eliminated by the reticuloendothelial system.

Adolescent↗