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Biomedical subjects

R Neumann

Publications and source records attributed to R Neumann.

At least 37 records · Page 2Linked to original sources

[Angiolymphoid hyperplasia with eosinophilia. Histologic study and successful therapy with the argon laser].

We report a case of angiolymphoid hyperplasia with eosinophilia (AHE) with regional lymphadenopathy. The multiple papules were composed of both a lymphoid infiltrate of predominant T-cell type with eosinophils and anomalous vascular proliferation lined by "histiocytoid" endothelial cells, which were in close association with a ruined artery at the subcutaneous level in the largest nodule. Immunoelectron microscopy revealed factor-VIII-related antigen to be concentrated within the Weibel-Palade bodies of the endothelial cells. Their cytoplasmic filaments consisted of vimentin. In the pericytes large amounts of actin were demonstrable. Since AHE has a benign progressive course and only local recurrence is noted, the lesions were treated with argon laser. Subsequently, lymphadenopathy resolved spontaneously and the blood parameters normalized. There is no evidence of recurrence 1 year after treatment.

Angiolymphoid Hyperplasia with Eosinophilia

Repeat unit sequence variation in minisatellites: a novel source of DNA polymorphism for studying variation and mutation by single molecule analysis.

Variation in internal minisatellite structure can be analyzed by mapping variant repeat units within amplified alleles. A system capable of distinguishing greater than 10(70) allelic states at the human hypervariable locus D1S8 has been developed. Population surveys of internal allelic structure indicate that D1S8 alleles evolve rapidly along haploid chromosome lineages. Internal mapping of deletion mutant alleles physically selected from genomic DNA provides further evidence that germline and somatic mutations altering the number of allelic repeat units seldom if ever arise by unequal exchange between alleles. The existence of low level germline mosaicism for new mutants further indicates that many germline mutation events are premeiotic. Physical selection of new mutants also allows minisatellite mutation rates to be estimated directly in human DNA.

Alleles

"Major minisatellite loci" detected by minisatellite clones 33.6 and 33.15 correspond to the cognate loci D1S111 and D7S437.

G. Chimini et al. (1989, Genomics 5: 316-324) have recently reported that the two multilocus DNA fingerprinting probes 33.6 and 33.15 each detect a single major site in the human genome, at 1q23 and 7q35-q36, respectively, and speculate that these sites represent particularly large loci homologous to these probes. However, the human minisatellite loci cloned in 33.6 and 33.15 can themselves be assigned by somatic cell hybrid analysis to 1cen-q24 and 7q31.3-qter, respectively, corresponding to the "major loci" of Chimini et al. Furthermore, under their hybridization conditions, both 33.6 and 33.15 act largely as locus-specific minisatellite probes. The "major minisatellite loci" postulated by Chimini et al. do not therefore appear to represent major localized clusters of minisatellites in the human genome, but rather the loci cloned in 33.6 and 33.15.

Base Sequence

Decline of erythropoietin formation at continuous hypoxia is not due to feedback inhibition.

Serum erythropoietin (EPO) levels in response to hypoxia are known to decline before an increase in blood oxygen carrying capacity. To define the possible mechanisms underlying this phenomenon, we have investigated 1) how renal EPO mRNA content and EPO production rate underlying the early kinetics of serum EPO levels change under different degrees of normobaric hypoxia, and 2) if a feedback inhibition of either EPO formation or EPO survival in the circulation exists by the hormone itself. We found that serum immunoreactive EPO levels in rats peaked after 12-h exposure to 7.5 or 9% oxygen (2,949 +/- 600 and 756 +/- 108 mU/ml, respectively, mean +/- SE) and declined to 29 and 64% of peak levels, respectively, after 36 h of hypoxia. EPO levels in response to 11.5% oxygen showed no consistent change between 12 (122 +/- 21 mU/ml, mean +/- SE) and 36 h (182 +/- 35 mU/ml) of hypoxia. The decline in EPO levels under severe hypoxia (7.5% O2) was paralleled by a marked reduction in renal EPO mRNA content, indicating that it was primarily a result of diminished hormone production. The observed reductions in serum EPO after 36 h corresponded to preceding declines of calculated EPO production rates from 163- to 62-fold (7.5% O2) and 36- to 25-fold (9% O2) basal values. Application of 50 IU recombinant human EPO to rats 12 h, 6 h, or immediately before hypoxic exposure to mimic the early increase in EPO levels did not affect endogenous EPO formation during a subsequent hypoxic exposure of 12 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Fistula carcinoma 62 years following roller crush trauma of the hand].

The development of carcinoma after trauma is a rare event. A case of an eighty-two-year old man is reported, who had massive trauma to his hand at the age of twenty. After a more or less symptomless interval of twenty-three years he began a period of recurrent osteomyelitis. Thirty-nine years later still a carcinoma was diagnosed in the same region. The relationship of carcinoma development to trauma is discussed.

Aged

[Clinical relevance of nucleic acid detection of human papillomaviruses (HPV) in cells from smears of the cervix uteri].

Cervical smears from 516 women were investigated cytologically and for the presence of papilloma virus (HPV) type 16/18 DNA sequences. From the cytologically normal smears (Pap I, II, IIw) 57/424 (13%) 16/18 were found HPV positive and from the pathological ones (Pap III, IIID, IVa, IVb, V), 30/92 (33%). The age prevalence of the HPV infection--provided a cytologically normal smear--appears compatible with the period of sexual activity, but persistence of the HPV infection has to be considered as a complicating factor. Our investigations on successive smears nevertheless permit the hypothesis that an HPV infection may disappear. The use of biotin-labeled nucleic acid probes yields results at least as reliable as those obtained with radioactive probes. The test for HPV positivity appears at present to be of limited diagnostic and prognostic benefit, particularly for the individual case. Investigations on fundamental oncogenic mechanisms are a different matter.

Adult

Cortisol deficiency in metomidate anesthetized bacteremic pigs: results in circulatory failure--beneficial effect of cortisol substitution.

Etomidate and the closely related metomidate are known to inhibit cortisol synthesis. We studied the influence of metomidate on hemodynamic performance and survival time of bacteremic pigs. Thirty pigs, 30.2 +/- 0.8 kg, were anesthetized with intravenous metomidate (2.5 mg.kg-1.h-1) plus ketamine (3.0 mg.kg-1.h-1), and were then mechanically ventilated. The animals were randomly allocated to three groups of 10 pigs each. Group A received an infusion of live Pseudomonas aeruginosa bacteria (2.5.10(9).kg-1.h-1 organisms until death), Group B additionally received a bolus of 1 mg.kg-1 cortisol (followed by an infusion of 0.1 mg.kg-1.h-1) starting 1 h prior to the bacterial infusion, and Group C served as anesthesia control without receiving bacteria or cortisol. The experiments in Group C were terminated after 10 h. In Group A the cortisol level was severely suppressed from the very beginning. The animals died of circulatory failure after 4.3 +/- 0.4 h. In contrast, Group B exhibited fairly stable hemodynamics, but the animals died due to pulmonary edema after 11.1 +/- 1.3 h. Cortisol deficiency in metomidate anesthetized pigs facilitates the development of circulatory failure in the course of Pseudomonas bacteremia, which does not occur if cortisol is infused to reconstitute a physiological level. However, this cortisol substitution did not prevent the development of pulmonary edema caused by Pseudomonas aeruginosa. Possible mechanisms of the deleterious effect of cortisol deficiency and implications in regard to the clinical use of metomidate/etomidate are discussed.

Anesthesia, Intravenous

Possibilities and limitation of prenatal diagnosis and carrier determination for Duchenne and Becker muscular dystrophy using cDNA probes.

Two cDNA probes, cf23a and cf56a, identify deletions of selected exons in about 50% of our DMD/BMD patients. We have estimated the most likely order of the 11 exons detectable with both probes with respect to the different extensions of the deletions. In one of our BMD pedigrees, the observed deletion could be traced in the affected males through three generations. This result shows that with the use of cDNA probes detecting deletions, the only risk of error in genomic prenatal diagnosis is the general high frequency of new mutations for DMD/BMD. This is important progress in diagnosis compared to the 2 to 5% risk of misdiagnosis because of crossing over events using conventional linkage analysis with bridging or intragenic probes. The first prenatal diagnosis of an unaffected fetus of a woman who is a DMD carrier according to ultrasound examination is described. In one of our DMD males, the cDNA probe cf56a detects a deletion breakpoint. His sister also shows the altered band and is therefore a DMD carrier, while his mother has a totally normal band pattern. The interpretation of this observation could be either germline mosaicism or two identical new mutations. The identification of deletion breakpoints is a new diagnostic strategy, especially for carrier determination, which excludes misdiagnosis owing to crossing over events and the problems of dosage estimation. It is, however, limited by the low frequency of breakpoints detectable with cDNA probes. Therefore, the generation of new intron probes in this region is an important goal.

Chromosome Deletion

Erythropoietin in polycystic kidneys.

Erythropoietin (EPO) formation in kidneys of 18 patients with autosomal dominant polycystic kidney disease (ADPKD) was investigated. In 12 patients on hemodialysis and in 6 patients with preterminal renal failure serum, EPO was 29 +/- 7 and 16 +/- 1.5 mU/ml and hemoglobin concentrations were 11.0 +/- 0.6 and 12.7 +/- 1.2 g/dl, respectively. Cyst fluid from a total of 357 renal cysts was obtained by either in vivo aspiration or immediately after nephrectomy. The cysts contained variable concentrations of bioactive EPO from undectable values up to 3.2 U/ml. A pronounced enrichment of EPO was observed in cysts with sodium concentrations greater than 100 mmol/liter, suggesting an association with proximal tubular malformations. The EPO concentrations in the cysts were neither correlated with the protein concentration nor with the oxygen pressure of the cyst fluid. Using a cDNA probe for human EPO, mRNA for EPO was localized in stroma cells of the cyst walls by an in situ hybridization technique. Our findings suggest that single interstitial cells juxtaposed to proximal tubular cysts may produce EPO independent of the oxygen pressure inside the cysts, which ameliorates the anemia during end-stage polycystic kidney disease.

Animals

[Femorogluteal manifestation of lymphogranuloma venereum].

We report on a case of lymphogranuloma venereum in a 40-year-old man who acquired the disease while on vacation in Tunisia. After 4 years, a fibrosing, fistulating inflammation developed in an atypical distribution that involved the scrotum, perineum, and left gluteal and upper femoral regions; the disease progressed because of insufficient therapy. The diagnosis was established on serological examination, and treatment with doxycycline (2 x 100 mg for 4 weeks) improved the chronic inflammatory process.

Adult

[Apocrine chromhidrosis].

Apocrine chromhidrosis is an extremely rare and impressive skin disorder. Primarily after emotional stress patients complain of coloured sweat secretion (black, green, blue or yellow). The deposition of lipofuscin in the apocrine glands may be the cause of this disease, the different colours of sweat being due to various oxidation stages of lipofuscin. We report two patients, one with blue and one with green axillae; the clinical features, histopathology, differential diagnosis, and pathogenesis of apocrine chromhidrosis are discussed.

Aged

[The malignant neuroleptic syndrome and malignant hyperthermia].

We report on a patient with neuroleptic malignant syndrome (NMS) caused by a therapy for endogenous depression. The symptoms were hyperpyrexia (39.2 degrees C), rigidity, elevated creatine kinase (CK: 594 U/l) and coma. After transfer from an outside hospital, he was treated, at first without effect with dantrolene p.o. (80 mg q.i.d.) and i.v. (1 mg/kg-1/h-1). Clinical improvement and temperature reduction were noted when the levels of neuroleptic drugs fell during unspecific intensive care with mechanical ventilation, sedation (flunitrazepam, barbiturates), relaxation (pancuronium), and hydration. After uncomplicated weaning from the ventilator the patient became more cooperative and was returned to the psychiatric ward. Further treatment took the form of combined drug therapy with biperiden and flunitrazepam and in addition a series of 12 electroconvulsive therapies (ECT). The elevated CK levels initially decreased, serum potassium levels were found to be within normal limits, and myoglobinuria was not detected during the further course. Trigger agents for NMS are antipsychotic drugs such as thioxanthenes, phenothiazines and butyrophenones. Because the signs and symptoms are so similar to those of malignant hyperthermia (MH), it has been suggested that NMS and MH are related diseases. The postulated mechanisms of NMS become apparent in the CNS, whereas those of MH affect the muscle cell itself. An abnormal in vitro contraction test after NMS should suggest to triggering of MH crisis after succinylcholine administration in anaesthesia for ECT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Polyvinylpyrrolidone iodine--its significance in dermatology].

In an open comparative study, 40 patients suffering from pyoderma, combustion (1st and 2nd degrees), leg ulcer, or inflammatory white atrophy were treated with a topical preparation containing either polyvinyl pyrrolidone iodine or neomycin. Both preparations were well-tolerated. There was no local hypersensibility. With regard to the therapeutic effect, we did not observe any differences between the two groups of patients. We discuss the properties, modes of action, and contraindications, as well as the possible systemic influences of topically applied PVP iodine.

Administration, Topical

Amplification of human minisatellites by the polymerase chain reaction: towards DNA fingerprinting of single cells.

Hypervariable minisatellites can be amplified from human DNA by the polymerase chain reaction, using primers from DNA flanking the minisatellite to amplify the entire block of tandem repeat units. Minisatellite alleles up to 5-10 kb long can be faithfully amplified. At least six minisatellite loci can be co-amplified from the same DNA sample and simultaneously detected to provide a reproducible and highly variable DNA fingerprint which can be obtained from nanogram quantities of human DNA. The polymerase chain reaction can also be used to analyse single target minisatellite molecules and single human cells, despite the appearance of spurious PCR products from some hypervariable loci. DNA fingerprinting at the level of one or a few cells therefore appears possible.

Alleles