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Biomedical subjects

M Wilhelm

Publications and source records attributed to M Wilhelm.

At least 145 records · Page 8Linked to original sources

[Incidence, clinical aspects and therapy of late pericardial tamponade following heart surgery].

Late cardiac tamponade is a very severe condition that presents with subtle signs and symptoms within days or weeks after cardiac surgery. In a consecutive series of 3782 patients, 33 developed this complication, mostly due to overdosage of anticoagulants or to unsafe combination of 2 anticoagulation regimen. Diagnosis can be difficult and is best confirmed by echocardiography; in patients with primary uneventful recovery and sudden cardiocirculatory deterioration, intensive work-up should be performed to exclude or confirm the suspicion of late pericardial tamponade. The treatment of late pericardial tamponade should not be delayed and consists in subxyphoidal drainage. Re-sternotomy might be necessary to assume complete decompression of the heart in case of well-localized and posterior tamponade and/or organized pericardial fluid. Since this complication can happen in any patient transferred to peripheral hospital for postoperative recovery after cardiac surgery, we believe that this complication should be recognized very early and should be treated, in case of necessity, by general surgeons. Usually, no active bleeding is found at revision.

Adult↗

Pneumonia during remission induction chemotherapy in patients with AML or MDS.

We analyzed the 67 of 278 patients with newly-diagnosed AML or 'high-risk' MDS, treated in 1994 and 1995, who developed pneumonia during course 1 of their induction therapy. Pneumonia responded to treatment in 66%, but outcome depended on when pneumonia was diagnosed. Patients with pneumonia diagnosed during week 1 or 2 (group 2 patients) had the lowest response rate (43%). Patients who developed pneumonia in the 3rd week after treatment initiation had the best outcome with all 16 patients recovering. Patients presenting with pneumonia had an intermediate response rate (75%). The different patient groups were comparable with regard to age, underlying disease, prophylactic therapy, and G-CSF application. Although a lower CR rate was not entirely responsible for the lower response rate in group 2, failure to achieve CR predicted unsuccessful treatment of pneumonia in all groups. Fungal pathogens appeared more common in group 2 patients. However, in these patients, administration of amphotericin B was associated with a significantly higher failure rate (15/21 failures vs 2/9 who received no amphotericin B). We conclude that patients who develop pneumonia during week 1 or 2 are a high-risk group, and that use of amphotericin B indicates a particularly poor prognosis, although we present data suggesting that earlier use of amphotericin might be beneficial. Furthermore, since achievement of CR was an important prognostic factor in all groups, WBC transfusions particularly from donors given G-CSF should be considered as a therapeutic option. Finally, since time to failure of induction therapy and time to CR were similar in high-risk patients, new chemotherapy regimens could potentially improve both the CR rate and the outcome of pneumonia.

Acute Disease↗

Hair analysis in environmental medicine.

Hair analysis comprises the determination of minerals, trace elements and drugs. It is applied in Germany with increasing frequency in the recently established field of environmental medicine for biological monitoring of the internal metal/metalloid exposure. Besides a number of advantages hair analysis is impaired by the difficulty-to distinguish between endogenous and exogenous sources of metals in hair. Except for methylmercury, there are no critical limit values for trace elements in hair available. However, valid reference values for some metals and for nicotine in hair have been recently presented in the German Environmental Survey. The significance of selected substances in hair are as follows: Aluminium in hair is of no value in environmental medicine. For assessment of cadmium and inorganic arsenic exposure hair analysis is only suitable as a screening method based on large populations. Monitoring of lead in hair is a valuable screening method also for small groups, especially for children. Based on toxicokinetics and under consideration of practicability the optimal biomarker of methylmercury exposure is the hair concentration. For other mercury compounds hair analysis is of lower significance. Nicotine and cotinine measurements in hair provide a practical and proper method for estimating environmental tobacco smoke exposure and to validate smoker status in epidemiological studies.

Adolescent↗

Terminal deletion of chromosome 3p sequences in nonpapillary renal cell carcinomas: a breakpoint cluster between loci D3S1285 and D3S1603.

Deletion of chromosome 3p13-pter sequences is a specific genetic change in nonpapillary renal cell carcinomas (RCC). The VHL gene, a putative tumor suppressor gene, has already been cloned from the 3p25-26 chromosomal region. Conflicting cytogenetic and RFLP studies, however, suggest multiple interstitial deletions and additional tumor suppressor genes at chromosome 3p. To investigate the loss of DNA sequences on chromosome 3p in nonpapillary RCCs, we analyzed 41 paired normal and tumor DNAs obtained from short-term cultures of pure tumor cells with 12 polymorphic microsatellite markers covering the 3p11.2-p25 region. Deletion mapping provided evidence for terminal deletion with the most distal breakpoint between D3S1300 and D3S1285 loci, which is the site of breakpoint in familial 3;8 translocation predisposing to nonpapillary RCC. All breakpoints, including those occurring in familial translocation 3;6, were clustered in a more than 20-cM-large region between loci D3S1285 and D3S1603. Interestingly, 7 of the 28 cases with 3p deletion showed a recurrent breakpoint between D3S1603 and D3S1595, which cover about 1 cM genetic distance. The results suggest that a tumor suppressor gene, in addition to the VHL gene, might be localized somewhere on chromosome 3p distal to the familial 3;8 translocation, or it might be at the breakpoint cluster. Alternatively, the breakpoint serves as a mechanism to lose distal DNA sequences.

Carcinoma, Renal Cell↗

[Sarcoidosis in monozygotic twins].

Identical (monozygotic) female twins both simultaneously developed acute sarcoidosis with unusual manifestations. Additional to pulmonary involvement they both also had hypercalcaemia with compensated renal failure. When seen at the age of 33 years, these findings were more marked in one of them (case 2) than in the other, and she also had granulomatous conjunctivitis, while in the other one (case 1) the dominant sign was widespread lymph node enlargement. Both were also found by magnetic resonance imaging to have multiple lesions in the white matter, interpreted as the morphological correlate of neurosarcoidosis. But they caused clinical symptoms (visual disorder, unsteady gait) in only one sister (case 1). Treatment with prednisolone largely normalized the lung functions in case 2, completely in case 1, and renal functions in both. But when the daily prednisolone dose was reduced to below 10 mg, the pulmonary symptoms recurred. These observations indicate that even in chronic sarcoidosis acute episodes may occur, with involvement of multiple organs and other rare complications. The manifestations of the underlying disease in identical twins and the similarities of its course in the two sisters underline the possible role of genetic factors in the pathogenesis of sarcoidosis.

Acute Disease↗

Diagnosis and prognosis of renal-cell tumors: a molecular approach.

This review discusses the impact of molecular genetics on the diagnosis and prediction of the prognosis for renal-cell tumors. Through the use of molecular techniques, it has become possible to divide renal-cell tumors into genetically and biologically well-defined entities. The new classification has many advantages over morphological ones: (1) in contrary to tumor phenotype, genetic markers are constant during tumor progression and allow a precise diagnosis; (2) genetic analysis discriminates between papillary (multiple origin) and nonpapillary renal-cell carcinomas (solitary tumors); (3) genetic analysis allows a precise diagnosis of renal adenoma; (4) the new classification system offers a genetic prognostic system; and (5) the new diagnostic-prognostic system could easily be adapted to modern detection systems such as automated sequence and fragment-length analysis, which allow a quick and correct diagnosis with a high throughput.

Adenocarcinoma↗

Interleukin-6 (IL-6) levels in febrile children during maximal aplasia after bone marrow transplantation (BMT) are similar to those in children with normal hematopoiesis.

Interleukin-6 (IL-6) has been shown to be an inducer of the acute-phase response (APR) and to be involved in the pathogenesis of several disease states, including graft-versus-host disease (GvHD) following allogeneic bone marrow transplantation (BMT). As blood cells of the monocyte lineage are known to be major producers of this cytokine, we wondered whether extreme peripheral leukopenia following total ablation of hematopoiesis could compromise IL-6 production during the first days after allogeneic or autologous BMT. In the absence of detectable circulating leukocytes we measured elevated IL-6 levels in six children having fever (> or = 38 degrees C) of presumed infectious origin with an average of 74 +/- 60 units/ml (range 19-309 units/ml). IL-6 levels in febrile children having a normal hematopoiesis (118 +/- 254 units/ml, range 17-1213 units/ml) were not significantly higher than those found in the febrile BMT group (p > 0.05). Moreover, there was a clear association between elevated IL-6 levels and the presence of fever. C-reactive protein (CRP) was also elevated (> or = 1 mg/dl), whereas tumor-necrosis factor alpha (TNF) was undetectable (< 1 pg/ml). Two transplanted patients without fever during the period of total aplasia had neither detectable CRP nor IL-6, thus demonstrating that the transplant procedure itself does not induce an APR. Our data obtained during maximal leukopenia following BMT show that a functional hematopoietic system is not necessary for regular production of IL-6, which is associated with fever. Cells of nonhematopoietic origin may contribute to this production.

Bone Marrow↗

Application of a fast charge-pulse technique to study the effect of the dipolar substance 2,4-dichlorophenoxyacetic acid on the kinetics of valinomycin mediated K(+)-transport across monoolein membranes.

We report on a modified charge-pulse relaxation technique applied at planar lipid membranes. The method has an improved time resolution of 20-30 ns. It is based on the capacitive coupling of a voltage-jump to the membrane. The method was used to study the fast relaxation processes induced by valinomycin/K+ in the presence of 2,4-dichlorophenoxyacetic acid (2,4-D). The change of the rate constants of the ion carrier valinomycin was analysed as a consequence of the adsorption of the dipolar substance 2,4-D to the membrane/water interface of monoolein membranes. The effect of 2,4-D can be explained solely via the influence of the introduced dipole potential, VD. The latter was found to act (primarily) on the inner membrane barrier experienced by the positively charged carrier-ion complex and on the interfacial barriers responsible for complex formation and dissociation. No evidence for a change of the microviscosity of the membrane interior was obtained.

2,4-Dichlorophenoxyacetic Acid↗

Macronutrient, copper, and zinc intakes of young German children as determined by duplicate food samples and diet records.

Daily energy, protein, fat, carbohydrate, zinc, and copper intakes of 47 healthy 5- to 9-year-old children living in Duisburg, an industrial area of North Rhine-Westphalia, and consuming self-selected diets were calculated using a 4-day weighed dietary records and food composition values. In addition, the parents of the subjects also collected a 24-hour food composite on 2 of the recording days for analysis of the nutrients. This allowed us to compare the calculated value of the nutrients on days when only dietary records were made with those on which also duplicate samples were collected. Daily analyzed intakes were also compared with those calculated from the recording days. Zinc and copper were estimated by atomic absorption spectrometry. The results show that there were reductions in the intake of all nutrients on days when duplicate samples were also collected as compared with the days when only dietary records were made. Median daily calculated intakes for all children on the 4 record days were: energy 1,578 kcal, protein 46.5 g, fat 67.3, carbohydrates 174.7 g, zinc 5.3 mg, and copper 1.0 mg. The median analyzed intakes were: energy 1,367.7 kcal, protein 37.1 g, fat 49.1, carbohydrates 178.7 g, zinc 5.3 mg, and copper 0.7 mg. The use of the duplicate diet method has shown that a 4-day recording period gives an overestimation of the nutrient intake. The calculated and the analyzed zinc intakes did not meet the recommended levels of the Deutsche Gesellschaft für Ernährung. The median copper intakes were in the lower range of the levels recommended by the Deutsche Gesellschaft für Ernährung.

Child↗

[Duplicate study on the dietary intake of some metals/metalloids by children in Germany. I. Arsenic and mercury].

The dietary intake of arsenic and mercury by 47 children (aged 5-8 years) living in West-Germany (Duisburg) is reported. Duplicate portions of all food and beverages were obtained on 2 days. Arsenic and mercury were measured by atomic absorption spectrometry under careful quality control. Results of are shown in the following table. [table: see text] Fish was consumed at 3 of 94 sampling days only. The arsenic and mercury intake on days with fish consumption was much higher compared with the other days (median, range): arsenic 8821; 4431-11954; mercury 123.7; 80, 0-167.5 ng/kg b.w. and day. The dietary arsenic and mercury intake was much lower than the FAO/WHO PTWI. For mercury the median intake amounted to 1.7% on days without and to 16.6% on days with fish consumption, for arsenic on days without fish consumption to 5.2% PTWI (only for inorganic arsenic compounds established) and on days with fish consumption (in fish mainly organic arsenic occur) 411% of PTWI. Based on the PTWI our data indicate no health risks for German 5-8-year-old children due to arsenic and mercury dietary intake.

Animals↗

[Duplicate study on the dietary intake of some metals/metalloids by children in Germany. part II. Aluminum, cadmium and lead].

The dietary intake of aluminium, cadmium and lead by 47 children (aged 5-8 years) living in West-Germany (Duisburg) is reported. Duplicate portions of all food and beverages were obtained on 2 days. Aluminium, cadmium and lead were measured by atomic absorption spectrometry under careful quality control. Results are shown in the following table. [table: see text] The dietary intake of aluminium was low. The median amounted to 2.9% and the maximum value to 11.2% of the FAO/WHO PTWI. The correspondent data for cadmium were 30.2 and 98.7% and for lead 22.2% and 72.1% respectively.

Aluminum↗

Yeast Ty1 retrotransposon: the minus-strand primer binding site and a cis-acting domain of the Ty1 RNA are both important for packaging of primer tRNA inside virus-like particles.

Reverse transcription of the yeast retrotransposon Ty1 is primed by the cytoplasmic initiator methionine tRNA (tRNA(iMet)). The primer tRNA(iMet) is packaged inside virus-like particles (VLPs) and binds to a 10 nucleotides minus-strand primer binding site, the (-)PBS, complementary to its 3' acceptor stem. We have found that three short sequences of the Ty1 RNA (box 1, box 2.1 and box 2.2) located 3' to the (-)PBS are complementary to other regions of the primer tRNA(iMet) (T psi C and DHU stems and loops). Reconstitution of reverse transcription in vitro with T7 transcribed Ty1 RNA species and tRNA(iMet) purified from yeast cells shows that the boxes do not affect the efficiency of reverse transcription. Thus the role of the boxes on packaging of the primer tRNA(iMet) into the VLPs was investigated by analysing the level of tRNA(iMet) packaged into mutant VLPs. Specific nucleotide changes in the (-)PBS or in the boxes that do not change the protein coding sequence but disrupt the complementarity with the primer tRNA(iMet) within the VLPs. We propose that base pairing between the primer tRNA(iMet) and the Ty1 RNA is of major importance for tRNA(iMet) packaging into the VLPs. Moreover the intactness of the boxes is essential for retrotransposition as shown by the transposition defect of a Ty1 element harboring an intact (-)PBS and mutated boxes.

Amino Acid Sequence↗

[Sensible diagnosis in suspected immune deficiency].

Patients reporting a marked proclivity for developing infections often present the care-providing physician with a diagnostic problem. If the available diagnostic possibilities are to be used rationally and with proper understanding, a thorough knowledge of the nature of an immune reaction is essential. The present paper contains a step-by-step scheme that may serve as an aid for the diagnostic approach. In addition to the clinical examination and routine laboratory investigations, simple tests such as Mérieux multitest and serum antibody titer serve to orientate the doctor on the patient's immune status. More sophisticated time-consuming and expensive tests, such as flow cytometric analysis of immune cells or functional in vitro investigations permit the identification of immune deficiency syndromes. These tests should, however, be undertaken only when severe immunodeficiency is suspected clinically or the orienting studies make it appear likely.

Antibody Formation↗

Tachykinin NK1 and NK2 receptors mediate atropine-resistant ileal circular muscle contractions evoked by capsaicin.

The atropine-resistant contractile action of the sensory stimulant drug capsaicin was examined on guinea-pig ileum circular muscle in vitro, with special regard to the involvement of endogenous tachykinins acting through tachykinin NK1 and NK2 receptors. A protocol, using ruthenium red was developed for overcoming desensitization to capsaicin so that two reproducible responses to this drug were obtained. Capsaicin (10(-6) M) caused tonic and phasic contractions of the tissue. This effect was significantly inhibited by the tachykinin NK1 receptor blocking drug FK 888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl)carbonyl-L-proly]-N- methyl-N-phenylmethyl-3-(-2-naphthyl)-L-alaninamide) or the tachykinin NK2 receptor inhibitor GR 94,800 (PhCO-Ala-Ala-D.Trp-Phe-D.Pro-Pro-NleNH2) (10(-6) M each) and was practically abolished by the combined administration of the two tachykinin receptor blockers. Likewise, the neuronal Na+ channel inhibitor tetrodotoxin abolished the response to capsaicin. It is concluded that the contractile effect of capsaicin in the circular muscle is predominantly mediated by tachykinin release and both subtypes of tachykinin receptor (NK1 and NK2) play an important role in this process. The source of tachykinins, however, is probably intrinsic neurons of the myenteric plexus, indirectly activated by capsaicin-sensitive nerves, as shown by the sensitivity of the response to tetrodotoxin.

Amino Acid Sequence↗

[Treatment of patients with acquired (non-HIV) immune deficiencies].

Infection continues to remain a major problem in immunodeficient patients. The spectrum of pathogens differs, depending on whether one is dealing with an unspecific immune defect or a specific hormonal or cellular defect. This means that a knowledge of the type of deficiency presenting is of importance for the empirical treatment that is often required. Infection can be prevented by the replacement of immunoglobulins, in particular in the case of hormonal immune defects. The use of cytokines holds out some promise of achieving a similar effect in the treatment of cellular immune defects.

Combined Modality Therapy↗

Cadmium, copper, lead and zinc concentrations in hair and toenails of young children and family members: a follow-up study.

In a follow-up study concentrations of cadmium, copper, lead and zinc (measured by atomic absorption spectrometry) in scalp hair and toenail clippings of 47 children (5-9 years) were compared with previous values (2 years earlier). Family members were also monitored. Twenty-five of the children selected have had either high hair values of Cd, Cu, Pb or low hair Zn concentrations or combinations of these (group A) in the first study. Control group comprised 22 children (B). At the follow-up study, there were no more differences between group A and B. Between the first and follow-up study Cd and Pb levels in hair and toenails of group A children declined (geometric means; hair Cd: 265 vs. 111 ng/g; hair Pb: 10.1 vs. 3.8 micrograms/g; toenail Cd: 720 vs. 335 ng/g; toenail Pb 18.5 vs. 5.8 micrograms/g) and hair Zn values increased (54 vs. 103 micrograms/g). Fathers of exposed children had more Cd and Pb in hair and toenails than fathers of control children (hair Cd: 88 vs. 48 ng/g; hair Pb: 4.4 vs. 1.3 micrograms/g; toenail Cd: 46 vs. 23 ng/g; toenail Pb: 1.3 vs. 0.7 microgram/g). No conclusive findings were obtained for Cu. With respect to heavy metal levels of mothers and brothers and sisters there was no uniform pattern. Children < 5 years of age are especially prone to higher Cd, Pb exposure and to lower Zn status compare with older children.

Adolescent↗