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Biomedical subjects

M Wolf

Publications and source records attributed to M Wolf.

At least 433 records · Page 24Linked to original sources

[A complex symphalangia syndrome with brachydactyly, humeroradial synostosis and other multiple joint dysplasias].

Two members of a family affected with autosomal dominant multiple synostosis syndrome and malformations of various joints are presented, the most prominent signs being humeroradial synostosis and symphalangism. Moreover, dysplastic hip joints and familial conductive deafness as well as craniofacial abnormalities are observed. The present report may serve as an introduction to the complex radiological pattern in patients with hereditary brachydactyly syndrome.

Abnormalities, Multiple↗

[Value of the preventive use of antibiotics following vaginal obstetric operations].

For a period of 6 years 838 puerperal cases after vaginal obstetric operations (forceps delivery, vacuum extraction, delivery with speculum, manual placenta separation, palpation of the uterus) were critically analysed. The result of the studies suggest that an antibiotic or chemoprophylaxis after vaginal obstetric operations is not successful because of the relatively low infectious morbidity. In obstetrics this prophylaxis is indicated only in delivery by caesarean section as a perioperative short-time prophylaxis.

Chloramphenicol↗

Purification and further characterization of antithrombin III Milano: lack of reactivity with thrombin.

The functional abnormality of Antithrombin III "Milano", a previously described variant with monomeric and dimeric forms of abnormal AT III, has been further characterized. Affinity chromatography on heparin-Sepharose led to the separation and purification of two distinct fractions: fraction I is identical to normal AT III; fraction II (abnormal AT III) reproduces the abnormalities of the AT III "Milano", i.e. lack of thrombin inhibition, increased mobility by two-dimensional immunoelectrophoresis in the absence of heparin and migration as two bands with molecular weights of 60 K and 120 K by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The interaction of both fractions with purified alpha-thrombin was studied by the formation of complexes as well as by affinity chromatography on thrombin-Sepharose. No thrombin-AT III complexes could be demonstrated with either the monomeric or dimeric forms of purified variant AT III at both concentrations of thrombin used. Similarly, no binding to thrombin-Sepharose was observed, thus indicating that the molecular defect of AT III Milano is related to its absence of reactivity with thrombin.

Antithrombin III↗

Alternating versus sequential chemotherapy in small cell lung cancer. A randomized German multicenter trial.

A total of 306 patients with small cell lung cancer (SCLC) were randomized to receive chemotherapy in a sequential or alternating mode. Sequential chemotherapy consisted of eight cycles of cyclophosphamide, Adriamycin (doxorubicin), and vincristine (CAV) and alternating chemotherapy consisted of three cycles (1, 3, 5) of etoposide, vindesine, and ifosfamide (EVI); three cycles (2, 4, 6) of cisplatin, Adriamycin, and vincristine (PAV); and two cycles (7, 8) of cyclophosphamide, methotrexate, and CCNU (CMC). Responsive patients received prophylactic cranial irradiation after three cycles and chest irradiation after eight cycles of chemotherapy. No maintenance therapy was applied to patients achieving complete remission. Minimum follow-up was 2 years. Of the 302 patients evaluable, overall response rate was 59% in the sequential arm and 70% in the alternating arm. Patients treated with CAV had a complete response rate of 21% in contrast to 36% for those receiving alternating therapy. The median survival for all patients was 9.8 versus 11.3 months, for limited disease 11.1 versus 13.4 months, and for extensive disease 8.9 versus 9.9 months, all in favor of the alternating treatment. Two-year survival rate for all patients was 6% versus 9%, for limited disease 11% versus 14%, and for extensive disease 3% versus 6%, all preferring the alternating treatment mode. Progression-free survival demonstrated a strong correlation to the extent of response irrespective of the treatment regimen applied. Toxicity included 11 lethal and 8 life-threatening complications with a higher frequency in the alternating treatment arm. These results suggest that alternating treatment of SCLC with different drug combinations is more effective than sequential application of CAV.

Antineoplastic Combined Chemotherapy Protocols↗

Multicenter comparison of five functional and two immunological assays for protein C.

Five functional assays and two immunoassays for protein C (PC) were evaluated in parallel for the same plasma samples collected from healthy subjects, patients with congenital and acquired PC deficiencies or patients with conditions associated with high PC levels. For 7 patients starting warfarin therapy and for 15 patients during stabilized warfarin therapy, there were significant between-assay differences. For these groups immunoassays gave higher values than most functional assays and the latter also gave varied results, probably depending on their respective capacity for recognizing a carboxylated PC. On the other hand, there were no significant between-assay differences nor discrepancies between PC activity and antigen levels for healthy subjects (n = 39), patients with congenital PC deficiency (n = 10), myocardial infarction (n = 25), chronic liver disease (n = 19), disseminated intravascular coagulation (n = 35), in the post-operative period (n = 20) or in women taking oral contraceptives (n = 20). This comparison of PC assays indicates that PC levels measured by different functional or immunological assays are very close in the majority of clinical conditions, but not for patients on oral anticoagulants.

Blood Coagulation Tests↗

Ultrastructural investigations on the question of mechanical activation of blood platelets.

The present study addresses the question whether platelets are activated by mechanical stresses as they occur in pathologically accelerated blood flow. Their potential mechanoreceptive properties were tested by subjecting human platelets to defined fluid mechanical forces for periods of milliseconds. Platelet activation was assessed by quantitative morphology, revealing besides activated platelets, irreversibly ballooned, lytic platelets. However, this morphometrically documented "shear activation" of platelets can be suppressed almost completely by the addition of enzyme-substrate systems, capable of removing adenosine diphosphate from the suspending medium. This is in keeping with a recent study from our laboratory showing that the behaviour of lactic dehydrogenase as marker for platelet lysis and beta-thromboglobulin as release marker refuted earlier data, suggesting a direct activation of platelets by shear. It is concluded that former evidence of "shear induced platelet activation" must be interpreted as the consequence of lytic damage to a small proportion of platelets.

Adenosine Diphosphate↗

[Contamination of game in Schleswig-Holstein. 2. Residues of dieldrin, heptachlor epoxide and other cyclodiene insecticides in the liver fat of hares (Lepus europaeus L.)].

Increased levels of Dieldrin (0.01-2.94 mg/kg fat, median mean = 0.38 mg/kg fat) and cis-Heptachlor Epoxide (less than 0.01-1.38 mg/kg fat, mean = 0.20 mg/kg fat) were determined by GC/ECD in liver fat of 199 hares (Lepus europaeus L.) from Schleswig-Holstein, North Germany. This investigation was carried out within the scope of a game investigation program. The dependence of these residues on endogenous and exogenous factors are discussed. Oxychlordane and trans-Nonachlor, residues of Chlordane, were also analysed in liver fat by GC/MS. The application of the cyclodiene insecticides Aldrin/Dieldrin, Heptachlor and Chlordane has been prohibited in West Germany for several years; the residues indicate the high soil persistence of these substances.

Animals↗

The prognostic value of response to the first cycle of chemotherapy in small cell lung cancer. Results of a multicenter German trial.

The prognostic significance of evaluation of response according to chest X-ray after only one cycle of treatment was investigated in patients with small cell lung cancer (SCLC). Three hundred and six patients entered a multicenter randomized German trial testing alternating vs. sequential chemotherapy. Decrease of tumor size after the first cycle was seen to be 78% in the alternating group and 70% in the sequential group. Stable disease occurred in 25% of the sequentially treated and 19% of the alternatingly treated patients. No substantial differences in pretreatment characteristics were noticed between patients with stable disease in sequential and alternating treatment. In sequential therapy, median survival was 323 days for patients with decrease of tumor size after the first cycle and 219 days for patients with no change. Only five out of 21 patients with no change after one cycle responded to continuous administration of this regimen including one complete remission. In alternating therapy, median survival was 347 days for patients with decrease in tumor size after the first cycle and 378 days for patients with no change indicating no difference in prognosis. Twelve out of 18 patients with no change responded to continuous administration of alternating treatment including six complete remissions. We concluded that response to the first cycle according to chest X-ray is a reliable and prognostically valid response criterion if sequential therapy is used. In this treatment modality no change in tumor size after the first cycle indicates poor prognosis, and improvement of the patients' outcome may be achieved by a switch to a second non-cross resistant drug combination.

Antineoplastic Combined Chemotherapy Protocols↗

Low-frequency Wiener spectra of radiographic screen-film systems.

Wiener spectra of radiographic screen-film systems were measured in the low-frequency range from 0.05 to 0.8 mm-1 with a special photometric set-up capable of scanning large film areas with a very long slit. It appears that inhomogeneities in radiographic film and film processing produce a strong low-frequency component of the Wiener spectrum below approximately 0.4 mm-1. Similar disturbances over the whole measured frequency range less than 1 mm-1 can be introduced by technologically-caused inhomogeneities in radiographic screens (low-frequency screen noise). Low-frequency film and screen noise must be considered for calculation of the detectability, especially of large low-contrast details from Wiener spectral data.

Evaluation Studies as Topic↗

Disability glare increased by hydrogel lens wear.

Decreased tolerance to glare is a common complaint in hydrogel contact lens wearers; yet, to our knowledge, the effect has never been quantified. By measuring increment thresholds as a function of background luminance and glare source location in two experimental conditions, while wearing a hydrogel contact lens correction and while wearing the spherical equivalent of their contact lens correction in a trial frame, we were able to quantify a significant contact lens-induced increase in glare-related visual disability. The effect is maximal at low background luminance levels, increases as the angle between the glare source and target decreases, and becomes lost in noise at high background luminance levels.

Adult↗

Participation and interactions of neutrophil elastase in haemostatic disorders of patients with severe infections.

The prognosis of septicaemia depends on the occurrence of complications such as shock and coagulation defects. The damage to haemostasis is usually explained by the action of the main coagulation and fibrinolysis enzymes, thrombin and plasmin. This paper presents data concerning the role of a third protease, granulocytic elastase. 82 patients who had been admitted to our hospital with suspected septicaemia were examined. Septicaemia was proven in 22 patients by the growth of microorganisms in blood cultures, and was clinically diagnosed in 9 patients. The plasma levels of neutrophil elastase-like protease complexed to a1antitrypsin (a1AT-ELP) were measured by zone immunoelectrophoresis assay (ZIA). The a1AT-ELP values were significantly increased in the 31 septic as compared to the 51 non-septic patients. In patients with complicated septicaemia, negative correlations of a1AT-ELP with factor XIII and the coagulation inhibitor antithrombin III were demonstrable. Among the patients with septic complications, the 3 who survived exhibited a dramatic decrease of a1AT-ELP, whereas in the other 16 patients who died the levels remained elevated. It might be of therapeutic significance that in 9 patients receiving fresh plasma and AT III-concentrate substitution for DIC the a1AT-ELP levels dropped, whereas they remained high in the other septicaemia patients. There were no correlations between a1AT-ELP and the a2antiplasmin-plasmin complexes (a2AP-P1), but strong correlations with signs of coagulation. The data suggest an interaction of coagulation and elastase release, probably involving the Hageman factor.

Anti-Bacterial Agents↗

[Incidence of recurrence and long-term survival in small cell bronchial carcinoma].

Analyses of relapse in small cell lung cancer (SCLC) were performed in 443 evaluable patients included in two multicenter trials. The time to first progression mainly depended on best response to therapy. Nearly all patients with no change (NC) suffered from progression within 6 months. In patients with partial remission (PR), progression occurred within 12 months in nearly all cases. If complete remission (CR) was achieved, no relapse was seen within the first 6 months after the onset of treatment. Between the 6th and 8th month a slowly increase and after the 8th month a rapid increase of relapse was noticed. In the majority of patients with limited disease relapse was localized in the area of the primary tumor, whereas in patients with extensive disease relapse mostly was due to the development of distant metastases. Of the 443 patients, 35 achieved 2-year survival (8%). Main prognostic factors for the achievement of 2-year survival were extent of disease and sex. Patients with distant metastases and CR had a poor chance of achieving a 2-year survival, while patients without distant metastases and CR had a 30% chance. Females with limited disease and a Karnofsky score of 70% or more had a 40% chance of achieving 2-year survival, the corresponding probability for males was less than 10%. Because of the high frequency of relapse in SCLC, the stabilization of best response has to be considered as a main objective in therapy. In our opinion, two different strategies may be useful in order to achieve higher 2-year survival rates: a) periodic controls and renewal of therapy as soon as possible after relapse has occurred or b) reinduction therapy in intervals of about 8 weeks or more in order to delay or prevent the development of relapse. To find out if one of these strategies is superior to the other, is one of the objectives of our new randomized trial in SCLC.

Antineoplastic Combined Chemotherapy Protocols↗

Cisplatin/etoposide versus ifosfamide/etoposide combination chemotherapy in small-cell lung cancer: a multicenter German randomized trial.

A total of 144 patients with small-cell lung cancer (SCLC) were randomized to receive cisplatin/etoposide (PE) or ifosfamide/etoposide (IE) combination chemotherapy. PE consisted of cisplatin, 80 mg/m2, intravenously (IV) on day 1, and etoposide, 150 mg/m2, IV on days 3 through 5. IE consisted of ifosfamide, 1,500 mg/m2, IV on days 1 through 5, and etoposide, 120 mg/m2, IV on days 3 through 5. Six cycles were administered in 3-week intervals. Nonresponders were switched immediately to CAV, consisting of cyclophosphamide, 600 mg/m2, IV on days 1 and 2, Adriamycin (Adria Laboratories, Columbus, OH), 50 mg/m2, IV on day 1, and vincristine, 2 mg, IV on day 1. Patients obtaining complete remission (CR) received prophylactic cranial irradiation with 30 Gy. After completion of chemotherapy, patients with limited disease received chest irradiation with 45 Gy. No maintenance therapy was given to patients in CR. Minimum follow-up was 2 years. Of the 141 patients evaluable, the overall response rate was 65% in PE therapy and 68% in IE therapy. The CR rate was 32% v 20% for all patients, 50% v 24% for limited disease, and 22% v 18% for extensive disease, all in favor of PE therapy. Median survival for all patients was 11.6 months v 9.4 months, for limited disease 14.8 months v 11.0 months, and for extensive disease 8.9 months v 7.5 months, all preferring PE therapy. The 2-year survival rate was higher in PE therapy than in IE therapy for all patients (12% v 9%) and for limited disease (23% v 10%), but not for extensive disease (5% v 9%). Median progression-free survival was 7.5 months v 6.0 months for all patients, 12.2 months v 8.8 months for limited disease, and 5.9 months v 4.4 months for extensive disease, all in favor of PE. Relapse in the area of the primary tumor was found less often after PE than after IE therapy (25% v 38%). Response to second-line CAV was seen in 30% of patients with prior PE and 43% with prior IE therapy, but was usually short lasting, and only one patient achieved CR. Toxicity included three lethal complications. Nausea, vomiting, diarrhea, and skin lesions occurred more often after PE than after IE therapy. These results suggest that PE is superior to IE chemotherapy in limited-stage, but not in extensive-stage SCLC, and that CAV is cross-resistant to PE, as well as to IE in the majority of patients.

Adult↗

Randomized, double-blind, cross-over study comparing prochlorperazine and lorazepam with high-dose metoclopramide and lorazepam for the control of emesis in patients receiving cytotoxic chemotherapy.

To further define optimal combinations of antiemetics, high-dose metoclopramide and lorazepam (M+L) were compared with prochlorperazine and lorazepam (P+L) in a randomized, double-blind, cross-over study. Both patient and observer assessments were documented in 66 patients receiving cisplatin and noncisplatin chemotherapy. M+L significantly reduced the severity of vomiting (P = 0.01), duration of vomiting (P = 0.05), and number of vomiting episodes (P = 0.003). Comparing the severity or duration of nausea, M+L and P+L were not significantly different. M+L significantly reduced severity of vomiting (P = 0.005) and number of vomiting episodes (P = 0.03) in the cisplatin subset. The number of vomiting episodes was also reduced in the noncisplatin subset (P = 0.03). When asked to nominate a preferred regimen, 41% of patients preferred P+L, 35% preferred M+L, and 24% rated them equally. M+L was associated with significantly more anxiety and less sedation than P+L. Patient assessments produced similar results to observer assessments but gave a broader understanding of our patients' tolerance to chemotherapy. M+L is a superior regimen in controlling vomiting induced by chemotherapy.

Adult↗