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Biomedical subjects

M Lehnert

Publications and source records attributed to M Lehnert.

At least 55 records · Page 3Linked to original sources
PubMed1993

Sinus histiocytosis with massive lymphadenopathy. Skeletal involvement.

A 64-year-old female patient has been suffering from sinus histiocytosis with massive lymphadenopathy (SHML) for 2 years. After 12 months of illness, the patient developed swelling and pain in various skeletal regions. Scintigraphic, radiological and CT imaging revealed multiple osseous lesions. Subsequent biopsies yielded the histomorphological findings typical for SHML. After operative resection of the left cuboid, which was the most painful region during walking, the defect was filled with an autologous bone transplant. At this time no other osteolytic region was treated surgically, because the patient had first to undergo ENT treatment.

Bone Diseases↗
PubMed1993

Chemohormonal and immunohormonal approaches in advanced prostatic carcinoma.

The standard palliative treatment for patients with advanced prostate cancer has for the past 50 years been androgen withdrawal. However, owing to the presence of hormone-insensitive cell clones, the benefits of this approach have now appeared to reach their optimum. It is now generally believed that further major therapeutic advances in the treatment of prostate cancer are unlikely, unless consideration is given to these hormonally independent cells. Two possible alternative strategies which address this problem are chemohormonal and immunohormonal approaches, both of which are discussed in detail in this article.

Androgen Antagonists↗
PubMed1993

In vitro evaluation of chemosensitizers for clinical reversal of P-glycoprotein-associated Taxol resistance.

The purpose of this study was to estimate the potential usefulness of currently available chemosensitizers (CS) for clinical reversal of P-glycoprotein-mediated Taxol resistance. The 8226/DOX6 human myeloma cells were used to evaluate CS effects in serum-rich medium by means of the human tumor cloning assay. The 8226/DOX6 cells express low levels of P-glycoprotein as typically found in clinical cancer specimens and are approximately 40-fold resistant to Taxol when continuously exposed to the drug in serum-rich medium. The CS were used at maximum tolerated plasma levels (Cmax) and at the concentrations achieved in human plasma by oral administration (Coral). Of nine CS tested, cyclosporine A (CSA), verapamil (VER), quinidine (QD), and quinine (Q) were able to overcome Taxol resistance. QD and Q were effective at Coral, whereas CSA and VER required Cmax to significantly enhance Taxol cytotoxicity. The most potent agent was CSA, which increased sensitivity to Taxol by 8-, 12-, and 18-fold when used at concentrations of 1.0, 2.0, and 4.0 microM, respectively. At 5.0 microM, CSA was capable of fully normalizing Taxol sensitivity. On the basis of these data, infusional CSA might prove useful for clinical reversal of P-glycoprotein-associated Taxol resistance. It remains to be seen, however, whether the CSA concentrations needed to reverse Taxol resistance effectively can be safely achieved in human plasma when CSA is coadministered with Taxol.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

[Free vascularized bone transplantation].

A report is presented on 4 years of experience with free vascularized bone transplants for extremity preservation and the postoperative management developed in this connection. The successful results so far were achieved not least by virtue of a strict unified postoperative treatment scheme extending from direct postoperative blood-flow monitoring through the raising of a skin flap and angiographic control of anastomosis patency to immobilization/mobilization and orthotic management. Thus far, 33 patients have been treated with free vascularized bone transplants (20 fibula, 13 iliac crest grafts).

Angiography↗
PubMed1993

[Sensory recovery after finger replantation].

Criteria for digital replantation is not only revascularization the prerequisite for success, but above all functional recovery of sensibility. In cases of digital replantation, it is necessary to pay special attention to the technical details of nerve repair, for recovery of tactile gnosis. 202 patients with 247 digital amputations were successfully replanted. 138 patients with 172 successfully replanted fingers and 302 digital nerve reconstructions returned for follow-up evaluations. Our aim was to determine the level of sensory recovery depending on the Highet (1954) sensory recovery scheme. Nerve reconstruction was divided into three groups: primary nerve repair, primary nerve grafting, and secondary nerve grafting. 69.4% primary nerve coaptations, 58.3% primary nerve grafting, and 61.9% secondary nerve grafting reached S3 to S4. Most of the replanted fingers regained useful 2PD with S3+. Factors that influenced digital sensibility following replantation including level and mechanism of injury, length of the nerve grafts, cold intolerance, and patient's age are finally discussed in detail.

Adolescent↗
PubMed1992

VIP21, a 21-kD membrane protein is an integral component of trans-Golgi-network-derived transport vesicles.

In simple epithelial cells, apical and basolateral proteins are sorted into separate vesicular carriers before delivery to the appropriate plasma membrane domains. To dissect the putative sorting machinery, we have solubilized Golgi-derived transport vesicles with the detergent CHAPS and shown that an apical marker, influenza haemagglutinin (HA), formed a large complex together with several integral membrane proteins. Remarkably, a similar set of CHAPS-insoluble proteins was found after solubilization of a total cellular membrane fraction. This allowed the cloning of a cDNA encoding one protein of this complex, VIP21 (Vesicular Integral-membrane Protein of 21 kD). The transiently expressed protein appeared on the Golgi-apparatus, the plasma membrane and vesicular structures. We propose that VIP21 is a component of the molecular machinery of vesicular transport.

Amino Acid Sequence↗
PubMed1991

Multidrug-resistant myeloma: laboratory and clinical effects of verapamil as a chemosensitizer.

Verapamil was evaluated as a chemosensitizer for reversing multidrug resistance in multiple myeloma both in vitro and in clinical trials. Bone marrows from 59 myeloma patients in relapse were evaluated for several resistance parameters: expression of p-glycoprotein (MDR1), doxorubicin (Adriamycin) and vincristine sensitivity, and the ability of added verapamil to reduce resistance to the cytotoxic agents. We found that verapamil was capable of sensitizing myeloma cells that exhibited resistance to doxorubicin and vincristine in vitro, but did not enhance sensitivity of cells that were drug sensitive (P less than .001). Myeloma cells expressing MDR1 immunohistochemically tended to be more doxorubicin resistant in vitro than MDR1-negative cells. In the clinical trials, 22 patients with myeloma refractory to vincristine-Adriamycin-dexamethasone (VAD) were treated with VAD plus high-dose intravenous verapamil (Ve). Among the 22 patients treated with VAD/Ve, five achieved a partial remission (23%). The median relapse-free survival for the VAD/Ve responders was 5.4 months and their overall survival from the start of VAD/Ve was better than that of the nonresponders. Among the subset of 10 patients whose myeloma cells were MDR1 positive, four responded clinically (40%), whereas none of five patients with MDR1-negative myeloma cells achieved remission with VAD/Ve. We also observed that myeloma cells from three of four VAD/Ve clinical responders exhibited in vitro chemosensitization with verapamil, whereas in vitro verapamil chemosensitization was seen in only one of six clinical nonresponders. Our observations demonstrate that clinical reversal of multidrug resistance can be achieved in some patients with VAD-refractory myeloma with the use of verapamil. In addition to their value in drug development, in vitro tests of MDR1 expression and of chemosensitizers plus cytotoxic drugs on the patients' bone marrow myeloma cells may identify patients who will respond clinically to chemosensitizer-containing regimens. We anticipate that chemosensitizer regimens capable of inhibiting multidrug resistance will play an increasing role in the treatment of hematologic malignancies, including B-cell neoplasms such as multiple myeloma and the non-Hodgkin's lymphomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Synergistic inhibition by verapamil and quinine of P-glycoprotein-mediated multidrug resistance in a human myeloma cell line model.

In an effort to develop a clinically useful approach to overcoming P-glycoprotein-mediated multidrug resistance (MDR1), we evaluated combined chemosensitization with verapamil and quinine in a multidrug-resistant (MDR) human myeloma cell line model. In clonogenic assay, verapamil was used at concentrations from 0.1 to 1.0 micrograms/mL, bracketing the plasma levels achieved by oral administration and high-dose intravenous (IV) infusion, respectively. The dose of quinine was held constant at 1.0 micrograms/mL, a plasma concentration readily achieved by oral administration. At each dose level of verapamil tested, the combination with quinine proved more effective than either drug individually in reversing resistance to doxorubicin and vinblastine and synergistic chemosensitizing interaction was observed. Verapamil at 0.1 microgram/mL combined with quinine was capable of restoring sensitivity to doxorubicin fully and reduced resistance to vinblastine as effectively as verapamil alone at 1.0 micrograms/mL. Furthermore, the combination of 1.0 mumol verapamil with 10 mumols quinine increased accumulation and retention of anthracycline in the resistant cells to a greater extent than did either drug individually (P less than .001) and inhibited drug efflux as effectively as verapamil alone at 10 mumols. Our findings suggest that combined chemosensitization with verapamil and quinine may prove useful for overcoming MDR1 in patients with drug-refractory B-cell neoplasms such as multiple myeloma or non-Hodgkin's lymphomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

[Whipple's disease: abdominal lymphoma, intermittent fever and recurrent arthralgias].

A diagnostic laparotomy was performed on a 41-year old woman who, having suffered from recurrent arthralgias for several years and intermittent fever for many months, was found to have extensive enlargement of abdominal lymph-nodes, raising the suspicion of malignant lymphoma. Frozen-tissue biopsy was highly suspicious of Hodgkin's lymphoma, but light- and electron-microscopy revealed Whipple's disease, confirmed in an endoscopically obtained duodenal mucosal biopsy. The arthralgia quickly responded to antibiotic treatment. This case demonstrates the potential difficulties and errors in the diagnosis of Whipple's disease.

Abdominal Neoplasms↗
PubMed1989

[Factors modifying remission in cytostatic chemotherapy of squamous cell carcinoma recurrence in the area of the head and neck].

From 1981 to 1986 eighty-five patients underwent palliative chemotherapeutic treatment at the E.N.T. Department of the University Hospital in Graz. In seventy-three recurrent tumours comparable RR were achieved with ADM/CDDP as well as with MTX/5-FU. In 39 patients a second treatment after failure or relapse of previous therapy was applied, containing predominantly CDDP/BLM resulting in a RR of 18%. The tumour stage proved to be the single most important factor concerning response to treatment in first as well as second line chemotherapy. Stage IV tumours showed a significantly lower RR compared to neoplasms without large neck masses (stages II, III), the RR being 59% versus 19% (p = 0.01). Furthermore, performance status, preceding therapeutical modalities, and location of the tumours were shown to be of secondary prognostic importance. In the latter group, age and the time interval between recurrences appeared to be of no significance. To evaluate the most effective regimen, highly differentiated analysis of all available data is imperative.

Aged↗
PubMed1989

Vindesine-epirubicin versus vindesine-mitoxantrone in metastatic breast cancer.

UNLABELLED: The present study was designed to assess the toxicity and efficacy of two chemotherapy protocols in patients with metastatic breast cancer. Starting in December 1985, 230 patients were randomized to receive vindesine (V) (3 mg/m2 i.v.) and mitoxantrone (M) (10 mg/m2 i.v.) or V and epirubicin (E) (40 mg/m2 i.v.) every 3 weeks x 3 and every 4 weeks thereafter. Patients were stratified according to site of disease (visceral, bone or soft tissue dominant) and prior therapy. Patient groups were comparable with respect to menopausal status, age, estrogen receptor status and disease-free interval. About two-thirds of the patients presented with visceral recurrence and 30% with bone lesions: only 8% had soft tissue metastases. RESULTS: We observed a significant difference (p = 0.003) in the frequency of alopecia (WHO grade 3-4, 36% vs. 60% favoring regimen VM); gastrointestinal and hematologic side effects and neurotoxicity were mild and similar for both groups. In 182 evaluable patients there was a 26% response rate (CR + PR. UICC criteria) for VM and 35% for VE (not significant). NC was observed in 37% and 43% of patients treated with VM or VE respectively. There was no significant difference between these two groups with regard to time to progression and survival. The median time of follow-up was 8 months and therefore too short to draw definite conclusions. Both regimens were well tolerated and seem to be equally effective, although the response rate for VM and VE was lower than expected.

Adult↗
PubMed1989

Efficacy of adjuvant carboplatin-epirubicin chemotherapy in advanced ovarian cancer after radical surgery.

Postoperatively, 13 patients with stage III ovarian cancer received a combination of carboplatin and epirubicin (PE) at 300 and 60 mg/m2 respectively. The results of the 13 patients receiving the PE regimen were retrospectively compared to those of 24 patients who received the conventional PAC schedule (cisplatin, Adriamycin and cyclophosphamide at a dosage of 50, 50 and 750 mg/m2, respectively). All 37 patients had undergone radical debulking surgery including pelvic and paraaortic lymphadenectomy. At 8 months, relapse-free rates of 42.2 and 79.2% were observed in the PE and PAC groups, respectively. This difference was highly significant (p = 0.011). The data suggest that the PE combination has less antineoplastic activity than the PAC schedule and thus cannot be recommended in the adjuvant treatment of advanced ovarian cancer.

Adult↗
PubMed1988

[Computer-assisted diagnosis of bone tumors and tumor-like skeletal diseases: critical evaluation of its clinical use].

Thirty-four patients with bone tumours and tumour-like abnormalities of the skeleton, of varying ages, were examined by a computer-aided diagnostic program; the accuracy, clinical usefulness and specific advantages and disadvantages of the program have been evaluated. This was done by two statistical methods, both with showed high accuracy and reliability of the system (97% and 88.2%). In addition to the diagnostic results, the growth rate of the lesion could be estimated. This indicates the biological behaviour of the tumour independently of the histological diagnosis.

Bone Neoplasms↗
PubMed1988

Vindesine-mitoxantrone (VM) versus vindesine-4'-epidoxorubicin (VE) in metastatic breast cancer: a prospective randomized trial.

182 patients with metastatic breast cancer were randomized to V (mg/m2 i.v.) and M (10 mg/m2 i.v.) or E (40 mg/m2 i.v.) every 3 weeks x 3 and then every 4 weeks; they were stratified by sites of disease (visceral, bone, or soft-tissue dominant) and by prior chemotherapy. In a preliminary analysis there is a significant difference regarding frequency of alopecia (WHO Grade 3 or 4) favoring regimen VM; gastrointestinal, hematologic and neurotoxic side effects were mild and similar for both groups. Of 114 evaluable women there is a response rate (CR + PR) of 26% and 34% for VM and VE respectively (n.s.), and there is no significant difference between the 2 groups in time to progression and survival. Both regimens are well tolerated and seem to be equally effective. The median follow-up time is too short to draw final conclusions.

Antineoplastic Combined Chemotherapy Protocols↗