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Biomedical subjects

M Mentzel

Publications and source records attributed to M Mentzel.

At least 37 records · Page 2Linked to original sources

The effectiveness of ADCON-T/N, a new anti-adhesion barrier gel, in fresh divisions of the flexor tendons in Zone II.

In a prospective randomized clinical trial, ADCON-T/N was investigated with regard to its effectiveness in fresh traumatic injuries of the flexor tendons in Zone II of the hand. Thirty patients participated in the trial. Following a standardized technique of tendon repair, the total active motion (TAM) and total extension lag (TEL) were determined after 12 weeks and evaluated according to the Buck-Gramcko score. Excellent results were achieved in 15 out of 16 patients in the ADCON-T/N group and 12 out of 14 in the control group. However, no statistically significant difference was found between the mean TAM and TEL in the two groups.

Administration, Topical↗

[DIGITOS-prosthesis for the proximal interphalangeal joint. A 2-year follow-up].

The treatment of osteoarthrosis of the proximal interphalangeal joint by prosthesis bears several specific problems. With the DIGITOS-prosthesis a new implant is now available. It is a cemented modular hinged prosthesis. We report our experiences with this implant from a prospective clinical trial. Seven patients with osteoarthrosis of the proximal interphalangeal joint had ten prosthetic middle joint replacements performed with DIGITOS-prostheses. Over an observation period of two years, the functional results were found to be good. The mean preoperative range of motion in the affected joints was 51.5 degrees. Three months after surgery, this had improved to 60.5 degrees, but then decreased to 53.0 degrees after one year and to 49.5 degrees, i.e. the original range of motion, by the end of the second postoperative year. No implant became loose. Nearly all patients were free from pain. The only serious complication was an iatrogenic lesion of the middle slip of the extensor aponeurosis resulting in a buttonhole deformity. In spite of these encouraging two-year results, the further follow-up has to be observed carefully.

Aged↗

Dynamic treatment of displaced proximal phalangeal fractures.

We report a splint system for a protected mobilization program (termed dynamic treatment) of proximal phalangeal fractures. This program can be used for nonoperative treatment or after operative treatment. Intra-articular fractures of the proximal phalanx at the metacarpophalangeal joint were included. The custom-molded 2-component thermoplastic splint allows motion of the proximal and distal interphalangeal joints. It was developed to allow bone healing and recovery of motion at the same time. We evaluated the clinical and radiologic results of a consecutive series of 48 displaced proximal phalangeal fractures in 45 patients who received dynamic treatment. Fracture consolidation was achieved in all patients and bone healing and recovery of full active motion was achieved simultaneously in all but 4 patients by 6 weeks. The advantage of this splint system is the variability of its application. The splint can be used both for nonsurgical and surgical management. It can be removed to change dressings and for radiologic evaluations. The period of dynamic treatment can be determined individually in each case.

Adult↗

Optimization of chemotherapy administration for clinical 41.8 degrees C whole body hyperthermia.

Preclinical data is consistent with the concept that the timing of chemotherapy during radiant heat-whole body hyperthermia (WBH) should affect therapeutic index. In order to test this hypothesis, a controlled clinical investigation was initiated. Patients received carboplatin (CBDCA) on an early or late schedule with respect to achieving target temperature (i.e. 41.8 degrees C) in alternating treatment cycles. The first cycle was randomized between patients regarding the early or late schedule for two planned sets per patient (i.e. four cycles). Ifosfamide, etoposide and granulocyte colony stimulating factor were delivered during all cycles with a standardized schedule. A total of 53 cycles involving 17 patients were analyzed. Detailed toxicity evaluation (i.e. delay in therapy secondary to thrombocytopenia, need for platelet transfusions, and days of hospitalization) taken collectively demonstrated a statistically and clinically significant advantage to delivering CBDCA 10 min after target temperature, during the plateau phase of WBH.

Antineoplastic Combined Chemotherapy Protocols↗

[Acetabular fractures in elderly persons. Primary endoprosthetic treatment].

In the Department of Traumatology at the University of Ulm, 26 elderly patients with displaced acetabular fractures were treated with primary implantation of a hip joint endoprosthesis between 1986 and 1996. The principles of operative therapy are stabilization of the acetabular ring, grafting of acetabular defects with autogenous corticocancellous bone and cranial buttressing with a reinforcing ring. This concept permits immediate mobilization of elderly patients and full weight-bearing and thus results in favorable early postoperative results. Secondary complications typically caused by immobilization can therefore be avoided.

Acetabulum↗

Ifosfamide, carboplatin and etoposide (ICE) combined with 41.8 degrees C whole body hyperthermia in patients with refractory sarcoma.

Two earlier studies resulted in the design of a phase II trial of 41.8 degrees C (x 60 min) extracorporeal whole body hyperthermia (WBH) with ICE, i.e. ifosfamide (5 g/m2), carboplatin (300 mg/m2), and etoposide given with WBH, as well as, day 2 and 3 post-WBH (100 mg/m2) for adult patients with refractory sarcoma. 12 patients entered this trial; all were evaluable. 8 patients had a history of prior chemotherapy associated with disease progression. Following WBH/ICE, 7 partial remissions were observed (58%); 3 patients experienced disease stabilisation; the aforementioned 10 patients each received four cycles of therapy. 2 patients exhibited progressive disease. Episodes of WHO graded (grade 3; grade 4) toxicity observed included: anaemia (2;2); leucopenia (5;7); thrombocytopenia (1;6); renal (0;1). Other toxicities (grade 1 and 2) included: anasarca, diarrhoea, ventricular arrhythmias, pressure sores, and perioral herpes simplex.

Adolescent↗

Treatment with the anti-tumor drugs, cis-platin and mafosfamide, does not affect the structure of prekinetochores in a human breast cancer cell line. An immunofluorescence study using human anti-centromere autoantibodies.

The goal of the present article was to determine whether a nuclear parameter, centromere structure of interphase cells, could serve as an indicator to assess cellular damage caused by anti-tumor drugs. These were cis-platin and mafosfamide, which are widely used for the management of solid tumors. To visualize the centromeres, we probed treated and untreated cells of a human breast cancer cell line, MX-1, with a human anti-centromere serum. The serum was obtained from a scleroderma patient and detects antigens associated with prekinetochores of the decondensed chromosomes. The DNA was simultaneously displayed by a specific fluorescent dye. The cells were grown on coverslips, incubated for 1 h in a drug-containing medium, transferred into a drug-free medium and observed 24 h later. Since the efficiency of many anti-tumor drugs increases with the temperature, two different temperatures, 37 and 42 degrees C, were used. The analysis revealed that the treatment did not visibly alter the labeling pattern. We conclude that chromosome structure remains largely intact and is not suitable for the cytological evaluation of the efficiency of anti-tumor drugs. This is in contrast with, for example, the microtubular cytoskeleton and mitochondria, which were extensively damaged under the conditions applied here (compare Wolf et al. 1995). Independent of the drug and the temperature selected, the nuclear lumen of mononucleated and multinucleated cells contained small fluorescent spots. Double dots corresponding to the sister centromeres in the G2 phase of the cell cycle were rare. In addition to the voluminous nuclei, some cells possessed micronuclei in the lateral cytoplasm and these were regularly labeled by the autoantibodies. A small subset of the mononucleated MX-1 cells had unusually large nuclei. It is reasonable to assume that they are polyploid. The fluorescent spots marking the prekinetochores were very large in these cells. This may indicate that the chromosomes remain associated after replication.

Antineoplastic Agents↗

DNA-containing cytoplasmic bridges in a human breast cancer cell line, MX-1: morphological markers of a highly mobile cell type?

We have used a CREST anti-centromere serum and a DNA-specific fluorescent dye to study the composition of extended cytoplasmic bridges between interphase cells of a human carcinoma cell line, MX-1, grown on coverslips. Under natural conditions, approximately 8% of the cells possessed cytoplasmic bridges up to 60 microns long. Elongated extensions from the cell surface were also observed and were interpreted as severed cytoplasmic bridges. The bridges were extremely slender throughout most of their lengths and could not be properly resolved by phase-contrast microscopy. Staining with a DNA-specific fluorescent dye revealed, however, the presence of a thin DNA thread. This finding strongly suggests that the bridges arise during mitosis through faults in chromosome segregation. The bridges persist and most probably elongate, when the cells separate from one another after completion of mitosis. Some bridges showed also highly fluorescent DNA masses, which were detected by a CREST anti-centromere serum. Thus, a subset of the cytoplasmic bridges contained centromeres. The DNA-containing bridges between carcinoma cells in culture signal continuous rearrangements of the karyotype at a relatively high rate. The presence of extended cytoplasmic bridges between the cells could be a morphological marker for highly mobile tumor cell types and has, therefore, diagnostic value.

Adult↗

The morphology of xenotransplanted human breast carcinoma MX-1 growing in nude mice. A light and transmission electron microscopic study.

The present investigation is concerned with the morphological features of the human breast carcinoma MX-1, transplanted subcutaneously into nude mice. Three weeks after transplantation the tumor tissue is clearly distinct from the dermis. Solid tumor cell groups are separated incompletely by thin connective tissue septa, giving rise to a lobular appearance. The tumor cells are characterized by very irregularly formed nuclei with three or more nucleoli. The cytoplasm of these cells displays some lysosomes, the cisternae of the rough endoplasmic reticulum, mitochondria and a variable number of ribosomes. The Golgi fields are frequently observed, particularly near the nucleus. The cells are connected to each other by desmosomes, which also persist during mitotic activity. Ductular formations can occasionally be seen. The ultrastructure of the blood vessels discloses the morphological features necessary for the regulation of blood flow. Capillaries present a sinusoidal aspect with distended and narrow lumina. Interruptions of the endothelial wall, however, were not observed. This morphological appearance was found in all the MX-1 tumors investigated, reflecting the stable growth of this tumor cell line in nude mice.

Animals↗

Ifosfamide and carboplatin combined with 41.8 degrees C whole-body hyperthermia in patients with refractory sarcoma and malignant teratoma.

The purpose of this study was to evaluate the pharmacokinetics, biological interactions, and toxicities of ifosfamide and carboplatin combined with 41.8 degrees C whole-body hyperthermia (WBH) for 1 h in a pilot clinical study. Nineteen patients with refractory sarcoma or malignant teratoma were treated. To obtain baseline pharmacokinetic data for ifosfamide, the first chemotherapy course was given without WBH in six patients. This enabled comparison of systemic toxicity and pharmacokinetics of the drug combination with and without WBH (+/- WBH). All other patients received three thermochemotherapy treatments every 3 weeks. Ifosfamide was escalated from 5 to 10 g/m2 with a fixed carboplatin dose of 480 mg/m2. WBH was induced by extracorporally heated blood (in a hemodialysis apparatus) with general anesthesia. The drugs were given at target temperature. A total of 49 thermochemotherapy treatments was administered. The use of the hemodialysis device resulted in an approximate one-third reduction of blood concentrations of 4-hydroxyifosfamide, one activated intermediate metabolite of ifosfamide and carboplatin, but in an increase of chloroacetaldehyde, the other main ifosfamide metabolite. The WBC counts and the platelet nadirs (up to WBH grade 4) were not significantly different +/- WBH. Of 19 evaluable patients, 7 partial remissions, 8 disease stabilizations (average duration, 3 months), and 4 patients with progressive disease were observed. There was no WBH-related mortality. Toxicities observed included mild (anasarca, diarrhea, pressure sores, and perioral herpes simplex) and severe (reversible neuropathy, cardiopulmonary distress, and severe renal dysfunction). No hepatic or central nervous system toxicity occurred. Nephropathy was the dose-limiting toxicity. In conclusion, ifosfamide and carboplatin can be administered with extracorporally induced WBH with acceptable toxicity. Results obtained are consistent with continued evaluation of this combined modality approach.

Adolescent↗

The effect of ifosfamide on tumor oxygenation at different temperatures.

In MX1 human breast cancer xenografts grown on the hind paw of thymusaplastic nude mice the effect of ifosfamide on tumor oxygenation, tumor pH and the concentration of lactic acid have been determined at mean tumor temperatures of 32 degrees C, 37 degrees C and 41 degrees C. For histological studies tumors were shock-frozen or fixed with formalin or glutaraldehyde. Treatment with Ifosfamide (250 mg/kg b.w.) reduced intratumoral laser Doppler flow, oxygenation and pH. This suggests that ifosfamide or its metabolites may have an effect on tumor vasculature.

Animals↗

Effects of temperature on the therapeutic efficacy and pharmacokinetics of ifosfamide.

The influence of tumor temperature (28, 32, 37, 39, 41, or 43 degrees C for 1 h) on the therapeutic efficacy of i.v. single bolus injections of ifosfamide (IFO) (32, 65, 125, or 250 mg/kg body weight) in human tumor xenografts (MX1 breast carcinoma) grown in nude mice (n = 240) was studied. Tumor temperature was controlled by water bath immersion. Sixty days after treatment the percentage of tumor-free survival was determined. For example, at 37 degrees C IFO in a dose of 65 mg/kg body weight led to 10% tumor-free survival in the treated animals. At 43 degrees C the same dose resulted in 60% tumor-free survival. A clear drug dose- and temperature-dependent increase of the therapeutic efficacy of an active oxazaphosphorine compound was also demonstrated in vitro. The concentrations of IFO and of 4-hydroxyifosfamide in blood and tumors at different body temperatures (controlled by water bath immersion) were determined over 120 min and WBC counts were obtained. The half-lives and the areas under the curve for IFO in blood were not significantly different at 37 degrees C and 41 degrees C. Since the half-life of IFO depends mainly on hepatic metabolism, the similarity of half-lives and of areas under the curve for IFO at 37 degrees C and 41 degrees C indicates a constant activation rate. However, significantly lower plasma concentrations of the activated drug at a liver (body) temperature of 41 degrees C, compared with 37 degrees C, were found, indicating a higher elimination rate. The concentration of the activated drug in the tumors within the initial 60 min at 41 degrees C, however, exceeded by > 2-fold that at 37 degrees C. The bone marrow toxicity of the same drug dose did not significantly increase with body temperature.

Animals↗