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Biomedical subjects

M Falk

Publications and source records attributed to M Falk.

At least 91 records · Page 5Linked to original sources

[Preparation of a cytostatic-containing bone cement].

Local application of cytostatic during therapy of tumors in bones is desirable. In these cases the drugs had to be incorporated in bone glue. Liberation, stability and side-effects have been estimated using methotrexate and doxorubicin (Adriblastin) in vitro. The liberation were determined in combination with auxiliary substances and even solidity of the bone glue was maintained.

Antineoplastic Agents↗

Radiofrequency hyperthermia as adjuvant therapy following surgical resection of an experimental malignant neoplasm.

Local recurrence after radical surgery is a major problem with many primary solid cancers. The use of radiofrequency hyperthermia (RFHT) as adjuvant therapy to surgery was explored in the Fischer bladder carcinoma (FBCa)/F344 rat tumor system. After subcutaneous innoculation of 34 rats with 10(6) FBCa cells in suspension, RFHT was administered to 17 animals on days 1, 5, 8, and 12. The development of palpable tumors was delayed but not prevented, and tumor growth was retarded in RFHT-treated animals. In another experiment 40 rats were innoculated by subcutaneous trocar injection with a 1 mm3 piece of FBCa. After tumor excision on day 17, adjuvant therapy (untreated control, mitomycin C, RFHT, or RFHT plus mitomycin C) was started on day 20 (10 rats/treatment). The 20 RFHT-treated rats had only 1 incisional recurrence as compared to 9 recurrences in sham-heated rats (P less than 0.005). The authors conclude that RFHT has considerable value as adjuvant therapy to surgery in these tumors. Additional studies of RFHT as adjuvant treatment after surgical excision of tumors are planned.

Animals↗

Further experience with regional radiofrequency hyperthermia and cytotoxic chemotherapy for unresectable hepatic neoplasia.

The authors report on 178 patients with unresectable hepatic tumors who have been treated with 1 to 25 (median, 6) courses of radiofrequency hyperthermia (RFHT) and chemotherapy. In 137 patients, the hepatic tumors consisted of metastases from colorectal adenocarcinomas. For patients who had no previous therapy and who had colorectal metastases with no extraheptic disease, cumulative survival at 52 weeks' follow-up was 80.5% and partial tumor regression was seen in 78.4%. Among the 69 patients who previously had conventional treatment for their hepatic disease, partial regression was seen in 43.5%. We are no longer monitoring tumor core temperature routinely, as the invasive methods currently in use yield irreproducible results; the risks to the patient cannot be justified in view of the questionable relevance of the data obtained. A prospective randomized study of systemic chemotherapy with or without RFHT in patients with colorectal hepatic metastases is in progress.

Adenocarcinoma↗

Ethanol intoxication stimulates lipolysis in isolated Golgi complex secretory vesicle fraction from rat liver.

Ethanol (0.6 g/100 g) was administered orally to rats by means of an intragastric tube. This caused an accumulation of secretory vesicles laden with VLDL particles which were seen 90 min after administration and later disappeared. Lysosomes and Golgi complex secretory vesicle (GCSV) fractions were isolated. The proteolytic and lipolytic activities of these fractions were measured in order to assess their possible role in the elimination of the initially retained secretory material. There was no change in proteolysis neither in lysosomes or in the GCSV-fraction from ethanol-intoxicated rats when measured by the release of degradation products during incubation. Similarly, the activities of acid hydrolases were unaffected by acute ethanol intoxication. On the other hand, lipolysis increased by some 50-100% in the GCSV fraction, whereas the lysosomes displayed unchanged lipolytic levels compared with controls. Ultrastructurally, the GCSV-fraction from ethanol-intoxicated rat livers showed signs of disintegrated VLDL particles. It is concluded that acute ethanol intoxication causes an increase in lipolysis but not in proteolysis in the operationally defined GCSV fraction. Since triacylglycerol lipase activities did not change in the GCSV fraction, increased amounts of substrate seem to cause the enhanced lipolysis observed.

Alcoholic Intoxication↗

Enhanced survival in antibiotic-treated murine fecal peritonitis by administration of copovithane, a selective immunostimulative polymer.

The purpose of this study was to determine the effect of an immunostimulative polymer, Copovithane (Cpv), plus antibiotics (netilmicin and clindamycin) in a murine model of fecal peritonitis. Cpv augments humoral immunity with little effect on T cells and is nontoxic. Cpv 100 mg/kg iv administered at the onset of sepsis increased median survival time (MST) by 40-55% over untreated controls. Four experiments were performed. Cpv in combination with antibiotics when given at the time of onset of sepsis was significantly more effective than antibiotics alone (MST 235 vs 105 hr, P less than 0.05 at 144, 168, 192, 216 hr). In the second and third experiments Cpv alone and with antibiotics was administered 15 hr after the onset of sepsis. Cpv significantly augmented survival over controls in the second experiment (MST 87 vs 60 hr, P less than 0.025 at 96 hr). Cpv plus antibiotics was significantly better than antibiotics alone in the third experiment (MST 111 vs 64 hr, P less than 0.05 at 72 hr, P less than 0.005 at 120 hr). In the final experiment, Cpv did not inhibit growth of 20 bacterial species in agar and liquid media. Cpv significantly enhances survival in murine fecal peritonitis even when administered after the onset of sepsis; furthermore Cpv plus antibiotics in established peritonitis produces longer survival than antibiotics alone. Synthetic immunomodulators such as Cpv could eventually play a significant role in the management of peritoneal infection in humans.

Animals↗

Reversal of cyclosporine-induced mortality with a synthetic polymeric immunostimulant in a murine model of fecal peritonitis.

We have been investigating the effects of a synthetic immunostimulative polymer known as copovithane (Cpv). This agent appears to enhance humoral immunity in untreated and cyclosporine-immunosuppressed mice and is nontoxic in rodents and man. The purpose of this study was to determine whether cyclosporine (CsA) is deleterious to survival in a murine cecal ligation, puncture, and excision (CLPE) model of fecal peritonitis, and--if so--whether this effect could be ameliorated by Cpv without interfering with skin allograft acceptance. Cpv significantly prolongs survival in the CLPE model; the optimal dose for this effect was found to be 100 mg/kg. CsA was found to have a significant and deleterious effect on survival at several dosage levels when administrated 48 and 24 hr before cecal ligation, and immediately before and 16 hr after cecal ligation. Using a dose of CsA sufficient for skin allograft acceptance and the same schedule of administration outlined above, Cpv 100 mg/kg was administered 48 hr prior to cecal ligation. Mice treated with CsA plus Cpv had significantly longer survival than mice treated with CsA alone; furthermore, the survival of CsA-plus-Cpv-treated animals was not significantly different from that of saline-treated controls. Acceptance and survival of H-2 incompatible skin allografts in mice treated with CsA were not affected by Cpv 100 mg/kg/week. We conclude that CsA-induced mortality in the CLPE model can be abrogated by Cpv without adversely affecting skin allograft survival. It may eventually be possible to reduce the incidence of septic complications in clinical allotransplantation by prophylactically administering Cpv to patients on CsA immunosuppression.

Animals↗

Phenotypic and genotypic analysis of Hodgkin's disease derived cell lines: histopathological and clinical implications.

Five Hodgkin's disease (HD) derived cell lines were established in vitro in our laboratory in the last seven years. Morphological, cytochemical, immunological and cytogenetic marker analysis demonstrated that the in vitro cells represent genotypically and phenotypically the in vivo Hodgkin (H) and Sternberg-Reed (SR) cells in biopsy specimens. The cultured cells resemble haematolymphoid cells at different stages of maturation. Four of the five continue to grow in vitro as suspension cells after more than 50 months. Four more in vitro HD-derived lines were described recently by several authors. A summary of the various marker characteristics of these in vitro lines is given as a synopsis of the phenotypic marker spectrum and is discussed in comparison with our own cell lines. There is a striking similarity between two of the newly established lines (CO, HDLM-2) and our lines whereas the two other in vitro established cultures seem to resemble cell species further along the line of maturation to B lymphocytes (DEV) and monocytes (SU-HD-1). Gene rearrangement experiments undertaken with the L428, L540, L591 and the CO cell line show that the L428 and 591 cells have undergone gene rearrangement, the L428 being compatible with the genotypic state of a pre-B cell; the L591 cells, similarly rearranged furthermore demonstrated functional light chain rearrangement, compatible with B-cell development. By cytogenetic analysis chromosome 7 was found to be affected in all our described lines. This chromosome appears to be particularly unstable and vulnerable in patients with HD, since all tested cell lines revealed multiple abnormalities of this chromosome, a finding which is in accordance with observations made by other investigators in HD-biopsy cells. Since similar structural changes or loss of chromosome 7 is a characteristic event in cases of secondary acute non-lymphocytic leukaemia, it is speculated that this form of secondary neoplasia could resemble the blast crisis, as observed in chronic myeloid leukaemia.

Cell Line↗

[Orotic acid].

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Animals↗

Improving the ketchup bottle method with positive expiratory pressure, PEP, in cystic fibrosis.

We studied the acute effects of 4 different chest physical therapy regimens using a randomised cross-over design in 14 patients with cystic fibrosis. Treatment A consisted of postural drainage, percussion and vibration; treatment B of postural drainage and periodic application of a face mask with positive expiratory pressure (PEP); treatment C of PEP in the sitting position; treatment D of the forced expiration technique in the sitting position. In terms of sputum expectorated, treatments B and C were superior to treatment D and especially to treatment A (p less than 0.05). Skin oxygen tension, PSO2 was monitored continuously during and for 35 min after treatment. A substantial and prolonged decay in PSO2 was observed during treatment A, quite different from other patterns seen. During and even following treatment C, an increase in PSO2 was noted. PEP was well accepted by the patients, who preferred treatment C, and we suggest it is incorporated in chest physical therapy regimens if the therapeutic objective is to increase expectoration.

Adolescent↗