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Biomedical subjects

L Boros

Publications and source records attributed to L Boros.

At least 19 recordsLinked to original sources
PubMed1992

Distribution characteristics of mitoxantrone in a patient undergoing hemodialysis.

The pharmacokinetic profile of mitoxantrone in a patient undergoing hemodialysis is described. Significant characteristics of our patient included lymphoma with liver involvement, tumor lysis syndrome, renal and hepatic failure. Combination chemotherapy consisted of mitoxantrone, vincristine, and cyclophosphamide. Mitoxantrone plasma samples were obtained prior to dosing and at 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.5, 7.0, and 12 h after the intravenous infusion of a 17-mg dose over 20 min. Serum concentrations were determined by high-performance liquid chromatography. The serum concentration versus time curve was consistent with a three-compartment model. However, rebounds in serum drug concentrations were detected during the last portion of dialysis and after its completion. The gamma elimination half-life could not be determined due to the continued detection of rebounds in drug concentrations throughout the postdialysis sampling period. The alpha and beta distribution phases did not appear to be affected by hemodialysis. The peak mitoxantrone concentration fell within the reported range. Mitoxantrone does not appear to be eliminated by hemodialysis, and dose adjustments are not needed in patients undergoing this procedure.

Aged↗
PubMed1991

13-cis-retinoic acid in the treatment of elderly patients with acute myeloid leukemia. A phase II pilot study of the Eastern Cooperative Oncology Group.

The management of acute myeloid leukemia in the elderly (65 years and older) is unsatisfactory because of poor patient tolerance of standard myeloablative chemotherapy. The authors conducted a Phase II study to evaluate the effectiveness and toxicity of 13-cis-retinoic acid (CRA) in the therapy of elderly patients with acute myeloid leukemia (AML). Patients presenting with leukocyte counts less than 20,000/microliters were treated with CRA alone. Those with leukocyte counts of 20,000/microliters or greater were pretreated with hydroxyurea, followed by CRA. Twelve of 18 patients received at least 4 weeks of CRA and were thus considered evaluable for toxicity and response. No objective responses were observed. Cis-retinoic acid administration was well tolerated; only modest dermatologic, musculoskeletal, and gastrointestinal toxicity was observed. Alternative therapeutic strategies should be investigated in this subpopulation of AML patients.

Aged↗
PubMed1991

Essential role of cholecystokinin in pancreatic regeneration after 60% distal resection in rats.

The essential role of cholecystokinin (CCK) in pancreatic regeneration after pancreatitis or resection has been supposed, but not yet clearly demonstrated. In rats, 6-8 weeks after 60% distal resection of the pancreas a gradual increase in pancreatic weight and contents of DNA, protein, trypsin, chymotrypsin and amylase, occurred (there was no increase in lipase); Pancreatic regeneration stopped thereafter. Nonparallel increases in enzyme values were similar to those seen after CCK administration. Indeed, basal CCK levels increased significantly by the 6th week and declined thereafter. A one month s.c. administration of CCK-octapeptide (CCK-8) (3 x 300 ng/kg/d) accelerated regeneration in the first month, but it had almost no effect during the second or third postoperative months. A two week s.c. administration of a specific CCK antagonist, CR 1409 (3 x 4 mg/kg/d) totally prevented regeneration by the fifth and sixth weeks, but did not diminish pancreatic weight or DNA and protein contents during the first two weeks. Alcohol administration (12 g/kg/d) reduced CCK release and prevented pancreatic regeneration during the three-month experimental period. These data indicate that CCK has an essential role in pancreatic regeneration and that the deleterious effect of alcohol on regeneration involves inhibition of CCK release.

Amylases↗
PubMed1990

Pharmacokinetics of very high-dose oral melphalan in cancer patients.

The pharmacokinetics and systemic availability of melphalan after high-dose oral administration with and without 1,3-bis(2-Chloroethyl)-1-nitrosourea (BCNU) or etoposide were examined in three patients undergoing autologous bone marrow transplantation. Patient 1 (advanced melanoma) received melphalan at 80 mg/m2/day p.o. on days -6, -5, and -4, followed by BCNU at 300 mg/m2/day i.v. on days -3, -2, and -1 prior to bone marrow transplantation. Patient 2 (advanced colon carcinoma) received melphalan at 75 mg/m2/day p.o. on days -3, -2, and -1. Patient 3 (advanced refractory lymphoma) received etoposide at 800 mg/m2/day i.v. on days -7, -5, and -3, followed by melphalan at 157 mg/m2/day p.o. on days -2 and -1. Melphalan was administered as a bolus oral dose, using 2-mg tablets. Blood samples were collected at 0, 5, 10, 15, 30, and 45 min and 1, 2, 3, 4, 6, 8, 12, and 24 h after each dose of melphalan. Peak plasma melphalan concentrations in the three patients ranged from 0.354 (patient 2) to 1.768 micrograms/ml (patient 1). Plasma melphalan concentration X time products (C x Ts) showed extreme variability in one patient (patient 2), ranging from 0.76 to 4.48 micrograms.h/ml. To determine the relative systemic availability of orally administered melphalan, i.v. C X Ts proportional to the p.o. doses were extrapolated from previously reported i.v. bolus pharmacokinetic data. The p.o.:i.v. plasma C X T ratios for high-dose melphalan ranged between 0.09 (patient 3) and 0.58 (patient 2). Although these C X T data suggest a dose-response for orally administered melphalan, the systemic availability of these high p.o. melphalan doses was extremely variable, both within and between study patients. Thus, we cannot recommend the use of high-dose p.o. melphalan regimens in patients undergoing autologous bone marrow transplantation.

Adenocarcinoma↗
PubMed1989

Alcohol-induced chronic pancreatitis in rats after temporary occlusion of biliopancreatic ducts with Ethibloc.

Chronic obstructive pancreatitis-like histological and biochemical alterations were provoked in male Wistar rats with Ethibloc occlusion of the common bile duct and the main pancreatic ducts. After the disappearance of the glue from the ducts, a gradual and almost total recovery was demonstrated during a 2-month observation period. About 12 g/kg of alcohol (20% vol/vol) given daily by gastric intubation and ad libitum intake inhibited the recovery of pancreatic weight and enzyme contents in the occluded rats, and within a 2-month period chronic calcifying-type pancreatitis became evident with some signs of remaining obstructive pancreatitis-like lesions. Cessation of alcohol administration after 2 months resulted in a recovery of pancreatic weight and enzyme contents, although morphological regeneration was less pronounced and calcification remained visible in some rats. A 50% raw soy flour diet provoked some further changes in the proportion of enzymes without any supplementary increases of pancreatic weight and protein content. This animal model of chronic pancreatitis demonstrates that chronic obstructive and calcifying pancreatitis can appear together and earlier if the etiological factors act in combination. Suppression of pancreatic regeneration by alcohol seems to be necessary to maintain chronic pancreatitis-like lesions and to develop calcification.

Animals↗
PubMed1988

Leukemic dermal infiltrates as a complication of central venous catheter placement.

A leukemic dermal infiltrate at the site of a central venous catheter placement was the first manifestation of relapse in a 58-year-old woman in clinical remission of acute myelomonocytic leukemia. The patient developed a large hematoma around the site of an unsuccessful attempt to place a central venous (CV) catheter. Although the hematoma resolved completely by the time that complete remission was achieved, an indurated, erythematous mass subsequently developed, which when biopsied revealed leukemic cells in the dermis. The patient had a relapse in her peripheral blood shortly thereafter. The authors reviewed recent literature and their own experience with CV catheters and report on localized dermal relapse as a previously unpublished risk of CV catheter placement. They also speculate on the role of the dermis as a sanctuary for leukemic cells and a potential source for relapsing disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Trisomy 5 as sole anomaly in acute lymphoblastic leukemia.

We present a case of B-cell acute lymphoblastic leukemia (ALL) in whose leukemic cells trisomy 5 (+5) was the only cytogenetic anomaly observed. This is the first report of +5 as the sole cytogenetic abnormality in ALL; two cases (one questionable) of acute nonlymphocytic leukemia with such a change have been reported. The findings are presented in relation to other cases with +5 as part of a more complicated cytogenetic picture in hematologic disorders.

Adult↗
PubMed1987

5-Fluorouracil and high-dose folic acid treatment for metastatic colon cancer.

Twenty-two patients with metastatic colorectal cancer were treated with a regimen of 5-fluorouracil 600 mg/m2 (maximum, 1.0 g) i.v./week and folic acid 140 mg/m2 i.v. given 1 h prior to the 5-FU. This study was undertaken in an attempt to confirm the in vitro finding that inhibition of thymidylate synthetase by 5-fluorouracil is prolonged by the presence of folates. There were four partial responses (18%) with mean duration 4 months. Dose-limiting toxicity was enteritis, seen in 12 patients (58%), and causing hospitalization in seven patients. Enteritis was shown to be due to the folic acid in most patients. Two patients died from leukopenia, enteritis, and sepsis. Mean serum folate levels at the time of 5-FU injection were 36 microM. This regimen is no more effective than 5-FU alone and has significantly more serious toxicity. Further investigation of this regimen is not recommended.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Evaluation of CCNU and misonidazole in the treatment of advanced colorectal cancer.

Eighteen adult colorectal cancer patients, previously untreated with systemic chemotherapy, were given CCNU and MISO. One patient had an excellent partial response of pulmonary metastases, but the overall response rate was only 6%. Gastrointestinal toxicity was modest, hematologic toxicity was similar to what would have been predicted for CCNU alone, and there was no neurotoxicity detected. This Phase II study demonstrates that these two agents can be administered safely, but have no advantage over CCNU alone.

Adult↗
PubMed1986

Long-term survival in limited-stage small cell lung carcinoma. Experience in Rochester, New York from 1975 to 1981.

All patients with limited-stage small cell lung carcinoma (SCLC) diagnosed between January 1975 and 1981 in Rochester, New York, were collected. One hundred one patients were evaluable. By reviewing an entire community's experience with long follow-up, we were able to describe the response rates and survival in a large unselected population and compare them to results from concurrent cooperative group studies. Median survival for the entire group was 51 weeks, with only 18% alive at 130 weeks. There was no evidence for improvement in response or survival during the 6 years of study. Treatment results in the community as a whole were no different from that seen with cooperative group studies. A group who had initial surgery followed by adjuvant therapy had a significantly better survival and more long-term survivors than those not receiving surgery, but rare long-term survivors were seen with all treatment categories. Except for this small surgical subgroup, no other characteristics could be identified which were predictably associated with long-term disease-free survival. The overall poor survival of patient with localized SCLC suggests a need for the development of novel initial approaches to therapy.

Adult↗
PubMed1986

Toxicities of human recombinant interferon-alpha 2 in patients with advanced prostate carcinoma.

Nine patients with hormone-resistant prostate carcinoma were treated with subcutaneous injection of recombinant human interferon-alpha 2 (rHuIFN-alpha 2), 5-10 X 10(6) U/m2, three times a week. One patient had a mixed clinical response with reduction of bone pain. The study was closed due to intolerable grade III and IV toxicities including weight loss (8/9), fatigue/malaise (7/9), central nervous system toxicity (4/9), leukopenia (3/9), and uncontrollable nausea and vomiting (2/9). These toxicities resulted in deterioration of performance status. It is concluded that rHuIFN-alpha 2, at least at the dose and schedule studied, should not be used for the treatment of patients with hormone-resistant prostate carcinoma.

Aged↗
PubMed1985

Leukemia in Rochester (NY). A 17-year experience with an analysis of the role of cooperative group (ECOG) participation.

Every adult acute nonlymphocytic leukemia patient in Rochester, New York seen from January 1975 to January 1982 was studied. Fifty percent of the patients did not receive combination chemotherapy. Among those who did, there was a significant selection bias toward placing patients with better prognostic features on protocol. Protocol patients were also treated with higher doses of chemotherapy than nonprotocol patients. However, these factors did not completely explain the significantly better complete response (CR) rate and survival among protocol patients. Eastern Cooperative Oncology Group (ECOG) participation remained an independent variable associated with a better outcome. An improvement in CR rate was seen during the 7-year period studied as compared to that seen between 1965 and 1974. The study provided evidence that the availability and use of ECOG protocols was a positive factor in the improvement of leukemia treatment in Rochester.

Acute Disease↗
PubMed1976

Large cerebral vessel disease in sickle cell anaemia.

An 18 year old male with documented sickle cell disease was admitted to the hospital for the final time in coma. Cerebral angiography revealed multiple stenotic lesions of the large cerebral vessels. The pathology of this large vessel involvement is demonstrated and the potential contribution of large as opposed to small cerebral vessel disease in the neurological manifestations of sickle cell anaemia is discussed.

Adolescent↗