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Biomedical subjects

I Lewis

Publications and source records attributed to I Lewis.

At least 19 recordsLinked to original sources
PubMed1992

Pilot study of high-dose vincristine, etoposide, carboplatin and melphalan with autologous bone marrow rescue in advanced neuroblastoma.

The efficacy and toxicity of a high-dose multiagent consolidation regimen, OMEC (vincristine, melphalan, etoposide and carboplatin), with autologous bone marrow rescue was studied in patients with poor-prognosis neuroblastoma, 20 patients were treated with OMEC, 18 after induction chemotherapy and 2 following relapse. All patients received, per m2, vincristine 4 mg, etoposide 1 g, carboplatin 1.0-1.75 g and melphalan 180 mg followed by bone marrow rescue. 4 patients (20%) died of treatment-related complications. Severe gastrointestinal toxicity occurred in all of these patients, and in 75% of patients overall. 1 of 5 patients with evaluable disease achieved complete remission. 13 patients (65%) have relapsed a median of 10 months (range 3-26) after receiving OMEC. Thus, OMEC was not more effective, yet more toxic, than high-dose melphalan given alone, and the use of similar multiagent regimens with overlapping toxicities in advanced neuroblastoma appears inadvisable.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

N-hydroxy-MeIQx is the major microsomal oxidation product of the dietary carcinogen MeIQx with human liver.

2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), one of the most abundant of the heterocyclic aromatic amines formed during the cooking of meat, is genotoxic and carcinogenic in rodents. MeIQx requires metabolic activation by P450 before it can exert these effects. Whilst there is indirect evidence that the mutagenic product is N-hydroxy-MeIQx (N-OHMeIQx), we have now identified this unequivocally following incubation of the amine with human hepatic microsomal fraction. A mixture of unlabelled MeIQx, [13C,15N2]MeIQx and [14C]MeIQx was used as substrate and the products analysed by HPLC-thermospray mass spectrometry. Characteristic doublet ions, 3 mass units apart, were found at m/z 214/217 ([M+H]+) from the parent compound, MeIQx and at 230/233 ([M+H]+) from N-OHMeIQx. The presence of a doublet ion at m/z 214/217 with the doublet at 230/233 [M+H+] provided additional evidence that this was N-OHMeIQx, as facile loss of 'O' is characteristic of N-hydroxylamines. Further evidence for the identity of the major metabolite, which accounted for approximately 90% of all microsomal metabolism, was obtained by comparing the mutagenicity of the HPLC eluate using Salmonella typhimurium YG1024, which is particularly sensitive to N-hydroxylamines, and TA98/1,8-DNP6 which is resistant to most N-hydroxylamines. Ninety-five per cent of direct-acting mutagenicity present in the reaction mixture was associated with a single peak, which co-eluted with N-OHMeIQx, as indicated by mass spectrometry. In the presence of a metabolic activation system, only one additional mutagenic peak, corresponding to unchanged MeIQx, could be detected. MeIQx (5 microM) was N-hydroxylated at a rate of 77 +/- 11 pmol/mg/min (mean +/- SEM, n = 4) by human liver microsomes. The specific inhibitor of human CYP1A2, furafylline (5 microM) inhibited the N-hydroxylation of MeIQx by > 90%. These data show that N-OHMeIQx is both the major oxidation product and the major genotoxic product of MeIQx generated by microsomal fractions of human liver and that the reaction is catalysed almost exclusively by CYP1A2.

Carcinogens↗
PubMed1992

Childhood lymphoma in Yorkshire.

AIMS: A histopathological review of 43 cases of childhood non-Hodgkin's lymphoma (NHL) in an attempt to identify histological variables of prognostic importance. METHOD: Each case was reclassified according to the Working Formulation and an attempt made to allocate an immunophenotype using a panel of monoclonal antibodies. Results were correlated with clinical data on site and survival. RESULTS: Of the 43 cases, 30 were males and 13 females. There were 17 cases of lymphoblastic lymphoma, 15 cases of small non-cleaved cell lymphoma (SNCC), and four cases of large cell lymphoma. The SNCC group was subdivided into 10 cases of Burkitt's lymphoma and five cases of non-Burkitt's lymphoma. An immunophenotype was allocated in 65.1% of cases (23 B, 5 T). The SNCC cases were spread throughout the 0-16 year age range while the lymphoblastic lymphoma cases tended to occur in older children. Most mediastinal tumours were lymphoblastic lymphoma and most abdominal tumours were SNCC. Statistical analysis failed to show a significant difference in survival among histological subgroups or immunophenotypes. CONCLUSION: No histological variables of prognostic importance were identified partly due to the great variation in treatment regimens, standard of supportive care, and prognosis over the period of the study (1972 to 1988).

Adolescent↗
PubMed1992

Measurement of dopamine, HVA and HMMA in untimed urine samples: establishment of age-related reference data in children.

We describe assays for homovanillic acid, hydroxymethylmandelic acid and dopamine that have proven practical and reliable during 3 years of routine use. Homovanillic and hydroxymethylmandelic acids were measured as trimethyl silyl derivatives by capillary gas chromatography. Dilution of samples prior to extraction was found to be necessary to achieve consistent recoveries of these acidic metabolites. Dopamine was assayed by high pressure liquid chromatography with electrochemical detection using an optimized method of catecholamine isolation that involved both ion exchange and alumina extraction. Untimed urine samples were collected from 140 hospitalized children. Age related reference data for the excretion of all three metabolites are reported. We suggest certain precautions that should be observed when using untimed samples and relating the results to creatinine excretion.

Adolescent↗
PubMed1991

Dosimetry of iodine 131 metaiodobenzylguanidine for treatment of resistant neuroblastoma: results of a UK study.

In 1987, the United Kingdom Children's Cancer Study Group (UKCCSG) set up a multi-centre study to investigate the toxicity of iodine 131 metaiodobenzylguanidine (mIBG) in the treatment of resistant neuroblastoma. Since December 1987, 25 children suffering from neuroblastoma have been treated with 131I-mIBG at six UK centres. All centres followed standardised physics and clinical protocols to provide consistent toxicity and dosimetry data. These protocols describe the methods employed for both the tracer study using 131I-mIBG and the subsequent therapy. Whole-body dosimetry calculations were performed on data from the tracer study. The activity administered for therapy was the amount predicted to deliver a predefined whole-body dose. Estimates of doses delivered to various organs during treatment are given in Table 1.

3-Iodobenzylguanidine↗
PubMed1990

Interactive effects of alpha-interferon A/D and interleukin 2 on murine lymphokine-activated killer activity: analysis at the effector and precursor level.

Studies from our laboratory and others have demonstrated that alpha-interferon (IFN alpha) can regulate natural killer cells and lymphokine-activated killer (LAK) cell activation. In vitro experiments have shown that IFN alpha has differential effects on both natural killer cells and LAK activity when combined with interleukin 2 (IL2); IFN alpha synergized with IL2 to augment natural killer cells activity while it suppressed the IL2-induced LAK response. Here we demonstrated that IFN alpha A/D can also regulate IL2-induced LAK activity in vivo with enhanced or suppressed activity depending on the IFN alpha A/D dose. The enhanced response was observed with the combination when 80,000 units/day of IFN alpha A/D were used and was detectable in the spleen, lung, and peritoneum. When a high dose of IFN alpha A/D was combined with IL2, a moderate reduction in LAK activity was noted in the spleen and peritoneum. In contrast, a high dose IFN alpha A/D augmented IL2-induced LAK activity in the lung even though it reduced the level of cellular infiltration. We have also evaluated the effect that IL2, IFN alpha A/D, and IL2 plus IFN alpha A/D have on the frequency of LAK precursors in the spleen and lung using limiting dilution analysis. Treatment of normal mice with IL2 alone increased the frequency of LAK precursor (LAKp) in the lung. This increase was associated with an infiltration of Thy-1+, asialo-GM1+, Lyt-2- lymphocytes into the lungs. Moreover, treatment with IL2 plus IFN alpha A/D enhanced the frequency of LAKp over that observed with IL2 alone. Treatment with the combination did not change the phenotype of LAKp in the lung from that seen with IL2. The increase in LAKp frequency induced by the combined treatment may not be a direct effect of IFN alpha A/D on precursor cells since IFN alpha A/D alone did not increase the frequency of LAKp in vivo or in vitro when added to limiting dilution analysis cultures. In contrast to what occurred in the lung, a consistent increase in LAKp was not seen in the spleen after treatment with IL2 or with the combination, although LAK activity was observed. These results demonstrated that in addition to inducing lytic activity from LAK effectors in vivo, IL2 treatment increased the number of precursor cells within the lung. Moreover, IFN alpha A/D in combination with IL2 influenced the level of LAKp in situ.

Animals↗
PubMed1989

Pharmacokinetics of prednisolone in children with acute lymphoblastic leukaemia.

The pharmacokinetics of soluble oral prednisolone were studied during induction therapy in six children with acute lymphoblastic leukaemia. There was a three- to four-fold variation in the pharmacokinetics of total and free prednisolone. For total prednisolone, the mean elimination half-life was relatively short (1.37 h) and the total clearance, relatively high (15.1 ml min-1 kg-1). The mean free fraction was high (0.37).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

In vitro activation of lymphocytes by interleukin 2 in patients with renal cell carcinoma.

Interleukin-2-stimulated lymphocytes or lymphokine-activated killer cells (LAK) have been shown to have anti-tumor activity which is not present in the fresh untreated peripheral blood lymphocytes. This activity has been evaluated in our laboratory using renal cell carcinoma as a target tumor. Two of 8 patients demonstrated significant lysis of autologous tumor while an additional 3 patients lysed the target cells but to a less significant degree. It is not clear why the LAK phenomenon against autologous tumors occurs in vitro in some patients and not others. By identifying the response of patients in vitro, one might be able to select an appropriate population for meaningful clinical trials.

Carcinoma, Renal Cell↗
PubMed1989

Hard-shell cardiotomy reservoir for reinfusion of shed mediastinal blood.

We conducted a prospective, randomized, controlled trial comparing homologous blood consumption between groups of patients receiving conventional mediastinal drainage (group 1) or reinfusion of shed mediastinal blood (group 2) using hard-shell cardiotomy reservoir. One hundred consecutive patients who had elective coronary artery or valvular operations were studied. The two groups were comparable with regard to age, sex, weight, preoperative and postoperative hemoglobin levels, and surgical procedure. Group 2 patients had their shed mediastinal blood reinfused for up to 18 hours postoperatively; otherwise, the two groups were treated identically. For groups 1 and 2, average mediastinal blood losses were 705 +/- 522 and 822 +/- 445 mL and homologous blood consumption was 3.83 +/- 2.58 and 3.15 +/- 2.05 U, respectively (neither measure was significantly different). However, if blood losses exceeded 500 mL, there was a statistically significant reduction in homologous blood requirements in group 2 as compared with matched controls in group 1. This difference was most significant in patients with the greatest mediastinal losses.

Blood Transfusion, Autologous↗
PubMed1985

Mass-analysed ion kinetic energy spectra and B1E-B2 triple sector mass spectrometric analysis of phosphoinositides by fast atom bombardment.

Fast atom bombardment is shown to produce useful spectra of the three phosphoinositides and the metabolically related phospholipids, lysophosphatidylinositol and phosphatidic acid. Analysis of the [M-H]- ions for fatty ester composition by mass-analysed ion kinetic energy spectra (MIKES) is shown to be inadequate to resolve fatty acyl daughter ions when the parent ion contains isobaric species. However, analysis on a triple sector instrument with and without collisional activation does provide complete compositional information. Quantitative analysis of the fatty ester content of each lipid molecular species is complicated by dissimilar ion yields from fatty acyl-bearing fragments from compositionally different parent ions.

Animals↗
PubMed1976

Sex differences in visual persistence: experiments on the Ganzfeld and afterimages.

Sex differences were investigated in two experiments on visual persistence: the Ganzfeld and the afterimage. Males were found to hold visual sensation longer than females, particularly in the Ganzfeld where there was little overlap of scores. Variability of experience in the Ganzfeld was also greater for males and they commonly reported 'blank-out' effects while females did not. There was further evidence from both experiments that females are more responsive to the long-wave region of the frequency spectrum.

Adolescent↗
PubMed1976

Aggression in captive pigtail monkey groups: effects of provision of cover.

To assess the influence of provision of "cover" on aggressive behavior in captive nonhuman primate groups, concrete cylinders were introduced into rooms in which six groups of pigtail monkeys resided. Basal incidence of aggression was measured prior to introduction of the cylinders and during their presence in the rooms. Four groups, which underwent little or no change in group composition during the study, exhibited substantially less aggression when cover was available than when it was not. Moderate and extreme changes in group composition occurred in two groups; these changes resulted in slight and dramatic increases in aggression, respectively, at the times when the changes occurred. Subjects frequently used the cylinders to avoid the concrete cylinders resulted in decreased aggression in stable groups but did not prevent aggression in groups which underwent moderate or extreme social change.

Aggression↗
PubMed1975

Pentazocine-induced fibrous myopathy.

Fibrous myopathy was found in three patients who had taken pentazocine intramuscularly for years. Fibrotic induration in the quadriceps and deltoid muscles, the considerable limitation of motion due to the fibrotic muscle contracture, and the minimal weakness of involved muscles are the most characteristic findings in this condition. Results of animal experiments support the close relationship between myopathy and pentazocine. This serious complication emphasizes more judicious use of pentazocine

Adult↗