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Biomedical subjects

B D Evans

Publications and source records attributed to B D Evans.

At least 37 records · Page 2Linked to original sources
PubMed1992

Ondansetron reduces chemotherapy induced nausea and vomiting refractory to standard antiemetics.

Ondansetron, a selective 5HT3 (serotonin) antagonist, was used in patients refractory to standard antiemetics. Seventy-five patients receiving chemotherapy without cisplatin were given ondansetron 4 mg IV and 4 mg orally immediately prior to chemotherapy, then 8 mg orally after six and 12 hours, followed by 8 mg orally eight hourly during days 2-5. Complete control of vomiting occurred in 52 patients (69%) on the first day and 45 patients (60%) on days 2-5. Sixty patients (80%) preferred ondansetron to their previous antiemetics. The efficacy of ondansetron was maintained over multiple chemotherapy cycles. Ondansetron was also given to 16 patients receiving cisplatin chemotherapy. They received 8 mg IV immediately prior to chemotherapy followed by an infusion of 1 mg/hr for 8 hr, with 8 mg orally at the end of the infusion and then 8 mg orally eight hourly during days 2-6. Some control of vomiting (less than = 5 vomits) was achieved in eight patients (50%) on the first day and in 14 patients (87%) on subsequent days. Eight patients (50%) preferred ondansetron to their previous antiemetics. Adverse events with ondansetron were frequent but mild, with constipation and headache being most common. Ondansetron is highly effective in patients refractory to standard antiemetics, especially after noncisplatin chemotherapy.

Adult↗
PubMed1991

Reduction of carboplatin induced emesis by ondansetron.

Ondansetron is a selective 5-HT3 antagonist with significant antiemetic properties in patients receiving cytotoxic chemotherapy. Patients who had suffered severe vomiting on carboplatin alone (23 patients with ovarian carcinoma) or in combination (two patients with testicular cancer) despite intensive antiemetic regimens were treated with ondansetron, given as 8 mg immediately prior to carboplatin followed by 8 mg orally, 8 hourly for 5 days. Twenty-five patients received 58 courses of ondansetron. In the first 24 h after the first course of chemotherapy with ondansetron, 17 patients (68%) experienced no vomiting, five patients (20%) had almost complete control and the other three patients had partial control. During the subsequent 4 days slightly lesser control was achieved. Nausea was similarly controlled in most patients. Twenty-two patients stated a preference for ondansetron with future chemotherapy. Fourteen patients received additional chemotherapy with ondansetron and in only three patients did the efficacy of therapy lessen. Toxicity was mild and transient with headache and constipation predominant. No extrapyramidal reaction was seen. Sedation was absent. Ondansetron is highly effective in refractory vomiting associated with carboplatin chemotherapy. It may be particularly beneficial when an extrapyramidal reaction has occurred on previous antiemetics and when sedation is unacceptable.

Antiemetics↗
PubMed1991

A randomized comparison of single-agent doxorubicin and epirubicin as first-line cytotoxic therapy in advanced breast cancer.

One hundred forty-one patients with advanced breast cancer who had not received prior chemotherapy were randomly assigned to receive doxorubicin 60 mg/m2 or epirubicin 90 mg/m2 every 3 weeks. These doses were selected to produce equivalent toxicities. All patients were assessed for toxicity, and 138 patients were assessable for response. After a median of five treatment cycles, 47% (32 of 68) of doxorubicin-treated patients achieved a partial or complete response. Response duration and survival were 10 and 12 months for doxorubicin and 8 and 10 months for epirubicin, respectively. Noncardiac toxicities were similar for both drugs. Of 41 patients receiving doxorubicin who had serial left ventricular ejection fraction assessments, seven sustained a fall of 10% or more, and one patient developed congestive cardiac failure at a cumulative doxorubicin dose of 489 mg/m2. Of 39 patients receiving epirubicin who had serial cardiac assessments, five sustained left ventricular ejection fraction falls of 10% or more and two patients developed congestive cardiac failure at cumulative doses of 178 mg/m2 and 833 mg/m2. These data indicate that an epirubicin dose of 90 mg/m2 produces toxicity equivalent to doxorubicin 60 mg/m2 but does not improve response rates, response duration, or survival in advanced breast cancer.

Adult↗
PubMed1990

Carbon monoxide diffusing capacity is a poor predictor of clinically significant bleomycin lung. New Zealand Clinical Oncology Group.

In a retrospective analysis, serial lung function tests from 81 patients receiving bleomycin were studied to determine the accuracy of carbon monoxide diffusing capacity (DLCO) as a predictor of clinically significant bleomycin lung. Six of 81 patients developed clinically significant bleomycin lung, and the DLCO predicted its development in only one patient (sensitivity, one of six patients; 16.7%). Respiratory symptoms and chest x-ray abnormalities were the earliest manifestations in the other five patients. Seventy-five of 81 patients did not develop clinically significant bleomycin lung, and 12 of these had major falls (greater than or equal to 35% pretreatment level) in DLCO (specificity, 63 of 75 patients; 84.0%). In eight patients, bleomycin was continued after a major fall in DLCO, and none developed clinically significant lung toxicity. In this study, the DLCO failed to predict the development of serious bleomycin lung toxicity in all but one case. Furthermore, in some patients, it would appear that bleomycin may be stopped inappropriately after low DLCO measurements. It is important to monitor for respiratory symptoms and chest x-ray abnormalities during bleomycin treatment as these will be the earliest signs of lung toxicity in most cases.

Adolescent↗
PubMed1989

Phase I trial and pharmacokinetics of trimelamol (N2,N4,N6-trihydroxymethyl-N2,N4,N6-trimethylmelamine).

Trimelamol is an analogue of hexamethylmelamine and pentamethylmelamine which does not require metabolic activation and is sufficiently soluble to allow parenteral administration. A Phase I trial has been performed at the Royal Marsden Hospital in which two schedules of administration have been evaluated, a single i.v. infusion repeated every 3 weeks and 3 daily doses repeated every 3 weeks. Pharmacokinetic analysis was performed at all dose levels on both schedules and a linear correlation was demonstrated between dose and area under the curve. Myelosuppression was dose limiting for single dose administration with a maximum tolerated dose of 2400 mg/m2. Median leukocyte nadirs at 1800, 2100, and 2400 mg/m2 were 3.2, 2.6, and 1.5 x 10(9)/liter. Thrombocytopenia and anemia also occurred but were not dose limiting. Doses greater than 1500 mg/m2 caused WHO grade 3 nausea and vomiting but no acute sedation. Three day administration appeared to be less myelosuppressive, giving a maximum tolerated dose of 1000 mg/m2. Median leukocyte nadirs at 800, 900, and 1000 mg/m2 daily for 3 days were 3.0, 2.3, and 1.5 x 10(9)/liter. Nonhematological toxicities were also less marked on the fractionated schedule. Antitumor effects were observed including 1 complete and 9 partial responses. Demonstration of activity in ovarian cancer has led to further evaluation in this disease using the 3-day schedule at a dose of 800 mg/m2 daily for 3 days.

Adult↗
PubMed1989

Small cardioactive peptide-like immunoreactivity and its colocalization with FMRFamide-like immunoreactivity in the central nervous system of the leech Hirudo medicinalis.

The distributions of small cardioactive peptide (SCP)- and FMRFamide-like immunoreactivities in the central nervous system of the medicinal leech Hirudo medicinalis were studied. A subset of neurons in the segmental ganglia and brains was immunoreactive to an antibody directed against SCPB. Immunoreactive cell bodies were regionally distributed throughout the nerve cord, and occurred both as bilaterally paired and unpaired neurons. The majority of the unpaired cells displayed a tendency to alternate from side to side in adjacent ganglia. A small number of neurons were immunoreactive only in a minority of nerve cords investigated. Intracellular injections of Lucifer yellow dye and subsequent processing for immunocytochemistry revealed SCP-like immunoreactivity in heart modulatory neurons but not in heart motor neurons. FMRFamide-like immunoreactivity was also detected in cell bodies throughout the central nervous system. A subset of neurons contained both SCP- and FMRFamide-like immunoreactivities; others stained for only one or the other antigen. These data suggest that an antigen distinct from FMRFamide is responsible for at least part of the SCP-like immunoreactivity. This antigen likely bears some homology to the carboxyl terminal of SCPA and SCPB.

Animals↗
PubMed1988

Metastasizing leiomyoma of the uterus.

This report describes a patient who underwent a subtotal hysterectomy 6 years ago for fibroids. She re-presented recently with lung metastases and a pelvic mass. Macroscopic appearances at laparotomy suggested a leiomyosarcoma of the uterine stump, but histological appearances suggested the patient was suffering from the rare condition 'metastasizing leiomyoma'. Subsequent response to hormone manipulation supported the latter diagnosis.

Adult↗
PubMed1988

Lack of passive transfer of renal tubulointerstitial disease by serum or monoclonal antibody specific for renal tubular antigens in the mouse.

Mice immunized with rabbit renal basement membranes form autoantibodies to their kidney glomerular and tubular basement membranes (GBM/TBM). Development of renal tubular disease (RTD) consists of deposition of autoantibodies along the GBM/TBM with the inter- and intratubular accumulation of lymphocytes and macrophages and destruction of the TBM. Transfer of this disease in mice with either serum or monoclonal antibodies, however, has been difficult to demonstrate and, therefore, attempts were made to confirm a report that RTD is passively transferred by anti-TBM autoantibodies. Using the revised protocol in this later report, we found that 12 weeks after transfer autoantibodies were deposited along the GBM and/or TBM of the recipients, yet RTD was not observed. Although qualitative and quantitative characteristics of the antibody may play a role in the pathogenesis in the murine model of RTD, we could not obtain evidence to support and confirm this study.

Animals↗
PubMed1987

Effect of zinc on lysis of sheep erythrocytes by guinea pig C4-deficient serum.

The divalent cation Zn2+ enhanced the lysis of sheep erythrocytes (ShE) by guinea pig C4-deficient (C4D) serum. Enhancement by Zn2+ (0.1 mM) was demonstrated in the presence of cobra venom factor (CoVF, 2 units/ml) and optimal Mg2+ (1.0 mM). Moreover, Zn2+ (0.1 mM) in the presence of Mg2+ (1.0 mM) caused the lysis of ShE by C4D serum without the addition of CoVF. Further studies were therefore performed in the absence of CoVF. Although addition of Zn2+ or Mg2+ alone to some pools of C4D serum caused lysis of ShE, the greatest extent of lysis occurred when Zn2+ and Mg2+ were both added to the reaction mixtures. When C4D serum was resin-treated, both Mg2+ and Zn2+ were required for lysis. Addition of Ca2+ had no effect. This pathway required high concns of serum and was inhibited by pretreating the serum with zymosan (2 mg/ml serum, 37 degrees C, 1 hr) or by heating the serum at 56 degrees C for 20 min. K76-COOH monocarboxylic acid also inhibited this pathway. These results suggest that Zn2+ together with Mg2+ activates the alternative pathway on the nonactivator surface (ShE).

Animals↗
PubMed1987

Carboplatin (Paraplatin; JM8) and etoposide (VP-16) as first-line combination therapy for small-cell lung cancer.

Fifty-two previously untreated patients with small-cell lung carcinoma (SCLC) were treated with a combination of carboplatin 300 mg/m2 intravenously (IV) on day 1 and etoposide 100 mg/m2 IV on days 1 through 3 every 28 days for four courses. Patients with limited disease (LD) subsequently received thoracic radiotherapy; no prophylactic cranial radiotherapy was used. Forty-four patients (85%) achieved an objective response, including 82% (29% complete remissions) of LD patients and 88% (13% complete remissions) of extensive-disease (ED) patients. Median response duration for LD patients was 7 months and 5.5 months for ED patients. Median survival for both LD and ED patients was 9.5 months. Myelosuppression was the main toxicity, with World Health Organization (WHO) grade 3/4 leucopenia occurring in 44% of patients. There was one (2%) treatment-related neutropenic death. Treatment was otherwise well tolerated, and in particular no renal toxicity, neurotoxicity, or ototoxicity was seen. This new combination is highly active in terms of response rate, but response duration and survival is disappointing, and might be improved by prolonged treatment or by the use of additional drugs in combination.

Adult↗
PubMed1985

High-dose cyclophosphamide with autologous bone marrow rescue after conventional chemotherapy in the treatment of small cell lung carcinoma.

Within an original consecutive series of 94 patients, 36 eligible patients with small cell lung carcinoma were treated with high-dose cyclophosphamide 7 g/m2 after conventional chemotherapy with VP16, adriamycin, and vincristine. The first 17 also underwent autologous bone marrow rescue. Treatment was well tolerated apart from one treatment-related death. Measurable tumour was still present in 15 patients before high-dose cyclophosphamide, and although 12 (80%) of these achieved further tumour response, these responses were all short-lived, with a median duration of 9 weeks. In 14 limited-disease patients already in complete remission before high-dose therapy the initial result was better, but 11 (79%) have now relapsed following overall median response duration of 10 months. High-dose cyclophosphamide after conventional chemotherapy is feasible and achieves a high response rate, but it does not appear to be associated with significant survival benefit either overall or in patient subgroup.

Adult↗
PubMed1985

Carboplatin (JM8) as a single agent and in combination in the treatment of small cell lung cancer.

Carboplatin, a cisplatin analogue without significant nephrotoxicity, was used as a single agent in the treatment of 56 patients with small cell lung carcinoma at a dose of 300-400 mg/m2 i.v. monthly. Twenty-three patients (41%) achieved a response including 5 (9%) complete remissions. Eighteen (60%) of 30 previously untreated patients achieved a response. The drug was well tolerated with nausea or vomiting in only 43% of patients and no nephrotoxicity was seen. Myelosuppression was dose limiting and 39% of patients developed leukopenia. In a subsequent study carboplatin in a dose of 300 mg/m2 was used in combination with etoposide 100 mg/m2 i.v. days 1-3, repeating monthly for 4 courses. So far 32 (89%) of 36 evaluable patients have achieved a response. In patients with limited disease 20/23 patients (87%) have responded including 7 (30%) complete remissions. Leukopenia was dose limiting and occurred in 83% of patients. Carboplatin is a highly active new drug in the treatment of small cell lung cancer.

Antineoplastic Agents↗
PubMed1985

Carboplatin: a very active new cisplatin analog in the treatment of small cell lung cancer.

Carboplatin, a cisplatin analog without significant clinical nephrotoxicity, has been evaluated in the treatment of 56 patients with small cell lung carcinoma at a dose of 300-400 mg/m2 iv monthly in a phase II study. Twenty-three patients (41%) achieved a response, including five (9%) complete remissions. Of 30 previously untreated patients, 18 (60%) achieved a response, including three (10%) complete remissions. Median response duration was 4.5 months (range, 2-9). No nephrotoxicity was seen and hydration was not required. Nausea or vomiting occurred in only 24 patients (43%) and was rarely severe. Myelosuppression was dose-limiting: 20 patients (36%) developed leukopenia and eight (14%) developed thrombocytopenia, but leukopenic infections occurred in only three patients. Carboplatin is a very active new agent in the treatment of small cell lung cancer, with less toxicity and better tolerance than cisplatin. It merits further investigation in combination chemotherapy and against non-small cell lung cancer.

Adult↗
PubMed1984

The effect of ethylenedinitrilotetraacetic acid (EDTA) on the reaction between the guinea-pig C5 convertase and guinea-pig C5.

Guinea-pig C5 was reacted with EAC1423 in the washed-cell intermediate assay in the presence of glucose gelatin veronal buffer (GGVB), Zn2+-GGVB (0.025 mM), GGVB2+ containing Ca2+ and/or Mg2+ or EDTA (0.013 M)-GGVB. The EDTA inhibited the formation of competent SAC14235, while Ca2+ and/or Mg2+ had a slight enhancing effect compared to GGVB alone and Zn2+ gave a four-fold increase. Similar results were obtained by using human C5 with guinea-pig C5 convertase and functionally pure guinea-pig C6, C7, C8 and C9. When guinea-pig C6 was incorporated into these various reaction mixtures with guinea-pig C5, its addition markedly reduced the inhibition by EDTA, while Zn2+ still showed an enhancing effect. These results demonstrate that EDTA inhibited formation of competent SAC14235 by preventing activation of C5. The association of C6 with C5 can partially overcome the inhibition of C5 conversion by EDTA and may account for C5 activity in reaction mixtures containing C-EDTA.

Animals↗
PubMed1984

Interaction of Zn2+ with guinea-pig C5 convertase and guinea-pig C5.

A comparison of two methods of C5 activation, the standard method (EAC14 + C2, C3, C5, C6, and C7) and the washed-cell intermediate method (EAC1423 + C5 and washed), demonstrated that formation of hemolytically competent SAC14235 was reduced in the washed-cell method. Addition of Zn2+ in this method increased the formation of competent SAC14235 to the approximate level of the standard method. The optimum concn range of Zn2+ was 0.006-0.025 mM. In the standard method Zn2+ had no significant enhancing effect on the formation of competent SAC14235. Zn2+ had a greater affinity for EAC1423 than for fluid-phase C5 when reacted with each separately. Maximum enhancement, however, was obtained when Zn2+ was present during the reaction of C5 with EAC1423. The effect of Zn2+ on C5 activity was not related to the stabilizing property of C6 on cell-bound C5. In the washed-cell method there was an inverse relationship between the concn of C2 or C3 and the concn of C5 required to generate one competent SAC14235/cell. Over a 10-fold range of C2 or C3 concn there was an approximate four-fold increase in the number of competent SAC14235/cell formed in the presence of Zn2+. Zn2+ enhances formation of competent SAC14235 on cells that have a limited ability to activate C5 even though the C2 and C3 on the convertase are present in excess.

Animals↗