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Biomedical subjects

B A Robinson

Publications and source records attributed to B A Robinson.

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

Pharmacokinetics and efficacy of rectal versus oral sustained-release morphine in cancer patients.

Sustained-release morphine (MST) given by the rectal route was compared with oral MST in an open randomised cross-over trial in ten patients with cancer who received stable doses of MST. No significant difference was found in the areas under the curve of the concentration-time profiles (AUC) following oral or rectal administration for parent morphine. The AUCs determined for morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) after oral administration were approximately twice those obtained following rectal administration. The maximal concentration achieved was lower and the time to maximal concentration was longer following rectal administration for morphine, M6G and M3G. The relative mean arrival times following rectal administration were significantly longer for morphine and M3G but not for M6G. These findings suggest slower absorption but less first-pass metabolism of MST after rectal administration. No significant difference was noted between the oral and the rectal route in measurements on visual-analogue scales for pain or side effects. We recommend the rectal route as being suitable for MST administration when the oral route is no longer available. In changing from oral to rectal administration, the same dose and dose interval may be used, but dose adjustment may be needed.

Administration, Oral↗
PubMed1992

Neutropenic sepsis complicating treatment of solid tumours, lymphoma and myeloma.

Ninety-three episodes of fever or infection while neutropenic (defined as neutrophil count < 2.0 x 10(9)/l) occurred in 76 patients treated for solid tumours, lymphoma and myeloma over a 4-year period. Most followed the first (39%) or second (18%) cycle of chemotherapy. The neutrophil count at onset of sepsis was < 0.5 x 10(9)/l in 69%. Pathogens were isolated in 32 episodes (34%) and a clinical focus detected in a further 19 (20%). Gram negative bacteria accounted for 51% of pathogens; 49% of bacteria were isolated from blood, 65% of them were Gram negative. The initial antibiotic regimen was cefuroxime with gentamicin or tobramycin in 76 episodes. Fever or infection resolved on first line antibiotics in 78%. The mean duration of antibiotic therapy was 7.6 days. Antibiotic therapy was changed following urine culture in 1.5% of 66 episodes and following chest radiography in 5.8% of 69 episodes, where these tests were performed. Nine (9.6%) patients died from infection, all of whom were receiving second line salvage chemotherapy. Three other patients died of progressive malignancy with sepsis present. In six major diagnostic groups, 56 episodes of infection or fever complicated 4% of chemotherapy cycles.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Moderate to heavy infections of Trichuris trichiura affect cognitive function in Jamaican school children.

A double-blind placebo trial was conducted to determine the effect of moderate to high loads of Trichuris trichiura (whipworm) infection on the cognitive functions of 159 school children (age 9-12 years) in Jamaica. Infected children were randomly assigned to Treatment or Placebo groups. A third group of randomly selected uninfected children were assigned to a Control for comparative purposes. The improvement in cognitive function was evaluated using a stepwise multiple linear regression, designed to control for any confounding variables. The expulsion of worms led to a significant improvement in tests of auditory short-term memory (P less than 0.02; P less than 0.01), and a highly significant improvement in the scanning and retrieval of long-term memory (P less than 0.001). After 9 weeks, treated children were no longer significantly different from an uninfected Control group in these three tests of cognitive function. The removal of T. trichiura was more important than Ascaris lumbricoides in determining this improvement. The results suggest that whipworm infection has an adverse effect on certain cognitive functions which is reversible by therapy.

Albendazole↗
PubMed1992

Fasting plasma lipid measurements following cisplatin chemotherapy in patients with germ cell tumors.

PURPOSE: Elevated total serum cholesterol levels have been reported recently in a group of patients with metastatic testicular cancer after treatment with cisplatin combination chemotherapy. We have studied the lipid profile of a similar group of patients in an attempt to confirm this observation. PATIENTS AND METHODS: Fasting plasma lipid concentrations were measured in 47 patients with advanced germ cell tumors who were previously treated with a cisplatin combination chemotherapy. The values obtained for mean total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, apolipoprotein A1, and apolipoprotein B concentrations were compared with those obtained from a control group of 59 patients with germ cell tumors who were not treated with chemotherapy and with data from the New Zealand male population. Median time from the completion of chemotherapy to lipid measurement in the treated group was 50 months (range, 2 to 138 months). The median total dose of cisplatin given was 720 mg (range, 300 to 1,625 mg). RESULTS: Mean total plasma cholesterol concentrations in the cisplatin group (5.87 mol/L) and the control group (5.70 mmol/L) did not differ significantly (P > .4). There was no significant difference for any of the variables between the chemotherapy and control groups and those of the New Zealand male population. There was a trend toward higher mean triglyceride concentrations in the chemotherapy group, but this did not reach significance. CONCLUSIONS: We have not demonstrated an elevation in total plasma cholesterol after cisplatin chemotherapy as has been reported by previous investigators. Our results suggest that in these patients, cisplatin-containing combination chemotherapy is not associated with a significant adverse effect on plasma lipid profile.

Adult↗
PubMed1991

The management of small cell lung cancer in Christchurch 1979-89.

The management of 215 consecutive patients with small cell lung cancer referred to the oncology service at Christchurch Hospital, 1979-89, was reviewed. After staging, 118 patients were treated with combination chemotherapy (cyclophosphamide, vincristine and doxorubicin), with (87) or without (31) thoracic irradiation. Patients with other medical problems were treated with alternative chemotherapy (34) or irradiation alone (54). Nine received symptomatic care alone. Eighty-five (40%) had limited disease, with no extrathoracic metastases beyond supraclavicular nodes. The response rate to treatment was 66%. Median survival for the whole group was 33 weeks, 51 weeks for those with limited and 26 weeks for extensive disease. The cumulative risk of developing cerebral metastases was 40% at one year. Patients surviving 26 weeks spent one third of their time as hospital inpatients or outpatients. Twenty-two patients survive, five progression free for 4-8 years, including two who had initial surgical resection. The study supports the policy of reserving intensive staging for fit patients who appear to have limited disease and for those entered into clinical trials. Fit patients with limited disease warrant treatment with combination chemotherapy and thoracic irradiation.

Aged↗
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

Comparison of methods of assessment of renal function in patients with cancer treated with cisplatin, carboplatin or methotrexate.

In patients with cancer treated with cisplatin, carboplatin or methotrexate creatinine clearance calculated using the Cockcroft-Gault formula was compared with measured clearance and with the glomerular filtration rate. In 106 patients the average squared difference for calculated and 24 hour urine creatinine clearance was 0.288, n = 606; and for calculated creatinine clearance and glomerular filtration rate (measured using diethylenetriaminepenta-acetic acid, DTPA), 0.212, n = 34. On 35 of 606 occasions (6%) in 18 patients (17%), the calculated clearance overestimated the 24-hour urine creatinine clearance when it was less than 1 mL/s. In all but one patient, this was explained by factors leading to renal impairment (seven patients) or overestimation of clearance (ascites in two patients) or by an isolated low value of 24-hour urine creatinine clearance (eight patients). Declining renal function with increasing total dose of cisplatin was detected by both calculated and 24-hour urine creatinine clearance in patients with germ cell tumours. Derivation of an equation to predict creatinine clearance showed a linear association with plasma creatinine concentration, patient age, weight and gender. Variability in cancer patients was similar to that in the original Cockcroft-Gault study. Calculation of creatinine clearance can be used in cancer patients to monitor treatment with renally-eliminated chemotherapy agents.

Adult↗
PubMed1990

Childhood pica. Some aspects of the clinical profile in Manchester, Jamaica.

The clinical profile of 108 children aged 1 1/2 years to 10 years who practised pica was compared to that of 50 non-pica patients aged 2 years to 10 years. Of the patients with pica, 85% were less than 5 years of age and 29% were aged 1 1/2 years to 2 years. The male to female ratio was 1:1.4. Ninety-two patients ingested dirt, 35 marl, 33 stone, 17 coal and 10 ashes. Twenty-two patients ingested multiple substances. Family history for pica was positive in 44 patients. Forty-six per cent of pica patients and 12% control patients had poor nutritional status (p less than 0.05). Ten per cent of pica patients were constipated while 26% had persistent diarrhoea. Intestinal parasites were identified in 70.3% of cases and were distributed as follows: Trichuris species 66%, Ascaris lumbricoides 26.6%, Giardia lamblia 17%, and mixed infestations 28.8%. Initial haemoglobin values were less than 8 gm/dl in 34.8% and 11 gm/dl or greater in 20.9% of pica patients compared with 12% and 56%, respectively, in control patients (p less than 0.05) It is concluded that, in our country, the children who practise pica are prone to malnutrition, anaemia, diarrhoea/constipation and worm infestation. Geophagia is most frequently involved and there is often a family history of pica.

Child↗
PubMed1989

Circadian pharmacokinetics of methotrexate.

Six patients with intermediate- and high-grade non-Hodgkin's lymphoma were treated with 400 mg/m2 i.v. methotrexate (MTX) at 0600 and 1800 hours. Despite evidence of circadian rhythms in renal function, the pharmacokinetics of total and free serum MTX showed no significant difference between these two times. The marked two-fold circadian variation in MTX pharmacokinetics previously reported in rats was not observed in these patients.

Aged↗
PubMed1989

Cisplatin/carboplatin cross-resistance in ovarian cancer.

Forty-six patients who were treated with cisplatin or carboplatin for ovarian cancer developed resistant disease (no change in measurable disease or progressive disease) and 'crossed over' to the other platinum compound. Three patients (6.5%) responded to this second treatment but these patients had no survival advantage compared to the non-responders. One responder had progressive disease on cisplatin before crossing over to carboplatin.

Adult↗
PubMed1988

High grade nonHodgkin's lymphoma: management with moderate dose combination chemotherapy.

We have reviewed the management of high grade nonHodgkin's lymphoma in a regional cancer centre over an eight year period. Forty-seven patients were referred with diffuse histiocytic, diffuse undifferentiated and lymphoblastic lymphomas or true histiocytic neoplasms. Twenty-six were treated with doxorubicin, cyclophosphamide, vincristine and prednisone (ACOP). The overall complete remission rate was 73%, 83% for stage I and II disease and 62% for stages III and IV. Kaplan-Meier analysis shows 49% surviving at a median follow up time of 23 months (range 1-108 months) with 11 of the 13 survivors continuously disease free. Toxicity was not severe except for one treatment-related death. Most were treated as outpatients. Patients 70 years of age or older were treated less intensively and only 3 of 14 survive. We conclude that treatment with ACOP is simple and effective in the management of high grade nonHodgkin's lymphoma. Currently our protocol includes the same agents, but at higher dosage, with the addition of methotrexate; we believe this should be tested against the recent more intensive, multiagent alternating regimens in a prospective, randomised clinical trial.

Aged↗
PubMed1986

Effects of verapamil and alcohol on blood flow, melphalan uptake and cytotoxicity, in murine fibrosarcomas and human melanoma xenografts.

Verapamil had previously been shown to increase cellular melphalan uptake and cytotoxicity in fibrosarcomas, and increased the area under the blood concentration versus time curve (AUC) for melphalan in CBA mice. Verapamil (10 mg kg-1 i.p.) had no effect on the fractional distribution of cardiac output (FDCO), measured with 86Rb-rubidium chloride, to subcutaneous fibrosarcomas. 14C-Melphalan uptake by FS13 fibrosarcomas was increased 60 min after verapamil (10 mg kg-1 i.p.), but not after lower doses which did not affect the AUC. Flunarizine (5 mg kg-1 i.p.) also had no effect on FDCO to FS13 fibrosarcomas, and tended to increase 14C-melphalan content of blood and the fibrosarcomas and to promote growth delay by melphalan. Alcohol increased FDCO to FS13 fibrosarcomas, maximally at a 1:20 dilution in saline, but had no effect on 14C-melphalan uptake or growth delay. Thus, melphalan cytotoxicity correlated with tumour melphalan uptake, and both followed changes in the AUC for melphalan but not changes in FDCO. In these murine fibrosarcomas melphalan uptake and cytotoxicity were not limited by blood flow. In subcutaneous human melanoma HX46 xenografts, verapamil had no effect on the FDCO, nor on 14C-melphalan uptake, and did not affect blood 14C-melphalan levels, suggesting absence of effects on the AUC and on cellular uptake. Alcohol did not increase the FDCO to HX46 xenografts, providing evidence for a different vascular supply.

Animals↗
PubMed1986

A phase I evaluation of the quinazoline antifolate thymidylate synthase inhibitor, N10-propargyl-5,8-dideazafolic acid, CB3717.

CB3717 is a quinazoline antifolate whose cytotoxic activity is mediated by inhibition of thymidylate synthase (TS). A phase I clinical trial commenced in September 1981 and 99 patients have received 296 treatments. Doses were dissolved in 0.15 mol/L NaHCO3 (pH 9.0) at a concentration of 4 mg/mL infused over one hour or in a total volume of 1 L infused over 12 hours. Doses were repeated every 3 weeks. The starting dose of 140 mg/m2 was escalated to 600 mg/m2. Renal toxicity, detected by a decrease in the 51Cr EDTA clearance, was dose-related and occurred in seven of ten patients receiving greater than 450 mg/m2. Reversible hepatic toxicity often associated with malaise occurred in 223 of 288 assessable courses (77%). Fifty-nine courses (20%) were associated with increases in alanine transaminase (ALT) levels to greater than 2.5 times the upper limit of the normal laboratory range. Increases in alkaline phosphatase levels also occurred, but were less marked. The severity and prevalence of these elevations were unaffected by the duration of the infusion. A self-limiting rash appeared in 12 patients and a radiation recall reaction was seen in two. Leukopenia developed in 17 patients (WBC less than 3 X 10(9)/L), and thrombocytopenia occurred in six patients (platelets less than 100 X 10(9)/L). The mean leucocyte nadir occurred on day 10 and was followed by recovery at 11 to 19 days. Neither the incidence nor the severity of any of these latter toxicities was dose related. The maximum tolerated dose was in the region of 600 mg/m2 with renal toxicity being dose limiting, although the inter-patient variation did not allow a precise definition. Seventy-six patients were evaluable for response. Responses occurred at doses greater than or equal to 200 mg/m2 and were ovary, one complete response (CR), one partial response (PR), seven minor responses (MR) in 30 cases; breast, two PRs and one MR in eight cases; adenocarcinoma of the lung, one MR in 5 cases; mesothelioma, one PR in five cases; and colon, two MRs in four cases. CB3717 has activity in heavily pretreated patients. The recommended phase II dose for good-risk patients is 400 mg/m2 using the one-hour infusion schedule of administration.

Acetylglucosaminidase↗
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

Epidermal growth factor (hEGF) has no effect on murine intestine epithelial damage and regeneration after melphalan.

The effect of epidermal growth factor (hEGF) on intestinal epithelial damage by melphalan was explored in CBA mice. Human EGF was administered in doses of 100 micrograms kg-1 or 1000 micrograms kg-1 using a variety of schedules. Mucosal damage was assessed 4, 8 and 13 days later, by [14C]-xylose uptake and by microcolony survival of jejunum, ileum and colon. The only regimen to show enhanced jejunal crypt survival was administration of hEGF, 100 micrograms kg-1, i.p., 8 hourly, beginning 24 h before melphalan treatment. Oral administration of hEGF had no effect on melphalan induced damage nor on subsequent recovery of intestinal mucosa. Activity of hEGF in mice was confirmed by demonstration of precocious eyelid opening in newborn mice. No consistent protective or restorative effect of hEGF on melphalan-induced intestinal epithelial damage could be demonstrated with the doses and schedules used.

Animals↗
PubMed1985

Verapamil potentiation of melphalan cytotoxicity and cellular uptake in murine fibrosarcoma and bone marrow.

Growth delay by melphalan of two fibrosarcomas in CBA mice was prolonged by intraperitoneal (i.p.) verapamil, 10 mg kg-1. Verapamil also increased the area under the blood concentration time curve and the gastrointestinal toxicity of melphalan. Verapamil promoted melphalan cytotoxicity to murine bone marrow both in vivo, by CFU-S assay, and in vitro, by CFU-GM assay. In 1 microgram ml-1 [14C]-melphalan, verapamil (10 micrograms ml-1) increased by 1.5 times the [14C]-melphalan accumulation by murine bone marrow, reversibly and independently of external calcium. Efflux of [14C]-melphalan from murine bone marrow was retarded by verapamil. Verapamil increased [14C]-melphalan uptake by disaggregated fibrosarcoma cells but had no effect on melphalan accumulation and cytotoxicity in human bone marrow. Although verapamil affected melphalan pharmacokinetics, enhancement of cellular melphalan uptake by verapamil in murine fibrosarcoma and bone marrow appeared to account for much of the increase in melphalan cytotoxicity. The lack of potentiation of melphalan by verapamil in human marrow suggests differences in melphalan transport or in verapamil membrane interactions in mouse and man.

Animals↗