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Biomedical subjects

J Purvis

Publications and source records attributed to J Purvis.

At least 19 recordsLinked to original sources
PubMed2000

Effects of a medicine review and education programme for older people in general practice.

AIMS: To determine whether a medicine review and education programme influences the compliance and knowledge of older people in general practice. METHODS: Older people taking at least three medicines were randomly allocated to a control or intervention group. Both groups received three visits from a clinical pharmacist: Visit 1: Assessment and patients' medicines rationalized in intervention group. Visit 2: Intervention group given medicines education. Visit 3: Knowledge and compliance in both groups assessed by structured questionnaire RESULTS: Compliance in the intervention group was 91.3%, compared with 79.5% in the control group (P < 0.0001). The number of intervention group patients correctly understanding the purpose of their medicines increased from 58% to 88% on the second visit, compared with 67% to 70% in the control group (P < 0.0005). CONCLUSIONS: A general practice based medication review and education programme improved medicine compliance and knowledge of older people in the short term.

Aged↗
PubMed2000

Phase I pharmacokinetic study of the novel antitumor agent SR233377.

SR233377 is a novel thioxanthenone analogue that demonstrated solid tumor selectivity in vitro with activity confirmed in vivo against several murine tumors including those of colon, pancreas, and mammary origin. Its primary preclinical dose-limiting toxicities included myelosuppression and neurological toxicity. The neurological toxicity was acute and could be ameliorated in mice when the drug was administered as a 1-h infusion instead of rapid i.v. injection. As a result of its preclinical efficacy profile, SR233377 entered Phase I clinical investigation. The compound was administered i.v. over 2 h on day 1 repeated every 28 days. The starting dose was 33 mg/m2 (one-tenth the mouse LD10). Escalations continued to 445 mg/m2 (six escalations), where dose-limiting toxicity was observed. At this dose, acute ventricular arrhythmias, including one patient with torsades de pointes and transient cardiac arrest, occurred. Because this toxicity might have been related to the plasma peak, the protocol was amended to a 24-h infusion beginning at 225 mg/m2. With this dose, prolongation of the corrected QT interval (QTc) over the pretreatment levels resulted. Because prolonged QTc is a known forerunner to acute ventricular arrhythmias, clinical development of SR233377 was stopped. However, preclinical antitumor and toxicity studies with analogues are underway with hopes of identifying a new clinical candidate with similar antitumor effects that is devoid of cardiac toxic effects.

Adult↗
PubMed1998

Transposed basilic vein versus polytetrafluorethylene for brachial-axillary arteriovenous fistulas.

BACKGROUND: Both transposed basilic vein (BV) and polytetrafluorethylene (PTFE) upper arm arteriovenous fistulas (AVF) are common angioaccess operations. To evaluate the patency and complication rates after AVF, a concurrent series of patients was reviewed. METHODS: Ninety-eight patients underwent brachial artery to axillary vein AVF: 30 BV and 68 PTFE. The PTFE grafts were performed in the standard fashion, whereas the basilic veins were translocated subcutaneously to the brachial artery. RESULTS: Risk factors were similar between the two groups. Basilic vein AVF had better patency at 24 months (70% BV versus 46% PTFE, P = 0.023). The dialysis access complications were higher in the BV group (20%) versus PTFE (5%), but the PTFE group had a higher infection rate (10%) than BV (0%). CONCLUSIONS: The primary and secondary patency rates were superior in the BV AVFs. The BV AVF preserves the venous outflow tract after AVF thrombosis for a future PTFE AVF operation.

Arteriovenous Shunt, Surgical↗
PubMed1998

Influence of insulin on follicular development and the intrafollicular insulin-like growth factor I (IGF-I) system in sows after weaning.

Twenty-four crossbred primiparous sows were used to investigate the influence of insulin administration after weaning on the intrafollicular insulin-like growth factor i (IGF-I) system. Sows received 0.4 i.u. insulin kg-1 bodyweight or an equivalent volume of saline for 3 days (n = 5 insulin; n = 4 saline) or 5 days (n = 5 insulin; n = 6 saline) after weaning or served as untreated controls on day 1 (n = 4). The number and diameters of ovarian follicles were recorded, and fluid was aspirated from the 20 largest follicles for determination of oestradiol and IGF-I by radioimmunoassay and of insulin-like growth factor-binding proteins (IGFBPs) by western ligand blotting. The walls of the follicles were collected for mRNA analysis by RNase protection assay or granulosa cells were collected for estimation of apoptosis by flow cytometry. Insulin treatment resulted in smaller diameters of all follicles (P < 0.05) and tended (P < 0.07) to increase the number of follicles available on day 5 compared with saline-treated animals (19.8 versus 17.8). The concentration of oestradiol in follicular fluid from large (7-10 mm) follicles on days 3 and 5 was reduced (treatment by size class interaction; P < 0.05) by insulin treatment. Insulin also reduced intrafollicular concentrations of IGF-I at days 3 and 5 after weaning (treatment by day interaction; P < 0.02) while the amounts of IGFBP-3 and IGFBPs of molecular mass 30 and 22 kDa decreased from day 3 to day 5 in saline-treated animals only (treatment by day interaction; P < 0.05). Gene expression for IGF-I increased in saline-treated animals but decreased fourfold in insulin-treated sows from day 3 to day 5 (treatment by day interaction; P < 0.002). Gene expression for IGFBP-d decreased (P < 0.04) from day 3 to day 5, while expression of IGFBP-2 was unaffected by treatment or day. Overall, insulin influenced the IGF-I system in a manner consistent with slowing follicular growth and possibly allowed more follicles to become available for ovulation.

Animals↗
PubMed1995

Effects of self medication programme on knowledge of drugs and compliance with treatment in elderly patients.

OBJECTIVE: To determine whether a programme of self medication for inpatients improves compliance with treatment and knowledge of their drugs after discharge from hospital. DESIGN: Patients were prospectively recruited from four wards: two with a self medication programme and two acting as controls. Ten days after discharge the patients were visited at home. They were questioned about their drugs, and a tablet count was undertaken. SETTING: The pharmacy department and four medical wards with an interest in elderly patients at a district general hospital, and the patients' homes. PATIENTS: 88 patients discharged to their own homes who were regularly taking one or more drugs. INTERVENTION: A hospital self medication programme in which patients are educated about their medicines and given increasing responsibility for taking them in hospital. MAIN OUTCOME MEASURES: Compliance with and knowledge of the purpose of their medicines 10 days after discharge from hospital. RESULTS: The mean compliance score in patients taking part in the self medication programme was 95% compared with 83% in the control group (difference 12%, 95% confidence interval 4% to 21%; P < 0.02). Of the patients in the self medication group, 90% (38/42) knew the purpose of their drugs compared with 46% (17/37) in the control group (difference 44%, 26% to 63%; P < 0.001). CONCLUSION: A self medication programme is an effective aid for improving compliance with and knowledge of patients' drugs after discharge.

Aftercare↗
PubMed1995

Biloma and biliary fistula following hepatorraphy for liver trauma: incidence, natural history, and management.

From 1986-1992, more than 6250 patients were admitted to a Level I Trauma Center, with 175 patients requiring hepatorraphy. Eleven patients (6%) developed either a biloma (1), biliary fistula (2), or both (8 patients). Patients' ages ranged from 15-40 years with a mean Injury Severity Score of 23. Seven patients (64%) suffered penetrating injury and four (36%) were victims of blunt trauma. The right lobe was injured in 10 patients (91%), with one patient (9%) sustaining left lobe injury. All liver injuries were either grade 3 (seven patients, 64%) or grade 4 (four patients, 36%). No patient sustained extrahepatic biliary tract injury. Bilomas and fistulas were diagnosed 14-30 days post injury (mean 24 days) by CT and HIDA scans. All were managed by CT-guided percutaneous drainage. One patient also required percutaneous transhepatic cholangiography with biliary stent placement due to bile ascites. Fistulas persisted from 5-120 days (mean 44 days). No patient required further operative intervention and all fistulas closed spontaneously without complication.

Adolescent↗
PubMed1992

Phase I study of BCNU and intravenous 6-mercaptopurine in patients with anaplastic gliomas.

On the basis of response rates of up to 50%, BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] is the primary drug used in the chemotherapy of anaplastic gliomas. Preclinical data obtained in several experimental systems show that the cytotoxicity of chloroethylnitrosoureas can be increased by the concomitant use of thiopurines. In this phase I trial, patients with anaplastic gliomas received standard-dose BCNU (200 mg/m2 x 1) in combination with escalating doses of intravenous 6-mercaptopurine (200, 350, 500, and 750 mg/m2 daily x 3), with BCNU being given on day 3 to maximize the effect of the drugs on cellular DNA. No increase in hematologic toxicity was demonstrated as the dose of 6-mercaptopurine was increased. Responses and stabilization of disease were observed in several patients. Due to the safety of and the evidence of activity found for this regimen in the present trial, 750 mg/m2 6-mercaptopurine has been incorporated into subsequent studies.

Adolescent↗
PubMed1991

Clinically unsuspected inclusion body myositis.

We describe a patient with inclusion body myositis presenting as chronic, therapy resistant polymyositis. Our report highlights the slow evolution of inclusion body myositis in some patients, and emphasizes the diagnostic importance of examining one or more muscle biopsy specimens by both frozen section and electron microscopy.

Biopsy↗
PubMed1991

The initial electrocardiogram in patients seen by a mobile coronary care unit.

The advent of thrombolytic therapy for patients with suspected acute myocardial infarction has highlighted the importance of the initial electrocardiogram (ECG) in decision making. Thus we analysed the initial ECGs of 94 consecutive cases with suspected myocardial infarction who were seen within six hours after the onset of chest pain by a mobile coronary care unit. The study included 91 patients (three patients admitted twice) (61 male), aged 27-83 years (mean 60.5). Median time from onset of chest pain to arrival of the mobile coronary care unit was 75 minutes (range 15-345), and mean mobile coronary care unit response time was 12.3 +/- 7 (SD) minutes (range 5-45). The majority of cases (65 of 94, 69.1 per cent) were seen within two hours of the onset of symptoms. A final diagnosis of myocardial infarction was made in 48 of 94 (51.1 per cent) cases; 38 had unstable angina and eight other diagnoses. Of the 48 with myocardial infarction the initial ECG showed ST segment elevation in 37, ST depression and or T wave inversion in six, Q waves only in three and left bundle branch block in two. No patient with an initially normal ECG had a myocardial infarction. Thrombolytic therapy was given out of hospital to 33 of 38 patients with ST segment elevation. In seven patients with ST elevation (median delay time to intensive care 60 minutes), rapid resolution of ST segment elevation occurred following thrombolytic therapy and there was no significant elevation of cardiac enzymes, suggesting that the infarct had been aborted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Phase I and clinical pharmacology trial of 502U83 using a monthly single dose schedule.

502U83 is an arylmethylaminopropanediol derivative exhibiting significant antineoplastic activity in a number of murine and human tumor models. In this Phase I trial, a 1-h or 4-h infusion of the agent was administered i.v. in 250 ml of 5% dextrose in water every 28 days. Fifty-three courses at doses of 25 to 2000 mg/m2 were administered to 36 patients with refractory solid tumors. Prolongation of the PR, QRS, and QT intervals on electrocardiograms was dose limiting at 2000 mg/m2. This prolongation appeared dose related and was reversible upon discontinuation of the infusion. No hematological toxicity was observed. Other toxicities included only sporadic and mild to moderate nausea and vomiting. No tumor responses were noted. 502U83 plasma concentrations were determined by high-pressure liquid chromatography. Complete pharmacokinetic profiles were obtained for 21 of the 36 patients. After infusion, plasma concentrations declined in a biexponential or in a triexponential manner with a harmonic mean terminal t 1/2 of 8.83 h. Using a three-compartment model, the mean apparent volume of distribution at steady state and total-body clearance were 195 liters/m2 and 42.5 liters/h/m2, respectively, indicative of extensive tissue distribution. No correlation could be found between the pharmacokinetic parameters and prolongation of the cardiac conduction intervals. Because of the cardiac effects with the drug, the schedule of administration of 502U83 used in this study cannot be recommended.

Adult↗
PubMed1988

Cytokeratins in cervical dysplasia and neoplasia: a comparative study of immunohistochemical staining using monoclonal antibodies NCL-5D3, CAM 5.2, and PKK1.

The expression of low molecular weight cytokeratins (normally expressed only in simple epithelia) in intraepithelial neoplasia of grade CIN III or greater in cervical biopsies has recently been described by Bobrow et al. Our study of 127 cases confirms this finding and in addition we compare the use of three monoclonal antibodies, namely NCL-5D3, CAM 5.2, and PKK1, in demonstrating the phenomenon. Both NCL-5D3 and CAM 5.2 give consistently negative results for non-neoplastic stratified squamous epithelium, as well as CIN I and CIN II lesions, whilst staining about 30 per cent of CIN III biopsies and most carcinomas. PKK1, on the other hand, stained 50 per cent of non-neoplastic epithelia and thus did not serve as a marker of severe dysplasia. The possible implications of these observations are discussed.

Antibodies, Monoclonal↗
PubMed1988

Alternating non-cross-resistant chemotherapy for metastatic hormone-independent breast cancer.

A phase II clinical trial was designed to apply the treatment strategy of alternating non-cross-resistant chemotherapy regimens to patients with metastatic estrogen-receptor negative or hormone-refractory breast cancer. Twenty-six patients received Adriamycin and cyclophosphamide alternating at 3-week intervals with the combination of vinblastine, mitomycin-C, and 5-fluorouracil (5-FU). Toxicity was moderately severe. Two patients developed grade 2 and three developed grade 1 stomatitis. A single patient developed a WBC count of less than 1000/mm3, whereas five had a lowest recorded WBC count of 1,000-1,999/mm3. Two patients displayed thrombocytopenia of less than 50,000/mm3, one in conjunction with a fatal hemolytic-uremic syndrome. There were six complete and eight partial responses (PRs) for an objective response rate of 54% (64% of fully evaluable patients). The median survival after onset of protocol therapy was 13.3 months. These results are no better than those reported for other Adriamycin-containing regimens.

Adult↗
PubMed1988

Clinical modulation of doxorubicin resistance by the calmodulin-inhibitor, trifluoperazine: a phase I/II trial.

Drug resistance to chemotherapy agents such as doxorubicin appears to be an important cause of therapeutic failure in cancer treatment. Based on preclinical information demonstrating that the phenothiazine calmodulin-inhibitor trifluoperazine can enhance retention and cytotoxicity of doxorubicin in resistant cells, a phase I/II trial of the combination was performed to determine the maximally tolerated dose (MTD) of trifluoperazine that could be administered with doxorubicin. Patients with intrinsic (no previous response) and acquired (previous response with relapse) doxorubicin resistance were eligible. Doxorubicin was administered as a 96-hour continuous infusion (60 mg/m2) on days 2 through 5. Trifluoperazine was administered in divided doses orally on days 1 through 6, with dose escalation from 20 to 100 mg/d. Thirty-six patients were evaluable. The MTD of trifluoperazine was 60 mg/d, with dose-limiting toxicity being extrapyramidal side effects. No alteration of doxorubicin toxicity was observed. Seven of the 36 patients responded (one complete response [CR], six partial responses [PR]), with seven of 21 patients having acquired resistance, and zero of 15 with intrinsic resistance demonstrating responses. Doxorubicin plasma levels were not affected by trifluoperazine, and the maximal trifluoperazine plasma levels achieved were 129.83 ng/mL. This trial demonstrates the combination of trifluoperazine and doxorubicin is well tolerated, and the schedule recommended for phase II trials is doxorubicin, 60 mg/m2 (continuous infusion) days 2 through 5, and trifluoperazine, 15 mg four times per day orally days 1 through 6. Continued investigation of this combination is indicated for patients with acquired doxorubicin resistance.

Adult↗
PubMed1987

NCL-5D3: a new monoclonal antibody recognizing low molecular weight cytokeratins effective for immunohistochemistry using fixed paraffin-embedded tissue.

Production of a new monoclonal antibody designated NCL-5D3 is described. The antibody recognizes several low molecular weight cytokeratins, in particular cytokeratin Moll number 8 as determined by immunoblotting studies, and is highly effective for immunocytochemistry using routinely processed paraffin-embedded material. Staining is enhanced by prior treatment of the sections with trypsin. Assessment using a wide variety of normal and neoplastic tissue indicates reactivity with all tissues of simple or glandular epithelial origin, and in addition with many squamous carcinomas. Thus the antibody should prove of value in diagnostic histopathology.

Antibodies, Monoclonal↗