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Biomedical subjects

P Phillips

Publications and source records attributed to P Phillips.

At least 55 records · Page 3Linked to original sources
PubMed2000

A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse.

A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL). TMZ was given orally at 200 mg/m(2)/day or 150 mg/m(2)/day (prior chemotherapy) for 5 days, repeated every 28 days. PCB was given orally at 150 mg/m(2)/day or 125 mg/m(2)/day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20 (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met the protocol objective. The 6-month PFS rate for those who received PCB was 8% (P = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group (P = 0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for PCB patients (P = 0.019). Freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received. TMZ had an acceptable safety profile; most adverse events were mild or moderate in severity.

Adult↗
PubMed2000

Peritoneal coccidioidomycosis: case report and review.

Peritonitis is an unusual extrapulmonary manifestation of coccidioidomycosis. Peritoneal involvement often has an indolent course and may resolve spontaneously. Optimal management has not been defined; however, fluconazole's spectrum of activity, pharmacokinetic profile, and efficacy in dialysis-related yeast peritonitis suggest that it may be an effective treatment. To our knowledge, we report the first case of coccidioidal peritonitis treated with fluconazole and review the literature.

Aged↗
PubMed2000

Natural history of haemoglobin levels in female blood donors with haemoglobin levels of 120-124 g/l at presentation.

BACKGROUND AND OBJECTIVES: In order to assess the effects of proposed changes to UK guidelines, female blood donors with venous haemoglobin (Hb) levels of 120-124 g/l were followed up over a period of 18 months in order to assess frequency of attendance and ability to donate in relation to changes in Hb and red cell indices, and to determine the effects of inter-donation interval and iron supplementation on outcomes. MATERIALS AND METHODS: Venous samples were analysed using the Haemocue haemoglobinometer at each attendance, and a donation was taken if the Hb was 120 g/l or greater. Full blood counts were done on each sample using the Coulter Model T890. A postal questionnaire was used to elicit additional information, including use of iron supplements. RESULTS: The 392 donors enrolled in the study gave 655 subsequent attendances, resulting in 468 donations (1.5 donations/donor/year). Donors who subsequently had Hb <120 g/l had a tendency to lower initial mean corpuscular volume (MCV), but MCV could not be used as an indicator of future performance. 23% of donors reported use of iron supplements, but those donating 3 times or more were no more likely to use iron supplementation (20%). No statistical relationship was found between inter-donation interval and ability to donate at subsequent attendances. CONCLUSIONS: Female donors with borderline Hb levels proved to be highly committed, with a donation rate of 1. 5/donor/year during the period of follow-up. MCV is not a useful predictor of ability to donate in the future. This subset of the donor population shows wide variation in Hb level over time, and this is largely independent of iron supplementation or inter-donation interval.

Anemia, Iron-Deficiency↗
PubMed2000

Osteoblast-derived cells express functional glucose-dependent insulinotropic peptide receptors.

Glucose-dependent insulinotropic peptide (GIP) is a 42-amino acid peptide synthesized and secreted from endocrine cells in the small intestine. The role of GIP in coupling nutrient intake and insulin secretion, the incretin effect, is well known. We report that GIP receptor messenger RNA and protein are present in normal bone and osteoblast-like cell lines, and that high affinity receptors for GIP can be demonstrated by [125I]GIP binding studies. When applied to osteoblast-like cells (SaOS2), GIP stimulated increases in cellular cAMP content and intracellular calcium, with both responses being dose dependent. Moreover, administration of GIP results in elevated expression of collagen type I messenger RNA as well as an increase in alkaline phosphatase activity. Both of these effects reflect anabolic actions of presumptive osteoblasts. These results provide the first evidence that GIP receptors are present in bone and osteoblast-like cells and that GIP modulates the function of these cells.

Alkaline Phosphatase↗
PubMed2000

Osteoporosis and men. Don't forget the blokes.

BACKGROUND: There is a clear analogy between osteoporosis and hypertension. After all, the fractures associated with osteoporosis can be as disastrous as a cardiovascular event associated with hypertension and both fractures and cardiovascular events, can be greatly reduced by modern treatment. However, osteoporosis is still relatively underdiagnosed, especially in men where it may not be considered an important aspect of men's health. OBJECTIVE: This case study may trigger readers to look for osteoporosis in men at risk and to use the available medications and interventions to preserve bone and avoid falls in such men, thus reducing fractures and associated disability and pain. DISCUSSION: The risk factors for osteoporosis and fracture are known and easily identified and measurement of bone mineral density quantifies bone loss and fracture risk. There are well established strategies to protect bone, to prevent fractures and to maintain comfort. Osteoporosis is already a major public health problem in Australia and will become more important as the proportion of old and the 'old old' increase over the next two decades. Osteoporosis is recognised as an important component of the health of older women and should not be forgotten in older men.

Aged↗
PubMed2000

Phase I clinical trial of the chimeric monoclonal antibody (c30.6) in patients with metastatic colorectal cancer.

The murine antibody 30.6 recognizes an antigen that is expressed on a high proportion of colorectal carcinomas and their metastases. We report the results of single-dose escalation studies of the chimeric 30.6 (c30.6) monoclonal antibody in metastatic colorectal cancer, to evaluate its safety, pharmacokinetics, and biodistribution. Recombinant c30.6 (IgG1kappa) antibody was secreted from Chinese hamster ovary cells and purified by a multistep chromatography process. Seventeen patients with metastatic colorectal cancer were enrolled in this dose escalation study. The first four patients were treated with 3 mg of 123I-labeled c30.6, whereas the next 13 received a single dose of unlabeled antibody (maximum dose, 50 mg/m2). The most frequent side effect was a novel syndrome of severe burning and erythema of the face, chest, neck, ears, palms, soles, and genitalia. The frequency of this syndrome was markedly reduced in those patients premedicated with high doses of histamine receptor 1 and histamine receptor 2 blockers. Other side effects were mild and predictable. Biodistribution studies showed a rapid and intensive hepatic uptake. At the 50 mg/m2 level the half-life and maximum serum concentration were 81 +/- 15 h and 7.9 microg/ml, respectively. One patient developed a low-level human anti-c30.6 response. Tumor response was assessed by computed tomography, positron emission tomography scanning, and serial carcinoembryonic antigen measurements. There were no partial responses, although positron emission tomography scanning demonstrated some reduction in tumor activity in three individuals. The chimerized c30.6 antibody is not immunogenic in humans and appears worthy of further study. It does, however, produce a unique profile of side effects that can be well controlled with premedication.

Adult↗
PubMed1999

Predictors of survival and eradication of Mycobacterium avium complex bacteremia (MAC) in AIDS patients in the Canadian randomized MAC treatment trial. Canadian HIV Trials Network Protocol 010 Study Group.

OBJECTIVE: To assess the importance of baseline characteristics including medical history, indicators of current disease status, therapeutic drug use, in vitro drug susceptibility, immune status and mycobacterial load on bacteriologic response and survival in HIV-positive patients with Mycobacterium avium complex (MAC) bacteremia. DESIGN: An observational substudy of an open-label randomized controlled trial of two alternative therapeutic regimens for MAC. SETTING: Twenty-four hospital-based HIV clinics in 16 Canadian cities. MAIN OUTCOME MEASURES: The main outcome measures were survival and bacteriologic response, defined by consecutive negative blood cultures for MAC at least 2 weeks apart within 16 weeks of study entry. RESULTS: Prior AIDS diagnosis, low Karnofsky score, active unstable AIDS-related conditions, absence of antiretroviral therapy and absence of Pneumocystis carinii pneumonia prophylaxis were associated with shorter survival by univariate regression using the proportional hazards model. On multivariate analysis, antiretroviral therapy was not an independent predictor of mortality, and previous rifabutin prophylaxis was independently associated with poor survival outcomes, a result consistent across study treatment. Using a logistic regression model, baseline quantitative mycobacterial load [relative odds of clearing, 1.97 for a decrease of 1 log10 colony forming count; 95% confidence interval (CI), 1.36-2.87; P < 0.001] and Karnofsky score were the only statistically significant univariate predictors of clearance, although previous prophylaxis with rifabutin was also a significant predictor in a multivariate model (relative odds of clearing, 0.39; 95% CI, 0.17-0.88; P < 0.05). CONCLUSIONS: This study indicates that although the level of MAC bacteremia is an important predictor of clearance, it is not associated with survival.

AIDS-Related Opportunistic Infections↗
PubMed1999

Mycobacterial lymphadenitis associated with the initiation of combination antiretroviral therapy.

OBJECTIVE: To characterize the impact of combination antiretroviral therapy on the clinical and laboratory features of mycobacterial lymphadenitis, we conducted a retrospective chart review of HIV-related mycobacterial lymphadenitis at St. Paul's hospital between 1989 and 1997. Among 52 evaluable patients, 12 presented within 12 weeks of initiating combination antiretroviral therapy (group 1, n = 12); the others developed lesions while receiving no antiretrovirals, monotherapy, or a stable combination regimen of >12 weeks duration (group 2, n = 40). RESULTS: Group 1 patients had higher absolute CD4 lymphocyte counts (median, 150 versus 20 cells/mm3, respectively; p = .001) and hemoglobin levels (median, 113 versus 88 g/L, respectively; p = .002) at the time of mycobacterial diagnosis. Clinical comparison showed that group 1 patients were more likely to develop a draining sinus (50% versus 0%; p < .001), but less often to have weight loss (17% versus 74%; p < .0001) or disease which was disseminated (25% versus 70%; p = .04) or caused by Mycobacterium tuberculosis (0% versus 33%; p = .04). CONCLUSIONS: Mycobacterial lymphadenitis developing within 12 weeks of initiating combination antiretroviral therapy is often localized Mycobacterium avium complex disease, associated with a relatively high CD4 count. The clinical course is often complicated by the development of a draining sinus. The close temporal association suggests that such treatment may unmask subclinical infection by enhancing the immune response to mycobacterial antigens.

AIDS-Related Opportunistic Infections↗
PubMed1999

Questionable history of immediate-type hypersensitivity to penicillin in Staphylococcal endocarditis: treatment based on skin-test results vers-us empirical alternative treatment--A decision analysis.

Approximately 10% of the population claim to be allergic to penicillins, but only approximately 10%-30% of these have IgE-mediated reactions to penicillin skin tests. Alternatives to penicillins may be less effective, more toxic, and more expensive. Therefore, we used decision analysis to calculate maximum expected utility and minimum cost for skin-testing or not skin-testing patients who have endocarditis due to Staphylococcus aureus that is susceptible to cloxacillin and who have a questionable history of immediate-type hypersensitivity to penicillin. We used known probabilities of intermediate outcomes, actual costs, and measured utilities and included one-way sensitivity analysis. Whether utility, cost, or average cost-utility was the outcome of interest, skin-testing was preferred to no skin-testing in most conditions. Patients who have endocarditis due to S. aureus that is susceptible to cloxacillin and who also have a questionable history of immediate-type hypersensitivity to penicillin should be skin-tested before starting antibiotic therapy.

Cloxacillin↗
PubMed1999

Quality of life of adult survivors of germinomas treated with craniospinal irradiation.

OBJECTIVE: To assess the quality of life (QOL) of a group of patients treated for intracranial germinoma with biopsy followed by prophylactic whole-neuraxis radiation therapy. METHODS: The Short-form-36 and Functional Assessment of Cancer Therapy QOL questionnaires were completed by 22 of 27 eligible adults treated with whole-neuraxis irradiation for biopsy-proven, marker-negative intracranial germinomas between 1976 and 1996. In addition, data were obtained regarding height and weight, medications, ability to work, and educational achievement. RESULTS: The patients' QOL was generally good. All of the patients are in or have completed high school; nine are in or have completed college, and five have advanced degrees. Patients rated themselves lower on the physical composite scale of the Short-form-36 (average, 46 versus 54 in a normal population). On the mental composite scale, patients rated themselves more favorably than the normal population (average, 54 versus 49 in a normal population). Patients were normally proportioned for height and weight, but female patients tended to be short. Age at radiation did not correlate with QOL. CONCLUSION: The QOL of adults treated for marker-negative germinoma with prophylactic whole-neuraxis irradiation is generally good. These data should serve as a benchmark for newer treatment protocols eliminating or reducing radiation.

Achievement↗
PubMed1999

The antihypertensive efficacy of the combination of irbesartan and hydrochlorothiazide assessed by 24-hour ambulatory blood pressure monitoring. Irbesartan Multicenter Study Group.

In a multicenter, double-blind, randomized trial, 178 patients with ambulatory diastolic blood pressure (BP) > or =85 mm Hg and seated diastolic BP (SeDBP) 95-110 mm Hg received either once-daily irbesartan 75 mg/hydrochlorothiazide (HCTZ) 12.5 mg, irbesartan 150 mg/HCTZ 12.5 mg, or placebo for 8 weeks to assess reductions in 24-hour ambulatory BP and office BP. Safety and tolerability of all treatment regimens were also evaluated. BP results and therapeutic response (trough SeDBP normalized to <90 mm Hg) were expressed as change from baseline to Week 8. Mean reductions in 24-hour ambulatory BP and office seated BP for irbesartan/HCTZ combinations were significantly greater compared with placebo (all, p<0.01). More patients were normalized with irbesartan/HCTZ (65%-69%) than placebo (24%, p<0.01). The frequency of adverse events was similar in all groups. Irbesartan/HCTZ given once-daily appears to be a well-tolerated, safe, and effective antihypertensive treatment.

Adult↗
PubMed1999

Quality assurance for cell substrates.

Animal cell lines are increasingly used in the manufacture of viral vaccines. They may play a key role in the preparation of seed stock virus and vaccine production. However, the same animal cell substrates may also be used for diagnosis of viral infection and surveillance of prevalent virus strains. Quality control of cell lines intended for use in this range of procedures is vital to ensure the absence of contaminating organisms and correct identity of the substrate cells used. Furthermore, the qualification and validation of the procedures, facilities and staff involved in the cell culture and testing are also important issues addressed in regulatory guidelines and regulations. The standards to which these activities are performed are dependent on whether the cells are intended for diagnostic and surveillance work or for seed stock virus isolation and production. This paper indicates when and how some of the relevant quality standards and quality control issues apply to cell lines intended for the different procedures involved in virus isolation and vaccine production.

Animals↗
PubMed1999

p53-independent increase in E2F-1 expression enhances the cytotoxic effects of etoposide and of adriamycin.

The transcription factor E2F-1 drives cell cycle progression at the G1- to S-phase boundary; however, overexpression of E2F-1 can induce apoptosis. We show here that E2F-1 protein levels increase in human medulloblastoma, glioma, lung, colon, and bladder cancer cell lines (n=7) following treatment with the DNA damaging agents adriamycin or etoposide. This induction of E2F-1 occurs independently of Rb or p53 status and involves new protein synthesis. Although E2F-1 protein levels increase following DNA damage, several genes transcriptionally targeted by E2F-1 are not similarly induced. Rather, induction of E2F-1 in the tumor cells correlates with their sensitivity to adriamycin or to etoposide. Correspondingly, fibroblasts from E2F-1 knockout mice are more resistant to DNA damage than cells from normal mice. Overexpression of E2F-1 protein in tumor cell lines infected with an adenovirus encoding wild-type E2F-1 leads to enhanced cytotoxicity following exposure to DNA damaging agents, which results from enhanced apoptosis. The results of this study implicate a role for E2F-1 in p53-independent cytotoxicity of chemotherapy and provide a pharmacological tool for increasing levels of the apoptosis-inducing E2F-1 protein.

Animals↗