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Biomedical subjects

P A Andrews

Publications and source records attributed to P A Andrews.

At least 19 recordsLinked to original sources
PubMed2001

Cytomegalovirus infection and abdominal pain with mycophenolate mofetil: is there a link?

Mycophenolate mofetil (MMF) is an immunosuppressive agent that exerts relatively selective antiproliferative effects on T and B lymphocytes. Efficacy has been demonstrated in large-scale randomised studies, but the use of MMF is complicated by gastrointestinal upset and is associated with an increased incidence of tissue-invasive cytomegalovirus (CMV) disease. The gastrointestinal tract is a well recognised site for invasive CMV disease, and it has therefore been hypothesised that the abdominal pain commonly seen with MMF is related to CMV infection. This has only been tested in a single small uncontrolled study, where abdominal pain was associated with the presence of CMV on endoscopic biopsy. In contrast, the toxicity profile in 85 patients with psoriasis who had received relatively high dosages of mycophenolic acid, the active moiety of MMF, for up to 13 years showed that the incidence of gastrointestinal upset fell dramatically over time. We can find little evidence that CMV disease explains the gastrointestinal adverse event profile associated with MMF, and instead support the contention that high local concentrations of MMF have a direct toxic effect on cells of the small intestine. We do not recommend any changes to current policy on CMV prophylaxis in patients receiving MMF, although we recognise that some severe gastrointestinal adverse effects may be CMV-associated. The use of trough plasma concentration monitoring, divided doses and a gradually increasing dosage schedule may be of value in limiting toxicity.

Cytomegalovirus Infections↗
PubMed2001

Breast cancer: incidence, mortality, and early detection in Louisiana, 1988-1997.

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death among Louisiana women. The incidence data from Louisiana Tumor Registry were used to calculate breast cancer incidence rates, which were compared with the combined rates from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program. Breast cancer mortality rates for Louisiana were compared with the US death rates from the National Center for Health Statistics (NCHS). Our data revealed that Louisiana women were not at a higher risk for developing breast cancer than women in the SEER areas, but that mortality rates in Louisiana were not correspondingly low. Although the percentage of cases diagnosed at an early stage (in situ and localized) increased in Louisiana from 1988 through 1997, the average in Louisiana was still below the level for the SEER areas (65.9% and 71.6%) in 1993-1997. The rates of in situ breast cancer significantly increased (on average 5.3% for whites per year and 7.1% for blacks), and localized breast cancer also significantly increased (2.6% for whites and 2.5% for blacks), while the incidence of distant stage breast cancer significantly decreased (3.4% for whites and 2.0% for blacks). Compared with white women, black women still were less likely to be diagnosed with early stage breast cancer in 1993-1997 (56.4% and 68.9%). Women residing in the parishes with high percentages of persons in poverty were less likely to be diagnosed with early stage of disease.

Black People↗
PubMed2000

Decreased cisplatin/DNA adduct formation is associated with cisplatin resistance in human head and neck cancer cell lines.

PURPOSE: To evaluate the correlation between cisplatin sensitivity, intracellular glutathione, and platinum/DNA adduct formation (measured by atomic absorption spectroscopy) in a series of seven head and neck cancer cell lines, and to evaluate the effect of biochemical modulation of glutathione on platinum/DNA adduct formation and repair. METHODS: Cisplatin/DNA adducts were measured by atomic absorption spectroscopy. Glutathione content was measured by enzymatic assay and was modulated with buthionine sulfoximine. Apoptosis was measured by double-labeled flow cytometry. RESULTS: Intracellular glutathione concentration was strongly correlated with cisplatin resistance (P = 0.002, R2 = 0.7). There was also a statistically significant inverse correlation between cisplatin/DNA adduct formation and the IC50 for cisplatin in these cell lines. (P = 0.0004, R2 = 0.67). In addition, resistant cells were able to repair approximately 70% of cisplatin/DNA adducts at 24 h, while sensitive cells repaired less than 28% of adducts in the same period. However, despite the positive correlation between cellular glutathione and cisplatin resistance, there was no direct correlation between intracellular glutathione concentration and platinum/DNA adduct formation. Further, depletion of intracellular glutathione by buthionine sulfoximine did not dramatically alter formation of cisplatin/DNA adducts even though it resulted in marked increase in cisplatin cytotoxicity and was associated with increased apoptosis. CONCLUSIONS: These results suggest that glutathione has multiple effects not directly related to formation of cisplatin/DNA adducts, but may also be an important determinant of the cell's ability to repair cisplatin-induced DNA damage and resist apoptosis.

Antineoplastic Agents↗
PubMed1999

Cancer of the colon and rectum in Louisiana.

Cancer of the colon and rectum ranks fourth for incidence and second for mortality among Louisiana residents. Incidence rates calculated from Louisiana Tumor Registry data for 1991-95 show that whites in Louisiana were diagnosed with colon cancer at approximately the same rates as those in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, but rates for African Americans were significantly lower in Louisiana than nationally. For rectal cancer, Louisiana incidence rates approximate the national rates for all but African-American males, whose rate was significantly lower. Mortality rates for colon and rectal cancer in Louisiana were comparable to the SEER rates, suggesting Louisiana blacks, once diagnosed, have a poorer survival than their national counterparts. Risk factors for colorectal cancer and guidelines for screening are discussed, as is an upcoming study of patient care for colon cancer.

Adult↗
PubMed1999

Louisiana Tumor Registry: new developments and activities.

New developments in the Louisiana Tumor Registry (LTR) over the past 3 years have enhanced the operation of the LTR and broadened its functions. Recent funding for numerous special studies and research collaborations have expanded the registry activities from data collection and special etiologic studies to more completely address the mandates of registry law, which require the LTR to participate in studies of cancer causes, treatment, and survival in order to reduce cancer morbidity and mortality in Louisiana.

Humans↗
PubMed1999

Predictive value of preclinical toxicology studies for platinum anticancer drugs.

Rodent and nonrodent toxicology studies are currently expected to support Phase I trials of antineoplastic drugs in the United States. To determine the predictive value of these studies, we initiated a project to compare preclinical and clinical toxicity data within various drug classes. The first class analyzed was the platinum anticancer drugs. Twelve platinum analogues that had both preclinical (mice, rats and/or dogs) and clinical data from matching drug administration schedules were identified. The rodent LD10 (the dose that causes lethality in 10% of treated animals) or dog toxic dose high (a dose that when doubled causes lethality in dogs) correlated well with the human maximally tolerated dose on a mg/m2 basis. For every platinum analogue investigated, one-third the rodent LD10 or one-third the dog toxic dose high in mg/m2 gave a starting dose and a first escalation dose that did not exceed the clinical maximally tolerated dose. The dose-limiting toxicities in patients were previously observed in 7 of 7, 7 of 8, and 9 of 11 mouse, rat, and dog studies, respectively. Our data indicate that mice, rats, and dogs all had value in predicting a safe starting dose and the qualitative toxicities in humans for platinum anticancer compounds. The efficiency of Phase 1 trials could have been improved without sacrificing patient safety by allowing higher starting doses for this drug class than conventionally permitted.

Animals↗
PubMed1998

Heart failure.

Explore the source record for details and available documents.

Cardiac Output, Low↗