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Biomedical subjects

A McDonald

Publications and source records attributed to A McDonald.

At least 55 records · Page 3Linked to original sources
PubMed1999

Phase I/pharmacokinetic study of the topoisomerase I inhibitor GG211 administered as a 21-day continuous infusion.

BACKGROUND: Preclinical results support a prolonged schedule of administration for topoisomerase I inhibitors, and we have previously demonstrated the safety and activity of the novel water-soluble topoisomerase I inhibitor GG211 when given as a 72-hour continuous infusion to cancer patients. PATIENTS AND METHODS: In a three-center international phase I trial, 38 patients received GG211 doses from 0.3 to 0.5 mg/m2/day by continuous intravenous infusions for seven, 14, and 21 days. Patients' median performance status was 1; nearly half had colorectal cancer, and 35 patients had prior chemotherapy. RESULTS: The first patient cohort received 0.3 mg/m2/day for seven days with no significant toxicities. Subsequent cohorts received continuous infusions for 14 and 21 days at this dose level with only mild myelosuppression noted. Dose-escalation on the 21-day schedule was then performed. No dose-limiting toxicity occurred at the 0.4 mg/m2/day dose level. Thrombocytopenia was dose-limiting with 0.5 mg/m2/day dosing but was not cumulative. Other grade 3 4 toxicities included neutropenia, nausea, vomiting, diarrhea, and fatigue. Partial responses occurred with 21-day infusion in two patients with breast and ovarian cancer at the 0.3 and 0.4 mg/m2/day dose levels, respectively. Mean GG211 lactone Css ranged from 0.17 to 0.64 ng/ml. CONCLUSION: The maximum tolerated dose of GG211 administered as a 21-day continuous infusion is 0.4 mg/m2/day with antitumor activity noted at tolerable doses.

Adult↗
PubMed1999

The persistence and clonal spread of a single strain of Acinetobacter 13TU in a large Scottish teaching hospital.

This study describes the persistence and spread of a single strain of Acinetobacter 13TU in a large Scottish teaching hospital. Acinetobacter spp. are reported with increasing frequency as a cause of nosocomial infection. The species most implicated in these infections is Acinetobacter baumannii. Following an outbreak of infection with Acinetobacter 13TU within the intensive therapy unit (ITU) of Edinburgh Royal Infirmary (ERI) during 1994-1995, the current epidemiological Acinetobacter situation within the hospital was monitored to determine whether or not control of infection procedures instigated at that time had been successful in controlling the outbreak. Sixty-eight strains of Acinetobacter spp were isolated from clinical specimens received from various wards in the ERI and other associated hospitals over a 7-month period. Each isolate was typed phenotypically by the API20NE system and genotypically by pulsed field gel electrophoresis (PFGE) in order to compare them with the previous outbreak strain. Fifty-three percent of the isolates collected were originally identified as A. junii by API 20 NE, of which 83% (mainly from ITU) were shown to be genotypically related to the previous outbreak strain. Subsequent tDNA fingerprinting of one of the original outbreak strains showed it to be a member of the genospecies 13TU and not A. junii as originally thought.

Acinetobacter↗
PubMed1999

(Alpha)3(beta)1 integrin regulates epithelial cytoskeletal organization.

Epithelial cell morphology and cytoskeletal organization are determined by interactions, with both adjacent cells and the extracellular matrix, which are mediated by integrins and cadherins. Little is known, however, of the relative contributions of integrins and cadherins to maintaining the sub-cortical cytoskeleton characteristic of epithelial cells. Since most studies that utilize integrin-blocking antibodies result in a loss of both cell-cell adhesion and sub-cortical cytoskeletal organization, it has been difficult to distinguish whether integrins and cadherins both mediate cytoskeletal assembly in epithelial cells. Therefore, cells derived from kidney collecting ducts of (alpha)3(beta)1 integrin-deficient mice were used to examine the role of integrins in epithelial cell morphology and cytoskeletal organization. In primary cell culture, (alpha)3(beta)1 integrin-deficient kidney collecting duct cells maintain cadherin-mediated cell-cell adhesions but fail to form the sub-cortical cytoskeleton that is characteristic of epithelial cells, and instead assemble actin stress fibers. Moreover, the cell-cell junctions in mutant cells were irregular, rather than being uniformly oriented perpendicular to the culture substrate. These results demonstrated that integrins have an primary and essential function in establishing and maintaining the sub-cortical cytoskeleton that is characteristic of epithelial cells. To further study the role of (alpha)3(beta)1 integrin in establishing and maintaining cytoskeletal organization in tubular epithelial cells, we derived immortalized cell lines from wild-type and (alpha)3(beta)1 integrin-deficient kidney collecting ducts that duplicated the cytoskeletal and cadherin organization observed in primary cells. E-cadherin and (alpha)- and (beta)-catenin were complexed together in equal amounts in membranes of wild-type and (alpha)3(beta)1 integrin-deficient cells. However, association of the cadherin:catenin complex with (alpha)-actinin was greatly decreased in mutant cells, indicating that integrin-mediated assembly of the sub-cortical cytoskeleton is essential for subsequent association of the cytoskeleton with the cadherin:catenin complex. These results present direct evidence for integrin:cadherin cross-regulation in which cadherin function is dependent on the presence of an integrin.

Animals↗
PubMed1999

Trauma aetiology and cost in the Accident and Emergency Unit of the University Hospital of the West Indies.

Trauma accounted for 37% of 22,311 patients seen in the Accident and Emergency Unit (A&E Unit) at the University Hospital of the West Indies (UHWI) during 1996. Thirty-nine per cent of injuries were intentional and 18% were due to motor vehicle accidents. Knives, machetes and rocks accounted for 75% of the injuries compared with 5% for gunshot wounds. Passengers were injured in about 40% of motor vehicle accidents and pedestrians in 19%. The admission rate was 16% and the orthopaedic clinic received 75% of the patients referred to specialist clinics. Victims of motor vehicle accidents made up a greater proportion of admissions (24%) than those of intentional violence (13%). The average cost of caring for each patient in the A&E unit was US$70 resulting in an annual cost of US$578,000.

Adolescent↗
PubMed1999

Alcohol, cannabis and cocaine usage in patients with trauma injuries.

Sera from 111 patients with trauma injuries, who presented to the Accident and Emergency Unit (A&E), University Hospital of the West Indies, during a 3-month period, were screened for blood alcohol. Urine specimens were analysed for metabolites of cannabis and cocaine. Sixty-two per cent (62%) of patients were positive for at least one substance and 20% for two or more. Positivity rates were as follows: cannabis (46%), alcohol (32%) with 71% of these having blood alcohol levels (BAC) greater than 80 mg per decilitre; cocaine (6%). Substance usage was most prevalent in the third decade of life. The patients who yielded a positive result were significantly younger than those who were negative. There was no significant difference in age or substance usage between the victims of interpersonal violence or road traffic accidents. In the group designated "other accidents", patients were significantly older and had a lower incidence of substance usage than the other two groups. Cannabis was the most prevalent substance in all groups. Fifty per cent (50%) and fifty-five per cent (55%) of victims of road accidents and interpersonal violence, respectively, were positive for cannabis compared with 43% and 27% for alcohol, respectively. There was no significant difference in Hospital Stay or Injury Severity Score between substance users and non-users.

Adolescent↗
PubMed1997

Setting air quality standards for carcinogens: an alternative to mathematical quantitative risk assessment-discussion paper.

It has been accepted in many countries that the regulation of ambient air quality should involve the use of health-based air quality standards. Setting standards for air pollutants which are genotoxic carcinogens presents difficult problems to the regulator, in that the prediction of the effects on health of low levels of exposure is suspected to be inaccurate, and is not currently amenable to either experimental or epidemiological verification. In some countries, techniques of mathematical quantitative risk assessment have been adopted to calculate acceptable levels of exposure to, or the unit risk factors for, genotoxic carcinogens. We regard these approaches as unsatisfactory. An alternative approach, based upon a number of argued premises, a strategy which identifies decision points and the cautious application of uncertainty factors, is described.

Air Pollutants↗
PubMed1997

Torsion of an intra-abdominal testicle in a neonate. Case report and review of the literature.

The thirty-ninth reported case of torsion of an intra-abdominal testicle is described in a neonate. The gonad was excised as is recommended because of the high incidence of malignancy (60% of 37 cases). Torsion of an intra-abdominal testicle should be considered where an abdominal mass with calcification is found in an infant with undescended testis. Ultrasonography improves the diagnostic accuracy in infants because of the cystic nature of these masses in this age group.

Cryptorchidism↗
PubMed1997

Factors to consider while treatment planning dental implants in the partially edentulous patient.

Although short-term studies of dental implants in the partially edentulous patient appear very promising, multicenter long-term studies are not yet available. Since the differences between dental implants and teeth are significant, treatment planning for the partially edentulous patient is more difficult. This paper will discuss important areas to be examined in treatment planning the partially edentulous patient.

Alveolar Process↗
PubMed1997

Phase I and pharmacokinetic study of tirapazamine (SR 4233) administered every three weeks.

Tirapazamine (SR 4233; 3-amino-1,2,4-benzotriazine-1,4-di-N-oxide) is a bioreductive agent exhibiting up to 200 x greater toxicity for hypoxic cells as compared to oxygenated cells. In murine studies, a selective increase in tumor kill was observed when tirapazamine was coadministered with other agents, notably cisplatin. A Phase I study of single-agent tirapazamine administered i.v. every 3 weeks was conducted to determine the toxicity of a schedule for use with systemic chemotherapy. A total of 28 patients were given 50 courses of tirapazamine at doses ranging from 36-450 mg/m2. No tumor responses were observed. Reversible deafness and tinnitus were dose-limiting, with ototoxicity observed in 1 of 6 patients treated at 330 mg/m2, 1 of 4 patients treated at 390 mg/m2, and 3 of 3 patients treated at 450 mg/m2. Muscle cramps, nausea, and vomiting were also observed. Pharmacokinetic studies revealed a greater than dose-proportional increase in the area under the plasma concentration x time curve (AUCs) of the two major metabolites. Patients who developed ototoxicity generally showed higher plasma AUC values for the parent drug and metabolites. The mean plasma tirapazamine AUC at 330 mg/m2 was 1026.5 microgram/ml x min (range 863. 8-1252.3), but no pharmacokinetic data are available for the solitary patient who developed otoxicity at this dose level. These AUC values were in the (estimated) range required for therapeutic effect in murine studies. Ototoxicity was not observed when the AUC of tirapazamine was equal to or less than 1252 microgram/ml x min. The dose of 330 mg/m2 was therefore chosen as an appropriate level for combination chemotherapy studies.

Adult↗
PubMed1996

Methanol potentiation of carbon tetrachloride hepatotoxicity: the central role of cytochrome P450.

Evidence to explain the enhanced hepatotoxicity of carbon tetrachloride (CCl4) following methanol exposure by inhalation is presented. Hepatic microsomes prepared from male F344 rats exposed to methanol at concentrations up to 10,000 ppm showed increased p-nitrophenol hydroxylase activity but no increase in pentoxyresorufin-O-dealkylase or ethoxyresorufin-O-deethylase activities. Hepatic antioxidant levels, glutathione levels and glutathione-S-transferase activity in methanol-treated animals were not different from controls. In vitro metabolism of CCl4 was also increased in microsomes from methanol-treated animals. Pretreatment with allyl sulfone, a specific chemical inhibitor of cytochrome P450 2E1, abolished the difference in microsomal metabolism between exposed and control animals. This study shows that methanol exposure induces cytochrome P450 2E1, which appears to be the principal toxicokinetic mechanism responsible for the increased metabolism and thus the increased hepatotoxicity of CCl4.

Animals↗
PubMed1996

Age-specific HIV incidence among homosexually active men in Australia.

OBJECTIVE: To estimate age at HIV infection among homosexually active men in Australia. DESIGN: Age-specific back-projection estimates of HIV incidence. METHODS: Monthly counts of AIDS among homosexually active men diagnosed by 30 June 1994 and reported by 31 March 1995 were obtained from the National AIDS Registry and were adjusted for reporting delays. The progression rate to AIDS was estimated from a large cohort study of HIV-infected homosexual men, with adjustment for the effect of age at HIV infection and the effect of antiretroviral and prophylactic treatments. RESULTS: The median age at HIV infection was estimated to have decreased from 31 years of age between 1982 and 1984 to between 23 and 27 years in the periods 1987 to 1989 and 1990 to 1994. Despite the trend to a younger median age at HIV infection during the current epidemic, HIV incidence was estimated to have declined in all age groups from a peak in the mid-1980s. This decline was more pronounced in the older age groups, with more modest reductions in age groups under 30 years. CONCLUSION: Most HIV infections among homosexually active men since 1987 appear to have occurred in men aged under 30 years. This has implications for education programs aimed at preventing HIV infection among homosexually active men.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Pulmonary aspiration in a long-term care setting: clinical and laboratory observations and an analysis of risk factors.

OBJECTIVE: To determine the incidence and risk factors associated with aspiration in a high risk group in a long-term care setting. DESIGN: A prospective study of demographic, nutritional, clinical, dental, and survival characteristics in 69 patients who suffered 98 aspirations events from May 1, 1990, to December 31, 1990. Demographic and nutritional data from 192 patients who did not aspirate were collected from September 1991 to December 1991. SETTING: A long-term care VA facility. PATIENTS: Long-term care residents, most of whom were neurologically debilitated. MEASUREMENTS: The incidence of aspiration was measured and the clinical and microbiological characteristics of aspiration-associated nosocomial pneumonia described. Mortality and demographic, clinical, and nutritional characteristics were compared between patients who aspirated and those who did not. MAIN RESULTS: Twenty-five percent of the study group aspirated during the 8-month observational period, and 56% of the aspiration events progressed to roentgenographically proven cases of nosocomial pneumonia. Six bacteremic episodes were documented, and results of sputum cultures were consistent with mixed Gram-positive and Gram-negative infections. During the study period, patients who aspirated were at three times the risk of dying compared with patients who did not aspirate. Three years later, only 17% of the original group of patients who aspirated were still alive compared with 60% of the patients who had not aspirated. Multivariate analysis identified tube feeding, presence of a hyperextended neck or contractions, malnutrition, and the use of benzodiazepines and anticholinergics as risk factors. CONCLUSIONS: Pulmonary aspiration is a common and serious event in neurologically impaired long-term care patients. Some risk factors are amenable to change.

Aged↗
PubMed1996

The use of back projection to estimate HIV prevalence among pregnant women in Australia.

A statistical method similar to back projection was used to estimate the number of children infected with HIV perinatally from the number of children with AIDS due to perinatal HIV infection. By 31 December 1994 there were 18 children born in Australia and reported to have AIDS due to perinatal HIV infection. Based on these 18 AIDS cases, it was estimated that to the end of 1994 there were between 35 and 57 children born in Australia and infected with HIV perinatally, with a preferred estimate of 43 children. Assuming that the transmission rate of HIV from infected mothers to their babies was in the range 15 to 35%, it was estimated that the prevalence of HIV infection among women giving birth in Australia had increased from 0.03 per 1000 (range 0.02-0.07 per 1000) in 1983-1985 to 0.09 per 1000 (range 0.05-0.20 per 1000) in 1992-1994. This range for the prevalence of HIV infection among pregnant women in 1992-1994 was consistent with estimates of the prevalence from screening studies, and suggests that the prevalence of HIV infection in pregnant women in Australia remains low.

Acquired Immunodeficiency Syndrome↗