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Biomedical subjects

P Ross

Publications and source records attributed to P Ross.

At least 55 records · Page 3Linked to original sources
PubMed1997

A phase I/II study of leucovorin, carboplatin and 5-fluorouracil (LCF) in patients with carcinoma of unknown primary site or advanced oesophagogastric/pancreatic adenocarcinomas.

Carcinoma of unknown primary site (CUPS) accounts for 5-10% of all malignancies. Forty patients with metastatic CUPS or advanced oesophagogastric/pancreatic adenocarcinomas were recruited. Eligibility included ECOG performance status 0-2, minimum life expectancy of 3 months and measurable disease. The regimen consisted of bolus intravenous 5 fluorouracil (5-FU) and leucovorin (20 mg m-2) days 1-5 and carboplatin (AUC5) on day 3. The leucovorin/carboplatin/5-FU (LCF) was repeated every 4 weeks. The starting dose of 5-FU was 350 mg m-2 day-1 with escalation to 370 and then 400 mg m-2 day -1 after the toxicity at the previous level had been assessed. The maximum tolerated dose (MTD) was defined as the dosage of 5-FU that achieved 60% grade 3/4 toxicity. In addition, objective and symptomatic responses, quality of life and survival were assessed. The MTD of 5-FU in the LCF regimen was 370 mg m-2. The predominant toxicity was asymptomatic marrow toxicity. The 350 mg m-2 level was then expanded. There were two toxic deaths due to neutropenic sepsis, one at 370 mg m-2 after one course and one at 350 mg m-2 after four courses. The objective response rate was 25% with one complete response (CR) and nine partial responses (PRs). The median duration of response was 3.4 months (range 1-10). The CR and eight of the nine PRs were in CUPS patients. Twelve patients developed progressive disease on LCF. Median survival for all 40 patients was 7.8 months (10 months median survival for those treated at 350 mg m-2). The majority of patients described a symptomatic improvement with LCF chemotherapy. The recommended dose of 5-FU for future studies is 350 mg m-2 combined with leucovorin 20 mg m-2 and carboplatin (AUC5).

Adenocarcinoma↗
PubMed1997

The need to educate primary care physicians to provide oncologic services: a changing focus.

BACKGROUND: The traditional role of primary care physicians (PCPs) in cancer care has been primarily cancer detection, and their training and education were similarly oriented. Propelled by the changing health care delivery system, this role is now expanding substantially. METHODS: A survey of 31 health maintenance organizations active in the New York market area was performed. The HMOs were grouped into three main categories according to method of payment of the physician. Patient care responsibilities vary depending on the method of payment but stay constant within the group. Of 19 HMOs that responded to the survey, 13 had shifted much of the responsibilities for diagnosis and treatment decisions to the PCP. RESULTS: A national survey of all academic radiation oncology program directors in the United States, as well as training programs of primary care physicians, showed a unanimous lack of educational or training programs or opportunities to familiarize the PCP with radiation oncology as a therapeutic discipline and with its after-therapy requirements. This deficiency extended also to multimodality training and other aspects. The internal medicine programs surveyed scored only an average of 1.25 out of a possible 5 in education areas directly related to oncology training. These programs comprised 78% of the residents of all programs surveyed. CONCLUSION: The information gathered from these surveys reveals a shift towards mandating the provision of oncologic services by PCPs, who have inadequate training in oncology, with no system in place to remedy the deficiencies except on-the-job training. The inevitability of the changing role of the PCP must be accompanied by either an expansion of residency programs to encompass training in important aspects of oncology care or expansion and formalization of continuing education programs to achieve the same objective.

Aftercare↗
PubMed1997

Development and validation of a discriminative quality of life questionnaire for osteoporosis (the OPTQoL).

We report the development and validation of an osteoporosis-targeted quality of life questionnaire to measure the impact of the disease in the general population. From multiple focus groups with women with osteoporosis, healthy women at risk for osteoporosis, spouses and relatives of women with osteoporosis, and health care providers, we identified over 300 potential items related to the disease. A lengthy questionnaire incorporated these items and was administered to a second large study cohort of 222 women with clinical osteoporosis (history of fracture, significant height loss, and/or kyphosis); 101 women with known low bone mineral density levels that would categorize them as osteoporotic but who had not yet shown obvious physical manifestations of the disease; and 142 women with other conditions (such as arthritis, cancer, depression) expected to also have an impact on quality of life. Final items from among the original 300 were chosen for their demonstrated relationship with osteoporosis as measured by clinical manifestations and low bone density and with quality of life measured by a standard generic questionnaire, the SF-36. The final questionnaire contains 26 scored items in three domains-physical activity, adaptations, and fears- and six nonscored questions relating to osteoporotic changes and diagnosis. This instrument is unique among osteoporosis-targeted questionnaires in that it attempts to measure the total impact of the disease on quality of life within a population at a single point in time.

Community-Institutional Relations↗
PubMed1997

I. NGD 94-1: identification of a novel, high-affinity antagonist at the human dopamine D4 receptor.

NGD 94-1 was evaluated for selectivity and in vitro functional activity at the recombinant human D4.2 receptor stably expressed in Chinese hamster ovary cells. NGD 94-1 showed high affinity for the cloned human D4.2 receptor (Ki = 3.6 +/- 0.6 nM) and had greater than 600-fold selectivity for the D4.2 receptor subtype compared with a wide variety of monoamine or other neurotransmitter receptor or modulatory sites except for 5-HT1A and 5-HT3 receptors, in which NGD 94-1 was approximately 50- and 200-fold selective, respectively, for the D4.2 receptor. In measures of in vitro functional activity, NGD 94-1 showed an antagonist profile at the cloned human D4.2 receptor subtype. NGD 94-1 completely reversed the decrease in forskolin-stimulated cAMP levels produced by the dopamine receptor full agonist quinpirole. Furthermore, NGD 94-1 produced a complete reversal of GTPgamma35S binding induced by quinpirole, but was unable on its own to affect GTPgamma35S binding. These data suggest that NGD 94-1 functions as an antagonist rather than a full or partial agonist at the human D4.2 receptor. In addition, NGD 94-1 binding affinity at the D4.2 receptor subtype was unaffected by G-protein activation by GTP, consistent with the binding affinity seen for other antagonists at the D4 receptor. The binding of tritiated NGD 94-1 was saturable and of high affinity at cloned human D4.2 receptors. Furthermore, the binding of [3H]NGD 94-1 to cloned human D4.2 receptors expressed in Chinese hamster ovary cells displayed a pharmacological profile similar to that observed with the nonselective dopamine receptor ligand [3H]YM 09151-2. Saturation and pharmacological analyses of [3H]NGD 94-1 binding at cloned human D4.2, D4.4 and D4.7 receptor variants showed no difference between the three variants. NGD 94-1 is a novel, high-affinity, D4 receptor-selective antagonist. The clinical use of this subtype-specific compound should permit direct evaluation of the role of D4 receptors in psychiatric disorders.

Animals↗
PubMed1997

[Tricentric study of the sensitivity of Pseudomonas aeruginosa serotyping to beta-lactams and aminoglycosides].

The aim of this study was to evaluate the susceptibility of 300 Pseudomonas aeruginosa strains to 6 beta-lactams and to 2 aminoglycosides and to compare this susceptibility according to the serotype, the sample nature, the unit activity and the geographic situation of the hospital. The susceptibility level was ascertained using the disk method. Serotyping of the strains was also performed. Susceptibility level was 67% for ticarcillin, 82% for piperacillin-tazobactam combination, 85% for ceftazidim, 81% for cefepim, 74% for aztreonam, 83% for imipenem, 73% for tobramycin and 86% for amikacin. Non-serotypable strains represented 20.6%. The most common serotypes were O6 (19%) and O11 (13%). Discrepancies between cefepime and ceftazidime were found in 15 strains after MIC determination, 6 of them were O12 strains. It appears that strain susceptibility was function of the serotype distribution. Cefepime exhibited outstanding activity against P. aeruginosa, similar to ceftazidim activity.

Aminoglycosides↗
PubMed1996

Contaminant-induced immunotoxicity in harbour seals: wildlife at risk?

Persistent, lipophilic polyhalogenated aromatic hydrocarbons (PHAHs) accumulate readily in the aquatic food chain and are found in high concentrations in seals and other marine mammals. Recent mass mortalities among several marine mammal populations have been attributed to infection by morbilliviruses, but a contributing role for immunotoxic PHAHs, including the polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) was not ruled out. We addressed this issue by carrying out a semi-field study in which captive harbour seals were fed herring from either the relatively uncontaminated Atlantic Ocean or the contaminated Baltic Sea for 2 years. We present here an overview of results obtained during this study. An impairment of natural killer (NK) cell activity, in vitro T-lymphocyte function, antigen-specific in vitro lymphocyte proliferative responses, and in vivo delayed-type hypersensitivity and antibody responses to ovalbumin was observed in the seals fed the contaminated Baltic herring. Additional feeding studies in PVG rats using the same herring batches suggested that an effect at the level of the thymus may be responsible for changes in cellular immunity, that virus-specific immune responses may be impaired, and that perinatal exposure to environmental contaminants represents a greater immunotoxic threat than exposure as a juvenile or adult. Together with the pattern of TCDD toxic equivalents of different PHAHs in the herring, these data indicate that present levels of PCBs in the aquatic food chain are immunotoxic to mammals. A review of contaminant levels in free-ranging harbour seals inhabiting polluted areas of Europe and North America suggests that many populations may be at risk to immunotoxicity. This could result in diminished host resistance and an increased incidence and severity of infectious disease.

Animals↗
PubMed1996

Laboratory-scale purification of microcystins using flash chromatography and reversed-phase high-performance liquid chromatography.

Microcystins were extracted from 7 l (equivalent to 313 g dry weight) of cyanobacterial scum collected from Rutland Water in Leicestershire, UK in 1989. The resulting aqueous extract was rapidly concentrated on a C18 flash chromatography cartridge and microcystins were eluted using a step gradient. Fractions were collected manually and monitored by UV spectrophotometer and analytical HPLC. Fractions containing microcystins of similar polarity were pooled to give three fractions. Simple isocratic methods for separating each fraction were developed on an analytical column and scaled up to a 15 x 7.5 cm I.D. column. Closed-loop recycling was used to maximise yield and purity of two hydrophobic microcystins.

Amino Acid Sequence↗
PubMed1996

Toxicity identification evaluation of Lake Orta (Northern Italy) sediments using the Microtox system.

Pore waters extracted by centrifugation from Lake Orta (Northern Italy) sediments were studied with a modified Toxicity Identification Evaluation (TIE) procedure using the Microtox bacterial luminescence toxicity test system. The most toxic pore water samples were from stations near a rayon factory, known as a source of copper and ammonium discharges. The TIE manipulations used were filtration, EDTA chelation, and C18 solid-phase resin adsorption. The most effective treatments to remove toxicity were the EDTA and C18, indicating that both metals and nonpolar organic compounds contribute to the observed toxicity.

Ammonia↗
PubMed1996

The role of helper lipids in cationic liposome-mediated gene transfer.

In the procedure for cationic liposome-mediated transfection, the cationic lipid is usually mixed with a "helper lipid" to increase its transfection potency. The importance of helper lipids, including dioleoylphosphatidylcholine (DOPC) and phosphatidylethanolamine (dioleoyl PE), DO was examined. Freeze-fracture electron microscopy of DNA:cationic complexes containing the pSV-beta-GAL plasmid DNA, the cationic lipid dioleoyl trimethylammonium propane, and these helper lipids showed that the most efficient mixtures were aggregates of ensheathed DNA and fused liposomes. PE-containing complexes aggregated rapidly when added to culture media containing polyanions, whereas PC-containing complexes did not. However, more granules of PC-containing complexes were formed on cell surfaces after the complexes were added to Chinese hamster ovary (CHO) cells in transfection media. Pronase treatment inhibited transfection, whereas dilute poly-L-lysine enhanced transfection, indicating that the attachment of DNA:liposome complexes to cell surfaces was mediated by electrostatic interaction. Fluorescence spectroscopy studies confirmed that more PC-containing complexes than PE-containing complexes were associated with CHO cells, and that more PC-containing complexes were located in a low pH environment (likely to be within endosomes) with time. Cytochalasin-B had a stronger inhibitory effect on PC-containing liposome-mediated than on PE-containing liposome-mediated transfection. Confocal microscopic recording of the fluorescently label lipid and DNA uptake process indicated that many granules of DNA:cationic liposome complexes were internalized as a whole, whereas some DNA aggregates were left out on the cell surfaces after liposomes of the complexes fused with the plasma membranes. For CHO cells, endocytosis seems to be the main uptake pathway of DNA:cationic liposome complexes. More PC-containing granules than PE-containing granules were formed on cell surfaces by cytoskeleton-directed membrane motion, after their respective DNA:liposome complexes attached to cell surfaces by electrostatic means. Formation of granules on the cell surface facilitated and/or triggered endocytosis. Fusion between cationic liposomes and the cell membrane played a secondary role in determining transfection efficiency.

Animals↗
PubMed1996

Cost of treating advanced colorectal cancer: a retrospective comparison of treatment regimens.

Introduction of new agents on to hospital drug formularies requires the demonstration of efficacy, safety and cost advantages. An audit of the total monthly costs of 'Tomudex' (raltitrexed; administered every 3 weeks), a drug recently introduced for the treatment of advanced colorectal cancer, and three 5-fluorouracil-based regimens [5-day daily bolus (Mayo); continuous ambulatory pump; 48-h continuous infusion (De Gramont)] was undertaken. Patient-specific costs associated with fluids, concomitant medication and consumables were largely negligible, but chemotherapy was the main cost driver in the raltitrexed and De Gramont groups. Fixed inpatient costs were highest for the patients receiving the De Gramont regimen which required more impatient stays each month. Total costs (patient-specific plus fixed costs) were lowest in patients on the Mayo regimen (mean 954.03 Pounds; median 659.68 Pounds), followed by patients in the ambulatory pump (mean 1207.61 Pounds; median 749.19 Pounds), raltitrexed [mean 1256.93 Pounds; median 1087.14 Pounds (mean 1117.85 Pounds; median 959.34 Pounds when costs of protocol-driven visits were excluded)], and De Gramont groups (mean 2028.52 Pounds; median 1775.66 Pounds). The pattern of costs varied considerably between regimens, such that high drug costs, for example those associated with raltitrexed therapy, were partially offset by reductions in hospital visits and stays.

Adult↗
PubMed1996

Total quality management practices in the NSW hospital system--an overview.

A two-phase descriptive study involving a questionnaire survey was undertaken during 1994 and 1995 to evaluate the extent of implementation of total quality management practices in New South Wales hospitals accredited by the Australian Council on Healthcare Standards. A survey response rate of 72 per cent was attained. Results indicated that most hospitals were aware of and consciously implemented aspects of the total quality management philosophy in some way. There is little evidence that whole systems have embraced the total quality management approach as a fully integrated endeavour.

Community-Institutional Relations↗
PubMed1996

Infection with Ureaplasma urealyticum and Mycoplasma hominis and the development of chronic lung disease in preterm infants.

In a prospective cohort study in a tertiary referral neonatal intensive care unit, the endotracheal secretions of 40 consecutively intubated newborn infants, less than 31 weeks' gestation, were examined weekly for the genital mycoplasmas and all other common bacterial pathogens. Fifteen (37%) infants were positive for Ureaplasma urealyticum and/or Mycoplasma hominis. There were no differences in gestation, birthweight, use of surfactant, or time on ventilator between the culture-positive and negative babies. Thirteen (87%) of the culture-positive group developed chronic lung disease (CLD) compared with 11 (41%) of the negative group (p = 0.0196). Of those culture-positive, 37% were not identified on the first specimen taken at the time of admission. These data suggest a significant association between infection with the urogenital mycoplasma and CLD and also stress the need for repeated cultures to identify these organisms.

Chronic Disease↗
PubMed1996

Respiratory health in a total very low birthweight cohort and their classroom controls.

AIMS: To compare the respiratory health and function at 8 to 9 years of age of a total population based cohort of 300 very low birthweight (VLBW) children with that of two classroom controls (n = 590) matched for age and sex. STUDY DESIGN: Cohort study with controls. SETTING: Schools throughout Scotland. RESULTS: The VLBW children were more likely than their peers to use an inhaler, to be absent from school, and to be admitted to hospital because of respiratory illness. They were significantly shorter than their classroom controls, but even after adjusting for differences in height, the VLBW children had reduced forced vital capacity (FVC); this was associated with a history of prolonged ventilation (> 28 days) and pneumothorax in the neonatal period. There were no significant differences between the groups in forced expiratory volume in one second (FEV1)/FVC but twice as many (7.9% v 3.7%) of the VLBW children had ratios < 70%, denoting obstructive airways disease. Poor expiratory function was associated with neonatal respiratory distress syndrome, prolonged ventilation, and the need for > 40% oxygen. Exercise induced airway narrowing was increased in VLBW children (odds ratio = 2.0; 95% confidence interval 1.2 to 3.4) and was very little changed by adjustment for inhaler use and exposure to cigarette smoke. CONCLUSIONS: As in other low birthweight cohorts, respiratory morbidity was increased. Unlike previous studies, FVC was more affected than expiratory function in this VLBW population. Our findings support the hypothesis that poorer lung function is associated with very low birth weight, but not with intrauterine growth retardation.

Asthma, Exercise-Induced↗
PubMed1995

Characterisation of the copper uptake mechanism and isolation of the ceruloplasmin receptor/copper transporter in human placental vesicles.

In this paper we have studied copper (Cu) uptake by microvillar vesicles isolated from human term placenta. We have characterised Cu uptake from CuHis2 complexes and shown that ceruloplasmin (Cp) inhibits uptake. Inhibition is complex and variable; in one series of experiments, the Vmax for uptake drops from 31.3 +/- 1.2 nmol/min per mg vesicle protein without added Cp to 11.3 +/- 1 nmol/min per mg vesicle protein at 91 micrograms/ml Cp. Similarly, the K0.5 increases from 0.35 +/- 0.08 microM to 1.35 +/- 0.25 microM, while the n value (the Hill coefficient) falls from 1.9 +/- 0.23 in the absence of Cp to 1.1 +/- 0.13 In another series, Cp had no effect below concentrations of about 100 micrograms/ml and in a third series only increased K0.5. The variability in effect seems to be related to the specific activity of the ceruloplasmin, which in turn is related to the copper complexes of the protein. The effect is specific for Cp; apotransferrin and a2-macroglobulin have no effect. 67Cu-labelled ceruloplasmin binds specifically to vesicles of term placenta with an affinity of 2.8 microU/mg vesicle protein and a Bmax of 79 microU/mg vesicle protein. CuHis2, but not histidine alone, can block the uptake. The data can be reconciled by proposing that the binding site of the transporter is relatively small and recognises a Cu-dihistidine structure common to the low-molecular-weight complex and to the Type I and Type II coppers of ceruloplasmin. We have used these observations to develop an isolation method for the transporter and have identified it as a protein of M(r) 90,000 which is closely associated with alkaline phosphatase. There are also two proteins of M(r) 45,000 and 40,000 which may be breakdown products of the larger complex. Antibodies to the 45,000 protein block Cu binding and uptake from CuHis2 complexes, strongly implicating it as the copper transporter/ceruloplasmin receptor of human term placenta.

Carrier Proteins↗
PubMed1995

Evidence for competition between vitamin K-dependent clotting factors for intracellular processing by the vitamin K-dependent gamma-carboxylase.

This study demonstrates an apparent competition between newly synthesized precursors of prothrombin and factor X for binding to and processing by the gamma-carboxylase in the ER membrane of hepatocytes. The precursor of factor X appears to exhibit a strong affinity for the carboxylase than the prothrombin precursor. This conclusion is supported by the findings that 1) in normal hepatocytes, the factor X precursor prevents increased prothrombin precursor binding to the ER membrane, 2) increased prothrombin binding to the ER membrane was measured in H4-II-E-C3 Reuber H-35 cells where factor X synthesis is suppressed. The variations in the concentrations of the prothrombin and the factor X precursors that were as associated with the ER membrane correlated with the available prothrombin and factor X substrate pools for the gamma-carboxylase.

Animals↗
PubMed1995

Predicting vertebral deformity using bone densitometry at various skeletal sites and calcaneus ultrasound.

We investigated the usefulness of bone density measurements from multiple skeletal sites and calcaneus ultrasound for evaluating the probability of vertebral deformation. Bone mineral density (BMD) was measured at the second metacarpal and middle phalanges using radiographic absorptiometry of hand radiographs, and at the lumbar spine using dual-energy x-ray absorptiometry. Distal radius and proximal radius were measured using single-energy x-ray absorptiometry (SXA), expressed as bone mineral content (BMC, grams per centimeter), and as BMD (grams per square centimeter). The calcaneus was measured using both SXA (BMD) and broadband ultrasound attenuation (BUA). Among the women in this study (mean age 74, SD = 5), 84 women developed new vertebral deformations (57 cases with one and 27 cases with two or more deformations), which were identified on serial radiographs during an average of 9 years prior to the measurements of bone density. Logistic regression analysis was used to calculate odds ratios for risk of deformation corresponding to a 1-SD difference in density or ultrasound, adjusted for age. All bone measurements were significantly associated with vertebral deformation, with odds ratios (95% confidence intervals) ranging from 1.40 (1.10, 1.78) for proximal radius BMD to 1.88 (1.45, 2.44) for calcaneus BMD measurements. Measurements of calcaneal BUA, calcaneal BMD, and hand BMD generally remained significant when included simultaneously with another measurement in the same model, suggesting that spine or radius BMD may not provide much additional information about risk of deformation. It appears that all of the measurements of bone density and ultrasound provide useful information regarding the probability of deformation. These findings await confirmation in a prospective study.

Absorptiometry, Photon↗