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Biomedical subjects

S Hilton

Publications and source records attributed to S Hilton.

At least 73 records · Page 4Linked to original sources
PubMed1995

Moclobemide: relationships between dose, drug concentration in plasma, and occurrence of adverse events.

The relationship between exposure to moclobemide and the occurrence of adverse events (AEs) was quantified by applying a population approach to data collected during phase III/IV studies. A total of 965 measurements of moclobemide concentration in plasma were available from 357 depressed patients included in a series of clinical studies; 539 AEs were reported by the 236 patients with at least one concentration measurement > or = 400 micrograms/liter. Using relatively few blood samples per patient (mean, 2.7), the average concentration in plasma on the day an AE was observed was calculated (CAE,pred) from population kinetic parameter estimates. The frequency of AEs, normalized by exposure time in months (AEs/Mo), was grouped according to dose and concentration categories and examined in relation to age, gender, adverse event severity, and concomitant medication. CAE,pred was more powerful than the observed concentration or daily dose in detecting relationships between exposure to moclobemide and the occurrence of AEs. There was a relationship between CAE,pred and AEs/Mo, with 0.58 events at concentrations between 1,000 and 1,999 micrograms/liter and 2.78 events at concentrations of 4,000 micrograms/liter and above. Within each concentration category, the number of AEs decreased with increasing severity. Advancing age was not associated with an increase of AEs/Mo. AEs were more frequent in females than in males in all treatment intensity categories (ratio, 1.4). There was no indication of supra-additive effects by concomitant medication, including all drugs used in the study population. This investigation demonstrates the successful use of observational data from clinical studies in the assessment of quantitative relationships between drug exposure and the occurrence of AEs.

Adult↗
PubMed1995

Annual night visiting rates in 129 general practices in one family health services authority: association with patient and general practice characteristics.

BACKGROUND: Rates of night visiting by general practitioners have increased steadily over the last 30 years and vary widely between general practices. AIM: An ecological study was carried out to examine night visiting rates by general practices in one family health services authority, and to determine the extent to which differences in night visiting rates between practices could be explained by patient and practice characteristics. METHOD: The study examined the variation in annual night visiting rates, based on night visit fees claimed between April 1993 and March 1994, among 129 general practices in Merton, Sutton and Wandsworth Family Health Services Authority, London. RESULTS: Practices' annual night visiting rates varied from three per 1000 to 75 per 1000 patients. The percentages of the practice population aged under five years and aged five to 14 years were both positively correlated with night visiting rates (r = 0.38 and r = 0.35, respectively), as were variables associated with social deprivation such as the estimated percentage of the practice population living in one-parent households (r = 0.24) and in households where the head of household was classified as unskilled (r = 0.20). The percentage of the practice population reporting chronic illness was also positively associated with night visiting rates (r = 0.26). The percentages of the practice population aged 35 to 44 years and 45 to 54 years were both negatively associated with night visiting rates (r = -0.34 and r = -0.31, respectively) as was the estimated list inflation for a practice (r = -0.31). There was no significant correlation between night visiting rates and the distance of the main practice surgery from the nearest hospital accident and emergency department. There was also no association between night visiting rates and permission to use a deputizing service. In a stepwise multiple regression model, the multiple correlation coefficient was 0.56 with four factors (percentage of the practice population aged under five years, percentage aged 35-44 years, percentage who were chronically ill and estimated list inflation) explaining 32% of the variation in night visiting rates. CONCLUSION: Only about one third of the variation in night visiting rates between practices could be explained by patient and practice variables derived from routine data. Population-based research using data collected on individual patients and practices is required to improve current understanding of the patient and practice characteristics that influence the demand for night visits and of why night visiting rates vary so widely between practices.

Adolescent↗
PubMed1995

Phase I radioimmunotherapy trial with iodine-131-CC49 in metastatic colon carcinoma.

UNLABELLED: CC49 is a murine monoclonal antibody (MAb) that reacts against the TAG-72 antigen. We carried out a Phase I study with escalating doses of 131I-CC49 in patients with advanced colorectal cancer expressing the TAG-72 antigen to determine the dose-limiting toxicity and therapeutic efficacy, if any, of the radioimmunoconjugate. METHODS: Twenty-four patients with TAG-72- expressing colorectal cancer were treated with escalating doses of 131I-CC49 starting at 15 mCi/m2 and going up to 90 mCi/m2 of 131I labeled to 20 mg MAb CC49. Patients were selected if TAG-72 was expressed in > or = 50% of cells in previously resected tumor and at least one metastasis was demonstratable on standard imaging such as CT. All patients had failed conventional chemotherapy and had not received prior radiotherapy or murine MAb. Patients were under radiation isolation precautions until whole-body radioactivity decreased to < or = 5 mR/hr at 1 m. Whole-body scintigrams were obtained prior to discharge and 1 and 2 wk after infusion in all patients. SPECT imaging was carried out at least once in all patients. RESULTS: All patients had excellent targeting of radioactivity to known tumor sites. There was no nonhematologic toxicity. Hematologic toxicity was more pronounced in those patients who had received extensive prior chemotherapy. There were no major responses. All patients developed an immune response (HAMA) within 4 wk of therapy. CONCLUSION: Radioimmunotherapy with 131I-CC49 is safe and there is significant therapeutic efficacy in this Phase I trial at the doses studied. There is excellent targeting of radioactivity to antigen-positive tumors. Dose-limiting toxicity is hematopoietic, with the maximum tolerated dose in this group of heavily pretreated patients being 75 mCi/m2.

Abdominal Neoplasms↗
PubMed1994

Using patient and general practice characteristics to explain variations in cervical smear uptake rates.

OBJECTIVES: To produce practice and patient variables for general practices from census and family health services authority data, and to determine the importance of these variables in explaining variation in cervical smear uptake rates between practices. DESIGN: Population based study examining variations in cervical smear uptake rates among 126 general practices using routine data. SETTING: Merton, Sutton, and Wandsworth Family Health Services Authority, which covers parts of inner and outer London. MAIN OUTCOME MEASURE: Percentage of women aged 25-64 years registered with a general practitioner who had undergone a cervical smear test during the five and a half years preceding 31 March 1992. RESULTS: Cervical smear uptake rates varied from 16.5% to 94.1%. The estimated percentage of practice population from ethnic minority groups correlated negatively with uptake rates (r = -0.42), as did variables associated with social deprivation such as overcrowding (r = -0.42), not owning a car (r = -0.41), and unemployment (r = -0.40). Percentage of practice population under 5 years of age correlated positively with uptake rate (r = 0.42). Rates were higher in practices with a female partner than in those without (66.6% v 49.1%; difference 17.5% (95% confidence interval 10.5% to 24.5%)), and in computerised than in non-computerised practices (64.5% v 50.5%; 14.0% (6.4% to 21.6%)). Rates were higher in larger practices. In a stepwise multiple regression model that explained 52% of variation, five factors were significant predictors of uptake rates: presence of a female partner; children under 5; overcrowding; number of women aged 35-44 as percentage of all women aged 25-64; change of address in past year. CONCLUSIONS: Over half of variation in cervical smear uptake rates can be explained by patient and practice variables derived from census and family health services authority data; these variables may have a role in explaining variations in performance of general practices and in producing adjusted measures of practice performance. Practices with a female partner had substantially higher uptake rates.

Adult↗
PubMed1994

Influence of active site and tyrosine modification on the secretion and activity of the Aeromonas hydrophila lipase/acyltransferase.

Aeromonas sp. secrete a lipase/acyltransferase that shares several properties with the mammalian plasma enzyme lecithin:cholesterol acyltransferase. Reaction of the enzyme with tetranitromethane led to modification of 2 tyrosines and a nearly 80% decline in enzyme activity. Replacing Tyr230 with Phe altered the activity of the enzyme in the same way as did treatment with tetranitromethane. Unlike the wild type enzyme, which preferentially hydrolyzes the 2-position acyl chain of phosphatidylcholine, the Y230F mutant enzyme did not discriminate between the 1- and 2-positions of the phospholipid. Tyr230 may be necessary to correctly position phospholipid substrates at the active site. Several amino acids around the active site Ser16 of the lipase were also changed. Replacing Ser18 with Gly, bringing the enzyme's sequence into line with the "lipase consensus sequence," resulted in reduced secretion of the protein and complete loss of activity. Changing this serine to Val led to an inactive protein that was not secreted at all. Substituting Phe13 in the hydrophobic region of the consensus sequence with Ser also prevented secretion, although the mutant protein appeared to be active. The Aeromonas lipase may represent a distinct group of lipolytic enzymes which have a novel active site structure.

Acyltransferases↗
PubMed1994

Clinical comparison of radiolocalization of two monoclonal antibodies (mAbs) against the TAG-72 antigen.

Ten patients with colorectal cancer metastases received 125I-B72.3 and 131I-CC49 prior to laparotomy (five patients received 1 mg, and five 20 mg of each mAb). Tumor:serum ratios of 131I-CC49 were better than those of 125I-B72.3 (P < 0.01 at 1 mg; P = 0.05 at 20 mg; P < 0.01 at both doses). All known lesions > or = 1 cm in diameter were visualized at the 20 mg dose. There was no difference in absolute tumor uptake of 125I-B72.3 or 131I-CC49. We conclude that mAb CC49 has better relative uptake in colorectal cancers than mAb B72.3.

Adrenal Gland Neoplasms↗
PubMed1994

Patients' experiences of health checks in general practice: a sample survey.

The 1990 contract for general practitioners in the UK offered incentives for them to organize health promotion clinics and required them to perform 'lifestyle' checkups of their patients every 3 years, despite uncertainty about the impact of such checks on patient health. To address this lack of appropriate evaluation, a follow-up study to assess benefits in terms of patient behaviour and health resulting from the introduction of lifestyle checkups in general practice in a sample of more than 7000 patients aged 30-70 from 18 practices in three FHSA areas (in south London, Surrey and Yorkshire) has been performed. Eighteen per cent of the random sample of patients reported having a health check in the previous year. A full health check comprising measurement of blood pressure, height and weight, urinalysis and questioning about smoking habits, alcohol consumption, exercise, diet and family illnesses had been given to 29% of respondents reporting a health check of any kind. Respondents in less privileged socioeconomic groups were more likely to have had a health check, but less likely to have had a 'full' check. Reactions to the checks were mainly positive; 81% regarded the check as helpful, and only 6% reported it to be worrying and 6% a waste of time. The implications for the new health promotion banding system in the UK are discussed.

Adult↗
PubMed1994

Preselection of patients with high TAG-72 antigen expression leads to targeting of 94% of known metastatic tumor sites with monoclonal antibody I-131-CC49.

We studied 18 consecutive patients with advanced colorectal cancer where primary tumors were preselected for high expression of TAG-72 antigen and who underwent a phase I radioimmunotherapy trial with an intravenously administered monoclonal antibody CC49, 20 mg, labeled with I-131 in amounts varying from 15 mCi/m2 to 75 mCi/m2. Whole-body images and SPECT of the abdomen obtained 1 week after infusion were compared with pretreatment CT scans. A total of 66 lesions were evaluated. SPECT revealed 2/66 lesions (3%) that were not detected by CT; 4/66 were only detected by CT: lungs (1.8 cm and < 1 cm), axilla (1.5 cm), adrenal (2.5 cm). Thus, based on immunohistopathological testing in paraffin-embedded tissue blocks of primary tumors stained for TAG-72 antigen, we have selected a subset of patients (about 70% of referrals) with colorectal cancer for whom I-131-CC49 was shown to target to 62/64 CT positive lesions (97%) and 62/66 (94%) of all known positive lesions. We conclude that in patients with significant TAG-72 tumor expression there is excellent targeting of I-131-CC49 in therapeutic doses to colorectal cancer with respect to lesions detected with CT scanning. It should be noted that this study was not designed as a comparison of the sensitivity of CT versus I-131-CC49 SPECT/planar imaging. Instead, the observed results are consistent with a biological hypothesis that in general, the primary tumor histology vis-à-vis TAG-72 expression reflects the TAG-72 expression of the metastatic sites.

Aged↗
PubMed1994

Near patient testing in general practice: attitudes of general practitioners and practice nurses, and quality assurance procedures carried out.

BACKGROUND: The evaluation of near patient testing in British general practice has largely been confined to studies examining individual tests or comparing equipment. AIM: This study set out to determine the attitudes of practice staff to near patient testing, and the extent to which staff undertook quality assessment. METHOD: Four types of near patient testing machines were introduced into 12 general practices in two regions of England, south west Thames and west Midlands. General practitioner and practice nurse attitudes to near patient testing were assessed by semi-structured interview before and six months after the introduction of the machines. The extent to which routine quality assurance procedures were carried out within the surgery and as part of local and national schemes was examined. RESULTS: Although 80% of general practitioners anticipated changing patient management with near patient testing, only two fifths reported having done so after six months. Nurses generally were enthusiastic at the outset, although one third were unhappy about incorporating near patient testing into their work schedules. Time pressure was the most important factor restricting uptake of near patient testing. Nurses performed quality control regularly but complete local external quality assurance procedures were established in only half the practices. All the practices participated in a national scheme for cholesterol assays. CONCLUSION: General practitioners in this study did not find near patient testing a very useful addition to their resources. Pressure on nurses' time was the most frequently reported limitation.

Attitude of Health Personnel↗
PubMed1994

Clinical validation of SPECT and CT/MRI image registration in radiolabeled monoclonal antibody studies of colorectal carcinoma.

UNLABELLED: Registration methods combine the anatomic localizing ability of CT or MRI with SPECT images of radiolabeled monoclonal antibodies (Mabs), allowing the accurate staging of patients prior to surgery or following treatment. METHODS: Twenty-four patients (15 males and 9 females, mean age 55 yr, range 29-70 yr) were studied with this technique. Ten patients had suspected colorectal cancer recurrence and were infused with 10 mCi of 131I-CC49 prior to staging laparotomy. Fourteen patients treated in a Phase I radioimmunotherapy study with 131I-CC49 were also studied. All patients underwent SPECT imaging of the abdomen and pelvis 5-7 days following infusion of Mab. RESULTS: Phantom studies demonstrated a 3.6-mm surface fitting mean accuracy of datasets for the liver and 1.8 mm for an intrahepatic tumor. In the presurgical group, SPECT and CT/MRI registration allowed more accurate identification of uptake abnormal sites. Areas of metastatic disease > 1 cm confirmed at surgery were found in six of nine patients with liver lesions and in two patients with extrahepatic (including one patient with pelvic) disease. In patients imaged following radioimmunotherapy, all lesions > 1.5 cm seen on CT/MRI were identified, and activity distribution in tumor and normal tissue could be more accurately assessed. CONCLUSIONS: Routine registration of SPECT and CT/MRI images is feasible and allows more accurate anatomic assessment of sites of abnormal uptake in radiolabeled Mab studies.

Adrenal Gland Neoplasms↗
PubMed1994

Perceptions of U.S. Navy medical reservists recalled for Operation Desert Storm.

Operations Desert Shield/Storm involved the recall of 9,700 Navy medical reservists. A demographically representative sample of 3,804 medical reservists (39%) responded to a survey between June and September 1991. The purpose was to identify major issues associated with the recall experience. Results indicated that reservists felt well prepared for their recall assignments; however, they did not strongly endorse the Reserve training program. Responses across operationally oriented issues were moderately positive. Reservists assigned to CONUS hospitals rated items more positively than those assigned to Marine Corps support, and officers were more positive than hospital corpsmen. Results are presented as a descriptive heuristic for policy considerations.

Adolescent↗
PubMed1993

Impact of introducing near patient testing for standard investigations in general practice.

OBJECTIVE: To assess the clinical and economic impact of surgery based near patient testing in general practice for six commonly used biochemical and bacteriological tests. DESIGN: After four months' monitoring, equipment for two bacteriological and four biochemical tests was introduced without cost into 12 practices using a crossover design. Structured request forms were used to monitor laboratory investigations. SETTING: 12 general practices in west midlands and south west Thames with list sizes above 9000. MAIN OUTCOME MEASURES: Investigation rates per 1000 consultations. Changes from baseline rates. Reasons for requesting investigations and provisional diagnoses. Cost per test and sensitivity of costs to rate of use. RESULTS: Investigation rates for the six tests rose by 16.5% (from 78.6/1000 consultations to 91.6/1000) when equipment was available in the surgery and reverted to baseline rates when it was withdrawn. The average weekly number of tests when equipment was available ranged from 0.5 to 10.5 (mean 9.0). Cholesterol tests were used as an addition to laboratory testing, usually for screening. Midstream urine analysis was often done in the surgery instead of in the laboratory, although 30% of samples were tested by both methods. Doctors' reasons for investigation and conditions tested were largely unaffected by availability of surgery tests. Costs for surgery tests were higher for all tests except midstream urine. CONCLUSIONS: Availability of surgery based testing increased the number of tests performed. It was cost effective only for midstream urine analysis.

Cholesterol↗
PubMed1993

A placebo controlled double-blind evaluation of the pharmacodynamics of fengabine vs amitriptyline following single and multiple doses in elderly volunteers.

1. The effects of fengabine were compared with those of amitriptyline in healthy elderly volunteers. Doses were administered double-blind and assessments were made before and after ingestion. 2. Psychomotor performance and cognitive ability were measured using tests of choice reaction time, tracking, critical flicker fusion threshold, memory scanning and word recognition. Subjective feelings were assessed using the Leeds sleep evaluation questionnaire (LSEQ) and line analogue rating scales (LARS). 3. Pharmacokinetic data suggest that fengabine may induce its own metabolism following repeated dosing. 4. The findings of this study show that fengabine 200 mg and 400 mg does not produce any noticeable behavioural toxicity in elderly volunteers, in contrast to amitriptyline which had a disruptive effect throughout.

Administration, Oral↗
PubMed1993

Lesion-by-lesion comparison of computerized tomography and indium-111-labeled monoclonal antibody C110 radioimmunoscintigraphy in colorectal carcinoma: a multicenter trial.

C110 is an anti-carcinoembryonic antigen murine IgG1 monoclonal antibody. Indium-111-labeled C110 radioimmunoscintigraphy (RIS) in colorectal cancer was studied in 51 presurgical patients at four institutions. Planar and SPECT images were obtained at least twice between 48 and 96 hr after injection of 5 mCi/5 mg of 111In-C110. Fifty-one patients had 87 biopsy-proven lesions at surgery (57 hepatic, 30 extra-hepatic). Thirty-three patients (64.7%) had positive radionuclide scans, while 32 (62.8%) had positive CT scans (p = NS). While CT was better at overall lesion detection (62.1% versus 56%, p < 0.05), radionuclide scans were better than CT for extra-hepatic disease (60% versus 46.7%, p < 0.01). Hepatic metastases (52.6%) were visualized by Mab scans to selectively concentrate radioactivity. Uptake in draining lymph nodes was a significant limitation, making evaluation of these sites difficult. Indium-111-C110 shows selective uptake in metastatic colorectal cancer, including more than half of all hepatic lesions evaluated.

Adult↗
PubMed1992

Histidinuria: defective transport of histidine.

A-7-year-old boy was found to have histidinuria without histidinemia. Low concentrations of histidine in plasma were consistent with impaired intestinal and renal tubular absorption of histidine. The patient was developmentally delayed and had some minor anomalies. Only 4 other patients in 3 families have been reported. Each had abnormality of the central nervous system. All were male.

Child↗
PubMed1992

Stereochemical and positional specificity of the lipase/acyltransferase produced by Aeromonas hydrophila.

Aeromonas species secrete a glycerophospholipid-cholesterol acyltransferase (GCAT) which shares many properties with mammalian plasma lecithin-cholesterol acetyltransferase (LCAT). We have studied the stereochemical and positional specificity of GCAT against a variety of lipid substrates using NMR spectroscopy as well as other assay methods. The results show that both the primary and secondary acyl ester bonds of L-phosphatidylcholine can be hydrolyzed but only the sn-2 fatty acid can be transferred to cholesterol. The enzyme has an absolute requirement for the L configuration at the sn-2 position of phosphatidylcholine. The secondary ester bond of D-phosphatidylcholine cannot be hydrolyzed, and this lipid is not a substrate for acyl transfer. In contrast to the phospholipases, but similar to LCAT, the enzyme does not interact stereochemically with the phosphorus of phosphatidylcholine. In fact, the phosphorus is not required for enzyme activity, as GCAT will also hydrolyze monolayers of diglyceride, although at much lower rates.

Acyltransferases↗