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Biomedical subjects

C Hamilton

Publications and source records attributed to C Hamilton.

At least 37 records · Page 2Linked to original sources
PubMed1993

Pharmacokinetics of the anticancer agent sulofenur in mice, rats, monkeys, and dogs.

The absorption and pharmacokinetics of sulofenur [N-(indan-5-sulfonyl)-N'-(4-chlorophenyl)urea, LY186641] and its major metabolites were examined in mice, rats, monkeys, and dogs. The compound is a diarylsulfonylurea currently being evaluated as an oncolytic agent in phase I and II trials. In all species, sulofenur was well absorbed after an oral dose, but over a prolonged period, and sulofenur exhibited a fairly long half-life of elimination from plasma. These values ranged from 6 h in rats up to 30, 110, and 200 h in mice, monkeys, and dogs, respectively, at doses (240-1000 mg/m2) within the range of those used in clinical trials. Experiments describing the high degree of binding of sulofenur to plasma proteins (consistently > 99%) help to explain these relatively long half-lives. There is, however, a large difference between these plasma half-lives in the species studied. Sulofenur was previously found to be extensively metabolized to products that are excreted primarily into the urine. In this study, its major metabolites, which are found mainly in the urine, were also minor components of the drug-related material (< 10% of the sulofenur concentrations) in the plasma of rats treated with sulofenur. The absorption, binding characteristics, and elimination of these major metabolites after their administration to rats were also compared with sulofenur.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Strain gauge plethysmography for the detection of deep venous thrombosis.

Deep venous thrombosis is a widely recognized medical problem which results in significant morbidity and mortality. Venography is the current 'gold standard' diagnostic test for deep venous thrombosis; however it is costly, invasive and is unnecessarily performed in 50% of cases. This paper describes a self-contained, non-invasive system for automatic venous occlusion plethysmographic measurement and analysis. An examination of 274 symptomatic limbs was conducted using strain gauge plethysmography and a subsequent venographic examination was then performed. The plethysmographic results were then compared with venography so as to develop a means of discrimination for thrombotic and non-thrombotic limbs. Strain gauge plethysmography using the Belfast DVT Screener yielded a sensitivity of 100% and a sensitivity of 66.3% for proximal segment DVT. The efficacy of the discriminatory algorithm was then tested for the diagnosis of DVT in a further 101 symptomatic patients. A sensitivity of 94.7% and a specificity of 81.7% were observed for strain gauge plethysmography for proximal segment thrombosis in this patient group. The Belfast DVT Screener is highly sensitive for deep venous thrombosis and may be used to reduce the need for venography, which is of benefit to both the patient and clinician.

Adult↗
PubMed1993

Vascular smooth muscle response to ouabain. Relation of tissue Na+ to the contractile response.

Smooth muscle responses to Na+ pump inhibition are thought to reflect two elements: a neurogenic contribution, involving catecholamine release from nerve terminals, and a myogenic response, attributed to relations between pump activity, [Na+]i, and [Ca2+]i. In the present study, we describe the time course and magnitude of cell Na+ changes, assessed by two methods, atomic absorption and nuclear magnetic resonance spectroscopy during the myogenic contractile response of rabbit aorta strips to ouabain. A threshold concentration of 3 x 10(-7) mol/L induced a gradual rise in [Na+]i. Both methods showed an essentially identical monotonic rise over 4 to 8 hours from a baseline level of 8 to 10 mmol/L water to a peak, which was approximately fivefold higher. The neurogenic (rapid) and myogenic (delayed and gradual) contractile responses were temporally distinct. Ouabain at 10(-7) mol/L, a concentration 10- to 100-fold lower than the threshold for catecholamine-dependent rapid-onset responses, induced only a delayed and gradual contractile response, which reached a maximum at 6 to 8 hours. With 10(-6) mol/L ouabain, the delayed response of 1.6 +/- 0.2 g peaked at 7.3 +/- 1.1 hours and was sustained for 16 hours. The time course was similar to that for change in [Na+] but somewhat later. Ouabain at 10(-5) and 10(-4) mol/L induced a delayed response that was identical in magnitude but also induced an early rapid contractile response, which was prevented by reserpine or phentolamine pretreatment. These agents did not influence the delayed response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Increased urinary excretion of pyridinium cross-links in cancer patients.

Pyridinoline (PYD) and deoxypyridinoline (DPD), two collagen-based cross-links found in bone, were measured by high-performance liquid chromatography in urine samples from 65 control subjects and 97 patients with either untreated or progressive cancer. Patients with cancer had significantly (P < 0.001) higher urine concentrations of PYD and DPD than did control subjects. Both cross-links were increased in cancer patients with and without clinically detectable bone metastases, although patients with bone and liver involvement had higher mean concentrations. The mean concentrations of both cross-links were also significantly higher in the urine samples of inpatients than in an outpatient ambulatory population. These findings suggest that the measurement of PYD and DPD in urine may be useful in assessing bone metastases and bone resorption in cancer patients.

Adult↗
PubMed1992

Age-related changes in human blood lymphocyte subpopulations.

Flow cytometric analysis of major lymphocyte populations and their subsets reveals age-related changes in the cellular human immune system. Immunophenotypic markers were evaluated in 110 normal pediatric subjects, divided into groups of newborn infants, infants aged 2 days to 11 months, and children aged 1 to 6 years and 7 to 17 years; results were then compared with those obtained from 101 normal adults aged 18 to 70 years. Comparisons among age groups from newborn infants through adults reveal progressive declines in the absolute numbers of leukocytes, total lymphocytes, and T, B, and natural killer (NK) cells. The percentages of T cells within the total lymphocyte population increase with age, in both CD4+ and CD8+ subsets. Percentages of B and NK cells are higher in newborn infants than in adults. The expression of the activation markers interleukin-2R and HLA-DR on T cells increases with age, as does the NK-associated expression of CD57 on CD8 cells. The proportions of B lymphocytes that coexpress CD5 or CDw78 decrease with age, whereas expression of Leu-8 and CD23 increases. The proportion of CD4 cells bearing the CD45RA and Leu-8 markers is consistently lower in adults than in children. These data may serve as a reference range for studies of pediatric subjects.

Adolescent↗
PubMed1992

Loco-regional recurrence and survival after wide local excision, radiotherapy and axillary clearance for early breast cancer.

After breast conservation for early breast cancer which comprised wide local excision, axillary clearance and radiotherapy to the breast, 145 women have been followed prospectively for a median of 42 months. Local recurrence occurred in 11 (7%) and axillary recurrence in three (2%). Distant recurrence has occurred in 32 and accounted for 80% of all first recurrences. Local treatment failure has occurred in three women and would not have been prevented by mastectomy. Loco-regional recurrence in the absence of preceding or synchronous distant disease was unusual and did not pose a significant clinical problem.

Adult↗
PubMed1989

Canine pythiosis--isolation and identification of Pythium insidiosum.

Pythium insidiosum was isolated from the subcutaneous tissue of a 1-year-old tan crossbreed dog and from the intestinal tract of an 18-month-old Samoyed male. Gomori's methenamine silver stain was superior to hematoxylin and eosin in demonstrating the organism in tissue sections. The agent was identified as P. insidiosum by zoospore formation in an aqueous yeast extract solution containing grass blades. Exoantigens produced in culture were shown to be identical to known P. insidiosum antigens by microimmunodiffusion.

Animals↗
PubMed1988

The effect of nonnutritive sucking on heart rate in preterm infants.

A laboratory and a field experiment used within-subject designs to test the hypothesis that nonnutritive sucking (NNS) reduces heart rate (HR) in preterm infants. Infants in Experiment A were provided a standard pacifier nipple for 30 min under strictly controlled conditions. In the field Experiment B, nursing staff provided infants with a standard pacifier during alternate intervals in a sequence of four interfeed intervals spanning 12 hr. NNS significantly reduced average HR in each experiment. Given the strongly positive relationship between HR and energy expenditure, these results suggest that NNS reduces energy expenditure in preterm infants. Such an effect, in turn, could help to explain how the opportunity to engage in NNS enhances growth in preterms.

Arousal↗
PubMed1986

The reduction of alpha-ketocarboxylic acids and alpha-dicarbonyl compounds with titanium(III) chloride.

Thirteen model alpha-ketocarboxylic acids and alpha-dicarbonyl compounds have been observed to be reduced by titanium(III) chloride. The products of these reactions were shown by melting (boiling) points, mixed melting points, derivatives, refractive indices, infrared, and NMR comparisons with authentic compounds or literature information to be the corresponding alpha-hydroxycarboxylic acids or alpha-hydroxyketones.

Carboxylic Acids↗
PubMed1986

Radiotherapy for stage I seminoma testis: results of treatment and complications.

The results of treatment by infradiaphragmatic lymph node irradiation and orchiectomy in 232 patients with Stage I testicular seminoma seen between 1963 and 1983 are reported. Of this group, only five (2%) patients relapsed and none died from seminoma. Contralateral testicular tumours occurred in 12 patients and five developed second non-testicular malignancies. The acute and late morbidity of radiotherapy was low although 15 patients developed peptic ulceration. There was a significant association between prior abdominal surgery and a history of dyspepsia with ensuing peptic ulceration. Future management policy is discussed on the basis of these observations.

Adult↗
PubMed1986

Mortality study of workers in the man-made mineral fiber production industry in the United Kingdom.

The workforces of two factories in the United Kingdom have been followed up to the end of 1984 as part of the collaborative European study of the health of workers in the man-made mineral fiber industry. In the cohort from an English glass-wool plant there was no suggestion of any excess mortality compared to national or local rates, except for lung cancer among men in comparison to the national level. However, the data indicate that the workers were largely local persons by place of birth, occupation, and death, and they therefore suggest that the national comparison was inappropriate. Lung cancer mortality showed little relationship to length of employment, duration of time since first exposure, occupational classification, or level of exposure. In the cohort from a continuous-filament plant in Northern Ireland no excess mortality from cancer was found. There were, however, raised death rates from violent causes and cardiovascular disease, but these rates were not exceptional for the area of the country in which the factory was located. No deaths from mesothelioma were reported in either cohort.

Construction Materials↗