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Biomedical subjects

K Hughes

Publications and source records attributed to K Hughes.

At least 127 records · Page 7Linked to original sources
PubMed1989

High incorporation of [3H]inositol into phosphoinositides of human platelets during reversible electropermeabilisation.

A new method for high incorporation of [3H]inositol into human platelets is described. The method involves incorporation of [3H]inositol during reversible electropermeabilisation by high voltage discharge, followed by resealing the cells during incubation at 37 degrees C. Between 10- and 20-fold increase of isotope uptake is achieved compared to control intact cells. Permeabilised resealed platelets maintain good responses to thrombin and collagen. Analysis of the incorporation of the label amongst the phosphoinositides shows 70% to be in PI, 20% in PIP, and 10% in PIP2. Stimulation with thrombin and analysis of the formation of IP1, IP2 and IP3 shows the labelling to occur in a hormone-sensitive pool. These studies indicate that reversible electropermeabilisation can be used to achieve good uptake of non-membrane penetrating substances such as inositol.

Blood Platelets↗
PubMed1989

Reversible electropermeabilisation of human and rat blood platelets: evaluation of morphological and functional integrity 'in vitro' and 'in vivo'.

A high-voltage discharge procedure has been developed for permeabilising the plasma membranes of both human and rat blood platelets. The cells can be resealed by incubation at 37 degrees C, show less than 4% loss of lactate dehydrogenase (LDH) implying minimal cell lysis and also have well maintained morphological and functional integrity. The prototype apparatus used at field strengths between 6 and 8 kV/cm produces membrane pores which allow free diffusion of low molecular weight substances such as adenine nucleotides, inositol phosphate and fluorescent dyes. Two properties, namely Ca2+-induced secretion of granule stored 5-hydroxytryptamine (5HT) and inositol 1,4,5-trisphosphate (IP3)-induced release of intracellularly sequestered 45Ca, which are both well expressed immediately after permeabilisation, are essentially abolished after resealing. The efficiency of permeabilisation and resealing can be simply monitored by shifts in 'apparent platelet volume' using a resistive particle counter (Coulter). Permeabilised platelets show a shift in modal volumes from a control range 4-7 fl to 10-15 fl. Resealing restores these modal volumes to the original control range. Encapsulation of the fluorochrome, Lucifer yellow (Mr 550), during permeabilisation revealed that after resealing greater than 85% of rat platelets, and close to 100% human platelets, contained the encapsulated dye. The initial rates and % aggregation responses of both human and rat platelets to collagen, thrombin and the thromboxane A2-mimetic U46619 remained essentially normal after permeabilisation and resealing further illustrating the maintenance of functional competence following treatment. Resealed rat platelets reinfused into the circulation after labelling with [111In]indium oxine gave survival curves similar to those of control platelets. Therefore, this reversible permeabilisation procedure may allow the use of autologous or heterologous platelets as carrier vehicles for the delivery of drugs and other agents 'in vivo'.

Adenine Nucleotides↗
PubMed1989

Surgery for colorectal cancer metastatic to the liver. Optimizing the results of treatment.

Overall, hepatic resection appears to be an important means of curing patients with metastatic colorectal cancer isolated to the liver. The only absolute contraindication to surgery was the impossibility of a radical removal of tumor: if residual disease will remain after the hepatic resection, this operation is not indicated. A possible second contraindication to surgery is the presence of tumor in the hepatic or celiac lymph nodes. Such metastases from liver metastases signal a biologic grade of tumor that is almost sure to spread to other sites. However, one patient of the 25 in this group did survive long term when positive lymph node groups were dissected. Further clinical experience with this form of the disease along with trials of regional adjuvant therapies such as intraperitoneal chemotherapy may be needed. The presence of extrahepatic metastases at the time of liver resection should be considered a relative contraindication to this surgery, but if the patient can be made clinically disease free, long-term disease-free survival may result. It seems imperative that all patients with hepatic metastases be evaluated by an experienced hepatic surgeon for a curative resection. If the patient has between one and four metastases, a 25 per cent long-term disease-free survival rate can be expected. Patients who have a radical resection of more than four metastases should be considered to be in an experimental group in whom more data are needed. In our current state of knowledge, making such patients clinically disease free is their only chance for long-term survival. Other factors besides the number of metastases that will affect the prognosis of the patient include the disease-free interval between colorectal resection and liver resection, the pathologic margin of resection on the liver specimen, and the presence or absence of mesenteric lymph node metastases from the primary cancer. These factors should be considered when determining the prognosis in a given patient and should be used as stratification variables in prospective trials. However, from our analysis of available data, these factors should not be considered contraindications to hepatic resection.

Adult↗
PubMed1989

Mortality from cardiovascular diseases in Chinese, Malays and Indians in Singapore, in comparison with England and Wales, USA and Japan.

Age-standardised death rates, for ages 35-64 years in both sexes, from ischaemic heart disease, cerebrovascular disease, and hypertensive disease for Chinese, Malays, and Indians in Singapore (1980-84) have been compared with those in England and Wales, USA and Japan (1982). For ischaemic heart disease Indians have the highest mortality, then Malays, with Chinese less than the Western countries but more than Japan. For cerebrovascular disease the Malays have highest mortality, then Indians, then Chinese, followed by Japan, England and Wales, and USA in that order. For hypertensive disease it is again Malays, then Indians, then Chinese, but followed by the different order of USA, England and Wales, and Japan. The differences are discussed in the light of declining trends in mortality from these disease in Singapore over the preceding 25 years. The special problems of ischaemic heart disease in Indians and hypertension and it's sequelae in Malays are highlighted.

Adult↗
PubMed1989

Ischaemic heart disease and its risk factors in Singapore in comparison with other countries.

Mortality from ischaemic heart disease in Singapore is now reaching comparability with the West. For the early 1980s, rates for Indians and Malays were higher than in U.S.A. and England and Wales and while those for Chinese were lower they were considerably higher than in Japan. In keeping with this the levels of the major risk factors in Singapore are now comparable to the West. Cigarette smoking in males is virtually the same as in Britain, while the proportion of hypertensives on medication is higher than in the West. The main cause for concern is the current high levels of serum cholesterol in Singapore and strenuous health education efforts are needed to bring about dietary changes.

Adolescent↗
PubMed1988

Ultraviolet microbeam irradiation of microtubules in vitro. The action spectrum for local depolymerization of marginal band microtubules in vitro matches that for reducing birefringence of chromosomal spindle fibres in vivo.

Marginal bands were isolated from newt red blood cells and, using monochromatic light from an ultraviolet microbeam, the marginal band microtubules were irradiated in vitro to produce areas of reduced birefringence (ARBs). The ARBs neither moved nor changed shape after they were formed, though the marginal bands sometimes changed shape during the irradiation. Marginal band ARBs were regions in which the microtubules were locally depolymerized, as determined by electron microscopy and immunofluorescence. The action spectrum for producing ARBs on marginal band microtubules in vitro matches very closely the action spectrum for producing ARBs on crane-fly spermatocyte chromosomal spindle fibres in vivo, which indicates that ARBs in vivo are produced by the ultraviolet light acting directly on the microtubules (as opposed to an intermediate component), and confirms, without complications inherent in the fixation of living cells, that ARBs on spindle fibres in vivo are regions in which microtubules are locally depolymerized.

Animals↗
PubMed1987

Trends in mortality from hypertensive and cerebrovascular diseases in Singapore, 1959 to 1983.

Secular trends in mortality from hypertensive and cerebrovascular diseases have been studied in Singapore from vital statistics for the years from 1959 to 1983. Males were found to have higher mortality than females from hypertensive disease (by about 25%) and cerebrovascular disease (by about 20%). After an initial slight rise mortality from hypertensive disease fell markedly from the mid-1960s (slightly more in males than females) but the rate of decline has levelled off in the last few years. A more modest decline in cerebrovascular disease mortality started in the early 1970s in males and the mid-1970s in females, with the decline to date being slightly more in males. These declines started at the same point in time in both sexes and in all age groups, with the rate of decline falling with age. The timing and patterns of these declines are consistent with the theory that treatment of hypertension has played a significant role.

Adult↗
PubMed1986

Insulin release from a cloned hamster B-cell line (HIT-T15). The effects of glucose, amino acids, sulphonylureas and colchicine.

Insulin release from statically incubated HIT-T15 cells was maximally stimulated by glucose, L-arginine and L-leucine. L-arginine stimulated insulin release in the absence of glucose. Glucose induced insulin release was potentiated by the addition of L-leucine, L-arginine and the two in combination. Both glibenclamide and chlorpropamide stimulated insulin release from HIT-T15 cells. Glibenclamide was the more potent and equivalent in insulinotrophic action to 7.5 mmol/l glucose. Only chlorpropamide significantly potentiated glucose induced insulin release. Perifused HIT-T15 cells produced a reproducible biphasic insulin response to glucose challenge which was characterised by a pronounced and sustained first phase and a reduced second phase. The stimulation of phase I by glibenclamide alone and the inhibition of phase II of glucose induced insulin release by colchicine suggested the presence of a readily available pool of insulin granules which was not rapidly restored by insulin biosynthesis and granule margination.

Amino Acids↗
PubMed1986

Trends in mortality from ischaemic heart disease in Singapore, 1959 to 1983.

Mortality from ischaemic heart disease in Singapore has been studied from vital statistics for the 25 years from 1959 to 1983. The age-standardized rates for ages 30 to 69 years increased in men from 106.8 per 100 000 in 1959-1963 to 204.5 in 1979-1983, while for women they increased from 30.7 to 72.0 per 100 000. The male to female ratios in the age-standardized rates for ischaemic heart disease fell from 3.5 to 2.8 in the period, while remaining steady for all causes. However, while mortality rates for ischaemic heart disease have increased steadily over the period in the older age groups, they have recently declined in the younger ages with a birth cohort effect. For males the decline started with the 1932-1936 birth cohort (men now aged around 50 years), while for females it was the 1937-1941 birth cohort (women now aged around 45 years). The reasons for this decline are discussed but no clear explanation is at present apparent and it would be useful to have future monitoring of lifestyles and coronary risk factors.

Adult↗
PubMed1986

Ethnic group differences in low birthweight of live singletons in Singapore, 1981-3.

All singleton live births occurring in Singapore in the three years 1981-3 were computed, and birthweight was examined in the different ethnic groups (Chinese, Malay, and Indian). Overall the proportions of babies of very low birthweight (less than 1500 g) and low birthweight (less than 2500 g) were: Chinese 0.3% and 6.1%, Malays 0.4% and 8.5%, and Indians 0.5% and 10.0%. The important finding was that in all gestational periods and virtually all maternal age and live birth order groups Indians had the highest proportion of very low and low birthweight babies. However for prematurity Indians at 6.7% had a higher rate than Chinese (5.1%) but lower than Malays (9.9%). Likewise for neonatal mortality Indians at 8.7 per 1000 live births were between Chinese (7.1) and Malays (9.1). The evidence seems to indicate that the reason for Indians having a higher proportion of low birthweight babies is partly ethnic/genetic, and the cut-off point of 2500 g should perhaps be lowered for babies from the Indian subcontinent when international comparisons are being made.

Adult↗
PubMed1985

Comparison of birthweight and infant mortality between Singapore and England and Wales, 1980.

For 1980 Singapore was found to have overall a more favourable birthweight distribution than England and Wales. The proportion of very low birthweight babies (less than 1500 g) and heavy babies (3500 g and over) was 0.4% and 18.5% in Singapore and 0.7% and 34.9% in England and Wales for live births, and 0.6% and 18.5% against 0.9% and 34.7% for total births. However, for low birthweight (less than 2500 g) Singapore with 7.5% in live births and 7.9% in total births had higher rates than England and Wales (6.7% and 7.2%). While infant mortality rates were very similar, Singapore had a somewhat higher neonatal mortality rate but a considerably lower postneonatal mortality rate than England and Wales. The effects on mortality of standardising for birthweight are examined. The problems of interpretation and the implications of the findings are discussed.

Birth Weight↗
PubMed1985

Singapore in international comparisons of birthweight and perinatal mortality.

The position of Singapore as regards birthweight distribution and perinatal mortality has been compared with six countries in the 1973 WHO study namely, Austria, Cuba, Hungary, Japan, New Zealand and Sweden. Birthweight distribution and perinatal mortality reflect both the social and health conditions of a population and the standards of obstetric and paediatric care, and seeing where a country ranks in the international comparison of them may play a role in the formulation of health policy for that country. Singapore was well placed for the proportion of very low birthweight babies (less than 1,500 grams), ranking 2nd for both live births (0.5%) and total births (0.7%). It was however not so well placed for proportion of low birthweight babies (less than 2,500 grams), ranking 5th for both live births (8.8%) and total births (9.2%). With regard to perinatal mortality Singapore at 20.0 per 1,000 total births ranked 4th and this improved to 3rd after standardizing for birthweight and in fact was little different from Hungary (1st) and Sweden (2nd). Given that standardization for birthweight largely removes the effect of "socioeconomic and demographic factors" so that remaining differences to a large extent reflect medical care, this indicates a relatively high standard of perinatal care in Singapore. The problems of interpretation, the implications of the findings and suggestions for improving birth statistics in Singapore are discussed.

Austria↗