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Biomedical subjects

P A Harris

Publications and source records attributed to P A Harris.

12 recordsLinked to original sources
PubMed1992

Do current regimes of hormone replacement therapy protect against subsequent fractures?

It is now accepted that unopposed oestrogen therapy reduces osteoporotic fractures by about 50%. Although current regimes with added progestogens are thought to act similarly to unopposed oestrogens, no study has yet demonstrated an effect on fractures with the former. Using a retrospective cohort design we studied fracture rates in women attending a menopause clinic for hormone replacement therapy (HRT) and compared them with women derived from the general population. Data were analysed from 1075 women exposed to HRT and 1741 non-exposed postmenopausal women. In all 226 fractures were reported between 1977 and 1986, the commonest site being the distal radius, occurring in 28 of the HRT women and in 37 of the non-exposed women. The incidence density rate for fracture of the distal radius is 3.5/1000 woman-years (wy) in non-exposed women. This was similar to the rate in the HRT women prior to HRT use, the rate falling by 30% after exposure from 3.2 to 2.2/1000 wy. The protective effect on osteoporotic fractures increased progressively with duration of use. After 5 years of use the relative risk fell to 0.5 (95% confidence interval, 0.2-1.2) for all osteoporotic fractures and for the distal radius to 0.18 (95% confidence interval, 0.05-1.3). No similar changes were seen for non-osteoporotic fractures. There were 6 (0.6/1000 wy) reported fractures of the hip in the non-exposed group compared with none in the HRT group (when 1.7 were expected based on non-exposed rates) (p = 0.15).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Radiological progression of osteoarthritis: an 11 year follow up study of the knee.

A follow up study was carried out in 1990 on 169 well documented patients initially presenting with osteoarthritis of the hands or knees between 1975 and 1977. Radiographic change in the knee was used as the outcome measure. Sixty three subjects had paired knee radiographs a mean of 11 years apart and were 69 (range 52-87) years old at follow up. Thirty subjects were known to have died, 28 were untraceable, and 48 were traced but did not have paired films available. The films were read independently and blind to time sequence by two observers using five different radiological scoring methods. Most of the knees did not increase in Kellgren and Lawrence grade, with only 33% deteriorating over the time period. The results were similar when a subject was categorised by their worst knee. When a more sensitive global score on paired films was used 50% of knees showed a slight deterioration and 10% improved. Visual analogue pain scores remained unchanged. Those with knee pain at baseline had a greater chance of progressing, as did those with existing osteoarthritis in the contralateral knee. These results suggest that most patients with osteoarthritis attending rheumatology clinics do not deteriorate radiographically or symptomatically over an 11 year period. More work is needed in the selection and early detection of subjects with a poor prognosis and in focusing early intervention on this high risk group.

Aged↗
PubMed1991

Enzyme purification using temperature-induced phase formation.

A new type of aqueous two-phase system composed of an ethylene oxide and propylene oxide random co-polymer, UCON 50-HB-5100, as the upper phase polymer and either dextran or hydroxypropyl starch as the lower phase polymer has been characterized and used to purify 3-phosphoglycerate kinase (EC 2.7.2.3) and hexokinase (EC 2.7.1.1) from bakers' yeast. The UCON 50-HB-5100 polymer has a cloud point of 55 degrees C at which temperature it phase separates from water. This cloud point can be lowered to 40 degrees C by the addition of 0.2 M sodium sulfate salt. The low cloud point of this UCON polymer makes it possible to obtain the target enzymes in a water and buffer solution, and to recover and recycle the UCON 50-HB-5100 polymer. The phase diagrams for the systems UCON 50-HB-5100/Dextran T500 and UCON 50-HB-5100/hydroxypropyl starch have been determined. Yeast homogenate was first partitioned in a system composed of a top phase containing UCON 50-HB-5100 and a bottom phase containing either dextran or hydroxypropyl starch. The top phase containing the enzyme free of cell debris was removed and the temperature increased above the cloud point of the UCON until a new two phase system composed of water as the top phase and a concentrated liquid UCON 50-HB-5100 bottom phase was formed. The water phase containing the enzyme was removed and the bottom phase containing the UCON 50-HB-5100 could be recycled to perform a second extraction.

Hexokinase↗
PubMed1990

An outbreak of the equine rhabdomyolysis syndrome in a racing yard.

An outbreak of muscle stiffness and poor performance among 59 thoroughbreds at a Newmarket flat racing yard was investigated between the beginning of May and the end of June 1986. Over a third of the horses showed signs of muscular stiffness, and 38 had, at one or more of the sampling times, creatine kinase (CK) activities above 200 iu/litre and, or, aspartate aminotransferase (AST) activities above 300 iu/litre when they were sampled six to eight hours after exercise. The following season, at a similar time and stage of training, only four of 39 horses sampled had CK activities between 200 and 300 iu/litre, and three had AST activities between 500 and 600 iu/litre. Plasma samples from 18 animals sampled at the start of the investigation and 13 days later were tested for the presence of antibodies to equine herpesvirus (EHV). Ten of them showed a response highly suggestive of an EHV-1 infection. No significant abnormality was found in the fractional electrolyte values from seven randomly selected animals. Unusually high numbers of normally sized and stained fibres with centrally placed nuclei as well as groups of small muscle fibres were found in muscle biopsies taken from three animals which continued to have high enzyme activities and show recurrent signs of muscle stiffness.

Animals↗
PubMed1990

Quantitative relation between gastric acid secretion and changes in urinary acid excretion.

This study was designed to investigate the relations between gastric acid secretion and alkalinisation of the urine. Normal subjects underwent standard pentagastrin (6 micrograms/kg) (n = 5) and sham feeding (n = 6) tests, with additional collection of urine samples before and two and three hours after the start of the test for measurement of titratable urine acidity. Nine subjects provided urine before and two hours after a test meal. Sham feeding (n = 5) and meal (n = 6) tests were carried out in patients who had had a successful vagotomy for duodenal ulcer. There was a significant correlation of gastric acid response in the standard tests with simultaneous changes in urine acidity (r = -0.79, p less than 0.001) and also with urine acid output after the test meal, on another day (r = -0.73; p less than 0.02). The correlation was insufficient to predict gastric function from changes in urinary acidity, but there was clear separation of the results in normal subjects and patients with vagotomy. Changes in urine acidity after a standardised meal may prove to be useful as a screening test after vagotomy to select patients who are likely to have a persisting high gastric acid response to vagal stimulants.

Acids↗
PubMed1985

A comparison of faecal blood loss caused by tenoxicam and piroxicam in normal healthy male volunteers.

Faecal blood loss arising from tenoxicam at a dose of 20 mg/day was compared to that arising from piroxicam at a dose of 20 mg/day in a double-blind, parallel comparative study in 12 healthy male volunteers. Faecal blood loss was measured for a 1-week run-in on placebo, during 4 weeks of treatment and for a 2-week post-treatment period in both groups. Plasma levels for tenoxicam and piroxicam confirmed good compliance in all subjects. Mean blood loss during the placebo run-in period was 0.35 ml/day. Mean blood loss during treatment with tenoxicam was 0.84 ml/day and with piroxicam 0.81 ml/day. There was no significant difference between these measurements. On cessation of treatment, faecal blood loss continued both in the tenoxicam group (mean 1.30 ml/day) and piroxicam group (mean 1.41 ml/day). The difference between these was not statistically significant. No significant haematological or biochemical abnormality resulted from either of the two trial drugs during the period of the study. Urinalysis and NAG/creatinine ratio also remained unaltered in both treatment groups.

Adult↗
PubMed1977

Endo- and exoglycosidases in an experimental rat osteosarcoma.

Glycosidases capable of degrading intercellular matrix components were investigated in a 32P induced rat osteosarcoma. Homogenates of ossifying tumour were shown to readily degrade hyaluronic acid, chondroitin sulphates 4 and 6 but not dermatan sulphate. High levels of the exoglycosidases, beta-glucuronidase and beta-N-acetylglucosaminidase were found in tumour homogenates, and it was demonstrated that these enzymes contribute to the degradation of high molecular weight hyaluronic acid. The levels of these enzymes were compared with activities found in homogenates of neonatal bone and muscle surrounding tumours. Exoglycosidases, but not hyaluronidase, were found to be produced by cultures of osteosarcoma in vitro.

Animals↗
PubMed1975

Reduction of doxorubicin (adriamycin) bone marrow toxicity.

Doxorubicin (adriamycin), an antineoplastic antibiotic, is a potent suppressant of bone marrow. Previous studies on doxorubicin disposition indicated that its diversion from bone marrow in the first few minutes after administration should result in a marked decrease in total exposure to the drug (concentration X time) with a concomitant reduction in concentration-time-dependent toxicity. To test this hypothesis, the descending aorta of rabbits was occluded just proximal to the iliac bifurcation for 30 min to deprive bone marrow of blood flow. Both these rabbits and the control rabbits were given 5 mg/kg of doxorubicin intravenously, and the total white cell could in peripheral blood was monitored periodically for 15 days. The decrease in toxicity produced by the occlusion was quite evident by comparison of white cell counts and deaths in all groups. A possible mechanism of this effect was shown to be a decreased doxorubicin exposure of bone marrow tissue in the occluded animals as judged by relative doxorubicin concentration-time curves in rabbits with and without the aortic occlusion.

Animals↗
PubMedDate not supplied

The effects of food and of antacid on the single oral dose pharmacokinetics of tenoxicam.

A single oral dose (40 mg) of tenoxicam (Ro12-0068) was administered to six normal male volunteers pre- and post-prandially and to a further six volunteers with and without antacid to determine the effect of food and and of antacid on absorption. The rate of absorption was slower with post-prandial than with pre-prandial administration, resulting in a significantly later time for peak plasma drug levels (4.1 h compared to 1.3 h). No effect was evident on the extent of absorption or other pharmacokinetic parameters. Similarly, the rate of absorption was significantly slower after concurrent antacid than without antacid (t1/2 0.47 h compared to 0.18 h) resulting in a later peak time (4.7 h compared to 2.3 h) and significantly lower peak level (4.2 micrograms X ml-1 compared to 5.1 micrograms X ml-1) of parent drug in plasma. Again, no effect was evident on the extent of absorption or other pharmacokinetic parameters. It is concluded that food and antacids both tend to reduce the rate of absorption of tenoxicam, but that the extent of absorption is essentially unchanged. The influence on the overall kinetic profile is relatively minor, and thus unlikely to affect the therapeutic response.

Antacids↗
PubMedDate not supplied

The equine rhabdomyolysis syndrome in the United Kingdom: epidemiological and clinical descriptive information.

The paper provides some basic epidemiological and clinical descriptive information for the equine rhabdomyolysis syndrome (ERS) in the United Kingdom. Information was obtained retrospectively from laboratory submission data as well as cases investigated by the author via their veterinary surgeon. Sex appeared to be a significant variable, with females being more likely than males to suffer from ERS compared to other conditions (P less than 0.01). More samples were submitted in the period November-February than at other times of the year (P less than 0.01). The condition appeared to be found in many breeds/types. Most episodes occurred whilst animals were being worked, although 38% occurred after exercise. In the majority of instances the affected animal was still able to walk. A clinical description of a very mild, mild, moderately severe and severe case of ERS is given. Utilizing all the information the syndrome was divided into five grades according to the severity of the stiffness and the presence or absence of auxiliary signs such as sweating and discoloured urine.

Animals↗
PubMedDate not supplied

Preliminary pharmacokinetic model for adriamycin (NSC-123127).

The systematic chemical control of cancer requires a quantitative knowledge of the pharmacologic disposition of antitumor drugs in both healthy and malignant tissues in the body. Pharmacokinetic models can predict the drug concentration in both tumor sites and healthy organs and hence may provide a predictive capability regarding both antitumor action and concomitant toxicity. Adriamycin is an anthracycline antibiotic that has been demonstrated to possess a broad spectrum of antitticularly solid tumors. Its major toxicity is manifested by the depression of normal cell proliferation in the bone marrow and a delayed dose-dependent cardiac toxicity eventually resulting in congestive heart failure. This study is concerned with the development of a predictve analytic model for the pharmacokinetics of adriamycin. The analytic approach embodies a physiologic multicompartmental model as a framework. This model postulates that specific organs or tissue masses may be simulated by a compartment whose elements consist of physiologic properties such as tissue volume and blood flow and pharmacologic behavior such as tissue binding and metabolic activity. A mass balance is set up across each compartment and all compartments are linked by an independent blood compartment. The mass balance includes terms representing inflow and outflow of the drug as well as its metabolism, protein-binding, and other pharmacologic behavior. A model has been developed that has ten compartments which represent the plasma, heart, liver, kidney, lung, lean tissue, adipose tissue, gut, bone marrow, and spleen. Solutions of the system of equations yield the time course of the drug in each organ. Predictions of adriamycin concentration-time curves in the ten tissues after intravenous (iv) administration were generated using this model. With few exceptions, agreement between predicted and actual tissue data in rabbits was excellent. Human plasma levels of adriamycin were predicted and comparison with patient data demonstrated a reasonable first approximation.

Animals↗