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Biomedical subjects

J R Lawrence

Publications and source records attributed to J R Lawrence.

At least 73 records · Page 4Linked to original sources
PubMed1982

Protein binding of piretanide in normal and uraemic serum.

The protein binding of piretanide was assessed by continuous ultrafiltration of sera from six normal subjects and seven uraemic subjects (samples taken immediately pre-dialysis). Throughout the range of piretanide concentrations studied (0.5-4.5mM), the mean protein binding for uraemic serum was less than that for normal serum. This difference was significant (p less than 0.05) at piretanide concentrations of 1.5 mM and above, but not at 1mM where mean protein binding for uraemic serum was 88.1% compared to 94.2% for normal serum. Analysis of piretanide protein binding characteristics using the Rosenthal plot showed no significant differences between uraemic and normal serum with respect to primary or secondary binding sites. Parallel assessment by the Scatchard method suggests, as expected, that albumin is the principle protein moiety responsible for binding piretanide.

Blood Proteins↗
PubMed1982

Twinning in mares: A survey of veterinarians and analyses of theriogenology records.

Responses of 22 veterinarians to a questionnaire and the records of three brood-mare farms were examined to obtain information on twinning. The incidence rates of multiple ovulations on the three farms were 9%, 11%, and 22%. The multiple ovulation rate was reduced 42-67% in foaling mares compared to barren and maiden mares. Multiple ovulations were significantly more frequent in Thoroughbreds (19%) than in Quarter Horses (9%) and Appaloosas (8%). Both the questionnaire and the farm records indicated a high degree of repeatability of multiple ovulations and twin pregnancies within mares and within certain family lines. The likelihood of multiple ovulations was approximately doubled when the preceding cycle also had multiple ovulations. On two of the farms, breeding was withheld or postponed until after the first ovulation when multiple follicles were present. There were no significant differences in overall reproductive efficiency (pregnancy and foaling rates) among the three farms and the incidence of observed twin abortions or births was low on all three farms (0.4, 0.2, and 0%, respectively).

Journal Article↗
PubMed1981

The protein binding of methotrexate in the serum of patients with neoplastic disease.

1. Serum protein binding of methotrexate was studied in 14 patients with various forms of malignant disease and in eight age- and sex-matched subjects (control group) attending outpatient clinics for various clinical conditions. 2. Protein binding was determined by continuous ultrafiltration and methotrexate concentrations by double-antibody radioimmunoassay. 3. Protein binding of the drug is critically dependent on albumin concentration, as shown by results in individual subjects and a significant regression of methotrexate binding on albumin concentration. Moreover, at high methotrexate concentrations drug binding becomes non-linear, resulting in disproportional elevation of free methotrexate levels. Both these findings have important implications for the treatment of hypoalbuminaemic patients. 4. Two classes of binding sites were observed in both groups of patients, viz a high-affinity, low-capacity group and a low-affinity group with higher capacity. 5. No significant difference was found between patient and control groups either in the percent bound drug or in the binding parameters. 6. In conclusion, while there appear to be no factors specific to malignant disease which perturb methotrexate's protein binding, it may be important to determine the extent of drug binding before methotrexate can be used judiciously, particularly when total drug level is related to likely toxicity and in the design of an appropriate folinic acid rescue regimen after high-dose therapy.

Adult↗
PubMed1981

Effect of iron poly (sorbitolgluconic acid) complex on urinary cellular excretion.

The intramuscular injection of 250 mg iron poly (sorbitol-gluconic acid) complex caused no increase in urinary cellular or bacterial excretion in 8 patients with chronic pyelonephritis, 4 patients with non-infective renal disease, and 4 controls. However, in 4 patients with chronic infective disease of the renal tract given 500 g there was a significant increase in cellular excretion. This response was not seen in 2 control patients, nor in 2 patients with non-infective renal disease. Using a differential staining technique, this increase in urinary cellular excretion was found to be due, not to leucocytes, but to renal tubular cells. The precise significance of this is unclear, but there would be concern that the high concentration of excreted iron was providing a 'toxic' insult to susceptible, infection-damaged cells.

Gluconates↗
PubMed1981

The congenital "magnesium-losing kidney". Report of two patients.

A 39-year-old man with a lifelong history of tetany and hypocalcaemia was found to have hypomagnesaemia (0.29 mmol/l) due to renal magnesium loss. His asymptomatic 29-year-old brother had a similar disorder. Both were infertile and had severe oligospermia but normal endocrine function. They had medullary nephrocalcinosis and glomerular filtration rate was reduced. Renal biopsy showed patchy interstitial fibrosis and some glomerular sclerosis. Electron microscopy showed thickened basement membranes in damaged glomeruli and in tubules in areas of fibrosis. Tests of renal tubule function were normal. Hypocalcaemia and tetany were corrected by oral magnesium supplements which raised the serum magnesium level to around 0.54 mmol/l.

Adult↗
PubMed1980

Dose dependent methotrexate elimination following bolus intravenous injection.

The pharmacokinetics of methotrexate have been assessed at two dose levels in six patients receiving the drug for treatment of malignant disease. Each patient received bolus intravenous doses of 25 mg and 100 mg given at least one week apart, the order of administration being random. Blood and urine were collected until 48 h for methotrexate analysis by radioimmunoassay and data analysed by a model-independent pharmacokinetic approach. In each patient area under the methotrexate serum concentration-time curve (o to chi) increased out of proportion to the increase in methotrexate dose. This was reflected in a mean clearance value after the 100 mg dose of 31 +/- 16 (SD ml x min(-1) compared with a mean clearance of 62 +/- 19 ml x min(-1) following injection of 25 mg methotrexate. Renal clearance of methotrexate was markedly lower following the 100 mg dose (18 +/- 6 ml x min(-1) than after 25 mg (53 +/- 19 ml x min(-1). Saturation of the proximal tubular organic acid transport system is the likely cause of methotrexate's capacity limited elimination.

Dose-Response Relationship, Drug↗
PubMed1980

Comparative pharmacokinetics and pharmacodynamics of cardiac glycosides.

1 The pharmacokinetics and pharmacodynamics of ouabain, digoxinn and beta-methyl digoxin (medigoxin) have been investigated in a crossover study in four normal healthy volunteers. 2 Pharmacokinetics were studied using [3H]-labelled glycosides and the shortening of the left ventricular ejection time (LVET) was used as a measure of the effect of the drugs. A graded exercise protocol was used to correct for the effects of heart rate on LVET. 3 In three of the four subjects, both digoxin and beta-methyl digoxin produced a shortening in the LVET, but no such change could be detected with ouabain in any of the four subjects. 4 There was a good linear correlation between the shortening of the LVET and the amounts of digoxin or beta-methyl digoxin present in the body tissues. 5 One subject who showed no drug-related LVET shortening had greatly enhanced clearances of all three drugs studied.

Adult↗
PubMed1980

Immunological function in glomerulonephritis.

Aspects of humoral and cellular immunity and of the complement system were examined in 44 patients with glomerulonephritis, and in control subjects. A number of patients with glomerulonephritis were shown to have evidence of altered immunity which may reflect underlying mechanisms of glomerular injury. Mesangial IgA glomerulonephritis was associated with elevation of serum IgA levels (P less than 0 . 001), and focal sclerosing glomerulonephritis with raised serum IgM (P less than 0 . 001). Serum IgG levels were abnormal in 15 patients with glomerulonephritis. The haemagglutinating antibody response to tetanus toxoid was reduced in patients compared with controls. Levels of serum complement components were increased, with some exceptions, and C-reactive protein levels were also significantly raised (P less than 0.001), findings consistent with an ongoing inflammatory process. No impairment in response to recall antigens or sensitisation to dinitrochlorobenzene was found, but phytohaemagglutinin induced lymphocyte transformation was reduced in some forms of the disease.

Adolescent↗
PubMed1980

The insulin response to intravenous fructose in maturity-onset diabetes mellitus and in normal subjects.

Insulin responses to intravenous fructose and glucose were measured in 15 patients with maturity-onset diabetes mellitus. In eight patients given fructose first the insulin responses to fructose and glucose were similar. In seven patients given glucose first the insulin response to subsequently infused fructose was significantly greater than to glucose. Multiple regression analysis showed that the ratio of the fructose to glucose insulin response, assessed by area under the insulin serum concentration-time curve (F/G ratio) in individual patients, correlated most closely with prefructose infusion plasma glucose. Similar analysis, applied to results in 27 normal subjects, showed that the most important determinant of the insulin response to fructose in this group also was the immediate prefructose infusion plasma glucose. Thus in diabetics, as in normal controls, the response of the beta cell to intravenous fructose appears to be sensitively set by the ambient plasma glucose concentration at the onset of fructose infusion.

Adult↗
PubMed1980

A pharmacokinetic and clinical evaluation of iron poly (sorbitol-gluconic acid) complex.

The pharmacokinetics of iron poly (sorbitol-gluconic acid) complex (IPSG) were studied following a single intramuscular injection of 59Fe-labelled IPSG to 4 iron deficient-patients. The results showed a more rapid uptake of iron from the site of injection than that reported with iron dextran while there was a lower urinary excretion than found with iron sorbitol citrate. A clinical study was carried out in 11 patients with iron deficiency anaemia. Patients were allocated at random to receive IPSG as either 250 mg or 500 mg elemental iron per week for 8 weeks. A satisfactory response to therapy was obtained with each regimen whether measured by an increase in haemoglobin concentration or in serum ferritin concentration. Few side-effects were encountered but discomfort and staining at the injection site was found on the higher dose schedule.

Anemia, Hypochromic↗