Search PubMed⌕ Search

Biomedical subjects

N Lawson

Publications and source records attributed to N Lawson.

At least 37 records · Page 2Linked to original sources
PubMed1997

Phase I and pharmacokinetic study of tirapazamine (SR 4233) administered every three weeks.

Tirapazamine (SR 4233; 3-amino-1,2,4-benzotriazine-1,4-di-N-oxide) is a bioreductive agent exhibiting up to 200 x greater toxicity for hypoxic cells as compared to oxygenated cells. In murine studies, a selective increase in tumor kill was observed when tirapazamine was coadministered with other agents, notably cisplatin. A Phase I study of single-agent tirapazamine administered i.v. every 3 weeks was conducted to determine the toxicity of a schedule for use with systemic chemotherapy. A total of 28 patients were given 50 courses of tirapazamine at doses ranging from 36-450 mg/m2. No tumor responses were observed. Reversible deafness and tinnitus were dose-limiting, with ototoxicity observed in 1 of 6 patients treated at 330 mg/m2, 1 of 4 patients treated at 390 mg/m2, and 3 of 3 patients treated at 450 mg/m2. Muscle cramps, nausea, and vomiting were also observed. Pharmacokinetic studies revealed a greater than dose-proportional increase in the area under the plasma concentration x time curve (AUCs) of the two major metabolites. Patients who developed ototoxicity generally showed higher plasma AUC values for the parent drug and metabolites. The mean plasma tirapazamine AUC at 330 mg/m2 was 1026.5 microgram/ml x min (range 863. 8-1252.3), but no pharmacokinetic data are available for the solitary patient who developed otoxicity at this dose level. These AUC values were in the (estimated) range required for therapeutic effect in murine studies. Ototoxicity was not observed when the AUC of tirapazamine was equal to or less than 1252 microgram/ml x min. The dose of 330 mg/m2 was therefore chosen as an appropriate level for combination chemotherapy studies.

Adult↗
PubMed1995

Modulation of hepatic apolipoprotein B, 3-hydroxy-3-methylglutaryl-CoA reductase and low-density lipoprotein receptor mRNA and plasma lipoprotein concentrations by defined dietary fats. Comparison of trimyristin, tripalmitin, tristearin and triolein.

Different dietary fatty acids exert specific effects on plasma lipids but the mechanism by which this occurs is unknown. Hamsters were fed on low-cholesterol diets containing triacylglycerols enriched in specific saturated fatty acids, and effects on plasma lipids and the expression of genes involved in hepatic lipoprotein metabolism were measured. Trimyristin and tripalmitin caused significant rises in low-density lipoprotein (LDL) cholesterol which were accompanied by significant reductions in hepatic LDL receptor mRNA levels. Tripalmitin also increased hepatic expression of the apolipoprotein B gene, implying an increased production of LDL via very-low-density lipoprotein (VLDL) and decreased removal of LDL in animals fed this fat. Hepatic levels of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA did not vary significantly between the groups. Compared with triolein, tristearin had little effect on hepatic gene expression or total plasma cholesterol. However, it caused a marked decrease in VLDL cholesterol and a rise in LDL cholesterol such that overall it appeared to be neutral. Lipid analysis suggested a rapid desaturation of much of the dietary stearate. The differential changes in plasma lipids and hepatic mRNA levels induced by specific dietary fats suggests a role for fatty acids or a metabolite thereof in the regulation of the expression of genes involved in lipoprotein metabolism.

Adipose Tissue↗
PubMed1995

Fecal alpha 1-antitrypsin detection of colorectal neoplasia. An evaluation using HemoQuant.

Fecal alpha 1-antitrypsin measurement may be of value for the detection of colorectal neoplasia and is compared with the HemoQuant test in 119 subjects with either a screen-positive Hemoccult result (N = 78) or iron-deficiency anaemia (N = 41). Nineteen patients were found to have colorectal cancer, 35 had colorectal adenomatous polyps, 5 had inflammatory bowel disease, and 60 had no detected cause of occult blood loss. Of the cancer patients, 63% (12/19) were detected by fecal alpha 1-antitrypsin and 63% (12/19) by HemoQuant. Of the adenomas > 1 cm in diameter 33% (7/23) were detected by fecal alpha 1-antitrypsin and 26% (6/23) by HemoQuant. There was a poor correlation between fecal alpha 1-antitrypsin and HemoQuant results for colorectal cancers (r = 0.37, P > 0.05), and combining the tests, the sensitivity for colorectal cancer was increased to 84% (16/19). Fecal protein loss, as measured using alpha 1-antitrypsin, appears to involve largely different mechanisms from that of blood loss from colorectal cancers.

Adenomatous Polyps↗
PubMed1995

The information and learning needs of the caregiving family of the adult patient with cancer.

The need for information by the caregiving family of an adult patient with cancer has been identified by research. This paper is a literature review of the information and learning needs of caregiving relatives. By meeting these needs the health care professional is able to help support the family, and therefore the patient, with the difficult adjustment to the diagnosis and through the subsequent course of the disease. The health care professional facilitates the individual caregivers' coping mechanisms and the benefits can be seen in the caregiving outcome for both the family and the patient. Information needs vary from individual to individual and are dynamic throughout the cancer experience. This paper describes the role of the nurse in this area, and encourages the nurse to act as a resource person for the caregiver by the appropriate delivery of information and by ensuring that the information given to the family by other health care professionals is understood and fulfils their needs.

Adaptation, Psychological↗
PubMed1994

Assessment of retinol-binding protein excretion in normal children.

Retinol-binding protein (RBP) is a low molecular weight protein freely filtered at the glomerulus. The fractional tubular reabsorption of RBP is 99.97% and increased excretion is therefore a sensitive marker of tubular dysfunction. We obtained early-morning urine specimens from 151 well children, from newborn to 16 years of age. RBP was measured using an enzyme-linked immunosorbent assay, albumin by a radioimmunoassay and creatinine by a modified Jaffé reaction. Protein excretion was assessed by calculating the protein:creatinine ratio for early-morning urine samples. We found a fall in both RBP and albumin excretion with increasing age, particularly in the 1st year of life, with a much wider variation in values from the infants studied. The mean excretion of RBP for children aged 0-6 months [51.4 (0.6-4,719) micrograms/mmol] was significantly higher (P < 0.001) than the mean for children aged 6 months to 16-years [15.0 (3.8-60) micrograms/mmol]. It has been shown that measurement of tubular proteinuria using the RBP: creatinine ratio is useful in the assessment of children with renal disease and we propose a value two standard deviations above the geometric mean for the age of the patient as an upper limit of normal.

Adolescent↗
PubMed1993

Value of faecal alpha-1-antitrypsin, haemoglobin and a chemical occult blood test in the detection of gastrointestinal disease.

Specimens from hospital out-patients and in-patients sent for faecal occult blood tests were also analysed for faecal alpha-1-antitrypsin and faecal haemoglobin. 453 stool specimens from 222 patients were analysed. The clinicians were only aware of the faecal occult blood test results, and diagnoses were made using conventional clinical and investigative criteria. Gastrointestinal bleeding or putative sites of bleeding were diagnosed in 98 patients, whereas in 81 patients putative sites of bleeding were not found or other cause of anaemia diagnosed. In 41 patients there was insufficient information to reach a definitive diagnosis. Comparison of the 3 faecal tests using these grouping methods showed that faecal alpha-1-antitrypsin performed best, with an accuracy of 89%, specificity of 90% and sensitivity of 88%, all significantly better (P < 0.001) than the faecal occult blood test (68%, 60% and 73%, respectively). There was no significant difference between the performance of the faecal occult blood and faecal haemoglobin tests. Faecal alpha-1-antitrypsin measurement may be a useful investigation in situations where a faecal occult blood test would normally be requested.

Adolescent↗
PubMed1993

Lymphocyte beta adrenoceptor upregulation and improved cardiac response to adrenergic stimulation following converting enzyme inhibition in congestive heart failure.

To determine the effect of ACE inhibitor therapy on lymphocyte beta-adrenoceptor function and density, as well as the in vivo myocardial response to beta-agonist stimulation, we studied 12 patients with chronic severe heart failure before and after 16 weeks' treatment with quinapril. Lymphocyte beta-adrenoceptor function (intracellular cAMP production in response to isoprenaline) was studied as a surrogate tissue for myocardium, and increased significantly after quinapril at concentrations of isoprenaline between 10(-3) and 50 mmol.l-1. Lymphocyte beta-adrenoceptor density (six patients) measured by [125I] iodocyanopindolol binding, increased from 242 +/- 72 (mean +/- SEM) to 884 +/- 17 receptors/cell (P < 0.05). Changes in functional myocardial beta-adrenoceptor status were determined by measuring changes in haemodynamic responses to exercise and to incremental dobutamine infusion. Following quinapril there were significant improvements in cardiac index, stroke volume and cardiac power output during sub-maximal exercise testing and dobutamine infusion; stroke work index in response to dobutamine (but not exercise) improved significantly. ACE inhibitors cause lymphocyte beta-adrenoceptor upregulation in heart failure, which is associated with an improved cardiac pumping capacity in response to beta-agonist stimulation.

Adult↗
PubMed1993

Placebo-controlled trial of lisinopril in normotensive diabetic patients with incipient nephropathy.

To study the effects of an angiotensin converting enzyme inhibitor, lisinopril, on renal function in incipient diabetic nephropathy, a prospective double-blind randomised placebo-controlled single centre study was set up at our outpatient diabetic-renal clinic. There were 27 patients with Type I and Type II diabetes with an albumin excretion rate of between 20 micrograms/min and 200 micrograms/min, respectively and no hypertension. Intervention treatment with placebo or low dose lisinopril was for 48 weeks. The main outcome changes were in urinary albumin excretion rate, urinary prostaglandin excretion, and glomerular filtration rate. Secondary outcome measures included changes in BP and heart rate. Of the 32 patients entered into the study, 27 completed 48 weeks treatment (12 lisinopril, 15 placebo). Mean (+/- SD) urinary albumin excretion rate fell from 57.6 (25.7) micrograms/min (n = 15) at visit 1 to 26.8 (26.7) micrograms/min (n = 12) at visit 7 after 48 weeks treatment in the lisinopril group but not in the placebo group: 119.2 (116.6) micrograms/min (n = 17) vs. 113.7 (77.0) micrograms/min (n = 15). There was a least squares mean treatment difference of -67.6 micrograms/min (95% confidence interval (CI), -115.0 to -20.2, P < 0.01) in favour of lisinopril compared with placebo. After 48 weeks treatment seven lisinopril treated patients were normoalbuminuric and five were microproteinuric; three placebo treated patients were normoalbuminuric, nine were microalbuminuric and three were macroproteinuric. Excretion of prostaglandin-F1 alpha (PGF1 alpha) and thromboxane-B2 (TXB2) fell in the lisinopril treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Comparison of the effects of an angiotensin converting enzyme inhibitor and a calcium antagonist in hypertensive, macroproteinuric diabetic patients: a randomised double-blind study.

The objective of this study was to compare the effects of an angiotensin converting enzyme inhibitor, lisinopril, with those of a calcium blocker, nifedipine, on BP control and renal function, in a prospective randomised double-blind, double-dummy trial lasting 19 weeks in patients with diabetic nephropathy. We enrolled 28 diabetic patients with hypertension and macroproteinuria from the out-patient diabetic-renal clinic. The antihypertensive treatment consisted of lisinopril or nifedipine, and their effect on arterial BP, urinary albumin excretion, glomerular filtration rate, and renal blood flow were measured. BPs at entry were 166/99 (SD 23/9) mmHg for the lisinopril group and 165/99(21/7) mmHg for the nifedipine group. BPs fell to 143/88 (17/13) mmHg for the lisinopril group and 148/85(25/10) mmHg for the nifedipine group at the end of the study. The albumin excretion rate fell in the lisinopril group from 738.7 (635.2) micrograms/min to 644.6 (965.2) micrograms/min and rose in the nifedipine group from 981.2 (1022.2) micrograms/min to 1072.5 (908.5) micrograms/min (P = NS). Glomerular filtration rates fell from 105.2 (57.5) ml/min per 1.73 m2 to 72.1 (39.4) ml/min per 1.73 m2 in the lisinopril group and from 109.9 (50.0) ml/min per 1.73 m2 to 82.9 (53.9) ml/min per 1.73 m2 in the nifedipine treated group. Renal blood flow fell from 446.8 (217.9) ml/min per 1.73 m2 to 435.1 (243.3) ml/min per 1.73 m2 for the lisinopril group and from 473.0 (216.4) ml/min per 1.73 m2 to 419.0 (278.6) ml/min per 1.73 m2 for the nifedipine group. Differences between the groups were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Arachidonic acid and docosahexaenoic acid are increased in human colorectal cancer.

Increased arachidonic acid concentrations in experimental rodent colonic cancer have been described recently. In humans, a reduced erythrocyte stearic acid to oleic acid ratio has been reported in patients with colorectal cancer and it has been proposed that similar changes exist in the cancer tissue. The long chain fatty acids in the cancers of 15 patients with colorectal cancer were measured and compared with values in the unaffected mucosa. The values were expressed as mean (SD) mg fatty acid/g tissue and compared by analysis of variance. In the cancer tissue arachidonic acid was increased (0.703 (0.109) mg/g v 0.603 (0.127) mg/g, p less than 0.05) as was docosahexaenoic acid (0.211 (0.066) mg/g v 0.148 (0.039) mg/g, p less than 0.001). In contrast, the stearic acid to oleic acid ratio in the cancer tissue was increased rather than decreased, as previously suggested (0.36 (0.05) v 0.29 (0.7), p less than 0.01). Increased arachidonic acid and docosahexaenoic acid concentrations may be related to reduced lipid peroxidation, which is a feature of rapidly growing cells. Alternatively, the increased arachidonic acid values could be due to enhanced desaturase activity upon linoleic and linolenic acid, leading perhaps to increased formation of prostaglandins and other lipoxygenase products.

Aged↗
PubMed1991

Creatine kinase activity in patients with brittle asthma treated with long term subcutaneous terbutaline.

Infused beta 2 agonists have been shown to cause focal myocardial necrosis. Serum creatine kinase activity was compared in 13 patients with brittle asthma currently being treated with subcutaneous terbutaline and an age and sex matched control group of patients with moderate asthma having inhaled treatment only. The median serum total creatine kinase activity for patients receiving subcutaneous terbutaline (211 units/l) was greater than that for the control group (120 units/l). The cardiac specific isoenzyme component of creatine kinase was not raised in either group, and the electrocardiograms and serum aspartate aminotransferase activity were normal. Electromyograms in five patients receiving subcutaneous terbutaline with high creatine kinase activity showed changes consistent with myositis in two, one of whom was subsequently shown to have a metabolic myopathy, which is thought to be long standing. No pathological changes were seen in the myocardium at necropsy in a patient who died from an acute attack of asthma while taking subcutaneous terbutaline. These results suggest that the raised creatine kinase activity seen in patients receiving this treatment is unlikely to be myocardial in origin.

Adult↗
PubMed1991

Abnormal blood pressure response to exercise in normoalbuminuric insulin dependent diabetic patients.

Eight male normoproteinuric Type I (insulin dependent) diabetic patients and eight age- and sex-matched non-diabetic control subjects were studied for their response to exercise. Systolic blood pressure showed an exaggerated response to exercise in the diabetic group (median 123, range 98-151 mmHg, pre-exercise vs. 187, 163-217 mmHg, immediately post exercise P less than 0.01) compared to the control group (median 112 (100-145) pre-exercise, 153 (138-178) post exercise). Resting noradrenaline levels were lower in the diabetic (D) compared with the control (C) group (D: 1.66, 0.55-3.92 nmol/l vs. C: 2.96, 2.04-4.49 nmol/l, P less than 0.02). Levels rose during exercise by 79% (25-307%) and 43% (4-90%) respectively (NS). Resting urinary sodium was raised in the diabetic group and fell during exercise (P less than 0.05) (D: 146, 74-244 mumol/min, C: 108.5 (83.4-151.0) pre-exercise vs. D: 73, 48-264 mumol/min, C: 81.7 (23.0-92.0) post exercise). Resting atrial natriuretic peptide levels were lower in the diabetic group (D: 10.1, 4.3-16.9 pmol/l vs. C: 16.0, 9.5-22.9 pmol/l, P less than 0.02) and levels rose significantly in both groups during exercise (D: 25.9, 5.2-38.9 pmol/l vs. C: 28.6, 17.3-47.2 pmol/l, P less than 0.05). We conclude that exercise provokes an exaggerated rise in systolic blood pressure and decrease in urinary sodium excretion in normoalbuminuric diabetic patients. These findings may reflect increased sensitivity to the renin-angiotensin-aldosterone system. Reduced atrial natriuretic peptide levels may stimulate sodium retention and increased blood pressure in early diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1990

Phase I and pharmacokinetic study of intraperitoneal thioTEPA in patients with ovarian cancer.

A total of 15 patients with residual ovarian cancer confined to the peritoneal cavity after first-line systemic chemotherapy were treated with triethylene-thiophosphoramide (thioTEPA) in a phase I study. A total of 50 courses of thioTEPA were given intraperitoneally in doses ranging from 30 to 80 mg/m2. The dose limiting toxicity was myelosuppression, which occurred at 80 mg/m2 and was frequently prolonged. Short-lived nausea and vomiting was easily controlled, and there was no local toxicity. Three patients remain free of disease progression at 6, 6 and 12 months. ThioTEPA concentrations were measured by gas chromatography. Peritoneal fluid concentrations declined rapidly in a first-order fashion, with a half-life of 0.96 +/- 0.1 h. A mean of 93% of the drug was absorbed during the 4-h dwell time. Peak plasma levels were achieved 30-60 min after drug instillation and were substantially lower than corresponding peritoneal levels. A pharmacokinetic advantage for intraperitoneal delivery was detected for peak drug concentration (24.9 +/- 8.5) and AUC (9.2 +/- 4.8). Based on this study, the recommended dose for intraperitoneal thioTEPA is 60 mg/m2 every 3-4 weeks. However, the rapid absorption of this drug from the peritoneum, secondary to thioTEPA's small molecular weight and lipophilic nature, suggests that it has only a limited role in intraperitoneal therapy.

Adult↗