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Biomedical subjects

M Muirhead

Publications and source records attributed to M Muirhead.

At least 19 recordsLinked to original sources
PubMed1999

Prevalence of gestational diabetes mellitus among Swampy Cree women in Moose Factory, James Bay.

BACKGROUND: Although high rates of gestational diabetes mellitus have been documented in native populations, few studies have examined rates of the disease among native Indians in Canada. The authors conducted a study to estimate the prevalence of gestational diabetes among Swampy Cree women, to identify factors predictive of the occurrence of gestational diabetes, and to identify delivery and infant outcomes related to the presence of the disease. METHODS: Information on Swampy Cree women who gave birth at Weeneebayko Hospital, Moose Factory, James Bay, Ont., between 1987 and 1995 was obtained from medical charts. Patients with and without gestational diabetes were compared. Logistic regression analysis was used to identify independent predictors of gestational diabetes. Delivery and infant outcomes that occurred secondary to gestational diabetes were also identified by means of logistic regression. RESULTS: A total of 1401 deliveries occurred at Weeneebayko Hospital over the study period, of which 1298 were included in the study. Gestational diabetes was diagnosed in 110 (8.5% [95% confidence interval (CI) 6.9%-9.9%]) of the 1298 pregnancies. Factors predictive of gestational diabetes were age 35 years or more (relative risk [RR] 4.1, 95% CI 1.5-11.7), a history of gestational diabetes in a previous pregnancy (RR 6.4, 95% CI 3.5-11.7), diastolic blood pressure of 80 mm Hg or higher at the first prenatal visit (RR 1.7, 95% CI 1.1-2.8), weight greater than 80 kg at the first prenatal visit (RR 4.9, 95% CI 1.8-12.9) and having a first-degree relative with diabetes (RR 3.0, 95% CI 1.4-6.1). The only delivery outcome independently associated with the presence of gestational diabetes was an increased likelihood of needing assisted delivery (forceps or vacuum extraction) (RR 2.8, 95% CI 1.1-7.0). Shoulder dystocia was indirectly associated with gestational diabetes owing to increased infant birth weight. Infant outcomes associated with the presence of gestational diabetes were birth weight greater than 4500 g (RR 2.4, 95% CI 1.4-3.8), hyperbilirubinemia (RR 2.9, 95% CI 1.4-6.1), hypoglycemia (RR 7.3, 95% CI 3.7-14.4) and hypocalcemia (RR 8.9, 95% CI 2.3-33.7). INTERPRETATION: Gestational diabetes occurred in a significant minority of Swampy Cree women and was associated with a number of adverse outcomes.

Adolescent↗
PubMed1996

Evaluation of cisplatin, carboplatin, and etoposide in metastatic nonsmall cell lung carcinoma. A phase II study of the Southwest Oncology Group.

BACKGROUND: The combined use of cisplatin and carboplatin chemotherapy offers a unique means of platinum dose intensification. Response rates using either of these agents in combination with etoposide are comparable. In a Phase II trial, the authors investigated the combination of cisplatin and carboplatin with etoposide for the treatment of patients with advanced nonsmall cell lung carcinoma. METHODS: Eligible patients were chemotherapy naive and had histologically confirmed, evaluable, or measurable selected Stage IIIB and Stage IV nonsmall cell lung carcinoma. Based upon the results of an earlier Phase I and II pilot study, patients received carboplatin, 225 mg/m2, on Day 1; cisplatin, 50 mg/m2, on Days 2 and 3; and etoposide, 75 mg/m2, on Days 1, 2, and 3 every-4-weeks. RESULTS: Eighty-three patients (75 eligible patients) received chemotherapy with cisplatin, carboplatin, and etoposide. Two patients refused therapy after registration and were not analyzable. Thirty-six of the remaining 75 patients had Grade 4 toxicities, mostly hematologic, and 6 patients died of toxicity. The confirmed response rate was 24% (95% confidence interval, 15-35%). Median progression-free survival was 4 months and the median survival was 8 months. CONCLUSIONS: Combination cisplatin, carboplatin, and etoposide chemotherapy appears to be no better than cisplatin/etoposide or carboplatin/etoposide for the treatment of patients with nonsmall cell lung carcinoma. The toxicity of this regimen may be higher, and therefore it cannot be recommended for general use.

Adult↗
PubMed1994

Purification of class I medullipins from the venous effluent of isolated normal kidneys perfused under high pressure with saline.

Medullipin I (Med I) is a vasodepressor prohormone which is continuously elaborated into the renal venous effluent (RVE) of isolated rat kidneys perfused under high pressure. We have improved the yield of Med I by substituting saline for the albumin perfusate previously reported; and considerably improved refinement by directly fractionating the crude lipid extract of the RVE with high pressure liquid chromatography. The results show that Med I, as defined by previous physiologic and pharmacologic criteria, is not a single molecule. The 3 Class I medullipins described here are distinguished by subtle or overt differences in polarity and biologic activity.

Animals↗
PubMed1992

Use of a modified Transwell culture to quantitate the contribution of non-IL-7 substances to growth of an IL-7-dependent pre-B cell clone.

Clone 3 is a mouse pre-B cell line that cannot grow in standard tissue culture media but is immortalized by coculture with a bone marrow-derived feeder layer. In addition, clone 3 cells can be passaged indefinitely in recombinant interleukin-7 (IL-7) in the absence of a feeder layer if maintained at high cell density. Using monoclonal antibody to IL-7 and Transwells ligated to dialysis membranes, we have examined the relative contributions of IL-7, both endogenous and exogenous, and of "non-IL-7" feeder layer factors to growth promotion of clone 3 cells. There is synergy between feeder layers and exogenous IL-7 that is most marked when the latter is present in suboptimal concentrations. The synergizing activity is not neutralized by antibody to IL-7 and appears to be freely dialyzable. This "non-IL-7" effect is common to two different feeder layers, the one derived from bone marrow (3E) being an IL-7 producer, and the other, 3T3 fibroblasts, making no detectable IL-7. These experiments reveal a substantial contribution of the dialyzable moiety to the total feeder layer effect, and are the first to demonstrate cytokine-dependent low-molecular-weight synergy in a coculture. This demonstration is possible because the synergizing cofactor(s) can cross a semipermeable membrane whereas the cytokine and its neutralizing antibody cannot.

3T3 Cells↗
PubMed1991

The characteristics of respiratory ill health of wool textile workers.

The relations of lung function and chest radiographic appearances with exposure to inspirable dust were examined in 634 workers in five wool textile mills in west Yorkshire, randomly selected to represent fully the range of current exposures to wool mill dust. Most of these workers could be categorised into three large sex and ethnic groups; European men, Asian men, and Asian women. Exposures to inspirable dust had been measured at a previous survey and time spent in current job, and in the industry were used as surrogates for lifetime cumulative exposures. Chest radiographs were interpreted on the International Labour Office (ILO) scale by three medically qualified readers, and the results combined. Profusions of small opacities of 0/1 on the ILO scale, or greater, were present in only 6% of the population, and were not positively associated with current exposure to wool mill dust, or duration of exposure. In general, statistically significant relations between exposure and lung function indices were not found, with the exception of an inverse relation between the forced expiratory volume/forced vital capacity ratio and dust concentration in European women. A suggestive but not statistically significant inverse relation between FVC and current dust concentration was seen in Asian men. Substantial differences were found between mills in mean values of lung function variables after adjustment for other factors but these were not apparently related to the differences in dust concentrations between these mills. Dyeworkers and wool scourers (mostly European men in relatively dust free jobs) on average experienced an FEV1 251 ml lower than other workers when age, height, smoking habits, and occupational factors had been taken into account. Twenty four per cent of the workforce responded to intracutaneous application of one or more common allergens (weal diameter at least 4 mm), only 12 (7.9%) of these responding to wool extracts. Atopic subjects did not appear to have an increased susceptibility to the effects of inspirable wool dust on lung function. These studies suggest that exposure to wool mill dust may cause functional impairment in some workers but there is little indication from these data of frequent or severe dust related functional deficits. More detailed estimates of cumulative dust exposure by reconstruction of exposure histories might clarify associations between exposure to dust and lung function. These chest radiographic findings provide no evidence that exposure to wool mill dust is related to lung fibrosis.

Adult↗
PubMed1990

Several types of adherent cells elaborate a dialyzable lymphopoietic cofactor (Abelson Growth Promoter).

We have cloned a stromal cell from mouse bone marrow selected on the basis of its ability to promote the growth of an Abelson virus-transformed pre-B cell line. These stromal cells have smooth muscle features, and the ultrafiltrate of stromal cell-conditioned medium has proliferative effects on all feeder layer-responsive mouse pre-B cell lines tested, as well as on normal pre-B cells. One of these low MW substances is a protease-resistant factor with an MW of approximately 450 Da which we designate Abelson Growth Promoter (AGP). AGP was initially characterized as an activity which promotes the growth of Abelson virus-transformed mouse pre-B cells, but it also promotes the growth of a ras-transformed pre-B cell line as a single agent and in synergistic fashion with recombinant interleukin (IL) 7. AGP as a single agent has no effect on normal pre-B cells, which have a brisk response to IL-7. In contrast, transformed pre-B cells display a blunted response to IL-7. We propose that AGP plays a role in normal lymphopoiesis by expanding clones of pre-B cells which have been activated by other stromal cell-derived signals, such as IL-7, and directly promotes the growth of nascently transformed pre-B cells.

Abelson murine leukemia virus↗
PubMed1990

Amiloride disposition in geriatric patients: importance of renal function.

1. The absorption and disposition of the potassium sparing diuretic amiloride were determined in nine elderly patients aged 71 to 87 years and in eight young (25 to 38 years) subjects following oral administration of 5 mg amiloride HCl daily to steady-state. 2. The maximum and steady-state plasma amiloride concentrations were significantly (P less than 0.05 and P less than 0.001) higher in the elderly patients. The renal clearance of amiloride was lower in the elderly than in young subjects (102 +/- 36 ml min -1 vs 300 +/- 64 ml min-1, P less than 0.001) as was the urinary excretion of amiloride (36 +/- 13 vs 62 +/- 18% of the dose, P less than 0.01). 3. The steady-state plasma amiloride concentration correlated significantly (r2 = 0.61, P less than 0.001) with amiloride renal clearance and with creatinine clearance (r2 = 0.59, P less than 0.001). There was a very strong positive correlation between renal amiloride clearance and creatinine clearance (r2 = 0.76, P less than 0.001). The slope of the regression line was 2.5 indicating substantial proximal tubular secretion of amiloride. 4. Sodium and potassium excretion, along with urine volume were significantly (P less than 0.05) lower in the elderly (by 39, 45 and 34% respectively). 5. The disposition of amiloride was highly dependent on renal function, with higher plasma amiloride concentrations in the elderly reflecting diminished renal function. The dose of amiloride should be titrated to individual response, and the lower potassium excretion in the elderly patients suggests that the dose of amiloride could be reduced in this group of patients.

Adult↗
PubMed1988

Pharmacokinetic drug interactions between triamterene and ranitidine in humans: alterations in renal and hepatic clearances and gastrointestinal absorption.

Ranitidine reduces the renal tubular secretion of the organic cations procainamide and N-acetylprocainamide in humans through competition for transport via the organic cation transport system. Ranitidine is thought to spare phase I hepatic metabolism mediated by cytochrome P-450, unlike its counterpart H2-receptor antagonist cimetidine. The aim of the present study was to determine, in eight human subjects, the effect of ranitidine on the disposition of the potassium-sparing diuretic triamterene, which undergoes renal tubular secretion, hepatic hydroxylation and subsequent sulphate conjugation to a pharmacologically active metabolite. Multiple blood and urine samples were collected throughout a dosing interval after chronic administration of triamterene alone, ranitidine alone or the two in combination. Ranitidine significantly (P less than .05) reduced the renal clearances of triamterene (51%) and p-hydroxytriamterene sulphate conjugate (47%), the clearance by hydroxylation of triamterene (30%) and the apparent absorption of triamterene (52%). In turn, triamterene reduced the renal clearance of ranitidine (14%). The interaction resulted in a small attenuation of the pharmacodynamic response to triamterene. These results necessitate consideration of the underlying mechanisms of the interactions and fall outside of our present understanding of the renal clearance of sulphate conjugates and the metabolic inhibitory effects of ranitidine. Competition for translocation across membranes is postulated as a common mechanism for the observed renal and hepatic interactions.

Adult↗
PubMed1987

Pharmacokinetic interactions of cimetidine 1987.

The number of studies on drug interactions with cimetidine has increased at a rapid rate over the past 5 years, with many of the interactions being solely pharmacokinetic in origin. Very few studies have investigated the clinical relevance of such pharmacokinetic interactions by measuring pharmacodynamic responses or clinical endpoints. Apart from pharmacokinetic studies, invariably conducted in young, healthy subjects, there have been a large number of in vitro and in vivo animal studies, case reports, clinical observations and general reviews on the subject, which is tending to develop an industry of its own accord. Nevertheless, where specific mechanisms have been considered, these have undoubtedly increased our knowledge on the way in which humans eliminate xenobiotics. There is now sufficient information to predict the likelihood of a pharmacokinetic drug-drug interaction with cimetidine and to make specific clinical recommendations. Pharmacokinetic drug interactions with cimetidine occur at the sites of gastrointestinal absorption and elimination including metabolism and excretion. Cimetidine has been found to reduce the plasma concentrations of ketoconazole, indomethacin and chlorpromazine by reducing their absorption. In the case of ketoconazole the interaction was clinically important. Cimetidine does not inhibit conjugation mechanisms including glucuronidation, sulphation and acetylation, or deacetylation or ethanol dehydrogenation. It binds to the haem portion of cytochrome P-450 and is thus an inhibitor of phase I drug metabolism (i.e. hydroxylation, dealkylation). Although generally recognised as a nonspecific inhibitor of this type of metabolism, cimetidine does demonstrate some degree of specificity. To date, theophylline 8-oxidation, tolbutamide hydroxylation, ibuprofen hydroxylation, misonidazole demethylation, carbamazepine epoxidation, mexiletine oxidation and steroid hydroxylation have not been shown to be inhibited by cimetidine in humans but the metabolism of at least 30 other drugs is affected. Recent evidence indicates negligible effects of cimetidine on liver blood flow. Cimetidine reduces the renal clearance of drugs which are organic cations, by competing for active tubular secretion in the proximal tubule of the kidney, reducing the renal clearances of procainamide, ranitidine, triamterene, metformin, flecainide and the active metabolite N-acetylprocainamide. This previously unrecognised form of drug interaction with cimetidine may be clinically important for both parent drug, and metabolites which may be active.(ABSTRACT TRUNCATED AT 400 WORDS)

Cimetidine↗
PubMed1985

Increased plasma proteinase activity of mice bearing the BCL1 leukemia.

Plasma samples from mice bearing the BCL1 leukemia were shown to express elevated levels of neutral proteinase activity when assayed with radioiodinated casein as a substrate. Increased plasma proteinase activity reached levels 3-4-fold higher than controls. The increased levels of activity did not correlate with the degree of hepatosplenomegaly or the number of tumor cells in the blood. The onset of the increase in plasma activity correlated with the onset of the leukemic phase of the disease. These findings with the murine leukemia may be analogous to recent findings of abnormal proteinase activity in plasma from patients with acute leukemia.

Aminocaproic Acid↗
PubMed1983

Use of an antibody-ricin A-chain conjugate to delete neoplastic B cells from human bone marrow.

Affinity-purified rabbit antibody to human lambda and kappa chains (R alpha H lambda kappa) was conjugated to the A-chain of the plant toxin, ricin. The resulting immunotoxin (R alpha H lambda kappa-A) killed cells from the tumor cell line Daudi, which bears surface immunoglobulin, but was nontoxic to the CFU-E, BFU-E, and CFU-GM of human bone marrow. R alpha H lambda kappa-A eliminated 99% of clonogenic Daudi cells that had been mixed with marrow cells in vitro, without demonstrable toxicity to hematopoietic cells. Thus, in vitro treatment of marrow with R alpha H lambda kappa-A may increase the incidence of cure following autologous bone marrow transplantation for the treatment of human B-cell malignancies.

Antibodies, Anti-Idiotypic↗
PubMed1981

Immunosuppression in a murine B cell leukemia (BCL1): role of an adherent cell in the suppression of primary in vitro antibody responses.

The ability of lymph node cells from mice bearing the BCL1 tumor to respond in vitro to mitogens, allogeneic cells, and both TI and TD antigens was investigated. The lymph nodes of such mice are not invaded with tumor cells and contain normal numbers of T and B cells. Nevertheless, at the peak of tumor burden in the spleen and blood (approximately 8 to 12 wk after injection with tumor cells), the lymph node cells from the tumor-bearing mice display markedly decreased responsiveness both to allogeneic cells and to antigens. In addition, small numbers of lymph node cells from the tumor-bearing mice suppress primary antibody responses of normal lymph node cells. This nonspecific suppression of antibody responses is mediated by a G-10 Sephadex adherent, non-T, non-B cell present in the nodes of the tumor-bearing mice. Since the BCL1 tumor model is in many respects similar to the prolymphocytic type of human chronic lymphocytic leukemia, the present results may be helpful in elucidating the mechanisms underlying the in vivo immunosuppression associated with lymphocytic neoplasms in humans.

Animals↗
PubMed1975

Role of the gonads in hypertension-prone rats.

In a genetically hypertension-prone (S) strain of rats it was observed previously that males generally developed hypertension more rapidly on a high salt diet than did females although final pressure ultimately were similar in both sexes. A genetic study had shown that there was no sex-linkage involved in setting blood pressure levels, so it was thought that the gonads might be involved. In the present work, castration of males had no effect on blood pressure but in the females it caused a rise in pressure that could not be distinguished from that in males, both on a high and low salt diet. Castration resulted in greater growth in females than in controls, whereas it had the opposite effect in males. It was speculated that these changes were due to influences on pituitary growth hormone with castration increasing the net output of growth hormone (or enhancing receptor sensitivity to it) in the female and the opposite in the male. From the work of others, there are some data compatible with such an interpretation. Experimentally, growth hormone will induce hypertension in rats. Therefore, it is conceivable that growth hormone is involved in the increment in hypertension observed in these castrate females. Because the effect on blood pressure was observed in castrate females on both high and low NaCl diets, it was considered unlikely that the blood pressure effect was simply due to increased NaCl intake in the food associated with greater growth. It was suggested that this rise in blood pressure with cessation of ovarian function might bear on the unsettled question of "menopausal" hypertension in women: in the genetically susceptible individual an increase in growth hormone associated with declining ovarian funtion in the menopause could provide the stimulus for the appearance of hypertension some years earlier than would otherwise have been the case.

Animals↗