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Biomedical subjects

A M Walker

Publications and source records attributed to A M Walker.

At least 145 records · Page 8Linked to original sources
PubMed1994

Effects of estrogen on thermoregulatory evaporation in rats exposed to heat.

The purpose of this study was to determine the effects of estrogen (E2) replacement on thermoregulation in ovariectomized rats exposed to heat. Female Sprague-Dawley rats were ovariectomized and splenectomized and implanted with a temperature-sensitive transmitter. Each rat was studied when E2 treated (after an E2 pellet implant) and untreated. Animals were divided into two groups with opposite order of treatment and were studied over a 9-wk period. Measurements of body core temperature (Tc) and evaporative water loss (EWL) were made on unrestrained animals resting at 38 degrees C air temperature. E2-treated animals increased EWL at all levels of Tc, reduced the threshold Tc for onset of saliva spreading, and regulated Tc at a lower level during heat exposure. E2 treatment elevated plasma E2 and reduced hematocrit but did not affect plasma osmolality. These effects of E2 on evaporative cooling and Tc in heat-stressed rats are similar to those that have been reported in human females. The mechanisms of the thermoregulatory effects of E2 remain to be studied.

Animals↗
PubMed1994

Autocrine interaction between prolactin and its receptor occurs intracellularly in the 235-1 mammotroph cell line.

We have previously demonstrated that PRL acts as an autocrine growth factor in the pituitary tumor GH3 cell line. In this study we present evidence that the 235-1 cell line also uses PRL as an autocrine growth factor, and that in this case interaction between PRL and its receptor occurs intracellularly. First, the PRL produced by 235-1 cells was shown to be capable of initiating a proliferative response by placement in the Nb2 bioassay. Second, PRL receptors were demonstrated to be present, but, unusually, primarily in the Golgi complex by light and electron microscope immunocytochemistry. Incubation of the cells in anti-PRL had no effect on 235-1 cell proliferation until interleukin-1 treatment caused the PRL receptors to move to the cell surface, whereupon cell proliferation was inhibited. Specific interference with PRL biosynthesis in noninterleukin-1-treated cells also inhibited cell proliferation. Thus, the essential elements of an autocrine loop are present and can be demonstrated to be functional by antibody inhibition of growth after movement of the receptors to the cell surface and by antisense inhibition of growth with the receptors in their normal intracellular location.

Animals↗
PubMed1994

Circulating fibroblast growth factor-like autoantibodies in two patients with multiple endocrine neoplasia type 1 and prolactinoma.

Basic fibroblast growth factor (bFGF) is a potent endothelial cell mitogen found in a variety of normal and tumor tissues. bFGF lacks a classical amino-terminal signal sequence and is not readily detectable in plasma from normal subjects. In earlier studies we showed increased bFGF-like mitogenic activity for parathyroid-derived endothelial cells and (increased) bFGF immunoreactivity (0.24-1.28 ng/mL) in plasma of subjects with multiple endocrine neoplasia type 1 (MEN-1). In the present study we examined the proliferative activity of MEN-1 and normal plasmas (applied to protein-A columns) in calf pulmonary artery endothelial cells. Protein-A-eluted activity in plasma from MEN-1 prolactinoma plasma exceeded activity from normal and MEN-1 nonprolactinoma plasma in three of eight MEN-1 subjects with untreated or recurrent prolactinoma. Protein-A-eluted active fractions from MEN-1 prolactinoma plasma had several properties of an immunoglobulin G, including affinity for antihuman immunoglobulin G (IgG) agarose, sensitivity to thiols, and (prepared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions) apparent mol wt corresponding to those of the heavy and light chains of IgG. The IgG fraction of MEN-1 prolactinoma plasma had far more activity in endothelial cells than did optimal concentrations of known growth factors or conditioned medium from prolactinoma cells. Endothelial cell bioactivity in protein-A-eluted fractions from MEN-1 prolactinoma plasma was neutralized 70% by rabbit antibodies to intact bFGF. These results imply novel growth stimulatory bFGF-like autoantibodies in a subset of MEN-1 patients with prolactinoma.

Adult↗
PubMed1994

Hepatitis B immunization in UK renal units: failure to put policy into practice.

A postal questionnaire survey of renal units, and an analytical study of surveillance data on acute hepatitis B were undertaken to discover the numbers of renal units (a) routinely immunizing staff and patients against hepatitis B and (b) with recent experience of managing patients with hepatitis B. Seventy-three (86%) of 85 units returned completed questionnaires. Most (63, 84%) of the responding units routinely immunized staff but only 4 (5%) routinely immunized patients. A third (25) of the units had treated at least one HBsAg-positive patient between 1987 and 1991, and 11 units had cared for at least one patient with acute hepatitis B. Units with recent experience of treating an HBsAg-positive patient were no more likely to immunize staff or patients than those without. Guidance on hepatitis B immunization of staff has generally been implemented by UK renal units; that on immunization of patients has not. Renal unit patients remain largely susceptible to hepatitis B and the potential for outbreaks remains. Renal units need further encouragement to implement fully guidance on immunization.

Health Policy↗
PubMed1994

Examination of the early 'learning curve' for transcatheter closure of patent ductus arteriosus using the Rashkind occluder. PDA Closure Comparative Study Group.

BACKGROUND: Results of transcatheter implantation of the Rashkind double umbrella occluder for treatment of patent ductus arteriosus (PDA) have improved over time. We evaluated factors associated with changes in outcomes seen in the early clinical experience with this device. METHODS AND RESULTS: We reviewed records of otherwise healthy pediatric patients undergoing occluder implantation for isolated PDA between 1982 and 1987 at six major US and Canadian referral centers. Logistic regression was used to assess the impact of ductal size, patient age and weight, calendar time, prior intrainstitutional occluder experience, and residual center effects on closure rates. There were no study deaths. Of 180 occluder placement attempts, 76.7% (95% confidence limits = 70.5%, 83.0%) produced PDA closure by auscultation at 14-month cardiology follow-up or its equivalent. Success probabilities increased in a linear fashion as ductus size decreased, ranging from 41.7% for large (4.1 to 9.0-mm) ducts to 89.4% for small (1.5 to 2.5-mm) lesions. PDA occluder closure rates also improved over time, increasing from 47.4% in 1982-1983 to 84.6% in 1986 and 83.1% in 1987. Multivariate logistic regression indicated that improved outcomes were mainly attributable to decrease in the size of treated ducts over time. Independent of this patient selection, improvements in outcome were less strongly associated with cumulative intracenter experience, calendar time, and age. CONCLUSIONS: Increasing closure rates seen over time primarily reflected more judicious selection of patients as experience accumulated. However, other factors also contributed to the observed trends. An analysis of current treatment results would be of considerable interest.

Age Factors↗
PubMed1994

Falciparum malaria in eastern Thailand: a randomized trial of the efficacy of a single dose of mefloquine.

Reported are the results of a randomized trial of a single dose of mefloquine (15 mg/kg or 25 mg/kg body weight) for the treatment of uncomplicated multidrug-resistant falciparum malaria. Of the 110 adult patients enrolled in the study 57 were randomly assigned to the 15 mg/kg group and 53 to the 25 mg/kg group. The baseline characteristics of the patients did not differ significantly in the two groups, except that those in the 15 mg/kg group had lower haemoglobin levels. Adverse effects following treatment were commoner in the 25 mg/kg group, but not significantly so. Seven patients (6%) did not complete the 42-day follow-up. The parasitological failure rates in the 15 and 25 mg/kg groups were, respectively, 50% (28/56) and 43% (25/53) on day 28, and 62% (33/53) and 56% (28/50) on day 42. Treatment failures were not correlated with the serum mefloquine concentrations on day 2, and 13 out of 19 patients with serum mefloquine concentrations > 2000 micrograms/l on day 2 showed an R response during the follow-up. The mean ratio between the concentrations of the (SR)-(-) and (RS)-(+) enantiomers of mefloquine on day 2 was 3.37, indicating that there are differences in their pharmacokinetics. Re-treatment of patients who showed an R response with seven days of quinine (30 mg.kg-1.day-1)+tetracycline (25 mg.kg-1.day-1) was successful in 93% of the cases.

Adult↗
PubMed1993

Clinical outcomes and costs of transcatheter as compared with surgical closure of patent ductus arteriosus. The Patient Ductus Arteriosus Closure Comparative Study Group.

BACKGROUND: Transcatheter implantation of the Rashkind PDA occluder is an alternative to conventional surgical closure of isolated patent ductus arteriosus. Neither the clinical outcomes nor the costs of these procedures have been formally compared. METHODS: We performed a retrospective cohort study to evaluate the clinical outcomes within a seven-month period for comparable patients with patent ductus arteriosus who underwent either placement of an occluder or surgical closure. The patients were treated between 1982 and 1987 at 14 major North American centers where patent ductus arteriosus was closed predominantly by a surgical procedure or by the occluder technique. To estimate inpatient and follow-up costs, we multiplied the observed use of resources by 1989 unit costs based on hospital-accounting and physician-reimbursement data. RESULTS: On the basis of cardiac auscultation at follow-up, the initial procedure resulted in closure of the ductus arteriosus in 77.3 percent of 185 patients in whom the occluder was implanted (95 percent confidence interval, 70.6 to 83.1 percent) and 99.8 percent of 446 surgical patients (95 percent confidence interval, 98.8 to 100.0 percent). Second procedures increased the percentage of successful closures to 87.6 percent (95 percent confidence interval, 81.9 to 92.0 percent) and 100.0 percent (95 percent confidence interval, 99.3 to 100.0 percent) for patients in the occluder and surgical groups, respectively. There were no deaths. Major complications occurred in 2.7 percent of the patients in whom the occluder was implanted (95 percent confidence interval, 0.9 to 6.2 percent) and 0.2 percent of the patients who underwent surgery (95 percent confidence interval, 0.0 to 1.2 percent); moderate complications in 16.8 percent (95 percent confidence interval, 11.7 to 22.9 percent) and 15.0 percent (95 percent confidence interval, 11.8 to 18.7 percent), respectively; and minor complications in 11.4 percent (95 percent confidence interval, 7.2 to 16.8 percent) and 24.9 percent (95 percent confidence interval, 20.9 to 29.2 percent). Including the cost of follow-up care, the mean estimated cost per case treated surgically was $8,838 (in 1989 U.S. dollars), as compared with $11,466 per case treated with the occluder technique. Sensitivity analyses based on our data identified no plausible situations in which the costs of surgery and of implantation of the occluder would be equal. CONCLUSIONS: The more effective and less costly surgical procedure was superior to transcatheter placement of the occluder for closure of isolated patent ductus arteriosus. Consequently, our results do not support the wide-spread dissemination of the occluder procedure for the management of this common congenital lesion.

Cardiac Catheterization↗
PubMed1993

Cigarette smoking, alcohol, tea and coffee consumption and pancreas cancer risk: a case-control study from Opole, Poland.

A population-based, case-control study of pancreas cancer was undertaken in Opole, Poland, within the framework of the SEARCH Programme of the International Agency for Research on Cancer: this is the first aetiological study of pancreas cancer reported from Poland where the reported mortality rate has doubled since 1963. This study of pancreas cancer has provided some further supporting evidence of an association between increased pancreas risk with increasing levels of cigarette smoking. The risk rose with increasing lifetime cigarette consumption with a trend which was weakly significant (p = 0.061). Findings regarding lifetime tea and coffee consumption were not consistent with intake of either beverage increasing the risk of this disease. There was a strongly significant trend of decreasing risk with increasing lifetime consumption of tea (p < 0.001), which was also apparent when the analysis was restricted to subjects who were interviewed directly. For coffee consumption, which is low in Poland, there was also a negative association apparent in the data which was not statistically significant among the sub-set of subjects who were directly interviewed. The findings regarding alcoholic beverages were overall null, although the weakly positive trend in risk with spirits consumption (p = 0.71) may deserve further investigation in view of the special nature of the source of spirits (vodka) in Poland.

Adult↗
PubMed1993

Determinants of serious liver disease among patients receiving low-dose methotrexate for rheumatoid arthritis.

OBJECTIVE: To assess the risk of serious liver disease in patients with rheumatoid arthritis (RA) taking methotrexate (MTX). METHODS: We surveyed members of the American College of Rheumatology to determine previous use of MTX in the treatment of rheumatoid arthritis and to identify cases of cirrhosis and liver failure. Cases were confirmed by review of pathology specimens, findings from diagnostic testing, and clinical presentations. A case-control study was then conducted to ascertain prognostic factors. Case and control medical records were reviewed for information on MTX therapy as well as other possible determinants of serious liver disease. RESULTS: Twenty-four cases of cirrhosis and liver failure were identified, giving a 5-year cumulative incidence of approximately 1/1,000 treated patients. Six of the 24 patients had died: 4 died of the initial liver disease, 1 of hepatic complications of another illness, and 1 of unrelated causes. Two patients continue to have active liver disease. Late age at first use of MTX and duration of therapy with MTX were independent predictors of serious liver disease. CONCLUSION: Serious liver disease is an uncommon, age- and dose-related complication of low-dose MTX therapy for RA.

Aged↗
PubMed1993

Incidence of rheumatoid arthritis in central Massachusetts.

OBJECTIVE: To determine whether there is a secular decline in the incidence of rheumatoid arthritis (RA), as has been suggested by previous studies. METHODS: In the absence of comprehensive data in the United States population, we estimated RA incidence in a health maintenance organization population from 1987 through 1990 and compared the rates with those in an earlier, similarly performed study from Rochester, Minnesota, which covered the years 1950 through 1974. RA estimates were based on our review of medical records of patients who had been diagnosed as having RA or related diseases during the period of January 1, 1987 through December 31, 1990. RESULTS: Annual age-standardized incidence of classic or definite RA (according to the American College of Rheumatology [formerly, the American Rheumatism Association] 1958 criteria) in patients aged 18 or older was 22 per 100,000 in men and 60 per 100,000 in women. The incidence of RA increased with age, with a marked increase in women older than 50. CONCLUSION: We found no secular change in RA incidence compared with the similarly ascertained historical data.

Adolescent↗
PubMed1993

An equilibrium model of drug utilization.

We propose an equilibrium model to assess the dispensing pattern of non-steroidal anti-inflammatory drugs (NSAIDs) among members of a health maintenance organization. The model incorporates observed patterns of patient switching among NSAIDs and identifies an implicit equilibrium distribution of drug dispensing, which may be used both to identify aberrations in prescription practice and to forecast the expected utilization of newly introduced drugs. NSAID dispensing patterns were stable for most quarters from 1987 to 1990. Introduction of two new NSAIDs and initiation of a pharmacy co-payment coincided with transient perturbation of the patterns. Dispensings of recently introduced NSAIDs achieved their equilibrium values in less than 2 years.

Adult↗
PubMed1993

Verotoxin producing Escherichia coli O 157 infections associated with the consumption of yoghurt.

Sixteen cases of verotoxin producing Escherichia coli (VTEC) O 157:H7 Phage Type 49 infection were identified in the North West of England from 1 September to 1 November 1991, eight of whom lived in or around the same large town. Eleven of the cases were aged 10 years or less, and five of the affected children developed haemolytic uraemic syndrome. A case control study demonstrated a strong association between VTEC O 157:H7 PT 49 infection and the consumption of a locally produced live yoghurt. This is the first time that an outbreak of VTEC O 157 infection has been linked to the consumption of yoghurt and this vehicle of infection should be considered when investigating such outbreaks in future.

Adolescent↗
PubMed1993

Estrogens, progesterone, and endometrial cancer.

We conducted a case-control study to evaluate the effect of replacement estrogen use alone, and the combined effect of estrogen and progesterone use, on the risk for endometrial cancer. We studied women age 50-64 years at Group Health Cooperative of Puget Sound. We identified 172 incident cases of endometrial cancer diagnosed during the years 1979-1989, and controls of similar age and duration of membership in the plan. Women who had used conjugated estrogens alone for 5 or more years were at increased risk for developing endometrial cancer compared with nonusers [adjusted rate ratio (RR) = 22.0; 95% confidence interval (CI) = 6.5-74.1]. Users of unopposed estrogens of 3-4 years' duration had a relative risk of 1.9 (95% CI = 0.4-8.7). Women who had used medroxyprogesterone acetate in combination with the estrogen therapy for 3 or more years had a risk near that of nonusers (adjusted RR = 1.3; 95% CI = 0.5-3.4) and that of users of unopposed estrogens for less than 5 years. There were insufficient women who used estrogen and progesterone together for 5 or more years to derive a separate risk estimate for these women.

Cross-Sectional Studies↗
PubMed1993

Secretion of specific nonphosphorylated and phosphorylated rat prolactin isoforms at different stages of the estrous cycle.

The biological activity and immunoreactivity of serum prolactin (PRL) has been shown to fluctuate throughout the estrous cycle of the rat. Since the 24-kDa nonphosphorylated and phosphorylated isoforms from several species have also been shown to differ in their biological and immunoreactivities, we have investigated the possibility that the 24-kDa monomer isoform profile varied throughout the estrous cycle of the rat. The PRL isoform profile was assessed in homogenates of pituitaries and in short-term incubation media. Comparisons between homogenates, which always contained isoforms 1, 2, 3, and 3' (numbered according to increasing acidity), and media showed nonproportional release of the isoforms at all stages. Of great interest were the release of isoform 1 (a nonphosphorylated form) only at estrus and the lack of release of isoform 3' (a phosphorylated form) only in the afternoon of proestrus. This lack of release of 3' was accompanied by a marked increase in the release of isoform 2 (the unmodified polypeptide). These results suggest a unique function for isoform 1 during estrus and a role for increased isoform 2 and absent isoform 3' during the proestrus surge of PRL. Moreover, they suggest that fluctuations in the biological activity and immunoreactivity of serum PRL during the estrous cycle could be due, at least in part, to fluctuations in the isoform profile.

Animals↗
PubMed1993

Dephosphorylation of standard prolactin produces a more biologically active molecule: evidence for antagonism between nonphosphorylated and phosphorylated prolactin in the stimulation of Nb2 cell proliferation.

Charge isomers of monomer PRL have been described for all species thus far examined. For the rat, cow, and chicken, at least a major proportion of the more acidic isomers have been shown to be phosphorylated. The physiological relevance of this posttranslational phosphorylation, however, remains unclear. In this study we have compared the growth-promoting activities of dephosphorylated and standard rat PRL (partially phosphorylated) in the widely used Nb2 bioassay. Dephosphorylated PRL was produced by treatment of standard rat PRL with acid phosphatase, resulting in the conversion of a 91.9% nonphosphorylated/8.1% phosphorylated preparation to a 98.6% nonphosphorylated preparation. These two preparations were added separately or in combination to stationary Nb2 cells. Cell number was assessed 3 days later using a colorimetric assay. Dephosphorylated PRL showed significantly higher growth-promoting activity than standard PRL at concentrations up to 10 ng/ml. In the 1-5 ng/ml concentration range, dephosphorylated PRL was twice as active. Given that the conversion of 6.7% phosphorylated PRL to nonphosphorylated PRL resulted in a doubling of activity, one can deduce not only that phospho-PRL acted as an antagonist to nonphosphorylated PRL in this assay, but also that it did not do so on an equimolar basis. Titration of the two PRL preparations produced data confirming this latter deduction. These data are of importance in our understanding of PRL-promoted cell proliferation.

Acid Phosphatase↗
PubMed1993

Predictors of treatment failure in multiple drug-resistant falciparum malaria: results from a 42-day follow-up of 224 patients in eastern Thailand.

We report here the results of a 42-day follow-up of 224 patients treated with mefloquine for uncomplicated falciparum malaria in Eastern Thailand. The risk of treatment failure among the 209 patients who completed the follow-up was 57% (95% confidence interval [CI] = 50,64). The daily risk of treatment failure, estimated through an exponential survival function, was constant during the follow-up period and equal to 1.9%. Five patient characteristics were found to be independent and important predictors of treatment failure in a Cox proportional hazards model: a young age (adjusted hazard ratio [AHR] for an increase of 10 years of age = 0.75 [95% CI = 0.62, 0.90]); a history of at least three documented mefloquine treatments in the past year (AHR = 1.89 [95% CI = 1.10, 3.24]); a parasitemia count > 100,000/microliter (AHR = 1.80 [95% CI = 1.16, 2.80]); and a history of diarrhea in the first two days after treatment (AHR = 1.51 [95% CI = 0.99, 2.31]). A hemoglobin level < or = 10 g/dl on the day of consultation was also a predictor of treatment failure, but only among patients who had been treated for malaria in the past 120 days (AHR = 4.38 [95% CI = 1.55, 12.1]). These latter patients may have become anemic while they were unsuccessfully treated with mefloquine for an infection by a multiple drug-resistant strain in the past 120 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Oral contraceptives and endometrial cancer.

OBJECTIVE: To evaluate the effect of ever-use of oral contraceptives (OCs) on the risk of endometrial cancer in women aged 50-64 years. METHODS: A case-control study was carried out using 142 incident cases of endometrial cancer and 1042 matched controls, aged 50-64. All subjects were members of Group Health Cooperative of Puget Sound in Seattle, Washington. Relative risk (RR) estimates were calculated for ever-users of OCs compared to never-users. RESULTS: Twenty-six cases (18%) and 270 controls (26%) had taken OCs at some time, yielding an RR of 0.48 (95% confidence interval [CI] 0.26-0.89) for ever-users compared to never-users. This estimate was adjusted for multiple risk factors. There was little effect of duration of OC use, age at first use, or number of years since last use in these data. CONCLUSION: Women aged 50-64 years at Group Health Cooperative who had taken OCs at some time appear to be protected from developing endometrial cancer later in life, compared to women who had never taken OCs.

Case-Control Studies↗