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Biomedical subjects

A M Walker

Publications and source records attributed to A M Walker.

At least 199 records · Page 11Linked to original sources
PubMed1990

Regional cerebral blood flow after hemorrhagic hypotension in the preterm, near-term, and newborn lamb.

Developmental changes in regional cerebral blood flow (CBF) responses to hemorrhagic hypotension during normoxia and normocapnia were determined using radioactively labeled microspheres to measure flow to the cortex, brainstem, cerebellum, white matter, caudate nucleus, and choroid plexus in three groups of chronically catheterized lambs: 90- to 100-d preterm fetal lambs (n = 9); 125- to 136-d near-term fetal lambs (n = 9); and newborn lambs 5- to 35-d-old (n = 8). Heart rate, central venous pressure, and arterial blood pressure were monitored continuously and arterial blood gas tensions, pH, Hb, and oxygen saturation together with regional CBF were measured periodically. Hemorrhagic hypotension produced a mean decrease in arterial blood pressure of 27 +/- 4, 23 +/- 2, and 41 +/- 4% in the three groups, respectively, whereas reinfusion of the lamb's blood resulted in a return to control blood pressure within 3% in all three groups. In the pre-term fetal lamb, CBF decreased significantly in all regions during hypotension. In the near-term fetal lamb, only blood flow to the cortex decreased significantly during hypotension. In the newborn lamb, only the choroid plexus demonstrated a significant decrease in blood flow during hypotension. The lower limit of regional CBF autoregulation was identical to the resting mean arterial pressure in fetal life but significantly lower in newborn lambs. These experiments demonstrate for the first time that vulnerability to hypotension decreases with increasing maturity and that the brainstem, the phylogenetically oldest region of the brain, is the least vulnerable to the effects of hypotension at any age in the lamb model.

Animals↗
PubMed1990

Alterations in in situ prolactin secretory granule morphology and immunoactivity by thiols and divalent cations.

The mechanisms involved in PRL storage in secretory granules are generally poorly understood. Recent studies with isolated granules, however, have suggested that granule storage forms may be relatively osmotically inactive due to oligomerization involving hormonal intermolecular disulfide bonds. Thus, expenditure of metabolic energy by the cell in order to maintain granule integrity would be reduced. When secretion is stimulated, oligomer depolymerization by thiol exchange mechanisms has been proposed to occur before or even concomitant with exocytosis. The present studies were designed to investigate the influence of metabolic inhibitors, thiols, and divalent cations on PRL storage in situ, rather than in isolated granules. The results suggest that 1) PRL granules require little energy to maintain their structure, since a combination of azide (10 mM), fluoride (10 mM), and cyanide (1 mM) had no effect on PRL granule morphology in normal anterior pituitary cells in primary culture; 2) disulfide linkages are involved in the osmotic activity of the PRL granule contents, since thiols induced granule swelling in lightly fixed cells; and 3) thiols and divalent cations are capable of altering the arrangement of stored hormone molecules, since PRL immunoactivity could be modified by these agents in glycol methacrylate-embedded exposed granule cores.

Animals↗
PubMed1990

Maternal dietary leucine supplementation affects apparent lactational activity and pup development in rats.

Previous work from this laboratory has shown mildly elevated dietary leucine to alter the rhythm of prolactin secretion and to interfere with normal estrous cycling in the intact female rat. In this study, we have determined whether these observed effects on prolactin and cycling in turn affected fertility, gestation, mammary gland development or mammary gland morphology during lactation. Groups of control and leucine-supplemented mothers were mated with tested male breeders and a daily record was kept of pup births, pup deaths and general health and development of the pups. The day after weaning, mammary tissue was removed from dams in both groups and prepared for histological examination. In light of the previous results showing estrous cycle interruption and altered prolactin secretion, we report what was a surprising lack of effect of leucine supplementation of fertility, maintenance of gestation or overall development of the mammary glands in this species. Interestingly, however, dietary leucine supplementation was found to markedly after the histological appearance of lactating mammary tissue and to cause a significant increase in the number of litters that contained notably underdeveloped pups.

Animals↗
PubMed1990

Autonomic control of heart rate differs with electrocortical activity and chronic hypoxaemia in fetal lambs.

We aimed to determine the effects of the electrocortical (ECoG) cycle on fetal heart rate and its autonomic control under normoxaemic and hypoxaemic conditions. Heart rate was measured and selective pharmacological blockade was used to quantify sympathetic and parasympathetic tone in low voltage (LV) and high voltage (HV) ECoG. We studied 3 groups of fetal lambs: 6 normal-sized, normoxaemic fetuses (control); 5 growth-retarded, normoxaemic carunclectomy fetuses (carunclectomy-normoxaemic); and 5 growth-retarded, hypoxaemic carunclectomy fetuses (carunclectomy-hypoxaemic). We found slower heart rate in LV compared to HV ECoG in all groups. This was explained by greater parasympathetic tone in LV in all groups, and by a complementary change of sympathetic tone in control fetuses. Hypoxaemic fetuses had slower heart rate than normoxaemic fetuses in both ECoG states. This was due to augmented parasympathetic tone (in LV ECoG) and reduced sympathetic tone (in LV and HV ECoG). We conclude that complementary changes of autonomic tone underly the normal variation of fetal heart rate with the ECoG cycle, with the parasympathetic arm dominant in LV and the sympathetic arm dominant in HV ECoG. In chronic hypoxaemia, complementary changes of autonomic tone contribute to slowing of fetal heart rate. Increased parasympathetic tone and decreased sympathetic tone may enhance cardiac efficiency when the oxygen supply is chronically reduced.

Animals↗
PubMed1990

The incidence of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. A population-based study with particular reference to reactions caused by drugs among outpatients.

We carried out a study to estimate the incidence of erythema multiforme (EM), Stevens Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) requiring hospitalization and to determine which drug therapies were associated with these reactions. We reviewed the clinical records of all patients who were hospitalized with these discharge diagnoses at Group Health Cooperative (GHC) of Puget Sound, Seattle, Wash, from 1972 through 1986. During this 14-year period, an average of about 260,000 persons, with demographic characteristics similar to those of the general population, received their care from GHC, and there were about 25,000 admissions to hospitals per year at the GHC hospitals. Based on International Classification of Diseases-Adapted coding, a total of 61 suspect cases of EM, SJS, or TEN were identified from the computerized hospital discharge file. Based on record review and the application of a uniform set of diagnostic criteria, a total of 37 patients (61%) were classified as having EM, SJS, or TEN. Of these, 16 cases (43%) were attributed to drugs administered to these patients prior to hospitalization. The overall incidence of hospitalization for EM, SJS, or TEN due to all causes was 4.2 per 10(6) person-years. The incidence of TEN alone due to all causes was 0.5 per 10(6) person-years. The incidence of EM, SJS, or TEN associated with drug use were 7.0, 1.8, and 9.0 per 10(6) person-years, respectively, for persons younger than 20 years of age, 20 to 64 years of age, and 65 years of age and older. Drug therapies with reaction rates in excess of 1 per 100,000 exposed individuals include phenobarbital (20 per 100,000), nitrofurantoin (7 per 100,000), sulfamethoxazole and trimethoprim, and ampicillin (both 3 per 100,000), and amoxicillin (2 per 100,000). Overall, our data suggest that cases of EM, SJS, and TEN sufficiently severe to require hospitalization are infrequent among outpatients using well-established drug therapies. A continuing challenge is the evaluation of these severe cutaneous reactions that are associated with newly marketed or less frequently prescribed drug therapies.

Adolescent↗
PubMed1989

Follow-up study of tolmetin users.

A follow-up study of 8370 outpatients who filled over 24,000 prescriptions for tolmetin revealed no hospital admissions for acute allergic, blood, skin, or central nervous system illness within 90 days of filling a prescription or refill for the drug. There were two cases of liver disease and two cases of nephrotic syndrome in which an etiologic relationship to tolmetin seemed unlikely but could not be entirely ruled out. In addition, 11 patients were hospitalized for peptic ulcer disease and its complications. In all but two patients other risk factors were present that could readily explain the illness. The rate of hospitalization for peptic ulcer disease and its complications among tolmetin recipients appears to be of the same magnitude as that in patients who take other nonsteroidal antiinflammatory drugs in this population, and close to that of the population at large.

Adult↗
PubMed1989

A comparison of wax matrix and microencapsulated potassium chloride in relation to upper gastrointestinal illness requiring hospitalization.

The frequency of hospitalization for documented upper gastrointestinal illness among recipients of either wax matrix or microencapsulated potassium chloride was similar in a study in which clinics were randomly assigned to dispense one or the other preparation. The results indicate that there is no material difference between the two preparations in relation to serious upper gastrointestinal illness.

Adult↗
PubMed1989

Epidemiology of pancreas cancer (1988).

This article reviews the epidemiology of cancer of the pancreas, both descriptive and analytical, at all times cognizant of the problems of misdiagnosis, particularly underdiagnosis, of this lethal disease that continue to hinder epidemiological studies. Pancreas cancer is consistently reported to occur more frequently in men than in women, in blacks than in whites, and in urban rather than rural population groups. In some countries, the mortality rates continue to rise, whereas in others, declining levels of disease can be seen among members of younger birth cohorts. Although some of these patterns can be explained by variation in pancreas cancer risk factors, many cannot. Analytical studies consistently demonstrate that cigarette smoking increases the risk of cancer of the pancreas, and this appears, at the present time, to be the only clearly demonstrated risk factor for pancreatic cancer. Although the association with disease risk and coffee consumption, alcohol consumption, occupational exposures, diabetes, pancreatitis, and other factors requires clarification, it appears likely that the most fruitful research area in the coming years may involve exploration of pancreatic cancer risk and nutritional practices.

Adult↗
PubMed1989

Blood flow to the respiratory muscles during hypercapnic hyperpnoea in the newborn lamb.

The blood flow to the diaphragm, external and internal intercostal muscles, abdominal oblique muscles, and other rib-cage and abdominal muscles was measured, using radio-labelled microspheres, in 6 newborn lambs quietly breathing in air and during 3 different levels of CO2 induced hypercapnic hyperpnoea (inspired gas containing 4%, 5.5%, or 7% CO2). We also calculated the oxygen uptake of the diaphragm (VO2di). While the lambs were breathing air diaphragmatic blood flow (Qdi, 38.2 +/- 4.0 SEM ml.min-1.100 g-1) was similar to external intercostal muscle blood flow (Qei, 37.1 +/- 8.1 ml.min-1.100 g-1), and both were greater than internal intercostal muscle blood flow (Qii, 24.8 +/- 6.1 ml.min-1.100 g-1; P less than 0.05). During hyperpnoea Qdi, Qei, and Qii were augmented with Qdi equal to 200.1 +/- 12.2 ml.min-1.100 g-1 in 7% CO2 and Qei equal to 88.4 +/- 14.1 ml.min-1.100 g-1 in 7% CO2 (Qdi was greater than Qei, P less than 0.01). Qii was 40.7 +/- 5.6 ml.min-1.100 g-1 in 7% CO2 being less than Qdi (P less than 0.01) and Qei (P less than 0.05). The abdominal oblique muscles also had augmented flow in response to hyperpnoea. The level of hypercapnia that resulted in an augmentation of Qdi (5.5% inspired CO2) was lower than that which augmented Qei and Qii (7% inspired CO2). VO2di was linearly related to Qdi (r = 0.98). Our results suggest that in the newborn lamb the diaphragm is the dominant respiratory muscle in response to hypercapnia.

Animals↗
PubMed1989

Diaphragm VO2, diaphragm EMG, pressure-time product and calculated ventilation in newborn lambs during hypercapnic hyperpnoea.

We examined the relationship between diaphragmatic EMG (EMGdi) and pressure-time index (Pt'), and diaphragmatic oxygen consumption (VO2di) in 6 newborn lambs quietly breathing air and during 3 levels of hypercapnic hyperpnoea (PaCO2 was equal to 48, 53, or 60 Torr). We also determined minute ventilation (VI), whole body oxygen consumption (VO2), diaphragmatic oxygen consumption (VO2di), and respiratory muscle oxygen consumption (VO2resp). VO2 did not change significantly throughout the experiment. While breathing air VO2di was 0.46 +/- 0.03 ml.min-1, VO2resp was 1.40 +/- 0.22 ml.min-1, and VI was 1.98 +/- 0.11 L.min-1. These values increased significantly during hyperpnoea and reached 3.88 +/- 0.45 ml.min-1, 7.22 +/- 1.12 ml.min-1, and 6.99 +/- 1.03 L.min-1, respectively. EMGdi, and Pt' also increased significantly during hyperpnoea. A strong linear relationship was found between the normalized values of EMGdi and Pt' (r = 0.90), between VO2di and EMGdi (r = 0.88), and between VO2di and Pt' (r = 0.88). The relationship between both EMGdi and VI and PaCO2 was logarithmic. We found that (i) both EMGdi and Pt' correlate well with VO2di, and (ii) VI, VO2di, and EMGdi increased significantly when PaCO2 was greater than 48 Torr.

Animals↗
PubMed1989

Production and secretion of the 21-23.5 kDa prolactin-like molecules.

We recently described the presence of a series of prolactin (PRL)-like molecules (PLMs) in the rat pituitary gland and showed that their formation was not due to artifactual proteolysis of 24 kDa PRL during extraction or to degradation of PRL in lysosomes. In this study we have found (1) in vitro translation of pituitary cell RNA to result in the production of only 24 kDa monomer isoform 2 and no PLMs, (2) that secretion of newly synthesized PLMs is differently regulated than at least a proportion of newly synthesized monomers, (3) that secretion of newly synthesized PLMs occurs after at least a 6 h delay, (4) that cysteamine (a) inhibits the release of the PLMs, (b) causes an increase in their amount versus isoform 2, and (c) causes an intracellular accumulation of pleiomorphic, immature secretory granules, and (5) that cells grown under degranulating culture conditions do not contain PLMs. These results, using normal anterior pituitary cells in primary culture, demonstrate the potential for differential release of the PLMs versus monomer PRL in vivo and are consistent with the production of the PLMs from 24 kDa monomer isoform 2 during secretory granule condensation.

Animals↗
PubMed1989

Oral contraceptives and breast cancer.

A population-based case-control study of oral contraceptive use and breast cancer was carried out among young women (less than 43 years of age) at Group Health Cooperative of Puget Sound, Seattle, Washington. Use of oral contraceptives before first pregnancy did not materially differ between cases or controls. The rate ratio estimate of breast cancer incidence in women who had used oral contraceptives before first pregnancy compared to those who had not was 0.9 (95% CI = 0.4, 2.1). There were no meaningful patterns of association between breast cancer and duration of use or formulation of oral contraceptive used before first pregnancy.

Adult↗
PubMed1989

Atracurium--a post-marketing surveillance study: methods and U.S. experience.

Two companion post-marketing studies have evaluated the frequency of adverse events amongst patients receiving atracurium. In this first report, we describe the study methods used in both centres and the findings of the study conducted at the Group Health Co-operative of Puget Sound, U.S.A. In this study, the frequency of adverse events in 1013 patients receiving atracurium was substantially the same as that in 851 patients receiving other neuromuscular blocking agents. In both groups there were no instances of cardiac arrest, anaphylaxis or death, no adverse effects associated with failure to antagonize neuromuscular block, and no instances of previously unreported types of adverse effects. We conclude that the safety profile of atracurium is similar to that of other neuromuscular blocking agents and that this type of observational study of anaesthetic agents may prove a useful tool for surveillance of new drugs used primarily in hospitals.

Anesthesia Recovery Period↗
PubMed1989

Gallstone growth, size, and risk of gallbladder cancer: an interracial study.

To investigate gallstone size, growth, and the relation between stone size and gallbladder cancer we have used cholecystectomy reports from 1676 female subjects (169 Whites, 531 Blacks, and 976 Native American Indians). Although the prevalence of gallstones differs markedly in these groups it appears that the estimated growth rate of gallstones in younger subjects, 2.0 mm per year (95% confidence interval: 1.7-2.3 mm) is homogeneous for all three groups. In both Indian and non-Indian populations the proportion of small stones diminished and the proportion of large stones increased over time. We found a strong relationship between gallstone size and gallbladder cancer. Large stones (greater than or equal to 3 cm) were found in 40% of patients with gallbladder cancer but in only 12% of all subjects of similar age. The relative risk for gallbladder cancer in subjects with stones greater than or equal to 3 cm was 9.2 compared with subjects with stones less than 1 cm. (95% confidence interval: 2.3-37). We estimate that one-third of all gallbladder cancers in subjects with calculi will be associated with large (greater than or equal to 3 cm) stones. We believe that stone size might be used to determine the risk of gallbladder cancer in patients with gallstones.

Adult↗
PubMed1989

Evaluating the impact of a home screening test for streptococcal pharyngitis.

Home screening tests must be evaluated as an aid to self-referral to a physician and should not be judged as if they were diagnostic procedures, i.e. the sole determinants of a therapeutic decision. The performance characteristics of a test are properly compared to those of the patient or parent, operating in the absence of the test. For streptococcal pharyngitis there would be a net increase in the number of cases correctly treated whenever the sensitivity of the home test (multiplied by the probability that the patient will act upon the test results) exceeds the a priori probability that the patient will be seen by a physician in the absence of the test. Use of home screening tests is likely to increase the number of patient-physician contacts among persons with sore throats and will do so proportionately more frequently among those with streptococcal pharyngitis.

Home Nursing↗
PubMed1989

Distribution of a prolactinlike material in human eccrine sweat glands.

Because prolactin has been implicated in the transport of electrolytes in several mammalian tissues, we have looked for the presence of prolactin in human eccrine sweat glands where a primary isotonic secretion, rich in sodium chloride, is produced and subsequently modified by recovery of some sodium and chloride in excess of water. Sweat glands were microdissected from skin biopsies and then fixed overnight in phosphate-buffered 4% formaldehyde. The fixed tissue was dehydrated (to 95%) in ethanol and then embedded in glycol methacrylate. Sections were cut (5 microns) and immunostained with antihuman prolactin (NIDDK IC2) and the specifically-bound antibody was visualized using a biotinylated second antibody and Vector ABC reagents. Prolactinlike immunoreactivity was localized in the clear cells of the secretory coil and, to a much lesser extent, in the basal layer of duct cells. In many of the clear cells, the immunoreactive material appeared as a lateral strip and occasionally, in favorable sections, as a horseshoe of reaction product a few microns in from the apical and lateral membranes. In a subset of clear cells, with more euchromatic nuclei and a long, thin cellular profile, the immunostaining was more intense and was localized in a more juxtanuclear position. Controls for endogenous peroxidase, and those using normal serum or antihuman prolactin serum preabsorbed with purified human prolactin, gave no peroxidase localization in the tissue. These results are important because 1) they represent the first demonstration of prolactin or a prolactinlike substance in the sweat gland, 2) the prolactinlike material was localized to clear cells that are thought to be responsible for much of the fluid secretion, 3) the necessity for prolactin or pituitary extract in primary cultures of sweat gland epithelium is potentially explained, although not fully understood, and 4) it means that further studies concerned with the possible influence of prolactin on ion transport in the sweat gland are warranted.

Humans↗