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Biomedical subjects

A M Walker

Publications and source records attributed to A M Walker.

At least 217 records · Page 12Linked to original sources
PubMed1989

Cardio-respiratory responses to cool ambient temperature differ with sleep state in neonatal lambs.

1. Responses to cool ambient temperature were tested with reference to the sleep-wakefulness cycle in six chronically instrumented newborn lambs which were exposed to warm (20-25 degrees C) and cool (10-15 degrees C) ambient temperatures (Ta) in fifteen studies. 2. We measured cardio-respiratory variables (cardiac output, heart rate, stroke volume, arteriovenous O2 difference and O2 consumption) together with body temperature (Tb) during behavioural states of quiet wakefulness (QW), quiet sleep (QS) and rapid-eye-movement sleep (REM). 3. In cool Ta, significant increases (P less than 0.05) occurred in cardiac output, O2 uptake and O2 consumption in QW (10 +/- 3%, 23 +/- 4% and 35 +/- 6%, respectively, mean +/- S.E.M.) and QS (12 +/- 3%, 21 +/- 7% and 35 +/- 8%, respectively), but these responses were absent in REM. Increases in heart rate (6 +/- 2%) and stroke volume (6 +/- 3%) were present during QS, but not during REM. 4. In REM, Tb was dependent upon the prevailing Ta, increasing in the warm Ta and tending to decrease in the cool Ta. 5. In cool Ta, REM sleep epochs were shorter and more frequent with no changes in total REM time. These changes were not seen in QS. 6. Thus, the behavioural state determines both the thermogenic and the associated cardio-respiratory responses to cool stress in lambs. The consequences of disrupted thermogenesis during REM sleep include dependence of Tb upon the prevailing ambient temperature, and abbreviation of the REM epoch by arousal, possibly as a defence against falls in Tb in cool Ta.

Animals↗
PubMed1989

Effect of sinoaortic denervation on arousal responses to hypotension in newborn lambs.

To examine whether hypotension reflexly initiates arousal from sleep and the mechanisms involved, we subjected sleeping lambs to hypotensive stimuli of 1-min duration, before and after sinoaortic denervation (SAD). In intact lambs, hypotension increased the probability of arousal from both quiet sleep (QS) and rapid-eye-movement (REM) sleep. Hypotension resulted in nonarousal in 42% (QS) and 47% (REM) of tests. Arousal time was significantly longer in REM (34.9 +/- 1.8 s, means +/- SE) than in QS (26.0 +/- 1.8 s). Arterial saturation of O2 (SO2) and PO2 measured at the point of arousal were unchanged from control values in those tests in which arousal occurred. In nonarousal tests, there was a significant fall in both SO2 (4.9 +/- 1.2%) and PO2 (21.6 +/- 4.2 mmHg). After SAD, hypotension did not increase the probability of arousal. Nonarousals significantly increased to 75% (QS and REM, P less than 0.02). We conclude that acute hypotension is a potent stimulus for arousal from sleep in newborn lambs. As the arousal response is abolished by SAD and is not correlated with arterial oxygenation, hypotensive arousal appears to be mediated via arterial baroreceptors.

Animals↗
PubMed1989

Left and right ventricular myocardial morphometry in fetal, neonatal, and adult sheep.

This study has examined left (LV) and right ventricular (RV) myocardial morphometry in perfusion-fixed hearts of late-gestation sheep fetuses, neonatal lambs, and adult sheep. During development, myocyte size, intercapillary distance, and myocyte myofibrillar and mitochondrial volume densities increased, whereas capillary density, the myocyte-to-capillary ratio, and the myocyte matrix volume density decreased. RV myocytes were larger than LV myocytes in cross section in fetuses and 4-day-old lambs. LV and RV myocytes were of similar size in 7-day-old lambs. LV and RV myocytes were of larger in older lambs and adult sheep. Differences between LV and RV myocyte volume densities of myofibrils, mitochondria, and matrix were also observed in fetuses and young lambs. As well, variation in capillary size and density was apparent between ventricles in the fetal and neonatal periods. We conclude that, in the sheep heart, 1) LV and RV morphometric differences exist during fetal and postnatal development, 2) fetal LV and RV myocardial morphometry is consistent with an RV dominance in utero, 3) rapid growth of LV and RV myocytes occurs in the perinatal period, and 4) the relative size of LV and RV myocytes does not reflect a postnatal LV dominance until between 1 and 4 wk after birth.

Age Factors↗
PubMed1989

Mammotroph autoregulation: the differential roles of the 24K isoforms of prolactin.

In this study we have attempted to determine which of the secreted 24K isoforms was responsible for autocrine regulation of PRL secretion by comparing the isoforms synthesized and secreted by normal cells, which do autoregulate, with those synthesized and secreted by GH3 cells, which do not normally autoregulate. Comparable numbers of cells were washed free of serum and then extracted into Tris-buffered saline by sonication and detergent treatment. Proteins present in these cell extracts and in samples of culture medium were then precipitated with cold acetone (-20 C; 48 h) and subsequently dissolved in urea-lysis buffer for 2-dimensional (2-D) electrophoresis. The 2-D patterns for normal cells showed four 24K PRL isoforms inside the cells and three 24K PRL isoforms (designated 2, 3, and 3') secreted into the medium. The 2-D patterns for GH3 cells showed very little intracellular storage of PRL, but what was present was identified as 24K PRL isoform 2. The GH3 cells secreted large amounts of only 24K PRL isoform 2. Preparations of PRL containing only isoforms 1,2, and 3 (at a total radioimmunoassayable concentration of 5 micrograms/ml PRL) were capable of inducing autoregulation in GH3 cells, as evidence by decreased secretion of prelabeled intracellular PRL. Initiation of autoregulation in GH3 cells caused granulation and the intracellular production of isoform 3. Since a) a preparation containing isoforms 1, 2, and 3 was found to induce autoregulation in GH3 cells, b) isoform 1 is not a secreted form, and c) isoform 2 does not cause autoregulation (at least in GH3 cells), it is deduced that isoform 3 is an autocrine form of PRL. Since initiation of autoregulation in GH3 cells caused those cells to produce isoform 3, it is further deduced that the autoregulatory defect in GH3 cells lies in the actual lack of production of isoform 3 and not in an inherent inability of these cells to produce isoform 3.

Animals↗
PubMed1989

Biosynthesis of the secreted 24 K isoforms of prolactin.

PRL exists within the mammotroph population in a number of different molecular forms. Several of these forms are best described as isoforms, as they have the same mol wt (24 K), but differ in their net charges. In this study we have used in vitro translation assays to ascertain the number of 24 K translation products of normal pituitary messenger RNA (mRNA), and, finding only one, have used both in vitro translation assays and subcellular fractionation to determine the intracellular site of the posttranslational modification of this single translation product. Translation of mRNA from normal pituitary tissue or GH3 cells resulted in the apparent production of a number of pre-PRLs, but in only a single rough microsome-processed form of PRL, 24 K isoform 2. Longer term translation assays utilizing a variety of isotopes failed to show any evidence for rough microsomal posttranslational modification of isoform 2. Subcellular fractionation, using a discontinuous sucrose gradient, however, produced a membrane-bound large secretory granule fraction which, when isolated, contained essentially only isoform 2, and which had the capacity to convert isoform 2 to isoforms 3 and 3' by posttranslational phosphorylation.

Animals↗
PubMed1989

Hospitalizations for pulmonary reactions following nitrofurantoin use.

Acute pulmonary illness compatible with previously described nitrofurantoin toxicity and requiring hospitalization occurred three times among 16,101 first courses of therapy with nitrofurantoin. One case of fatal pulmonary fibrosis was ascribed to long-term use of nitrofurantoin among 742 observed recipients of ten or more prescriptions.

Acute Disease↗
PubMed1988

Choice of non-steroidal anti-inflammatory drug in persons treated for dyspepsia.

Prior use of analgesics among 1327 new users of cimetidine over the age of 65 at Group Health Cooperative of Puget Sound was much more common than among 5308 members of similar age and sex who had never taken cimetidine. The excess included not only most non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin, but also extended to paracetamol. New users of cimetidine who had not received analgesics in the preceding 2 years were preferentially given recently introduced NSAIDs if an NSAID was subsequently prescribed. Review of prior studies of analgesic use and ulcer diseases reveals a regular association between ulcer and preceding use of paracetamol, a drug for which no causal association to ulcer is thought to exist. General increases in use of analgesics by elderly dyspeptic patients may have given rise to artefact in reported associations between manifestations of ulcer disease and NSAIDs.

Acetaminophen↗
PubMed1988

Obesity and knee osteoarthritis. The Framingham Study.

STUDY OBJECTIVE: To determine whether obesity preceded knee osteoarthritis and was thus a possible cause. DESIGN: Cohort study with weight and other important variables measured in 1948 to 1951 (mean age of subjects, 37 years) and knee arthritis evaluated in 1983 to 1985 (mean age of subjects, 73 years). SETTING: Population-based participants; a subset (n = 1420) of the Framingham Heart Study cohort. METHODS: For those subjects in the Framingham Study having knee radiographs taken as part of the 18th biennial examination (1983 to 1985), we examined Metropolitan Relative Weight, a measure of weight adjusted for height at the onset of the study (1948 to 1951). Relative risks were computed as the cumulative incidence rate of radiographic knee osteoarthritis in the heaviest weight groups at examination 1 divided by the cumulative rate in the lightest 60% weight groups at examination 1. Relative risks were adjusted for age, physical activity level, and uric acid level. RESULTS: In 1983 to 1985, 468 subjects (33%) had radiographic knee osteoarthritis. For men, the risk of knee osteoarthritis was increased in those in the heaviest quintile of weight at examination 1 compared with those in the lightest three quintiles (age-adjusted relative risk, 1.51; 95% confidence interval [CI], 1.14 to 1.98); risk was not increased for those in the second heaviest quintile (relative risk, 1.0). The association between weight and knee osteoarthritis was stronger in women than in men; for women in the most overweight quintile at examination 1, relative risk was 2.07 (95% CI, 1.67 to 2.55), and for those in the second heaviest group, relative risk was 1.44 (95% CI, 1.11 to 1.86). This link between obesity and subsequent osteoarthritis persisted after controlling for serum uric acid level and physical activity level, and was strongest for persons with severest radiographic disease. Obesity at examination 1 was associated with the risk of developing both symptomatic and asymptomatic osteoarthritis. CONCLUSIONS: These results and other corroborative cross-sectional data show that obesity or as yet unknown factors associated with obesity cause knee osteoarthritis.

Activities of Daily Living↗
PubMed1988

Penicillin and the marked decrease in morbidity and mortality from rheumatic fever in the United States.

There has been a marked decline in mortality due to rheumatic fever in the United States. We present evidence for the important role of penicillin in changing the severity of rheumatic carditis, beginning about 1946. Since that year, mortality due to rheumatic carditis has rapidly decreased to zero at the hospital we studied (House of the Good Samaritan, Boston), the rate of loss of all murmurs in patients at the study hospital accelerated simultaneously and exceeded 40 percent by 1970, and the rates of decline in national mortality due to rheumatic carditis accelerated fourfold with the advent of antibiotics. These data, together with reports of recent outbreaks of rheumatic fever, emphasize the importance of continued efforts to diagnose and treat Group A streptococcal pharyngitis.

Adolescent↗
PubMed1988

Laboratory and clinical variables to predict outcome in hemolytic-uremic syndrome.

To develop a guide to the prognosis of children with hemolytic-uremic syndrome, we reviewed the medical records of 78 patients with this diagnosis seen at The Children's Hospital, Boston, from 1976 through 1986. Two outcome groups were defined as follows: a "good outcome" group, which contained 6 patients with no serious sequelae at hospital discharge, and a "bad outcome" group, which contained 12 patients who died, had chronic renal failure, or had central nervous system sequelae at hospital discharge. Differences between the two groups in routine laboratory tests available within 48 hours of admission were identified by bivariate analysis. Using serum calcium (less than or equal to 2 mmol/L) plus urine output (less than 0.4 mL/kg/h) over a 24-hour period as a test to predict outcome, we identified patients who died, had chronic renal failure, or had serious central nervous system sequelae, with 75% sensitivity, 98% specificity, and 90% positive predictive value.

Adolescent↗
PubMed1988

Developmental changes in regional cerebral blood flow in fetal and newborn lambs.

Developmental changes in regional cerebral blood flow (CBF) were determined using radioactively labeled microspheres to measure flow to the cortex, brain stem, cerebellum, white matter, caudate nucleus, and choroid plexus in three groups of chronically catheterized lambs under physiological conditions: 90- to 100-day preterm fetal lambs (n = 14), 125- to 136-day near-term fetal lambs (n = 11), and newborn lambs 5-44 days old (n = 10). We continually monitored heart rate, central venous pressure, and mean arterial blood pressure (MAP) and periodically measured arterial blood O2 and CO2 tensions (PaO2, PaCO2, respectively), pH, hemoglobin, and oxygen saturation (SaO2). The regional CBF measurements (ml.100 g-1.min-1) revealed that in all three age groups the high flow areas are the choroid plexus and caudate nucleus, whereas the lowest flow area is the white matter. There is, however, a different hierarchy of regional CBF in utero (cortex less than cerebellum and brain stem) compared with extrauterine life in the newborn lamb (cortex and cerebellum greater than brain stem). Analysis of regional cerebral oxygen delivery [CBF times arterial oxygen content (CaO2)] demonstrated a progressively increasing oxygen transport to the cortex with increasing gestational maturity and after birth. Oxygen transport to the brain stem, cerebellum, and white matter increased with gestational age, but did not increase after birth. Relationships between regional CBF and natural physiological variations of cardiorespiratory parameters (PaO2, SaO2, CaO2, pH, PaCO2, and MAP) were assessed using regression analysis. Correlations of regional CBF with PaO2 and SaO2 suggest that cerebral perfusion is not primarily determined by CaO2 when variations occur within the physiological range.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effect of changing lung liquid volume on the pulmonary circulation of fetal lambs.

During fetal life the lung develops as a liquid-filled structure with low blood flow compared with postnatal life. We studied the effects of liquid expansion of the fetal lung by measuring vascular conductance in perfused lungs in situ and arterial diameters in excised lungs of fetal lambs. Pulmonary vascular conductance invariably rose as the lung was deflated from its initial volume; maximal deflation to residual volume increased conductance 122%. With reexpansion, conductance fell progressively, culminating in cessation of flow at lung volumes of twice the initial volume. These changes persisted after vagotomy and thoracic sympathectomy and therefore were mechanical in character. Lung expansion from residual volume initially expanded 300- to 500-micron arteries but compressed arteries greater than 1,500 micron. Further expansion reduced the caliber of all arteries. Thus increasing lung liquid volume progressively constricts the pulmonary circulation in the fetus. Because the fetal pulmonary vascular resistance-lung volume relationship differs from that of the U-shaped form found in adult lungs, concepts based on the adult pulmonary circulation are not appropriate for liquid-filled fetal lungs.

Animals↗
PubMed1988

Odd man out: a graphical approach to meta-analysis.

The areas of overlap of confidence intervals from several studies can be used to create summary confidence regions. These summary regions lend themselves to graphical display, have readily derivable statistical properties, and can carry information about the influence both of available studies and of hypothetical future investigations. The case of a region covered by at least N-1 out of N confidence intervals is presented in some detail.

Child↗
PubMed1988

Neurologic events following diphtheria-tetanus-pertussis immunization.

The frequency of serious neurologic events following the administration of 106,000 doses of diphtheria-tetanus-pertussis vaccine at Group Health Cooperative of Puget Sound was determined using a population-based case-control study with disease ascertainment through pharmacy and hospitalization records. There were no cases of acute unexplained encephalopathies in close temporal relation to vaccination. There was the new onset of one serious seizure disorder in the three days following immunization, with 1.13 expected on the basis of chance alone.

Brain Diseases↗
PubMed1988

A survey of household food purchases and dietary habits in relation to affluence among Singapore Chinese.

A survey of 40 Singapore Chinese households was performed, obtaining information on major perishable foods purchased for home consumption in the previous week, extent of home consumption (eating in), household dietary habits and housing type, the last as a measure of affluence. Eating out was very common: nine (23 per cent) households ate less than 50 per cent of meals at home. Excluding these nine households, consumption and habits were compared between more affluent and less affluent households. The more affluent households purchased more red meat/offal (P = 0.001), poultry (P = 0.002), vegetables other than green leafy (P = 0.04), fruit (P = 0.007) and eggs (P = 0.04); they also differed significantly in various dietary habits. Significant differences were also observed between English-speaking and Chinese-speaking households. The results suggest that increasing affluence may have brought about substantial dietary change in Singapore, thus meriting further study of the role of diet in changing disease patterns in Singapore.

Acculturation↗