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Biomedical subjects

J R Webster

Publications and source records attributed to J R Webster.

At least 19 recordsLinked to original sources
PubMed1999

Effects of photoperiod on the cessation of growth during autumn in male red deer and growth hormone and insulin-like growth factor-I secretion.

Male red deer undergo seasonal cycles of food intake and growth rate, which are high during spring and low during winter, despite high quality food ad libitum. Hormonal profiles during the cessation of growth in autumn and the potential role of photoperiod in the timing of the observed changes have been investigated. Whether this seasonal decrease in growth affected the response of GH and IGF-I to fasting was also examined. Two groups of six male 1-year-old red deer were exposed to different photoperiods after the summer solstice. One group (C) was given a simulated natural photoperiod while the other group (SS) was maintained on a summer solstice photoperiod (16L:8D). GH was measured in blood collected continuously and divided into pools every 5 min for 24 h in the fed state and after a 48-h fast on two occasions; the first was in November before photoperiod manipulation began and the second was in April approximately 16 weeks after initiating treatments. IGF-I, prolactin, and testosterone were measured in weekly samples. Individual live weight and group food intake were also measured each week. The normal growth pattern seen in the C group was delayed in the SS group. Thus, from 7 March until the second GH sampling on 11 April the live weight of deer in group C fell; in contrast, deer in group SS continued to grow (-43 vs 186 g/day s.e.d. = 65.5, P < 0. 01). Food intake changes reflected the pattern of growth in both groups. Mean GH (P < 0.05), GH pulse amplitude (P < 0.01), and IGF-I (P < 0.001) declined in both groups from November to April. This decline was more marked in group C and in April these parameters were all lower in group C than in group SS (GH, P < 0.05; IGF-1, P < 0.01). Prolactin levels in April were also lower in group C than in group SS (P < 0.01); testosterone was not affected by treatment. Fasting increased mean GH and GH pulse amplitude in both groups in November (P < 0.05). In April, the fasting response differed between the groups. In group C, mean GH, pulse amplitude, and pulse frequency were all greater in the fasted state than in the fed state (P < 0.05), while in group SS there were no significant differences (P > 0.05). IGF-I was lower in the fasted state than in the fed state at both sampling dates (P < 0.001). The seasonal decline in food intake and growth is associated with decreased GH, IGF-I, and prolactin concentrations, and increased testosterone and the GH response associated with fasting. All these changes except those of testosterone were delayed or reduced by continued exposure to a summer solstice photoperiod in autumn. The decreased photoperiod in autumn may thus influence the normal timing of the seasonal growth cycle.

Animals↗
PubMed1998

An integrated nanoliter DNA analysis device.

A device was developed that uses microfabricated fluidic channels, heaters, temperature sensors, and fluorescence detectors to analyze nanoliter-size DNA samples. The device is capable of measuring aqueous reagent and DNA-containing solutions, mixing the solutions together, amplifying or digesting the DNA to form discrete products, and separating and detecting those products. No external lenses, heaters, or mechanical pumps are necessary for complete sample processing and analysis. Because all of the components are made using conventional photolithographic production techniques, they operate as a single closed system. The components have the potential for assembly into complex, low-power, integrated analysis systems at low unit cost. The availability of portable, reliable instruments may facilitate the use of DNA analysis in applications such as rapid medical diagnostics and point-of-use agricultural testing.

Costs and Cost Analysis↗
PubMed1998

Correlates of cognitive status of old patients with isolated systolic hypertension: the Syst-Eur Vascular Dementia Project.

OBJECTIVE: To assess cognitive functions and their correlates for a dementia-free cohort of old patients with isolated systolic hypertension. DESIGN: Cross-sectional data from the randomization period of the European Trial in Elderly with Systolic Hypertension (Syst-Eur Vascular Dementia Project). SETTING: Sixteen European countries and Israel. PARTICIPANTS: We studied 2252 patients aged 60-100 years (mean 70). MAIN OUTCOME MEASURES: Mini Mental State Examination (MMSE) and Spearman correlation of MMSE scores to demographic data or blood pressure. RESULTS: The MMSE was successfully completed for 1474 women and 751 men. The baseline blood pressure averaged 173 +/- 10/86 +/- 6 mmHg (means +/- SD). Median age at which education of patients at school had stopped was 15 years. Men and women who consumed alcohol (28%) had median intakes of 8 and 3 g/day, respectively. The median MMSE score was 29 (range 15-30). The maximum score of 30 was attained by 609 (30%) subjects. Fifty-nine (3%) patients had a MMSE score of 23 or less. The MMSE score decreased with advancing age (r = -0.21, P < 0.001). Both for men and for women, it was positively correlated to the level of education (r = 0.30 and r = 0.32, P < 0.001). For women after adjustment for age and the level of education, the score was correlated negatively to systolic blood pressure (r = -0.07, P < 0.05) but positively to intake of alcohol (r = 0.06, P < 0.05). CONCLUSION: In a cohort of elderly patients with isolated systolic hypertension, baseline cognitive function measured in terms of the MMSE score was high, probably due to selective recruitment of patients who were not clinically demented. Blood pressure was a weak contributor to cognitive status compared with age and level of education. Baseline cognitive function of women was negatively and independently correlated to systolic blood pressure.

Aged↗
PubMed1998

A morbidity study of former pentachlorophenol-production workers.

Pentachlorophenol (PCP) is a pesticide that was once widely used for wood preservation. Commercial PCP contained impurities including higher chlorinated dibenzo-p-dioxins (CDDs) and chlorinated dibenzofurans (CDFs). We investigated the effects of occupational exposure to PCP and its CDD and CDF contaminants on the skin, liver, porphyrin metabolism, and central and peripheral nervous systems. In 1986 we conducted a medical survey of 366 workers who had been engaged in the production of PCP at a single plant between 1938 and 1978. The referent group consisted of 303 workers from the same plant who were not exposed to these or related compounds. Exposure was determined from computerized personnel records. The medical survey included an administered questionnaire, medical record review, physical examination by dermatologists, internists, and neurologists, and analysis of 24-hr urine for quantitative porphyrins among other tests. In this paper we present the results of analyses of the general health, chloracne, and porphyrin metabolism end points. The general health status of PCP workers was similar to unexposed workers, but 17.8% of PCP workers had evidence of current or past chloracne. PCP workers with chloracne had significantly higher mean urinary excretion of coproporphyrins (117. 0 vs. 90.6 microg/24 hr) than unexposed workers after controlling for potential confounders. Workers with chloracne who had worked with both PCP and polychlorinated biphenyls had significantly higher mean urinary excretions of hepta-, penta-, and coproporphyrins than unexposed workers. We conclude that occupational exposure to PCP is associated with chloracne and biochemical abnormalities which may persist years after exposure.

Acne Vulgaris↗
PubMed1997

Prolactin does not enhance glucose-stimulated insulin release in red deer stags.

Red deer stags have a seasonal pattern of insulin secretion that is characterized by both elevated basal and glucose-stimulated insulin release in summer compared with winter. Since the seasonal timing of this pattern is similar to that of prolactin and growth rate, the objectives of this study were: first, to determine whether prolactin is associated with the enhanced secretion of insulin during the summer growth period, and second, to determine whether a chronic reduction in plasma prolactin levels would alter body composition. Prolactin was suppressed in plasma using a long-acting form of the dopamine agonist bromocriptine (parlodel LA), which was administered at one of four doses (0-0.3 mg/kg) to each of four groups of castrate stags. Bromocriptine was administered during two 6-wk periods; the first in winter and the second in summer. During the sixth wk of each period, each animal was given three IVGTT at the following glucose doses (10 mg/kg, 70 mg/kg, and 200 mg/kg). Two d later, ovine prolactin was administered to each animal (0.08 mg/kg) and a single IVGTT (70 mg/kg) was given 2 hr later. Body composition was determined by the tritriated water dilution method at the beginning and end of each 6-wk treatment. Chronic suppression of prolactin during winter or summer did not significantly alter the amount of insulin released after each IVGTT, nor did it significantly alter body composition. Furthermore, acute administration of prolactin did not significantly enhance the release of insulin following an IVGTT, during winter or summer treatment periods. It is concluded that elevated levels of prolactin in summer do not enhance the release of insulin to glucose in red deer. Furthermore, a reduction in growth rate following a reduction in plasma prolactin is not associated with a change in body composition.

Animals↗
PubMed1996

Microfabricated structures for integrated DNA analysis.

Photolithographic micromachining of silicon is a candidate technology for the construction of high-throughput DNA analysis devices. However, the development of complex silicon microfabricated systems has been hindered in part by the lack of a simple, versatile pumping method for integrating individual components. Here we describe a surface-tension-based pump able to move discrete nanoliter drops through enclosed channels using only local heating. This thermocapillary pump can accurately mix, measure, and divide drops by simple electronic control. In addition, we have constructed thermal-cycling chambers, gel electrophoresis channels, and radiolabeled DNA detectors that are compatible with the fabrication of thermocapillary pump channels. Since all of the components are made by conventional photolithographic techniques, they can be assembled into more complex integrated systems. The combination of pump and components into self-contained miniaturized devices may provide significant improvements in DNA analysis speed, portability, and cost. The potential of microfabricated systems lies in the low unit cost of silicon-based construction and in the efficient sample handling afforded by component integration.

Automation↗
PubMed1996

Effects of glucose or insulin infusions on growth hormone secretion in male red deer.

The growth hormone (GH) secretory pattern in male red deer is associated with the seasonal growth cycle. During this cycle metabolic state changes from weight gain in spring to weight loss in winter. However, short-term metabolic changes due to feeding could also alter the GH pattern. To investigate the effect of such changes on GH secretion, the acute feedback of blood glucose level on the GH secretory pattern was examined. Six yearling male red deer were infused iv with glucose (G; 150 mg/kg/hr) or insulin (I; 30 mU/kg/hr) for a 12-hr period, 1 week apart. GH was measured in jugular venous blood every 10 min, for 12 hr before, during, and 6 hr after the infusions. Glucose, insulin, IGF-1, and haematocrit were also measured. There was no difference (P > 0.05) in glucose levels between G and I prior to infusions (5.8 vs 6.0 mmol/liter, SED = 0.42). Glucose levels rose to 8.7 mmol/liter during G and fell to 3.4 mmol/liter (SED = 0.72, P <0.001) during I, then returned towards normal postinfusion. Insulin levels increased during G and I (P < 0.01) with no difference (P > 0.05) between G and I during preinfusion (163 +/- 7.6 pmol/liter) or infusion (259 vs 264 +/- 16. 5 pmol/liter) periods. There were no differences (P > 0.05) in GH secretory characteristics, mean IGF-1, or haematocrit between G and I. However, there were significant effects of infusion within the treatments. Mean GH declined (P < 0.05) from 1.8 ng/ml (both treatments) preinfusion to 1.13 and 1.31 ng/ml during G and I infusion, respectively. GH pulse amplitude was lower during I infusion (5.6 ng/ml vs 8.2 ng/ml preinfusion, P < 0.05, SED = 1.0) and the change in amplitude from preinfusion to infusion differed (P > 0.05) with an increase in G and a decrease in I (+0.6 and -2.6, SED = 1.1). IGF-1 levels were stable and averaged 555 and 520 ng/ml (SED = 34.9) for G and I, respectively. Haematocrit declined from 34.3 +/- 1.85% over the first 4 hr of sampling to 25.7 +/- 0.97% for the remainder of the sampling period. The finding that there were no major alterations in GH secretory patterns during 12 hr of hypoglycemia and hyperglycemia suggests that GH secretion in the male red deer is relatively insensitive to short-term changes in metabolic state.

Animals↗
PubMed1996

Effects of season and nutrition on growth hormone and insulin-like growth factor-I in male red deer.

GH and insulin-like growth factor (IGF)-I are important components of the growth axis. We undertook to determine how plasma levels of these hormones altered with different seasonal and nutritional states in young male red deer to provide an insight into how the growth axis changes under these conditions. Growth rate alters dramatically with season in male red deer, providing an opportunity to sample the same animals at two different growth rates within a short period of time. GH was measured every 15 min for 24 h in the fed state and after a 48-h fast, during slow growth in winter (23 June to 16 July), and during rapid growth in spring (8 September to 2 October). At the end of each sampling period, the animals were treated with N-methyl-D, L-aspartic acid (NMDA) (5 mg/kg live weight) and sampled for a further 1 h, 45 min. Glucose and IGF-I were measured hourly during each sampling period. Live weight was measured at weekly intervals. GH was secreted in a characteristic pattern in which pulses tended to occur in rapid succession, termed a volley, that was separated from the subsequent volley by a period of baseline GH levels, termed a latent period. There were more GH pulses/24 h in the fasted state than in the fed state in winter (12.4 vs. 7.8, standard error of the difference [SED] = 1.07, P < 0.001) and in spring (11.5 vs. 8.8, SED = 1.04, P < 0.05). The increased number of GH pulses in the fasted state could be attributed to a higher number of pulses per volley (winter = 3.7 vs. 2.5, SED = 0.16, P < 0.001; spring = 3.1 vs. 2.8, SED = 0.19). Consequently, the volleys were wider in the fasted state than the fed state (winter = 197 min vs. 122 min, SED = 25, P < 0.05; spring = 173 min vs. 154 min, SED = 24, P > 0.05), and the latent periods between volleys were shorter in the fasted state than the fed state (winter = 175 min vs. 280 min, SED = 14, P < 0.001; spring = 183 min vs. 262 min, SED = 11, P < 0.001). The main differences between seasons in the fed state were larger amplitude pulses (12.4 vs. 8.3 ng/ml, SED = 1.57, P < 0.05) and higher mean GH concentrations (4.1 vs. 2.3 ng/ml, SED = 0.44, P < 0.01) in spring than in winter. The number of volleys and the intravolley pulse interval did not change significantly with nutritional state or season. NMDA administration was followed by an increase in GH with higher GH levels found in the fed state than in the fasted state in both seasons. Fed animals also had a larger initial increase in GH (until 60 min post NMDA) than fasted animals in spring (P < 0.01). Plasma IGF-I was higher in the fed state than the fasted state in both winter (315 vs. 221 ng/ml, SED = 21.0, P < 0.001) and spring (651 vs. 494 ng/ml, SED = 37.5 P < 0.001) and in the fed state was higher in spring than in winter (SED = 29.1, P < 0.001). Blood glucose was higher in the fed state than fasted state in winter (6.1 vs. 5.5 mmol/l, SED = 0.07, P < 0.001) and there was a strong trend toward this same effect in spring although it did not reach statistical significance (6.0 vs. 5.7 mmol/l, SED = 0.26, P > 0.05). Growth rate in winter at 117 g/day was less than that in spring when 220 g/day was recorded (SED = 36.8, P < 0.05). These results demonstrate that the secretory pattern of GH and plasma IGF-I levels alter in response to changes in season and nutrition. The alterations in response to a 48-h fast show that the control of GH and IGF-I secretion may be rapid and is probably a response to maintain energy balance, whereas alterations with season reflect long term control that underlies the seasonal growth pattern of the animal.

Animal Nutritional Physiological Phenomena↗
PubMed1995

COPD in the elderly. A reversible cause of functional impairment.

OBJECTIVES: To determine the frequency of referral of patients age 69 years and older to the pulmonary function laboratory at a tertiary-care hospital for airflow limitation studies; to determine the point prevalence of a significant reversible component in patients with COPD as an age-related function; and to determine the proportion of patients who were prescribed bronchodilators following a pulmonary function test (PFT) demonstrating significant reversibility. DESIGN: A retrospective review of pulmonary function tests of patients 69 years and older within calendar year 1990 was performed. Chart review of those showing significant reversibility to bronchodilators during a PFT was performed to determine level of follow-up. SETTING: Referral-based pulmonary division in a tertiary-care hospital. PATIENTS: Men and women 69 years and older who had interpretable PFTs at Northwestern Memorial Hospital (NMH) during the calendar year 1990 (n = 405). Patients whose PFTs were uninterpretable due to poor effort (n = 10) were excluded from the study. INTERVENTIONS: No specific interventions were performed as a part of the study. Referring physicians may have requested a PFT with postbronchodilator (albuterol by nebulizer) testing and may have subsequently prescribed bronchodilators for their patients. MEASUREMENTS: We studied the effect of age, gender, smoking history, and degree of airflow obstruction on changes in spirometry values and reversibility status after bronchodilator (if applicable) as determined by a PFT. MAIN RESULTS: Of the 405 consecutive elderly patients studied, 193 (47.7%) received bronchodilators and 60 (31.1%) of these patients had significant improvement as judged by the criteria listed in the Methods section. The improvement occurred equally across all age groups (p > 0.05) and the percent responding to bronchodilators increased as the degree of obstruction increased (p < 0.001). Those who had never smoked were twice as likely to respond than were current or former smokers; men were more likely to respond than women. Most patients (84%) who responded were subsequently prescribed bronchodilators. CONCLUSIONS: Responses to inhaled bronchodilators occur at all ages. Older patients showed greater reversibility as the degree of obstruction increased, while a smoking history reduced the likelihood of a bronchodilator response. COPD in the elderly may differ from the traditional form of the disease.

Administration, Inhalation↗
PubMed1992

Effects of melatonin implants on insulin-like growth factor 1 in male red deer (Cervus elaphus).

Red deer stags have a seasonal pattern of growth, alternating between periods of summer weight gain and winter weight loss that are influenced by photoperiod and by exogenous melatonin. A seasonal pattern of plasma insulin-like growth factor 1, also influenced by photoperiod, underlies the seasonal growth pattern. The present studies aimed to determine the influence of exogenous melatonin, administered at various times of the year, on plasma IGF1 in adult red deer stags in New Zealand at 45 degrees S. In one study, 7-year-old stags (N = 9) were allocated to one of three treatment groups, either control or subcutaneous melatonin (3 x 18-mg coated implants (Regulin) per month) from November to February or from December to February. Blood was sampled, the stags were weighed, and antler status was recorded over 17 months. Melatonin treatment advanced the seasonal patterns of rise and fall of plasma IGF1 and of weight gain and loss. The cessation of melatonin treatment in February produced early antler casting and a second (out-of-season) antler and increased IGF1. In a second study, 4-year-old stags (N = 30) were allocated to one of six treatment groups as follows: three melatonin implants per months for 6 consecutive months beginning on 22 June, i.e., winter solstice, 4 August, 16 September, and 23 October; three melatonin implants per month for 12 months beginning on 22 June; and an untreated group. All animals were sampled as before for 12 months. Melatonin treatment beginning in July and August did not prevent the seasonal peak in IGF1, but the amplitude was lowered and antler casting delayed.

Animals↗
PubMed1992

Iatrogenic complications in high-risk, elderly patients.

BACKGROUND: This study explores the quality improvement potential of reviewing care for long-stay, elderly medicine service patients hospitalized for congestive heart failure, acute myocardial infarction, or pneumonia at a large Midwestern teaching hospital. METHODS: Medical records were reviewed for 120 patients aged 65 years or older who were discharged between January 1987 and June 1989, with hospital stays of 15 days or longer. Patients' severity of illness on admission was rated using the Medicare Mortality Predictor System; process quality of care was rated using a structured implicit review form for judging several dimensions of clinical assessment and decision making. Serious complications were coded by etiology and type and judged as possibly or probably preventable. Logistic regression was used to identify risk factors for iatrogenic events; multiple regression was used to assess potential outcome bias in ratings of overall quality of care. RESULTS: Of 120 medical records reviewed, 70 (58.3%) suffered at least one iatrogenic complication. Forty-three patients (35.8%) suffered an iatrogenic complication rated as potentially preventable. Significant predictors of all iatrogenic complications were quality ratings of initial physician assessment, patients' inability to walk unassisted, and low Glasgow Coma Score. For potentially preventable complications, quality ratings for physician documentation of functional status were also significant. Ratings for overall quality of care were not significantly influenced by the mere presence of death or complications. CONCLUSIONS: Iatrogenic complications are likely to be an extremely common experience for elderly medicine service patients with long lengths of stay. A significant portion of these complications may be potentially preventable with closer attention to initial assessment and documentation of patients' functional status.

Aged↗
PubMed1991

Role of the thyroid gland in seasonal reproduction. II. Thyroxine allows a season-specific suppression of gonadotropin secretion in sheep.

A series of four experiments was conducted to examine the previously described phenomenon that the thyroid gland is required for the breeding season to end in female sheep. Exp 1 tested the hypothesis that the thyroid is required because of its secretion of T4. Ewes thyroidectomized (THX) in the anestrous season either received T4 replacement or no further treatment; seasonal reproductive shifts were compared to those of thyroid-intact controls. All ewes were housed in conditions in which the end of the breeding season results from the expression of an endogenous annual rhythm. The ewes were ovariectomized and given constant-release estradiol (E) implants; reproductive state was assessed from serum LH levels to monitor seasonal shifts in response to E negative feedback. THX did not alter onset of the breeding season (LH rise) but, in the absence of T4 replacement, blocked its end (LH fall). T4 replacement reversed this effect of THX. Exp 2 tested the hypothesis that the thyroid is required only until the onset of the breeding season for reproductive activity to end at its normal time. THX after the breeding season began, however, sustained the elevation in LH, suggesting that the thyroid is required after reproductive onset for the breeding season to end. Exp 3 tested the hypothesis that THX causes a widespread disruption of steroid feedback responses. No effect of THX, however, was observed with respect to either the ability of an E rise to elicit the LH surge or the ability of E, or progesterone, to suppress LH secretion in the breeding season. Of the steroid feedback responses tested, THX altered only the seasonal shift in potency of E negative feedback. Exp 4 examined circulating T4 in thyroid-intact ewes over a 2-yr period. An annual cycle of serum T4 was detected; values reached a peak in winter (late breeding season) and a nadir in summer (late anestrus). Our findings support the concept that the thyroid gland plays a fundamental role in seasonal reproduction in the ewe. In this regard, secretion of T4 after the onset of reproductive activity is required for an endogenously generated change in the neuroendocrine axis that leads to an intensified E negative feedback and an end to the breeding season.

Anestrus↗
PubMed1991

Role of the thyroid gland in seasonal reproduction. III. Thyroidectomy blocks seasonal suppression of gonadotropin-releasing hormone secretion in sheep.

Previous studies demonstrated that the thyroid gland is required for the changes in LH secretion that lead to the end of the breeding season of female sheep, a reproductive transition generated within the ewe by an endogenous annual rhythm. The present study tested the hypothesis that this role of the thyroid is mediated via the GnRH neurosecretory system. The pulsatile secretion of GnRH into hypophyseal portal blood and LH into peripheral blood, as well as the neuroanatomical distribution of GnRH neurons and their light microscopic morphology, were compared among anestrous ewes and thyroidectomized (THX) ewes that failed to make the transition to the anestrous season. The study was conducted under photoperiodic conditions in which the transition to anestrus was generated by the endogenous rhythm. Each animal was ovariectomized and treated sc with a constant release implant of estradiol to normalize gonadal steroid status among thyroid-intact and THX ewes. High frequency pulses of GnRH and LH were evident in THX ewes that failed to make the transition to anestrus, whereas pulsatile secretion of GnRH and LH was generally not observed in thyroid-intact controls that had entered anestrus. This marked effect of thyroidectomy on GnRH secretion was not associated with widespread changes in the total number, distribution, or light microscopic morphology of GnRH neurons in the hypothalamus and preoptic area. Our finding that pulsatile secretion of GnRH is elevated in THX ewes that fail to make the transition to anestrus supports the hypothesis that the thyroid gland is required for the endogenously generated switch in function of the GnRH neurosecretory system that leads to the end of the breeding season of the ewe.

Animals↗