[Role of the central nervous system in the development of obesity].
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Animals↗
Biomedical subjects
P Doyle
Publications and source records attributed to P Doyle.
Alterations of local cerebral glucose utilization in lean and obese fa/fa rats after acute adrenalectomy.
An animal model often used to investigate the aetiology of obesity is the genetically obese fa/fa rat. It has many abnormalities, including hyperphagia, hyper-insulinemia, insulin resistance, low cerebral glucose utilization and an overactive hypothalamo-pituitary adrenal (HPA) axis with resulting hypercorticism. Due to the latter consideration, the aim of this work was to study the impact of acute adrenalectomy (ADX) on the local cerebral glucose utilization (LCGU) of lean and obese fa/fa rats. ADX resulted in discrete increases in LCGU of regions common to both lean and obese rats. These common regions were found to belong to be related to the limbic system. Within this system, the LCGU of the brain of obese rats was either normalized to lean sham operated values or increased by ADX to a similar degree in both groups on a percentage basis. It was concluded that the LCGU of both lean and obese animals appears to be negatively regulated, albeit to different extents, by glucocorticoids. Such negative regulation is particularly salient within the limbic system of the lean rat and even more so in the fa/fa rat. It is suggested that the long-term hypercorticism of obese fa/fa rats due to abnormal regulation of the HPA axis may result in a decreased LCGU in limbic and related regions of the brain of fa/fa rats and contribute to the expression of the obese phenotype.
Adrenalectomy↗
Effects of corticosterone administration on local cerebral glucose utilization of rats.
The local cerebral glucose utilization (LCGU) of control and 2 day corticosterone-administered rats was investigated using the method of Sokoloff (labelled 2-deoxy-D-glucose). The overall LCGU of both groups was similar, but discrete areas of the corticosterone-administered rat brains displayed both increases and decreases in their utilization of 2-deoxyglucose. These areas were associated with the limbic cortex and included the hippocampus, the septum and some thalamic and hypothalamic nuclei. It is well known that these regions are interconnected and that acetylcholine is one of the main neurotransmitters. Some of these pathways (as measured electrophysiologically) have reportedly inhibitory influences, whilst others have excitatory ones within the limbic region. It was therefore striking to observe that these inhibitory or stimulatory effects were corroborated by a selective, corticosterone-induced decrease or increase in 2-deoxyglucose uptake, respectively. This gives corticosterone a putative role in the regulation of the limbic system. As the latter has been reported to be abnormal in genetically obese hypercorticosteronemic fa/fa rats, it is suggested that these corticosterone-induced changes within the limbic system may contribute to the overall phenotypic expression of this obesity state.
Animals↗
Cumulative conception and live-birth rates after in vitro fertilization with and without the use of long, short, and ultrashort regimens of the gonadotropin-releasing hormone agonist buserelin.
OBJECTIVE: Our purpose was to compare cumulative conception and live-birth rates after in vitro fertilization with and without the use of the long, short, and ultrashort regimens of the gonadotropin-releasing hormone agonist buserelin. STUDY DESIGN: Life-table analysis of conception and live-birth rates in relation to ovarian stimulation regimen used in 2893 women who had one of five stimulation regimens exclusively throughout all treatment cycles, namely, human menopausal gonadotropin with or without clomiphene citrate; follicle-stimulating hormone with or without clomiphene citrate; and long, short, and ultrashort protocols of buserelin, plus follicle-stimulating hormone or human menopausal gonadotropin; and in an additional 347 women who had been administered both human menopausal gonadotropin and follicle-stimulating hormone with or without clomiphene citrate. RESULTS: The cumulative conception rate and cumulative live-birth rate were significantly higher in those women treated exclusively with the long buserelin regimen (59% and 55%, respectively, after three cycles) compared with those who only had human menopausal gonadotropin or follicle-stimulating hormone with or without clomiphene citrate (39% and 29%, respectively, after three cycles) (p = 0.001 and p = 0.0001) or compared with those who had only short or ultrashort buserelin regimens (22% and 17% after two cycles) (p = 0.0001 and p = 0.005). The pregnancy failure rate in patients on the long buserelin regimen was 22.4% (95% confidence interval 14.8% to 30.0%) compared with 33.3% (95% confidence interval 29.6% to 37.0%) in those who had human menopausal gonadotropin or follicle-stimulating hormone with or without clomiphene citrate (p = 0.03). When the probabilities of first conception and first live birth were examined by treatment regimen, after we allowed for the effects of age, cause of infertility, calendar year of treatment, and treatment cycle number (with a multiple logistic regression model), it was found that, relative to human menopausal gonadotropin or follicle-stimulating hormone with or without clomiphene citrate, the odds of conceiving with the long buserelin regimen was 1.63 (95% confidence interval 1.31 to 2.03) (p < 0.001) and the odds of a live birth was 1.97 (95% confidence interval 1.53 to 2.54) (p < 0.001). Similarly, relative to short or ultrashort buserelin the odds of conceiving with long bureselin was 1.88 (95% confidence interval 1.39 to 2.55) (p < 0.001) and the odds of a live birth was 1.79 (95% confidence interval 1.25 to 2.56) (p = 0.001). CONCLUSION: Pituitary desensitization with the long protocol of buserelin significantly increases the probabilities of conception and live birth after in vitro fertilization.
Adult↗
Pregnancy and birth rates of live infants after in vitro fertilization in women with an without previous in vitro fertilization pregnancies: a study of eight thousand cycles at one center.
OBJECTIVE: Our aim was to compare the cumulative conception and live-birth rates after in vitro fertilization in women undergoing their first course of in vitro fertilization treatment with those in women undergoing their second course of treatment, having previously achieved an in vitro fertilization pregnancy. This study occurred in a tertiary referral-assisted conception unit. STUDY DESIGN: The cumulative conception rates obtained by life-table analysis in 4115 women having their first course of in vitro fertilization therapy (7327 treatment cycles leading to 1123 pregnancies) were compared by means of the log-rank test with those of 331 women in their second course of treatment, having previously achieved an in vitro fertilization pregnancy (561 treatment cycles leading to 138 second in vitro fertilization pregnancies). Similarly, the cumulative live birth rates of 3824 women in their first course of treatment (7136 treatment cycles leading to 732 live births) were compared with those of 105 women in their second course of treatment, having previously achieved an in vitro fertilization live birth (205 treatment cycles leading to 33 second in vitro fertilization live births). RESULTS: The cumulative conception rates and cumulative live birth rates were significantly higher in women having their second course of in vitro fertilization treatment than in those having their first course (cumulative conception rate: p = 0.0001; cumulative live birth rate, p = 0.007). After five cycles of in vitro fertilization, the cumulative conception rates and cumulative live birth rates were 49.8% (95% confidence interval, 46.3% to 53.5%) and 39.0% (95% confidence interval, 35.4% to 42.9%), respectively, in those having their first course of treatment compared with 69.9% (95% confidence interval, 57.6% to 81.3%) and 68.6% (95% confidence interval, 46.1% to 88.5%), respectively, in those having their second course. The estimated median numbers of cycles taken to achieve a pregnancy and live birth (assuming all women could potentially undergo the same number of cycles) were six and eight, respectively, in the first course of treatment compared with only three and five in the second course. CONCLUSION: Women who have achieved a previous in vitro fertilization pregnancy have significantly higher cumulative conception rate and cumulative live birth rates compared with those of women having their first course of treatment.
Adult↗
Sodium balance in very-low-birth-weight infants.
Maintaining sodium balance in the VLBW infant is not straightforward. Several predisposing factors appear in more than one imbalance constellation. In addition, the same patient circumstance can produce two types of imbalance. Understanding the physical properties of electrolytes and water enables critical care nurses to anticipate outcomes of specific situations in the neonatal ICU. Careful assessment of renal function, urine output, and water balance are crucial in determining proper treatment of sodium balance disorders. The high potential risk of errors in the neonatal ICU requires verification of all fluid and electrolyte orders, as well as serial safety checks of IV fluids and additives to avoid complications. An expert nurse's ability to predict the needs of VLBW infants places the nurse in a pivotal position to recognize subtle changes before actual physiologic change occurs. Although the multiple variations can be confusing to the bedside clinician, sorting through them helps in selecting interventions that are timely and improve the outcomes and morbidity of our smallest patients at risk.
Humans↗
The ethical dilemmas of general practice.
It is not possible, and perhaps not even desirable to construct a code of ethics that covers all eventualities, and yet we are swamped with ethical problems and decisions every day in general practice. In my experience, most doctors are predominantly ethical people, and hold the interests of their patients as the prime reason for their existence. In the final instance, it is our own conscience that will dictate our behaviour, and it is the opinion of our peers that will guide us in difficulty. This poses more questions than it does answers, but we must continue in our tradition of service, practising only to the highest standards of ethical behaviour.
Australia↗
Ionising radiation and childhood cancer in Seascale. Fathers' exposure may still be linked.
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Adolescent↗
Risk factors for overdose mortality: a case-control study within a cohort of intravenous drug users.
Overdose mortality is the major adverse health effect of drug injection. The potential determinants of overdose death are poorly understood; the aim of this study was to investigate risk factors for overdose mortality among intravenous drug users (IVDU). A cohort of 4200 IVDU attending methadone treatment centres in Rome during the period 1980-1988, was enrolled. Data were collected from clinical records. Vital status and cause of death were ascertained as of 31 December 1988. A matched case-control analysis within the cohort was performed to identify risk factors of death from overdose. All overdose deaths were included as cases and four controls, matched on year of birth and sex, were selected for each case from among the cohort members still alive at the time of death of the corresponding case. In all, 81 deaths from overdose were identified as cases and compared with 324 controls. A high risk of overdose death occurred among subjects who left treatment compared with those still in treatment (odds ratio [OR] = 3.55, 95% confidence interval [CI]: 1.82-6.90). The OR was particularly elevated in the first 12 months after drop-out compared with those retained in treatment (OR = 7.98, 95% CI: 3.40-18.73). The risk of overdose death was higher for unmarried compared with married people (OR = 2.48, 95% CI: 1.31-4.68); a higher risk of overdose death was also associated with lower educational status and younger age at first drug use, but such association was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Case-Control Studies↗
Effects of age, gravidity and male infertility status on cumulative conception rates following artificial insemination with cryopreserved donor semen: analysis of 2998 cycles of treatment in one centre over 10 years.
The effects of age, gravidity and male infertility status on cumulative conception rates after donor insemination were investigated in an analysis of 2998 treatment cycles undertaken on 443 patients. It was found that the cumulative conception rates after 3, 6 and 12 cycles of treatment were 21, 40 and 62% respectively for patients < 30 years of age compared with 17, 26 and 44% for those aged > or = 30 years (P = 0.008). There was also a significant difference (P < 0.001) in results depending on course of treatment and the cumulative conception rates were 19% after 3 cycles, 33% after 6 cycles and 54% after 12 cycles of treatment in the first course of treatment compared with 40, 67 and 79% respectively in those who returned for subsequent courses of treatment after having achieved a donor insemination pregnancy in the first treatment course. Gravidity and male infertility status (azoospermia or oligozoospermia/asthenozoospermia) did not significantly affect the cumulative conception rates.
Adult↗
Localised amyloidosis of the prostate.
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Aged↗
Local cerebral glucose utilization in brains of lean and genetically obese (fa/fa) rats.
The local cerebral glucose utilization (LCGU) of brains from Wistar, lean Zucker (FA/FA), and obese Zucker (fa/fa) rats was investigated using the method of Sokoloff et al. (L. Sokoloff, M. Reiwich, C. Kennedy, M.H. Des Rosiers, C.S. Patlak, K.D. Pettigrew, O. Sakurada, and M. Shinohara. J. Neurochem. 28: 897-916, 1977.). The LCGU of obese Zucker (fa/fa) rats was decreased in comparison to the relatively high values obtained for the lean Zucker (FA/FA) rats in all gray matter areas studied, on average to the extent of 50%. When compared with Wistar rats, several brain areas of lean Zucker (FA/FA) animals had a normal glucose uptake. When these normal areas were assessed for common efferent and afferent pathways, it was found that many of these common connections had normal glucose utilizations. In direct comparison to the obese fa/fa rat, the LCGU rates of these areas were decreased, hinting that this would also be the case for their functional activity. Because these areas (limbic, thalamic, hypothalamic, autonomic) have been reported to be potentially relevant for bringing about the behavioral and neuroendocrine alterations known to occur in obese fa/fa rats, it is proposed that they represent dysfunctions that are partly responsible for the obesity syndrome of the fa/fa strain.
Animals↗
AIDS update: the HIV epidemic: what lies ahead?
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Adolescent↗
Effective audit: reporting to the National Confidential Enquiry into Perioperative Deaths.
OBJECTIVE: To investigate the effectiveness of computer based and manual district and unit information systems for identifying hospital deaths eligible for reporting to the National Confidential Enquiry into Perioperative Deaths (NCEPOD). DESIGN: Prospective six to 10 week study of hospital (death register, immediate coding of medical records) and district information systems followed by six month assessment after modification to entry of data. SETTING: Acute units within Lewisham and North Southwark Health District. PATIENTS: All 290 patients dying in hospital during the six weeks, for whom the medical records were obtainable in 231. MAIN OUTCOME MEASURES: Sensitivity and specificity of the information systems in ascertaining eligible surgical deaths (patients dying in hospital who had during 30 days previously had a surgical procedure while under the care of a consultant in a surgical specialty) tested against validated list of screened medical records. RESULTS: Of 231 medical records, 30 (12 from Lewisham, 18 from North Southwark) met the national inquiry's criteria. The computer based systems of both units detected less than 60% of eligible deaths (sensitivity 53%, specificity 83%); the death register detected about 60% (sensitivity 61%, specificity 89%); manual systems detected all eligible deaths. Subsequent modification to ensure immediate coding of records into the computerised systems during follow up failed to show any improvement. IMPLICATIONS: Routine hospital information systems may miss up to half the deaths eligible for NCEPOD.
Hospital Information Systems↗
Obstetric outcome of in vitro fertilization pregnancies compared with normally conceived pregnancies.
OBJECTIVE: To compare the obstetric outcome of in vitro fertilization pregnancies with normally conceived pregnancies. STUDY DESIGN: The obstetric outcome of in vitro fertilization pregnancies achieved in 763 British residents at two in vitro fertilization clinics resulting in the births of 961 babies were compared by means of the relative risk statistic with a control group of naturally conceived primiparous pregnancies matched by maternal age and multiplicity of pregnancy. RESULTS: Twenty-five percent of in vitro fertilization pregnancies were multiple pregnancies. The incidence of singleton term breech presentation was similar to that among controls. As compared with controls there was an increased incidence among in vitro fertilization pregnancies of vaginal bleeding and hypertension requiring hospitalization (p less than 0.001) and cesarean births (p less than 0.001) and, among in vitro fertilization singleton pregnancies, an increased incidence of intrauterine growth retardation (p less than 0.05), placenta previa (p less than 0.05), and preterm delivery (p less than 0.001). The congenital malformation, stillbirth, and perinatal mortality rates were comparable with maternal age-standardized national rates. CONCLUSIONS: Although the majority of in vitro fertilization pregnancies have a satisfactory obstetric outcome, there are a number of increased obstetric risks that may reflect the history of infertility, the relatively high incidence of poor obstetric history, and the lower threshold for obstetric intervention in in vitro fertilization patients.
Adult↗
Preterm delivery, low birthweight and small-for-gestational-age in liveborn singleton babies resulting from in-vitro fertilization.
The Medical Research Council In-Vitro Fertilization (IVF) Register report on births resulting from assisted conception in Great Britain demonstrated a high incidence of preterm and low birthweight babies. This incidence remained high even when the analysis was restricted to singleton babies. The present paper investigates possible risk factors for prematurity, low birthweight and small-for-gestational-age (SGA) in singleton IVF births. Thirteen per cent of singleton IVF babies were preterm, 11% low birthweight and 17% small-for-gestational-age. Analysis by multiple regression indicated that hypertension during pregnancy was an independent risk for preterm delivery, low birthweight and SGA, bleeding during pregnancy for preterm delivery, and the number of embryos transferred and the type of infertility for low birthweight.
Female↗
Muscle insulin resistance may not be a primary etiological factor in the genetically obese fa/fa rat.
It is not known whether hyperinsulinemia of the genetically obese fa/fa rat occurs before insulin resistance and abnormal glucose handling or vice versa. Therefore, it was decided to study, as a function of age, the evolution of the insulin-stimulated glucose uptake measuring the in vitro uptake of its analog, 2-deoxy-D-glucose (2DG), by diaphragm. The expression of the insulin-sensitive glucose transporter (GLUT 4) mRNA and protein were also investigated in muscles. The maximum increase over baseline in 2DG uptake in response to increasing insulin concentrations in the medium was upward shifted in diaphragm from preweaned 21-day-old preobese rats relative to that in lean controls (increased responsiveness). By 31 days of age the maximum increase over baseline diaphragm 2DG uptake in response to insulin was similar in young lean and obese rats. At 70 days of age, the 2DG uptake muscle dose response to insulin was significantly downward shifted, i.e. clearly insulin resistant (decreased responsiveness). Muscle (diaphragm and extensor digitorum longus) expression of GLUT 4 mRNA and protein revealed no intergroup difference at any of the ages studied. Hyperinsulinemia was moderate in preobese animals and progressively increased with the duration of the obesity syndrome. Based on the observation that diaphragm glucose uptake of 21-day-old preobese rats was overresponsive to insulin, normoinsulin responsive at 31 days, and insulin resistant at a later time, it is concluded that muscle insulin resistance is not a primary etiological defect, but must be secondary to other pathological alterations, the nature of which remains to be elucidated.
Animals↗
The importance of the brain in the aetiology of obesity and type 2 diabetes.
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Adipose Tissue↗