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Biomedical subjects

J Roberts

Publications and source records attributed to J Roberts.

At least 91 records · Page 5Linked to original sources

Preterm delivery in women with pregestational diabetes mellitus or chronic hypertension relative to women with uncomplicated pregnancies. The National institute of Child health and Human Development Maternal- Fetal Medicine Units Network.

OBJECTIVE: The purpose of this study was to compare the rates of indicated and spontaneous preterm delivery among women with chronic hypertension or pregestational diabetes mellitus with the rates among healthy women. STUDY DESIGN: This was a secondary analysis of data from healthy women with singleton gestations enrolled in a prospective observational study for prediction of preterm delivery (control group, n = 2738), women with pregestational diabetes mellitus requiring insulin therapy (n = 461), and women with chronic hypertension (n = 761). The two latter groups were enrolled in a randomized multicenter trial for prevention of preeclampsia. The main outcome measures were rates of preterm delivery, either spontaneous (preterm labor or rupture of membranes) or indicated (for maternal or fetal reasons), and neonatal outcomes. RESULTS: The overall rates of preterm delivery were significantly higher among women with diabetes mellitus (38%) and hypertension (33.1%) than among control women (13.9%). Rates were also significantly higher for delivery at <35 weeks' gestation. Women with diabetes mellitus had significantly higher rates of both indicated preterm delivery (21.9% vs 3.4%; odds ratio, 8.1; 95% confidence interval, 6.0-10.9) and spontaneous preterm delivery (16.1% vs 10.5%; odds ratio, 1.6; 95% confidence interval, 1.2-2.2) than did women in the control group. In addition, they had significantly higher rates of both indicated preterm delivery (odds ratio, 4.8; 95% confidence interval, 3.0-7.5) and spontaneous preterm delivery (odds ratio, 2.1; 95% confidence interval, 1.4-3.0) at <35 weeks' gestation than did control women. Compared with control women those with chronic hypertension had higher rates of indicated preterm delivery at both <37 weeks' gestation (21.9% vs 3.4%; odds ratio, 8.1; 95% confidence interval, 6.2-10.6) and at <35 weeks' gestation (12.1% vs 1.6%; odds ratio, 8.2; 95% confidence interval, 5.7-11.9), but there were no differences in rates of spontaneous preterm delivery. CONCLUSION: The increased rate of preterm delivery among women with chronic hypertension relative to control women was primarily an increase in indicated preterm delivery, whereas the rates of both spontaneous and indicated preterm delivery were increased among women with pregestational diabetes mellitus.

Adult↗

Antioxidants: their role in pregnancy and miscarriage.

The aim of this study was to examine the role of antioxidants within the normal menstrual cycle, in healthy pregnancy, and in women suffering first-trimester miscarriage. The antioxidants chosen comprised of two from peripheral blood-plasma thiol and ceruloplasmin-and two extracellular parameters-superoxide dismustase (SOD) and red cell lysate thiol. We found that antioxidant levels varied little throughout the menstrual cycle. Pregnancies that went successfully to term were associated with increased levels of ceruloplasmin and SOD early in the first trimester. These changes were thought to offer the cell protection from the damage caused by the increased oxidative stress associated with pregnancy. First-trimester miscarriage was associated with significantly reduced levels of SOD. A subgroup of patients who miscarried in their first pregnancy, but whose second pregnancies were successful, had higher levels of plasma thiol and significantly reduced levels of red cell lysate thiol in the on-going pregnancy compared to levels at the time of miscarriage. Miscarriage and pregnancy appear to be associated with increased oxidative stress. In a successful pregnancy, however, changes occurred within the peripheral blood that offered protection from oxidant attack.

Abortion, Spontaneous↗

Family experiences and factors associated with the diagnosis of fragile X syndrome.

The authors interviewed 41 mothers of young boys with fragile X syndrome to determine the process by which they learned their child had fragile X syndrome. The average family had concerns about the child's development at 9 months of age. Developmental delay was determined at an average age of 24 months, and fragile X syndrome was diagnosed at a mean age of 35 months. Considerable variability was found in age of first concern, determination of delay, and diagnosis of fragile X syndrome. Three child variables (severity of delay, autistic behavior, temperament style) and four family variables (mother's age, mother's education, sibling status, social support) did not account for this variability, although birth year did (children born more recently were somewhat more likely to be identified earlier). Families often encountered physicians who initially discounted concerns or said that it was too early to determine whether a problem did indeed exist. Given current knowledge and practice, improving the early identification (under 3 years of age) of children with fragile X syndrome is likely to remain difficult if based solely on behavioral and clinical observations.

Child, Preschool↗

Well-adjusted children: an alternate view of children with inflammatory bowel disease and functional gastrointestinal complaints.

Previous studies have suggested impaired psychosocial adjustment in children and adolescents with inflammatory bowel disease (IBD). We examined 62 subjects referred to a regional Pediatric Gastroenterology Clinic with IBD or functional gastrointestinal (FGI) complaints. Characteristics of the clinic include a unified team approach, regularly scheduled appointments at 3-month intervals, proactive medical care emphasizing maintenance of full functioning, and close medical-surgical interaction (joint clinics). A research assistant administered a questionnaire regarding children's perceptions of their illness, as well as the Child Depression Inventory (CDI), the Piers-Harris (PH) test of self-concept, and the Child Behaviour Checklist (CBCL). The 36 children with IBD (25 Crohn's disease, 11 ulcerative colitis, mean age 13.3 +/- 3.0 years) were compared with 26 patients with FGI complaints (16 recurrent abdominal pain, 10 functional megacolon, mean age 11.4 +/- 2.8 years). The scores on the standardized tests were not clinically significant for either group. In comparison, however, children with IBD were less depressed and had fewer behaviour problems than the FGI group. Surprisingly, only 19% (7 of 36) of children with IBD described their illness as a problem to them, compared with 65% (17 of 26) of children with FGI symptoms. The latter children also considered themselves significantly sicker than did those with IBD. We conclude that normal psychosocial adjustment is possible in pediatric patients with IBD. We speculate that this group benefitted from the professional supports that our clinic specifically provides to patients with IBD. The FGI group may have suffered from a lack of such professional supports, as well as from the absence of a specific diagnosis.

Abdominal Pain↗

The association between vascular risk factor-mediating medications and cognition and dementia diagnosis in a community-based sample of African-Americans.

OBJECTIVE: To determine the association between medications that ameliorate vascular risk factors and the prevalence of cognitive impairment and dementia in an older African-American population. DESIGN: A community-based survey to identify subjects with and without evidence of cognitive impairment and subsequent diagnostic evaluation of a stratified sample of these subjects using formal diagnostic criteria for dementia and Alzheimer's disease (AD). SETTING: Urban neighborhoods in Indianapolis, Indiana. SUBJECTS: A random sample of 2,212 African-American adults aged 65 years and older residing in 29 contiguous census tracts. MEASUREMENTS: Subjects' scores on the Community Screening Instrument for Dementia (CSID), formal diagnostic and clinical assessments for dementia, current medication use and history of medical illnesses, both self-report and, where possible, from an informant. Four outcome measures were defined by the following criteria: (1) cognitive impairment as defined by the subject's performance on the CSID cognitive scale; (2) cognitive/ functional impairment as defined by the total CSID score that included a relative's assessment of the subject's functional abilities; (3) dementia as defined by explicit diagnostic criteria; and (4) possible or probable Alzheimer's Disease as defined by explicit criteria. RESULTS: The vascular risk factor mediating medications, when analyzed together, were associated with a significantly decreased risk of diagnosis of cognitive impairment after controlling for age, education, and stroke (OR 0.73, P = .01) and also a significantly decreased risk of cognitive/functional impairment (OR 0.66, P = .02). Antihypertensive agents, excluding centrally acting sympatholytic drugs were associated with a significantly reduced risk of diagnosis of cognitive impairment (OR 0.56, P < .01) and cognitive/functional impairment (OR 0.64, P = .01). Centrally acting sympatholytic agents were associated with an increased risk of diagnosis of cognitive impairment (OR 2.24, P < .01). There was a trend toward protection from a diagnosis of AD and dementia for the vascular risk factor mediating medications and for the antihypertensive medication, but this did not reach significant levels. CONCLUSIONS: These data suggest that the use of medications to ameliorate vascular risk factors, particularly antihypertensive medication, may also be useful in reducing the risk of cognitive impairment in older subjects. However, they also suggest that physicians should be cautious in prescribing antihypertensive drugs with centrally acting sympatholytic properties to older subjects.

Aged↗

Efficacies of two new antifungal agents, the triazole ravuconazole and the echinocandin LY-303366, in an experimental model of invasive aspergillosis.

The efficacy of ravuconazole, a new triazole antifungal agent, and the echinocandin LY-303366 were evaluated in an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis. Oral therapy with ravuconazole at a dosage of 30 mg/kg of body weight per day or the echinocandin LY-303366, given intravenously in a dosage of 5 or 10 mg/kg, was begun 24 h after a lethal or sublethal challenge, and results were compared with those for amphotericin B therapy and untreated controls. Prophylaxis was also studied with LY-303366 given at a dosage of 5 or 10 mg/kg/day 48 h before lethal or sublethal challenge. Ravuconazole eliminated mortality, cleared aspergillus antigen from the serum, and eliminated Aspergillus fumigatus organisms from tissues of both lethally and sublethally challenged immunosuppressed animals with invasive aspergillosis. Although LY-303366, at both doses, prolonged survival and reduced aspergillus antigenemia, it did not eliminate aspergillus organisms from organ tissues. The half-lives of ravuconazole and LY-303366 in rabbits were 13 and 12.5 h, respectively, and no accumulation of either drug was seen after 6 days of treatment. Although LY-303366 showed activity in this rabbit model of invasive aspergillosis, ravuconazole was the more active agent, comparable to amphotericin B. Additional studies are needed to determine the potential of ravuconazole for use in the treatment of this infection.

Anidulafungin↗

Strategic options for antenatal screening for syphilis in the United Kingdom: a cost effectiveness analysis.

OBJECTIVE: Antenatal screening for syphilis is well established in the United Kingdom. The prevalence of syphilis is now very low, prompting the question as to whether this screening programme is still necessary. This paper aims at identifying possible screening strategy options for the programme and comparing their effectiveness and cost effectiveness. METHODS: The cost of the screening programme in the United Kingdom was estimated. This was based on the cost of screening tests, treatment, and follow up of infected women and their infants. This information was obtained from laboratories, antenatal clinics, and genitourinary medicine clinics. Epidemiological data from a survey of women treated for syphilis in pregnancy were analysed to identify groups at increased risk of syphilis. Strategic options for the screening programme were then identified. The effectiveness, number needed to treat, and cost effectiveness of these options were compared. RESULTS: Antenatal screening in the United Kingdom detected at least 40 pregnant women who need treatment for syphilis every year. This means that 18602 women are screened for every woman detected who needs treatment for syphilis. The marginal annual cost of this screening programme in the United Kingdom is 672366 pounds sterling. This is equivalent to 90p per woman screened, or 16670 pounds sterling to detect one woman who needs treatment for syphilis. The screening programme could be targeted geographically at pregnant women in the Thames regions. This option has the potential to save 482185 pounds sterling. Other strategic options are to target pregnant women in non-white ethnic groups, or those born outside the United Kingdom. These targeted options would each detect between 70% and 77% of women needing treatment for syphilis. These options could potentially save 592938 pounds sterling and 562691 pounds sterling respectively. CONCLUSIONS: Targeting or stopping the screening programme would save relatively little money. Although selectively screening groups by country of birth or by ethnic group could detect at least 70% of cases, this would be politically and practically difficult. Targeting by region would facts and the changing international epidemiology of syphilis lead us to recommend that the current universal antenatal screening for syphilis should continue.

Cost-Benefit Analysis↗

Augmented vasoconstriction and thromboxane formation by 15-F(2t)-isoprostane (8-iso-prostaglandin F(2alpha)) in immature pig periventricular brain microvessels.

BACKGROUND AND PURPOSE: Oxidant stress, especially in the premature, plays a major role in the pathogenesis of hypoxic-ischemic encephalopathies mostly manifested in the periventricular region. We studied the vasomotor mode of actions of the peroxidation product 15-F(2t)-isoprostane (15-F(2t)-IsoP) (8-iso-prostaglandin F(2alpha)) on periventricular region during development. METHODS: Effects of 15-F(2t)-IsoP on periventricular microvessels of fetal, newborn, and juvenile pigs were studied by video imaging and digital analysis techniques. Thromboxane formation and intracellular Ca(2+) were measured by radioimmunoassay and by using the fluorescent indicator fura 2-AM. RESULTS: 15-F(2t)-IsoP-mediated constriction of periventricular microvessels decreased as a function of age such that in the fetus it was approximately 2.5-fold greater than in juvenile pigs. 15-F(2t)-IsoP evoked more thromboxane formation in the fetus than in the newborn, which was greater than that in the juvenile periventricular region; this was associated with immunoreactive thromboxane A(2) (TXA(2)) synthase expression in the fetus that was greater than that in newborn pigs, which was greater than that in juvenile pigs. 15-F(2t)-IsoP-induced vasoconstriction was markedly inhibited by TXA(2) synthase and receptor blockers (CGS12970 and L670596). Vasoconstrictor effects of the TXA(2) mimetic U46619 on fetal, neonatal, and juvenile periventricular microvessels did not differ. 15-F(2t)-IsoP increased TXA(2) synthesis by activating Ca(2+) influx through non-voltage-gated channels in endothelial cells (SK&F96365 sensitive) and N-type voltage-gated channels (omega-conotoxin sensitive) in astrocytes; smooth muscle cells were not responsive to 15-F(2t)-IsoP but generated Ca(2+) transients to U46619 via L-type voltage-sensitive channels. CONCLUSIONS: 15-F(2t)-IsoP causes periventricular brain region vasoconstriction in the fetus that is greater than that in the newborn, which in turn is greater than that in the juvenile due to greater TXA(2) formation generated through distinct stimulatory pathways, including from endothelial and astroglial cells. The resulting hemodynamic compromise may contribute to the increased vulnerability of the periventricular brain areas to oxidant stress-induced injury in immature subjects.

Animals↗

Analysis and treatment of finger sucking.

We analyzed and treated the finger sucking of 2 developmentally typical children aged 7 and 10 years. The functional analysis revealed that the finger sucking of both children was exhibited primarily during alone conditions, suggesting that the behavior was maintained by automatic reinforcement. An extended analysis provided support for this hypothesis and demonstrated that attenuation of stimulation produced by the finger sucking resulted in behavior reductions for both children. Treatment consisted of having each child wear a glove on the relevant hand during periods when he or she was alone. Use of the glove produced zero levels of finger sucking for 1 participant, whereas only moderate reductions were obtained for the other. Subsequently, an awareness enhancement device was used that produced an immediate reduction in finger sucking.

Awareness↗

Adrenalectomy reverses obese phenotype and restores hypothalamic melanocortin tone in leptin-deficient ob/ob mice.

In genetically obese leptin-deficient ob/ob mice, adrenalectomy reverses or attenuates the obese phenotype. Relative to lean controls, ob/ob mice also exhibit decreased hypothalamic proopiomelanocortin (POMC) mRNA and increased hypothalamic agouti-related peptide (AGRP) mRNA and neuropeptide Y (NPY) mRNA. It has been hypothesized that this profile of hypothalamic gene expression contributes to the obese phenotype caused by leptin deficiency. To assess if reversal of obese phenotype by adrenalectomy entails normalization of hypothalamic gene expression, male wild-type and ob/ob mice were adrenalectomized (with saline supplementation) or sham adrenalectomized at 2 months of age. Mice were sacrificed 2 weeks after adrenalectomy, during which time food intake and body weight were monitored daily. After sacrifice, hypothalamic gene expression was assessed by Northern blot analysis as well as in situ hybridization. In wild-type mice, adrenalectomy significantly decreased AGRP mRNA but did not significantly influence POMC or NPY mRNA. In ob/ob mice, adrenalectomy reduced the levels of plasma glucose, serum insulin and corticosterone, and food intake toward or below wild-type levels, and it restored hypothalamic POMC and AGRP mRNA but not NPY mRNA to wild-type levels. These studies suggest that adrenalectomy reverses or attenuates the obese phenotype in ob/ob mice, in part by restoring hypothalamic melanocortin tone toward wild-type levels. These studies also demonstrate that factors other than leptin may play a major role in regulating hypothalamic melanocortin function.

Adrenalectomy↗

Effect of ration and exercise on plasma creatine kinase activity and lactate concentration in Thoroughbred horses with recurrent exertional rhabdomyolysis.

OBJECTIVE: To determine the effects of 3 rations (low grain, fat, high grain) on plasma creatine kinase (CK) activity and lactate concentration in Thoroughbred horses with recurrent exertional rhabdomyolysis (RER). ANIMALS: 5 Thoroughbreds with RER and 3 healthy Thoroughbreds (control horses). PROCEDURES: Rations were formulated to meet (low-grain and fat rations) or exceed (high-grain ration) daily energy requirements. Each ration was fed to horses in a crossover design for 3 weeks. Horses were exercised on a treadmill Monday through Friday; maximum speed on Monday and Friday was 11 m/s (6% slope), on Tuesday and Thursday was 9 m/s, and on Wednesday was 4.5 m/s. Plasma CK activity and lactate concentration were determined before and after exercise. RESULTS: Horses with RER fed the high-grain ration had significantly greater CK activity and change in CK activity 4 hours after exercise, compared with those fed the low-grain ration. Horses with RER exercised at the trot or canter had significantly greater increases in CK activity, compared with those exercised at the gallop. Plasma lactate concentrations after exercise were similar in control and affected horses. Lactate concentration and CK activity were not correlated in horses with RER. CONCLUSIONS AND CLINICAL RELEVANCE: Rations high in grain and formulated to exceed daily energy requirements may increase episodes of rhabdomyolysis in thoroughbred horses susceptible to RER.

Animal Feed↗

Incorporating knowledge into commercially available systems.

The ways in which a potential commercial 'user' treats different knowledge types are explored in this paper. The issues are dealt with by the pragmatism with which a marketing manager might evaluate an opportunity. Academics are typically motivated by drivers that are different from a commercial 'push'. Thus partnership is needed for a productive compromise; addressing questions such as why should academic institutions let commercial organizations have their intellectual capital. The paper considers issues of hand-over, product maintenance and a continued development partnership, especially in a volatile [Inter] net-based age.

Commerce↗

"Special steps": an effective visiting/walking program for persons with cognitive impairment.

A program for elderly persons with cognitive impairment and their caregivers was evaluated for its effectiveness and efficiency with regard to caregiver burden, sense of coherence, satisfaction, and cost to the health-care system. The program consisted of a weekly 2-hour visit and walk by volunteers. During a 9-month period in 1997, all eligible referrals were randomly assigned to receive the service immediately (experimental group) or be placed on a waiting list to receive it 6 weeks later (control group). Eleven caregivers/recipients formed the experimental group; 10 caregivers/recipients formed the control group. All completed questionnaires at randomization and at 6-week follow-up. Perceived burden decreased by 8% only for the caregivers in the experimental group (F = 6.8, p = .02). They indicated that they appreciated the respite and support and that the care recipient enjoyed the visit/walk. Although this study was short in duration and small in sample size, improvements were noted in perceived caregiver burden and caregivers expressed satisfaction with the program. The program did not result in additional health and social-service expenditures.

Adult↗

Age-associated neuronal atrophy occurs in the primate brain and is reversible by growth factor gene therapy.

The effects of normal aging on the primate brain are incompletely understood. Although both human and nonhuman primates demonstrate clear functional declines in selective attention, "executive" functions, and some components of declarative memory with aging, most studies have failed to demonstrate extensive neuronal atrophy or loss as a substrate for these degenerative changes in primates. In particular, extensive age-related neuronal loss in memory-related brain regions such as the hippocampus and entorhinal cortex has not been found. However, it is possible that neuronal loss or atrophy might occur in subcortical nuclei that modulate the activity of neocortical regions, thereby accounting for altered cognitive function with aging. In the present study, we describe, to our knowledge for the first time, a significant and extensive decline in the number and size of immunolabeled neurons in subcortical cholinergic basal forebrain regions of aged rhesus monkeys, the best animal model of human aging, by using stereological methods. Notably, the loss of subcortical cholinergic neuronal markers in aged monkeys was nearly completely reversed by human nerve growth factor gene delivery. These findings (i) identify reversible cellular atrophy as a potential mechanism contributing to age-related cognitive decline in primates, (ii) suggest, when considered with other studies, that subcortical brain regions exhibit greater vulnerability to the effects of aging than cortical regions, and (iii) indicate that neurotrophin gene transfer may be an effective means of preventing neuronal atrophy or degeneration in age-related neurodegenerative disorders.

Age Factors↗

Cardiovascular effects of acute and chronic cocaine administration in pregnant and nonpregnant rabbits.

The effects of cocaine administration on cardiovascular parameters were studied in anesthetized nonpregnant and pregnant rabbits with no prior exposure to cocaine and in pregnant rabbits repeatedly administered cocaine (4 mg/kg, bid, iv) for 15-20 days prior to the experiment. Rabbits were instrumented to determine the effects of cocaine on blood pressure, heart rate, and organ blood flows. Administration of the 1 and 2 mg/kg doses of cocaine increased blood pressure and decreased heart rate in both pregnant and nonpregnant rabbits. In contrast, the 4 mg/kg dose of cocaine caused reductions in both blood pressure and heart rate. Cocaine (1, 2, and 4 mg/kg, iv) also caused dose-dependent reductions in organ blood flows. Interestingly, cocaine did not affect uterine blood flow in the nonpregnant rabbits, whereas uterine and placental flows were markedly reduced in both groups of pregnant rabbits. Chronic treatment with cocaine caused a significant increase in the basal blood flow to the placenta and spleen, and a more precipitous decrease in blood flow in both organs in response to an acute injection of cocaine. The chronically treated rabbits also had a greater incidence of cardiac arrhythmias in response to an acute injection of cocaine (4 mg/kg, iv). Rabbits that received repeated administrations of cocaine experienced more prolonged reductions in blood flow than rabbits with no prior exposure to cocaine. These studies show that cocaine has marked effects on organ blood flows and that pregnancy and repeated prior administrations of cocaine can enhance these effects.

Animals↗