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Biomedical subjects

C M Ryan

Publications and source records attributed to C M Ryan.

At least 19 recordsLinked to original sources

Effect of continuous positive airway pressure on ventricular ectopy in heart failure patients with obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) elicits a number of cardiovascular perturbations that could lead acutely or chronically to increased ventricular ectopy in patients with heart failure (HF). We tested the hypothesis that treatment of OSA with continuous positive airway pressure (CPAP) in patients with HF would reduce the frequency of ventricular premature beats (VPBs) during sleep in association with reduced sympathetic nervous system activity. METHODS: Following optimisation of medical treatment, 18 HF patients with OSA and >10 VPBs per hour of sleep were randomised to a control group (n = 8) or a treatment group who received CPAP (n = 10). The frequency of VPBs and urinary norepinephrine (noradrenaline) concentrations during total sleep time were determined at baseline and after 1 month. RESULTS: Control patients did not experience any significant changes in apnoea-hypopnoea index (AHI), mean nocturnal O(2) saturation, or the frequency of VPBs. In contrast, there was a significant reduction in AHI (p<0.001), an increase in minimum O(2) saturation (p = 0.05), a reduction in urinary norepinephrine concentrations (p = 0.009), and a 58% reduction in the frequency of VPBs during total sleep (from mean (SE) 170 (65) to 70 (28) per hour, p = 0.011) after 1 month of CPAP treatment. CONCLUSIONS: In patients with HF, treatment of co-existing OSA by CPAP reduces the frequency of VPBs during sleep. These data suggest that reductions in VPBs and other ventricular arrhythmias through treatment of OSA might improve the prognosis in patients with HF.

Arrhythmias, Cardiac↗

Changes in cognitive function after neuronal cell transplantation for basal ganglia stroke.

Reported is the change in cognitive function after neuronal cell transplantation as a treatment for basal ganglia stroke. Nine subjects (two controls, seven transplants), all over 2 years post stroke, completed a comprehensive neuropsychological test battery prior to and 6 months after treatment. Four transplanted subjects who had strokes in the nondominant hemisphere showed marked improvement on the Rey Complex Figure, a test of visuospatial/constructional ability and nonverbal memory.

Aged↗

BDNF and COMT polymorphisms: relation to memory phenotypes in young adults with childhood-onset mood disorder.

Recent investigations in several species have suggested a role for brain-derived neurotrophic factor (BDNF) in memory, which may be mediated by the influence of BDNF on neuronal plasticity in the hippocampus. BDNF polymorphisms have also been associated with mood disorders. Catechol-O-methyltransferase (COMT) metabolizes dopamine and has been implicated in prefrontal function, another area of the brain relevant for memory. In a sample of 63 young adults with a history of childhood-onset mood disorder, we typed three BDNF polymorphisms, including the BDNF Val66Met single nucleotide polymorphism (SNP), and the COMT Val108/158Met SNP. Multivariate analysis of variance was used to test the association between BDNF and COMT markers and measures of declarative memory. Variants at the three BDNF markers and one COMT marker were not associated with declarative memory function p-values ranged from 0.25 to 0.98. Higher IQ (F = 6.18, df = 4, 58, p = 0.0003) and female gender (F = 4.41, df = 4, 58, p = 0.0035) were associated with more optimal performance on the memory tasks. This study did not provide evidence supporting an association between BDNF and COMT genes and declarative memory phenotypes.

Adolescent↗

Effects of dry cow grouping strategy and prepartum body condition score on performance and health of transition dairy cows.

Multiparous Holstein cows (n = 337) on two commercial dairy farms were used to determine the effects of feeding a close-up diet for 21 (treatment S) or 60 d (treatment L). Milk yield was not affected by treatment; however, cows fed treatment S tended to have increased yields of fat, 3.5% fat-corrected milk, and protein during the first 5 mo of their subsequent lactation compared to treatment L. Cows fed treatment L gained more body condition score (BCS) during the dry period and had longer days to first service. As a secondary objective, relationships of BCS at dry off and subsequent performance were evaluated. Cows with initial BCS < or =3.0 (thinner) tended to produce more milk during early lactation than cows with initial BCS > or = 3.25 (fatter). A trend for an interaction of treatment and initial BCS existed for milk yield such that thinner cows fed treatment S produced the most milk and fatter cows fed treatment S produced the least amount of milk; cows fed treatment L regardless of BCS produced an intermediate amount of milk. Subsequent reproductive performance was similar among thinner and fatter cows. These data indicate that 2 group nutritional strategies for dry cows are preferred, and BCS at dry off should be considered when determining grouping and nutritional strategies for dry cows. Furthermore, moderately thin cows at dry off do not have impaired performance during their subsequent lactation compared to cows of greater BCS.

Animal Nutritional Physiological Phenomena↗

Cognitive efficiency declines over time in adults with Type 1 diabetes: effects of micro- and macrovascular complications.

AIMS/HYPOTHESIS: Mild cognitive dysfunction is not uncommon in adults with Type 1 diabetes, but its pathogenesis remains unclear. Previous cross-sectional studies had suggested that microangiopathy might affect brain integrity and lead to "central neuropathy." To assess the relationship between changes in cognitive performance and the incidence of new micro- and macrovascular complications, 103 young and middle-aged adults (mean age: 40 yrs) with childhood-onset Type 1 diabetes were followed over a 7-year period, and were compared to 57 demographically-similar adults without diabetes. METHODS: All subjects completed a comprehensive battery of neurocognitive tests on two occasions. Diabetic subjects also received repeated medical assessments to diagnose the onset of clinically significant complications. RESULTS: Relative to control subjects, diabetic adults showed significant declines on measures of psychomotor efficiency; no between-group differences were evident on learning, memory, or problem-solving tasks. The development of proliferative retinopathy and autonomic neuropathy during the follow-up period predicted decline in psychomotor speed (p<0.01), as did incident macrovascular complications (p<0.05), systolic blood pressure at follow-up (p<0.01), and duration of diabetes (p<0.01). CONCLUSION/INTERPRETATION: This study shows that cognitive efficiency may decline over time in diabetic adults, and that this neurocognitive change may be linked, at least in part, to the occurrence of complications like proliferative retinopathy and elevated blood pressure. Therapeutic interventions that reduce the risk of vascular complications may have a similarly beneficial effect on the brain and reduce the risk of neurocognitive dysfunction in diabetic patients.

Adult↗

Phosphorus feeding levels and critical control points on dairy farms.

A viable and cost-effective approach to managing P on dairy farms is to minimize excess P in diets, which in turn leads to less excretion of P in manure without impairing animal performance. A questionnaire survey was conducted, coupled with on-site feed and fecal sample collection and analysis on dairy farms in New York, Pennsylvania, Delaware, Maryland, and Virginia. The purpose was to assess dietary P levels and to identify critical control points pertaining to P feeding management. Survey responses, 612 out of 2500 randomly selected farms, revealed a wide range of dietary P concentrations for lactating cows, from 3.6 to 7.0 g/kg of feed DM. The mean was 4.4 g/kg, which was 34% above the level recommended by the NRC for 27.9 kg milk/d, the mean milk yield in the survey. Higher P concentrations in diets were not associated with higher milk yields (n = 98, R2 = 0.057 for the survey farms; n = 92, R2 = 0.043 for farms selected for on-site sampling). However, higher dietary P led to higher P excretion in feces (n = 75, R2 = 0.429), with much of the increased fecal P being water soluble. Phosphorus concentrations in diet samples matched closely with P concentrations in formulated rations, with 67% of the feed samples deviating <10% from the formulations. On 84% of the survey farms, ration formulation was provided by professionals rather than producers themselves. Most producers were feeding more P than cows needed because it was recommended in the rations by these consultants. In conclusion, P fed to lactating cows averaged 34% above NRC recommendations; to reduce excess dietary P, ration formulation is the critical control point.

Animal Feed↗

Severe hypokalemia as a cause of acute transient paraplegia following electrical shock.

Transient lower extremity paralysis has been previously reported following high voltage electrical injury. The following case report describes an unusual presentation of transient acute flaccid lower extremity paralysis following a high voltage electrical injury associated with profound hypokalemia and acid/base abnormalities similar to the periodic paralysis syndrome. The patient's symptoms resolved with correction of severe hypokalemia. Potential mechanisms for a metabolic neuromuscular disorder induced by electrical injury are proposed.

Adult↗

CD18 dependency of transendothelial neutrophil migration differs during acute pulmonary inflammation.

Neutrophil extravasation during inflammation can occur either by a mechanism that requires the neutrophil integrin complex, CD18, or by an alternative CD18-independent route. Which of the two pathways is used has been shown to depend on the site and nature of the inflammatory insult. More recent evidence suggests that selection may also depend on whether inflammation is chronic or acute, but why this is the case remains unknown. Using an in vitro model that supports both migratory mechanisms, we examined the CD18 dependency of migration of neutrophils isolated from patients with either chronic or acute pulmonary infection. Chronic neutrophils were found to behave like normal neutrophils by migrating to IL-8 and leukotriene B(4) using the CD18-independent pathway, but to the bacterial product, FMLP, using the CD18-dependent route. In contrast, migration of acute neutrophils to all of these stimuli was CD18 dependent. Normal neutrophils could be manipulated to resemble acute neutrophils by exposing them to FMLP before migration, which resulted in a "switch" from the CD18-independent to -dependent mechanism during migration to IL-8 or leukotriene B(4). Although treatment of normal neutrophils with FMLP caused selective down-regulation of the IL-8 receptor, CXCR2, and acute neutrophils were found to have less CXCR2 than normal, a functional relationship between decreased CXCR2 and selection of CD18-dependent migration was not demonstrated. Results indicate that selection of the CD18-dependent or -independent migration mechanism can be controlled by the neutrophil and suggest that the altered CD18 requirements of acute neutrophils may be due to priming in the circulation during acute infection.

Acute Disease↗

Cognitive function and reproductive hormones in adjuvant therapy for breast cancer: a critical review.

Deterioration in cognitive function-particularly learning, memory, and attention-has been reported by women with breast cancer who receive adjuvant chemotherapy. Deficits in cognitive function reported by women with breast cancer are similar to those experienced by women as a consequence of natural or surgical menopause. The basis of these deteriorations may include reductions in reproductive hormone levels, particularly estrogens and progesterones, that occur as a result of adjuvant chemotherapy. This paper critically examines the literature related to the impact of adjuvant chemotherapy and reproductive hormone changes on cognitive function in women with breast cancer and suggests direction for future research in this area. The paper proposes a framework for investigation of the problem and discusses the challenges associated with the conduct of this research.

Antineoplastic Agents↗

Prenatal tobacco effects on neuropsychological outcomes among preadolescents.

This study evaluated the relationships between maternal smoking during pregnancy and 10-year-old children's performance on measures of learning, memory, and problem-solving. In this prospective cohort study, mothers were recruited from an urban prenatal clinic in 1982 and 1983 and observed from their fourth prenatal month until the time of the study. At the 10-year visit, 593 children and mothers were evaluated. The prevalence of tobacco use was high in this cohort: 54.3%, 53.3%, and 60% of the women smoked in the first trimester, third trimester, and 10-year assessment, respectively. After controlling statistically for other prenatal substance use, current tobacco, other substance use variables, and multiple sociodemographic covariates, prenatal tobacco exposure was significantly associated with deficits in learning and memory. Specifically, prenatal tobacco exposure was associated with deficits in verbal learning and design memory, as well as slowed responding on a test of eye-hand coordination. In addition, these children demonstrated a reduced ability for flexible problem solving and more impulsivity, as indicated by an increase in perseverative responses on a card-sorting test. Prenatally exposed children did not show attention deficits or increased activity on a continuous performance test.

Adult↗

Arginine and ornithine kinetics in severely burned patients: increased rate of arginine disposal.

Arginine serves multiple roles in the pathophysiological response to burn injury. Our previous studies in burn patients demonstrated a limited net rate of arginine de novo synthesis despite a significantly increased arginine turnover (flux), suggesting that this amino acid is a conditionally indispensable amino acid after major burns. This study used [15N2-guanidino-5,5-2H2]arginine and [5-13C]ornithine as tracers to assess the rate of arginine disposal via its conversion to and subsequent oxidation of ornithine; [5,5-2H2]proline and [5,5,5-2H3]leucine were also used to assess proline and protein kinetics. Nine severely burned patients were studied during a protein-free fast ("basal" or fast) and total parenteral nutrition (TPN) feedings. Compared with values from healthy volunteers, burn injury significantly increased 1) fluxes of arginine, ornithine, leucine, and proline; 2) arginine-to-ornithine conversion; 3) ornithine oxidation; and 4) arginine oxidation. TPN increased arginine-to-ornithine conversion and proportionally increased irreversible arginine oxidation. The elevated arginine oxidation, with limited net de novo synthesis from its immediate precursors, further implies that arginine is a conditionally indispensable amino acid in severely burned patients receiving TPN.

Adult↗

Memory performance and the apolipoprotein E polymorphism in a community sample of middle-aged adults.

The apolipoprotein E genotype (APOE) is an established risk factor for Alzheimer disease, with the age-at-onset occurring earlier in individuals having at least one APOE epsilon 4 allele, relative to the APOE epsilon 3 or APOE epsilon 2 isoforms. Moreover, nondemented older adults with the APOE epsilon 4 allele also show diminished cognitive performance, particularly on tests of learning and memory, and an accelerated decline in memory performance with increasing age. The current investigation extends the study of the APOE epsilon 4 allele and cognitive performance to healthy, middle-aged adults. A community sample of 220 non-Hispanic Caucasian men and women, aged 24-60 (average age = 46), were genotyped for the APOE polymorphism and completed a battery of neuropsychological tests. Multivariate analyses were conducted on measures of verbal learning and memory (e. g., learning a list of words and recalling them 30 min later), visual memory (e.g., reproducing a previously copied figure from memory), and attention span (e.g., repeating long lists of digits), after adjustments for age, and estimated IQ. Results indicated that performance on learning and memory tasks was significantly poorer in adults having any APOE epsilon 4 allele, relative to adults with APOE epsilon 2 and epsilon 3 genotypes (P <.01). Attention span did not differ by genotype. These findings, the first in a sample of middle-aged adults, suggest that the APOE polymorphism is a marker for age-related decline in memory (detectable prior to overt, clinical manifestations of memory loss), and/or a marker for individual differences in memory ability across the life span. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:707-711, 2000.

Adult↗

Long-term outcome of children surviving massive burns.

CONTEXT: Major advances in treatment of burn injuries in the last 20 years have made it possible to save the lives of children with massive burns, but whether their survival comes at the cost of impaired quality of life is unknown. OBJECTIVE: To investigate the long-term quality of life in children who have survived massive burns. DESIGN AND SETTING: Retrospective, cross-sectional study conducted in a regional pediatric burn center. PATIENTS: Eighty subjects who were younger than 18 years at the time of injury, who survived massive burns involving > or =70% of the body surface, and who were admitted to the burn center between 1969 and 1992 were evaluated an average (SD) of 14.7 (6.0) years after injury. MAIN OUTCOME MEASURES: Short Form 36 (SF-36) scores of the 60 patients aged at least 14 years were compared with national norms and the impact of clinical variables on individual domain scores was assessed. RESULTS: The SF-36 domain scores of the study patients, who had survived massive burns at a mean (SD) age of 8.8 (5.5) years, were generally similar to the normal population). However, 15% and 20% of the burn patients had scores in the physical functioning and physical role domains, respectively, that were more than 2 SDs below the relevant norm, indicating that a few patients had continuing serious physical disability. Better functional status of the family predicted a higher score in physical role (P = .04). The child's early reintegration with preburn activities predicted higher scores in general health (P = .03), physical functioning (P = .003), and physical role (P = .01). Children followed up consistently in the multidisciplinary burn clinic for 2 years had higher physical functioning (P = .04). CONCLUSIONS: In this study, while some children surviving severe burns had lingering physical disability, most had a satisfying quality of life. Comprehensive burn care that included experienced multidisciplinary aftercare played an important role in recovery.

Adult↗

Current expectations for survival in pediatric burns.

BACKGROUND: Conventional wisdom and published reports suggest that children, particularly those younger than 48 months, have higher mortality rates after burns than young adults. However, coincident with refinements in resuscitation, operative techniques, and critical care, survival rates for children with burns seem to have improved. To document this change and to define current expectations, a review of deaths during two 7-year intervals separated by a decade was done. DESIGN: We examined the clinical course of children who died after admission for care of acute thermal burns during two 7-year intervals: calendar years 1974 to 1980 inclusive (group 1) and 1991 to 1997 inclusive (group 2). Dying children were stratified by total body surface area (TBSA) burned: small (0%-39%), midsize (40%-59%), and large (60%-100%) TBSA burns. Children who arrived with anoxic brain injury or in a moribund state with refractory shock were excluded from analysis (4 children in group 1 and 5 in group 2); 2 of these children in group 2 died and became solid organ donors. SETTING: Regional pediatric burn center. PATIENTS: Six hundred seventy-eight children in group 1 and 1150 children in group 2. MAIN OUTCOME MEASURE: Survival. RESULTS: In children with 0% to 39% TBSA burns, mortality was 0.6% in group 1 and 0% in group 2 (Fisher exact test, P = .04; chi2 test, P = .02). In children with 40% to 59% TBSA burns, mortality was 7.7% in group 1 and 0% in group 2 (Fisher exact test, P = .07; chi2 test, P = .047). In children with 60% to 100% TBSA bums, mortality was 33.3% ingroup 1 and 14.3% in group 2 (Fisher exact test, P = .04; chi2 test, P = .02). Although 59% of the children in group 2 were younger than 48 months, including 55% of those with 40% to 59% TBSA burns and 41% of those with 60% to 100% TBSA burns, there were no deaths in this age group. CONCLUSION: Survival rates after burns have improved significantly for children. At present, most children, even young children and children with large burns, should survive.

Adult↗

Effects of lovastatin on cognitive function and psychological well-being.

PURPOSE: Animal research and cross-sectional studies suggest that serum lipid concentrations may influence cognitive function, mood, and behavior, but few clinical trials have studied these effects. SUBJECTS AND METHODS: In this double-blind investigation, 209 generally healthy adults with a serum low-density-lipoprotein (LDL) cholesterol level of 160 mg/dL or higher were randomly assigned to 6-month treatment with lovastatin (20 mg) or placebo. Assessments of neuropsychological performance, depression, hostility, and quality of life were conducted at baseline and at the end of the treatment period. Summary effect sizes were estimated as z scores on a standard deviation (SD) scale. RESULTS: Placebo-treated subjects improved between baseline and posttreatment periods on neuropsychological tests in all five performance domains, consistent with the effects of practice on test performance (all P <0.04), whereas those treated with lovastatin improved only on tests of memory recall (P = 0.03). Comparisons of the changes in performance between placebo- and lovastatin-treated subjects revealed small, but statistically significant, differences for tests of attention (z score = 0.18; 95% confidence interval (CI), 0.06 to 0.31; P = 0.005) and psychomotor speed (z score = 0.17; 95% CI, 0.05 to 0.28; P = 0. 004) that were consistent with greater improvement in the placebo group. Psychological well-being, as measured several ways, was not affected by lovastatin. CONCLUSION: Treatment of hypercholesterolemia with lovastatin did not cause psychological distress or substantially alter cognitive function. Treatment did result in small performance decrements on neuropsychological tests of attention and psychomotor speed, the clinical importance of which is uncertain.

Adult↗

Cutaneous herpetic infections complicating burns.

Many people harbor herpes simplex virus, often with a known history of "cold sores". During the relatively immunosuppressed state associated with a serious burn, recrudescence of such infections can occur. We report four adults and two children who developed severe herpetic ulceration, over the face and neck in five patients and in a partial thickness wound in one patient. Herpetic infection was diagnosed by culture and direct immunofluorescence testing and treatment was immediately instituted with systemic and topical Acylovir(R) (Zovirax, Glaxo Wellcome). Ulceration healed under treatment and did not leave visible scarring in any of the patients. Although these infections are rapidly progressive, they respond to prompt treatment with antiviral chemotherapy. Rapidly progressive vesicles and ulceration appearing on the face or in the wounds of burn patients should prompt immediate evaluation for herpetic infection.

Acyclovir↗

Hypoglycemia: a complication of diabetes therapy in children.

Hypoglycemia is the most common acute complication in insulin-treated type 1 diabetic patients. Most surveys have demonstrated that the tighter the glycemic control, and the younger the patient, the greater the frequency of both mild and severe hypoglycemia. However, people in poor metabolic control, with high glycosylated hemoglobin levels, are not protected from experiencing severe hypoglycemia. Focusing on the pediatric population, we review new or controversial issues surrounding the prevalence of hypoglycemia, its causes, its consequences and preventive strategies, and discuss possible mechanisms underlying the variability of responses to hypoglycemia.

Brain↗