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Biomedical subjects

D H Ryan

Publications and source records attributed to D H Ryan.

At least 19 recordsLinked to original sources
PubMed2006

Prediction of response to sibutramine therapy in obese non-diabetic and diabetic patients.

BACKGROUND: Early weight loss is generally considered to predict long-term weight outcome in obese patients, and this is reflected in prescribing guidelines for antiobesity drugs. For example, the current prescribing guidelines for the antiobesity drug, sibutramine, indicate that if patients have not lost 2 kg (or 4 lb) in the first 4 weeks of treatment with sibutramine 10 mg, the physician should re-evaluate the therapy, which may result in increasing the dose to 15 mg or discontinuation. This regimen may deny treatment to a large group of patients who might otherwise benefit, particularly patients with type 2 diabetes who often find it more difficult to lose weight than non-diabetic obese individuals. MATERIALS: We have re-analysed pooled data from seven randomized, controlled studies of sibutramine-induced weight loss and maintenance in which patients (n = 928; 75% female) had taken sibutramine 10 or 15 mg continuously for 12 months, in order to determine the predictors of success in weight loss (defined as loss of at least 5% of initial body weight at Month 12) in both diabetic and non-diabetic patients. Sensitivity and specificity analyses were used to calculate optimal predictive values. RESULTS: In both diabetic and non-diabetic patients, weight loss of 4 kg at 3 months was identified as the optimal predictor for achieving at least 5% weight loss at 12 months. This target was associated with the best average values for sensitivity, specificity and accuracy, as well as high positive (78% vs. 84% for non-diabetics and 76% vs. 85% for diabetics, compared to existing guidelines target of 2 kg after 1 month treatment) and negative predictive values (63% vs. 71% for non-diabetics; 52% vs. 70% for diabetics). CONCLUSION: Sibutramine, in conjunction with diet and exercise, should be continued for at least 3 months (providing there are no adverse effects) to determine whether or not patients are likely to achieve a clinically valid outcome at 1 year. This highlights the need to ensure that regulatory restrictions reflect the needs of clinical practice.

Adult↗
PubMed2003

Field and temperature induced magnetic transition in Gd5Sn4: a giant magnetocaloric material.

Gd5Sn4 exhibits a giant magnetocaloric effect comparable to that reported in the Gd5(Si,Ge)(4) system. The giant magnetocaloric effect is associated with a first-order change that occurs at approximately 82 K in zero field, and can be reversed by the application of an external field of a few Tesla. 119Sn Mössbauer spectroscopy shows that this material is magnetically inhomogeneous over a wide range of temperatures and fields.

Journal Article↗
PubMed2002

The relation of gender, race and socioeconomic status to obesity and obesity comorbidities in a sample of US adults.

OBJECTIVE: To examine the obesity-related chronic diseases in the US adult population according to gender, race and socioeconomic status. METHODS: Data from the 1994-1996 Continuing Survey of Food Intakes by Individuals (1994-1996 CSFII) conducted by the US Department of Agriculture/Agricultural Research Service (USDA/ARS) were used in the analysis. Relevant data included self-reported weight and height, self-reported physician-diagnosed diabetes mellitus, hypertension, heart disease and high serum cholesterol. Analysis was conducted according to gender, race, income level and education level. RESULTS: There was a graded increase in diabetes, hypertension and high serum cholesterol with increasing body weight in nearly all gender, racial and socioeconomic groups. Among the obese individuals, the prevalence of hypertension was higher in black subjects and the prevalence of diabetes, hypertension and heart disease was higher in individuals with lower education compared to their counterparts. The odds of having diabetes, hypertension, heart disease and high serum cholesterol increased with increasing body weight after adjusting for age, gender, race, income, education and smoking. CONCLUSION: Although cross-sectional in nature, our results suggest that the disease burden associated with obesity in the population may be substantial. This burden increases with increasing severity of obesity. Our findings support the current opinion that, although the nature of obesity-related health risks is similar in all populations, the specific level of risk associated with a given level of obesity may be different depending on gender, race and socioeconomic condition.

Adolescent↗
PubMed2001

Spin dynamics in a frustrated magnet.

180 degrees spin flips have been identified as the dominant fluctuation mechanism at the transverse spin freezing transition in partially frustrated a-Fe92Zr8. The form of the selective excitation double Mössbauer spectra, coupled with the perfect agreement with zero-field muon spin relaxation data, eliminates other relaxation forms.

Journal Article↗
PubMed2001

Overexpression of agouti protein and stress responsiveness in mice.

Ectopic overexpression of agouti protein, an endogenous antagonist of melanocortin receptors' linked to the beta-actin promoter (BAPa) in mice, produces a phenotype of yellow coat color, Type II diabetes, obesity and increased somatic growth. Spontaneous overexpression of agouti increases stress-induced weight loss. In these experiments, other aspects of stress responsiveness were tested in 12-week-old male wild-type mice and BAPa mice. Two hours of restraint on three consecutive days produced greater increases in corticosterone and post-stress weight loss in BAPa than wild-type mice. In Experiment 2, anxiety-type behavior was measured immediately after 12 min of restraint. This mild stress did not produce many changes indicative of anxiety, but BAPa mice spent more time in the dark side of a light-dark box and less time in the open arms of an elevated plus maze than restrained wild-type mice. In a defensive withdrawal test, grooming was increased by restraint in all mice, but the duration of each event was substantially shorter in BAPa mice, possibly due to direct antagonism of the MC4-R by agouti protein. Thus, BAPa mice showed exaggerated endocrine and energetic responses to restraint stress with small differences in anxiety-type behavior compared with wild-type mice. These results are consistent with observations in other transgenic mice in which the melanocortin system is disrupted, but contrast with reports that acute blockade of central melanocortin receptors inhibits stress-induced hypophagia. Thus, the increased stress responsiveness in BAPa mice may be a developmental compensation for chronic inhibition of melanocortin receptors.

Adrenocorticotropic Hormone↗
PubMed2001

Short-term dietary energy restriction reduces lean body mass but not performance in physically active men and women.

We studied the effect of moderate, short-term energy restriction on physical performance in physically fit men (n = 13) and women (n = 11) in a controlled clinical research setting with a metabolic kitchen, exercise testing laboratory and training facility. The experiment consisted of a 10 d baseline period followed by either 2 wk of dietary energy restriction (750 kcal/d; n = 16) or energy balance (control; n = 8). During this 24 day study, exercise energy expenditure averaged 465 +/- 5.7 kcal/d in all subjects and was accomplished through treadmill running at a self-selected pace. Body weight was maintained in the control group (-0.36 +/- 0.24kg), but energy restriction resulted in weight loss of -1.29 +/- 0.16 kg (p < 0.001). There was a trend for lean body mass to decline more in the energy restriction group (p = 0.093), accounting for 61% of the weight loss, and urinary nitrogen excretion also tended to be higher in the energy restriction vs. control group (i.e., 13.2 +/- 1.1 vs. 11.2 +/- 1.0g/d; p = 0.089). Muscle strength (leg & shoulder press; 1 repetition maximum) was maintained or increased during the energy restriction period. Muscle endurance, assessed by leg squats to fatigue, and 5 mile run time improved following two weeks of energy restriction or balance. Anaerobic capacity (Wingate Test) increased slightly in the restriction (+ 368 +/- 219 joules) but declined in the control group 649 +/- 288 joules; p<0.05). We conclude that short-term (2 weeks) moderate energy restriction (approximately 750 kcal/d) results in weight loss but does not impair performance in physically fit young men and women.

Adult↗
PubMed2001

Regulation of inherently autoreactive VH4-34 B cells in the maintenance of human B cell tolerance.

The study of human B cell tolerance has been hampered by difficulties in identifying a sizable population of autoreactive B lymphocytes whose fate could be readily determined. Hypothesizing that B cells expressing intrinsically autoreactive antibodies encoded by the VH4-34 heavy chain gene (VH4-34 cells) represent such a population, we tracked VH4-34 cells in healthy individuals. Here, we show that naive VH4-34 cells are positively selected and mostly restricted to the follicular mantle zone. Subsequently, these cells are largely excluded from the germinal centers and underrepresented in the memory compartment. In healthy donors but not in patients with systemic lupus erythematosus (SLE), these cells are prevented from differentiating into antibody-producing plasma cells. This blockade can be overcome ex vivo using cultures of naive and memory VH4-34 cells in the presence of CD70, IL-2, and IL-10. VH4-34 cells may therefore represent an experimentally useful surrogate for autoantibody transgenes and should prove valuable in studying human B cell tolerance in a physiological, polyclonal environment. Our initial results suggest that both positive and negative selection processes participate in the maintenance of tolerance in autoreactive human B cells at multiple checkpoints throughout B cell differentiation and that at least some censoring mechanisms are faulty in SLE.

B-Lymphocytes↗
PubMed2001

Changes in rat adipocyte and liver glucose metabolism following repeated restraint stress.

Rats exposed to repeated restraint weigh less than controls even 8 weeks after stress. Stress-induced weight loss is lean tissue, but the post-stress difference in weight between control and restrained rats is lean and fat mass. Whole-body glucose clearance is enhanced 1 day after stress, but adipocyte glucose utilization is inhibited and muscle glucose transport is unchanged. The studies described here demonstrated that glucose transport was increased in both restrained and pair-fed rats, but that glycogen synthesis was increased only in restrained rats, which may account for the improved whole-body glucose clearance. Adipocyte glucose transport was inhibited and adipose plasma membrane beta-adrenergic receptor number was increased 1 day post-stress in restrained rats when weight loss was lean tissue, but were not different from control rats 5 days post-stress, when both fat and lean tissue were reduced. Thus, repeated restraint induces reversible changes in adipocyte metabolism that may represent a transition from the catabolic state of stress to a new energetic equilibrium in rats that maintain a reduced body weight for an extended period of time.

Adipocytes↗
PubMed2001

Incorporating new recipes into the Armed Forces Recipe File: determination of acceptability.

As part of a project of decrease fat, cholesterol, and sodium in soldiers' diets, new ethnic and breakfast items were developed and standardized for 100 portions. Acceptability data were collected after initial recipe development, during recipe validation at a collaborating university, and in an actual Army garrison. Acceptability was determined using a nine-point hedonic scale; products rating > or = 6.0 in initial tests were prepared in garrison. Acceptability data were compared among test settings, ethnic categories, and food type. When grouped by ethnic categories, acceptability ratings varied more than when grouped by food type. Ratings varied most between development and validation settings (7.2 vs. 6.6; p < 0.05) and least between validation and actual Army settings (6.6 vs. 6.6; not significant). Because acceptability ratings were similar between the validation site and the Army garrison, future recipe development may continue without additional testing at actual Army garrisons, leading to more timely armed forces recipe file additions.

Adult↗
PubMed2001

Increased dietary fat prevents sleep deprivation-induced immune suppression in rats.

BACKGROUND AND PURPOSE: Fatty acid composition of rodent diets can affect baseline immune function as measured in vitro and in vivo. Stress, in a variety of forms, can also affect immune function. Possible interaction between diet and other stressors has not been fully explored. We examined the interaction between sleep deprivation stress and dietary fatty acid composition in altering lymphocyte responses to mitogen stimulation. METHODS: Rats were fed diets containing various sources of fatty acids, then were subjected to sleep deprivation. Splenocytes were harvested and assayed for responsiveness to various mitogens, using a 72-h proliferation assay. RESULTS: Rats subjected to sleep deprivation experienced significant suppression of in vitro proliferative response to various mitogens. This immune suppression was dependent on duration of sleep deprivation. Feeding sleep deprived rats a diet enriched in fatty acids abrogated the effect of sleep deprivation. CONCLUSIONS: The fat content of rodent diets can have a marked effect on baseline and stress-modulated immune responses.

Animals↗
PubMed2000

Superparamagnetic spin dynamics studied using selective excitation double Mössbauer spectroscopy.

A detailed study of spin dynamics in a 6 nm Fe3O4 ferrofluid using a substantially improved selective excitation double Mossbauer (SEDM) experimental technique has led to the unambiguous separation of static disorder, collective excitations, and moment reversals. Superparamagnetic spin flips have been observed through the appearance of an additional line in the SEDM spectrum, defining the energy transitions during relaxation, with frequencies of 2.5+/-0.3 MHz at 70 K to 9.7+/-1.0 MHz at 110 K. SEDM offers a precise window into the dynamics and blocking behavior of fine particle systems.

Journal Article↗
PubMed2000

Magnetic nanostructured composites using alginates of different M/G ratios as polymeric matrix.

Alginate extracted from Sargassum fluitans and Macrocystis pyrifera with different molecular weights and mannuronic/guluronic ratios, M/G, were used as gel matrixes in order to obtain magnetic nanostructured composites. Magnetic nanocrystalline particles of iron oxides were formed inside the alginate matrix by in situ alkaline oxidation of ferrous ions. The magnetic materials obtained were subjected to several oxidative cycles and the increment in iron content was determined after each cycle. X-ray diffraction, magnetometry and Mössbauer spectroscopy were used to examine the materials. The high magnetic response, the absence of hysteresis, and the centered paramagnetic doublet in the Mössbauer spectra indicate the presence of nanocrystalline particles with a superparamagnetic behavior. X-ray diffractograms show peaks that correspond to maghemite. After the first cycle, Sargassum had four times the magnetic response of Macrocystis, which had more than twice the M/G ratio.

Alginates↗
PubMed2000

Neuroleptic malignant syndrome after venlafaxine.

A patient developed neuroleptic malignant syndrome after a single dose of venlafaxine with trifluoperazine treatment. A dopamine-inhibition effect induced by one dose of venlafaxine may have augmented dopamine-receptor inhibition by trifluoperazine.

Adult↗
PubMed2000

Identification of urocortin mRNA antisense transcripts in rat tissue.

Urocortin (UCN) has 45% sequence homology with corticotropin releasing factor (CRF) and binds to CRF receptors. We used reverse-transcriptase-polymerase chain reaction to demonstrate the presence of UCN RNA in various brain regions and in peripheral tissues. Ribonuclease protection assay (RPA) using sense and antisense riboprobes demonstrated the presence of a naturally occurring antisense UCN RNA transcript in a number of tissues. Northern blot indicated that the antisense transcript was the same size as sense UCN. RPA, using probes that covered bases 1 to 560 of 579 bp sequence of rat UCN, indicated that the antisense sequence was complementary to sense UCN but did not contain an open reading frame. Sense and antisense UCN RNA were co-expressed in all tissues that contained levels of either transcript detectable by RPA. Sense RNA expression was greater than antisense in the midbrain, the two transcripts were expressed equally in the hypothalamus and antisense was expressed at higher levels than sense in the liver, heart, and skeletal muscle. Antisense RNA expression was stress responsive, suggesting that it may play a role in regulating transcription or translation of UCN mRNA.

Animals↗
PubMed2000

Common apolipoprotein A-IV variants are associated with differences in body mass index levels and percentage body fat.

OBJECTIVE: To determine the relationship between two common apoA-IV variants (Thr347-->Ser; Gln360-->His), and body mass index (BMI) and percentage body fat. DESIGN: Cross-sectional study. SUBJECTS: Eight-hundred and forty-eight subjects screened for participation in ongoing clinical studies. MEASUREMENTS: ApoA-IV genotype, body mass index, waist-to-hip ratio and percentage body fat by bioelectric impedance. RESULTS: Participants had an average age of 41+/-12 y and an average BMI of 28.2+/-5.5 kg/m2. Individuals homozygous for the Ser347 allele had higher BMI (32.3+/-6.6 vs 28.6+/-5.3 kg/m2; P<0.01) and percentage body fat (36.9+/-7.8 vs 31.0+/-9.6%; P<0.05) compared with individuals homozygous for Thr347. In contrast, the presence of at least one copy of the His360 allele was associated with lower BMI (27.2+/-5.0 vs 28.4+/-5.6 kg/m2; P<0.05) and percentage body fat (28.6+/-8.2 vs 30.7+/-9.1%; P<0.05). The genotype effects persisted after normalization of the data for the potential confounding effects of gender, age and race. When grouped by BMI percentile, the frequency of the Ser347/Ser347 genotype increased while the frequency of the His360 allele decreased with increasing BMI. CONCLUSIONS: These data suggest a role for apoA-IV in fat storage or mobilization and that genetic variations in the apoA-IV gene may play a role in the development of obesity.

Adipose Tissue↗
PubMed2000

Recent progress in obesity pharmacotherapy.

Interest in obesity pharmacotherapy is intense, sparked by the public health threat of increases in obesity rates, as well as by increased knowledge of the biology underlying food intake and energy balance. After a hiatus of more than 20 years, three new medications approved by the US Food and Drug Administration for obesity treatment recently reached the marketplace. One of these, dexfenfluramine, has been withdrawn because of fenfluramine's and its isomer's association with valvular regurgitation. Sibutramine, a centrally acting reuptake inhibitor of monoamines, and orlistat, a pancreatic lipase inhibitor, have been approved for long-term obesity treatment. This review covers recent publications documenting clinical trial experience with these two agents and updates the evidence associating dexfenfluramine and fenfluramine with valvulopathy. As obesity rates increase throughout the world and as knowledge expands regarding the biology of obesity, an expansion of pharmacologic options for obesity treatment is certain.

Journal Article↗
PubMed2000

Clinical evaluation of the overweight patient.

Evaluation of an overweight patient is the first step in any therapeutic program. The syndromes of obesity can be classified in several ways. The first is an anatomic classification based on the size, number, and distribution of fat cells and fat tissue. The second is an etiologic classification based on identification of specific diseases and settings that produce obesity. Hypothalamic injury and endocrine disease such as Cushing's disease and the polycystic ovary syndrome are three identifiable causes of obesity. In this medicated society drugs are always candidates to produce weight gain. The most common causes, however, are stopping smoking, overconsumption of high-fat foods, a decrease in the level of activity, and aging. The natural history of obesity provides a useful framework in which to view both preventive and therapeutic strategies. Some individuals will never become overweight, but of those who do, about one-third will do so during the first two decades, and the remaining two-thirds will become overweight after age 20. A number of epidemiological and metabolic factors can serve as a guide to those individuals who are at high risk. Having overweight parents tops the list, but multiple births, cessation of smoking, and a sedentary lifestyle are additional factors. Therapeutic decisions should be based on risk-benefit decisions. The risk can be assessed from the body mass index, the distribution of fat in upper or lower body obesity, the rate of weight gain, and the degree of physical inactivity. After assessing risk, the therapeutic choices can be selected from the age category of the patient. With any therapeutic activity, involvement of the patient in a realistic approach to the treatment process is essential.

Adipose Tissue↗