Showing papers by "Wake Forest University published in 1997"
TL;DR: It is determined that the application of controlled subatmospheric pressure creates an environment that promotes wound healing.
Abstract: A series of basic animal studies using a new subatmospheric pressure technique (The V.A.C.) to expedite wound healing are presented. The technique entails placing an open-cell foam into the wound, sealing the site with an adhesive drape, and applying subatmospheric pressure (125 mmHg below ambient)
2,513 citations
TL;DR: A new subatmospheric pressure technique is presented: vacuum-assisted closure, which removes chronic edema, leading to increased localized blood flow, and the applied forces result in the enhanced formation of granulation tissue.
Abstract: Despite numerous advances, chronic and other difficult-to-manage wounds continue to be a treatment challenge. Presented is a new subatmospheric pressure technique: vacuum-assisted closure (The V.A.C.). The V.A.C. technique entails placing an open-cell foam dressing into the wound cavity and applying a controlled subatmospheric pressure (125 mmHg below ambient pressure). Three hundred wounds were treated: 175 chronic wounds, 94 subacute wounds, and 31 acute wounds. Two hundred ninety-six wounds responded favorably to subatmospheric pressure treatment, with an increased rate of granulation tissue formation. Wounds were treated until completely closed, were covered with a split-thickness skin graft, or a flap was rotated into the health, granulating would bed. The technique removes chronic edema, leading to increased localized blood flow, and the applied forces result in the enhanced formation of granulation tissue. Vacuum-assisted closure is an extremely efficacious modality for treating chronic and difficult wounds.
2,459 citations
TL;DR: In this article, the prevalence of aortic sclerosis and stenosis in the elderly and to identify clinical factors associated with degenerative aortric valve disease were determined using stepwise logistic regression analysis.
1,848 citations
TL;DR: The data suggest that exercise should be prescribed as part of the treatment for knee osteoarthritis, and modest improvements in measures of disability, physical performance, and pain from participating in either an aerobic or a resistance exercise program.
Abstract: Objective. —To determine the effects of structured exercise programs on self-reported disability in older adults with knee osteoarthritis. Setting and Degign. —A randomized, single-blind clinical trial lasting 18 months conducted at 2 academic medical centers. Participants. —A total of 439 community-dwelling adults, aged 60 years or older, with radiographically evident knee osteoarthritis, pain, and self-reported physical disability. Invervention. —An aerobic exercise program, a resistance exercise program, and a health education program. Main Outcome Measures. —The primary outcome was self-reported disability score (range, 1-5). The secondary outcomes were knee pain score (range, 1-6), performance measures of physical function, x-ray score, aerobic capacity, and knee muscle strength. Results. —A total of 365 (83%) participants completed the trial. Overall compliance with the exercise prescription was 68% in the aerobic training group and 70% in the resistance training group. Postrandomization, participants in the aerobic exercise group had a 10% lower adjusted mean (±SE) score on the physical disability questionnaire (1.71 ±0.03 vs 1.90±0.04 units; P Conclusions. —Older disabled persons with osteoarthritis of the knee had modest improvements in measures of disability, physical performance, and pain from participating in either an aerobic or a resistance exercise program. These data suggest that exercise should be prescribed as part of the treatment for knee osteoarthritis.
1,272 citations
TL;DR: To define the patient population that might benefit from cartilage grafting, 31,516 knee arthroscopies were reviewed and the majority were articular cartilage lesions; grade III lesions of the patella were the most common and Grade IV lesions were predominantly located on the medial femoral condyle.
Abstract: Although articular cartilage injuries of the knee are common, injured cartilage has a limited ability to heal. Recent data suggest that articular cartilage grafting may provide treatment for these injuries. To define the patient population that might benefit from cartilage grafting, 31,516 knee arthroscopies were reviewed. Between June 1991 and October 1995, 53,569 hyaline cartilage lesions were documented in 19,827 patients. The majority were articular cartilage lesions; grade III lesions of the patella were the most common. Grade IV lesions were predominantly located on the medial femoral condyle. Patients under 40 years of age with grade IV lesions accounted for 5% of all arthroscopies; 74% of these patients had a single chondral lesion (4% of the arthroscopies). No associated ligamentous or meniscal pathology was found in 36.6% of these patients.
1,270 citations
TL;DR: Observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetic action.
Abstract: Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics. The function of GABA(A) and glycine receptors is enhanced by a number of anaesthetics and alcohols, whereas activity of the related GABA rho1 receptor is reduced. We have used this difference in pharmacology to investigate the molecular basis for modulation of these receptors by anaesthetics and alcohols. By using chimaeric receptor constructs, we have identified a region of 45 amino-acid residues that is both necessary and sufficient for the enhancement of receptor function. Within this region, two specific amino-acid residues in transmembrane domains 2 and 3 are critical for allosteric modulation of both GABA(A) and glycine receptors by alcohols and two volatile anaesthetics. These observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetics.
1,236 citations
TL;DR: The results indicate that retrospective techniques have the potential to produce satisfactory results much of the time, but that visual inspection is necessary to guard against large errors.
Abstract: Comparison and evaluation of retrospective intermodality brain image registration techniques
835 citations
TL;DR: In this article, a meta-analytic review was conducted that included all relevant studies with sufficient information for the calculation of effect size, and the overall effect size was 0.25, suggesting that exercise has a small positive effect on cognition.
Abstract: Nearly 200 studies have examined the impact that either acute or long-term exercise has upon cognition. Subsets of these studies have been reviewed using the traditional narrative method, and the common conclusion has been that the results are mixed. Therefore, a more comprehensive review is needed that includes all available studies and that provides a more objective and reproducible review process. Thus, a meta-analytic review was conducted that included all relevant studies with sufficient information for the calculation of effect size (N = 134). The overall effect size was 0.25, suggesting that exercise has a small positive effect on cognition. Examination of the moderator variables indicated that characteristics related to the exercise paradigm, the participants, the cognitive tests, and the quality of the study influence effect size. However, the most important finding was that as experimental rigor decreased, effect size increased. Therefore, more studies need to be conducted that emphasize experimental rigor.
759 citations
TL;DR: Narrative literature reviews can tackle broader and more abstract questions, can engage in more post hoc theorizing without the danger of capitalizing on chance, can make a stronger case for a null-hypothesis conclusion, and can appreciate and use methodological diversity better.
Abstract: Narrative literature reviews serve a vital scientific function, but few resources help people learn to write them. As compared with empirical reports, literature reviews can tackle broader and more abstract questions, can engage in more post hoc theorizing without the danger of capitalizing on chance, can make a stronger case for a null-hypothesis conclusion, and can appreciate and use methodological diversity better. Also, literature reviews can draw any of 4 conclusions: The hypothesis is correct, it has not been conclusively established but is the currently best guess, it is false, or the evidence permits no conclusion. Common mistakes of authors of literature review manuscripts are described. Narrative literature reviews form a vital part of most empirical articles, theses, and grant proposals, and of course many articles and book chapters are devoted specifically to reviewing the literature on a particular topic. Literature reviews serve a scientific field by providing a much-needed bridge between the vast and scattered assortment of articles on a topic and the reader who does not have time or resources to track them down. Reviews also present conclusions of a scope and theoretical level that individual empirical reports cannot normally address. For individual researchers, writing a major literature review article is a very infrequent but often a very important career contribution. Yet, despite the importance of narrative literature reviews, no easy and available way to learn to write them is known. Research methods textbooks do not usually explain how to do them, even though reviewing literature is an important research method. Most graduate seminars in research methods likewise devote little or no time to them. Apprenticeship with an accomplished literature reviewer seems to be one possible strategy to learn this technique, but such specialists are rare, and moreover it is generally considered more important for stu
752 citations
TL;DR: A prospective study finds the 5 region technique of prostate biopsy to be safe, efficacious and superior to the sextant method of biopsy in identifying prostate cancer at an early but significant stage.
725 citations
TL;DR: A genome-wide search in 140 families with ≥2 asthmatic sibs, from three racial groups and report evidence for linkage to six novel regions, including 5p15 (P= 0.0008) and 17p11.1–q11.2 (/> = 0.0015) in African Americans and 11p15 and 19q13 (P =0.0013) in Caucasians and Hispanics.
Abstract: Asthma is an inflammatory airwaysdisease associated with intermittent respiratory symptoms, bronchial hyperresponsiveness (BHR) and reversible airflow obstruction and is phenotypically heterogeneous1,2. Patterns of clustering and segregation analyses in asthma families have suggested a genetic component to asthma3–6. Previous studies reported linkage of BHR and atopy to chromosomes 5q (refs 7–9), 6p (refs 10–12), 11q (refs 13–15), 14q (ref. 16), and 12q (ref. 17) using candidate gene approaches. However, the relative roles of these genes in the pathogenesis of asthma or atopy are difficult to assess outside of the context of a genome-wide search. One genome-wide search in atopic sib pairs has been reported18, however, only 12% of their subjects had asthma. We conducted a genome-wide search in 140 families with ≥2 asthmatic sibs, from three racial groups and report evidence for linkage to six novel regions: 5p15 (P= 0.0008) and 17p11.1–q11.2 (/> = 0.0015) in African Americans; 11p15 (P = 0.0089) and 19q13 (P = 0.0013) in Caucasians; 2q33 (P = 0.0005) and 21q21 (P = 0.0040) in Hispanics. Evidence for linkage was also detected in five regions previously reported to be linked to asthma-associated phenotypes: 5q23–31 (P = 0.0187), 6p21.3–23 (P = 0.0129), 12q14–24.2 (P = 0.0042), 13q21.3–qter (P = 0.0014), and 14q11.2–13 (P = 0.0062) in Caucasians and 12q14–24.2 (P = 0.0260) in Hispanics.
TL;DR: The accumulating evidence suggests that Ang-(1-7) may oppose the actions of Ang II either directly or by stimulation of prostaglandins and nitric oxide, which may explain the effective antihypertensive action of converting enzyme inhibitors in a variety of non-renin-dependent models of experimental and genetic hypertension as well as most forms of human hypertension.
Abstract: Angiotensin (Ang)-(1-7) is a bioactive component of the renin-angiotensin system that is formed endogenously from either Ang I or Ang II. The first actions described for Ang-(1-7) indicated that the peptide mimicked some of the effects of Ang II, including the release of prostanoids and vasopressin. However, Ang-(1-7) is devoid of vasoconstrictor, central pressor, or thirst-stimulating actions. In fact, new findings reveal depressor, vasodilator, and antihypertensive actions that may be more apparent in hypertensive animals or humans. Thus, the accumulating evidence suggests that Ang-(1-7) may oppose the actions of Ang II either directly or by stimulation of prostaglandins and nitric oxide. These observations are significant because they may explain the effective antihypertensive action of converting enzyme inhibitors in a variety of non–renin-dependent models of experimental and genetic hypertension as well as most forms of human hypertension. In this context, studies in humans and animals showe...
University of Tennessee Health Science Center1, University of Cincinnati2, University of Oklahoma3, University of Alabama at Birmingham4, George Washington University5, University of Southern California6, Wake Forest University7, University of Chicago8, Ohio State University9, Medical University of South Carolina10, Wayne State University11, University of Colorado Denver12, University of Pittsburgh13, National Institutes of Health14
TL;DR: It is recommended that women with expectantly managed PPROM remote from term receive antibiotics to reduce infant morbidity, and among GBS-negative women, significant pregnancy prolongation was seen with antibiotics.
Abstract: Context. —Intrauterine infection is thought to be one cause of preterm premature rupture of the membranes (PPROM). Antibiotic therapy has been shown to prolong pregnancy, but the effect on infant morbidity has been inconsistent. Objective. —To determine if antibiotic treatment during expectant management of PPROM will reduce infant morbidity. Design. —Randomized, double-blind, placebo-controlled trial. Setting. —University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Patients. —A total of 614 of 804 eligible gravidas with PPROM between 24 weeks' and 0 days' and 32 weeks' and 0 days' gestation who were considered candidates for pregnancy prolongation and had not received corticosteroids for fetal maturation or antibiotic treatment within 1 week of randomization. Intervention. —Interavenous ampicillin (2-g dose every 6 hours) and erythromycin (250-mg dose every 6 hours) for 48 hours followed by oral amoxicillin (250-mg dose every 8 hours) and erythromycin base (333-mg dose every 8 hours) for 5 days vs a matching placebo regimen. Group B streptococcus (GBS) carriers were identified and treated. Tocolysis and corticosteroids were prohibited after randomization. Main Outcome Measures. —The composite primary outcome included pregnancies complicated by at least one of the following: fetal or infant death, respiratory distress, severe intraventricular hemorrhage, stage 2 or 3 necrotizing enterocolitis, or sepsis within 72 hours of birth. These perinatal morbidities were also evaluated individually and pregnancy prolongation was assessed. Results. —In the total study population, the primary outcome (44.1% vs 52.9%;P=.04), respiratory distress (40.5% vs 48.7%;P=.04), and necrotizing enterocolitis (2.3% vs 5.8%;P=.03) were less frequent with antibiotics. In the GBS-negative cohort, the antibiotic group had less frequent primary outcome (44.5% vs 54.5%;P=.03), respiratory distress (40.8% vs 50.6%;P=.03), overall sepsis (8.4% vs 15.6%;P=.01), pneumonia (2.9% vs 7.0%;P=.04), and other morbidities. Among GBS-negative women, significant pregnancy prolongation was seen with antibiotics (P Conclusions. —We recommend that women with expectantly managed PPROM remote from term receive antibiotics to reduce infant morbidity.
TL;DR: Low ABI levels, particularly those of < 0.90, are indicative of generalized atherosclerosis, and are attenuated and often not statistically significant after further adjustment for LDL cholesterol, cigarette smoking, hypertension and diabetes.
TL;DR: It is shown that the magnitude of health effects attributable to caregiving can vary substantially, with the largest negative health effects observed among caregivers who characterize themselves as being strained.
Abstract: We propose that two related sources of variability in studies of caregiving health effects contribute to an inconsistent pattern of findings: the sampling strategy used, and the definition of what constitutes caregiving. Samples are often recruited through selfreferral and are typically comprised of caregivers experiencing considerable distress. In this study, we examine the health effects of caregiving in large population-based samples of spousal caregivers and controls using a wide array of objective and self-report physical and mental health outcome measures. By applying different definitions of caregiving, we show that the magnitude of health effects attributable to caregiving can vary substantially, with the largest negative health effects observed among caregivers who characterize themselves as being strained. From an epidemiological perspective, our data show that approximately 80% of persons living with a spouse with a disability provide care to their spouse, but only half of care providers report mental or physical strain associated with caregiving.
TL;DR: The findings suggest that several cardiovascular disease risk factors play a role in the pathogenesis of WMLs, an elements linked to hypoperfusion and/or fluid accumulation, which presumably lead to W MLs.
Abstract: White matter lesions (WMLs) detected by cerebral magnetic resonance imaging (MRI) are putatively a consequence of cerebral hypoperfusion or ischemia. We investigated the prevalence, severity and correlates of WMLs in a population-based sample of 1,920 African-American and European-American men and women aged 55-72 years, during the second follow-up examination of the Atherosclerosis Risk in Communities Study. The spin density images from 1.5-tesla MRI scans were used to define WMLs using a 0-9 scale with 0 for normal and 9 for most severe WMLs. Age was positively associated with the prevalence (percent) and severity of WMLs. African-Americans had lower overall prevalence of WMLs, but a higher prevalence of relatively more severe WMLs, than European-Americans. After adjusting for age, sex, and ethnicity, WMLs were significantly associated with smoking, lower education, hypertension, systolic blood pressure, and pulse pressure, and weakly associated with diastolic blood pressure. The associations of smoking, alcohol intake, systolic and diastolic blood pressure, pulse, pressure, and hypertension were stronger in African-Americans than in European-Americans (p < 0.15 for interactions by ethnicity). This population-based MRI study documents significant relationships between several cardiovascular disease risk factors and WMLs. The findings suggest that such factors play a role in the pathogenesis of WMLs, an elements linked to hypoperfusion and/or fluid accumulation, which presumably lead to WMLs. African-Americans exhibited both a higher proportion of normal white matter and a higher proportion of relatively more severe WMLs than European-Americans.
TL;DR: It is concluded that oral CEE inhibits the initiation and progression of coronary artery atherosclerosis and that continuously administered oral MPA antagonizes this atheroprotective effect of estrogen or the MPA-associated antagonism.
Abstract: Although estrogen replacement therapy is associated with reduced risk of coronary heart disease and reduced extent of coronary artery atherosclerosis, the effects of combined (estrogen plus progestin) hormone-replacement therapy are uncertain. Some observational data indicate that users of combined hormone replacement consisting of continuously administered oral conjugated equine estrogens (CEE) and oral sequentially administered (7 to 14 days per month) medroxyprogesterone acetate (MPA) experience a reduction in risk similar to that of users of CEE alone. However, the effects of combined, continuously administered CEE plus MPA (a prescribing pattern that has gained favor) on the risk of coronary heart disease or atherosclerosis are not known. We studied the effects of CEE (monkey equivalent of 0.625 mg/d) and MPA (monkey equivalent of 2.5 mg/d), administered separately or in combination, on the extent of coronary artery atherosclerosis (average plaque size) in surgically postmenopausal cynomolgus monkeys fed atherogenic diets and treated with these hormones for 30 months. Treatment with CEE alone resulted in atherosclerosis extent that was reduced 72% relative to untreated (estrogen-deficient) controls (P < .004). Atherosclerosis extent in animals treated with CEE plus MPA or MPA alone did not differ from that of untreated controls. Although treatment had marked effects on plasma lipoprotein patterns, statistical adjustment for variation in plasma lipoproteins did not alter the between-group relationships in atherosclerotic plaque size, suggesting that these factors do not explain substantially the atheroprotective effect of estrogen or the MPA-associated antagonism. Although the mechanism(s) remains unclear, we conclude that oral CEE inhibits the initiation and progression of coronary artery atherosclerosis and that continuously administered oral MPA antagonizes this atheroprotective effect.
TL;DR: Sinusitis, an inflammatory disease of the sinus, is one of the most commonly reported diseases in the United States, affecting an estimated 14% of the population.
Abstract: Sinusitis, an inflammatory disease of the sinus, is one of the most commonly reported diseases in the United States, affecting an estimated 14% of the population. The prevalence of sinusitis is rising. Between 1990 and 1992, persons with sinusitis reported approximately 73 million restricted activity days—an increase from the 50 million restricted activity days reported between 1986 and 1988. Because critical questions remain unanswered about its cause, pathophysiology, and optimal treatment, sinusitis continues to generate significant health care costs and affects the quality of life of a large segment of the U.S. population. To identify critical directions for research on sinus disease, the American Academy of Allergy, Asthma and Immunology and the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc., convened a meeting in January 1996 in collaboration with the National Institutes of Allergy and Infectious Disease. This document summarizes the proceedings of that meeting and presents what is intended to be the background for future investigation of the many unanswered questions related to sinusitis.
TL;DR: The 12-item bone marrow transplant subscale (BMTS) was able to discriminate patients on the basis of performance status rating and also demonstrated sensitivity to change over time, making it an excellent choice for use in BMT clinical trials.
Abstract: We developed a 12-item bone marrow transplant subscale (BMTS) for the general Functional Assessment of Cancer Therapy (FACT) measure. The subscale combined with the FACT, (FACT-BMT) is a 47-item, valid and reliable measure of five dimensions of quality of life in bone marrow transplant patients. The three-step validation process involved the generation and selection of BMT-specific items and the testing of the overall measure. Items were selected from a list produced by seven oncology experts and 15 patients and were designed to assess content not represented in the general FACT items. A total of 182 patients completed the FACT-BMT at baseline, prior to BMT. An analysis measuring sensitivity to change was performed with 74 patients after transplantation and 60 patients over the three time-points of baseline, hospital discharge and 100 days. The FACT-BMT and all subscales were correlated, sensitivity to change was measured, and the internal consistency for each scale was calculated. Coefficients of reliability and validity ranged from 0.86 to 0.89 for the entire FACT-BMT and 0.54 to 0.63 for the BMTS. The BMTS was able to discriminate patients on the basis of performance status rating and also demonstrated sensitivity to change over time. The FACT-BMT has good psychometric properties for use in assessing quality of life in bone marrow transplant patients. The addition of the bone marrow transplant subscale to the general FACT measure makes it an excellent choice for use in BMT clinical trials.
TL;DR: Auditory cortex on the exposed supratemporal plane in four anesthetized rhesus monkeys was mapped electrophysiologically with both pure‐tone (PT) and broad‐band complex sounds, and confirmed the existence of at least three tonotopic areas.
Abstract: Auditory cortex on the exposed supratemporal plane in four anesthetized rhesus monkeys was mapped electrophysiologically with both pure-tone (PT) and broad-band complex sounds. The mapping confirmed the existence of at least three tonotopic areas. Primary auditory cortex, AI, was then aspirated, and the remainder of the cortex on the supratemporal plane was remapped. PT-responses in the caudomedial area, CM, were abolished in all animals but one, in which they were restricted to the high-frequency range. Some CM sites were still responsive to complex stimuli. In contrast to the effects on CM, no significant changes were detectable in the rostral area, R. After mapping cortex in four additional monkeys, injections were made with different tracers into matched best-frequency regions of AI, R, and CM. Injections in AI and R led to retrograde labeling of neurons in all three subdivisions of the medial geniculate (MG) nucleus (MGv, MGd, and MGm), as well as nuclei outside MG, whereas CM injections led to only sparse labeling of neurons in a restricted zone of the lateral MGd and, possibly, MGm, in addition to labeling in non-MG sites. The combined results suggest that MGv sends direct projections in parallel to areas AI and R, which drive PT-responses in both areas. PT-responses in area CM, however, appear to be driven by input relayed serially from AI. The direct input to CM from MGd and other thalamic nuclei may thus be capable of mediating responses only to broad-band sounds.
TL;DR: Although family income has a stronger association with mortality than census tract, area socioeconomic status makes a unique and substantial contribution to mortality and should be explored in health policy and disease prevention research.
Abstract: We linked data from the National Longitudinal Mortality Study to census tract information on 239,187 persons to assess 11-year mortality risk among black and white women and women associated with median census tract income, adjusted for individual family income from the Current Population Survey. We stratified Cox proportional hazards models by ages 25-64 years and 65 years and older. We used a robust covariance matrix to obtain standard errors for the model coefficients that account for correlation among individuals in the same census tract. Both income indicators were independently related to all-cause mortality. Among persons age 25-64 years, the rate ratios (RR) for individual family income and the median census tract income, respectively, for low income relative to high income were RR = 2.10 vs. 1.49 for black men, RR = 2.03 vs 1.26 for white men; and RR = 1.92 vs 1.30 for black women and RR = 1.61 vs 1.16 for white women. Among persons age 65 years or greater, only individual family income was associated with mortality, and only for white men. Although family income has a stronger association with mortality than census tract, our results indicate that, more broadly, area socioeconomic status makes a unique and substantial contribution to mortality and should be explored in health policy and disease prevention research.
TL;DR: It is established that SLC10A2 mutations can cause primary bile acid malabsorption and underscore the ileal Na+/bile acid cotransporter's role in intestinal reclamation of bile acids.
Abstract: Primary bile acid malabsorption (PBAM) is an idiopathic intestinal disorder associated with congenital diarrhea, steatorrhea, interruption of the enterohepatic circulation of bile acids, and reduced plasma cholesterol levels. The molecular basis of PBAM is unknown, and several conflicting mechanisms have been postulated. In this study, we cloned the human ileal Na+/bile acid cotransporter gene (SLC10A2) and employed single-stranded conformation polymorphism analysis to screen for PBAM-associated mutations. Four polymorphisms were identified and sequenced in a family with congenital PBAM. One allele encoded an A171S missense mutation and a mutated donor splice site for exon 3. The other allele encoded two missense mutations at conserved amino acid positions, L243P and T262M. In transfected COS cells, the L243P, T262M, and double mutant (L243P/T262M) did not affect transporter protein expression or trafficking to the plasma membrane; however, transport of taurocholate and other bile acids was abolished. In contrast, the A171S mutation had no effect on taurocholate uptake. The dysfunctional mutations were not detected in 104 unaffected control subjects, whereas the A171S was present in 28% of that population. These findings establish that SLC10A2 mutations can cause PBAM and underscore the ileal Na+/bile acid cotransporter's role in intestinal reclamation of bile acids.
TL;DR: The prevalence of self reported sleep disturbances in older men and women and their relationships with health status and cardiovascular diseases (CVD) are described.
Abstract: OBJECTIVES: To describe the prevalence of self reported sleep disturbances in older men and women and to describe their relationships with health status and cardiovascular diseases (CVD).
DESIGN: Cross-sectional study of sleep disturbance, CVD, general health, psychosocial factors, physical function, and use of psychotropic medications.
SETTING: Participants of the Cardiovascular Health Study, 5201 adults aged 65 and older recruited from a random sample of noninstitutionalized Medicare enrollees in four US communities.
MEASURES: Self-reported sleep disturbances and standardized questionnaires for cardiopulmonary symptoms and diseases, depression, social support, activities of daily living, physical activity, cognitive function, and current medications, spirometry, ECG, echocardiography, and carotid ultrasound.
RESULTS: Women were twice as likely as men to report difficulty falling asleep (30% vs 14%). Daytime sleepiness, difficulty falling asleep, and frequent awakenings increased in prevalence with age. All symptoms were related strongly to depression. Symptoms of daytime sleepiness were also related strongly to poor health and limitations in activities of daily living in men and women. In multivariate analysis, men taking benzodiazepines were likely to report difficulty falling asleep and daytime sleepiness, whereas women taking benzodiazepines reported difficulty falling asleep and waking up too early. After accounting for these factors, the only cardiovascular disease independently associated with sleep disturbances was angina. Men and women with confirmed angina were 1.6 times more likely to report trouble falling asleep. Independent relationships between sleep disturbances and cardiovascular risk factors such as obesity, hypertension, smoking, and diabetes were relatively weak and inconsistent, though smokers were less likely to report frequent awakenings.
CONCLUSIONS: Sleep disturbances are relatively common in older men and women and are associated with poor health, depression, angina, limitations in activities of daily living, and the use of benzodiazepines.
TL;DR: The results of this experiment suggest that the stress of social subordination causes hypothalamic-pituitary-adrenal and ovarian dysfunction, and support the hypothesis that chronic, low-intensity social stress may result in depression in susceptible individuals.
TL;DR: The individual surgeon was a more important correlate of the decision to perform arthrodesis than clinical variables such as spondylolisthesis and instrumentation and noninstrumented arthrodenis resulted in superior relief of back pain after 6 and 24 months.
Abstract: Design A prospective, multicenter observational study Objectives 1) Identify correlates of the decision to perform arthrodesis in patients undergoing laminectomy for lumbar spinal stenosis 2) Compare symptoms, walking capacity, and satisfaction 6 and 24 months after laminectomy alone and laminectomy with noninstrumented and with instrumented arthrodesis Background data Few prospective studies have compared outcomes of laminectomy alone or laminectomy with noninstrumented or with instrumented arthrodesis in patients with degenerative lumbar spinal stenosis There is uncertainty regarding the optimal use of arthrodesis and instrumentation Methods Two hundred seventy--two patients undergoing--surgery for degenerative lumbar stenosis by eight surgeons at four centers were included in the study cohort Of these, 37 had noninstrumented and 41 had instrumented arthrodesis Logistic regression identified factors associated with arthrodesis The principal outcomes-health status, walking capacity, back and leg pain, and satisfaction with surgery-were assessed 6 and 24 months postoperatively with univariate and multivariate techniques Outcomes also were assessed in a restricted cohort of patients with at least 5 mm spondylolisthesis and/or 15 degrees scoliosis Hospital costs were obtained from a computerized hospital cost accounting system Results The major predictor of the decision to perform arthrodesis was the individual surgeon (P = 00001) Noninstrumented arthrodesis was associated with superior relief of low back pain at 6 months (P = 0004) and 24 months (P = 001) This difference persisted in multivariate analyses, with borderline statistical significance There were no significant differences in the other outcomes across treatment groups Mean hospital costs of laminectomy alone and noninstrumented and instrumented arthrodesis were $12,615, $18,495, and $25,914, respectively (P = 00001) Conclusion Findings were limited by the small number of participating surgeons, modest sample size that produced P values of borderline significance, and nonrandomized design With these caveats in mind, the authors conclude: (1) The individual surgeon was a more important correlate of the decision to perform arthrodesis than clinical variables such as spondylolisthesis (2) Noninstrumented arthrodesis resulted in superior relief of back pain after 6 and 24 months (3) Instrumented arthrodesis was the most costly option These results highlight the need for randomized controlled trials and cost effectiveness analyses of lumbar arthrodesis and instrumentation in patients with degenerative lumbar spinal stenosis
TL;DR: Like mammalian estrogens, dietary soy isoflavones enhance the dilator response to acetylcholine of atherosclerotic arteries in female monkeys.
TL;DR: The findings from this population-based, prospective study suggest that altered cardiac autonomic activity, especially lower parasympathetic activity, is associated with the risk of developing CHD.
Abstract: Cardiac autonomic activity, as assessed by heart rate variability, has been found to be associated with postmyocardial infarction mortality, sudden death, and all-cause mortality. However, the association of heart rate variability and the incidence of coronary heart disease (CHD) is not well described. The authors report on the association of baseline cardiac autonomic activity (1987-1989) with incident CHD after 3 years (1990-1992) of follow-up of the Atherosclerosis Risk in Communities Study cohort selected from four study centers in the United States by using a case-cohort design. The authors examined 137 incident cases of CHD and a stratified random sample of 2,252 examinees free of CHD at baseline. Baseline, supine, resting beat-to-beat heart rate data were collected. High- (0.16-0.35 Hz) and low- (0.025-0.15 Hz) frequency spectral powers and high-/low-frequency power ratio, estimated from spectral analysis, and standard deviation of all normal R-R intervals, calculated from time domain analysis, were used as the conventional indices of cardiac parasympathetic, sympatho-parasympathetic, and their balance, respectively. Incident CHD was defined as hospitalized myocardial infarction, fatal CHD, or cardiac revascularization procedures during 3 years of follow-up. The age, race, gender, and other CHD risk factor-adjusted relative risks (and 95% confidence intervals) of incident CHD comparing the lowest quartile with the upper three quartiles of high-frequency power, low-frequency power, high-/low-frequency power ratio, and standard deviation of R-R intervals were 1.72 (95% confidence interval (CI) 1.17-2.51), 1.09 (95% CI 0.72-1.64), 1.25 (95% CI 0.84-1.86), and 1.39 (95% CI 0.94-2.04), respectively. The findings from this population-based, prospective study suggest that altered cardiac autonomic activity, especially lower parasympathetic activity, is associated with the risk of developing CHD.
TL;DR: It is concluded that GH and IGF-1 have an important role in the decline in vascular density with age and it is suggested that decreases in vasculardensity may have important implications for the age-related decline in cerebral blood flow and brain function.
Abstract: Several reports have demonstrated that cerebral blood flow decreases with age and may contribute to neurodegenerative changes found in aging animals and man. Because GH and insulin-like growth factor 1 (IGF-1) decrease with age and have an important role in vascular maintenance and remodeling, we hypothesized that the decrease in cerebral blood flow is associated with a rarefaction of cerebral blood vessels resulting from a decline in GH and IGF-1. Measurements of vascular density (number of vessels/cortical surface area) in both Brown-Norway and Fisher 344/Brown-Norway rats were made at 5, 13, and 29 months of age using chronic cranial window chambers that allowed viewing of the cortical surface and its corresponding vasculature. Correlations were made with plasma levels of IGF-1. In Brown-Norway rats, arteriolar density decreased from 15.53 +/- 1.08 to 9.49 +/- 0.62 endpoints/mm2 in 7- and 29-month-old animals, respectively (P < 0.05). A decline was observed also in arteriolar anastomoses [3.05 +/- 0.21 to 1.42 +/- 0.24 connections/mm2 in 7- and 29-month-old animals (P < 0.05)]. Venular density did not decrease with age. Similar changes were observed in Fisher 344/Brown-Norway rats. The number of cortical surface arterioles was correlated with plasma IGF-1 levels at the time of vascular mapping (r = 0.772, P < 0.05), and injection of bovine GH (0.25 mg/kg, s.c., twice daily for 35 days) to 30-month-old animals increased both plasma IGF-1 and the number of cortical arterioles. These data indicate that: 1) vascular density on the surface of the cortex decreases with age; 2) vascular density is correlated with plasma levels of IGF-1; and 3) injection of GH increases cortical vascular density in older animals. We conclude that GH and IGF-1 have an important role in the decline in vascular density with age and suggest that decreases in vascular density may have important implications for the age-related decline in cerebral blood flow and brain function.
TL;DR: In this paper, the authors explored the relationship between extracellular dopamine concentrations and self-administration using a yoked littermate design and showed that the context in which cocaine was administered significantly altered the neurochemical response to equivalent brain concentrations of cocaine.
Abstract: Studies indicate that nucleus accumbens (NAcc) dopamine neurotransmission is involved in the reinforcing and direct effects of cocaine. The present study was initiated to explore further the relationship of NAcc extracellular dopamine concentrations ([DA]e) and cocaine self-administration using a yoked littermate design. In the first experiment, one rat from each litter was trained to self-administer cocaine i.v. (SA: 0.33 mg/inf) under a fixed ratio 2 schedule, while a second rat received simultaneous infusions of cocaine yoked to the infusions of the SA (YC). NAcc [DA]e and cocaine concentrations ([COC]) were assessed during the test sessions using in vivo microdialysis combined with microbore HPLC procedures. [DA]e and [COC] were significantly elevated in the SA and YC groups during the self-administration session; however, [DA]e were greater in the SA group compared to the YC group in the first hour of the session, even though [COC] were not significantly different. On the following day, the rats previously allowed to self-administer cocaine were administered response-independent cocaine infusions yoked to the infusion pattern from the previous day. [DA]e were significantly elevated above baseline levels during the session but were significantly less than concentrations obtained when cocaine was self-administered by these subjects. [COC] during the sessions were not significantly different between the two days. Baseline [DA]e were not significantly different between the SA and YC groups or between Day 1 and Day 2. Furthermore, there was no significant difference in the in vitro probe recovery between one and two days following probe implantation. These results suggest that the context in which cocaine was administered significantly altered the neurochemical response to equivalent brain concentrations of cocaine. NAcc [DA]e was significantly increased when the delivery of cocaine infusions was contingent on the behavior of the rat, indicative of a role in the neural processes underlying cocaine reinforcement.
TL;DR: The beneficial effects of soy protein on atherosclerosis appear to be mediated primarily by the phytoestrogen component, with greatest prevention of atherogenesis with soy+ and intermediate benefit with soy- relative to casein.
Abstract: Soy protein, long recognized as having cardiovascular benefits, is a rich source of phytoestrogens (isoflavones). To distinguish the relative contributions of the protein moiety versus the alcohol-extractable phytoestrogens for cardiovascular protection, we studied young male cynomolgus macaques fed a moderately atherogenic diet and randomly assigned to three groups. The groups differed only in the source of dietary protein, which was either casein/lactalbumin (casein, n = 27), soy protein with the phytoestrogens intact (soy+, n = 27), or soy protein with the phytoestrogens mostly extracted (soy-, n = 28). The diets were fed for 14 months. Animals fed soy+ had significantly lower total and LDL plus VLDL cholesterol concentrations compared with the other two groups. They soy+ animals had the highest HDL cholesterol concentrations, the casein group had the lowest, and the soy- group was intermediate. A subset was necropsied for atherosclerosis evaluations (n = 11 per group). Morphometric and angiochemical measures were done to quantify atherosclerosis. Coronary artery atherosclerotic lesions were smallest in the soy+ group (90% less coronary atherosclerosis than the casein group and 50% less than the soy- group), largest in the casein group, and intermediate in the soy- group. The effects of the diets on lesion size and arterial lipid measures of the peripheral arteries were similar to those in the coronary arteries, with greatest prevention of atherogenesis with soy+ and intermediate benefit with soy- relative to casein. We could not determine whether the beneficial effects seen in the soy- group relate to the protein itself or to the remaining traces of phytoestrogens. The beneficial effects of soy protein on atherosclerosis appear to be mediated primarily by the phytoestrogen component. Testicular weights were unaffected by the phytoestrogens.