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J Newman

Publications and source records attributed to J Newman.

At least 37 records · Page 2Linked to original sources

Does gender bias exist in the medical management of heart failure?

INTRODUCTION: The purpose of this study was to ascertain the presence of gender bias in the medical management of heart failure, and to assess its association with the specialty of the caregiver physician. METHODS: In 309 patients with documented left ventricular systolic dysfunction (ejection fraction <45%) and at least one hospitalization for heart failure, we assessed the frequency of use of effective medical therapy for heart failure among male (n=187) and female (n=122) patients at the time of hospital discharge. We constructed multivariate models relating patient gender and caregiver specialty to utilization of each class of medications (angiotensin-converting enzyme inhibitors, effective vasodilator therapy (i.e., angiotensin-converting enzyme inhibitors or hydralazine-nitrate therapy), diuretics, digoxin), and combination therapy (i.e., vasodilator plus diuretic plus digoxin). RESULTS: In crude analyses, we did not find any difference in utilization of medications between male and female patients. Multivariate analyses involving adjustment for age, race, coronary artery disease, ejection fraction, and other relevant variables, revealed higher utilization of combination therapy by cardiologists in male versus female patients (adjusted odds ratios=2.07; 95%CI=1.09-3.95), and higher utilization of digoxin therapy by non-cardiologists in female versus male patients (adjusted odds ratio=5.5; 95%CI=1.4-22.2). No gender or caregiver specialty differences were seen in models relating to the other classes of medications. CONCLUSIONS: Our findings suggest the presence of gender bias in the medical management of heart failure, and identify an interesting interaction between caregiver specialty and gender bias.

Aged↗

Activity of an alcohol-based hand gel against human adeno-, rhino-, and rotaviruses using the fingerpad method.

OBJECTIVE: To assess the activity against three non-enveloped viruses (an adeno-, a rhino- and a rotavirus) of a gel containing 60% ethanol, using experimentally contaminated thumb- and fingerpads of 12 panelists, as per standard procedure E-1838-96 of the American Society of Testing and Materials. DESIGN: Each digit received 10 microL of the test virus suspension. The inoculum from the thumbs was eluted immediately with 990 microL of Earle's balanced salt solution (EBSS) to assess the amount of virus on each digit (0-minute control). The inoculum on the fingers was allowed to dry (20-25 minutes), and virus was eluted from two fingerpads to determine the loss in virus infectivity upon drying (baseline titer). Then the dried inoculum on randomly selected fingers was exposed to 1 mL of the test product or standard hard water (200-ppm calcium carbonate) for 20 seconds. The virus remaining was eluted with 1 mL of EBSS, titrated to determine the amounts eliminated, and compared to the baseline titer. RESULTS: Each digit received at least 10(4) plaque-forming units of virus in 10 microL. The amounts of adeno-, rhino-, and rotaviruses surviving the drying were 30%, 75%, and 42%, respectively. The product reduced the infectivity titers of the three viruses by 3 to >4 log10 when compared to a reduction of < or =1 log10 for the hard-water rinse. CONCLUSION: The level of virus reduction by gel was statistically significantly higher than that seen with the water control. Evidence for such activity against non-enveloped viruses supports further investigation of the benefits of this product.

Adenoviridae↗

Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-beta family.

BACKGROUND: Primary pulmonary hypertension (PPH), resulting from occlusion of small pulmonary arteries, is a devastating condition. Mutations of the bone morphogenetic protein receptor type II gene (BMPR2), a component of the transforming growth factor beta (TGF-beta) family which plays a key role in cell growth, have recently been identified as causing familial PPH. We have searched for BMPR2 gene mutations in sporadic PPH patients to determine whether the same genetic defect underlies the more common form of the disorder. METHODS: We investigated 50 unrelated patients, with a clinical diagnosis of PPH and no identifiable family history of pulmonary hypertension, by direct sequencing of the entire coding region and intron/exon boundaries of the BMPR2 gene. DNA from available parent pairs (n=5) was used to assess the occurrence of spontaneous (de novo) mutations contributing to sporadic PPH. RESULTS: We found a total of 11 different heterozygous germline mutations of the BMPR2 gene in 13 of the 50 PPH patients studied, including missense (n=3), nonsense (n=3), and frameshift (n=5) mutations each predicted to alter the cell signalling response to specific ligands. Parental analysis showed three occurrences of paternal transmission and two of de novo mutation of the BMPR2 gene in sporadic PPH. CONCLUSION: The sporadic form of PPH is associated with germline mutations of the gene encoding the receptor protein BMPR-II in at least 26% of cases. A molecular classification of PPH, based upon the presence or absence of BMPR2 mutations, has important implications for patient management and screening of relatives.

Adolescent↗

Oxygen dependency and precision of cytochrome oxidase signal from full spectral NIRS of the piglet brain.

Oxidation changes of the copper A (Cu(A)) center of cytochrome oxidase in the brain were measured during brief anoxic swings at both normocapnia and hypercapnia (arterial PCO(2) approximately 55 mmHg). Hypercapnia increased total hemoglobin from 37.5 +/- 9.1 to 50.8 +/- 12.9 micromol/l (means +/- SD; n = 7), increased mean cerebral saturation (Smc(O(2))) from 65 +/- 4 to 77 +/- 3%, and oxidized Cu(A) by 0.43 +/- 0.23 micromol/l. During the onset of anoxia, there were no significant changes in the Cu(A) oxidation state until Smc(O(2)) had fallen to 43 +/- 5 and 21 +/- 6% at normocapnia and hypercapnia, respectively, and the maximum reduction during anoxia was not significantly different at hypercapnia (1.49 +/- 0.40 micromol/l) compared with normocapnia (1.53 +/- 0.44 micromol/l). Residuals of the least squares fitting algorithm used to convert near-infrared spectra to concentrations are presented and shown to be small compared with the component of attenuation attributed to the Cu(A) signal. From these observations, we conclude that there is minimal interference between the hemoglobin and Cu(A) signals in this model, the Cu(A) oxidation state is independent of cerebral oxygenation at normoxia, and the oxidation after hypercapnia is not the result of increased cerebral oxygenation.

Animals↗

Venous and arterial changes in pulmonary veno-occlusive disease, mitral stenosis and fibrosing mediastinitis.

The pathogenesis of pulmonary veno-occlusive disease (PVOD) is not known. The diagnosis of PVOD frequently relies on its histological changes since it is often difficult to distinguish clinically from primary pulmonary hypertension. This study carried out a systematic analysis of the pulmonary venous and arterial remodelling that occurs in PVOD (n=5) and compared these changes to two other diseases affecting the pulmonary veins, mitral stenosis (MS; n=6) and fibrosing mediastinitis (FM; n=2), using established morphometric techniques. In PVOD, pronounced intimal and adventitial thickening were noted in veins of all sizes and arterialization of veins >50 microm external diameter was found. Similar changes were evident in the arterial wall, but intimal thickening was less severe than in the veins and medial thickening was more pronounced in arteries <300 microm external diameter. Eccentric intimal fibrosis of the veins was also noted for the first time in PVOD, although this feature occurred less frequently (approximately one third) than in MS. Less pronounced structural remodelling was also encountered in the veins in cases of MS and FM. The severity of the venous changes in PVOD may aid its diagnosis and lend insight into its pathogenesis. However, the similarity of the vascular changes in each form of venous hypertension also suggests that pathology alone may not always differentiate between these disease states. The similarity of the vascular changes in the three forms of venous hypertension suggests that, as in pulmonary artery hypertension, pressure, per se, is one of the triggers to vascular remodelling.

Adult↗

Racial and ethnic differences in the use of cardiovascular procedures: findings from the California Cooperative Cardiovascular Project.

OBJECTIVES: This study used data from the California Cooperative Cardiovascular Project to examine the use of invasive and noninvasive cardiovascular procedures among Whites, African Americans, and Hispanics. METHODS: The use of catheterization, percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft (CABG) surgery, and several noninvasive tests among all patients 65 years or older with a confirmed acute myocardial infarction in nonfederal hospitals from 1994 to 1995 was studied. RESULTS: African Americans (n = 527) were less likely than Whites (n = 9489) to have received catheterization (adjusted odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.50, 0.76), PTCA (OR = 0.64, 95% CI = 0.49, 0.85), or CABG surgery (OR = 0.42, 95% CI = 0.27, 0.64); somewhat more likely to have received a stress test or an echocardiogram; and equally likely to have received a multiple-gated acquisition scan. Hispanics (n = 689) also were less likely than Whites to have received catheterization (OR = 0.82, 95% CI = 0.68, 0.98) or PTCA (OR = 0.58, 95% CI = 0.45, 0.75). CONCLUSIONS: African Americans were less likely than Whites to undergo costly invasive cardiovascular procedures. In addition, Hispanics were less likely than Whites to have received catheterization and PTCA.

APACHE↗

Haloalkane dehalogenases: structure of a Rhodococcus enzyme.

The hydrolytic haloalkane dehalogenases are promising bioremediation and biocatalytic agents. Two general classes of dehalogenases have been reported from Xanthobacter and Rhodococcus. While these enzymes share 30% amino acid sequence identity, they have significantly different substrate specificities and halide-binding properties. We report the 1.5 A resolution crystal structure of the Rhodococcus dehalogenase at pH 5.5, pH 7.0, and pH 5.5 in the presence of NaI. The Rhodococcus and Xanthobacter enzymes have significant structural homology in the alpha/beta hydrolase core, but differ considerably in the cap domain. Consistent with its broad specificity for primary, secondary, and cyclic haloalkanes, the Rhodococcus enzyme has a substantially larger active site cavity. Significantly, the Rhodococcus dehalogenase has a different catalytic triad topology than the Xanthobacter enzyme. In the Xanthobacter dehalogenase, the third carboxylate functionality in the triad is provided by D260, which is positioned on the loop between beta7 and the penultimate helix. The carboxylate functionality in the Rhodococcus catalytic triad is donated from E141. A model of the enzyme cocrystallized with sodium iodide shows two iodide binding sites; one that defines the normal substrate and product-binding site and a second within the active site region. In the substrate and product complexes, the halogen binds to the Xanthobacter enzyme via hydrogen bonds with the N(eta)H of both W125 and W175. The Rhodococcusenzyme does not have a tryptophan analogous to W175. Instead, bound halide is stabilized with hydrogen bonds to the N(eta)H of W118 and to N(delta)H of N52. It appears that when cocrystallized with NaI the Rhodococcus enzyme has a rare stable S-I covalent bond to S(gamma) of C187.

Amino Acid Sequence↗

Interferon-alpha does not improve outcome at one year in patients with diffuse cutaneous scleroderma: results of a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine whether interferon-alpha (IFNalpha) reduces the severity of skin involvement in early (<3 years) diffuse scleroderma. METHODS: In a randomized, placebo-controlled, double-blind trial, 35 patients with early scleroderma received subcutaneous injections of either IFNalpha (13.5 x 10(6) units per week in divided doses) or indistinguishable placebo. Outcomes assessed were the modified Rodnan skin score, as determined by a single observer at baseline, 6 months, and 12 months, as well as data on renal, cardiac, and lung function. Pre- and posttreatment skin biopsy samples were analyzed and blood was obtained for assessment of procollagen peptide levels. RESULTS: There were 11 withdrawals from the IFNalpha group and 3 from the placebo group due to either toxicity, lack of efficacy, or death. In the intent-to-treat analysis, there was a greater improvement in the skin score in the placebo group between 0 and 12 months (mean change IFNalpha -4.7 versus placebo -7.5; P = 0.36). There was also a greater deterioration in lung function in patients receiving active therapy, as assessed by either the forced vital capacity (mean change IFNalpha -8.2 versus placebo +1.3; P = 0.01) or the diffusing capacity for carbon monoxide (mean change IFNalpha -9.3 versus placebo +4.7; P = 0.002). Skin biopsy showed no significant decrease in collagen synthesis in the IFNalpha group, and no significant differences in the levels of procollagen peptides were seen between the 2 groups. CONCLUSION: This study suggests that IFNalpha is of no value in the treatment of scleroderma, and that it may in fact be deleterious.

Adolescent↗

The independent effects of left ventricular ejection fraction on short-term outcomes and resource utilization following hospitalization for heart failure.

BACKGROUND: While depressed left ventricular ejection fraction is clearly associated with poor long-term outcome in heart failure (HF), the effect of ejection fraction on short-term outcomes and resource utilization following hospitalization for HF remains unclear. HYPOTHESIS: We evaluated the independent effect of depressed ejection fraction (< or = 40%) on short-term outcomes and resource utilization following hospitalization for HF. METHODS: The study population included 443 consecutive patients hospitalized for DRG 127 (HF and shock) with known ejection fraction. For each patient, we assessed the hospitalization cost (1995 US$), length of stay, in-hospital mortality, 30-day mortality, and 30-day readmission rates. RESULTS: Despite similar disease severity at admission, patients with ejection fraction < or = 40% (Group 1) had longer length of stay (4.0 vs. 3.7 days; p = 0.03), a tendency toward higher hospitalization cost ($3,054 vs. $2,770; p = 0.08), more readmissions for any cause (0.4 vs. 0.3; p = 0.05) and for HF (0.2 vs. 0.1; p = 0.01), but similar in-hospital (2.5 vs. 2.6%) and 30-day mortality (4.0 vs. 4.6%) compared with patients with ejection fraction > 40% (Group 2). In multivariate analyses, Group 1 patients were more likely to have higher than median hospitalization cost [odds ratio (OR) = 1.98; 95% confidence intervals (CI) = 1.02-3.91] and longer than median hospital stay (OR = 1.68; CI = 1.08-3.91); they were also more likely to be readmitted for any cause (OR = 2.07; CI = 1.15-3.78) or for HF (OR = 5.71; CI = 1.64-21.94), and they tended to have a higher 30-day incidence of death or readmission (OR = 1.65; CI = 0.96-2.84). CONCLUSIONS: Depressed left ventricular ejection fraction is associated with higher resource utilization and readmission rates following hospitalization for HF. Greater focus on patients with depressed ejection fraction may increase cost savings from HF disease management programs.

Aged↗

Binding across time: the selective gating of frontal and hippocampal systems modulating working memory and attentional states.

Temporal binding via 40-Hz synchronization of neuronal discharges in sensory cortices has been hypothesized to be a necessary condition for the rapid selection of perceptually relevant information for further processing in working memory. Binocular rivalry experiments have shown that late stage visual processing associated with the recognition of a stimulus object is highly correlated with discharge rates in inferotemporal cortex. The hippocampus is the primary recipient of inferotemporal outputs and is known to be the substrate for the consolidation of working memories to long-term, episodic memories. The prefrontal cortex, on the other hand, is widely thought to mediate working memory processes, per se. This article reviews accumulated evidence for the role of a subcortical matrix in linking frontal and hippocampal systems to select and "stream" conscious episodes across time (hundreds of milliseconds to several seconds). "Streaming" is hypothesized to be mediated by the selective gating of reentrant flows of information between these cortical systems and the subcortical matrix. The physiological mechanism proposed for this temporally extended form of binding is synchronous oscillations in the slower EEG spectrum (< 8 Hz).

Attention↗

In memoriam

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Journal Article↗

Premature greying of the hair is not associated with low bone mineral density.

In two recent case-control studies premature greying of the hair was associated with a lowering of bone mineral density (BMD) and osteopenia, suggesting that this might be a clinically useful risk marker for osteoporosis. We report a further re-examination of this proposal in 52 prematurely grey-haired women from East Yorkshire who responded to an advertisement inviting them for bone densitometry. Thirty-five had no clinical or drug history that could influence bone density. All were Caucasian with a mean age of 52.8 years. In the group as a whole the mean BMD values at the lumbar spine and femoral neck were no different from those of a young adult, but there was a trend toward a greater than average BMD than that of the local age-matched population (p = 0.097 and 0.218, respectively). Twenty women were premenopausal, with an average age of 45.3 years. Mean BMD values at the lumbar spine and femoral neck in this group were no different from those of young adults. There was, however, a trend toward a BMD greater than that of the local age-matched population at the femoral neck (p = 0.117). Fifteen women were postmenopausal with an average age of 62.9 years and an average age at menopause of 51.1 years. Mean BMD values at both the lumbar spine and femoral neck in this group were lower than those of young adults, but no different from those of the local age-matched population. In conclusion, our group of prematurely grey-haired women had average BMD for their age, and we are therefore unable to support the proposed clinical usefulness of premature greying as a risk marker for osteoporosis.

Absorptiometry, Photon↗

In vitro alteration of macrophage phenotype and function by serum lipids.

Diabetes (type I and type II) affects approximately 13 million people in the United States. Delayed and incomplete healing of wounds can be a major problem for diabetic patients. Macrophages are an important cell in the complex process of wound repair representing the major source of cytokines throughout the wound-healing process. Cytokines mediate many of the cellular responses critical to timely wound repair. It has been suggested that diabetes impairs wound healing through disruption of local cytokine production. Our previous in vivo studies in rats demonstrated that diabetes-induced and diet-induced hyperlipidemia cause changes in macrophage phenotype and function (Iacopino 1995; Doxey et al. 1998), suggesting that alterations in macrophage cytokine profiles represent the cellular/molecular mechanism responsible for delayed wound healing. The purpose of this study was to investigate how monocyte maturation/differentiation and cytokine production were altered by serum lipids in an in vitro system using human cells. Commercially prepared purified human monocytes were cultured and exposed to serum lipids. Phenotypic analysis of differentiated macrophages was then performed by flow cytometry and fluorescent microscopy using surface antigens specific for various macrophage subsets. Selected cytokines in conditioned medium were assayed using commercial human enzyme-linked immunosorbent assay (ELISA) kits. We demonstrate that serum lipids cause an increase in monocytic differentiation leading to an inflammatory macrophage phenotype rather than a reparative/proliferative phenotype. We also show that serum lipids cause a generalized decrease in macrophage cytokine production using interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), platelet-derived growth factor (PDGF), and transforming growth factor beta 1 (TGF-beta 1) as marker cytokines. Our present in vitro results using human cells confirm our previous in vivo studies in the rat and support the hypothesis that diabetes-induced hyperlipidemia alters the monocyte differentiation process resulting in changes of macrophage subsets and cytokine release at the wound site, ultimately impairing the wound-healing process.

Animals↗

Hair removal using a long-pulsed alexandrite laser.

The use of lasers for hair depilation has become a common modality for physicians in the recent past. As new lasers are developed, the complex mechanisms affecting this form of treatment are now under close investigation. The long-pulsed alexandrite laser functioning at a wavelength of 755 nm has recently been added to the armamentarium of health care providers to assist patients with unwanted body hair. A review of the embryology and anatomy of the hair follicle are discussed, as well as the findings of recent studies using this form of laser therapy. Using the suggested treatment protocols offered laser assisted depilation may be effectively achieved. The degree and duration of reduction vary with anatomic site and improve with multiple treatments.

Face↗

Laser therapy of spider leg veins: clinical evaluation of a new long pulsed alexandrite laser.

BACKGROUND: The response of spider leg veins to laser or intense pulsed light therapy has generally been characterized by varying degrees of success and frequently inconsistent clinical response rates. OBJECTIVE: The purpose of this study was to examine the effectiveness of the 755 nm long pulsed infrared alexandrite (LPA) laser for the treatment of leg telangiectasias. METHODS: This study was constructed in four phases. Phase I examined 28 patients with variable sized telangiectasias using 5 treatment parameters (15 J/cm2 x 1 pulse, 20 J/cm2 x 1 pulse, 20 J/cm2 x 2 pulses, 20 J/cm2 x 3 pulses, or 30 J/cm2 x 1 pulse). Each patient received 3 treatments at 4 week intervals with the LPA. Patient diaries were obtained to examine the effects of the treatments. Subjective grading was performed at each follow-up visit by the investigators. Blinded objective grading was performed at the conclusion of the study by trained observers. Phase II examined the effects of these treatment parameters on varying vessel diameters. Vessels were grouped into small (<0.4 mm), intermediate (0.4-1.0 mm), and large (1.0-3.0 mm) subsets. Phase III examined the effects of a combination of LPA treatment followed by 23.4% hypertonic saline sclerotherapy. Subjective and blinded objective grading was used to determine improvement after a single treatment with the LPA at 20 J/cm2, single pulsed with a pulse duration of 5 or 10 msec followed by treatment with 23.4% hypertonic saline injected 3, 7, 14, or 28 days after laser therapy. Phase IV involved biopsies after LPA treatment alone at time intervals of immediately posttreatment and 5 and 21 days posttreatment. RESULTS: These evaluations revealed that the optimal treatment parameters for LPA therapy alone appeared to be 20 J/cm2, double pulsed at a repetition rate of one Hz. After 3 treatments at 4 week intervals, subjective grading indicated a 63% reduction in leg telangiectasias. Medium diameter vessels responded best with small vessel diameters responding poorly, if at all. The addition of 23.4% hypertonic saline sclerotherapy performed 3 to 7 days after laser therapy (LPA at 20 J/cm2, single pulsed with a pulse duration of 5 msec) produced 87% reduction in leg telangiectasias. Biopsies after LPA treatment revealed vessel wall endothelial cell necrosis at 5 days with fibrosis occurring at 3 weeks. The optimal clinical "window" for sclerotherapy seems to coincide with the period of endothelial cell necrosis. CONCLUSION: LPA therapy is most effective for leg telangiectasias 0.4-3.0 mm in diameter. This LPA technique is significantly improved with the addition of sclerotherapy.

Adult↗