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Biomedical subjects

J Lewis

Publications and source records attributed to J Lewis.

At least 37 records · Page 2Linked to original sources

Computerized weight loss intervention optimizes staff time: the clinical and cost results of a controlled clinical trial conducted in a managed care setting.

OBJECTIVE: To evaluate the costs and effects of incremental components of a weight-loss program. DESIGN: A 3-arm, 12-month randomized controlled clinical trial to evaluate 3 incremental levels of intervention intensity. SUBJECTS/SETTING: The study included 588 individuals (BMI > 25 kg/m2) in a freestanding health maintenance organizalion and achieved an 81% completion rate. INTERVENTION: Using a cognitive behavioral approach for tailoring lifestyle modification goals, the incremental levels of intervention included a) a workbook alone, b) the addition of computerized tailoring using onsite computer kiosks with touch screen monitors, and c) the addition of both computers and staff consultation. MAIN OUTCOME MEASURES: Endpoints included weight parameters, lipid profile, plasma glucose, blood pressure, intervention costs, dietary intake, and physical activity. STATISTICAL ANALYSIS PERFORMED: Study endpoints were analyzed using analysis of variance for normally distributed variables and analysis of covariance to control for any baseline differences. Regression and correlation analysis assessed the relationship between weight loss and other variables. RESULTS: For the increasing levels of intervention intensity, the mean 12-month weight losses were 2.2, 4.7, and 7.4 pounds, with the respective cost per participant being $12.33, $41.99, and $133.74. The decreases in mean BMIs for these respective intervelation levels were 0.4, 0.9 and 1.2. All groups reported a decrease in energy and fat intake and an increase in blocks walked (P<.01). Intervention variables that correlated with weight loss included more computer log-ons, achieving computer-selected goals, more self-monitoring, increased walking, and decreased energy and fat intake, as well as higher attendance in staff consultation group sessions for that treatment condition. Weight loss correlated with decreases in fasting glucose and blood pressure. APPLICATIONS/CONCLUSIONS: In a weight-loss program, computers can facilitate selecting behavioral change goals. More frequent usage resulted in greater weight loss. Staff counseling to augment the computer intervention achieved the most weight loss.

Analysis of Variance↗

Analysis of tauopathies with transgenic mice.

Intraneuronal filamentous inclusions composed of the microtubule-associated protein tau are a feature of several neurodegenerative diseases (including Alzheimer's disease) known as tauopathies. A pivotal finding was the identification in 1998 of mutations in tau associated with frontotemporal dementia with parkinsonism linked to chromosome 17. This demonstrated that tau dysfunction is sufficient to cause neurodegeneration, and indicated that tau is likely to play a crucial role in the pathogenesis of other tauopathies. However, the mechanism by which tau filamentous lesions form and their role in neurodegeneration remains uncertain. Recent progress in the development of transgenic mouse models of human tauopathy is allowing these questions to be addressed.

Animals↗

Sertraline, paroxetine, and venlafaxine in refugee posttraumatic stress disorder with depression symptoms.

Three new antidepressants were used in treating posttraumatic stress disorder (PTSD) and symptoms of depression in Bosnian refugees. Thirty-two Bosnian refugees seeking treatment at a mental health clinic participated in a case series study. All received open trials of Sertraline (n = 15), Paroxetine (n = 12), or Venlafaxine (n = 5), with standard clinical doses. Overall, Sertraline and Paroxetine produced statistically significant improvement at 6 weeks in PTSD symptom severity in depression, and in Global Assessment of Functioning. Venlafaxine produced improvement in PTSD symptom severity and in Global Assessment of Functioning, did not yield improvement in symptoms of major depressive disorder; and had a high rate of side effects. Notwithstanding improvement of symptoms, all 32 refugees remained PTSD positive at the diagnostic level at the 6-week follow-up.

Adult↗

Anxiety and depression in mothers of children undergoing bone marrow transplant: symptom prevalence and use of the Beck depression and Beck anxiety inventories as screening instruments.

This study examined anxiety and depressive symptoms among 115 mothers of children undergoing bone marrow transplant and evaluated the ability of the Beck Anxiety Inventory (BAI; A. T. Beck, N. Epstein, et al., 1988) and the Beck Depression Inventory (BDI; A. T. Beck, 1978) to serve as screening tools for assessing generalized anxiety disorder (GAD), panic disorder (PD), and major depressive disorder (MDD). Mothers with BAI or BDI scores greater than or equal to 14 were administered a structured clinical interview. An additional 20% was randomly selected for interview to determine whether the scale cutoff was an accurate screening method. Among the 64 mothers interviewed, 20% received at least I of the 3 diagnoses. Although the BAI did not demonstrate predictive accuracy in assessing GAD and PD, the BDI did in assessing MDD. The results suggest that a subset of mothers may have an anxiety or depressive disorder and that investigators should use caution before using the BAI as a screening instrument for anxiety disorder.

Adolescent↗

Pilot randomized controlled study of dexamphetamine substitution for amphetamine dependence.

AIMS: To test the feasibility of conducting a definitive randomized controlled trial of dexamphetamine substitution for amphetamine dependent people and provide preliminary data. DESIGN: An open, two-group pre-post randomized controlled trial. PARTICIPANTS: Forty-one long-term, dependent amphetamine users seeking treatment. INTERVENTION: Twenty subjects were offered weekly counselling. Twenty-one subjects were, in addition, prescribed up to 60 mg dexamphetamine daily. MEASUREMENTS: Immunoassay and mass spectrometric urinalysis techniques were used to identify the presence of amphetamine and methylamphetamine in urine. The Opiate Treatment Index and Severity of Dependence Scale were used to collect pre- and post-self-report data. Subjects were screened using the Composite International Diagnostic Interview. FINDINGS: Reduced street amphetamine use and amphetamine dependence was observed both in subjects prescribed dexamphetamine and subjects receiving counselling only. Treatment subjects appeared more likely to attend counselling. CONCLUSIONS: A definitive randomized controlled trial of dexamphetamine substitution using the techniques and instruments piloted in this study is feasible. Users appeared to be attracted and retained in substitution treatment. The intervention also appeared to be acceptable to clinicians.

Adrenergic Uptake Inhibitors↗

Delta4, an endothelial specific notch ligand expressed at sites of physiological and tumor angiogenesis.

Delta-Notch signalling regulates cell-fate choices in a variety of tissues during development. We report the expression of Delta4 (D14) in arterial endothelium during mouse embryogenesis and in the endothelium of tumor blood vessels. The expression of D14 in the mouse begins at 8 dpc in the dorsal aortae, umbilical artery and the heart. Subsequent expression is restricted to smaller vessels and capillaries and is reduced in most adult tissues. However, it is high in the vasculature of xenograft human tumors in the mouse, in endogenous human tumors and is regulated by hypoxia. These data implicate D14 and the Notch signalling pathway in angiogenesis and suggest possible new targets for antiangiogenic tumor therapy.

Adaptor Proteins, Signal Transducing↗

Comparison of cross-sectional renal function measurements in African Americans with hypertensive nephrosclerosis and of primary formulas to estimate glomerular filtration rate.

Renal function measurements were obtained in 1,703 African Americans with presumed hypertensive nephrosclerosis who were screened for entry into the African-American Study of Hypertension and Kidney Disease (AASK). We examined the effect of race on relationships involving renal variables by comparing African Americans enrolled into the AASK with non-African Americans enrolled into the Modification of Diet in Renal Disease (MDRD) study. We examined the effect of gender on renal variables by comparing African American men and women. We compared various methods for estimating glomerular filtration rate (GFR) with iodine 125-labeled ((125)I)-iothalamate GFR. AASK data were also used to derive a new formula for estimating GFR in African Americans. After adjusting for age, sex, and baseline GFR, African American patients on the AASK study were heavier and had larger body surface areas and body mass indices than either MDRD African Americans or non-African Americans. African Americans had greater serum creatinine levels and urinary creatinine excretions for any given level of GFR. Mean GFR was greater in African American men than African American women (59.7 versus 51.7 mL/min/1.73 m(2)), although serum creatinine levels were also greater in men (1.91 versus 1.73 mg/dL). Seventy-eight percent of women with serum creatinine levels between 1.2 and 1.5 mg/dL had GFRs less than 65 mL/min/1.73 m(2). For African Americans in the AASK, GFR was overestimated by the 24-hour creatinine clearance and underestimated by the Cockcroft-Gault formula. A prediction formula developed in the MDRD study more accurately predicted GFR in AASK patients than these measurements. AASK data were also used to derive a new five-term formula for estimating GFR that was slightly more accurate in the African Americans in the AASK than the MDRD formula (median percentage of error, 12.4% for the MDRD formula versus 12.1% for the AASK formula). Important differences exist in renal variables between African Americans and non-African Americans and between African American men and African American women. Formulas using demographic data and readily measured serum values estimate (125)I-iothalamate GFR.

Adolescent↗

Kasai portoenterostomy: differences related to race.

PURPOSE: The aim of this study was to evaluate the Kasai portoenterostomy in African-American and white children with respect to differences in presentation and outcome. METHODS: A retrospective review of all children with biliary atresia who underwent a portoenterostomy at our institution over the last 15 years (n = 63) was performed. Sex, age at the time of Kasai, preoperative laboratory tests, success rates (defined as postoperative total serum bilirubin < or = 2.0 mg/dL), and survival rate were recorded. Differences between African-American (AA; n = 30) and white (W; n = 33) children were analyzed. Long-term follow-up was available on 59 of 63 patients. RESULTS: Sixty-three percent of all patients (40 of 65) were girls, and 48% were AA (30 of 63). A higher percentage of AA children (73%) were girls than were white children (55%), although this difference did not achieve statistical significance. African-Americans underwent portoenterostomy at a later age, had higher alkaline phosphatase levels, and higher AST. These differences were statistically significant. Preoperative ALT, total bilirubin level, and GGTP levels all were greater in African-Americans, although these differences did not achieve statistical significance. There was a trend toward decreased success and survival rate, although these results also were not statistically significant. CONCLUSIONS: African-Americans underwent primary therapeutic intervention for biliary atresia at an older age than white children with a trend toward less favorable results. These differences related to race may be attributed to greater difficulty in diagnosing jaundice or poorer access to health care in this patient population. Increased effort at identifying biliary atresia in AA children may lead to earlier diagnosis and treatment and improved outcomes.

Biliary Atresia↗

In memory of a legendary athlete: measured success in diabetic nephropathy.

Historically diabetic nephropathy has been a devastating complication of both type I and type II diabetes. The past 2 decades have seen enormous conceptual advances in understanding the pathogenesis of diabetic nephropathy. The genetic determinants of diabetic renal disease have also been elucidated as well as biochemical events and cytokine interactions. Most importantly, key clinical trials have identified therapeutic interventions which can slow or halt the progression of diabetic nephropathy, specifically the therapeutic use of angiotensin-converting enzyme inhibition and intensive blood sugar control. Multiple treatment modalities for patients once they reach end-stage renal disease are also available and great strides have been improving outcomes in these areas as well.

Baseball↗

Use of the mycobacteriophage L5 excisionase in Mycobacterium tuberculosis to demonstrate gene essentiality.

UNLABELLED: SWTTING: Demonstrating that a gene is essential is always difficult, but this is particularly true for a slow-growing organism such as Mycobacterium tuberculosis. One method currently used is to show that homologous recombination leading to gene inactivation only occurs in the presence of a second copy of the gene, but obtaining statistically significant data can be prohibitively difficult. L5-based integrating plasmids have been widely used in the genetic analysis of mycobacteria. The L5 excisionase has been used in Mycobacterium smegmatis to excise and recover these plasmids from chromosome. OBJECTIVE: Our aims were to establish whether the L5 excisionase could function in M. tuberculosis to remove an L5-based integrated plasmid and, if so, to use this technology as the basis for an improved method for determining whether a gene is essential. DESIGN: We took two strains of M. tuberculosis carrying the essential gene glnE integrated into the chromosome on an L5-based plasmid, one of which lacked the functional chromosomal copy of the gene. We transformed these with vectors expressing the L5 excisionase and looked for loss of the integrated plasmid. RESULTS: We obtained efficient excision of an integrated vector from the wild-type strain. However, when the integrated vector carried the only functional copy of the essential gene glnE, the numbers of colonies recovered were reduced to background levels. CONCLUSION: The L5 excisionase does function in M. tuberculosis and can be used to confirm the essentiality of a gene. This technology also allows further analysis of essential genes that is difficult or impossible using current methods.

Blotting, Southern↗

A novel gamma 2-herpesvirus of the Rhadinovirus 2 lineage in chimpanzees.

Old World monkeys and, recently, African great apes have been shown, by serology and polymerase chain reaction (PCR), to harbor different gamma2-herpesviruses closely related to Kaposi's sarcoma-associated Herpesvirus (KSHV). Although the presence of two distinct lineages of KSHV-like rhadinoviruses, RV1 and RV2, has been revealed in Old World primates (including African green monkeys, macaques, and, recently, mandrills), viruses belonging to the RV2 genogroup have not yet been identified from great apes. Indeed, the three yet known gamma2-herpesviruses in chimpanzees (PanRHV1a/PtRV1, PanRHV1b) and gorillas (GorRHV1) belong to the RV1 group. To investigate the putative existence of a new RV2 Rhadinovirus in chimpanzees and gorillas we have used the degenerate consensus primer PCR strategy for the Herpesviral DNA polymerase gene on 40 wild-caught animals. This study led to the discovery, in common chimpanzees, of a novel gamma2-herpesvirus belonging to the RV2 genogroup, termed Pan Rhadino-herpesvirus 2 (PanRHV2). Use of specific primers and internal oligonucleotide probes demonstrated the presence of this novel gamma2-herpesvirus in three wild-caught animals. Comparison of a 1092-bp fragment of the DNA polymerase obtained from these three animals of the Pan troglodytes troglodytes subspecies, one from Gabon and the two others from Cameroon, revealed <1% of nucleotide divergence. The geographic colocalization as well as the phylogenetic "relationship" of the human and simian gamma2-herpesviruses support the model according to which herpesviruses have diversified from a common ancestor in a manner mediating cospeciation of herpesviruses with their host species. By demonstrating the existence of two distinct Rhadinovirus lineages in common chimpanzees, our finding indicates the possible existence of a novel human gamma2-herpesvirus belonging to the RV2 genogroup.

Animals↗

Dieulafoy's lesion of the small bowel causing massive gastrointestinal bleeding: two case reports and literature review.

Dieulafoy's lesions are an often unrecognized cause of obscure, massive GI hemorrhage. Their diagnosis may elude conventional investigations, including upper and lower endoscopy, arteriography, and even laparotomy. In this paper, we report two cases of small-bowel Dieulafoy lesions. The first, a jejunal lesion, occurred in a young patient and was discovered at laparotomy. The second was an ileal Dieulafoy's malformation in an older patient. An intraoperative endoscopy with surgical guidance may be needed for definitive localization of this lesion.

Adolescent↗

Antigenic variation within the CD4 binding site of human immunodeficiency virus type 1 gp120: effects on chemokine receptor utilization.

To assess the antigenicity of envelope glycoproteins derived from primary human immunodeficiency virus type 1 populations, their interactions with the receptor CD4, and their coreceptor usage, we have cloned and expressed multiple gp120 proteins from a number of primary virus isolates. Characterization of these proteins showed a high degree of antigenic polymorphism both within the CD4 binding site and in defined neutralization epitopes, which may partially account for the general resistance of primary isolates to neutralizing agents. Furthermore, chimeric viruses expressing gp120 proteins with reduced CD4 binding abilities are viable, suggesting that primary viruses may require a less avid interaction with the receptor CD4 to initiate infection than do their laboratory-adapted counterparts. The coreceptor usage of chimeric viruses was related to the ability of the virus to bind CD4, with reduced CD4 binding correlating with preferential usage of CXCR4. Changes in coreceptor usage mapped to sequence changes in the C2 and V4 regions, with no changes seen in the V3 region.

Amino Acid Sequence↗

Molecular cloning of ILP-2, a novel member of the inhibitor of apoptosis protein family.

Inhibitor of apoptosis protein (IAP)-like protein-1 (ILP-1) (also known as X-linked IAP [XIAP] and mammalian IAP homolog A [MIHA]) is a potent inhibitor of apoptosis and exerts its effects, at least in part, by the direct association with and inhibition of specific caspases. Here, we describe the molecular cloning and characterization of a human gene related to ILP-1, termed ILP-2. Despite high homology to ILP-1, ILP-2 is encoded by a distinct gene, which in normal tissues is expressed solely in testis. In contrast to ILP-1, overexpression of ILP-2 had no protective effect on apoptosis mediated by Fas (also known as CD95) or tumor necrosis factor. However, ILP-2 potently inhibited apoptosis induced by overexpression of Bax or by coexpression of caspase 9 with Apaf-1, and preincubation of cytosolic extracts with ILP-2 abrogated caspase activation in vitro. A processed form of caspase 9 could be coprecipitated with ILP-2 from cells, suggesting a physical interaction between ILP-2 and caspase 9. Thus, ILP-2 is a novel IAP family member with restricted specificity for caspase 9.

Amino Acid Sequence↗

Mechanical ventilation of isolated septic rat lungs: effects on surfactant and inflammatory cytokines.

The effects of mechanical ventilation (MV) on the surfactant system and cytokine secretion were studied in isolated septic rat lungs. At 23 h after sham surgery or induction of sepsis by cecal ligation and perforation (CLP), lungs were excised and randomized to one of three groups: 1) a nonventilated group, 2) a group subjected to 1 h of noninjurious MV (tidal volume = 10 ml/kg, positive end-expiratory pressure = 3 cmH(2)O), or 3) a group subjected to 1 h of injurious MV (tidal volume = 20 ml/kg, positive end-expiratory pressure = 0 cmH(2)O). Nonventilated sham and CLP lungs had similar compliance, normal lung morphology, surfactant, and cytokine concentrations. Injurious ventilation decreased compliance, altered surfactant, increased cytokines, and induced morphological changes compared with nonventilation in sham and CLP lungs. In these lungs, the surfactant system was similar in sham and CLP lungs; however, tumor necrosis factor-alpha and interleukin-6 levels were significantly higher in CLP lungs. We conclude that injurious ventilation altered surfactant independent of sepsis and that the CLP lungs were predisposed to the secretion of larger amounts of cytokines because of ventilation.

Animals↗