tbuckley/cabot-search huggingface dataset:
Pharmacogenetics of Efavirenz: Adherence and Virologic Outcomes
Authors: David J. Cennimo
Journal: Annals of Internal Medicine (2007)

Letters4 December 2007Pharmacogenetics of Efavirenz: Adherence and Virologic OutcomesDavid J. Cennimo, MDDavid J. Cennimo, MDFrom University of Medicine and Dentistry of New Jersey, Newark, NJ 07103.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-147-11-200712040-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Nachega and colleagues (1) describe the virologic response to nonnucleoside reverse transcriptase inhibitor (NNRTI) use across a spectrum of adherence in a predominantly (96.9%) black, South African patient cohort. Their findings suggest a superiority of efavirenz-based regimens over nevirapine even after adjustment for adherence and other baseline variables. One potential confounding variable is the delayed hepatic clearance of efavirenz noted in some U.S. patients of African descent (2). This has been attributed to mutation in the CPY2B6 gene (516G>T), which can prolong the efavirenz half-life to 48 hours in persons with TT homozygous mutations. In comparison, the ...References1. Nachega JB, Hislop M, Dowdy DW, Chaisson RE, Regensberg L, Maartens G. Adherence to nonnucleoside reverse transcriptase inhibitor-based HIV therapy and virologic outcomes. Ann Intern Med. 2007;146:564-73. [PMID: 17438315] LinkGoogle Scholar2. Pfister M, Labbé L, Hammer SM, Mellors J, Bennett KK, Rosenkranz S, et al. Population pharmacokinetics and pharmacodynamics of efavirenz, nelfinavir, and indinavir: Adult AIDS Clinical Trial Group Study 398. Antimicrob Agents Chemother. 2003;47:130-7. [PMID: 12499180] CrossrefMedlineGoogle Scholar3. Ribaudo HJ, Haas DW, Tierney C, Kim RB, Wilkinson GR, Gulick RM, et al. Pharmacogenetics of plasma efavirenz exposure after treatment discontinuation: an Adult AIDS Clinical Trials Group Study. Clin Infect Dis. 2006;42:401-7. [PMID: 16392089] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From University of Medicine and Dentistry of New Jersey, Newark, NJ 07103.Disclosures:Grants received: Bristol-Myers Squibb. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAdherence to Nonnucleoside Reverse Transcriptase Inhibitor–Based HIV Therapy and Virologic Outcomes Jean B. Nachega , Michael Hislop , David W. Dowdy , Richard E. Chaisson , Leon Regensberg , and Gary Maartens Pharmacogenetics of Efavirenz: Adherence and Virologic Outcomes Jean B. Nachega and Gary Maartens Metrics 4 December 2007Volume 147, Issue 11Page: 817KeywordsConflicts of interestPharmacogeneticsPopulation statisticsReverse transcriptase inhibitors ePublished: 4 December 2007 Issue Published: 4 December 2007 Copyright & PermissionsCopyright © 2007 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Book Review Love on the Rocks: Men, Women, and Alcohol in Post–World War II America (Gender and American Culture.) By Lori Rotskoff. 307 pp. Chapel Hill, University of North Carolina Press, 2002. $45 (cloth); $18.95 (paper). 0-8078-2728-2 (cloth); 0-8078-5402-6 (paper).
Authors: Morris Chafetz
Journal: New England Journal of Medicine (2003)
Innate lymphoid cells — a proposal for uniform nomenclature
Authors: Hergen Spits, David Artis, Marco Colonna, Andreas Diefenbach, James P. Di Santo, Gerard Eberl, Shigeo Koyasu, Richard M. Locksley, Andrew N. J. McKenzie, Reina E. Mebius, Fiona Powrie, Eric Vivier
Journal: Nature reviews. Immunology (2013)
Idiopathic osteonecrosis, hypofibrinolysis, high plasminogen activator inhibitor, high lipoprotein(a), and therapy with stanozolol
Authors: Charles J. Glueck, Richard Freiberg, Helen I. Glueck, Trent Tracy, Davis Stroop, Ying Wang
Journal: American Journal of Hematology (1995)

Abstract In five patients with idiopathic osteonecrosis (ON) of the hip, four having hypofibrinolysis mediated by high plasminogen activator inhibitor (PAI‐Fx), and one with high Lp(a), our specific aim was to determine whether therapy (Rx) with the anabolic‐androgenic steroid, Stanozolol(6 mg/day), would normalize PAI‐Fx and Lp(a) and thus potentially ameliorate ON. Prior to Rx, none of the four patients with high PAI‐Fx could normally elevate tissue plasminogen activator (tPA‐Fx) after 10 min venous occlusion at 100 mm Hg. After 12‐18 weeks on Rx, PAI‐Fx and stimulated tPA‐Fx normalized in all four patients. Prior to Rx, mean (SD) stimulated tPA‐Fx was low, 0.4 ± 0.3 IU/ml (lower limit of normal 2.28 IU/ml). On Rx, stimulated tPA‐Fx normalized, rising to 2.83 ± 1.9 IU/ml, P = 0.004. Prior to Rx, mean (SD) basal PAI‐Fx was high, 99 ± 68 (upper limit of normal 26.9 U/ml), and fell on Rx to 22.5 ± 22, P = 0.004. In two of the five patients normalization of hypofibrinolysis or high Lp(a) was accompanied by major symptomatic improvement. Prior to Rx, and 2 years after onset of unilateral hip pain, one of the four patients with high PAI‐Fx and low stimulated tPA‐Fx could walk only one block painfully. After 8 weeks on Stanozolol Rx, and continuing through 54 weeks on Rx, he walked 2 miles per day without pain, despite radiographic progression of ON. In three of the four patients with high PAI and with osteonecrosis present 0.3, 2, and 6 years prior to Stanozolol Rx, there was no clinical improvement after 14‐156 weeks of Rx despite normalization of stimulated tPA‐Fx and PAI‐Fx. The fifth patient, 1 month after onset of disabling hip pain, had normal PAI‐Fx but high Lp(a) (27 mg/dl), and MRI evidence of bone marrow edema (“transient osteoporosis”). After 3 weeks on Rx, Lp(a) normalized (14 mg/dl) and there was marked amelioration of symptoms. For the subsequent 11 weeks on Rx, this patient's Lp(a) was 5 mg/dl, and he became totally asymptomatic and remains asymptomatic 14 months later. We speculate that when ON is diagnosed prior to segmental collapse of the femoral head, it may be possible to reverse hypofibrinolysis, and/or to arrest the progression of ON. We postulate that high PAI or high Lp(a) lead to inadequate lysis of venous thrombi in bone, impaired bone venous circulation, venous hypertension of bone, and subsequent, potentially reversible development of ON. © 1995 Wiley‐Liss, Inc.
Confronting Multidrug-Resistant Tuberculosis
Authors: Richard E. Chaisson, Eric L. Nuermberger
Journal: New England Journal of Medicine (2012)

Microbial resistance to antituberculosis drugs has existed since the dawn of the antibiotic era.1 Multidrug-resistant (MDR) tuberculosis, defined by resistance to isoniazid and rifampin, requires treatment for up to 2 years with expensive second-line drugs that have poor side-effect profiles; success rates rarely exceed 65 to 75%. Extensively drug-resistant (XDR) tuberculosis, defined by additional resistance to two second-line drug classes, is more difficult to treat and may be incurable. Fewer than 3% of all patients with diagnosed tuberculosis worldwide have drug-susceptibility testing performed, and only about 10% of the estimated half-million new cases of MDR tuberculosis annually are treated appropriately. . . .
Late Recurrence after Marsupialization of Echinococcus Cyst of Liver
Authors: P. G. Konstam
Journal: BMJ (1948)

Late Recurrence After Marsupialization of Echinococcus Cyst of LiverThe following is a case of echinococcus cyst of the liver re- curring 20 years after operative removal.An additional interest lies in the fact that the cyst had become subcutaneous.
Postoperative pain control in children
Authors: J. Lockie
Journal: BMJ (1992)

Protocol for postoperative observationSedation and pain score-record hourly Level Sedation Pain I Awake Pain free 2 Drowsy Comfortable except on moving 3 Asleep but moves spontaneously Uncomfortable 4 Asleep responds to stimulation Distressed but can be comforted 5 Hard to rouse Distressed Action: Action: Level 4: Stop infusion until return to level 3 Level 2: NCA-give bolus PCA-encourage bolus (10 minutes before activity) Epidural-increase rate Level 5: Stop infusion.Call pain service Level 3: Contact pain service NCA-give bolus PCA -encourage bolus Epidural-increase rate Naloxone 4 tg/kg to be available at all times Level 4: Contact pain service NCA-give bolus or increase background infusion PCA -encourage bolus or increase background infusion Epidural-give bolus or increase rate Level 5: Contact pain service NCA=Nurse controlled analgesia.PCA=Patient controlled analgesia.
Quantitative Measurement of Melanoma Spread in Sentinel Lymph Nodes and Survival
Authors: Anja Ulmer, Klaus Dietz, Isabelle Hodak, Bernhard Polzer, Sebastian Scheitler, Murat Yildiz, Zbigniew Czyz, Petra Lehnert, Tanja Fehm, Christian Hafner, Stefan Schanz, Martin Röcken, Claus Garbe, Helmut Breuninger, Gerhard Fierlbeck, Christoph A. Klein
Journal: PLoS Medicine (2014)

Sentinel lymph node spread is a crucial factor in melanoma outcome. We aimed to define the impact of minimal cancer spread and of increasing numbers of disseminated cancer cells on melanoma-specific survival.We analyzed 1,834 sentinel nodes from 1,027 patients with ultrasound node-negative melanoma who underwent sentinel node biopsy between February 8, 2000, and June 19, 2008, by histopathology including immunohistochemistry and quantitative immunocytology. For immunocytology we recorded the number of disseminated cancer cells (DCCs) per million lymph node cells (DCC density [DCCD]) after disaggregation and immunostaining for the melanocytic marker gp100. None of the control lymph nodes from non-melanoma patients (n = 52) harbored gp100-positive cells. We analyzed gp100-positive cells from melanoma patients by comparative genomic hybridization and found, in 45 of 46 patients tested, gp100-positive cells displaying genomic alterations. At a median follow-up of 49 mo (range 3-123 mo), 138 patients (13.4%) had died from melanoma. Increased DCCD was associated with increased risk for death due to melanoma (univariable analysis; p<0.001; hazard ratio 1.81, 95% CI 1.61-2.01, for a 10-fold increase in DCCD + 1). Even patients with a positive DCCD ≤3 had an increased risk of dying from melanoma compared to patients with DCCD = 0 (p = 0.04; hazard ratio 1.63, 95% CI 1.02-2.58). Upon multivariable testing DCCD was a stronger predictor of death than histopathology. The final model included thickness, DCCD, and ulceration (all p<0.001) as the most relevant prognostic factors, was internally validated by bootstrapping, and provided superior survival prediction compared to the current American Joint Committee on Cancer staging categories.Cancer cell dissemination to the sentinel node is a quantitative risk factor for melanoma death. A model based on the combined quantitative effects of DCCD, tumor thickness, and ulceration predicted outcome best, particularly at longer follow-up. If these results are validated in an independent study, establishing quantitative immunocytology in histopathological laboratories may be useful clinically.
The −8503 G/A Polymorphism of the Adiponectin Receptor 1 Gene Is Associated With Insulin Sensitivity Dependent on Adiposity
Authors: Konstantinos Kantartzis, Andreas Fritsche, Fausto Machicao, Hans-Ulrich Häring, Norbert Stefan
Journal: Diabetes Care (2006)

Adiponectin has beneficial effects on insulin sensitivity. Unexpectedly, adiponectin knockout mice exhibit no or only mild insulin resistance. Nevertheless, under a high-fat/high-carbohydrate diet, severe insulin resistance was induced in those animals (1). Consistent with this, recent evidence (2) suggests that the relationship of adiponectin with insulin sensitivity is stronger with increasing adiposity. In addition, a haplotype in the adiponectin gene was associated with type 2 diabetes only in obese and morbidly obese subjects but not in lean subjects (3).

Single nucleotide polymorphisms (SNPs) of the genes encoding adiponectin receptor (ADIPOR) 1 …
680. Application of Gene Therapy to Tendon Healing: Modification of Tenocytes with Exogenous PDGF and VEGF Genes to Promote Collagen Production
Authors: Jin Bo Tang, Xiao Tian Wang, Paul Y. Liu
Journal: Molecular Therapy (2005)

Top of pageAbstract
Purpose: Gene therapy provides a useful method to enhance wound healing, but it has not been attempted in healing of wounds in flexor tendons in the hands, which inherently lack sufficient intrinsic healing capacity. To explore the potential of application of gene therapy to tendon wound healing, we genetically modified tenocytes with the platelet derived growth factor-B (PDGF-B) and the vascular endothelial growth factor (VEGF) gene and investigated the expression of the genes for collagen production in an in vitro model of the proliferating tenocytes.

Method: Tenocytes were obtained from cultures of rat intrasynovial tendons and randomly distributed to 34 dishes. The tenocytes in dishes in 2 experimental groups (n=9, each group) were treated for 12 hours with the plasmid containing the PDGF-B cDNA or the VEGF cDNA and were then cultured for 5 days; tenocytes in the other 8 dished received sham vector and the tenocytes in the control dishes (n=8) did not receive the vector and the gene. Efficiency of the gene transfer was evaluated by detection of the presence of the transgene in the tenocytes by reverse transcription polymerase chain reactions (RT-PCR). Levels of expression of type I and III collagen, and TGF-beta genes were determined by quantitative analysis of the products of RT-PCR and were statistically analyzed.

Results: Expression of the type I collagen gene was significantly increased by transfer of the exogenous PFDGF gene to the tenocytes (p<0.001). Transfer of the PDGF-B gene did not affect the expression of TGF-beta and the type III collagen genes significantly. Expression of TGF-beta gene increased significantly in the cells treated with exogenous VEGF cDNA (p=0.039). Expression of type I and III collagen genes by tenocytes was minimally affected by transfer of the VEGF gene to the tenocytes and was significantly weaker than that stimulated by PDGF-B gene therapy (p=0.001). Efficient gene transfer was confirmed by the presence of the PDGF-B gene or the VEGF gene in the tenocytes receiving the transferred genes.

Conclusions: Transfer of exogenous PDGF-B gene significantly enhances expression of the type I collagen gene of the tenocytes. Transfer of exogenous VEGF gene has very limited effects on promotion of collagen production in the proliferating tenocytes. In contrast, transfer of the VEGF gene significantly increases expression of the TGF-beta gene. This study suggests that transfer of the PDGF-B gene may offer a novel way of effectively promoting healing of intrasynovial flexor tendons. VEGF gene therapy is not as beneficial as PDGF-B gene therapy to tendon healing and may increase activities of TGF-beta that are associated with adhesion formations.
PROPOSED MEDICAL BRANCH OF THE NAVY LEAGUE
Authors: W. H. Clayton-Greene, G. L. Cheatle, M. Craig, J. Fawcett, A. D. Fripp, W. P. Herringham, A. Latham, W. T. Lister, E. D. Macnamara, H. S. Pendlebury, H. M. Rigby, J. R. Russell, L. Smith, R. P. Smith, J. M. G. Swainson, H. C. Thomson, H. G. Turney
Journal: BMJ (1910)
Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome
Authors: Jaroslaw P. Maciejewski, Dean Follmann, Ryotaro Nakamura, Yogen Saunthararajah, Candido E. Rivera, Toni Simonis, Kevin E. Brown, John A. Barrett, Neal S. Young
Journal: Blood (2001)
Down's syndrome: an atheroma-free model?
Authors: J C Murdoch, J C Rodger, S S Rao, C D Fletcher, M G Dunnigan
Journal: BMJ (1977)

Postmortem examination of five institutionalised patients with Down's syndrome (DS) aged 40-66 years showed a complete absence of atheroma, while a similar number of mental defectives with DS were found to have mild or severe atheroma. Previous investigation of risk factors for atheroma in 70 patients with DS and 70 age-and sex-matched mental defectives living in the same institution showed significantly lower systolic and diastolic blood pressures in the DS group, with the exception of systolic pressure in men under 40. Fasting serum cholesterol and triglyceride concentrations were similar in the two groups, but triglyceride concentrations were significantly lower than in normal people without a history of vascular disease. These unexplained observations may be relevant in further studies of the pathogenesis of atheroma.
Has guideline development gone astray? No
Authors: R. J Gibbons, E. M Antman, S. C Smith
Journal: BMJ (2010)

The move to evidence based medicine has led to a proliferation of guidelines. <b>R Grol</b> (doi: 10.1136/bmj.c343) is concerned that many are of poor quality, but <b>Raymond Gibbons and colleagues </b>argue that guidelines are important for improving health
Boxing and the risk of chronic brain injury
Authors: Paul McCrory
Journal: BMJ (2007)

<h3>Objectives</h3> We aimed to estimate the effect of pesticides on selected early biological effects among farmers, allowing for different effects of within-person and between-group (unexposed controls versus farmers) changes over time. Using a group-level estimate of exposure is a well-known approach to reduce impact of measurement error on estimated exposure-response relations. With only few exposure groups this results in an ecological study design, with potential for “aggregation” bias. By group-mean centering of individually assigned exposures it is possible to separately estimate within-individual and between-group exposure effects <h3>Method</h3> Pesticide exposure information, blood and urine were collected throughout a growing season from male corn farmers (n = 30), and non-farming controls (n = 10). We used a hierarchical mixed model to relate change in cumulative exposure to atrazine and 2.4-D from before to during the spraying season to plasma levels of 22 immuno-modulatory cytokines and compared this to a more conventional model using individual exposures only. <h3>Results</h3> Model fit for group-mean centred models averaged better than for non-centred models (lower AICs for 20/22 models for atrazine and 18/22 models for 2.4-D). Estimates for between-group differences in exposure were very similar to those from conventional (non-centred) models, while standard errors for estimates based on within-individual differences were relatively large (5x those for estimates based on between-group differences). <h3>Conclusions</h3> Group-mean centering of exposures allowed us to estimate and contrast exposure-response relations based on differences between groups and within individuals. Comparison with a more conventional approach, ignoring the clustering of individuals, showed that effect estimates were dominated by differences between groups.
Chlorpropamide and Foetal Damage
Authors: G. D. Campbell
Journal: BMJ (1963)

Post-operatively, haemoglobin was 63 %, and the patient was transfused with 2 pints (1.1 litres) of blood.Investigation showed bleeding-and clotting-time to be normal.The drainage tube was removed after 48 hours.There was a little oozing for the next few days and the patient was discharged well three weeks after admission.The second patient, whom we saw in October, 1962, was a young married woman aged 31, para 2, who had also had a nasty cough for two weeks.She had abdominal pain on coughing for a few days, and this became much worse one evening, when we were called to see her.She complained of sudden severe pain in the right iliac fossa, and felt nauseated.She did not vomit, but in the next hour had two bouts of diarrhoea.Straining at stool and rising from a lying position caused extreme pain.Pulse was 94/min., temperature 99.2°F.(37.30C.).Micturition was normal.Her last menstrual period was two weeks before.She was not shocked.B.P. 120/80.There was a tender mass to the right of the midline, ovoid in shape, with the long axis in the line of the rectus measuring about 4 in.by 3 in. (10.2 by 7.6 cm.).It was extremely tender, not movable, and felt relatively superficial.With the memory of the previous case fresh in our minds, a diagnosis of ruptured rectus abdominis was made and she was admitted to the surgical wards of the Gloucester Royal Infirmary.At operation on the following day a lower midline incision revealed a haematoma behind the right rectus muscle and the posterior wall of the rectus sheath.Blood clot amounted to 5 oz.(142 ml.).There was no evidence of torn muscle fibres or bleeding points.The abdomen was explored: the ovaries and uterus were normal.Routine appendicectomy was performed.The post-operative period was uneventful, the patient being discharged well after 11 days.Although this condition is said to be most common in middle-aged and elderly women with chronic bronchitis, it is of interest that our second case occurred in a well-nourished healthy woman of 31 during an isolated episode of mild bronchitis.
Adaptive mechanisms of the aorta and left ventricle to volume overloading following abrupt aortic regurgitation in rabbits
Authors: Y. Wainai
Journal: Cardiovascular Research (1991)

Compensatory mechanisms of the left ventricle for volume overloading caused by acute aortic regurgitation and associated changes in physiological properties of the aorta were studied in rabbits.Aortic regurgitation was produced by aortic valve perforation, and haemodynamic measurements were performed before, 1 h and 4 weeks afterwards. Characteristic impedance of the distensibility of the aorta were calculated.42 Japanese white rabbits were used. The animals were anaesthetised with intravenous urethane.Total systemic vascular resistance did not change significantly during the 4 weeks. When aortic regurgitation was produced, an immediate increase in circumferential distensibility was followed by the gradual dilatation of the aorta. An increase in circumferential distensibility resulted in decreased characteristic impedance, and the reduction in cardiac output caused by aortic regurgitation was compensated by increased systolic shortening of left ventricular dimensions at 1 h. After 4 weeks, however, decreased characteristic impedance was associated with increased aortic diameters during both systole and diastole, and dilatation and hypertrophy of the left ventricle were responsible for compensation of left ventricular performance.Volume overloading of the left ventricle by aortic regurgitation gave rise to a two stage compensatory process over a 4 week period and the aorta interacted with chronological changes in left ventricular performance.