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1.
JAMA Netw Open ; 3(5): e204803, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32407504

RESUMO

Importance: Perception of weight loss requirements before bariatric surgery varies among patients, physicians, and health insurance payers. Current clinical guidelines do not require preoperative weight loss because of a lack of scientific support regarding its benefits. Objective: To examine the association of preoperative body mass index (BMI) and weight loss with 30-day mortality after bariatric surgery. Design, Setting, and Participants: This cohort study used data from 480 075 patients who underwent bariatric surgery from 2015 to 2017 in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program, which covers more than 90% of all bariatric surgery programs in the United States and Canada. Clinical and demographic data were collected at all participating institutions using a standardized protocol. Data analysis was performed from December 2018 to November 2019. Exposures: Preoperative BMI and weight loss. Main Outcomes and Measures: 30-day mortality after bariatric surgery. Results: Of the 480 075 patients (mean [SD] age 45.1 [12.0] years; 383 265 [79.8%] women), 511 deaths (0.1%) occurred within 30 days of bariatric surgery. Compared with patients with a preoperative BMI of 35.0 to 39.9, the multivariable-adjusted odds ratios for 30-day mortality for patients with preoperative BMI of 40.0 to 44.9, 45.0 to 49.9, 50.0 to 54.9, and 55.0 and greater were 1.37 (95% CI, 1.02-1.83), 2.19 (95% CI, 1.64-2.92), 2.61 (95% CI, 1.90-3.58), and 5.03 (95% CI, 3.78-6.68), respectively (P for trend < .001). Moreover, compared with no preoperative weight loss, the multivariable-adjusted odds ratios for 30-day mortality for patients with weight loss of more than 0% to less than 5.0%, 5.0% to 9.9%, and 10.0% and greater were 0.76 (95% CI, 0.60-0.96), 0.69 (95% CI, 0.53-0.90), and 0.58 (95% CI, 0.41-0.82), respectively (P for trend = .003). Conclusions and Relevance: In this study, even moderate weight loss (ie, >0% to <5%) before bariatric surgery was associated with a lower risk of 30-day mortality. These findings may help inform future updates of clinical guidelines regarding bariatric surgery.


Assuntos
Cirurgia Bariátrica/mortalidade , Índice de Massa Corporal , Período Pré-Operatório , Redução de Peso , Canadá/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Estados Unidos/epidemiologia
2.
J Vasc Interv Radiol ; 31(7): 1143-1147, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32457012

RESUMO

PURPOSE: To determine whether a single 10-mg intravenous dose of the promotility agent metoclopramide reduces the fluoroscopy time, radiation dose, and procedure time required for gastrojejunostomy (GJ) tube placement. METHODS: This prospective, randomized, double-blind, placebo-controlled trial enrolled consecutive patients who underwent primary GJ tube placement at a single institution from April 10, 2018, to October 3, 2019. Exclusion criteria included age less than 18 years, inability to obtain consent, metoclopramide allergy or contraindication, and altered pyloric anatomy. Average fluoroscopy times, radiation doses, and procedure times were compared using t-tests. The full study protocol can be found at www.clinicaltrials.gov (NCT03331965). RESULTS: Of 110 participants randomized 1:1, 45 received metoclopramide and 51 received placebo and underwent GJ tube placement (38 females and 58 males; mean age, 55 ± 18 years). Demographics of the metoclopramide and placebo groups were similar. The fluoroscopy time required to advance a guide wire through the pylorus averaged 1.6 minutes (range, 0.3-10.1 minutes) in the metoclopramide group versus 4.1 minutes (range, 0.2-27.3 minutes) in the placebo group (P = .002). Total procedure fluoroscopy time averaged 5.8 minutes (range, 1.5-16.2 minutes) for the metoclopramide group versus 8.8 minutes (range, 2.8-29.7 minutes) for the placebo group (P = .002). Air kerma averaged 91 mGy (range, 13-354 mGy) for the metoclopramide group versus 130 mGy (range, 24-525 mGy) for the placebo group (P = .04). Total procedure time averaged 16.4 minutes (range, 8-51 minutes) for the metoclopramide group versus 19.9 minutes (range, 6-53 minutes) for the placebo group (P = .04). There were no drug-related adverse events and no significant differences in procedure-related complications. CONCLUSIONS: A single dose of metoclopramide reduced fluoroscopy time by 34%, radiation dose by 30%, and procedure time by 17% during GJ tube placement.


Assuntos
Nutrição Enteral/instrumentação , Derivação Gástrica/instrumentação , Fármacos Gastrointestinais/administração & dosagem , Motilidade Gastrointestinal/efeitos dos fármacos , Metoclopramida/administração & dosagem , Duração da Cirurgia , Radiografia Intervencionista , Administração Intravenosa , Adulto , Idoso , Método Duplo-Cego , Nutrição Enteral/efeitos adversos , Fluoroscopia , Derivação Gástrica/efeitos adversos , Fármacos Gastrointestinais/efeitos adversos , Humanos , Metoclopramida/efeitos adversos , Pessoa de Meia-Idade , North Carolina , Estudos Prospectivos , Doses de Radiação , Exposição à Radiação , Radiografia Intervencionista/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
3.
Surg Endosc ; 34(4): 1812-1818, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31240476

RESUMO

BACKGROUND: The Roux-en-Y gastric bypass (RYGB) isuery ID="Q1" Text="Author:Kindly check the edit made in the article title." -->the most efficacious procedure of choice for obese patients with gastroesophageal reflux disease (GERD). The laparoscopic sleeve gastrectomy (LSG) has high rates of worsening GERD post operatively. Little evidence exists as to whether the use of objective foregut investigations has a meaningful impact on surgical procedure selection. This study examined whether a standard preoperative foregut evaluation protocol effected procedure selection in bariatric patients presenting for surgical evaluation with subjective symptoms of GERD. METHODS: Patients presenting for bariatric surgery evaluation with subjective symptoms of GERD entered into a predetermined protocol of foregut evaluation. Patients initially underwent upper endoscopy and esophagram. If the patient desired a LSG, further testing with esophageal pH testing and high-resolution manometry was ordered. If significant pathology was discovered on any of these investigations RYGB was recommended, if investigations were normal LSG was felt to be permissible. Data were collected prospectively from July 2016 to December 2018 and reviewed. RESULTS: One hundred and thirty-three patients were identified as being eligible to have progressed through the protocol. Pathology was commonly discovered on preoperative evaluations. On EGD Barrett's esophagus was discovered in 4%, grade C or D esophagitis in 18% and hiatal hernia in 36% of patients. On esophagram, hiatal hernia was discovered in 42.3% of patients. Abnormal esophageal motility was discovered in 41% and abnormal DeMeester scores in 83% of tested patients. Of the 133 patients evaluated, the final procedure the patient ultimately underwent was primarily determined based on protocol test results in 24.8% of cases. CONCLUSIONS: Foregut pathology is common in bariatric patients with subjective symptoms of GERD. Implementing a comprehensive protocol to objectively assess these patients leads to a significant clinical impact on which procedure these patients ultimately undergo.


Assuntos
Cirurgia Bariátrica/métodos , Derivação Gástrica/métodos , Refluxo Gastroesofágico/etiologia , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Cuidados Pré-Operatórios/métodos , Adulto , Idoso , Feminino , Refluxo Gastroesofágico/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Adulto Jovem
5.
Obes Surg ; 30(2): 451-455, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31606840

RESUMO

BACKGROUND: The laparoscopic sleeve gastrectomy (LSG) is now the most commonly performed bariatric surgery in the world. Multiple studies have demonstrated the equivalence between the LSG and Roux-en-Y gastric bypass (RYGB) with regard to weight loss and comorbidity resolution. Few studies have examined the differences in body mass composition change between the two procedures. METHODS: Sixty-three patients undergoing either LSG or RYGB underwent calculation of total body mass, ideal body mass, lean mass, and fat mass by air displacement plethysmography (BodPodtm) prior to surgery and at 12 months postoperatively. Calculations of excess body weight, % excess weight loss, change in % fat mass, and change in % lean mass were then performed at each time interval. RESULTS: Thirty-three patients underwent LSG and 30 patients underwent RYGB. Mean percent excess weight loss in the LSG and RYGB group was 47.2% and 53.4% respectively (p = 0.165, 95% CI - 14.8-2.6). Mean percent change in fat mass for the LSG group and RYGB group was 9.2% and 10.51% respectively (p = 0.249, 95% CI - 0.86-3.2). Mean percent change in lean mass for the LSG group and RYGB group was 9.4% and 10.49% respectively (p = 0.383, 95% CI 2.85-1.13). CONCLUSION: The LSG and RYGB both impart dramatic meaningful loss in excess body weight. In addition, both the LSG and RYGB impart dramatic reductions in fat mass. However, both procedures induce loss of lean mass and there appears to be no difference between the two procedures in this regard despite their anatomic and physiologic differences.


Assuntos
Composição Corporal/fisiologia , Gastrectomia , Derivação Gástrica , Obesidade Mórbida/cirurgia , Adulto , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/métodos , Comorbidade , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/diagnóstico , Pletismografia/métodos , Período Pós-Operatório , Estudos Retrospectivos , Redução de Peso/fisiologia
6.
J Toxicol Environ Health A ; 82(6): 387-400, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31064277

RESUMO

Epidemiological associations were reported in several studies between persistent organochlorine organic pollutants and type 2 diabetes mellitus (T2D). Mississippi is a highly agricultural state in the USA, particularly the Delta region, with previous high usage of organochlorine (OC) insecticides such as p,p'- dichlorodiphenyltrichloroethane (DDT). In addition, there is a high proportion of African Americans who display elevated prevalence of T2D. Therefore, this State provides an important dataset for further investigating any relationship between OC compounds and metabolic diseases. The aim of this study was to assess whether soil and serum levels of OC compounds, such as p,p'- dichlorodiphenyldichloroethylene (DDE), arising from the heavy historical use of legacy OC insecticides, might serve as an environmental public health indicator for T2D occurrence. Soil samples from 60 Delta and 60 non-Delta sites randomly selected were analyzed for the presence of OC compounds. A retrospective cohort study of adult men (150 from each region) was recruited to provide a blood sample for OC compound quantitation and select demographic and clinical information including T2D. Using multivariable logistic regression, an association was found between increasing serum DDE levels and T2D occurrence in non-Delta participants (those subjects with lower serum DDE levels), as opposed to Delta participants (individuals with higher serum DDE levels). Thus, while there was a relationship between serum DDE levels and T2D in those with lower burdens of DDE, the lack of association in those with higher levels of DDE indicates a complex non-monotonic correlation between serum DDE levels and T2D occurrence complicating the goal of finding a public health marker for T2D. Abbreviations: BMI, body mass index; CVD, cardiovascular disease; CDC, Center for Disease Control, United States of America; DDE, p,p'- dichlorodiphenyldichloroethylene; DDT, p,p'- dichlorodiphenyltrichloroethane; GC/MS, gas chromatography/mass spectrometry; GIS, geographic information system; GPS, global positioning system; HDL, high-density lipoprotein; HTN, hypertension; IDW, inverse distance weighting; IRB, Institutional Review Board; LDL, low-density lipoprotein; LOQ, limit of quantitation; NHANES, National Health and Nutrition Examination Surveys; POPs, persistent organic pollutants; OC, organochlorine; PCB, polychlorinated biphenyl; SIM, single-ion monitoring; T2D, type 2 diabetes mellitus; USA, United States of America.


Assuntos
Clordano/análogos & derivados , Diabetes Mellitus Tipo 2/epidemiologia , Diclorodifenil Dicloroetileno/sangue , Poluentes Ambientais/sangue , Hidrocarbonetos Clorados/sangue , Solo/química , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Clordano/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Mississippi/epidemiologia , Praguicidas/sangue , Prevalência , População Branca/estatística & dados numéricos
7.
Am J Med ; 123(6): 502-4, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20569751

RESUMO

Subclinical thyroid disease, a term applied to patients with no or minimal thyroid-related symptoms with abnormal laboratory values, is diagnosed more frequently with the use of thyroid-stimulating hormone (TSH) screening and newer high-sensitivity assays. These are laboratory diagnoses, with subclinical hypothyroidism defined as an elevated TSH with a normal free thyroxine and triiodothyronine concentration, and subclinical hyperthyroidism as a subnormal TSH with normal free thyroxine and triiodothyronine levels. Although studies defining which patients require treatment are few, decisions should be individualized based upon laboratory values and symptoms. This article reviews the etiologies, diagnoses, treatments and indications, and monitoring of patients with subclinical thyroid disease.


Assuntos
Antitireóideos/uso terapêutico , Radioisótopos do Iodo/administração & dosagem , Doenças da Glândula Tireoide , Tireotropina/sangue , Tiroxina/administração & dosagem , Tiroxina/sangue , Tri-Iodotironina/sangue , Antitireóideos/administração & dosagem , Relação Dose-Resposta a Droga , Humanos , Índice de Gravidade de Doença , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/diagnóstico , Doenças da Glândula Tireoide/terapia , Resultado do Tratamento
8.
AIDS ; 23(9): 1135-42, 2009 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-19390418

RESUMO

OBJECTIVE: Human papillomavirus (HPV) is a common sexually transmitted agent that causes anogenital cancer and precancer lesions that have an inflammatory infiltrate, may be friable and bleed. Our aim was to determine the association between anal HPV infection and HIV acquisition. DESIGN: A prospective cohort study. METHODS: We recruited 1409 HIV-negative men who have sex with men from a community-based setting in Boston, Denver, New York and San Francisco. We used Cox proportional hazards regression modeling and assessed the independent association of HPV infection with the rate of acquisition of HIV infection. RESULTS: Of 1409 participants contributing 4375 person-years of follow-up, 51 HIV-seroconverted. The median number of HPV types in HPV-infected HIV-seroconverters was 2 (interquartile range 1-3) at the time of HIV seroconversion. After adjustment for sexual activity, substance use, occurrence of other sexually transmitted infections and demographic variables, there was evidence (P = 0.002) for the effect of infection with at least two HPV types (hazard ratio 3.5, 95% confidence interval 1.2-10.6) in HIV seroconversion. CONCLUSION: Anal HPV infection is independently associated with HIV acquisition. Studies that incorporate high-resolution anoscopy to more accurately identify HPV-associated disease are needed to determine the relationship between HPV-associated disease and HIV seroconversion.


Assuntos
Doenças do Ânus/virologia , Soropositividade para HIV/virologia , HIV-1 , Homossexualidade Masculina , Lesões Pré-Cancerosas/virologia , Adulto , Boston , Soropositividade para HIV/transmissão , Humanos , Masculino , Pessoa de Meia-Idade , New York , Infecções por Papillomavirus/transmissão , Infecções por Papillomavirus/virologia , Estudos Prospectivos , RNA Viral , São Francisco
9.
J Invertebr Pathol ; 97(2): 159-64, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17897669

RESUMO

The endophytic fungus, Muscodor albus produces several volatile compounds (alcohols, esters, ketones, acids and lipids) that are biocidal for a range of organisms including plant pathogenic bacteria and fungi, nematodes and insects. We studied the effects of these volatiles on 3-day-old potato tuber moth larvae within infested tubers inside sealed chambers. The length of exposure to M. albus significantly affected mortality of larvae, calculated as percentage of larvae failing to survive to the adult stage. Exposure durations of 3, 7, or 14 days at 24 degrees C followed by incubation in fresh air at 27 degrees C until emergence resulted in mortalities of 84.2, 95.5 and 99.6%, respectively. However, the longer exposures also resulted in increased levels of carbon dioxide (CO(2)) that are unacceptable for tuber storage. Effects of M. albus on larval survival was also monitored at 10, 15 and 24 degrees C, using an exposure duration of 7 days followed by incubation in clean air at 27 degrees C until emergence. Mortality of larvae was sharply reduced at the lower temperatures resulting in 50.8, 76.8, and 95.4% mortality, respectively. Tuber storage conditions, especially cooling rates, are discussed with respect to using M. albus as a fumigant without simultaneously producing unacceptable (for tuber storage) levels of CO(2).


Assuntos
Ascomicetos/patogenicidade , Temperatura Baixa , Fumigação/métodos , Lepidópteros/microbiologia , Lepidópteros/patogenicidade , Solanum tuberosum/parasitologia , Álcoois/metabolismo , Álcoois/farmacologia , Animais , Ascomicetos/metabolismo , Dióxido de Carbono/metabolismo , Dióxido de Carbono/farmacologia , Ésteres/metabolismo , Ésteres/farmacologia , Parasitologia de Alimentos , Cetonas/metabolismo , Cetonas/farmacologia , Larva/efeitos dos fármacos , Larva/microbiologia , Lepidópteros/efeitos dos fármacos , Fatores de Tempo
10.
J Exp Zool A Ecol Genet Physiol ; 307(1): 62-6, 2007 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-17109393

RESUMO

Anhydrobiotic animals protect cellular architecture and metabolic machinery in the dry state, yet the molecular repertoire supporting this profound dehydration tolerance is not fully understood. For the desiccation-tolerant crustacean, Artemia franciscana, we report differential expression of two distinct mRNAs encoding for proteins that share sequence similarities and structural features with late-embryogenesis abundant (LEA) proteins originally discovered in plants. Bioinformatic analyses support assignment of the LEA proteins from A. franciscana to group 3. This eucoelomate species is the most highly evolved animal for which LEA gene expression has been reported. It is becoming clear that an ensemble of micromolecules and macromolecules is important for establishing the physical conditions required for cellular stabilization during drying in nature.


Assuntos
Artemia/metabolismo , Proteínas de Plantas/metabolismo , RNA Mensageiro/metabolismo , Sequência de Aminoácidos , Animais , Clonagem Molecular , Biologia Computacional , Primers do DNA , Desidratação , Dados de Sequência Molecular , Análise de Sequência de DNA
11.
J Mol Diagn ; 8(4): 430-2; quiz 527, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16931582

RESUMO

The US Food and Drug Administration-cleared ViroSeq HIV-1 Genotyping System (ViroSeq) and other population sequencing-based human immunodeficiency virus type 1 (HIV-1) genotyping methods detect antiretroviral drug resistance mutations present in the major viral population of a test sample. These assays also detect some mutations in viral variants that are present as mixtures. We compared detection of the K103N nevirapine resistance mutation using ViroSeq and a sensitive, quantitative point mutation assay, LigAmp. The LigAmp assay measured the percentage of K103N-containing variants in the viral population (percentage of K103N). We analyzed 305 samples with HIV-1 subtypes A, C, and D collected from African women after nevirapine administration. ViroSeq detected K103N in 100% of samples with >20% K103N, 77.8% of samples with 10 to 20% K103N, 71.4% of samples with 5 to 10% K103N, and 16.9% of samples with 1 to 5% K103N. The sensitivity of ViroSeq for detection of K103N was similar for subtypes A, C, and D. These data indicate that the ViroSeq system reliably detects the K103N mutation at levels above 20% and frequently detects the mutation at lower levels. Further studies are needed to compare the sensitivity of different assays for detection of HIV-1 drug resistance mutations and to determine the clinical relevance of HIV-1 minority variants.


Assuntos
HIV-1/genética , Mutação Puntual , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNA/métodos , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Feminino , Genótipo , Humanos , Mutação , Nevirapina/uso terapêutico , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade
12.
J Acquir Immune Defic Syndr ; 42(5): 610-3, 2006 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-16773030

RESUMO

INTRODUCTION: We used a sensitive point mutation assay, LigAmp, to detect and quantify K103N-containing variants in African women who received single-dose nevirapine (NVP) to prevent mother-to-child HIV-1 transmission. METHODS: Plasma for testing was collected 6 to 8 weeks postpartum from 301 women (144 subtype A, 63 subtype C, and 94 subtype D). RESULTS: The portion of women with 0.5% or more K103N-containing variants was lowest for subtype A (60/144, 41.7%) and highest for subtype C (44/63, 69.8%; P < 0.0001). K103N was rarely detected in pre-NVP samples. In a multivariate model, K103N detection was associated with HIV-1 subtype (C > A), after adjusting for log10 delivery viral load, the number of days between NVP dosing and sample collection, age, and parity. Among women with K103N detected: (1) the median %K103N was lower for subtype A (2.2%) than C (11.7%, P = 0.0001) or D (5.5%, P = 0.04), and (2) in a multivariate linear model, higher log10 (%K103N) was associated with HIV subtype (C > A, P = 0.0001; D > A, P = 0.01; and C vs D, no difference), but not other factors. CONCLUSIONS: After administration of single-dose NVP, K103N was detected more frequently and at higher levels in women with subtypes C and D than A. Further studies are needed to evaluate the clinical significance of NVP-resistant variants in this setting.


Assuntos
Fármacos Anti-HIV/farmacologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Nevirapina/farmacologia , Complicações Infecciosas na Gravidez/virologia , Substituição de Aminoácidos , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Feminino , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , HIV-1/classificação , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Malaui , Mutação de Sentido Incorreto , Nevirapina/uso terapêutico , Mutação Puntual , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estatística como Assunto , Uganda
13.
AIDS Res Hum Retroviruses ; 22(3): 289-93, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16545016

RESUMO

We analyzed the nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) susceptibility of 29 subtype A HIV-1 clones isolated from 10 Ugandan women after single-dose nevirapine (NVP) administration. Six clones had no NNRTI resistance-associated mutations ("wild type"), eight had K103N, nine had Y181C, five had G190A, and one had Y181S. Three clones displayed unexpected phenotypic drug susceptibility/resistance based on their RT genotypes. One wild-type clone had reduced susceptibility to NVP, delavirdine (DLV), and efavirenz (EFV), one clone with K103N was susceptible to all three NNRTIs, and one clone with G190A had extreme hypersusceptibility to DLV. Three unusual HIV-1 RT amino acid substitutions may have contributed to the unexpected phenotypes of the clones: I31T, N136S, and N265D. These polymorphisms were rarely detected among 47,900 HIV-1 genotypes from clinical samples of predominantly United States origin. Further studies are needed to define the genetic correlates of antiretroviral drug resistance in nonsubtype B HIV-1.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral , HIV-1/classificação , HIV-1/efeitos dos fármacos , Mutação , Inibidores da Transcriptase Reversa/farmacologia , Alcinos , Substituição de Aminoácidos , Benzoxazinas , Células Clonais , Ciclopropanos , Delavirdina/farmacologia , Feminino , Transcriptase Reversa do HIV/genética , Humanos , Nevirapina/farmacologia , Oxazinas/farmacologia , Polimorfismo Genético
14.
AIDS Res Hum Retroviruses ; 21(4): 319-24, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15943576

RESUMO

The HIVNET 012 trial in Uganda demonstrated that a regimen of single-dose nevirapine (NVP) can prevent HIV-1 mother-to-child transmission. Previous studies show that HIV-1 with one or more NVP resistance (NVPR) mutations can be selected in many women as early as 7 days after single-dose NVP. We evaluated the genetic linkage of NVPR mutations in plasma from women in HIVNET 012 collected 7 days after single-dose NVP administration. The HIV-1 pol region was amplified and cloned from 20 plasma samples (16 with NVPR mutations detected by population sequencing and 4 with no NVPR mutations detected), and 10 clones from each sample were sequenced. Up to five different NVPR mutations were detected in clones from a single sample. K103N and Y181C were the most common mutations detected. Clones with two genetically linked mutations were detected in four samples. Different combinations of NVPR mutations were linked in individual clones, but none of the clones contained both K103N and Y181C. Further studies are needed to evaluate whether selection of minority variants with one or more NVPR mutations after single-dose NVP is clinically relevant.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/genética , Nevirapina/farmacologia , Substituição de Aminoácidos , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Feminino , Protease de HIV/genética , Transcriptase Reversa do HIV/genética , HIV-1/efeitos dos fármacos , HIV-1/isolamento & purificação , Humanos , Dados de Sequência Molecular , Mutação , Nevirapina/administração & dosagem , Nevirapina/uso terapêutico , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/uso terapêutico , Análise de Sequência de DNA , Uganda
15.
J Infect Dis ; 192(1): 24-9, 2005 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-15942890

RESUMO

BACKGROUND: The HIV Network for Prevention Trials (HIVNET) 012 trial showed that NVP resistance (NVPR) emerged in some women and children after the administration of single-dose nevirapine (SD-NVP). We tested whether K103N-containing human immunodeficiency virus (HIV)-1 variants persisted in women and infants 1 year or more after the administration of SD-NVP. METHODS: We analyzed samples from 9 women and 5 infants in HIVNET 012 who had NVPR 6-8 weeks after the administration of SD-NVP. Samples were analyzed with the ViroSeq system and with 2 sensitive resistance assays, LigAmp and TyHRT. RESULTS: ViroSeq detected the K103N mutation in 8 of 9 women and in 2 of 5 infants. LigAmp detected the K103N mutation at low levels in 8 of 9 women and in 4 of 5 infants. K103N was not detected by ViroSeq 12-24 months after the administration of SD-NVP but was detected by LigAmp in 3 of 9 women and in 1 of 5 infants. K103N was also detected in those samples by use of the TyHRT assay. CONCLUSIONS: K103N-containing variants persist in some women and infants for 1 year or more after the administration of SD-NVP. Sensitive resistance assays may provide new insight into the impact of antiretroviral drug exposure on HIV-1 evolution.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/genética , Infecções por HIV/prevenção & controle , HIV-1/efeitos dos fármacos , HIV-1/genética , Nevirapina/farmacologia , Fármacos Anti-HIV/administração & dosagem , Esquema de Medicação , Feminino , Genótipo , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Mutação , Nevirapina/administração & dosagem , Gravidez , Fatores de Tempo , Proteínas Virais/genética
16.
Vector Borne Zoonotic Dis ; 4(4): 296-305, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15671736

RESUMO

The genetic diversity of Bartonella species within a small mammal community and in individual cotton rats (Sigmodon hispidus) was examined by trapping, capturing, sampling, and releasing of marked animals over a 17-month interval. Based on sequence analyses of the Bartonella gltA gene, amplicons separated into four genogroups (A, B, C, and Pin) containing 11 variants. Although the prevalence of bacteremia due to different genogroups/variants of Bartonella was temporally variable, variants of genogroup A predominated during each sampling period. Multiple gltA variants were often (20.5% of individuals) isolated from a single cotton rat blood sample; a maximum of five variants was recovered from an individual during its sampling history. Among 92 cotton rats bacteremic at two or more sampling dates, 34 rats retained a single genetic variant, alone or in mixed infection, throughout their sampling history. The temporal course of individual infections was complex as the succession of gltA variants was variable and detectable bacteremia was often intermittent. No antibodies (titer of >1:8) were detected to homologous strains of Bartonella recovered from individual cotton rats during their sampling history. The temporal course of Bartonella infections could result from a single, persistent, and potentially multi-genogroup/variant infection, during which variants differentially dominate the detectable bacteremia.


Assuntos
Bacteriemia/veterinária , Infecções por Bartonella/veterinária , Bartonella/classificação , Bartonella/isolamento & purificação , Doenças dos Roedores/microbiologia , Sigmodontinae/microbiologia , Animais , Anticorpos Antibacterianos/sangue , Bacteriemia/microbiologia , Bartonella/genética , Infecções por Bartonella/microbiologia , Variação Genética , Genótipo , Fenótipo , Filogenia , Reação em Cadeia da Polimerase/veterinária , Estudos Prospectivos , Roedores , Estados Unidos
17.
Nat Methods ; 1(2): 141-7, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15782177

RESUMO

We developed the LigAmp assay for sensitive detection and accurate quantification of viruses and cells with single-base mutations. In LigAmp, two oligonucleotides are hybridized adjacently to a DNA template. One oligonucleotide matches the target sequence and contains a probe sequence. If the target sequence is present, the oligonucleotides are ligated together and detected using real-time PCR. LigAmp detected KRAS2 mutant DNA at 0.01% in mixtures of different cell lines. KRAS2 mutations were also detected in pancreatic duct juice from patients with pancreatic cancer. LigAmp detected the K103N HIV-1 drug resistance mutation at 0.01% in plasmid mixtures and at approximately 0.1% in DNA amplified from plasma HIV-1. Detection in both systems is linear over a broad dynamic range. Preliminary evidence indicates that reactions can be multiplexed. This assay may find applications in the diagnosis of genetic disorders and the management of patients with cancer and infectious diseases.


Assuntos
Análise Mutacional de DNA/métodos , Testes Genéticos/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Polimorfismo de Nucleotídeo Único/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Alinhamento de Sequência/métodos , Análise de Sequência de DNA/métodos , Biomarcadores Tumorais/análise , Farmacorresistência Viral/genética , HIV-1/genética , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Proteínas ras
19.
J Athl Train ; 36(1): 81-84, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12937518

RESUMO

OBJECTIVE: To describe the evaluation, diagnosis, and conservative treatment of a 15-year-old male high school football player with an avulsion fracture of the ischial tuberosity. BACKGROUND: Avulsion fracture of the ischial tuberosity is a rare and often missed diagnosis. A literature review offered limited information concerning the evaluation and conservative treatment of such an injury. DIFFERENTIAL DIAGNOSIS: Avulsion fracture of the ischial tuberosity. TREATMENT: The athlete's treatment goal was to return to football and weight lifting without surgical intervention. Treatment initially focused on controlling pain and normalizing gait. The athlete then advanced to a progressive resistance exercise program and functional sporting drills as he improved in hip range of motion, strength, and neuromuscular control. He returned to unrestricted sporting activities 14 weeks after the injury. UNIQUENESS: Avulsion of the ischial tuberosity is a rare injury. Most published case reports have recommended surgical intervention for this injury, with little information describing conservative treatment. CONCLUSIONS: Sports medicine practitioners must obtain an accurate history, perform a thorough physical examination, and obtain appropriate radiographs in order to correctly diagnose an ischial tuberosity avulsion fracture. Furthermore, they should consider conservative treatment for minimally displaced ischial tuberosity avulsion fractures. Should the athlete not show significant functional gains within a month of conservative treatment, the health care provider should consider surgical treatment.

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