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Biomedical subjects

J M Lang

Publications and source records attributed to J M Lang.

At least 19 recordsLinked to original sources

Increasing the number of hepatitis B vaccine injections augments anti-HBs response rate in HIV-infected patients. Effects on HIV-1 viral load.

Preventing hepatitis B by vaccination is essential in HIV-infected patients (higher progression rate of HBV infection to chronicity, lower rate of serum HBe Ag loss). However, it has been shown a decreased anti-HBs response in these individuals after a standard vaccination (3 doses of 20 micrograms). Thus, we tested the hypothesis that doubling the number of hepatitis B vaccine injections might increase anti-HBs response rate. HIV-infected patients with CD4 > 200/microliter, who were on stable antiretroviral treatment, as well as seronegative for HBV markers, and who have never been vaccinated against HBV, were given 3 intramuscular injections of Genhevac B 20 micrograms at 1 month intervals. Initial non responders were given 3 additional monthly injections. Anti-HBs titer was followed. We also evaluated the effects on HIV-1 viral load. Twenty patients with a median CD4 cell count of 470/microliter were enrolled. The response rate after three 20 micrograms injections was 55% (11/20), lower in individuals with CD4 between 200 and 500/microliter (4/12 = 33.3%), compared to patients with CD4 above 500/microliter (7/8 = 87.5%, P = 0.02). Among 9 initial non-responders, only 2 did not respond to 3 additional doses; thus, the overall response rate was 90% (18/20). Geometric mean titers of anti-HBs were 133 IU/l and 77.5 IU/l, after 3 and 6 Genhevac doses, respectively (P = 0.38). One year later, only 10/17 (58.8%) patients had protective anti-HBs. Five patients experienced a significant viral load increase, transient in 3 cases. These preliminary results suggest that doubling the number of hepatitis B vaccinations in HIV-infected patients might significantly improve anti-HBs response rate; however, close monitoring of anti-HBs is necessary because of its short-lived persistence. The effects on HIV-1 viral load are limited.

Adult↗

Fat distribution evaluated by computed tomography and metabolic abnormalities in patients undergoing antiretroviral therapy: preliminary results of the LIPOCO study.

BACKGROUND: Fat distribution abnormalities have been reported in patients treated with various antiretroviral drug regimens. The LIPOCO study is an ongoing observational study of unselected HIV-infected patients which aims to better characterize such disorders and their metabolic correlations. METHODS: Cross-sectional analysis of data collected at baseline in the first 154 male patients included. Investigators divided patients into four predetermined clinical categories of fat distribution: lipoatrophy, obesity, mixed condition and normal. Body composition (tetrapolar bioelectrical impedance analysis and skinfold thickness), fat distribution [computed tomography (CT) scan], plasma glucose and insulin concentrations both fasting and during an oral glucose tolerance test and endocrine and lipid profile were measured and compared between the four groups. RESULTS: Patients in the lipoatrophy group had significantly decreased abdominal and mid-thigh subcutaneous fat area values and elevated levels of plasma triglycerides. Patients in the obese and mixed groups had significantly increased intra-abdominal fat area values and elevated levels of plasma insulin and C-peptide. The CT scans identified some patients with isolated subcutaneous fat accumulation but no other alterations in fat distribution and no insulin resistance. Visceral adipose tissue measured by CT scan was positively correlated with fasting insulin and the sum of insulin levels (P < 0.0001). Fasting insulin as well as the sum of insulin levels were negatively correlated with the delta HIV-RNA (log(10)). In a multivariate logistic regression model, the use of stavudine significantly correlated with fat wasting in both nucleoside reverse transcriptase inhibitor and protease inhibitor groups: odds ratio (OR), 413 [95% confidence interval (CI), 5.2-999; P = 0.0068] and OR, 2.08 (95% CI, 0.92-7.0; P = 0.058) respectively, when compared with the use of zidovudine. Neither lamivudine or didanosine use, nor the use of protease inhibitors were significantly associated with fat distribution abnormalities or fat wasting. CONCLUSIONS: These preliminary results suggest that three major types of fat distribution abnormalities may occur in isolation or in association in HIV-infected patients undergoing active antiretroviral therapy: a fat depletion or 'lipoatrophy' syndrome which might be related to the use of stavudine; a mixed or fat redistribution syndrome related to an unusual side-product of effective virus control; and a subcutaneous adiposity syndrome reflecting increase in caloric intake.

Acquired Immunodeficiency Syndrome↗

[Emergence of resistant hepatitis B virus strains during long-term lamivudine therapy in human immunodeficiency virus co-infected patients].

Seven patients co-infected with hepatitis B virus (HBsAg and HBeAg carriers, quantifiable HBV DNA with the bDNA technic) and human immunodeficiency virus received a triple antiretroviral combination therapy, including lamivudine (150 mg twice a day). Hepatitis B viral load rapidly became undetectable in 6/7 patients. It remained below the level of detection in 2 subjects, after 20 and 22 months of treatment, with one of them achieving HBeAg/anti-HBe seroconversion. However, in the other 4 individuals, hepatitis B viremia increased again after 8 to 16 months of lamivudine-containing regimen. The last patient was a non-responder. The 4 relapsers developed a double mutation Leu(528) for Met(528) and Met(552) for Val(552), on hepatitis B virus polymerase, either concomitant (M8 and M16) with a hepatitis B virus DNA increase, or 2 months earlier (M10 and M12). The high frequency of hepatitis B virus resistance to lamivudine emphasizes the necessity of identifying more effective strategies, such as double combination therapies.

Adult↗

A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy.

OBJECTIVE: To compare body composition, body fat distribution and insulin secretion in patients taking nucleoside reverse transcriptase inhibitor (NRTI) therapy. DESIGN AND SETTING: Cross-sectional study in three French AIDS clinical centres. PATIENTS: Forty-three HIV-infected patients on long-term NRTI therapy including stavudine (n = 27) or zidovudine (n = 16) and 15 therapy-naive HIV-infected patients (control group). MAIN OUTCOME MEASURES: Fat wasting was assessed by physical examination and body composition by bioelectrical impedance. Regional fat distribution was estimated using caliper measurements of skinfold thickness at four sites and evaluated by computed tomography at abdominal and mid-thigh level. Fasting glucose, insulin, C-peptide, triglyceride, cholesterol, free fatty acid, testosterone, follicle stimulating hormone, luteinizing hormone, cortisol levels, CD4 cell count and HIV viral load were determined. Daily total caloric and nutrient intake were evaluated. RESULTS: The zidovudine group and the control group had similar body composition and regional fat distribution. Stavudine therapy was associated with a significantly lower percentage of body fat (12.9% versus 15.2% in the zidovudine group; P < 0.05), markedly decreased subcutaneous to visceral fat ratio (0.90 +/- 0.63 versus 1.92 +/- 1.34, P < 0.01) and higher mean intake of fat and cholesterol (P < 0.01). Fasting plasma glucose, insulin and C-peptide levels were similar among the three groups. Triglyceride levels were significantly higher in the stavudine group than in the controls (P < 0.05), but did not differ between the stavudine and the zidovudine group or between the zidovudine and the control group. Free fatty acids tended to be higher in the stavudine group but the difference did not reach statistical significance. Lipodystrophy was observed clinically in 17 (63%) patients taking stavudine, and in three (18.75%) patients taking zidovudine after a median time of 14 months. The relative risk of developing fat wasting was 1.95 in the stavudine group as compared with the zidovudine group (95% confidence interval, 1.18-3.22). Five out of 12 patients had a major or mild improvement in their lipodystrophy after stavudine was discontinued. CONCLUSION: Lipodystrophy may be related to long-term NRTI therapy, particularly that including stavudine.

Adipose Tissue↗

High prevalence of GB virus C/hepatitis G virus RNA in patients infected with human immunodeficiency virus.

Prevalence of GBV-C/HGV was determined in a cohort of HIV-infected patients, via a reverse transcription-polymerase chain reaction detection of RNA in serum, amplifying the NS5 region of GBV-C/HGV genome. GBV-C/HGV RNA was detected in 143 (37.7%) of 379 patients, with similar results in the different HIV risk groups: 25/56 (44.6%) in intravenous drug users, 66/161 (41%) in homo- and bisexual men, 35/108 (32.4%) in heterosexual patients, 6/20 (30%) in transfusion recipients (P=0.41). There was no difference according to the presence or absence of hepatitis C virus infection. In univariate analysis, GBV-C/HGV genome prevalence was lower in patients over 50 years old (18.2%), compared to other age groups (20-29 years: 34.2%; 30-39 years: 44.3%; 40-49 years: 36.7%, P=0.03), as well as in patients with normal CD4 cell count (29.2% vs. 45.4% between 200-500/mm3, and 35.3% below 200 CD4/mm3, P=0.012) and individuals with a chronic hepatitis B. However, in the multivariate analysis, the only prognostic factor of GBV-C/HGV RNA positivity was the presence of a chronic hepatitis B, compared to the absence of any HBV marker, or a previous exposition to HBV (presence of anti-HBc and/or anti-HBs, absence of HBsAg), or the presence of anti-HBs alone.

Adult↗

Isolated renal Aspergillus abscess in an AIDS patient with a normal CD4+ cell count on highly active antiretroviral therapy.

Isolated renal Aspergillus abscess is a very rare complication of HIV infection. It usually occurs in patients with severe immune deficiency. The case of a 29-year-old HIV-infected homosexual male, a nonintravenous drug abuser, who developed a right renal Aspergillus abscess despite normalization of the CD4+ cell count after highly active antiretroviral treatment is described. When antimicrobial treatment failed (amphotericin B followed by itraconazole), he was cured by right nephrectomy and remains in good health 3 months later with no recurrence. In cases of Aspergillus renal abscess in HIV-infected patients, surgery is the treatment of choice, especially in the current era of highly active antiretroviral therapy.

AIDS-Related Opportunistic Infections↗

Epidemiological issues in perinatal outcomes research.

Outcomes research takes an expansive view of health and seeks to improve the science of evaluating the quality of health care by refining traditional clinical measures and including measures of overall patient well-being. This broader view of health (rather than disease) is especially appropriate in perinatal research. Attention to the perinatal period requires recognition that pregnancy is in most cases a healthy life event, that there is a predictable progression and time course with a key definable outcome (delivery) and that there are two patients, mother and infant. Two issues stand out as methodological challenges in the design and conduct of perinatal outcomes studies. The first is to establish baseline comparability across study groups with regard to case-mix or perinatal risk, and also comparability of services other than the one under study. The second is the refinement of traditional perinatal outcomes, such as low birthweight and Caesarean section, and the inclusion of patient-based health status measures, such as health-related quality of life, for the peripartum woman and her newborn.

Adult↗

Practice effects on commonly used measures of executive function across twelve months.

Fifty men (age M = 32.50; education M = 14.98 years) were administered the Wisconsin Card Sorting Test (WCST), Ruff Figural Fluency Test (FFT), Verbal Concept Attainment Test (VCAT) Trail Making Test, Parts A and B (TMT), and F-A-S Verbal Fluency at baseline and 12 months later. WCST, FFT, and VCAT scores improved significantly over a 12-month interval. In contrast, TMT and F-A-S scores did not change. Level of intellectual ability failed to moderate the effect of previous testing upon performance. Suggestions concerning the use of these measures in longitudinal research designs and clinical follow-up examinations are offered, and reliable change indices concerning these measures are included.

Adult↗

Characteristics of nurse-midwife patients and visits, 1991.

OBJECTIVES: This study describes the patient populations served by and visits made to certified nurse-midwives (CNMs) in the United States. METHODS: Prospective data on 16,729 visits were collected from 369 CNMs randomly selected from a 1991 population survey. Population estimates were derived from a multistage survey design with probability sampling. RESULTS: We estimated that approximately 5.4 million visits were made to nearly 3000 CNMs nationwide in 1991. Most visits involved maternity care, although fully 20% were for care outside the maternity cycle. Patients considered vulnerable to poor access or outcomes made 7 of every 10 visits. CONCLUSIONS: Nurse-midwives substantially contribute to the health care of women nationwide, especially for vulnerable populations.

Adolescent↗

Nail changes in patients infected with human immunodeficiency virus. A prospective controlled study.

OBJECTIVES: To study the frequency of nail changes in a population of human immunodeficiency virus (HIV)-infected patients and to evaluate the specificity of these findings by comparison with HIV-negative control subjects. DESIGN: Prospective controlled study. Nail changes were recorded by a standardized clinical examination (curvature, nail plate, color, onychomycosis). In case of clinical diagnosis of onychomycosis, mycological culture was performed. SETTING: Primary care university hospital. PATIENTS: A total of 155 HIV-1-positive patients and 103 healthy HIV-negative control subjects of comparable age and sex ratio. INTERVENTION: None. MAIN OUTCOME MEASURE: Clinical examination findings. RESULTS: Nail symptoms were present in 67.7% of HIV-positive patients vs 34.0% of controls (P << .001). The following symptoms were significantly more frequent in the HIV group: clubbing (5.8%) (P < .05), transverse lines (7.1%) (P < .01), onychoschizia (7.1%) (P < .05), leukonychia (14.3%) (P < .001), and longitudinal melanonychia (14.8%) (P < .01). The main finding was onychomycosis in 30.3% of patients vs 12.6% of controls (P < .001). Trichophyton rubrum was present in 48% of onychomycoses and unusual Candida species were also recorded. Multiple fungi were frequently cultured in a single patient. The mean CD4+ cell count was lower in patients with onychomycosis and the frequency of onychomycosis increased in advanced stages of HIV disease. Acquired total leukonychia of the 20 nails was present in 4% of patients. CONCLUSION: Nail symptoms are much more frequent in patients with HIV than in healthy controls, and some of them could be linked to the level of immunosuppression.

Adult↗

Production of cytokines in patients infected by hepatitis C virus.

T helper type 1 (Th1) cytokines play an important role in antiviral defence. The purpose of this study was to quantify by ELISA IL2, soluble receptor of IL2 (IL2Rs), IFNgamma TNFbeta, IL4, IL6 and IL10 levels in the sera of 134 HCV-positive patients, 69 of whom were coinfected with HIV, and in 54 HIV-HCV-negative patients. The mean IL2Rs and IFN serum levels were much higher in patients with anti-HCV than in the control group, whereas the mean IL4 and IL6 levels were lower in patients infected with HCV. There were no significant differences in cytokine levels between patients with and without HIV. There were significantly less patients with HCV than controls with IFNgamma levels under cut-off, and significantly more patients with HCV with IL4 levels under cut-off. Although serum level of cytokines must be interpreted with caution, the results suggest that Th1 response is enhanced in HCV infection.

AIDS-Related Opportunistic Infections↗

Assessing the role of case mix in cesarean delivery rates.

OBJECTIVE: Implicit in comparisons of unadjusted cesarean rates for hospitals and providers is the assumption that differences result from management practices rather than differences in case mix. This study proposes a method for comparison of cesarean rates that takes the effect of case mix into account. METHODS: All women delivered of infants at our institution from December 1, 1994, through July 31, 1995, were classified according to whether they received care from community-based practitioners (N=3913) or from the hospital-based practice that serves a higher-risk population (N=1556). Women were categorized according to both obstetric history (nulliparas, multiparas without a previous cesarean, multiparas with a previous cesarean) and the presence of obstetric conditions influencing the risk of cesarean delivery (multiple birth, breech presentation or transverse lie, preterm, no trial of labor for a medical indication). We determined the percent of women in each parity-obstetric condition subgroup and calculated a standardized cesarean rate for the hospital-based practice using the case mix of the community-based practitioners as the standard. RESULTS: The crude cesarean rate was higher for the hospital-based practice (24.4%) than for the community-based practitioners (21.5%), a rate difference of 2.9% (95% confidence interval=0.4%, 5.4%; P=.02). However, the proportion of women falling into categories conferring a high risk of cesarean delivery (multiple pregnancy, breech presentation or transverse lie, preterm, no trial of labor permitted) was twice as high for the hospital-based practice (24.4% hospital, 12.1% community). The standardization indicates that if the hospital-based practitioners had the same case mix as community-based practitioners, their overall cesarean rate would be 20.1%, similar to the 21.5% rate of community providers (rate difference=-1.4%, 95% confidence interval =-3.1%, 0.3%; P=.11). CONCLUSION: Standardization for case mix provides a mechanism for distinguishing differences in cesarean rates resulting from case mix from those relating to differences in practice. The methodology is not complex and could be applied to facilitate fairer comparisons of rates among providers and across institutions.

Cesarean Section↗