Total absence of functional acid labile subunit, resulting in severe insulin-like growth factor deficiency and moderate growth failure

CONTEXT: Primary IGF deficiency (IGFD) describes the condition in which serum concentrations of IGF-I are low in the face of normal to elevated GH production. Because IGF-I, which circulates as part of a ternary complex with IGF binding protein (IGFBP)-3 and acid-labile subunit (ALS), mediates the growth-promoting effects of GH, IGFD is associated with severe growth failure in humans. OBJECTIVE: We investigated a case of IGFD in which serum IGF-I and IGFBP-3 were abnormally low, yet growth failure was modest (-2.1 sd score at 15.5 yr of age). RESULTS: The young male subject, from a consanguineous pedigree, had a postnatal growth profile consistently below the third percentile. The subject had a normal fasting GH level of 3.7 muU/ml and normal serum GH binding protein level (1258 pmol/liter; normal range 431-1892 pmol/liter), but serum IGF-I and IGFBP-3 were profoundly reduced (-5.8 and -7.2 sd score, respectively, at age 12.3 yr), even through puberty. A novel homozygous missense mutation was subsequently identified in the ALS gene, which resulted in severe deficiency of serum ALS (undetectable). CONCLUSIONS: ALS is critical for maintaining normal serum concentrations of IGF-I and IGFBP-3, most likely by prolonging the half-lives of both proteins. ALS deficiency can be associated with moderate growth failure, but in this patient, the onset and progression of puberty appear to be normal. Altogether the results support a modest role for the ternary complex in the regulation of stature.     

Bone mineral density in the complete androgen insensitivity and 5alpha-reductase-2 deficiency syndromes

CONTEXT: Subjects with complete androgen insensitivity (CAI) and 5alpha-reductase-2 deficiency (5alphaRD-2) are natural human models to study the direct effect of androgens on bone mineral density (BMD). OBJECTIVE: The objective of this study was to test the hypothesis that androgens have a direct effect on BMD in men. DESIGN: This was a prospective, observational study (1989-1999) using dual energy x-ray absorptiometry. SETTING: The study was set in an outpatient specialty referral center. PATIENTS OR OTHER PARTICIPANTS: All known subjects with these conditions (12 CAI and 16 5alphaRD-2) from diverse sociodemographic backgrounds were recruited for the study. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURE: Mean Z score and weight-matched Z score at lumbar spine and femoral neck for CAI and 5alphaRD-2 subjects were determined. RESULTS: Twelve CAI subjects had mean Z score at L2-L4 of -2.84 (+/-0.97, P < 0.001) and a mean weight-matched Z score of -2.52 (+/-0.94, P < 0.001). The mean Z score at the femoral neck was -1.33 (+/-0.91, P < 0.001) and the mean weight-matched Z score was -1.10 (+/-0.82, P = 0.001). Sixteen 5alphaRD-2 subjects had a mean Z score at L2-L4 of -0.84 (+/-1.29, P = 0.02) and a mean weight-matched Z score for 15 of 16 patients of -0.44 (+/-1.08, P = 0.14). The mean Z score at the femoral neck was 0.14 (+/-1.02, P = 0.58) and the mean weight-matched Z score for 15 of 16 patients was 0.49 (+/-0.94, P = 0.06). Therefore, in CAI subjects, BMD was significantly decreased in the spine and hip. 5alphaRD-2 subjects had normal BMD values. CONCLUSIONS: 1) Androgens are of direct importance in the development and/or maintenance of BMD; and 2) testosterone and/or low levels of dihydrotestosterone appear to be sufficient for BMD development and/or maintenance.     

Should drug therapy be personalized based on race?

The A-HeFT (African American Heart Failure Trial) showed that isosorbide/hydralazine was associated with significant reductions in mortality in African Americans with heart failure compared with placebo. The results of a recently published genetic substudy identified a gene variant related to nitric oxide synthase production that attributed to the treatment response observed in patients enrolled in the A-HeFT. This finding suggests that isosorbide/hydralazine's ability to improve heart failure outcomes is tied to a genetic trait that may be more prevalent in African Americans than whites, but is not necessarily related to perceived race.     

Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3'-kinase/Akt pathway and Bcl-2 family proteins

Prostate cancer is a major health problem in the U.S. and the available treatment and surgical options have proven to be inadequate in controlling the mortality and morbidity associated with this disease. It is therefore necessary to intensify our efforts to better understand this disease and develop novel approaches for its prevention and treatment. This study was conducted to evaluate the chemopreventive/antiproliferative potential of resveratrol (trans-3,4',5,-trihydroxystilbene) against prostate cancer and its mechanism of action. Treatment with resveratrol (0-50 micromol/L for 24 hours) resulted in a significant (a) decrease in cell viability, (b) decrease of clonogenic cell survival, (c) inhibition of androgen (R1881)-stimulated growth, and (d) induction of apoptosis in androgen-responsive human prostate carcinoma (LNCaP) cells. Interestingly, at similar concentrations, resveratrol treatment did not affect the viability or rate of apoptosis in normal human prostate epithelial cells. Furthermore, our data showed that resveratrol-treatment resulted in significant dose-dependent inhibition in the constitutive expression of phosphatidylinositol 3'-kinase and phosphorylated (active) Akt in LNCaP cells. Resveratrol treatment for LNCaP cells was also found to result in a significant (a) loss of mitochondrial membrane potential, (b) inhibition in the protein level of antiapoptotic Bcl-2, and (c) increase in proapoptotic members of the Bcl-2 family, i.e., Bax, Bak, Bid, and Bad. Taken together, our data suggested that resveratrol causes an inhibition of phosphatidylinositol 3'-kinase/Akt activation that, in turn, results in modulations in Bcl-2 family proteins in such a way that the apoptosis of LNCaP cells is promoted. Based on these studies, we suggest that resveratrol could be developed as an agent for the management of prostate cancer.     

Electronic healthcare communications in Vietnam in 2004

BACKGROUND: There is a lack of literature about health information systems (HIS) in "developing" countries, including Vietnam. However, computerization and network development are proceeding in these places, although not in a systematic, transparent way. OBJECTIVE: This is a preliminary overview of HIS's and healthcare communications in Vietnam's four-tiered public healthcare system. It is to indicate the direction that nation might take in order to establish a modern, standards-compliant, national HIS. METHODS: We conducted site visits and interviews in Hanoi and nearby provinces. Additional information was derived from publications of the Vietnamese government and the United Nations. RESULTS: Many of the top-level "central" hospitals have HIS's, although their quality and daily usage varies. Fewer provincial hospitals have networks; district hospitals have a few stand-alone computers, and commune health centers have no computers. Patients often go directly to higher-level providers, due to a widely held perception of better care at such sites. Communications among healthcare units are largely on paper, consisting mostly of administrative matters and some hand-written patient referrals. Telephones are used for discussions of specific matters. Internet connections are almost all dial-up and often belong to individual staff members rather than the healthcare units. Lower-level units derive much of their general medical information from television and newspapers. However, there is considerable interest in computerization among healthcare workers at all levels. CONCLUSION: Familiarization with computerized communications, i.e., training and hardware at all healthcare levels, must be the first step towards a modern healthcare communications network in Vietnam. The skills to do this already exist. The aim of such a network must be to raise the level of information and quality of care at the lower levels. Adherence to international standards, such as HL7, from the beginning would enable the country to bypass many years of haphazard development.     

High HIV sexual risk behaviors and sexually transmitted disease prevalence among injection drug users in Northern Vietnam: implications for a generalized HIV epidemic

BACKGROUND: HIV prevalence in Vietnam is currently concentrated among injection drug users (IDUs). The extent to which this core risk group represents a potential for broader HIV transmission to the general population is currently unknown. METHODS: A community-based cross-sectional study among IDUs in Vietnam assessed sexually transmitted disease (STD) prevalence and behavioral risk factors. Qualitative interview data enhanced quantitative findings. RESULTS: The prevalence of any STDs among 272 IDUs was 30% (chlamydia, 9%; herpes simplex virus type 2 [HSV-2], 22%; gonorrhea, 0%; and syphilis, 1%). Part-time work or unemployment (odds ratio [OR] = 2.74, 95% confidence interval [CI]: 1.1 to 6.9), sex with > or =2 sex workers in the past year (OR = 4.9, 95% CI: 1.91 to 12.6), having ever smoked heroin (OR = 4.5, 95% CI: 1.1 to 18.3), and injecting less frequently than daily (OR = 3.9, 95% CI: 1.43 to 10.6) were independently associated with chlamydial infection. Urban residency (OR = 4.0, 95% CI: 1.4 to 11.0) and daily injecting (OR = 2.2, 95% CI: 1.1 to 4.4) were independently associated with HSV-2. Odds of HSV-2 among older (> or =28 years of age) IDUs who had sex with <2 sex workers in the past year was higher than among younger IDUs who had sex with more sex workers (OR = 6.4, 95% CI: 2.1 to 18.4). CONCLUSIONS: High STD prevalence and high-risk sexual and parenteral behaviors among IDUs indicate the potential for HIV/STD transmission to the general Vietnamese population.     

Performance of methods of occlusal caries detection in permanent teeth under clinical and laboratory conditions

OBJECTIVES: To compare performance of visual inspection and Laser fluorescence methods to detect occlusal caries lesions under clinical and laboratory conditions in permanent teeth. METHODS: One hundred and ten sites in 57 third molars scheduled for extraction were examined with visual inspection and laser fluorescence (DIAGNOdent) device by two trained examiners. After the extraction, teeth were re-examined. Then, teeth were sectioned to perform histological validation. Best cut-off points were calculated with ROC analysis, and sensitivity, specificity and accuracy were calculated at D2 and D3 thresholds. Comparisons between the methods and conditions of examination were performed using McNemar test. Inter-examiner agreement in the same conditions and agreement between the methods performed in vivo and in vitro conditions were assessed by Kappa test. Laser fluorescence values obtained in two conditions were compared with Wilcoxon test. RESULTS: No difference was observed with visual inspection in both conditions. Laser fluorescence performed in vitro presented higher specificity and accuracy at D3 threshold. Visual inspection showed higher reproducibility. After adjustment of cut-off points for laser fluorescence method, there was no difference between the evaluated parameters. CONCLUSION: Only slightly differences were observed between the examinations performed under clinical and laboratory conditions in the detection of occlusal caries lesions in permanent teeth.