Decreased bone mineral density in pre-menopause women with prolactinoma

Tumoral hyperprolactinemia and consequent hypogonadism have been associated with osteoporosis. Bone mineral density (BMD) was measured by dual-energy RX absorptiometry in 24 patients with prolactinoma (15 macro and 9 micro adenomas; age range = 18 to 49 years). Student unpaired t or Mann-Whitney tests were used to compare groups, and Spearman test studied correlations. Lumbar spine (LS) was the most affected, as LS Z-score was < -2 SD in 20.83% of the patients. No difference was found in densitometric parameters for the comparison between macro and microprolactinoma, or those with normal prolactin versus hyperprolactinemia. LS BMD and LS Z-score were higher in the patients with > 8 menstrual cycles in the preceding year then in those with oligoamenorrhea (p = 0.030). The number of cycles was correlated to LS BMD (r = 0.515, p = 0.017) and body mass index to femoral neck BMD (r = 0.563, p = 0.006) and total femur BMD (r = 0.529, p = 0.011). CONCLUSIONS: Decreased bone mineral density was detected in 20.83% of our young patients with prolactinoma. The great involvement of trabecular bone skeletal regions, such as vertebrae, suggests the participation of hypogonadism in the pathogenesis of bone disease. Irrespective of prolactin levels, return to normal menses seems the best index of good control.     

Assessing disability and quality of life in systemic sclerosis: construct validities of the Cochin Hand Function Scale, Health Assessment Questionnaire (HAQ), Systemic Sclerosis HAQ, and Medical Outcomes Study 36-Item Short Form Health Survey

OBJECTIVE: To assess the construct validity of the Cochin Hand Function Scale (CHFS) and the relevance of using aggregate scores for the scleroderma Health Assessment Questionnaire (sHAQ) and Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) in systemic sclerosis (SSc). METHODS: We evaluated 50 patients with SSc (mean +/- SD age and disease duration 54 +/- 12 years and 9 +/- 8 years, respectively), of which 26 had limited cutaneous SSc (lcSSc) and 23 diffuse SSc (dSSc). Quality of life was assessed by the SF-36, global disability by the Health Assessment Questionnaire (HAQ) and sHAQ, and hand disability by the CHFS. Construct validity was assessed by convergent and divergent validity (Spearman's rank correlation coefficient) and factor analysis. RESULTS: The CHFS had good construct validity and its total score explained 75% of the variance of the HAQ. The HAQ had better construct validity than the aggregate sHAQ and their scores correlated well (r = 0.88). The aggregate sHAQ was no better than the HAQ in discriminating between lcSSc and dSSc. SF-36 physical and mental components had acceptable convergent and divergent validity. Factor analysis of the 8 subscales extracted 3 factors explaining 72% of the variance, which differed from the a priori stratification with physical and mental subscales extracted in the same factor. CONCLUSION: In patients with SSc, the CHFS has good construct validity, the HAQ should be preferred over the aggregate sHAQ for assessing physical functioning, and use of SF-36 physical and mental components aggregate scores is questionable.     

Genetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma

Smaller-scale evaluations suggest that common genetic variation in candidate genes related to immune function may predispose to the development of non-Hodgkin lymphoma (NHL). We report an analysis of variants within genes associated with immunity and inflammation and risk of NHL using a panel of 9412 single-nucleotide polymorphisms (SNPs) from 1253 genes in a study of 458 patients with NHL and 484 frequency-matched controls. We modeled haplotypes and risk of NHL, as well as the main effects for all independent SNPs from a gene in multivariate logistic regression models; we separately report results for nonsynonymous (ns) SNPs. In gene-level analyses, the strongest findings (P < or = .001) were for CREB1, FGG, MAP3K5, RIPK3, LSP1, TRAF1, DUSP2, and ITGB3. In nsSNP analyses, the strongest findings (P < or = .01) were for ITGB3 L59P (odds ratio [OR] = 0.66; 95% confidence interval [CI] 0.52-0.85), TLR6 V427A (OR = 5.20; CI 1.77-15.3), SELPLG M264V (OR = 3.20; CI 1.48-6.91), UNC84B G671S (OR = 1.50; CI 1.12-2.00), B3GNT3 H328R (OR = 0.74; CI 0.59-0.93), and BAT2 V1883L (OR = 0.64; CI 0.45-0.90). Our results suggest that genetic variation in genes associated with immune response (TRAF1, RIPK3, BAT2, and TLR6), mitogen-activated protein kinase (MAPK) signaling (MAP3K5, DUSP2, and CREB1), lymphocyte trafficking and migration (B3GNT3, SELPLG, and LSP1), and coagulation pathways (FGG and ITGB3) may be important in the etiology of NHL, and should be prioritized in replication studies.     

Targeted treatment using monoclonal antibodies and tyrosine-kinase inhibitors in pregnancy

An expanding knowledge of the signalling pathways involved in the cell cycle has led to great improvements in the understanding of the molecular events involved in carcinogenesis. The past decade has seen substantial advances with the introduction of several classes of targeted therapeutics for the treatment of various cancers and autoimmune disorders. However, the question arises as to whether pregnant women can take advantage of these new treatments in view of the potential risks to the fetus. Published work suggests that biological agents, like traditional treatments, have the potential to affect the fetus, and should, therefore, be used with caution during pregnancy. However, when targeted treatment is clearly indicated the magnitude of the risk to the fetus might not reach that of standard chemotherapy. In circumstances where better alternative treatments do not exist, or where failure to use targeted treatments would result in suboptimum patient care or survival, the risk-benefit analysis might favour the use of potentially effective molecular treatment during pregnancy.     

Urolithiasis in pregnancy

The presentation of urolithiasis is often dramatic, but rarely is it more anxiety provoking than during pregnancy. The evaluation and the intervention are often approached with trepidation as the health of the mother and the fetus must be taken into account. The typical diagnostic course and surgical management used in the nonpregnant population must be reevaluated in the expectant mother. Failure to promptly diagnose and manage urolithiasis during pregnancy may have adverse consequences for mother and child. The authors present a review of the relevant anatomic and physiologic changes of pregnancy as they affect stone disease and outline options for radiologic evaluation and surgical management.     

Blunted humoral response to influenza vaccination in patients exposed to zidovudine plus trimethoprim-sulfamethoxazole

STUDY OBJECTIVES: To determine as proof of principle the effect of combination exposure to zidovudine plus trimethoprim-sulfamethoxazole (TMP-SMX) on humoral immune responses to influenza vaccination in patients with human immunodeficiency virus (HIV). DESIGN: Prospective, open-label trial. SETTING: University-affiliated infectious diseases outpatient clinic. PATIENTS: Twenty-three HIV-infected adults receiving antiretroviral therapy, with CD4+ cell counts greater than 350 cells/mm3 and undetectable viral loads. INTERVENTION: Patients were assigned to one of four treatment groups: zidovudine (6 patients), TMP-SMX (7), zidovudine plus TMP-SMX (5), or neither drug (5); TMP-SMX was given as a 28-day course. Patients were subsequently immunized with the yearly influenza vaccine, and humoral responses were compared among groups 20-24 days after vaccination. MEASUREMENTS AND MAIN RESULTS: Antibody responses to influenza A and B were measured, and total and activated T and B cell percentages in the peripheral blood were determined. Mean influenza B-specific serum immunoglobulin (Ig)G titers were significantly lower in patients receiving TMP-SMX alone (0.98 +/- 0.60 reference value, p=0.010) or the combination of zidovudine plus TMP-SMX (0.73 +/- 0.29 reference value, p=0.003) compared with those receiving neither drug (1.95 +/- 0.38 reference value). This corresponded to a significantly lower percentage of patients in the combination group that achieved immunoprotective titers to influenza B compared with the group who received neither drug (control group; 20% vs 100%, p=0.048). In addition, the relationship between serum IgG titer and CD4+ cell count was statistically significantly different for patients exposed to zidovudine plus TMP-SMX versus control patients for both influenza A and B (F statistics 8.72 and 11.70, respectively, compared with critical F value 7.26 for p<0.025). Likewise, the relationship between influenza B serum IgG and CD4+ cell count was different among patients who received TMP-SMX versus those who did not receive TMP-SMX (F statistic 5.95 compared with critical F value 4.56 for p<0.025). No significant differences were observed among T and B cell percentages in the blood. CONCLUSION: Combination exposure to zidovudine plus TMP-SMX causes a clinically significant suppression of humoral immune responses to influenza vaccination in HIV-infected patients.     

Tuberculosis,focussed tools and the right schools: estimated impact and cost of a targeted student screening programme for tuberculosis infection

Background

The World Health Organization (WHO) recommends targeted screening for latent tuberculosis infection (LTBI) among high-risk populations. Recent studies that evaluate targeted school-based programmes in low burden settings are scarce.

Aims

To evaluate a school screening programme for recently arrived migrant students from moderate and high tuberculosis (TB) burden countries and estimate (1) the number of cases of active TB that were prevented and (2) the cost per case of active TB prevented.

Methods

Students were screened with tuberculin skin tests (TST) at schools with a high migrant population intake. Those with positive results were referred for specialist evaluation. Outcomes were retrospectively assessed using 5 years of prospectively collected data. Cost data were collected. Main outcomes measured were the number of children were diagnosed with LTBI who completed treatment, and programme costs.

Results

Of 4728 student screened, 295 (6.2%) were diagnosed with LTBI. Of these, 273 (92.5%) were offered preventive therapy, 242 (82.0%) commenced and 204 (69.2%) completed therapy. The number needed to screen (NNS) was 23 per completed course of preventive treatment for LTBI. Assuming a 10% lifetime risk of reactivation, the NNS was 386 per case of TB disease notification avoided. The cost of screening was A$23 932 per case of TB disease avoided.

Conclusions

This TB strategy is supported by the high rate of TB infection in the student group, the treatment uptake and completion rates. Cost–benefit is linked with lifetime risk of TB reactivation. Targeted school screening programmes represent an important opportunity for TB control in low-burden settings.