CDC staging based on absolute CD4 count and CD4 percentage in an HIV-1-infected Indian population: treatment implications

CD4⁺ T‐cell levels are an important criterion for categorizing HIV‐related clinical conditions according to the CDC classification system and are therefore important in the management of HIV by initiating antiretroviral therapy and prophylaxis for opportunistic infections due to HIV among HIV‐infected individuals. However, it has been observed that the CD4 counts are affected by the geographical location, race, ethnic origin, age, gender and changes in total and differential leucocyte counts. In the light of this knowledge, we classified 600 HIV seropositive antiretroviral treatment (ART)‐naïve Indian individuals belonging to different CDC groups A, B and C on the basis of CDC criteria of both CD4% and CD4 counts and receiver operating characteristic (ROC) curves were generated. Importantly, CDC staging on the basis of CD4% indicated significant clinical implications, requiring an early implementation of effective antiretroviral treatment regimen in HIV‐infected individuals deprived of treatment when classified on the basis of CD4 counts.     

Development of a species-specific PCR assay for detection of Leishmania donovani in clinical samples from patients with kala-azar and post-kala-azar dermal leishmaniasis

We have developed a PCR assay that is capable of amplifying kinetoplast DNA (kDNA) of Leishmania donovani in a species-specific manner among Old World leishmanias. With Indian strains and isolates of L. donovani the assay was sensitive enough to detect kDNA in an amount equivalent to a single parasite or less. The extreme sensitivity of the assay was reflected in its ability to detect parasite DNA from small volumes of peripheral blood of patients with kala-azar (KA) and from skin lesions from patients with post-KA dermal leishmaniasis (PKDL). A total of 107 clinical leishmaniasis samples were analyzed. Of these 102 (95.3%) were positive by PCR. The test provided a diagnosis of KA with 96% sensitivity using patient whole-blood samples instead of bone marrow or spleen aspirates that are obtained by invasive procedures. The assay was also successful in the diagnosis of 45 of 48 PKDL cases (93.8%). Cross-reactions with pathogens prevalent in the area of endemicity, viz., Mycobacterium tuberculosis, Mycobacterium leprae, and Plasmodium spp., could be ruled out. Eighty-one control samples, including dermal scrapings from healthy portions of skin from patients with PKDL were all negative. Two of twenty controls from the area of endemicity were found positive by PCR assay; however, there was a good possibility that these two were asymptomatic carriers since they were serologically positive for KA. Thus, this PCR assay represents a tool for the diagnosis of KA and PKDL in Indian patients in a noninvasive manner, with simultaneous species identification of parasites in clinical samples.     

Cardiopulmonary Bypass and Serum Thyroid Hormone Profile in Pediatric Patients with Congenital Heart Disease

Objective: To study the effect of cardiopulmonary bypass (CPB) on serum thyroid hormone profile in children undergoing open‐heart surgery. Design: Prospective cross‐sectional study. Setting: Multispecialty tertiary level referral center. Patients: One hundred consecutive patients (age 15.9 ± 14.6 months, weight 6.7 ± 2.5 kg) undergoing open‐heart surgery under CPB. Interventions: None. Outcome Measures: Levels and trends of serum total thyroxine (TT4), free thyroxine (FT4), total tri‐iodothyronine (TT3), free tri‐iodothyronine (FT3) and thyroid stimulating hormone (TSH), survival, inotropic score, duration of mechanical ventilation, postoperative complications. Results: TT4 levels were 9.08 ± 3.6, 6.4 ± 2.5, 6.24 ± 2.1, 6.43 ± 2.4, 7.20 ± 3.0 µg/dL at baseline and at 1, 24, 48 and 72 hours; FT4 levels were 1.82 ± 0.5, 1.49 ± 0.3, 1.29 ± 0.3, 1.32 ± 0.4, and 1.43 ± 0.5 ng/dL; TT3 levels were 1.81 ± 0.4, 1.31 ± 0.3, 0.99 ± 0.2, 1.0 ± 0.37, and 1.17 ± 0.48 ng/ml; FT3 levels were 4.09 ± 1.0, 3.02 ± 0.8, 2.21 ± 0.6, 2.22 ± 0.7, and 2.66 ± 1.05 pg/ml; TSH levels were 5.40 ± 3.8, 2.0 ± 3.1, 1.24 ± 1.1, 2.90 ± 3.3, and 4.03 ± 3.4 mIU/L. There was significant fall (29.1% for FT4, 32.1% for TT4, 77% for TSH, 46% for FT3 and 45% for TT3, p < 0.0001). When area under curve (AUC) TT4 was compared between survivors (n = 87) and nonsurvivors (n = 12), significantly larger AUC was seen in survivors (492.81 ± 158.6) than nonsurvivors (360.75 ± 179.6 p = 0.0125). In survivors >72 hours, AUC TT4 was larger in patients with uneventful postoperative course versus those with postoperative complications (516.48 ± 18.6 vs. 394.78 ± 29.9, p = 0.001). AUC TT4 showed significant inverse correlation with inotropic score and borderline inverse correlation with duration of mechanical ventilation. Conclusion: Children undergoing surgery under CPB showed significant fall in thyroid hormones. Because TT4 level is modifiable, prophylactic administration of TT4 for improving outcomes needs to be studied further.     

In vitro and in vivo antibacterial evaluation of DRF 8417, a new oxazolidinone

OBJECTIVES AND METHODS: DRF 8417, a novel oxazolidinone, has been evaluated against Gram-positive and fastidious Gram-negative bacteria. In vitro activity of DRF 8417 was determined by broth microdilution method and in vivo efficacy studies were carried out in different murine systemic infection models. RESULTS: DRF 8417 exhibited potent activity against Gram-positive pathogens with MIC(50) and MIC(90) values ranging from 0.06 to 1 mg/L. MICs against Haemophilus influenzae and Moraxella catarrhalis were one to two dilutions lower than those of linezolid. The in vivo efficacy, by oral route, in different susceptible and resistant Gram-positive systemic bacterial infection models ranged from 2.0 to 2.9 mg/kg. CONCLUSIONS: These studies displayed the excellent in vitro and in vivo activity of DRF 8417 against Gram-positive pathogens and lower MICs when compared with linezolid against H. influenzae and M. catarrhalis.     

A heteroaryldihydropyrimidine activates and can misdirect hepatitis B virus capsid assembly

Heteroaryldihydropyrimidines (HAPs) are a new class of antivirals inhibiting production of hepatitis B virus (HBV) virions in tissue culture. Here, we examine the effect of a representative HAP molecule, methyl 4-(2-chloro-4-fluorophenyl)-6-methyl-2-(pyridin-2-yl)-1,4-dihydropyrimidine-5-carboxylate (HAP-1), on the in vitro assembly of HBV capsid protein (Cp). HAP-1 enhances the rate and extent of Cp assembly over a broad concentration range. Aberrant particles, dominated by hexagonal arrays of Cp, were observed from assembly reactions with high HAP-1 concentrations. HAP-1 also led to dissociation of metastable HBV capsids, overcoming a kinetic barrier to dissociation by scavenging Cp and redirecting its assembly into hexamer-rich structures. Thus, HAP drugs act as allosteric effectors that induce an assembly-active state and, at high concentration, preferentially stabilize noncapsid polymers of Cp. HAP compounds may have multiple effects in vivo stemming from inappropriate assembly of Cp. These results show that activating and deregulating virus assembly may be a powerful general approach for antiviral therapeutics.     

Left atrial echocardiographic parameters predict the onset of atrial fibrillation: the SMASH2 scoring system

Journal of Interventional Cardiac Electrophysiology - As AF-associated morbidity and mortality are increasing, there is an acute need for improved surveillance and prevention strategies to reduce...     

Association between missing tooth count and mortality: A systematic review

Purpose

The purpose of this review was to analyze existing literature on the relationship between tooth count and mortality by evaluating the findings in the context of methodological variations. We aimed at addressing the question of whether preserving natural teeth can impact mortality.