Evaluations of HIV type 1 rev gene diversity and functional domains following perinatal transmission

The human immunodeficiency virus type 1 (HIV-1) rev exons 1 and 2 sequences were analyzed from six mother-infant pairs following perinatal transmission. The rev open reading frame was maintained with a frequency of 93.96% in six mother-infant pairs' sequences. There was a low degree of viral heterogeneity and estimates of genetic diversity in mother-infant pairs' rev sequences. However, the distances of rev sequences between epidemiologically unlinked individuals were greater than in epidemiologically linked mother-infant pairs. Furthermore, phylogenetic parameters revealed that the epidemiologically linked mother-infant pairs were closer evolutionarily to each other as compared with epidemiologically unlinked mother-infant pairs. Both mothers and infants were under positive selection pressure as determined by the ratios of nonsynonymous to synonymous substitutions. The functional domains required for Rev activity, including nuclear export of RNA, RNA binding domain, and nuclear import signals, were conserved in all mother-infant pairs' sequences. The conservation of functional domains of rev and a low degree of heterogeneity following vertical transmission are consistent with an indispensable role of rev in the HIV-1 life cycle.     

Post-transplant infections: single center experience from the developing world.

OBJECTIVE: To describe our experience of post-transplant infections in allogeneic stem cell transplants at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan. METHODS: From July 2001 to September 2006, patients with malignant and non-malignant hematological disorders having human leukocyte antigen (HLA)-matched sibling donors were selected for transplant. Pre-transplant infection surveillance was carried out, and strict prophylaxis against infection was observed. After admission to the hospital, patients were kept in protective isolation rooms, equipped with a HEPA filter positive-pressure laminar airflow ventilation system. Bone marrow and/or peripheral blood stem cells were used as the stem cell source. Cyclosporin and prednisolone were used as prophylaxis against graft-versus-host disease (GVHD). The engraftment was monitored with cytogenetic/molecular analysis and change of blood group. Survival was calculated from the date of transplant to death or last follow-up. RESULTS: One hundred and fifty-four patients received allogeneic stem cell transplants from HLA-matched siblings for various hematological disorders at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan between July 2001 and September 2006. Indications for transplant included aplastic anemia (n=66), beta-thalassemia major (n=40), chronic myeloid leukemia (n=33), acute leukemia (n=8), and miscellaneous disorders (n=7). One hundred and twenty patients were male and 34 were female. The median age of the patient cohort was 14 years (range 1 1/4-54 years). One hundred and thirty-six patients and 135 donors were cytomegalovirus (CMV) IgG-positive. One hundred and forty patients (90.9%) developed febrile episodes in different phases of post-transplant recovery. Infective organisms were isolated in 150 microbiological culture specimens out of 651 specimens from different sites of infections (23.0% culture positivity). Post-transplant infections were confirmed in 120 patients (77.9%) on the basis of clinical assessment and microbiological, virological, and histopathological examination. Mortality related to infections was 13.0%. Fatal infections included CMV disease (100% mortality, 6/6), disseminated aspergillosis (66.7% mortality, 4/6), pseudomonas septicemia (42.9% mortality, 9/21), and tuberculosis (25% mortality, 1/4). CONCLUSIONS: More than 90% of our patients developed febrile episodes with relatively low culture yield. The majority of infections were treated effectively, however CMV, aspergillosis, and pseudomonas infections remained problematic with high mortality.     

A Randomized,Placebo-Controlled Study to Investigate the Safety,Tolerability, and Pharmacokinetics of 3 Weeks of Orally Administered Gefapixant in Healthy Younger and Older Adults

Purpose

Patients with chronic cough are typically female and have a mean age of?~?60 years. However, initial pharmacokinetic (PK) characterization of the P2X3-receptor antagonist gefapixant, developed to treat refractory or unexplained chronic cough, was performed in healthy participants who were predominantly younger adult males. The objective of this Phase 1 study was to assess the safety, tolerability, and PK of gefapixant in younger (18–55 years) and older (65–80 years) males and females.

Methods

A randomized, double-blind, placebo-controlled study was conducted. Healthy adult participants were stratified into 4 cohorts by age and sex (younger males/females and older males/females) and randomized 4:1 (younger adults) or 3:1 (older adults) to receive gefapixant 300 mg twice daily (BID) for 1 week, followed by gefapixant 600 mg BID for 2 weeks or placebo. Safety, tolerability, and PK were assessed.

Results

Of 36 randomized and treated participants, 28 (100%) receiving gefapixant and 6 (75%) receiving placebo reported?≥?1 adverse event (AE). The most common treatment-related AEs in the gefapixant group were taste related. Predefined renal/urologic AEs were reported by 7 (25%) participants receiving gefapixant (all mild to moderate in severity). Gefapixant exposure was generally lower in younger males compared with younger females and older adults; however, differences may have been due to estimated glomerular filtration rate.

Conclusion

The safety profile of gefapixant 300–600 mg BID was generally consistent with previous studies. Additional characterization of gefapixant PK as a function of age and sex using population PK modeling is warranted.

     

Dengue Fever Outbreak in Delhi,North India: A Clinico-Epidemiological Study

Background:Dengue viruses, single-stranded positive polarity ribonucleic acid (RNA) viruses of the family Flaviviridae, are the most common cause of arboviral disease in the world. We report a clinico-epidemiological study of the dengue fever outbreak of 2010 from a tertiary care hospital in Delhi, North India.Objectives:Objectives of the study were to know the incidence of laboratory-confirmed dengue cases among the clinically suspected patients; to study the clinical profile of dengue-positive cases; and to co-relate the above with the prevalent serotype and environmental conditions.Results:Out of the 4,370 serum samples, 1,700 were positive for dengue-virus-specific IgM antibodies (38.9%). Prevalent serotype was dengue virus type-1. Thrombocytopenia and myalgia was seen in 23.1% and 18.3% of the 1,700 dengue IgM-positive patients, respectively. Also, 10.3% of 1,700 were dengue hemorrhagic fever (DHF) patients; and the mortality in serologically confirmed dengue fever cases was 0.06%.Conclusions:A change in the predominant circulating serotype, unprecedented rains, enormous infrastructure development, and increased reporting due to improved diagnostic facilities were the factors responsible for the unexpected number of dengue fever cases confronted in 2010.     

Management of moderate and severe corneal astigmatism with AcrySof? toric intraocular lens implantation – Our experience

Purpose

Visual performance following toric intraocular lens implantation for cataract with moderate and severe astigmatism.

Setting

Cataract services, Shroff Eye Centre, New Delhi, India.

Design

Case series.

Method

This prospective study included 64 eyes of 40 patients with more than 1.50 dioptre (D) of pre-existing corneal astigmatism undergoing phacoemulsification with implantation of the AcrySof® toric IntraOcular Lens (IOL). The unaided visual acuity (UCVA), best corrected visual acuity (BCVA), residual refractive sphere and refractive cylinders were evaluated. Toric IOL axis and alignment error was measured by slit lamp method and Adobe Photoshop (version 7) method. Patient satisfaction was evaluated using a satisfaction questionnaire at 3 months.

Results

The mean residual refractive astigmatism was 0.57 D at the final follow-up of 3 months. Mean alignment error was 3.44 degrees (SD = 2.60) by slit lamp method and 3.88 degrees (SD = 2.86) by Photoshop method. Forty-six (71.9%) eyes showed misalignment of 5 degrees or less, and 60 (93.8%) eyes showed misalignment of 10 degrees or less. The mean log MAR UCVA at 1st post-op day was 0.172 (SD = 0.02), on 7th post-op day was 0.138 (SD = 0.11), and on 30th post-op day was 0.081 (SD = 0.11). The mean log MAR BCVA at three months was −0.04 (SD = 0.76).

Conclusion

We believe that implantation of AcrySof® toric IOL is an effective, safe and predictable method to correct high amounts of corneal astigmatism during cataract surgery.