Efficacy and safety of atazanavir, with or without ritonavir, as part of once-daily highly active antiretroviral therapy regimens in antiretroviral-naive patients

BACKGROUND: Atazanavir (ATV), the first once-daily protease inhibitor approved for the treatment of HIV-1 infection, is recommended for use in antiretroviral (ARV) treatment-naive and -experienced patients. Study AI424-089 was a prospective, randomized, open-label, 96-week study comparing 2 ATV-based treatment regimens in ARV-naive HIV-infected patients. METHODS: Adults with HIV RNA levels > or =2000 copies/mL were randomized (1:1) to once-daily ATV at a dose of 300 mg with ritonavir at a dose of 100 mg (ATV300/RTV) or ATV at a dose of 400 mg (ATV400); both regimens included lamivudine and an investigational extended-release formulation of stavudine. The primary endpoint for this noninferiority study was the proportion of patients (response rate) with an HIV RNA load <400 copies/mL at week 48. RESULTS: Response rates at week 48 were 86% and 85% on the ATV300/RTV and ATV400 regimens, respectively (difference estimate [95% confidence interval] = 1.5 [-8.2 to 11.1]). There were 3 and 10 patients with virologic failure in the ATV300/RTV and ATV400 groups, respectively. One patient (ATV400) developed phenotypic resistance to ATV associated with an I50L substitution. Adverse event-related discontinuations were 8% among ATV300/RTV-treated patients and <1% among ATV400-treated patients. Plasma lipid elevations were low with both regimens. Both regimens were well tolerated. CONCLUSIONS: These findings demonstrate the safety and efficacy of the ATV300/RTV regimen and confirm the safety and efficacy of ATV400 in an ARV-naive patient population.     

Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11

In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia were analysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involving several DNA loci, while an additional patient had an inherited deletion. They were mapped to three different subregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second and third subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletions observed were not overlapping but the extension of the deleted Y DNA in each subregion was similar in each patient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phase when the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletion occurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesis loci in Yq11 and that each locus is active during a different phase of male germ cell development. As the most severe phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc. Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed.      

Evaluation of a scoring system for predicting lymph node malignancy in ultrasound guided fine needle aspiration practice

Ultrasound‐guided fine needle aspiration (USG‐FNA) has enabled cytopathologists to accurately diagnose smaller or non‐palpable lymph nodes (LN) on a regular basis. Pre‐FNA clinical and ultrasonographic factors, such as a patient's age, ratio of short to long axis diameter (S/L ratio), internal echogenicity, and the vascular pattern of a LN, are reported to be able to predict the benign or malignant nature of a LN. This study is designed to test the formula “0.06 × (age) + 4.76 × (S/L ratio) + 2.15 × (internal echo) + 1.80 × (vascular pattern)” generated from the study of Liao et al. as a scoring system for predicting LN malignancy in a cytopathologist operated USG‐FNA practice. Eighty‐three reports of USG‐FNA of LNs issued between 7/1/2008 and 4/28/2010 were reviewed. Patient's age, S/L ratio, internal echo, and vascular pattern were used to generate scores based on the aforementioned formula. A score of seven was used as a cutoff for predicting benign (<7) and malignant (>7) LNs. FNA cytology diagnosis, flow cytometric analysis as well as subsequent surgical diagnosis in some cases served as gold standard for statistical analysis. Among 46 USG‐FNA of LNs with scores > 7, 38 were malignant and eight were benign. All 37 USG‐FNA of LNs with scores < 7 were proven to be benign. The scoring system achieved 100% sensitivity, 82% specificity, 83% positive predictive value, 100% negative predictive value, and 90% accuracy. Further study of the eight “false‐positive” cases revealed that three of them (37.5%) were found to be malignant in follow‐up FNA and/or surgical biopsy. This scoring system may serve as a complementary tool in determining how aggressive a FNA procedure should be performed, how a FNA sample of LN should be triaged for ancillary study, and how closely a patient with lymphadenopathy should be followed up. Diagn. Cytopathol. 2013;41:1100–1106. © 2011 Wiley Periodicals, Inc.     

Expression of blood group antigens including HLA markers in human adult liver

The localisation of the principal blood group antigens has been studied in human liver. These blood group antigens included the erythrocyte antigens and the antigen of the major histocompatibility complex. This study was performed by the indirect immunofluorescence technique using polyclonal antibodies of human or animal origin and monoclonal antibodies from hybridomas. This study has shown that the normal hepatocyte is lacking in blood group antigens. On the contrary, the biliary cell was rich in antigenic markers: the main antigens expressed were Lewis, Pr, HLA-A and B antigens. In Kupffer cells, only i and HLA-DR antigens were clearly expressed. The endothelial cells of blood vessels mainly show A, B, H, HLA-A and B antigens; HLA-DR and Pr are slightly expressed. HLA-DR antigens were more strongly expressed on veins than on arteries. Dendritic cells have been identified in the portal space of human liver. They bore i and HLA-DR antigens.     

Long-term follow-up patients with leukemia receiving platelet transfusions: identification of a large group of patients who do not become alloimmunized

Alloimmunization is the major complication of platelet transfusion therapy in patients with acute leukemia. To evaluate whether alloimmunization continues to be a long-term problem in patients surviving induction therapy, 114 patients with acute nonlymphocytic leukemia (ANLL) who survived more than 6 mo and who received multiple courses of chemotherapy and abundant platelet transfusions were studied. Clinical response to random donor platelets and lymphocytotoxic antibody (LCTAb) were measured pretreatment and serially throughout the study period. Fourteen patients (12%) were alloimmunized upon admission, 34 (30%) patients became alloimmunized during remission induction therapy, and 66 (58%) patients did not become alloimmunized during that period. Sixty-one of these 66 patients (92%) never became alloimmunized and responded to random donor platelets during their subsequent course despite the fact they received multiple further platelet transfusions, whereas the alloimmunized patients tended to remain alloimmunized for their entire clinical course. There was no difference in age or sex between groups, and prognostic factors predicting alloimmunization could not be detected. In greater than 90% of patients not alloimmunized at admission, the presence or absence of LCTAb after induction predicts later alloantibody production. This information can be used to plan the type of platelet transfusions (HLA-matched or random donor) needed for subsequent maintenance and induction therapy. It may also help to identify a group of patients to whom more aggressive maintenance chemotherapy may be more safely administered.     

Renal Kallikrein Excretion in Alcoholic Cirrhosis

Severe liver disease is often associated with renal hemodynamic changes, and these changes may involve vasoactive hormones. The vasodilatory renal kallikrein-kinin system has received little previous study in these patients. We measured urinary kallikrein in nine patients with alcoholic cirrhosis under rigid metabolic conditions and simultaneously evaluated renin, aldosterone and urinary prostaglandins. Plasma renin und aldosterone were generally increased as expected but urinary kallikrein was surprisingly diminished (13.3 ± 3.7 vs. 38.8 ± 11.1 SE, E.U./day. P < 0.05). despite adequate creatinine clearance (81 ± 9 ml./min.). Administration of prostaglandin inhibitors reduced urinary prostaglandin E by 72% and creatinine clearance by 56% but did not alter urinary kallikrein. Mineralocor-ticoid inhibition by spironolactone induced a natriuresis in four patients with ascites (from 1.4–140 mEq. Na⁺/day) but also failed to alter kallikrein. Thus, kallikrein excretion is paradoxically reduced and seemingly unresponsive to alterations in the prostaglandin and renin-aldosterone systems. If urinary kallikrein quantitatively reflects intrarenal kallikrein-kinin activity, the impairment in this vasodilatory system may mediate the altered renal hemodynamics of severe liver disease.     

Piezoelectric lithotripsy: stone disintegration and follow-up results in patients with symptomatic gallbladder stones

One hundred symptomatic patients with radiolucent gallbladder stones were treated with a new piezoelectric lithotripter and oral chemolitholytic agents. Stone disintegration was achieved in 99 of these patients (99%) with a mean (+/- SD) maximum fragment size of 5.1 +/- 4.1 mm. Significant differences were found when the mean (+/- SD) fragment sizes of single stones less than or equal to 20 mm (4.2 +/- 2.5 mm) were compared with those of single stones greater than 20 mm (5.8 +/- 3.4 mm; P less than 0.05) and multiple stones (6.2 +/- 3.8 mm; P less than 0.05), respectively. None of the patients required anesthesia, analgesics, or sedatives before or during the treatment. The stone-free rates for all patients followed up for up to 4-12 months (mean +/- SD, 10.7 +/- 2.9 months) were 18% (1 month), 25% (2 months), 38% (4 months), 52% (8 months), and 67% (12 months). Partly significant differences were obtained in stone-free rates for single stones (less than or equal to 20 mm) compared with larger stones (greater than 20 mm) and multiple stones (P less than 0.05), respectively. Serious adverse reactions (i.e., cholestasis and pancreatitis) were observed in only 3 patients (3%). These conditions were induced by fragment impaction in the common bile duct. In 2 of these patients, endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy was required. It is concluded that piezoelectrically generated shock waves are suitable for the effective and safe disintegration of gallbladder stones in humans. The anesthesia-free and analgesia-free shock-wave application opens up the possibility to perform biliary lithotripsy as an outpatient procedure. The stone-free rate achieved in combination with oral bile acids is most promising for single stones (less than or equal to 20 mm).     

Cerebrovascular accidents in infective endocarditis: role of anticoagulation

Anticoagulation is still a matter of debate in infective endocarditis,since it can increase the risk of complications, mostly neurological.In our series of 269 patients with native valve endocarditisstudied between 1970 and 1982, 35 were anticoagulated. We observed14 patients with brain infarcts, of whom five died, and 12 patientswith cerebromeningeal or brain haemorrhage of whom six died.In a similar series of 63 patients with prosthetic valve endocarditis,all of whom were on anticoagulation and were studied between1972 and 1987, we observed five patients with brain infarcts,three of whom died, and two patients with brain haemorrhage,one of whom died. The frequency of cerebrovascular accident(CVA) was similar for both groups (111% in prosthetic endocarditisvs 11.5% in native valve endocarditis, P = ns), as was mortalityrate (57% vs 48–4%, P = ns). CVA are significantly morefrequent among anticoagulated patients (19/94 vs 19/238: P<0.01),but the mortality rate in CVA is similar for anticoagulatedand non-ant icoagulated patients (11/19 vs 8/19: P = ns). Theindications for anticoagulation in infective endocarditis remainsimilar to those in valvular heart disease. In patients withinfective endocarditis, anticoagulation with heparin shouldbe maintained whenever a brain infarct is present, unless itis large and/or haemorrhagic.     

Free deep inferior epigastric artery perforator flap for reconstruction of soft‐tissue defects in extremities of children

The deep inferior epigastric artery perforator (DIEP) flap has been a valuable tool in breast reconstruction, but seldom in extremity reconstruction. The aim of this report is to present our experience on the use of the DIEP flap for reconstruction of soft‐tissue defects in the extremities of pediatric patients. From January 2007 to February 2011, 22 consecutive free DIEP flap transfers were performed for reconstruction of complex soft‐tissue defects in the extremities of children with a mean age of 5.7 years old (ranging 2–10 years old). The flap design included transverse, oblique, and irregular DIEP flaps, containing one to three perforators in the flap. The flap size ranged from 7 × 4 cm to 18 × 17 cm. Primary donor‐site closure was accomplished in all of patients. The postoperative course was uneventfully in most of cases. The venous congestion was observed in two cases. One case of venous congestion was caused by flap inset with tension. The other case with venous thrombosis ended with partial loss of the flap after salvage procedure. There was one total flap loss due to the arterial thrombosis. The flap survival rate was 95.5%. The mean follow‐up was 12 months (ranging 6–36 months). All reconstructed extremities had satisfactory aesthetic and functional outcomes except two cases undergoing the secondary debulking procedures. The donor sites healed well in all cases without complications. Our experience showed that the free DIEP flap could be an alternative for reconstruction of soft‐tissue defects in the extremities of children. © 2013 Wiley Periodicals, Inc. Microsurgery 33:612–619, 2013.