Discordance in HIV-1 viral loads and antiretroviral drug concentrations comparing semen and blood plasma

Objectives

For individuals not on antiretroviral therapy, the risk of heterosexual transmission of HIV appears negligible when blood plasma (BP) viral loads are <1500 HIV‐1 RNA copies/mL. It is not clear whether this observation can be extrapolated to individuals on highly active antiretroviral therapy (HAART). Because of differential tissue penetration, antiretroviral drug concentrations may be sufficient to maintain an undetectable viral load in the BP yet not achieve adequate levels to suppress HIV in the genital tract. Therefore, we wanted to correlate HIV viral loads and drug concentrations in semen plasma (SP) and BP.

Methods

Thirty‐three men were included. All were on combination antiretroviral therapy with an undetectable BP viral load for at least 1 year. Blood and semen samples were collected within 2 h of each other and tested for HIV RNA by the NucliSens QT (bioMerieux, St Laurent, QC, Canada) method; drug concentrations were determined by liquid chromatography tandem mass spectrometry.

Results

Two of the 33 patients (6.1%) with BP viral loads below detection had time‐matched HIV viral loads in SP ≥700 copies/mL. Both patients were on efavirenz, the SP concentrations of which were ≤10% of the levels in BP and well below the minimal therapeutic drug monitoring target concentration required to suppress HIV.

Conclusions

Because, at least in part, of poor drug penetration into the genital tract, an undetectable HIV viral load in the BP does not guarantee an undetectable viral load in semen. In view of this, caution should be taken in concluding that patients on HAART with suppressed viraemia are sexually non‐infectious.     

Prevalence of the Neonatal Autopsy: A Report of the Study Group for Complications of Perinatal Care

Neonatal autopsy findings are valuable additions to the information base for current cases and future perinatal care, so the reported decline in the autopsy rate is disturbing. In order to estimate the prevalence of the neonatal autopsy among a large population of deaths, we surveyed participating institutions of the Study Group for Complications of Perinatal Care. Investigators from 37 neonatal intensive care units, located in 9 children's hospitals, 4 hospitals for women and infants, and 24 full-service pediatric and adult care hospitals, reported their neonatal death and autopsy rates for 1989. The overall neonatal autopsy rate was 51% among 1645 neonatal deaths. The rate was variable, ranging from 22 to 100%. We found the neonatal autopsy rate to be lower than previously reported and not apparently influenced by the type of center or by the type of medical staff at the centers. In order to assess and potentially reverse the current low rate, the influence of neonatal demographic and clinical factors, as well as physician-related factors, must be studied.     

Benefits from peer teaching in the dental gross anatomy laboratory

This study examined the impact of implementing a rotating dissection schedule on the attitudes and performance of first-year dental students in the gross anatomy laboratory at the University of Kentucky. In 2002-2003, half of the students assigned to each cadaver dissected the assigned objectives during the first 90 min of the laboratory session. During the last 30 min, the non-dissecting group members came into the laboratory and had the day's dissection demonstrated and explained to them via peer instruction. Dissection responsibilities rotated with each laboratory session. Eighty-eight percent of student participants were satisfied with the rotating dissection approach according to a mid-term survey, and this satisfaction level remained unchanged at the end of the semester for most students. Students' perceptions of the quality of peer laboratory presentations varied, with only 44% rating them as good or better. Eighty percent of students perceived that rotating dissection did not impede their performance, and this was confirmed by analysis of grade data. Student satisfaction and the ability to devote additional weekly curriculum time to studying anatomy in a very compressed curriculum were the main student-described benefits.     

Calciphylaxis – a topical overview

'Calciphylaxis', a calcification syndrome associated with ischaemic cutaneous necrosis, is acquired naturally in humans in disease states. It is a life and limb-threatening complication, usually observed in patients with renal disease and secondary hyperparathyroidism, but known to occur in the absence of renal or parathyroid disease. The reported mortality rate, which ranges from 60-80%, relates to wound infection, sepsis and organ failure. It is a small-vessel vasculopathy, which is estimated to occur in about 4% of haemodialysis patients. Clinically, violaceous, reticulate areas of cutaneous necrosis and eschar may be evident, particularly in the extremities. In addition to the clinical picture, a raised calcium phosphorous product, an elevated parathyroid hormone level, radiographic evidence of vessel and soft-tissue calcification and the finding of mural calcification affecting small arteries and arterioles on histopathology help to confirm the diagnosis of this entity which generally has a poor prognosis. A high index of suspicion and an active multidisciplinary management approach, with rigorous attention to wound care and prevention of sepsis, are vital in the management of these patients. In this overview, we discuss the pathophysiology, clinical features and associations, risk factors, diagnosis and management issues relating to calciphylaxis.     

Evaluation of an Algorithm To Identify Women with Carcinoma of the Breast

Although claims data are increasingly being used to measure and manage the cost and quality of health care, few studies have evaluated algorithms developed for such analyses. Therefore, the present study was performed to evaluate prospectively a previously published algorithm used to identify women with the new diagnosis of carcinoma of the breast. This algorithm had been developed from the patterns of claims that suggested common clinical presentations of carcinoma of the breast. In the present study, this algorithm was used to identify 177 potential cases of women with newly diagnosed carcinoma of the breast from the claims database of a large health maintenance organization (HMO). The algorithm's positive predictive value for cases identified in the present study was 83% (147/177). To attempt to improve upon the positive predictive value, multiple modifications of the algorithm were performed. The previously defined best modification of the initial algorithm yielded a positive predictive value of 84% (147/174) in the present study with the loss of none of the true positive cases. These results demonstrate that logic-based algorithms can be used as a valid and efficient method of identifying large numbers of new breast cancer cases from claims data. This algorithm provides a powerful tool to perform health care analysis and research for women with newly diagnosed carcinoma of the breast.     

Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy

The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal- specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.      

Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains

Systemic lupus erythematosus (SLE) is an autoimmune disorder of a largely unknown etiology. Anti-double-stranded (ds) DNA antibodies are a classic hallmark of the disease, although the mechanism underlying their induction remains unclear. We demonstrate here that, in both lupus-prone and normal mouse strains, strong anti-dsDNA antibody responses can be induced by dendritic cells (DC) that have ingested syngeneic necrotic (DC/nec), but not apoptotic (DC/apo), cells. Clinical manifestations of lupus were evident, however, only in susceptible mouse strains, which correlate with the ability of DC/nec to release IFN-gamma and to induce the pathogenic IgG2a anti-dsDNA antibodies. Injection of DC/nec not only accelerated disease progression in the MRL/MpJ-lpr/lpr lupus-prone mice but also induced a lupus-like disease in the MRL/MpJ-+/+ wild-type control strain. Immune complex deposition was readily detectable in the kidneys, and the mice developed proteinuria. Strikingly, female MRL/MpJ-+/+ mice that had received DC/nec, but not DC/apo, developed a 'butterfly' facial lesion resembling a cardinal feature of human SLE. Our study therefore demonstrates that DC/nec inducing a Th1 type of responses, which are otherwise tightly regulated in a normal immune system, may play a pivotal role in SLE pathogenesis.     

Cefotetan-induced hemolytic anemia: a case report and review of the literature

Cefotetan disodium-induced hemolytic anemia has been reported previously, and some of these cases have been severe or fatal. We describe a case of severe hemolytic anemia that occurred in an 80-year-old woman who received cefotetan prophylactically after surgery for a small bowel obstruction. Eight days after the first dose of cefotetan, the patient developed a severe Coomb test-positive hemolytic anemia. Using flow cytometry, we demonstrated cefotetan-specific antibodies in her posttreatment serum, which were detectable at a serum dilution up to 1:10 000. The patient received corticosteroid therapy and blood transfusions, with improvement of her hematologic parameters, but died 54 days after admission for respiratory failure. To our knowledge, this is the first use of flow cytometry for the detection of cefotetan-induced red blood cell antibodies. This technique offers a sensitive, rapid, objective method for detecting drug-induced antibodies.