Temporal Fluctuations in Behavior,Perceived HIV Risk,and Willingness to Use Pre-Exposure Prophylaxis (PrEP)

Individual perceptions of HIV risk influence willingness to use pre-exposure prophylaxis (PrEP) for HIV prevention. Among men who have sex with men (MSM) and male sex workers (MSWs), temporal or episodic changes in risk behavior may influence perceived risk and PrEP acceptability over time. We investigated fluctuations in perceived HIV risk and PrEP acceptability, comparing MSWs against MSM who do not engage in sex work. We conducted 8 focus groups (n = 38) and 56 individual interviews among MSM and MSWs in Providence, RI. Perceived HIV risk shaped willingness to use PrEP among both MSWs and MSM who did not engage in sex work, and risk perceptions changed over time depending on behavior. For MSWs, perceived risk cycled according to patterns of substance use and sex work activity. These cycles yielded an “access-interest paradox”: an inverse relationship between willingness to use and ability to access PrEP. MSM who did not engage in sex work also reported temporal shifts in risk behavior, perceived risk, and willingness to use PrEP, but changes were unrelated to access. MSM attributed fluctuations to seasonal changes, vacations, partnerships, behavioral “phases,” and episodic alcohol or drug use. Efforts to implement PrEP among MSM and street-based MSWs should address temporal changes in willingness to use PrEP, which are linked to perceived risk. Among MSWs, confronting the access-interest paradox may require intensive outreach during high-risk times and efforts to address low perceived risk during times of reduced sex work.     

G gamma and A gamma globin-chain biosynthesis by adult and umbilical cord blood erythropoietic bursts and reticulocytes

We examined gamma-globin-chain biosynthesis by adult and umbilical cord blood or erythropoietic bursts in methylcellulose clonal culture and gamma-chain synthesis by cord blood reticulocytes. Globin chains were labeled with 14C-amino acids and guantitated by using autoradiography or fluorography. Alpha, beta, and G gamma and A gamma chains were separated by isoelectric focusing in polyacrylamide gels containing 8 M urea and 3% Nonidet P-40 (a nonionic detergent). Time course examinations of the gamma-chains synthesized by the bursts revealed no changes in the G gamma:A gamma ratio between days 10 and 18 of culture. The ratio of G gamma/(G gamma + A gamma) in cultures of adult circulating erythroid precursors was 0.38 +/- 0.09, which corresponds to the known ratio in adult peripheral blood erythrocytes. The relative G gamma-chain biosyntheses in the cord blood bursts and reticulocytes were 0.56 +/- 0.02 and 0.66 +/- .008, respectively. Both are intermediate between the accepted newborn and adult ratios. Natal erythropoietic precursors appear to be in the transitional stage with respect to the switching of G gamma-A gamma ratios.     

Muckle–Wells syndrome in an Indian family associated with NLRP3 mutation

Muckle — Wells syndrome (MWS) is a rare autosomal dominant disease that belongs to a group of hereditary periodic fever syndromes. It is part of the wider spectrum of the cryopyrin-associated periodic syndrome (CAPS) which has only rarely been described in non-Caucasian individuals. It is characterized by recurrent self-limiting episodes of fever, urticaria, arthralgia, myalgia and conjunctivitis from childhood. Progressive sensorineural hearing loss and amyloidosis are two late complications. MWS is caused by gain of function mutations in the NLRP3 gene, which encodes cryopyrin, a protein involved in regulating the production of proinflammatory cytokines. We report two patients with MWS in an Indian family associated with the p.D303N mutation in the NLRP3 gene. These findings promote awareness of these hereditary periodic fever syndromes as a cause for recurrent fevers from childhood in the Indian population.KEY WORDS: Hereditary periodic fever, D303N mutation, Indian family, Muckle—Wells syndrome, p.D303N mutation     

Characterization of human erythroid burst-promoting activity derived from bone marrow conditioned media

Bone marrow conditioned media (BMCM) increases burst number and the incorporation of 59Fe into heme by bursts when peripheral blood or bone marrow cells are cultured at limiting serum concentrations. Burst- promoting activity (BPA) has now been purified approximately 300-fold from this source by ion-exchange chromatography on DEAE-Sephadex and absorption chromatography on hydroxyapatite agarose gel. Marrow BPA increased burst number and hemoglobin (Hb) synthesis in a dose- dependent manner. A larger increase in Hb synthesis than in burst number was consistently observed, which was probably a consequence of the increase in the number of cells per burst that occurs in the presence of BPA. The role of BPA in culture could be distinguished from erythropoietin (Ep), since no bursts grew in the absence of Ep, whether or not BPA was present, and since it had no effect on the growth of erythroid colonies scored at day 5 of culture. Our purified fraction did not support the growth of CFU-C in culture. Activity was stable at temperatures of 70 degrees C or lower for 10 min; exposure to 80 degrees C resulted in approximately 50% loss of activity. BPA was completely inactivated by treatment at 100 degrees C for 10 min. Thus, human bone marrow cells produce a heat-sensitive factor that specifically promotes the growth of early erythroid progenitors in culture.     

Determinants of exercise blood pressure response in normotensive and hypertensive women: role of cardiorespiratory fitness

PURPOSE: Exaggerated blood pressure (BP) response during physical exertion is associated with increased risk for cardiovascular events. Furthermore, it may be the predisposing factor for myocardial infarction triggered by physical exertion. The authors have shown that systolic BP achieved after 6 minutes of exercise is the strongest predictor of left ventricular hypertrophy. Furthermore, a 37 mm Hg increase in systolic BP above resting BP at 6 minutes of exercise was the threshold for left ventricular hypertrophy. The purpose of this study was to determine predictors of exercise BP response in normotensive and hypertensive women. METHODS: An exercise tolerance test (Bruce) was performed by 1411 normotensive (resting BP < 140/90 mm Hg) and hypertensive (resting BP > or = 140/90 mm Hg) women. These women were faculty, students, and staff at the University of Maryland, College Park, Maryland, and the George Washington University Medical Center, as well as patients undergoing a routine exercise tolerance test at West Coast Cardiology, Pinellas Park, Florida. Two fitness categories (low-fit and high-fit) were established on the basis of treadmill time to exhaustion adjusted for age. RESULTS: Significant associations were observed among the 6-minute exercise BP and age, body mass index, resting systolic and diastolic BP, heart rate, and exercise time to exhaustion. In a stepwise multiple-regression analysis, the determinants of BP after 6 minutes of exercise were resting systolic BP and treadmill time to exhaustion (R2 = 0.36) for normotensive women and treadmill time to exhaustion and resting systolic BP (R2 = 0.30) for hypertensive women. When fitness categories were contrasted, low-fit women in both the normotensive and hypertensive categories had higher BP and rate-pressure product after 6 minutes of exercise than the high-fit women (P <.05). CONCLUSIONS: Resting systolic BP and cardiorespiratory fitness are determinants of a submaximal exercise BP response for both hypertensive and normotensive women. Low cardiorespiratory fitness is associated with a higher BP response during submaximal exercise, suggesting that increased fitness may attenuate this abnormal rise in BP. Thus, low- to moderate-intensity physical activities for most days of the week should be encouraged for all women to increase cardiorespiratory fitness. This is likely to attenuate an abnormal rise in systolic BP that may occur during routine daily activities and protect against the associated health consequences.     

Prophylaxis in severe forms of von Willebrand's disease: results from the von Willebrand Disease Prophylaxis Network (VWD PN)

The bleeding patterns of severe von Willebrand's disease (VWD) adversely affect quality of life, and may be life threatening. There is a presumed role for prophylaxis with VWF‐containing concentrates, but data are scarce. The von Willebrand Disease Prophylaxis Network (VWD PN) was formed to investigate the role of prophylaxis in clinically severe VWD that is not responsive to other treatment(s).Using a retrospective design, the effect of prophylaxis was studied. Availability of records to document, or reliably assess, the type and frequency of bleeding episodes prior to, and after, the initiation of prophylaxis was required. Annualized bleeding rates were calculated for the period prior to prophylaxis, during prophylaxis and by primary bleeding indication defined as the site accounting for more than half of all bleeding symptoms. The Wilcoxon signed‐rank test of differences in the medians was used. Sixty‐one subjects from 20 centres in 10 countries were enrolled. Data for 59 were used in the analysis. The median age at onset of prophylaxis was 22.4 years. Type 3 VWD accounted for the largest number (N = 34, 57.6%). Differences in bleeding rates within individuals during compared with before prophylaxis were significant for the total group (P < 0.0001), and for those with primary bleeding indications of epistaxis (P = 0.0005), joint bleeding (P = 0.002) and GI bleeding (P = 0.001). The effect of prophylaxis was similar among those age < 18 years and those ≥18. One person developed an inhibitor during treatment. We conclude that prophylactic treatment of VWD is efficacious.     

Challenges of Childhood TB/HIV Management in Malawi

The diagnosis and management of childhood tuberculosis (TB) are major challenges in countries such as Malawi with high incidence of TB and human immunodeficiency virus (HIV) infection. Diagnosis of TB in children often relies only on clinical features but clinical overlap with the presentation of HIV and other HIV-related lung disease is common. The tuberculin skin test (TST), the standard marker of M. tuberculosis infection in immune competent children, has poor sensitivity in HIV-infected children and is not usually available in Malawi. HIV test should be routine in children with suspected TB as it improves clinical management. HIV-infected children are at increased risk of developing active disease following TB exposure which justifies the use of isoniazid preventive therapy (IPT) once active disease has been excluded but this is difficult to implement and appropriate duration of IPT is unknown. HIV-infected children with active TB experience higher mortality and relapse rates on standard TB treatment compared to HIV-uninfected children, highlighting the need for further research to define optimal treatment regimens. HIV-infected children should also receive appropriate supportive care including cotrimoxazole prophylaxis and anti-retroviral treatment (ART) if indicated. There are concerns about concurrent use of some anti-TB drugs such as rifampicin with some ARTs.     

CHANGING TRENDS OF LEPROSY IN ARMED FORCES

A total of 651 cases of leprosy were hospitalised from Jan 1987 to Dec 1992. Each patient underwent haemogram, total and differential white cell count, urinalysis, liver function tests, skin slit smear for AFB and skin biopsy. Nerve conduction studies, electomyographic studies and nerve/nerve sheath biopsies were undertaken as and when indicated. These patients were managed with multidrug therapy. Paucibacillary (PB) leprosy accounted for 476 (73.1%) cases which comprised of indeterminate leprosy 90 (13.8%), tuberculoid leprosy 14 (2.2%), borderline tuberculoid leprosy 310 (47.6%) and neuritic leprosy 62 (9.5%). The remaining 175 patients (26.9%) were multibacillary (MB) which included borderline leprosy 9 (1.4%), borderline lepromatous leprosy 129 (19.8%) and lepromatous leprosy 37 (5.7%) patients. There were total 153 patients in 1987. This number declined to 44 in 1992. PB declined from 113 in 1987 to 39 in 1992 and MB cases from 40 to 5.KEY WORDS: Leprosy     

Assessment of testicular metabolic integrity with P-31 MR spectroscopy

To evaluate the reliability of phosphorus-31 magnetic resonance (MR) spectroscopy in the assessment of acute testicular ischemia, vascular integrity, and spermatogenesis, the authors studied in vivo canine and primate testicles grouped as follows: group 1 testes (n = 8), in situ canine controls; group 2 (n = 11), canine testes subjected to warm ischemia; group 3, canine (n = 4) and primate (n = 4) testicles from hormone-treated animals. Group 1 control testicles showed high monophosphoester (MP) levels; low levels of inorganic phosphate (Pi), phosphodiester (PD), and phosphocreatine; and high levels of adenosine triphosphate (ATP). Group 2 testes revealed a time-dependent decay of MP/Pi ratios (from 2.1 to 0.70). Regeneration of ATP was noted in the acute reperfusion period. After 6 weeks of pituitary gonadotropin suppression, group 3 testes showed a significant decrease (P less than .05) in MP/PD ratios from a control level of 2.6 +/- 0.3 and a decrease in the MP/beta-ATP ratio from 2.4 +/- 0.1 to 1.8 +/- 0.3. P-31 MR spectroscopy appears to be a potential method for noninvasively assessing testicular ischemic injury and the metabolic integrity of spermatogenesis.