Vulnerabilities and risks of HIV infection among migrants in the Thane district, India.

OBJECTIVES: To explore the vulnerabilities and risks of HIV infection among female migrants compared with male migrants in the Thane district of Maharashtra, India. STUDY DESIGN: This is a cross-sectional epidemiological study. METHODS: Data from 35,841 migrants (men 96.2% and women 3.8%) were collected using the web-based 'Migrant Service Delivery System.' The data were then analysed in SPSS, version 23.0. Statistical analysis, including Chi-squared test and multivariate logistic regression, was used to identify factors influencing HIV infection for both male and female migrants. RESULTS: It was observed that 2.96% of female migrants had HIV infection compared with 0.77% of male migrants. We found that 12.1% of women consumed alcohol compared with 41.9% of men, and access to bars was 1.5% among women and 3.5% in men. We observed an even larger difference between men and women in their previous history of using brothels for sex; only 5.9% of female migrants reported previously having used brothels for sex, compared with 62.9% of male migrants. Approximately 12.3% of married women and 93.6% of married men had sex with someone other than their spouse. We found that 67.0% of married women and 73.9% of married men reported using a condom during their last sexual act compared with 60.9% of unmarried women and 68.1% of unmarried men. CONCLUSIONS: In Thane, female migrants faced higher vulnerabilities and risks of HIV infection than male migrants. Consequently, innovative strategies are required to address these particular needs of female migrants.

Neuroinflammation Induces Neurodegeneration.

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Multiple Sclerosis (MS) are characterized by neuronal degeneration and neuronal death in specific regions of the central nervous system (CNS). In AD, neurons of the hippocampus and entorhinal cortex are the first to degenerate, whereas in PD, dopaminergic neurons in the substantia nigra degenerate. MS patients show destruction of the myelin sheath. Once the CNS neurons are damaged, they are unable to regenerate unlike any other tissue in the body. Neurodegeneration is mediated by inflammatory and neurotoxic mediators such as interleukin-1beta (IL-1ß), IL-6, IL-8, IL-33, tumor necrosis factor-alpha (TNF-α), chemokine (C-C motif) ligand 2 (CCL2), CCL5, matrix metalloproteinase (MMPs), granulocyte macrophage colony-stimulating factor (GM-CSF), glia maturation factor (GMF), substance P, reactive oxygen species (ROS), reactive nitrogen species (RNS), mast cells-mediated histamine and proteases, protease activated receptor-2 (PAR-2), CD40, CD40L, CD88, intracellular Ca+ elevation, and activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-B (NF-kB). Activated microglia, astrocytes, neurons, T-cells and mast cells release these inflammatory mediators and mediate neuroinflammation and neurodegeneration in a vicious manner. Further, immune and inflammatory cells and inflammatory mediators from the periphery cross the defective blood-brain-barrier (BBB) and augment neuroinflammation. Though inflammation is crucial in the onset and the progression of neurodegenerative diseases, anti-inflammatory drugs do not provide significant therapeutic effects in these patients till date, as the disease pathogenesis is not yet clearly understood. In this review, we discuss the possible factors involved in neuroinflammation-mediated neurodegeneration.

Development and validation of liquid chromatography-tandem mass spectrometric method for quantification of meropenem in rat plasma and its application in a preclinical dose proportionality study.

A simple, rapid, sensitive and selective assay based liquid chromatography-tandem mass spectrometric method was developed and validated for quantitative analysis of meropenem in rat plasma using rolipram as internal standard. Efficient chromatographic separation of analyte from matrix components was achieved by using Kromasil 100 C18 (150×4.6 mm, 5 µm) reversed phase column with mobile phase consisting of acetonitrile and 2 mM ammonium acetate buffer (80:20, v/v) delivered in isocratic mode with constant flow rate of 0.7 mL/min. Detection of meropenem and rolipram was performed in positive mode using multiple reaction monitoring (MRM). The mass transitions 384.1→141.0 and 276.2→191.1 were used to quantify meropenem and rolipram, respectively. A fast and simple solid phase extraction method was optimized for extraction of meropenem from rat plasma. The developed method was validated for selectivity, accuracy, precision, linearity, recovery, stability, matrix effect, dilution integrity as per regulatory guidelines. The developed method was selective with no interfering components at the retention time of meropenem and rolipram. The assay demonstrated acceptable linearity (R(2)>0.99) over a dynamic range of 0.19-201.40 µg/mL. The method exhibited excellent and acceptable precision and accuracy, and produced consistent recoveries. The method demonstrated excellent stability of meropenem in rat plasma under studied conditions investigated. Finally, the validated method was successfully applied to quantify meropenem levels in rat plasma of a dose escalation study.

Mesenchymal stem cells and inflammatory lung diseases.

Mesenchymal stem cells (MSCs) are emerging as a therapeutic modality in various inflammatory disease states. A number of ongoing randomized Phase I/II clinical trials are evaluating the effects of allogeneic MSC infusion in patients with multiple sclerosis, graft-versus-host disease, Crohn's disease, and severe chronic myocardial ischemia. MSCs are also being considered as a potential therapy in patients with inflammatory lung diseases. Several studies, including our own, have demonstrated compelling benefits from the administration of MSCs in animal models of lung injury. These studies are leading to growing interest in the therapeutic use of MSCs in inflammatory lung diseases. In this Review, we describe how the immunoregulatory effects of MSCs can confer substantial protection in the setting of lung diseases such as acute lung injury, chronic obstructive pulmonary disease, asthma, and pulmonary hypertension. We also address potential pitfalls related to the therapeutic use of MSCs in fibrotic lung diseases such as idiopathic pulmonary fibrosis. In addition, we identify emerging areas for MSC- based therapies in modulating oxidative stress and in attenuating inflammation in alcohol-related acute lung injury.

Botulinum toxin A during pregnancy: a survey of treating physicians.

Botulinum toxin A (btxA) is widely used for cosmetic purposes, headaches, dystonia, spasticity, pain and other on and off label uses. Despite the widespread use of btxA in women of childbearing potential, there are few data on the effects of this drug on pregnant women and the fetus. The goal of this study was to survey physicians who use btxA, to determine their experience with pregnant women. We surveyed 900 physicians who used commercially available btxA. The questionnaire asked treating physicians if they had knowingly or unknowingly injected pregnant women and what was the outcome of each pregnancy. In total, 396 physicians (44%) returned questionnaires, of whom only 12 physicians reported injecting pregnant women with btxA. Sixteen pregnant women were injected, mostly in the first trimester, and only one patient, who had prior spontaneous abortions, suffered a miscarriage. Another woman had a therapeutic abortion. All other pregnancies went to term and there were no fetal malformations. Based on this limited survey of treating physicians in the USA, btxA appears to be relatively safe for both expectant mother and fetus. We need further data, however, and we would recommend that physicians and patients carefully consider the risks and benefits before using btxA in pregnant women.

Effects of peanut oil consumption on appetite and food choice.

OBJECTIVE: Peanut consumption may improve lipid profiles without promoting weight gain. Both properties have been attributed to their high-unsaturated fat content. Mono and polyunsaturated fatty acids reportedly hold stronger satiety value than saturated fats and may help appetite control. This study investigated the effects of chronic peanut oil consumption on appetite and food choice. RESEARCH METHODS AND PROCEDURES: A total of 129 healthy adults from three countries (Brazil, Ghana and US) were randomly assigned to one of four treatment arms: consumption of peanut oil, olive oil or safflower oil as 30% of individual resting energy expenditure (REE) for 8 weeks or no dietary intervention. Participants received no other dietary guidance. They completed appetite questionnaires eliciting information about hunger, fullness, desire to eat, and prospective consumption during all waking hours for 1 day at weeks 2 and 6 and for 1 or 3 days at weeks 0, 4 and 8. Diet records were completed at weeks 0, 4 and 8. RESULTS: No differences in appetitive ratings were observed over the 8-week trial. There were no significant treatment by time interactions. Total caloric intake was significantly higher at week 8 relative to baseline (F=10.08, P<0.05). The increases for each treatment were: peanut oil=197+/-114; olive oil=237+/-121; safflower oil=274+/-90; control=75+/-71. Free-feeding intake, an index of dietary compensation, was reduced significantly at weeks 4 and 8 compared to baseline (F=9.08, P<0.00). The declines (compensation scores) were (kcals): peanut oil=-208+/-105 (46%); olive oil=-235+/-105 (50%); safflower oil=-186+/-102 (44%). There were no significant differences across countries in appetite ratings. DISCUSSION: A prior intervention with whole peanuts reported a dietary compensation score of 66% over 8 weeks, this compares to a 46% compensation score observed with peanut oil. Our data suggests that the lipid fraction in peanuts elicits a weak effect on satiety.

Carotid artery stenting for the high surgical risk patients.

Obstructive atherosclerotic carotid bifurcation disease is responsible for approximately 30% of stroke cases in the United States. Any successful treatment of this disease should demonstrate significant and durable reduction in the related risk for stroke without compromising the patient safety. The indications for CAS are evolving as the techniques, the stents and catheter technology advance. There is an ongoing need to improve the equipment suitable for carotid stenting and a need to enhance the safety of the procedure. Often, when a technical problem is encountered, it is attributed to the inadequacy of the devices currently available. As the technology improves, particularly with the application of the anti-embolization devices, the indications and contraindication may need to be revised.

Microembolization during carotid stenting with the distal-balloon antiemboli system.

BACKGROUND: The distal-balloon protection system is being evaluated for its efficacy in preventing embolic neurological events during carotid stenting (CAS). We sought to determine the effect of this system on the frequency of the Doppler-detected microembolic signals (MES) during CAS. METHODS: Using transcranial Doppler, we compared the frequency of MES during CAS in 2 groups; 39 patients without distal protection and 37 with the distal-balloon protection system (GuardWire, Percusurge, Sunnyville, CA). There was no significant difference in the clinical or angiographic characteristics between the 2 groups. Three phases with increased MES counts were identified during the unprotected CAS; stent deployment, predilation, and postdilation (mean+/-SD: 75+/-57, 32+/-36, and 27+/-25, respectively). RESULTS: The distal-balloon protection significantly reduced the frequency of MES during CAS (MES-counts: 164+/-108 in the control vs 68+/-83 in the protection group, p=0.002) particularly during these 3 phases. MES in the protection group were detected predominantly during sheath placement, guidewire manipulation and during the distal-balloon deflation. CONCLUSIONS: Three phases with increased MES counts were identified during the unprotected CAS, e.g. stent deployment, predilation and postdilation. The distal-balloon protection system significantly reduced the frequency of MES during CAS, particularly during these 3 phases.

Subarachnoidal hemorrhage following carotid stenting with the distal-balloon protection.

A 61-year-old man underwent carotid stenting with the distal-balloon protection system for symptomatic carotid artery stenosis. During the procedure, progressive elevation of the systolic blood pressure occurred, reaching a peak of 220 mm Hg immediately following deflation of the distal balloon. This was associated with severe headaches and progressive deterioration in the mental status to a coma. Head CT scan showed massive subarachnoidal hemorrhage contralateral to the stented side and a secondary intracerebral hemorrhage. Despite immediate successful blood pressure control, his condition deteriorated and he died 2 days later.

Effect of the distal-balloon protection system on microembolization during carotid stenting.

BACKGROUND: The distal-balloon protection system is being evaluated for its efficacy in preventing embolic neurological events during carotid stenting (CAS). We sought to determine the effect of this system on the frequency of Doppler-detected microembolic signals (MES) during CAS. METHODS AND RESULTS: Using transcranial Doppler, we compared the frequency of MES during CAS in 2 groups: 39 patients without distal protection and 37 who used the distal-balloon protection system (GuardWire). There were no significant differences in the clinical or angiographic characteristics between the 2 groups. Three phases with increased MES counts were identified during unprotected CAS; these were stent deployment, predilation, and postdilation (75+/-57, 32+/-36, and 27+/-25 METS, respectively). The distal-balloon protection significantly reduced the frequency of MES during CAS (MES counts: 164+/-108 in the control versus 68+/-83 in the protection group; P=0.002), particularly during these 3 phases. MES in the protection group were detected predominantly during sheath placement, guidewire manipulation, and distal-balloon deflation. CONCLUSION: Three phases with increased MES counts were identified during unprotected CAS (eg, stent deployment, predilation, and postdilation). The distal-balloon protection system significantly reduced the frequency of MES during CAS, particularly during these 3 phases.

Procedural safety and short-term outcome of ambulatory carotid stenting.

BACKGROUND AND PURPOSE: Ambulatory procedures increase patient comfort and enhance cost-effectiveness. We sought to determine the feasibility and safety of ambulatory carotid stenting. METHODS: A selected group of patients was admitted and discharged the same day after the carotid stenting procedure. Immediate and short-term outcomes are reported. RESULTS: A total of 98 ambulatory carotid stenting procedures (98 hemispheres in 92 patients) were performed. There were 66 men (72%), and the mean age was 70+/-9 years. Of the patients, 28% had neurological symptoms related to the treated artery within 3 months before the procedure. Sixteen percent of the patients had prior carotid endarterectomy, 4% had prior ipsilateral neck radiation, and 8% had complete occlusion of the contralateral internal carotid artery. Successful access site hemostasis was ensured in all patients with suture-mediated vascular closure devices in 96 (98%) and manual compression in 2. Clinical follow-up was available for 96% of the patients at a mean time of 6+/-4 months. There were no neurological events, deaths, repeated procedures, or major access site complications. CONCLUSIONS: Ambulatory carotid stenting is both safe and feasible. This approach will enhance the applicability of the procedure by increasing patient comfort and potentially reducing procedural costs.

Immediate and late clinical outcomes of carotid artery stenting in patients with symptomatic and asymptomatic carotid artery stenosis: a 5-year prospective analysis.

BACKGROUND: Carotid stenting is a less invasive percutaneous procedure than carotid endarterectomy for the treatment of carotid stenosis. Reports suggest that it can be performed with periprocedural complication rates similar to those of carotid endarterectomy. The purpose of this study was to determine short- and long-term outcomes in the largest prospective cohort of carotid stenting patients. METHODS AND RESULTS: This study followed 528 consecutive patients (604 hemispheres/arteries) undergoing carotid stenting. There was a 0.6% (n=3) fatal stroke rate and 1% (n=5) nonstroke death rate at 30 days. The major stroke rate was 1% (n=6), and the minor stroke rate was 4.8% (n=29). The overall 30-day stroke and death rate was 7.4% (n=43). Over the 5-year study period, the 30-day minor stroke rate improved from 7.1% (n=7) for the first year to 3.1% (n=5) for the fifth year (P:<0.05 for trend). The best predictor of 30-day stroke and death was age >/=80 years. After the 30-day period, the incidence of fatal and nonfatal stroke was 3.2% (n=31). On Kaplan-Meier analysis, the 3-year freedom from ipsilateral or fatal stroke was 92+/-1%. CONCLUSIONS: Experience from a single group of operators demonstrates that carotid stenting can be performed with an acceptable 30-day complication rate. Late follow-up also demonstrates a low rate of fatal and nonfatal stroke. These results suggest that carotid stenting may be comparable to carotid endarterectomy, and it underscores the clinical equipoise and premise for the National Institute of Health-supported, randomized Carotid Revascularization Endarterectomy Versus Stent Trial comparing carotid stenting with carotid endarterectomy.

Carotid angioplasty with stenting in post-carotid endarterectomy restenosis.

Recurrent stenosis post-carotid endarterectomy (CEA) is not a solitary or unusual phenomenon. Compared to the initial CEA, the reoperation is often more technically challenging and frequently results in local and neurological complications. Carotid artery angioplasty with stenting (CAS) is currently being investigated as an alternative to carotid endarterectomy. In our study, ninety-nine patients underwent CAS in 110 arteries. Procedural success was 99% (109/110). Our results show that CAS treatment in post-CEA restenosis, especially with improved technique and distal protection, is safe with a low neurological complication rate, without any "local" complications and without any cranial nerve palsies. This study suggests that the future primary mode of treatment of post-CEA restenosis might be carotid stenting rather than surgery.

Mycobacterium tuberculosis phagosomes exhibit altered calmodulin-dependent signal transduction: contribution to inhibition of phagosome-lysosome fusion and intracellular survival in human macrophages.

Mycobacterium tuberculosis successfully parasitizes macrophages by disrupting the maturation of its phagosome, creating an intracellular compartment with endosomal rather than lysosomal characteristics. We have recently demonstrated that live M. tuberculosis infect human macrophages in the absence of an increase in cytosolic Ca(2+) ([Ca(2+)](c)), which correlates with inhibition of phagosome-lysosome fusion and intracellular viability. In contrast, killed M. tuberculosis induces an elevation in [Ca(2+)](c) that is coupled to phagosome-lysosome fusion. We tested the hypothesis that defective activation of the Ca(2+)-dependent effector proteins calmodulin (CaM) and CaM-dependent protein kinase II (CaMKII) contributes to the intracellular pathogenesis of tuberculosis. Phagosomes containing live M. tuberculosis exhibited decreased levels of CaM and the activated form of CaMKII compared with phagosomes encompassing killed tubercle bacilli. Furthermore, ionophore-induced elevations in [Ca(2+)](c) resulted in recruitment of CaM and activation of CaMKII on phagosomes containing live M. tuberculosis. Specific inhibitors of CaM or CaMKII blocked Ca(2+) ionophore-induced phagosomal maturation and enhanced the bacilli's intracellular viability. These results demonstrate a novel role for CaM and CaMKII in the regulation of phagosome-lysosome fusion and suggest that defective activation of these Ca(2+)-activated signaling components contributes to the successful parasitism of human macrophages by M. tuberculosis.

Integrated minimally invasive approaches for the treatment of atherosclerotic vascular diseases: Hybrid procedures.

Patients may develop simultaneous symptoms of atherosclerotic vascular disease from different arterial beds. A concurrent minimally invasive approach to the management of these clinical situations may be an advantage over conventional surgical procedures. This study describes two separate case series of patients undergoing coronary/peripheral (n = 38) and peripheral/peripheral procedures (n = 10). Technical and clinical success was achieved in all patients. There were two periprocedural complications (retroperitoneal bleed and septicemia) in the coronary/peripheral series and no complications in the peripheral/peripheral series. We also present five case reports to illustrate the utility of hybrid procedures in various clinical settings. This study suggests that the use of simultaneous or sequential minimally invasive procedures appears to be a safe and feasible strategy for the treatment of patients with symptoms from more than one vascular bed. Cathet Cardiovasc Intervent 2001;52:154-161.

Validity of duplex ultrasound as a diagnostic modality for internal carotid artery disease.

There is an increasing trend to rely on duplex ultrasound rather than angiography to measure an internal carotid artery stenosis. The aim of this study was to determine the validity of ultrasound assessment of carotid stenosis performed in community based vascular laboratories. We compared ultrasound with angiography in 225 patients referred to us for carotid intervention. Mild lesions were diagnosed by ultrasound with a sensitivity of 54%, specificity of 89%, and a positive predictive value of 89% compared with angiography. Severe lesions had a sensitivity of 93%, a specificity of 67%, and a positive predictive value of 45%. Receiver operator characteristic curves demonstrated the optimal ultrasound cut-off value of 66% stenosis as a predictor of >60% stenosis measured angiographically, is associated with a false positive rate of 38%, and a false negative rate of 9%. Similarly, if a cut-off of 76% on ultrasound is used to predict >70% stenosis measured angiographically, it would be associated with a 29% false positive rate and a false negative rate of 11%. Despite the value of non-invasive testing for carotid disease, duplex ultrasonography performed in non-accredited and some accredited laboratories may produce highly variable results. Using ultrasound as the sole diagnostic test to determine the severity of a carotid stenosis may result in a high number of inappropriate operations and a large proportion of patients who may not be offered treatment due to false negative diagnoses.

Carotid stenting with distal-balloon protection via the transbrachial approach.

PURPOSE: To document the feasibility of brachial artery access for carotid stenting with distal-balloon protection of the internal carotid artery (ICA). TECHNIQUE: Via percutaneous access to the brachial artery, a large double-curve catheter is advanced into the aortic arch over a hydrophilic guidewire to cannulate the left common carotid artery. Following sheath exchange, a GuardWire distal-protection balloon is positioned within the left ICA distal to the stenosis. The lesion is dilated, followed by deployment and dilation of a self-expanding stent. Transcranial Doppler monitoring shows only scarce microembolic signals during the procedure. CONCLUSIONS: Carotid stenting with distal balloon protection via the brachial artery appears feasible as an alternative to standard femoral access.

Carotid stent placement for extracranial carotid artery disease: current state of the art.

Percutaneous revascularization techniques have dramatically altered traditional approaches to the management of both coronary and peripheral vascular disease. Their major advantage is that they are less invasive than conventional surgical procedures, offering revascularization without the risk of general anesthesia and with lesser procedural morbidity and mortality, shorter hospital stay, and lower cost. In patients with comorbidities that increase their risk of surgical complications, percutaneous revascularization techniques are the procedures of choice. The Achilles heel of balloon angioplasty, the higher risk of lesion recurrence, restenosis, has been markedly reduced with the use of endovascular stents. Over the past 20 years, percutaneous angioplasty and stenting have become accepted alternatives to surgical revascularization of aortoiliac, renal, femoropopliteal, subclavian, brachiocephalic, and dialysis access lesions. The most recent application of percutaneous intervention has been to explore its clinical utility and safety for stroke prevention in stenotic extracranial carotid arteries. Cathet. Cardiovasc. Intervent. 51:339-346, 2000.

Safety, efficacy, and durability of carotid artery stenting for restenosis following carotid endarterectomy: a multicenter study.

PURPOSE: To present the results of a multicenter registry established to collect data on carotid stent procedures in patients with restenosis following carotid endarterectomy. METHODS: The procedural details, outcomes, and late follow-up results were collected from 14 centers in the United States. Thirty-day and late stroke and death rates were analyzed. RESULTS: Three hundred and thirty-eight patients (201 men; 71 +/- 8 years) underwent carotid stenting in 358 arteries. The average duration from carotid endarterectomy was 5.5 +/- 7.3 years. Sixty-one percent of the patients were asymptomatic. The overall 30-day stroke and death rate was 3.7%. The minor stroke rate was 1.7% (6/358), and the major nonfatal stroke rate was 0.8% (3/358). The fatal stroke rate was 0.3% (1/358), and the nonstroke-related death rate was 0.9% (3/338). There was 1 (0.3%) fatal and 1 (0.3%) nonfatal stroke during the follow-up period. The overall 3-year rate of freedom from all fatal and nonfatal strokes was 96% +/- 1% (+/- SE). CONCLUSIONS: Carotid artery stenting can be performed in patients with restenosis following carotid endarterectomy with 30-day complication rates comparable to those of most published studies on repeat carotid endarterectomy. Results of late follow-up suggest that this technique is durable and efficacious.