Background and Purose
Disruption of the blood-brain barrier (BBB) has been proposed to be important in vascular cognitive impairment (VCI). Increased cerebrospinal fluid (CSF) albumin and contrast-enhanced MRI provide supporting evidence, but quantification of the BBB permeability in patients with VCI is lacking. Therefore, we acquired dynamic contrast-enhanced MRI (DCEMRI) to quantify BBB permeability in VCI.
We studied 60 patients with suspected VCI. They had neurological and neuropsychological testing, permeability measurements with DCEMRI and lumbar puncture to measure albumin index (Qalb). Patients were separated clinically into subcortical ischemic vascular disease (SIVD), multiple and lacunar infarcts (MI/LAC), and leukoaraiosis (LA). Twenty volunteers were controls for the DCEMRI studies, and control CSF was obtained from 20 individuals undergoing spinal anesthesia for non-neurological problems.
Thirty-six patients were classified as SIVD, 8 as MI/LAC and 9 as LA. The Qalb was significantly increased in the SIVD group compared to 20 controls. Permeabilities for the VCI patients measured by DCEMRI were significantly increased over controls (p<0.05). Patient age correlated with neither the BBB permeability nor Qalb. Highest Qalb values were seen in SIVD group (p<0.05), and were significantly increased over MI/LAC. Ki values were elevated over controls in SIVD, but were similar to MI/LAC.
There was abnormal permeability in white matter in patients with SIVD as shown by DCEMRI and Qalb. Future studies will be needed to determine the relationship of BBB damage and development of WMHs.
Albumin; blood-brain barrier; vascular cognitive impairment; MRI; cerebrospinal fluid
Treatment outcomes for multidrug-resistant tuberculosis (MDR-TB) in South Africa have suffered as centralized, inpatient treatment programs struggle to cope with rising prevalence and HIV co-infection rates. A new treatment model is needed to expand treatment capacity and improve MDR-TB and HIV outcomes. We describe the design and preliminary results of an integrated, home-based MDR-TB/HIV treatment program created in rural KwaZulu-Natal. In 2008, a decentralized center was established to provide outpatient MDR-TB and HIV treatment. Nurses, community health workers, and family supporters have been trained to administer injections, provide adherence support, and monitor adverse reactions in patients’ homes. Physicians assess clinical response, adherence, and adverse reaction severity to MDR-TB and HIV therapy at monthly follow-up visits. Treatment outcomes are assessed by monthly cultures and CD4 and viral load every 6 months. Eighty patients initiated MDR-TB therapy from 2/2008–4/2010; 66 were HIV co-infected. Retention has been high (only 5% defaults, 93% of visits attended) and preliminary outcomes have been favorable (77% cured/still on treatment, 82% undetectable viral load). Few patients have required escalation of care (9%), had severe adverse events (8%), or died (6%). Integrated, home-based treatment for MDR-TB and HIV is a promising treatment model to expand capacity and achieve improved outcomes in rural, resource-poor, and high-HIV prevalent settings.
HIV/AIDS; Multidrug-resistant tuberculosis; Community-based treatment; Program development; AIDS
Neurogranin (NRGN) is the main postsynaptic protein regulating the availability of calmodulin-Ca(2+) in neurons. NRGN is expressed exclusively in the brain, particularly in dendritic spines and has been implicated in spatial learning and hippocampal plasticity. Genetic variation in rs12807809 in the NRGN gene has recently been confirmed to be associated with schizophrenia in a meta-analysis of genome-wide association studies: the T-allele was found to be genome-wide significantly associated with schizophrenia. Cognitive tests and personality questionnaires were administered in a large sample of healthy subjects. Brain activation was measured with functional magnetic resonance imaging (fMRI) during an episodic memory encoding and retrieval task in a subsample. All subjects were genotyped for NRGN rs12807809. There was no effect of genotype on personality or cognitive measures in the large sample. Homozygote carriers of the T-allele showed better performance in the retrieval task during fMRI. After controlling for memory performance, differential brain activation was evident in the anterior cingulate cortex for the encoding and posterior cingulate regions during retrieval. We could demonstrate that rs12807809 of NRGN is associated with differential neural functioning in the anterior and posterior cingulate. These areas are involved in episodic memory processes and have been implicated in the pathophysiology of schizophrenia in structural and functional imaging as well as postmortem studies.
NRGN; fMRI; memory; cingulate
During the last decade considerable attention has been focussed upon the development of new technologies and methodologies for detection of drug resistance in Mycobacterium tuberculosis. There is a growing acknowledgement that the redundancy in testing a full panel of first-line drugs is an unaffordable indulgence; since only resistance at baseline to either (or both) of the two most potent agents, isoniazid (H) and rifampicin (R), would usually prompt therapeutic modification there is a shift towards initial RH (or R alone for selected genotypic technologies) drug susceptibility testing (DST) followed, if necessary by further extended first and second line agent (currently phenotypic) DST. Most of the new drug susceptibility tests endorsed by the World Health Organization since 2007 deliver rapid RH (or R alone for selected genotypic technologies) DST. Targeting of patient groups with risk factors for drug resistance increases the proportion of tests that identify drug resistance, but in many settings at least as many patients with drug resistant disease will have no identifiable risk factors—equity of care demands that universal RH DST at baseline should be the goal. We review the bewildering array of choices facing TB program directors and attempt to provide objective information to help in deciding what tools may be best suited to different environments.
In patients with HIV and tuberculosis (TB) in resource-constrained settings, smear-negative disease has been associated with higher mortality than smear-positive disease. Higher reported mortality may be due to misdiagnosis, diagnostic delays, or because smear-negative disease indicates more advanced immune suppression.
We analyzed culture-confirmed, pulmonary TB among patients with TB and HIV in the United States from 1993–2008 to calculate prevalence ratios (PRs) for smear-negative disease by demographic and clinical characteristics. Allowing two years for treatment outcome to be reported, we determined hazard ratios (HRs) for survival by smear status, adjusted for significant covariates on patients before 2006.
Among 16,710 cases with sputum smear results, 6,739 (39%) were sputum smear-negative and 9,971 (58%) were sputum smear-positive. The prevalence of smear-negative disease was lower in male patients (PR: 0.89, 95% confidence interval [CI]: 0.86–0.93) and in those who were homeless (PR: 0.92, CI: 0.87–0.97) or used alcohol excessively (PR: 0.91, CI: 0.87–0.95), and higher in persons diagnosed while incarcerated (PR: 1.20, CI: 1.13–1.27). Patients with smear-negative disease had better survival compared to patients with smear-positive disease, both before (HR: 0.82, CI: 0.75–0.90) and after (HR: 0.81, CI: 0.71–0.92) the introduction of combination anti-retroviral therapy.
In the United States, smear-negative pulmonary TB in patients with HIV was not associated with higher mortality, in contrast to what has been documented in high TB burden settings. Smear-negative TB can be routinely and definitively diagnosed in the United States, whereas high-burden countries often rely solely on AFB-smear microscopy. This difference could contribute to diagnostic and treatment delays in high-burden countries, possibly resulting in higher mortality.
Tourette syndrome is a neuropsychiatric disorder characterized by motor and phonic tics. Deficient motor inhibition underlying tics is one of the main hypotheses in its pathophysiology. Therefore the question arises whether this supposed deficient motor inhibition affects also voluntary movements. Despite severe motor tics, different personalities who suffer from Tourette perform successfully as neurosurgeon, pilot or professional basketball player.
For the investigation of fine motor skills we conducted a motor performance test battery in an adult Tourette sample and an age matched group of healthy controls.
The Tourette patients showed a significant lower performance in the categories steadiness of both hands and aiming of the right hand in comparison to the healthy controls. A comparison of patients’ subgroup without comorbidities or medication and healthy controls revealed a significant difference in the category steadiness of the right hand.
Our results show that steadiness and visuomotor integration of fine motor skills are altered in our adult sample but not precision and speed of movements. This alteration pattern might be the clinical vignette of complex adaptations in the excitability of the motor system on the basis of altered cortical and subcortical components. The structurally and functionally altered neuronal components could encompass orbitofrontal, ventrolateral prefrontal and parietal cortices, the anterior cingulate, amygdala, primary motor and sensorimotor areas including altered corticospinal projections, the corpus callosum and the basal ganglia.
Gastric fundoplication (GF) for gastroesophageal reflux disease (GERD) may protect against the progression of chronic rejection in lung transplant (LT) recipients. However, the association of GERD with acute rejection episodes (ARE) is uncertain. This study sought to identify if ARE were linked to GERD in LT patients.
This single-center retrospective observational study, of patients transplanted from January 1, 2000, to January 31, 2009, correlated results of pH probe testing for GERD with ARE (≥International Society for Heart and Lung Transplantation A1 or B1). We compared the rates of ARE among patients with GERD (DeMeester Score > 14.7) versus without GERD as number of ARE per 1,000 patient-days after LT. Patients undergoing GF prior to LT were excluded.
The analysis included 60 LT subjects and 9,249 patient-days: 33 with GERD versus 27 without GERD. We observed 51 ARE among 60 LT recipients. The rate of ARE was highest among patients with GERD: 8.49 versus 2.58, an incidence density ratio (IDR) of 3.29 (P = .00016). Upon multivariate negative binomial regression modeling, only GERD was associated with ARE (IDR 2.15; P = .009). Furthermore, GERD was associated with multiple ARE (36.4% vs 0%; P < .0001) and earlier onset compared with patients without GERD: ARE proportion at 2 months was 0.55 versus 0.26 P = .004).
In LT recipients, GERD was associated with a higher rate, multiple events, and earlier onset of ARE. The efficacy of GF to reduce ARE among patients with GERD needs further evaluation.
A sensitive, accurate, precise and validated ion-pairing reverse-phase liquid chromatographic method for the quantitative determination of atenolol and indapamide in bulk and tablet dosage form was developed. The proposed ion-pairing reverse-phase high performance liquid chromatography method utilises C18 column with 5 μm, 150×4.6 mm i.d. column and mobile phase consisting of 0.1% w/v solution of octane sulphonic acid, sodium salt and methanol (55:45 v/v), (pH 2.8) and ultraviolet detection at 235 nm. A linearity range of 1-250 μg/ml and 1-25 μg/ml for atenolol and indapamide, respectively, was obtained. The mean recoveries are 100.48 and 99.82% for atenolol and indapamide, respectively. The method was validated as per International Conference on Harmonization guidelines.
Atenolol; indapamide; ion-pairing; reverse-phase high performance liquid chromatography
In modern day psychiatric practice, it is assumed as a matter of fact that when electroconvulsive therapy (ECT) is administered, it will be administered under anesthesia and with succinylcholine (or its equivalent) modification. Yet, as surveys indicate, there is considerable practice of unmodified ECT in developing countries and, to a small extent, in the developed world, as well.
Materials and Methods:
This document examines historical and recent literature on the geographical practice, physiology, efficacy, and adverse effects of unmodified ECT. Particular attention is paid to musculoskeletal risks.
Although almost all the research is of poor methodological quality, there is a good reason to accept that unmodified ECT is associated with a wide range of adverse consequences, important among which are musculoskeletal complications, pre-ECT anxiety, and post-ECT confusion. However, it appears from recent data that these risks are not as large as historically portrayed. Possibly explanations are suggested, with seizure modification using parenteral benzodiazepines as a special possibility.
Under exceptional circumstances, if ECT is strongly indicated and seizure modification with succinylcholine is not feasible, unmodified ECT, especially benzodiazepine-modified ECT, may be a viable option. A detailed set of recommendations for such use of unmodified ECT is proposed along with necessary checks and balances. This document has been approved by the Indian Psychatric Society, the Indian Association of Biological Psychiatry, and the Indian Association of Private Psychiatry (which commissioned the preparation of the document).
Adverse effects of ECT; benzodiazepine-modified ECT; electroconvulsive therapy; guideline; position statement; succinylcholine; unmodified ECT
To report three cases of Loa loainfestation presenting over the course of 12 months to ophthalmology departments in the South West Thames region around London.
Case series (three case histories are described) and literature review.
All three patients had a history of travel to West Africa. All had worms surgically removed and were referred to an infectious diseases hospital, where these were confirmed as adult Loa loanematodes and treatment was initiated.
Although ocular loiasis is endemic in West Africa, European ophthalmologists in areas of diverse ethnicity should be aware that it is presenting increasingly frequently, that there is often no history of recent travel abroad, and that loiasis is a differential diagnosis for any ‘at-risk' patient with an unexplained foreign body sensation.
loa; eye infections; parasitic
To evaluate the effect of single-dose intravitreal bevacizumab followed by panretinal and macular grid laser, early in the course of central retinal vein occlusion (CRVO).
It is a prospective, non-randomized, interventional study of nine eyes of nine patients with <10 days origin of CRVO who received 2.5 mg (0.1 ml) intravitreal bevacizumab, followed 3 weeks later by panretinal and macular grid photocoagulation. Its effect on visual acuity and anatomical features of CRVO were studied.
Nine eyes of nine patients (male : female=8 : 1, mean age 54 years), with <10days (average 2.67days) onset of CRVO, received intravitreal bevacizumab within 7 days of presentation (average 3.1days) followed 3 weeks later by panretinal with macular grid laser. Presenting mean baseline visual acuity was 20/320 (1.2 logarithm of the minimum angle of resolution (LOGMAR) units). All the patients showed rapid improvement in the form of rapid clearance of retinal hemorrhages, decreased optic disc swelling and venous dilation, and tortuosity. Mean final visual acuity was 20/63 (0.5 LOGMAR units). No patient showed conversion from non-ischemic to ischaemic CRVO, recurrence of macular edema, and disc collateral formation.
Early intravitreal bevacizumab followed by panretinal and macular grid laser may provide visually and anatomically favourable results in a case of CRVO. It may also obviate the need for repeated injection. It requires a large randomized study to substantiate the results.
bevacizumab; central retinal vein occlusion; intravitreal injection; macular edema; panretinal photocoagulation; vascular endothelial growth factor
To date, there are no studies from El Salvador among people with HIV to inform prevention programs. We
conducted a study in El Salvador in 2008 among people with HIV using audio computer-assisted interviews on risk
behaviors and access to health care. Blood was tested for syphilis and herpes simplex type 2 (HSV-2). Active syphilis was
defined as RPR titer ≥1:8. Genital specimens were tested for other sexually transmitted infections (STI) by PCR. We
evaluated factors associated with unprotected sex with last stable partner of HIV-negative or unknown status among those
reporting a stable partner. A total of 811 HIV-positive individuals participated: 413 men and 398 women. Prevalence of
Chlamydia and gonorrhea was low (≤1%), while prevalence of other STI was high: Mycoplasma genitalium (14%),
syphilis (15% seropositivity, active syphilis 3%) and HSV-2 (85%). In multivariate analysis, disclosing HIV status to
partner (OR 0.2, 95% CI: 0.1-0.3, p<0.001), participation in HIV support groups (OR 0.3, 95% CI: 0.1-0.8, p=0.01), easy
access to condoms (OR 0.4, 95% CI: 0.2-0.9, p=0.04) were protective factors for unprotected sex. Reporting a casual
partner in the last 12 months (OR 3.6, 95% CI: 1.5-8.5, p=0.004). and having an STI (OR 2.6, 95% CI:1.3-5.5, p=0.02)
were associated with an increased odds of unprotected sex. Prevention interventions among HIV-positives in El Salvador
should focus on increasing condom access, promoting HIV disclosure and couples testing and reducing the number of
partners. The positive role of support groups should be used to enhance behavioral change.
El Salvador; HIV; AIDS; Prevention; People living with HIV; Condoms; Sexually transmitted infections.
AIM: To determine the prevalence of restless legs syndrome (RLS) in patients with irritable bowel syndrome (IBS).
METHODS: Patients with diarrhea-predominant IBS (n = 30), constipation-predominant IBS (n = 30), or mixed-symptom IBS (n = 30) were recruited from the community between March 2008 and February 2009. Rifaximin 200 mg three times daily was administered empirically to alleviate small intestinal bowel overgrowth in all patients. The presence of RLS was assessed via an RLS questionnaire and polysomnography.
RESULTS: Twenty-six patients with IBS (29%) were diagnosed with RLS using the RLS questionnaire. Twenty-four of the 26 patients (92%) underwent polysomnography, and all had confirmation of RLS. A greater percentage of patients with RLS had diarrhea-predominant IBS (62%) compared with patients with constipation-predominant IBS (4%) or mixed-symptom IBS (33%).
CONCLUSION: Restless legs syndrome is prevalent in patients with IBS, especially those with diarrheal symptoms. Assessment of concomitant disorders may improve diagnosis and expand relevant treatment options for patients.
Restless legs syndrome; Irritable bowel syndrome; Small intestinal bacterial overgrowth; Prevalence
Pediatric brain tumors have always been challenging as well as intriguing in their anatomical, surgical, and postsurgical management-related issues. They are a heterogeneous set of pathologies involving different age groups in childhood and also differ widely from their adult counterparts as far as adjuvant therapies are concerned. Though neurosurgeons across the world are radical in surgery for most of the pediatric tumors, it can often be at the cost of future quality of life in suprasellar tumors. As the time has gone by, the pendulum has swung toward rather conservative and maximal safe surgical resections with adjuvant therapies coming to the forefront. Hence, the aim is to achieve a good quality of life for these children along with a control of tumor growth (rather than cure) and to again tackle the tumors, if required, once these children reach adolescence or adulthood. We have reviewed the literature for different pediatric suprasellar tumors and discussed their current management giving our perspective with illustrative cases.
Chemotherapy; pediatric brain tumors; radiotherapy; suprasellar
To evaluate in vivo the remineralizing efficacy of silver diamine fluoride (SDF), glass ionomer Type VII (GC VII) and calcium hydroxide (Dycal).
Materials and Methods:
60 subjects in the age group of 18-35 years, matching the inclusion criteria and having deep carious lesions in the permanent first and second molars were selected. The teeth were aseptically opened under rubber dam and after gross caries removal, approximately 0.4mg of soft discolored dentin was removed with a sharp spoon excavator from the mesial or distal aspect of the cavity. The test material was randomly selected and applied in a thickness of 1.5-2mm and the cavity sealed with cavit. The patients were followed up at regular intervals with radiographic evaluation at 12 weeks. At 3 months the temporary restoration was removed and dentin samples were collected from the other half of the cavity which was left in the first appointment. Atomic absorption spectrophotometry, Colorimetric test using UV-vis spectrometer and potentiometric titration were used for determining calcium, phosphorous and fluoride respectively.
Almost equivalent rise in the percentage of calcium level was seen in GC VII and Ca(OH)2 groups, followed by SDF group. Highest percentage rise in phosphate ions was seen in GC VII group followed by SDF group and Ca(OH)2 group. Highest percentage of fluoride rise was seen in GC VII group followed by SDF group and Ca(OH)2 group.
The results indicated that both GC VII and SDF can be potential indirect pulp capping materials.
Remineralisation; silver diamine fluoride; GC type VII; indirect pulp capping
In 2005 a cluster of 53 HIV-infected patients with extensively drug-resistant tuberculosis (XDR-TB) was detected in the Msinga sub-district, the catchment area for the Church of Scotland Hospital (CoSH) in Tugela Ferry, in KwaZulu-Natal province (KZN), South Africa. KZN is divided into 11 healthcare districts. We sought to determine the distribution of XDR TB cases in the province in relation to population density.
In this cross-sectional study, the KZN tuberculosis laboratory database was analysed. Results of all patients with a sputum culture positive for Mycobacterium tuberculosis from January 2006 to June 2007 were included. Drug-susceptibility test results for isoniazid, rifampicin, ethambutol, streptomycin, kanamycin and ofloxacin were available for all patients as well as the location of the hospital where their clinical diagnosis was made.
In total, 20858 patients attending one of 73 hospitals or their adjacent clinics had cultures positive for M. tuberculosis. Of these, 4170 (20%) were MDR-TB cases. Four hundred and forty three (11%) of the MDR tuberculosis cases displayed the XDR tuberculosis susceptibility profile. Only 1429 (34%) of the MDR-TB patients were seen at the provincial referral hospital for treatment. The proportion of XDR-TB amongst culture-confirmed cases was highest in the Msinga sub-district (19.6%), followed by the remaining part of the Umzinyati district (5.9%) and the other 10 districts (1.1%). The number of hospitals with at least one XDR-TB case increased from 18 (25%) to 58 (80%) during the study period.
XDR-TB is present throughout KZN. More than 65% of all diagnosed MDR-TB cases, including XDR-TB patients, were left untreated and likely remained in the community as a source of infection.
Indirect pulp capping (IPC) preserves the pulp vitality by disinfecting and remineralizing remaining carious dentin. In the present study, glass ionomer (GC, FUJI VII) and silver diamine fluoride (SDF) were tested and compared to calcium hydroxide for their antimicrobial efficacy and remineralizing potential.
Materials and Methods:
Dentin disks prepared from 45 freshly extracted first premolars were divided into three groups (n = 15). Each disk was cut into two equal parts, in which one half formed the control. Thirty dentin samples were used for ion estimation and the other 15 for microhardness testing. Atomic absorption spectrophotometry, colorimetric and potentiometric titration analyses were performed for calcium, phosphate and fluoride ion detection, respectively. The antimicrobial efficacy was analyzed using pure culture of Streptococcus mutans and mixed flora.
Increase in the levels of calcium and phosphate ions was the highest in calcium hydroxide group. Both SDF and GC VII groups showed significant increase in fluoride ion levels. Samples treated with GC VII showed maximum increase in micro hardness. The highest zone of bacterial inhibition was found with SDF group.
This in vitro study documented the remineralizing, re-hardening and antimicrobial efficacy of both SDF and GC VII and hence can act as effective IPC materials.
Calcium hydroxide; glass ionomer; high-fluoride releasing dental materials; indirect pulp capping; remineralization; silver diamine fluoride
We expanded second-line tuberculosis (TB) drug susceptibility testing for extensively drug-resistant Mycobacterium tuberculosis isolates from South Africa. Of 19 patients with extensively drug-resistant TB identified during February 2008–April 2009, 13 (68%) had isolates resistant to all 8 drugs tested. This resistance leaves no effective treatment with available drugs in South Africa.
Extensively drug-resistant tuberculosis; tuberculosis and other mycobacteria; HIV; drug resistance; second-line drugs; South Africa; dispatch
Extensively drug-resistant tuberculosis (XDR-TB) has been documented worldwide, but reports of XDR-TB in children are extremely limited.
To report the characteristics of pediatric XDR-TB patients in rural South Africa.
We retrospectively reviewed children with sputum culture-confirmed XDR-TB from Tugela Ferry, South Africa, from January 2006 to December 2007. Demographic, clinical and microbiologic data were abstracted from medical records.
Four children aged 6–8 years with XDR-TB were reviewed. Two had previous histories of TB. All were human immunodeficiency virus (HIV) infected orphans; three received highly active antiretroviral therapy (HAART) before XDR-TB diagnosis. All had clinical and radiographic improvement and sputum culture conversion while on standardized XDR-TB treatment and HAART. Two tolerated concomitant XDR-TB and HIV treatment well. Two experienced neuropsychiatric side effects related to cycloserine. All have survived >24 months and all were cured. Prior to XDR-TB diagnosis, the children had resided in the hospital’s pediatric ward for a median of 8 months (range 5–17), including a 3-month overlapping period.
XDR-TB is a microbiologic diagnosis that, even with HIV co-infection, can be successfully identified. Concurrent XDR-TB and HIV therapy is feasible and effective in children, although more research is needed into potential overlapping toxicities. Nosocomial transmission is suggested, calling for infection control policies in pediatric wards.
extensively drug-resistant tuberculosis; drug-resistant tuberculosis; tuberculosis; pediatrics; HIV/TB; co-infection
Considerable variability across individuals has been reported in both the behavioral and fMRI blood oxygen level-dependent (BOLD) response to nicotine. We aimed to investigate (1) whether there is a heterogeneous effect of nicotine on behavioral and BOLD responses across participants and (2) if heterogeneous BOLD responses are associated with behavioral performance measures. In this double-blind, placebo-controlled, cross-over study, 41 healthy participants (19 smokers)—drawn from a larger population-based sample—performed a visual oddball task after acute challenge with 1 mg nasal nicotine. fMRI data and reaction time were recorded during performance of the task. Across the entire group of subjects, we found increased activation in the anterior cingulate cortex, middle frontal gyrus, superior temporal gyrus, post-central gyrus, planum temporal and frontal pole in the nicotine condition compared with the placebo condition. However, follow-up analyses of this difference in activation between the placebo and nicotine conditions revealed that some participants showed an increase in activation while others showed a decrease in BOLD activation from the placebo to the nicotine condition. A reduction of BOLD activation from placebo to nicotine was associated with a decrease in reaction time and reaction time variability and vice versa, suggesting that it is the direction of BOLD response to nicotine which is related to task performance. We conclude that the BOLD response to nicotine is heterogeneous and that the direction of response to nicotine should be taken into account in future pharmaco-fMRI research on the central action of nicotine.
Electronic supplementary material
The online version of this article (doi:10.1007/s00213-010-2145-8) contains supplementary material, which is available to authorized users.
Nicotine; Functional magnetic resonance imaging (fMRI); Visual oddball; Reaction time
Little is known about the time to sputum culture conversion in MDR-TB patients co-infected with HIV, although such patients have, historically, had poor outcomes. We describe culture conversion rates among MDR-TB patients with and without HIV-co-infection in a TB-endemic, high-HIV prevalent, resource-limited setting.
Patients with culture-proven MDR-TB were treated with a standardized second-line regimen. Sputum cultures were taken monthly and conversion was defined as two negative cultures taken at least one month apart. Time-to-conversion was measured from the day of initiation of MDR-TB therapy. Subjects with HIV received antiretroviral therapy (ART) regardless of CD4 count.
Among 45 MDR-TB patients, 36 (80%) were HIV-co-infected. Overall, 40 (89%) of the 45 patients culture-converted within the first six months and there was no difference in the proportion who converted based on HIV status. Median time-to-conversion was 62 days (IQR 48-111). Among the five patients who did not culture convert, three died, one was transferred to another facility, and one refused further treatment before completing 6 months of therapy. Thus, no patients remained persistently culture-positive at 6 months of therapy.
With concurrent second-line TB and ART medications, MDR-TB/HIV co-infected patients can achieve culture conversion rates and times similar to those reported from HIV-negative patients worldwide. Future studies are needed to examine whether similar cure rates are achieved at the end of MDR-TB treatment and to determine the optimal use and timing of ART in the setting of MDR-TB treatment.
Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) have emerged in high-HIV-prevalence settings, which generally lack laboratory infrastructure for diagnosing TB drug resistance. Even where available, inherent delays with current drug-susceptibility testing (DST) methods result in clinical deterioration and ongoing transmission of MDR and XDR-TB. Identifying clinical predictors of drug resistance may aid in risk stratification for earlier treatment and infection control.
We performed a retrospective case-control study of patients with MDR (cases), XDR (cases) and drug-susceptible (controls) TB in a high-HIV-prevalence setting in South Africa to identify clinical and demographic risk factors for drug-resistant TB. Controls were selected in a 1∶1∶1 ratio and were not matched. We calculated odds ratios (OR) and performed multivariate logistic regression to identify independent predictors.
We enrolled 116, 123 and 139 patients with drug-susceptible, MDR, and XDR-TB. More than 85% in all three patient groups were HIV-infected. In multivariate analysis, MDR and XDR-TB were each strongly associated with history of TB treatment failure (adjusted OR 51.7 [CI 6.6-403.7] and 51.5 [CI 6.4–414.0], respectively) and hospitalization more than 14 days (aOR 3.8 [CI 1.1–13.3] and 6.1 [CI 1.8–21.0], respectively). Prior default from TB treatment was not a risk factor for MDR or XDR-TB. HIV was a risk factor for XDR (aOR 8.2, CI 1.3–52.6), but not MDR-TB. Comparing XDR with MDR-TB patients, the only significant risk factor for XDR-TB was HIV infection (aOR 5.3, CI 1.0–27.6).
In this high-HIV-prevalence and drug-resistant TB setting, a history of prolonged hospitalization and previous TB treatment failure were strong risk factors for both MDR and XDR-TB. Given high mortality observed among patients with HIV and drug-resistant TB co-infection, previously treated and hospitalized patients should be considered for empiric second-line TB therapy while awaiting confirmatory DST results in settings with a high-burden of MDR/XDR-TB.
Current research efforts have mainly concentrated on evaluating the role of substances present in animal food in the aetiology of chronic diseases in humans, with relatively little attention given to evaluating the role of transmissible agents that are also present. Meat workers are exposed to a variety of transmissible agents present in food animals and their products. This study investigates mortality from non-malignant diseases in workers with these exposures.
A cohort mortality study was conducted between 1949 and 1989, of 8520 meat workers in a union in Baltimore, Maryland, who worked in manufacturing plants where animals were killed or processed, and who had high exposures to transmissible agents. Mortality in meat workers was compared with that in a control group of 6081 workers in the same union, and also with the US general population. Risk was estimated by proportional mortality and standardised mortality ratios (SMRs) and relative SMR.
A clear excess of mortality from septicaemia, subarachnoid haemorrhage, chronic nephritis, acute and subacute endocarditis, functional diseases of the heart, and decreased risk of mortality from pre-cerebral, cerebral artery stenosis were observed in meat workers when compared to the control group or to the US general population.
The authors hypothesise that zoonotic transmissible agents present in food animals and their products may be responsible for the occurrence of some cases of circulatory, neurological and other diseases in meat workers, and possibly in the general population exposed to these agents.