Diabetes mellitus is strongly associated with tuberculosis in Indonesia.

SETTING: Diabetes mellitus is a known risk factor for tuberculosis (TB), but no studies have been reported from South-East Asia, which has a high burden of TB and a rapidly growing prevalence of diabetes. OBJECTIVE: To examine if and to what extent diabetes is associated with an increased risk of TB in an urban setting in Indonesia. DESIGN: Case-control study comparing the prevalence of diabetes mellitus (fasting blood glucose level >126 mg/dl) among newly diagnosed pulmonary TB patients and matched neighbourhood controls. RESULTS: Patients and control subjects had a similar age (median 30 years) and sex distribution (52% male), but malnutrition was more common among TB patients (median body mass index 17.7 vs. 21.5 kg/m2). HIV infection was uncommon (1.5% of patients). Diabetes mellitus was present in 60 of 454 TB patients (13.2%) and 18 of 556 (3.2%) control subjects (OR 4.7; 95%CI 2.7-8.1). Adjustment for possible confounding factors did not reduce the risk estimates. Following anti-tuberculosis treatment, hyperglycaemia reverted in a minority (3.7%) of TB patients. CONCLUSION: Diabetes mellitus is strongly associated with TB in young and non-obese subjects in an urban setting in Indonesia. This may have implications for TB control and patient care in this region.     

Brief review: History, concept and controversies in the neurological determination of death

PURPOSE: Despite general worldwide acceptance of the concept of neurological determination of death (NDD), inconsistencies in clinical criteria and ancillary testing requirements remain. Numerous guidelines for NDD may be applied in clinical practice by a variety of medical practitioners, but the scientific rationale for specific guideline recommendations often remains unclear. This review examines the evolution of NDD, and seeks to provide scientific validation for existing NDD criteria. SOURCE: English language peer-reviewed medical journals and established contemporary medical texts. PRINCIPAL FINDINGS: Currently published guidelines appear to have evolved from the work of the ad hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death. The Conference of the Royal Colleges and Faculties of the United Kingdom refined the criteria and subsequently adopted the principal of brainstem death. While the fundamentals of NDD guidelines are remarkably consistent worldwide, specific criteria and requirements are often inconsistent. CONCLUSION: Numerous controversies regarding NDD continue to exist, necessitating further scientific clarification of these issues. More recently published guidelines representing the collective opinion of world experts in NDD based upon best current scientific evidence are available in current medical journals.     

Peri-sleep-onset cortisol levels in children and adolescents with affective disorders.

BACKGROUND: Changes in the hypothalamic-pituitary-adrenal (HPA) axis, as evidenced by patterns of cortisol secretion, have been of interest in understanding depression and anxiety disorders across the life span. Previous studies of pediatric depression have pointed to the period around sleep onset as a key time point for observing alterations in cortisol secretion associated with affective disorders. Evidence also indicates that pubertal development may influence the expression of HPA dysregulation. We hypothesized that adolescents with depression and youth with anxiety disorders exhibit elevated peri-sleep-onset cortisol. METHODS: Plasma cortisol was sampled every 20 min around sleep onset from children and adolescents with major depressive disorder (n = 116), anxiety disorders (n = 32), or no history of psychiatric disorder (control; n = 76). Sleep onset was determined by polysomnography. Classification of participants as children or adolescents was based on Tanner staging of pubertal maturation. RESULTS: Children with anxiety disorders had higher peri-sleep-onset cortisol than children with depression or control children. Adolescents with depression had marginally higher peri-sleep-onset cortisol than control adolescents and significantly higher peri-sleep-onset cortisol than children with depression. CONCLUSIONS: Depression and anxiety are associated with altered cortisol secretion around sleep onset, and these changes appear to be influenced by pubertal maturation.     

Cervical nerve root stimulation. Part I: technical aspects and normal data.

OBJECTIVE: Cervical nerve root stimulation (CRS) is a technique of assessing the proximal segments of motor axons destined to upper extremity muscles. Few studies report normal values. The objective was to determine CMAP onset-latencies and CMAP amplitude, area, and duration changes in healthy controls for the abductor pollicis brevis (APB), abductor digiti minimi (ADM), biceps, and riceps muscles. In addition, to determine the tolerability of CRS, as measured by the visual analog scale (VAS). METHODS: We studied 21 healthy volunteers prospectively with CRS using four target muscles (APB, ADM, biceps, and triceps) bilaterally. Collision studies were used in all APB recordings. VAS was obtained in all subjects. RESULTS: Mean CMAP onset-latencies were: APB 14 +/- 1.5 ms; ADM 14.2 +/- 1.5 ms; biceps 5.4 +/- 0.6 ms; triceps 5.4 +/- 1.0 ms. Onset-latency significantly correlated with height for all nerves. The mean change in CMAP amplitude and area (%) between most distal stimulation and CRS was: APB reduction of 15.1 +/- 11.6 and 4.9 +/- 3.6%; ADM reduction of 21.1 +/- 10.7 and 17.2 +/- 8.8; biceps reduction of 10 +/- 11.5 and reduction of 8.7 +/- 6.8; triceps increase of 3.3 +/- 5.2 and 11.0 +/- 9.9% respectively. Mean CMAP duration change between most distal stimulation and CRS was: APB, increase of 20.4 +/- 7.4%; ADM, increase of 14.4 +/- 8.5%; biceps, increase of 13.9 +/- 10.8%; triceps, increase of 7.7 +/- 6.7%. The mean VAS score was 3.8 +/- 1.2, and all subjects completed the study. CONCLUSIONS: The present study establishes normative data and indicates that CRS is a well-tolerated technique. SIGNIFICANCE: The normal values may be used as reference data for the needle CRS technique in the assessment of proximal conduction abnormalities.     

Sources of Variability in the Detection of Cerebral Emboli with Transcranial Doppler During Cardiac Surgery

OBJECTIVE: The application of intensity thresholds for embolus detection with transcranial Doppler (TCD) can exclude from analysis an unrecognized proportion of high-intensity transient signals (HITS))whose intensities are below the threshold. The lack of consistent threshold criteria between clinical trials may explain part of the discrepancy in the reported HITS counts. We investigated the effect of choosing different thresholds on the sensitivity and specificity of detecting HITS during cardiopulmonary bypass (CPB). METHODS: Two observers independently analyzed TCD recordings from 8 patients under CPB. Doppler signals were classified as true HITS, equivocal HITS, artifacts, and Doppler speckles according to preestablished criteria. The relative intensity of Doppler signals was measured by two different methods (TCD software vs manual). Receiver Operating Characteristic curves determined the optimal threshold for each of the two intensity methods. RESULTS: Reviewers achieved agreement in 96% of 2190 Doppler signals (kappa = 0.90). Relative intensities calculated with the TCD-software method were 3 dB (95% CI: 3.0-3.4) higher than the manual method. The optimal threshold was found at 10 dB (sensitivity: 99%; specificity: 90.8%) with the software method and at 7 dB with the manual method (sensitivity: 96%; specificity: 83%). The use of an intensity threshold 2 dB higher than the optimal increased the rejection of true HITS by 8% and 14%, respectively. CONCLUSIONS: Using intensity thresholds higher than the optimal for embolus detection decreases HITS counts. Choosing a threshold depends on the type of method used for measuring the signal intensity. Uniform threshold criteria and comparative studies between different Doppler devices are necessary for making clinical trials more comparable.     

Rostral anterior cingulate cortex activity in the theta band predicts response to antidepressive medication.

During the last 10 years the knowledge about rostral anterior cingulate cortex (ACC) activity in major depression has substantially increased. Several groups have independently described a relationship between resting activity in this area and response to antidepressant treatment. We have recently confirmed a relationship between resting activity of rostral ACC activity and response in a group of 20 patients with major depression using resting theta activity. In this earlier study regions of interest (ROI) were defined in order to establish regional specificity. Differences between responders and nonresponders were only found in the ACC-ROI, but not in the posterior cingulate region. We have now reanalyzed our data using a whole brain voxelwise approach, in order not to miss any other relevant functional differences. In addition to major differences between responders and nonresponders in the rostral ACC, we have identified a nearby region in the midline orbito-frontal region.     

A profile of invasive cutaneous malignant melanoma in Malta: 1993–2002

BACKGROUND: The incidence of malignant melanoma of the skin has risen in every part of the world where reliable cancer registration data are found. OBJECTIVE: Our study aims to describe the changing incidence of and survival from invasive cutaneous malignant melanoma in Malta, by analysing the data from the 211 cases that were registered at the Malta National Cancer Registry between 1993 and 2002. RESULTS: The age standardized incidence rates for invasive cutaneous malignant melanoma rose from 3.7 per 100,000 population per year for males and 5.1 for females in the first 5-year period, to 8.0 per 100,000 population per year for males and 5.9 for females in the second 5-year period. In both sexes, numbers of thin (< or = 1.0 mm) invasive melanomas increased significantly between 1993 and 2002; males also registered a significant increase in intermediate-thickness (1.01-4.0 mm) melanomas. The increase in numbers of thin and intermediate-thickness melanomas between the two 5-year periods was greatest in patients aged 60 years and over. The overall absolute 5-year survival rate for the first period was 74% and for the second period 92%. CONCLUSION: Numbers of reported cases of invasive cutaneous malignant melanoma in Malta have more than doubled during the 10-year study period. This is mostly due to a marked rise in the diagnosis of thin melanomas in both sexes, occurring mainly in patients aged 60 years and over. As thin melanomas are of low metastasizing potential, this has resulted in an increase in survival between the two 5-year study periods.     

Right aortic arch detected in fetal life.

OBJECTIVE: To evaluate the prenatal distribution, associated conditions and outcome of the different types of right aortic arch (RAA) detected in fetal life. METHODS: This was a retrospective review of all cases of RAA detected prenatally between 1998 and 2005 in two tertiary referral centers. RESULTS: In the study period 71 cases of RAA were detected; 26 (37%) had RAA with aberrant left subclavian artery, 23 (32%) had RAA with mirror-image branching, 20 (28%) had RAA of unknown type and two (3%) had double aortic arch. While 20/26 cases with RAA and aberrant left subclavian artery were isolated findings, all 23 cases with RAA and mirror-image branching were associated with cardiac defects, namely tetralogy of Fallot (43%) or pulmonary atresia with ventricular septal defect (22%). Of the 20 cases with RAA, 19 of unknown type were associated with heterotaxy syndromes and had additional cardiac malformations and ambiguities of the situs. The two cases with DAA were isolated findings. Seven cases in our series (10%) had a microdeletion 22q11 and these were significantly associated with extracardiac malformations. The outcome in our series depended solely on the associated cardiac and extracardiac malformations, with the exception of one infant with isolated DAA, in whom a surgical correction was warranted. CONCLUSIONS: RAA detected in fetal life is associated frequently with other cardiac/non-cardiac malformations, heterotaxy syndromes and microdeletions 22q11. The associated conditions vary depending on the branching type of the brachiocephalic vessels and the presence of extracardiac malformations.     

Gamma-hydroxybutyric Acid Tolerance and Withdrawal in a Rat Model

Long-term daily use of gamma-hydroxybutyrate (GHB) and related compounds has recently been associated with a withdrawal syndrome. To the best of the authors' knowledge, there are currently no animal models of GHB withdrawal. OBJECTIVES: The authors studied and described the effect of chronic dosing of GHB (3-6 days) on tolerance and withdrawal in a rat model. METHODS: Rats were administered GHB every three hours via intraperitoneal catheter. Groups of rats (2 per group) were dosed with GHB for either 3 (24 doses), 4 (32 doses), 5 (40 doses), or 6 (48 doses) days. The GHB dose was 0.25 g/kg for doses 1-8, 0.75 g/kg for doses 9-12, 1 g/kg for doses 13-16, 1.25 g/kg for doses 17-24, 1.5 g/kg for doses 25-32, 1.75 g/kg for doses 33-40, and 2 g/kg for doses 41-48. Following the last dose of GHB, the rats were scored using a 16-point ethanol intoxication-withdrawal scale rating spontaneous behaviors, response to handling, grooming, and neurological signs. Lower scores indicate intoxication, while higher scores indicate withdrawal. Scores were recorded at hours 0, 1, 2, 3, 4, 5, 6, 9, 12, and 24. RESULTS: Tolerance: Rats dosed with GHB for more days were less intoxicated one hour after their last GHB dose despite receiving higher doses. WITHDRAWAL: The scores for all rats dosed with GHB increased at hours 4 (p = 0.028), 5 (p = 0.037), 6 (p = 0.007), and 9 (p = 0.024) after the last dose, indicating withdrawal. The scores demonstrated a linear increase dependent upon the number of days of GHB dosing at hours 3 (p < 0.000), 4 (p = 0.004), 5 (p = 0.002), and 12 (p = 0.039) as well as prior to the last dose at hour 0 (p = 0.000). No rats developed seizures. CONCLUSIONS: Tolerance and mild withdrawal in rats can be induced by administering intraperitoneal GHB every three hours for 3-6 days. More prolonged dosing and higher doses of GHB may be necessary to induce severe withdrawal.