Assessment of changes in brain metabolites in Indian patients with type-2 diabetes mellitus using proton magnetic resonance spectroscopy

BACKGROUND: The brain is a target for diabetic end-organ damage, though the pathophysiology of diabetic encephalopathy is still not well understood. The aim of the present study was to investigate the effect of diabetes on the metabolic profile of brain of patients having diabetes in comparison to healthy controls, using in-vivo magnetic resonance spectroscopy to get an insight into the pathophysiology of cerebral damages caused due to diabetes. METHODS: Single voxel proton magnetic resonance spectroscopy ((1)H-MRS) was performed at 1.5 T on right frontal, right parieto-temporal and right parieto-occipital white matter regions of the brain of 10 patients having type-2 diabetes along with 7 healthy controls. Absolute concentration of N-acetylaspartate (NAA), choline (cho), myo-inositol (mI), glutamate (Glu) and glutamine (Gln), creatine (Cr) and glucose were determined using the LC-Model and compared between the two groups. RESULTS: The concentration of N-acetylaspartate was significantly lower in the right frontal [4.35 ±0.69 vs. 5.23 ±0.74; p = 0.03] and right parieto-occipital region [5.44 ±0.52 vs.6.08 ±0.25; p = 0.02] of the brain of diabetics as compared to the control group. The concentrations of glutamate and glutamine were found to be significantly higher in the right frontal region of the brain [7.98 ±2.57 vs. 5.32 ±1.43; P = 0.01] in diabetics. Glucose levels were found significantly elevated in all the three regions of the brain in diabetics as compared to the control group. However, no significant changes in levels of choline, myo-inositol and creatine were observed in the three regions of the brain examined among the two groups. CONCLUSIONS: (1)H-MRS analysis indicates that type-2 diabetes mellitus may cause subtle changes in the metabolic profile of the brain. Decreased concentrations of NAA might be indicative of decreased neuronal viability in diabetics while elevated concentrations of Gln and Glu might be related to the fluid imbalance resulting from disruption of glucose homeostasis

The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment

Abstract Background Rifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV) and tuberculosis (TB) co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART) when co-administered with rifampicin-containing antituberculosis treatment (ATT) and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen. Methods 63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART. Results 97 out of 114 (85.1%) patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83) at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD) Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10), 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08), 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10) respectively and 3.04 μg/ml (in cases). Conclusions Good immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in antiretroviral effectiveness. Larger sample sized studies and longer follow-up are required to identify populations of individuals where the reduction in nevirapine concentration may result in lower ART response or shorter response duration

Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment

BACKGROUND: For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events. METHODS: In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. FINDINGS: A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05). Rates of adverse events were similar. INTERPRETATION: Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. TRIAL REGISTRATION: CTRI/2011/12/00226

Retropharyngeal abscess as a rare presentation of pulmonary tuberculosis

A tubercular retropharyngeal abscess is rare in immunocompetent adults. In the case of a tubercular retropharyngeal abscess, it is usually due to cervical spine tuberculosis and is seen mostly in children. A 19-year-old female patient presented to our Medicine Outpatient Department (OPD) at All India Institute of Medical Sciences (AIIMS) with odynophagia and neck pain for two months, without any other constitutional symptoms. On evaluation, she was diagnosed with tubercular retropharyngeal abscess along with pulmonary tuberculosis, without involvement of the cervical spine. This patient was successfully treated by antituberculosis drug therapy alone, without any need for surgical drainage

Severe hypoglycemia masquerading as cerebellar stroke

Hypoglycemia is a common presenting feature of diabetes in the emergency department. Cardiovascular and neuroglycopenia features are well documented in the literature. We here report a case of 55-year-old female who came to our emergency with clinical features suggestive of cerebellar stroke. Laboratory investigations revealed severe hypoglycemia. The cerebellar signs and symptoms improved completely with intravenous dextrose infusion. Her MR imaging and Doppler of carotid and vertebrobasilar arteries were noncontributory. Hypoglycemia causes behavioral changes, confusion, loss of consciousness, and seizures. It is also well known to cause hemiplegia and aphasia. Hypoglycemia presenting as cerebellar stroke is rarely reported in the literature. This case highlights an uncommon manifestation of a common clinical condition. Physician must rule out hypoglycemia in every stroke patients

Alzheimer disease in post-menopausal women: Intervene in the critical window period

Alzheimer disease (AD) is a crippling neurodegenerative disorder. It is more common in females after menopause. Estrogen probably has a protective role in cognitive decline. Large amount of research has been carried out to see the benefits of hormone replacement therapy with regards to Alzheimer still its neuroprotective effect is not established. Recent studies suggest a reduced risk of AD and improved cognitive functioning of post-menopausal women who used 17 β-estradiol in the critical period. Use of 17 β-estradiol in young and healthy post-menopausal women yields the maximum benefit when the neurons are intact or neuronal stress has just started. Hence intervention in the critical period is key in the prevention or delay of AD in post-menopausal women

Deliberate self-harm with parenteral chlorpyrifos: a case report

AbstractOrganophosphate (OP) pesticide poisoning is one of the most common poisonings in India. Most self-poisoning involves pesticide ingestion. Parenteral pesticide poisoning is unusual. Here we report a case of a middle-aged man who presented with history of deliberate self-harm by injecting chlorpyrifos. The patient presented to the Emergency Department with cholinergic symptoms and blisters and ulcers on the right arm. This case represents an uncommon mode of OP pesticide toxicity and distinctive set of local complications secondary to injection