Recent Discoveries of Nitrogen-Containing Heterocyclic Compounds as InhA Inhibitors against Mycobacterium tuberculosis: An Overview.

It is a formidable challenge to treat tuberculosis as there are increasing cases of multidrugresistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) cases. Moreover, the emergence of totally drug-resistant tuberculosis (TDR-TB) makes it vital and imperative to develop a new generation of anti-tubercular drugs to have control over resistance. The nitrogencontaining heterocyclic class of compounds is being studied extensively to ascertain their anti-TB potentials. Nitrogen-containing compounds have a broad range of targets; wherein, InhA is the most important one. Hence, the primary focus of this review is to summarize the recent developments in the discovery of nitrogen-containing heterocyclic compounds as InhA inhibitors to combat tuberculosis.

Plasma and Urinary Amino Acid Profile in Children with Infantile Tremor Syndrome.

BACKGROUND: Infantile Tremor Syndrome (ITS) is a disorder of infancy, and characterized by developmental delay and/or regression, pallor, skin hyperpigmentation and hypopigmented hair. It is commonly seen in infants in whom exclusive breastfeeding is given inappropriately for longer durations than recommended. ITS is predominantly reported from the Indian subcontinent and in children from a lower socioeconomic background. It is a clinical diagnosis and vitamin B12 deficiency is the most commonly accepted etiology of this entity. OBJECTIVES: The primary objectives of study were to compare the plasma and urine amino acid levels among children with ITS spectrum with those of healthy children. The secondary objectives were to compare the plasma and urine amino acid levels among children with ITS and Pre-ITS. STUDY DESIGN: This cross-sectional, observational study was carried out at a tertiary care hospital in North India. PARTICIPANTS: A total of 50 children aged < 36 months with ITS/Pre-ITS were enrolled. Children with Pre-ITS and ITS were compared with healthy age-matched study subjects. RESULTS: Thirty-nine (78%) cases and twelve (24%) healthy children had low serum vitamin B12 levels. Folate levels were normal in all the controls, while only one case had folate deficiency. There were significant differences (p < 0.05) in the values of 32 amino acids in plasma. Among 44 urinary amino acids, levels of 30 amino acids were significantly different in the cases compared with the controls (p < 0.05). CONCLUSIONS: Several changes in amino acids in the children suffering from ITS were observed. These changes may be a reflection of the metabolic derangements in ITS.

Glycosylated fibronectin point-of-care test for diagnosis of pre-eclampsia in a low-resource setting: a prospective Southeast Asian population study.

OBJECTIVE: To determine the performance of a glycosylated fibronectin (GlyFn) point-of-care (POC) test for pre-eclampsia (PE) in a large Southeast Asian cohort (India) in comparison to previously described biomarkers. DESIGN: A total of 798 pregnant women at ≥20 weeks of gestation were enrolled in a prospective case-control study. Study participants included 469 normotensive women with urinary mg protein/mmol creatinine ratio <0.3, 135 with PE (hypertension with urinary mg protein/mmol creatinine ratio ≥0.3) and 194 with gestational hypertension (hypertension with urinary mg protein/mmol creatinine ratio <0.3). METHODS: GlyFn levels were determined using a POC device and PIGF, sFlt-1 and PAPPA2 levels were determined by immunoassay. Performance was assessed using logistic regression modelling and receiver-operating characteristic (ROC) curves. Classification performance and positive and negative predictive values are reported at specific thresholds. RESULTS: Increased levels of GlyFn, soluble fms-like tyrosine kinase-1 (sFlt-1) and pregnancy-associated placental protein A2 (PAPPA2), and decreased levels of placental growth factor (PlGF) were significantly associated (P < 0.01) with clinically defined PE. Area under the ROC (AUROC) values with 95% confidence intervals were: GlyFn, 0.99 (0.98-0.99); PlGF, 0.96 (0.94-0.98); sFlt-1, 0.86 (0.83-0.89); and PAPPA2, 0.96 (0.94-0.97). Of subjects with GH, 48% were positive for more than two PE biomarkers, and 70% of these delivered preterm. CONCLUSIONS: The Lumella™ GlyFn POC test has been validated in a low/middle-income country setting for PE diagnosis and may be a useful adjunctive tool for early identification, appropriate triage, and improved outcomes. TWEETABLE ABSTRACT: The Lumella™ point-of-care test had excellent performance in diagnosing PE in a large Southeast Asian cohort.

Management Strategies of Melkersson-Rosenthal Syndrome: A Review.

Melkerrson-Rosenthal syndrome is a rare disorder of unknown aetiology and characterized by the triad of oro-facial edema, facial nerve palsy, and furrowing of the tongue. Two or more of the above are essential for making a clinical diagnosis. The mainstay of treatment is corticosteroids. Intralesional triamcinolone acetonide may be used for the treatment of oro-facial edema. Another treatment option for oro-facial edema includes intralesional betamethasone, along with oral doxycycline. The review discusses the management strategies in Melkersson-Rosenthal syndrome.

A Child with Tuberculous Meningitis Complicated by Cortical Venous and Cerebral Sino-Venous Thrombosis.

Stroke is common in tuberculous meningitis. Stroke commonly affects the tubercular zone, comprising the anterior part of the thalamus, caudate and the internal capsule (anterior limb and genu). Stroke, in tuberculous meningitis is predominantly arterial ischemic stroke, and is due to infiltrative, proliferative or necrotizing arteritis. Rarely, aneurysm formation and mycotic aneurysms have also been described. The authors describe the clinical and autopsy findings of a 27-mo-old boy with tuberculous meningitis whose course was complicated by arterial and venous strokes, and nonresponse to adequate and appropriate antitubercular therapy.

Pyogenic Meningitis Complicated with Extensive Central Nervous System Vasculitis and Moyamoya Vasculopathy.

Meningitis is an uncommon complications of head trauma. Vasculitis in bacterial meningitis is seen in 9%-25% of adults. Neurological deficits in bacterial meningitis are seen in about one-third of children. Isolated cranial nerve palsies are common, whereas major deficits such as hemiparesis and quadriparesis are rare. We describe a case of a 7-year-old boy who had post-traumatic meningitis complicated with quadriparesis and severe vasculitis of bilateral anterior and posterior circulation with moyamoya vasculopathy.

Reduced Diabetes Mellitus-related Comorbidities by Regular Self-monitoring of Blood Glucose: Economic and Quality of Life Implications.

OBJECTIVES: The objective of the study was to understand the role of self-monitoring of blood glucose (SMBG) for better management of glycemic fluctuations, reducing the risk of complications, and the associated cost benefits for diabetes patients in India. MATERIALS AND METHODS: An Excel-based Cost Impact Model was developed to analyze the impact of SMBG by calculating the savings over a 10-year time period. A literature review was undertaken to model the impact of SMBG on the risk of complications and cardiovascular morbidities. The model was developed based on inputs from previous studies. RESULTS: In the base case, SMBG cohort was associated with a 10-year discounted cost of INR 718,340, resulting in an estimated saving of INR 120,173 compared to no SMBG cohort. Implementation of a once-daily SMBG protocol, for a decade, can reduce the complication-related costs. More frequent SMBG and tri-monthly hemoglobin A1c tests along with lifestyle changes can significantly reduce the financial burden on the patient over the lifespan. CONCLUSION: Our study has shown that proactive management of diabetes with SMBG can improve treatment outcomes and reduce morbidity and mortality associated with this disease. Near-normal blood glucose levels can bring in cost savings in the form of reduced long-term complications and avoidance of repeated hospitalization for the management of such complications, along with an improved quality of life.

Infantile Tuberculous Meningitis Complicated by West Syndrome.

Tuberculous meningitis rarely causes refractory epilepsy and is a rare cause of West syndrome. We describe three infants, who had tuberculous meningitis complicated by stroke and paradoxical tuberculoma, and, who later developed West syndrome.

Salmonella typhimurium Meningitis in an Infant Presenting with Recurrent Meningitis.

Salmonella typhimurium meningitis in infancy is very uncommon and does not respond to usual duration of empirical antibiotic therapy. A 5-mo-old infant presented with clinical picture of acute pyogenic meningitis and was treated with empirical antibiotic therapy for 14 d. But, 2 wk after the discharge, the child presented again with similar complaints. CSF culture had grown Salmonella typhimurium following which dual antibiotic therapy was given for 6 wk.

Drug reaction with eosinophilia and systemic symptoms in a child on multiple antiepileptics.

Goswami JN, Vaidya PC, Saini AG, De D, Radotra BD, Singhi PD. Drug reaction with eosinophilia and systemic symptoms in a child on multiple antiepileptics. Turk J Pediatr 2017; 59: 197-199. Drug reaction with eosinophilia and systemic symptoms (DRESS) is an adverse drug-reaction that may mimic systemic illnesses and have a fulminant presentation. We describe an 8-year-old girl with epilepsy and exposure to multiple anti-epileptics who presented with fever, extensive maculopapular rash, cervical lymphadenopathy, hepatomegaly, progressive anemia and transaminitis. Infections, autoimmune disorders and hematological or reticuloendothelial malignancies were excluded. Based on the proposed diagnostic criteria, a diagnosis of DRESS was concluded. Her skin biopsy showed atypical findings consistent with erythema multiforme. Suspected anti-epileptic drugs were discontinued. She was administered pulse methyl-prednisolone therapy and broad-spectrum antibiotics along with adequate supportive management. Unfortunately, the child succumbed to nosocomial sepsis. Our case highlights the importance of early suspicion for diagnosis of pediatric DRESS, avoidance of polytherapy and institution of early immunomodulation to improve the outcomes in children in this condition.

An Indian Family with Tyrosine Hydroxylase Deficiency.

BACKGROUND: Tyrosine Hydroxylase deficiency is a rare neurotransmitter disorder. CASE CHARACTERISTICS: An Indian family with the disorder. OBSERVATIONS: Phenotypic variation, elevated serum prolactin, genetic confirmation, and partial treatment-responsiveness. MESSAGE: Tyrosine Hydroxylase deficiency is a treatable inborn error of metabolism and serum prolactin assists in diagnosis.

Multiple Intracranial Aneurysms in HIV Infection.

Neurological findings in HIV are common and include cognitive impairment, microcephaly, nonspecific white matter lesions and seizures. Cerebral vasculopathy and stroke are uncommon and may be due to primary HIV vasculopathy or opportunistic infections such as tuberculosis and cryptococcal meningitis. The authors describe a 7-y-old boy who presented with severe headache and was detected to have aneurysmal bleed due to intracranial aneurysm.

Large Artery Stroke in a Child With Hypoparathyroidism.

The association of hypoparathyroidism and ischemic stroke is rare in childhood. We report an interesting case of an 11-year-old girl diagnosed to have hypoparathyroidism and presented with an acute-onset right hemiparesis. Investigations revealed large artery ischemic stroke and uncontrolled hypoparathyroidism. Pediatricians and pediatric neurologists should be aware of this association in view of its potential preventive nature.