Ultrasonographic assessment of thyroid volume in Delhi children

BACKGROUND: Ultrasonographic measurement of thyroid volume is increasingly being used to assess prevalence of iodine deficiency in a community. OBJECTIVES: To assess thyroid volume by ultrasonography in normal Delhi children, and compare them with the recently adopted WHO reference standards. METHODS: One hundred and three children aged of 6-10 years were enrolled from the paediatric outpatient clinic in a prospective study. Thyroid volume was estimated by ultrasound, and urinary iodine levels were measured for all subjects by spot urine samples. RESULTS: Goitre prevalence was 24.3% on clinical assessment. Urinary iodine levels fell in the range of mild to moderate deficiency in 61% of the children. None of the children met the WHO recommended ultrasonographic criteria for goitre (thyroid volume >97th percentile of the reference standards), when WHO age-specific norms were used for comparison. On applying body surface area (BSA)-specific norms, only two children were classified as having goitre. CONCLUSIONS: The WHO standards for thyroid volume by ultrasonography tended to underestimate goitre prevalence.     

The ICH guidance in practice: stress decomposition studies on three piperazinyl quinazoline adrenergic receptor-blocking agents and comparison of their degradation behaviour

Stress degradation studies were carried out on three piperazinyl quinazoline alpha(1)-adrenergic receptor blockers, viz. prazosin, terazosin, and doxazosin, following the conditions prescribed in the parent drug stability testing guideline (Q1AR) issued by International Conference on Harmonization (ICH). All drugs showed significant decomposition at 80 degrees C in acidic conditions (0.1 M HCl) and complete degradation in alkaline conditions (0.1 M NaOH). Under both these conditions, 2-piperazinyl-6,7-dimethoxy-4-aminoquinazoline was formed as a major decomposition product in all three drugs. The degradation pattern under ICH-prescribed photolytic conditions in liquid and solid states was also similar for all the drugs. The light exposure resulted in the formation of a cluster of degradation products. No degradation was observed in neutral and oxidative conditions. In solid state, all drugs were stable at 50 degrees C in a 1-month study. In alkaline conditions, the order of sensitivity to degradation of the three drugs was doxazosin>terazosin>prazosin, while the same was terazosin>doxazosin>prazosin under acidic conditions. Mechanistic explanation is provided for the variable behaviour of decomposition.     

Gamma-linolenic acid therapy of human gliomas

OBJECTIVES: We investigated the effect of intratumoral administration of gamma-linolenic acid (GLA) in human gliomas. METHODS: We evaluated the effect of the administration of 1 mg of GLA for 7 d via a cerebral reservoir placed into the tumor bed or by direct intratumoral delivery in nine patients who had grade 4 disease and recurrent glioma after surgery, radiation, or chemotherapy. RESULTS: There was some, but not dramatic, improvement in patients' survival. No significant prolongation of life span was expected considering the advanced nature of the disease. Nevertheless, it was encouraging that GLA produced no significant side effects in any patient. Regression of the cerebral gliomas was visualized on computed tomography and magnetic resonance imaging. CONCLUSIONS: Based on results of the present and previous studies, we believe that GLA is a safe antitumor agent and that higher doses of GLA should be investigated in future studies.     

Neoadjuvant chemotherapy with ifosfamide and cisplatin combination in advanced head and neck cancer: a retrospective analysis of 519 patients: a single institution experience

Advanced head and neck cancer is a major therapeutic problem in India. Ifosfamide has shown significant activity as a single agent in head and neck squamous carcinoma. In this study, we present our experience with two cycles of ifosfamide and cisplatin in the neoadjuvant setting given to a total of 519 patients. The complete response rate was 20% and the overall response rate was 80%. The treatment was well tolerated, there was no need for dose reduction, and there were no life-threatening side effects. We feel that this high response rate is sufficient to warrant more studies using ifosfamide-based combinations in a neoadjuvant setting for squamous carcinoma of the head and neck.     

Selective caudate atrophy in multiple sclerosis: a 3D MRI parcellation study

Deep gray matter damage may be an important component of the multiple sclerosis (MS) disease process. We tested whether caudate atrophy occurs in MS, and whether it correlates with conventional MRI or clinical markers of disease progression. Caudate nuclei of 24 MS patients and 10 age-matched healthy controls were traced, normalized, reconstructed and visualized from MRI scans. Normalized bicaudate volume was 19% lower in MS controls ( p< 0.001), an effect that persisted after adjusting for whole-brain atrophy ( p< 0.008). Caudate volume did not correlate with disease duration, physical disability score, whole-brain atrophy, or total T2 hyperintense or T1 hypointense lesion load (all p > 0.05). We conclude that selective caudate atrophy is associated with MS and may occur through direct mechanisms.     

The ICH guidance in practice: stress degradation studies on ornidazole and development of a validated stability-indicating assay

The present study describes degradation of ornidazole under different ICH prescribed stress conditions (hydrolysis, oxidation and photolysis), and establishment of a stability-indicating reversed-phase HPLC assay. Degradation was found to occur in alkaline medium, under high acidic conditions, under oxidative stress, and also in the presence of light in acid conditions. Previously the drug is only known to decompose under alkaline conditions. Separation of drug and the degradation products under various conditions was successfully achieved on a C-18 column utilising water-acetonitrile in the ratio of 86:14. The detection wavelength was 310 nm. The method was validated with respect to linearity, precision, accuracy, selectivity, specificity and ruggedness. The response was linear in the drug concentration range of 5–500 μg ml⁻¹. The mean values (±RSD) of slope, intercept and correlation coefficient were 45251 (±1.59), 104418 (±2.49) and 0.9996 (±0.03), respectively. The RSD values for intra- and inter-day precision studies were <1 and <2.6%, respectively. The recovery of the drug ranged between 100–103% from a mixture of degradation products. The method was specific to drug and also selective to degradation products.     

Identification of bacterial genes required for in-vivo survival.

Genetic approaches used for in-vivo studies of bacterial pathogenesis are providing insights into how bacteria disrupt host defences and exploit host molecules for their own advantage. Signature tagged mutagenesis (STM) provides a means of identifying the genes involved in the process of infection, particularly those genes that are important for bacterial proliferation in-vivo. In this review, the application of STM to the understanding of bacterial pathogenesis and findings from work on three human pathogens, Salmonella typhimurium, Mycobacterium tuberculosis and Neisseria meningitidis, are discussed. The next challenge is to understand how these and other genes influence the infective process at the molecular and cellular levels and to design novel interventions to block the progression of disease.