Degradation studies of Ibrutinib under stress conditions: Characterisation and structural elucidation of novel degradants.

The aim of the research work is to study the degradation behaviour of Ibrutinib (IBN) which is performed under different stress conditions according to International Conference on Harmonization guidelines (ICH). The study included monitoring degradation of the Ibrutinib drug under acidic, base, oxidation, thermal and photolytic conditions followed by isolation and characterisation of degradation products (DP) by Liquid Chromatography Mass Spectrometry (LCMS), High resolution Mass Spectrometry (HR-MS/MS) and Nuclear Magnetic Resonance (NMR) studies. The IBN drug is stable under oxidation, thermal and photolytic conditions. The degradation of drug is observed under acidic and basic conditions. Two novel degradation products are formed which are not reported in the literature. The LCMS method has been developed for chromatographic separation of drug and its degradation products which were attained on C18 BEH UPLC column (50 mm X 2.1 mm, 1.7 µm). The combination of 0.05% Acetonitrile in water and 0.05% Formic acid in water are used as a mobile phase. The flow rate is 0.6 ml/min and UV wavelength monitored at 215 nm. Acetonitrile and water are used as diluents.

Association of L-DOPA with recovery following Ayurveda medication in Parkinson's disease.

Ayurveda, the Indian system of traditional medicine, uses a concoction of several spices, herbs and minerals for the treatment of diseases. In a clinical prospective study we have evaluated the efficacy of Ayurveda treatment (a concoction in cow's milk of powdered Mucuna pruriens and Hyoscyamus reticulatus seeds and Withania somnifera and Sida cordifolia roots) in 18 clinically diagnosed (with a mean Hoen and Yahr value of 2.22) parkinsonian patients. As per Ayurveda principles, 13 patients underwent both cleansing (for 28 days) and palliative therapy (56 days), 5 patients underwent palliative therapy alone (84 days). Only the former group showed significant improvement in activities of daily living (ADL) and on motor examination as per UPDRS rating. Symptomatically, they exhibited better response in tremor, bradykinesia, stiffness and cramps as compared to the latter group. Excessive salivation worsened in both the groups. Analyses of powdered samples in milk, as administered in patients, revealed about 200 mg of L-DOPA per dose. The study establishes the necessity of cleansing therapy in Ayurveda medication prior to palliative therapy. It also reveals contribution of L-DOPA in the recovery as observed in Parkinson' disease following Ayurveda medication.

Profile of stroke in Bahrain.

OBJECTIVE: As no report on the pattern of stroke in Bahrain is available, we sought to determine the stroke types, the annual incidence rate, and the risk factors associated with different types of stroke in Bahrain nationals and expatriates in Bahrain. METHODS: Case records of patients admitted with stroke from January 1995 to December 1995 in a tertiary level hospital, the only one with a well established neurology service in Bahrain were reviewed. Diagnosis of stroke and its type were confirmed by clinical and computerized tomography of brain. Risk factor analysis was made based on clinical, laboratory and other relevant investigational data. RESULTS: The majority of strokes occurred in middle and late age Bahrainis. Males predominated in all types of strokes, except in the hemorrhagic type, among the Bahrainis. The crude annual incidence rate was 57 per 100,000 Bahrainis. The frequency of stroke types in Bahrainis was cerebral infarction in 53%, cerebral hemorrhage in 30% and unspecified in 16.5%; as against 76%, 10% and 15% in non Bahrainis. Subarachnoid hemorrhage was rare (2%). Hypertension, dyslipidemia, diabetes mellitus and ischemic heart disease and smoking were common risk factors for ischemic and hemorrhagic strokes. CONCLUSION: Stroke incidence in Bahraini nationals is similar to that in developing countries and from other parts of the Arabian Peninsula. The differences observed in age and gender distribution and in the stroke types between Bahraini nationals and non Bahraini expatriates is most likely a reflection of the demographic structure existing in Bahrain.

Profile of stroke in Bahrain.

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Multimodality evoked potentials in aortoarteritis.

Brainstem auditory evoked potentials (BAEPs) have been used to detect early and even asymptomatic brain ischemia. There is a need to detect subclinical brain and/or spinal cord ischemia in patients with aortoarteritis so that ischemic deficits can be prevented by early intervention. We studied multimodality (Visual evoked potentials--VEPs, Somatosensory evoked potentials--SEPs and BAEPs) evoked potentials (EPs) in 10 neurologically asymptomatic subjects with aortoarteritis. EP latencies were normal in all the patients studied. The possible value of EP latencies in detection of early brain and/or spinal cord ischemia in patients with aortoarteritis is discussed.

Postal follow up of patients with epilepsy.

BACKGROUND: Epilepsy services in India are mostly located in urban areas and are often overcrowded. It is difficult, therefore, to organize long term management programmes. We report our experience at a tertiary referral centre on follow up of patients with epilepsy through regular postal review. METHODS: One hundred consecutive patients with epilepsy (63 men, 37 women, mean age 17 years) who had only seizures were followed up by post using a questionnaire, instead of reviewing them in a clinic. The safety, utility and efficiency of this system were evaluated. RESULTS: Sixty patients had generalized seizures, 30 had complex partial seizures and 10 had other types of seizures. The indication for shifting to postal review was good control of seizures in 87 cases and economic reasons in the remaining. Postal review constituted 60% of the total follow up period in 55 cases. Sixty-six patients could be maintained on postal review which was suspended or discontinued in 34 patients. Of these 34, 16 were returned to it after being seen in the clinic on a further occasion. Poor control of seizures, fresh medical or social problems, lack of confidence or a combination of these were the reasons for discontinuing the postal review. The economic benefit to a patient by way of savings in travel, incidental expenses and lost wages was estimated to be Rs 750 per annum. The work load in the epilepsy clinic was decreased by 40%. No serious medical problems or mortality were reported in the study population. CONCLUSION: Systematic postal review is a cost-effective alternative to clinic review in the long term follow up of a certain group of patients with epilepsy.

Prolonged brainstem auditory evoked potential latencies in tropical pancreatic diabetics with normal hearing.

Twenty patients with Tropical Pancreatic Diabetes (TPD) were evaluated by Brainstem Auditory Evoked Potentials (BAEP) in order to detect any possible subclinical involvement of auditory pathways. The latencies of BAEP Wave III (p < 0.009) and V (p < 0.47) as well as the Interpeak Latencies I-III (p < 0.002), and I-V (p < 0.019) were significantly prolonged in patients with TPD when compared to age and sex matched healthy volunteers. There was correlation between the abnormalities of BAEP and duration of diabetes (p < 0.006), male sex of patients (p < 0.05), and the presence of retinopathy (p < 0.003) and nephropathy (p < 0.38). There was no significant correlation with the age of the patients, type of treatment, blood sugar levels and presence of peripheral neuropathy. These changes suggest a subclinical involvement of the auditory pathways in TDP patients.

Mycotic aneurysms of the intracranial vessels.

The salient clinical and pathological features are reported of Aspergillus cerebral aneurysms in four young women who had undergone intra-abdominal surgery under spinal anaesthesia and developed clinical features of meningitis 7-16 days postoperatively. The circle of Willis showed ruptured aneurysm in the basilar artery and its branches. The role of iatrogenic factors in the pathogenesis of Aspergillus cerebral aneurysms is highlighted.

Necrotizing myelopathy--a report of two cases with review of literature.

Necrotizing myelopathy is an uncommon neurological disorder. Till 1991, only 31 cases have been described in the literature. In this report, clinical and neuropathological features in two patients with necrotizing myelopathy are described. The precise aetiological agent in first patient was undetermined, However in the second patient there was serological evidence, suggestive of Herpes simplex virus infection.

Diagnosis of tuberculous meningitis by enzyme-linked immuno-sorbent assay (ELISA), using an affinity chromatography purified mycobacterial antigen.

Using an immunoabsorbent affinity chromatography, a mycobacterial antigen was isolated from culture filtrate of H37Ra Mycobacterium tuberculosis (MTB). The immunoabsorbents were prepared by coupling cynogen bromide-activated Sepharose-4B with human IgG antibody to MTB. Cerebrospinal fluids (CSF) from 10 culture positive, 30 culture negative patients with tuberculous meningitis (TBM) were assayed, for IgG antibody to this mycobacterial antigen by ELISA. CSFs from 50 patients with non-tuberculous neurological diseases were selected as control group. At a selected 'cut off' titre of 1:80, 21 out of 30 CSFs from culture negative patients gave positive results. No false negative result was observed in CSF from 10 culture positive patients with TBM. No false positive results were recorded in CSFs of 50 patients with non-tuberculous neurological diseases. Technical aspects involved in the isolation of this myobacterial antigen and its potential applications in the laboratory diagnosis of TBM have been emphasised in this study.

Disseminated intra-cerebral microabscesses: a clinico-pathologic study.

In this retrospective study, clinical and neuropathological features were analysed in eight patients with disseminated intracerebral microabscesses. All the patients presented with clinical features, suggestive of an encephalopathic process of an acute onset. Neuroradiological and laboratory investigations were not helpful in establishing the diagnosis in any patient during their hospital stay. All the eight patients died in the hospital and at autopsy disseminated intracerebral microabscesses were the most striking feature. In two patients hyphae of Candida albicans were demonstrated within the microabscesses. Gram negative bacilli in two patients and gram positive and gram positive cocci in one patient were demonstrated in the microabscesses. Disseminated intra-cerebral microabscesses are usually an unrecognised manifestation of central nervous system infections and should be considered in the differential diagnosis of patients with encephalopathy of unknown aetiology.

Visual evoked potential changes in patients with tropical pancreatic diabetes.

Visual impairment is an important complication of diabetes. There are conflicting reports on Visual Evoked Potential (VEP) changes in diabetes. P100 latency of VEP was evaluated in twenty patients with Tropical Pancreatic Diabetes (TPD) and compared with that of age and sex matched controls. There was no statistically significant difference in the P100 latency between the two groups. There was no correlation between the P100 latency and the severity of diabetes or presence of defective vision or retinopathy. The defective vision in diabetes is likely to be due to ocular causes rather than due to a defect in the central visual pathways.

Syringohydromyelia: radiological evaluation of 82 patients in a developing country.

A series of 82 patients presenting with syringohydromyelia and confirmed at operation were studied by conventional radiological techniques and computed tomography (CT). Cord collapse was demonstrated in 71% of the patients with wide bony canals and only 11% of patients with normal bony canals. It was most reliably shown with high resolution CT. Intrathecal CT metrizamide myelography (CTMM) failed to demonstrate contrast percolation into many cavities shown in the plain scans. Obliteration of the subarachnoid space at C1-2 levels appreciated in the plain scans strongly indicated coexisting tonsillar herniation, making CTMM unnecessary. In almost all patients, CTMM was found to be non-contributory if the high resolution plain CT scan failed to reveal cord cavitation.

ELISA of IgG antibody to Mycobacterium tuberculosis antigen-5, PPD in CSF in tuberculous meningitis patients.

IgG antibody to M. tuberculosis antigen-5 and tuberculin purified protein derivative (PPD) was measured by enzyme linked immunosorbent assay (ELISA) in cerebrospinal fluid (CSF) specimens of 55 patients with tuberculous meningitis (TBM) and 55 patients with non-tuberculous neurological diseases (control group). The geometric mean antibody titre in CSF specimens of TBM patients was 82.4 with antigen-5 and 96.5 with PPD. In the control group, the geometric mean antibody titres for these antigens in CSF specimens were 4.6 and 10.8 respectively. The antibody titres did not show any correlation with tuberculin reactor status, duration of chemotherapy and IgG levels in CSF specimens in patients with TBM. At dilution end point 1:80, specificity of the assay was 100 per cent with antigen-5 and sensitivity of the assay was 70.9 per cent. False positivity observed in the control group with PPD antigen could be eliminated in 1:80 dilution in the assay with antigen-5. Antigen-5 is more specific than PPD antigen for the diagnosis of tuberculous meningitis.

Fatal outcome of group-G streptococcal meningitis (a case report).

An adult woman developed meningitis caused by Group-G streptococci. The organism was successfully isolated both from blood and cerebrospinal fluid of the patient. The woman succumbed to infection despite an appropriate antibiotic therapy.

Ambient ammonia effect on catalytic potential of muscle and gill AMP deaminase in fish.

AMP deaminase activity was inhibited in gill and muscle of Sarotherodon mossambicus, subjected to a week-long exposure to sublethal concentration of ambient ammonia. pH-dependent kinetic studies revealed decreased catalytic efficiency of the enzyme due to altered active site density and ionization pattern in the fish tissues at different phases of ammonia exposure.