Enhancement of dissolution rate of rapidly dissolving oral film of meclizine hydrochloride by complexation of Meclizine hydrochloride with ß-cyclodextrine.

Motion sickness is a very common disturbance of the inner ear that is caused by repeated motion such as from the swell of the sea, the movement of a car, the motion of a plane in turbulent air, etc. Most medications for motion sickness need to be taken at least 30 minutes prior exposure to the activity that can cause the problem. This project is based on the hypothesis that Mouth Dissolving Films (MDF) are rapidly dissolving dosage forms which when placed in the mouth release the drug immediately. These dosage forms would be preferred by pediatric and geriatric patients since these are not associated with fear of choking. The fast dissolving films prepared by solvent casting method with suitable appearance, mechanical strength, peelability and disintegration time were obtained using Methocel E-5 as a primary film former. Meclizine HCl, a poorly water soluble and bitter drug could be successfully incorporated in the fast dissolving films with the help of solubilizers such as β-Cyclodextrine and PEG-400.

Stent thrombosis.

Technology of drug-eluting stent (DES) implantation is relatively young. DES have remarkably reduced the incidence of stent-restenosis (SRS) and the need for target vessel revascularization (TVR). Yet it has added a small but significant risk of late and very late stent thrombosis (ST). The incidence of ST varies between 0.3-2.8% with a mean of 1.3%. ST occurs both with bare-metal stents (BMS) and drug-eluting stents (DES) but the time course differs with an excess of ST in the first six months of implantation with BMS while the number of ST is more with DES after 6 months of implantation. Despite this difference, there are no overall differences between BMS and DES regarding the end points of death or myocardial infarction (MI) on long term (3-5 years) follow-up. Endothelial dysfunction and incomplete neointimal coverage of stent strut remain the basic underlying mechanisms responsible for ST in DES. Stent thrombosis, though infrequent, is a dreadful condition. Over 30% may die suddenly. 60% develop massive MI with cardiogenic shock, poor LVEF and serious arrhythmias. The beneficial effects of primary percutaneous intervention (PCI) for ST are not spectacular, and TIMI flow grade III, is achieved in less than 80% cases, while distal embolization and residual dissection of coronary artery are frequently encountered. Proper selection and optimization of stent with prolonged dual antiplatelet therapy may prevent the undesirable stent thrombosis after DES implantation.

Heparin induced thrombocytopenia.

Heparin induced thrombocytopenia (HIT) is a serious and life endangering complication of heparin therapy. It usually occurs after 5-14 days of continuous heparin therapy. It is immune mediated. Heparin, in the affected individual binds with platelet factor 4 (PF-4) and forms a highly antigenic Heparin PF-4 complex which leads to the generation of specific IgG Heparin PF4 antibodies (also called HIT antibodies). HIT antibodies may activate the platelets via Fcy receptor causing the release of highly coagulable micro particles which promote thrombosis--both venous and arterial. However, all patients with HIT antibodies do not progress to HIT with thrombosis (HITT). HIT can present as asymptomatic thrombocytopenia. It can also present with alarming features of venous and/or arterial thromboembolism, for example, pulmonary embolism from deep vein thrombosis (DVT), limb gangrene warranting amputation, cerebrovascular attack (CVA) or myocardial infarction (MI). Rare manifestation of HIT includes necrotizing skin lesion, acute anaphylactoid reaction following IV heparin bolus and acute adrenal apoplexy due to massive adrenal vein thrombosis. The diagnosis is based upon the combination of unexplained thrombocytopenia, demonstration of HIT antibodies, clinical profile and outcome of the case following withdrawal of heparin and administration of non-heparin anticoagulant like Lepirudin, Argatroban or Danaparoid. The choice of alternative anticoagulant depends upon the availability, cost, monitoring facilities and administrative guidelines.

Pleiotropic morphological and abiotic stress resistance phenotypes of the hyper-abscisic acid producing Abo- mutant in the periwinkle Catharanthus roseus.

The pleiotropic properties of a abo abo (Abo-) gamma-ray induced mutant of Catharanthus roseus cv. Nirmal, selected among the M2 generation seeds for ability to germinate at 45 degrees C, are described. The mutant produced seeds possessing tricotyledonous embryos, unlike the typically dicotyledonous embryos present in the wild type Abo+ seeds. In comparison to Abo+ adults, the mutant plants had short stature and lanceolate leaves. The vascular bundles in the leaves and stem were poorly developed. Leaf surfaces were highly trichomatous, epidermal, cortex and mesophyll cells were small sized and a large majority of stomata were closed. Besides high temperature, the mutant was salinity and water-stress tolerant. The abscisic acid (ABA) content in the leaves was about 500-fold higher. The genetic lesion abo responsible for the above pleiotropy was recessive and inherited in Mendelian fashion. The seedlings and adult plants of the mutant accumulated higher proline than Abo+ plants. The phenotypes of abo abo mutants permitted the conclusions that (i) the mutant synthesizes ABA constitutively, (ii) both ABA-dependent and ABA independent pathways for proline and betaine accumulation are functional in the mutant, and (iii) cell division, elongation and differentiation processes in embryo and adult plant stages are affected in the mutant

Calcium imbalance in hypoparathyroidism.

Extracellular fluid calcium is a tightly controlled variable. Hypoparathyroid state may result in profound calcium imbalance and moderate to severe hypocalcaemia. During 1974-89, 108 cases of hypoparathyroidism (97 post-surgical and 11 idiopathic) were seen. In the post-thyroidectomy group, 83 cases (85%) presented with acute transient hypocalcaemia with spontaneous recovery within 7-10 days. Chronic hypoparathyroidism was seen in 25 cases (14 post-surgical and 11 idiopathic). Convulsions resembling epileptic fits were seen in 9 cases (36%). Pseudopapilloedema was seen in three cases presenting with fits. The administration of phenobarbitone and dilantin aggravated convulsions in 9 patients. The other manifestations were psychiatric illness, cataract and calcification of basal ganglion. Biochemical findings included persistent hypocalcaemia with normal or raised serum phosphorus and lowered daily urinary excretion of calcium. Twenty three of 25 chronic hypoparathyroid cases were treated with vitamin D3 (1-3 mg/day) and calcium supplements (600-1000 mg/day)while 1 alfa-calcidol or calcitriol was used in two patients. Four patients receiving treatment with vitamin D3 developed transient hypercalcaemia with raised plasma levels of 25 hydroxy-vitamin D3. They responded to a reduction in dosage of vitamin D3. One patient was later changed over to 1-alfa-calcidol and another to calcitriol.

Human leucocyte antigen and insulin dependent diabetes mellitus.

HLA typing was done in 25 cases of insulin dependent diabetes mellitus (IDDM) and compared with 60 healthy controls. There was a significantly increased frequency of HLA B-8, HLA B-12 and HLA DR-3 in IDDMO. The odds ratio (relative risk) of developing IDDM for HLA B-8 was 4.42 (p less than 0.10), for HLA B-12 was 3.56 (p less than 0.10) and for HLA DR3 9.75 (p less than 0.001). There was no correlation of HLA specificity with complications of diabetes.

Relative merits of various rapid biopsy urease tests for diagnosis of Helicobacter pylori (Campylobacter pylori).

Three rapid urease tests, i.e., liquid urea broth containing phenol red as indicator, liquid urea broth containing bromothymol blue as indicator and CLO gel were compared in 109 patients of dyspepsia for the diagnosis of Campylobacter pylori (Helicobacter pylori) infection. Mean time taken for positive reaction in liquid broth with phenol was 3 minutes (range 0.6 to 5.3 minutes) with bromothymol blue was 3.5 minutes (range 0.4 to 5.5 minutes) while with CLO gel it was 101 minutes (range 11-261 minutes). There was no difference in results of liquid urea broth containing phenol red and bromothymol blue. The difference in timing of urea broth containing phenol red and bromothymol blue was statistically significant as compared to CLO gel (p less than 0.05). Rapid urease tests employing liquid urea broth are quick, simple and reliable for the diagnosis of Helicobacer pylori infection.

Detection of mutagenicity in cervico-vaginal secretions--a plausible risk factor for cervical cancer.

The cervico-vaginal secretions from 51 women with various grades of dysplastic lesions of uterine cervix were assessed for mutagenic potential by Ames test using histidine deficient mutant strain of Salmonella typhimurium TA-98: with S-9 mix. Twenty three per cent of samples from women with cervical dysplasia were found significantly positive (P less than 0.001) for mutagenic activity compared to 3% positive from control. The frequency of mutagenic secretions detected were almost uniform, irrespective of the severity of cervical lesions. None of cervico-vaginal secretions, positive for mutagenicity could revert the tester strain when tested in absence of S-9 mix (liver microsomal enzymes). This indicates that mutagens in cervico-vaginal secretions are effective only when activated enzymatically.

A clinical study of adult leukaemias.

The incidence of adult leukaemias, their response to therapy and the complications of therapy were studied in 121 cases over seven years (1981-1987). All cases were followed up till recovery or death for periods ranging from seven days to seven years. Adult leukaemias accounted for 2.56% of all admissions due to malignancies. There were 21 cases of acute lymphoblastic leukaemia, 61 of acute myelogenous leukaemia, 36 of chronic myelocytic leukaemia and 3 chronic lymphocytic leukaemia. All received aggressive combination chemotherapy. Remission could be achieved in 57% to 60% of cases. Infection (34%), bleeding (34%), and central nervous system involvement (25%) were the complications during therapy. The cause of death was ascertained in 87 of 90 deaths by a detailed postmortem. Haemorrhage (34.5%), infection (31%) and uncontrolled leukaemia (22%) were the leading causes, either singly or in combination. Some of the uncommon causes of death were fulminant hepatic failure, coronary artery disease, gangrene of the colon and disseminated tuberculosis.

Systemic manifestations of systemic lupus erythematosus.

Twenty five cases with systemic lupus erythematosus admitted to a referral service hospital over a period of 6 years have been studied to analyse the pattern of multisystem involvement. Febrile polyarthritis, renal involvement and skin changes dominated the clinical picture. Important serological abnormalities included the presence of antinuclear antibody and anti ds DNA. Renal biopsy carried out in all cases helped to reveal lupus nephritis in subclinical cases. The pattern of renal involvement varied, with diffuse proliferative glomerulonephritis being the commonest. Oral steroids was given to all cases and cyclophosphamide was given to severe and resistant cases. The severity of system involvement, especially renal, influenced the response to treatment. Changes in presentation between Indian and Western patients are highlighted.

Primary hyperparathyroidism.

11 cases of primary hyperparathyroidism were seen during 1975-1988. Follow up has varied from 1-10 years. Renal disease in the form of renal calculi and nephro-calcinosis was observed in nine cases (81.8%). Two presented in chronic renal failure and required dialysis. Bone disease was found radiologically in six patients (54.5%); two had bone cysts in multiple bones while all six had subperiosteal bone erosion. Hypertension was found in three patients (27.3%). Proximal myopathy was observed in two cases (18.1%). One patient each presented with hypercalcaemic crisis, chondrocalcinosis and acute pancreatitis. The calcification of blood vessels and cornea was seen in two cases.

Medical emergencies associated with disorders of calcium homeostasis.

Medical emergencies due to severe hypercalcaemia and hypocalcaemia are relatively rare in clinical practice. 89 cases of hypercalcaemia were seen during 1975-1987 and 16 presented as medical emergencies; renal colic (7) acute renal failure (3), spontaneous fractures (3), acute pancreatitis (1), cardiac arrhythmia (1) and acute hypercalcaemic crisis resulting in death (1). 81 cases of severe hypocalcaemia were seen during the same period. 22 presented initially as epileptic seizures with one ending fatally due to status epilepticus. The other emergencies were severe laryngeal stridor and inability to speak (7), papilloedema (3) and acute behavioural disorder (4). A few illustrative cases have been briefly described.