Do geriatrics require dose titration for antidiabetic agents?

OBJECTIVE: To evaluate the antidiabetic drug dosage differences between geriatric and nongeriatric diabetics with reference to duration of disease and creatinine clearance (Crcl). MATERIALS AND METHODS: Prospective study conducted for 6 months in a tertiary care hospital. Patients with type 2 diabetes mellitus were grouped into geriatric (age ≥60 years) and nongeriatric (age <60 years). Patients' demographic data, duration of diabetes, medication, and serum creatinine were recorded. Crcl was calculated using Cockcroft-Gault formula. Doses of sulfonylureas (SU) were converted into equivalent doses, taking glibenclamide as standard. Univariate analysis was done for comparison of drug doses between groups. RESULT: A total of 320 geriatric and 157 nongeriatric diabetics completed the study. The duration of diabetes and Crcl adjusted dose reduction of glibenclamide (mean dose: Geriatrics 7.2±0.4 mg, nongeriatrics 9.6±0.7 mg; P=0.01) and gliclazide (mean dose: Geriatrics 85.5±11.5 mg, nongeriatrics 115.3±32.7 mg; P=0.42) was 25%, glimepiride (mean dose: Geriatrics 1.62±0.13 mg, nongeriatrics 2.1±0.18 mg; P=0.06) was 22%. Glipizide did not require dose reduction. Mean converted equivalent dose of sulfonylurea monotherapy was significantly lower in geriatrics than nongeriatrics (3.2±0.5 vs 6.4±1.02 mg; P=0.01) and showed 50% dose reduction. Mean dose of metformin was lower in geriatrics (901±32.2 mg vs 946.7±45.8 mg; P=0.45) and showed 5% reduction in dosage. There was no difference in the mean drug doses of thiazolidinediones and insulin between the groups. CONCLUSION: A substantial dose reduction of glibenclamide (25%), gliclazide (25%), glimepiride (22%), and metformin (5%) in geriatrics compared to nongeriatrics was observed. Smaller dosage formulations like 0.75 mg glibenclamide, 0.5 mg glimepiride, 20 mg gliclazide, and 250 mg metformin may be of value in geriatric diabetic practice.

Co-administration of haloperidol and drugs affecting the angiotensin pathway: effect on the extrapyramidal system.

The present study investigates the extrapyramidal effects of co-administration of enalapril (angiotensin-converting enzyme inhibitor) or losartan (angiotensin receptor blocker) with haloperidol in mice. Enalapril/losartan (as a suspension in 1% gum acacia) was administered by oral gavage and haloperidol was administered as an intraperitoneal injection to all the animals for seven days. Catalepsy was measured 30 min after the administration of haloperidol (1 mg/kg i.p.) on days 1 and 7. Observations on day 1 constituted the acute study (single dose administration) and observations on day 7, constituted the chronic study (repeated dose administration). Both acute and chronic administration of enalapril/losartan produced an increase in the duration of haloperidol induced catalepsy at the highest dose (20 mg/kg). Enalapril produced a more pronounced increase in the duration of catalepsy as compared to losartan on both acute and chronic administration. Results of our study suggest that co-administration of anti-psychotics and drugs affecting the angiotensin system can lead to an increase in motor side effects and therefore should be used with caution in patients with these co-morbid conditions.

Prevalence of metabolic syndrome (METS) using IDF 2005 guidelines in a semi urban south Indian (Boloor Diabetes Study) population of Mangalore.

OBJECTIVE: To identify metabolic syndrome (MetS) prevalence using International Diabetes Federation (IDF) 2005 guidelines in a semi urban south Indian (Boloor Diabetes Study) population of Mangalore. METHODS: Population of randomly selected adults > or =20 years living in Boloor locality who were available for the house to house survey were assessed for the following: anthropometric variables; blood pressure; fasting blood glucose and lipid profile. Among 800 responders; 300 men, 500 women, 551 were examined (68.8%). Fasting plasma glucose as well fasting lipid profile could be done for 451 (147 men, 304 women) 81.85%; Data was analysed for prevalence of MetS and its individual components. Diagnosis of MetS was based on IDF 2005 criteria for Asian men and women. Intergroup comparisons were performed using student 't' test and Chi-square test. RESULTS: MetS was prevalent in 134 of 451 (29.7%); men 39 (26.5%) and women 95 (31.2%). Prevalence of individual components of MetS were as follows: increased waist circumference, (common component) present in all; elevated TG in 38.8%; low HDL-C in 59.7%; increased FPG in 57.4%; elevated SBP in 80.5% and DBP in 56.7%; body mass index (BMI) > or =25 kg/sq.m (obesity) in 58.9% Barring increased waist circumference which is the essential criteria for diagnosis of Mets, Systolic hypertension emerged as the most frequent component in the population followed by low HDL-C and elevated FPG. Elevated TG was less prevalent in this population. CONCLUSION: Prevalence of MetS in this semi urban population (Boloor) of Mangalore compares with MetS prevalence identified in cross sectional studies in India. Prevention and treatment of the predictive factors: dyslipidemias, hyperglycaemia, hypertension, together with enhanced physical activity may together reduce the prevalence of MetS.

Metabolic syndrome among inmates of a 'home for aged' using IDF 2005 criteria.

To identify the metabolic syndrome (MetS) among inmates of a 'home for aged' using IDF 2005 criteria. 100 subjects from inmates of a 'home for aged' studied for the identification of metabolic syndrome using International Diabetes Federation (IDF) 2005 criteria. Presence of waist circumference (WC) (Men > or =90 cm, Women > or =80 cm) plus any two of the following four factors; triglycerides (TG) >150 mg/dl (1.7 mmol/l), (II) HDL-Cholesterol (HDL-C) <40 mg/dl (1.0 mmol/l) for men, <50 mg/dl (1.3 mmol/l) for women, fasting plasma glucose (FPG) > or =100 mg/dl (6.1 mmol/l) and blood pressure (BP) > or = 130/85 mm of Hg. Indicated the MetS. MetS was present in 57.0%. WC was common component, TG was increased in 71.9%, low HDL-C present in 86.0%, raised FPG present in 66.7% and hypertension in 45.6%. MetS was more common in older women than in men (63.6% vs. 48.8%) and decreased HDL-C is core components of the MetS in this population. High calorie diet and sedentary life style may be contributing factors of MetS in this population. MetS is common in elderly subjects. It is age-related, and is more common in elderly women.

Serum bicarbonate: can it be a marker of metformin induced acidosis in geriatrics?

Metformin is an oral antidiabetic agent, widely used in the treatment of type 2 diabetes mellitus. The serious side effect of metformin therapy is lactic acidosis. Contraindications for metformin therapy include renal insufficiency. A cut off value of 60 ml/min in creatinine clearance is suggested. Hundred type 2 diabetics receiving metformin as monotherapy or in combination with insulin/other oral antidiabetic agents, were enrolled in the study. Patients were on metformin for atleast one month prior to being enrolled. Patients' demographic data were taken. Baseline serum creatinine and bicarbonate were estimated. Creatinine clearance (Clcr ml/ min) was calculated. Patients were grouped into group 1-4 depending upon the doses of metformin they received. Patients were again grouped based on their Clcr as groupA (Clcr < 60 ml/min), group B (Clcr > 60.01 ml/min). Data was analysed using student's t test. Out of 100 patients 52 were males, 48 females. Mean age and SD of males and females were 69.92 +/- 6.95 and 66.85 +/- 5.72 respectively. Comparison of mean bicarbonate level in different doses of metformin did not show any statistical significance. But comparison of bicarbonate levels based on Clcr were highly statistically significant (p = 0.0084). In three patients whose bicarbonate level was very low (15, 16.4 and 19.2 mmol/L), doses of metformin was reduced and after one month their bicarbonate levels returned to normal (27.4, 25.6 and 26.2 mmol/L). Hence serum bicarbonate can be a marker to assess metformin induced acidosis in geriatrics patients with low creatinine clearance.

Safety and radiosensitizing efficacy of sanazole (AK 2123) in oropharyngeal cancers: randomized controlled double blind clinical trial.

UNLABELLED: Oropharynx is an important site of cancer in India. Global comparison indicates higher incidences in India. Radiotherapy remains an important treatment modality. Efforts to improve loco-regional treatment and prolong survival are areas of focus. Radiosensitizers in hypoxic tumors have shown promise. AIM: To study the safety and radiosensitizing efficacy of sanazole in oropharyngeal squamous cell carcinoma (stage T2-4, N0-3, M0) as phase-II double blind controlled trial in patients treated with conventional radiotherapy. SETTINGS AND DESIGN: Single institutional, randomized, double-blind, placebo-controlled trial. MATERIALS AND METHODS: Group 1 (control; n = 23) received normal saline infusion, group 2 (test; n = 23) received sanazole biweekly 1.25 g intravenous infusion 15 minutes before radiotherapy. Surrogate end points of efficacy were tumor and nodal size; safety parameters were mucositis, salivary and skin reactions, dysphagia, vomiting, dysgeusia and neurological deficit. Investigators blinded to the trial evaluated patients, weekly during treatment for six weeks and thereafter monthly for three months. STATISTICAL METHODS: Non-parametric, Friedman's, Chi square, Mann-Whitney U tests. RESULTS: In the test, 15 (65%) patients had complete response, five (22%) partial/no response, two (9%) died, one (4%) lost to follow up. In the control, five (22%) patients had complete response, 16 (70%) partial/no response, one (4%) died, one (4%) lost to follow up. Short-term loco-regional response was better in the test (DF = 3, 95% Confidence Interval 0.418, 0.452, P = 0.0048). In the test group significant vomiting and one case of grade 3 neurological deficit was observed. CONCLUSION: The study validates the usefulness of sanazole for initial loco-regional control in oropharyngeal cancers.

Preclinical evaluation of the antidiabetic effect of Eugenia jambolana seed powder in streptozotocin-diabetic rats.

The world is facing an explosive increase in the incidence of diabetes mellitus and cost-effective complementary therapies are needed. The effects of Eugenia jambolana, a household remedy for diabetes, were studied. Streptozotocin diabetic female albino Wistar rats weighing 150-200 g (N = 6) were fed E. jambolana seed powder (250, 500 or 1000 mg/kg) for 15 days. Diabetic rats fed 500 and 1000 mg/kg seed powder showed an increase in body weight on day 20 in relation to day 5 (6 +/- 4.7, 9 +/- 7.8 vs diabetic control -16 +/- 7.1 g, P < 0.001), a decrease in fasting blood glucose (75 +/- 11.9, 123 +/- 14.4 vs diabetic control -34 +/- 12.1 mg/dl, P < 0.001), a difference in post-treatment fasting and peak blood glucose (38 +/- 11.9, 36 +/- 14.2 vs diabetic control 78 +/- 11.9 mg/dl, P < 0.001), and a difference in liver glycogen (50 +/- 6.8, 52 +/- 7.5 vs normal control 90 +/- 6.6 microg/g of liver tissue, P < 0.001). Tri-terpenoids, tannins, gallic acid, and oxalic acid were the chemical constituents detected in E. jambolana seed. The best results were obtained with an oral dose of 500 mg/kg. Subacute toxicity studies with a single administration of 2.5 and 5.0 g/kg seed powder showed no mortality or abnormality. These data on the antidiabetic effect of E. jambolana seed are adequate for approval of phase 2 clinical trials to evaluate this seed powder as complementary therapy in type 2 and type 1 diabetes.

Preclinical evaluation of the antidiabetic effect of Eugenia jambolana seed powder in streptozotocin-diabetic rats

The world is facing an explosive increase in the incidence of diabetes mellitus and cost-effective complementary therapies are needed. The effects of Eugenia jambolana, a household remedy for diabetes, were studied. Streptozotocin diabetic female albino Wistar rats weighing 150-200 g (N = 6) were fed E. jambolana seed powder (250, 500 or 1000 mg/kg) for 15 days. Diabetic rats fed 500 and 1000 mg/kg seed powder showed an increase in body weight on day 20 in relation to day 5 (6 ± 4.7, 9 ± 7.8 vs diabetic control -16 ± 7.1 g, P < 0.001), a decrease in fasting blood glucose (75 ± 11.9, 123 ± 14.4 vs diabetic control -34 ± 12.1 mg/dl, P < 0.001), a difference in post-treatment fasting and peak blood glucose (38 ± 11.9, 36 ± 14.2 vs diabetic control 78 ± 11.9 mg/dl, P < 0.001), and a difference in liver glycogen (50 ± 6.8, 52 ± 7.5 vs normal control 90 ± 6.6 æg/g of liver tissue, P < 0.001). Tri-terpenoids, tannins, gallic acid, and oxalic acid were the chemical constituents detected in E. jambolana seed. The best results were obtained with an oral dose of 500 mg/kg. Subacute toxicity studies with a single administration of 2.5 and 5.0 g/kg seed powder showed no mortality or abnormality. These data on the antidiabetic effect of E. jambolana seed are adequate for approval of phase 2 clinical trials to evaluate this seed powder as complementary therapy in type 2 and type 1 diabetes.

The effect of two different dental gels and a mouthwash on plaque and gingival scores: a six-week clinical study.

AIM: To evaluate the clinical efficacy of two gel formulations containing chlorhexidine gluconate and neem extract with a commercially available chlorhexidine gluconate mouthwash. METHOD: An open labelled randomised six-week clinical study with parallel group design in 48 subjects divided into four groups. Plaque accumulation and gingival condition were recorded using plaque index and gingival index. On the basis of mean baseline plaque and gingival scores, subjects were allocated to four different groups, using their assigned products twice a day, before bed and after breakfast. Plaque and gingival scores were recorded after three and six weeks. RESULTS: Mean plaque and gingival scores were reduced over the six-week trial period for experimental and control groups. Chlorhexidine gluconate gel reduced the plaque and gingival scores significantly more (p<0.05) than the chlorhexidine gluconate mouthwash. Neem extract gel also showed significant (p<0,05) reduction in plaque and gingival scores when compared with the control group. But there was no significant difference between the groups treated with chlorhexidine gel and neem extract gel. CONCLUSION: The results of this clinical study indicate that better therapeutic efficacy can be achieved using gels for treating oral infections than conventional treatments using mouthwash.

Comparative evaluation of efficacy and safety profile of three anti-tuberculous regimens in Mangalore.

The aim of our study was to evaluate and compare the therapeutic efficacy & safety profile of three different antituberculous regimens for pulmonary tuberculosis. The study sample size included 90 newly diagnosed, sputum positive patients of pulmonary. tuberculosis. 30 each from different groups. The parameters studied were, therapeutic efficacy included weight gain, cough, sputum examination and safety profile: nausea, vomiting, anorexia, gastritis, hepatitis, jaundice diarrhoea, rashes, dizziness, tingling & numbness, flu like symptoms & joint aches. Group-I showed statistically significant weight gain when compared to Group-II. Improvement in cough and conversion to smear negative were seen in 100% of patients in Group-I, 83.3% of patients in Group-II and 93.3% of patients in Group-III. Therapeutic efficacy was highest with Group I regimen, followed by Group III and Group II which was least efficacious. Group II also registered; the maximum cost and highest incidence of adverse effects.

Fine Needle Aspiration cytology versus Fine Needle Sampling without aspiration. A prospective study of 200 cases.

In the present prospective study of 200 patients with superficial swelling of various sites, FNS followed by FNA were performed. Fifteen cases were excluded due to inadequate material. In the 80 lymph node cases, FNS was diagnostic in 85% cases as compared to FNA in 87.5%. The diagnostic accuracy was higher for FNA (87.5%) than for FNS (81.25%). However FNS smears were much superior qualitatively than FNA smears and for the diagnosis of malignant conditions FNS was found to be much better. Regarding the 68 thyroid swellings, FNS obtained a diagnosis in 82.4% cases while FNA got it in 77.9%. The diagnostic accuracy with FNS (89%) was much better compared to FNA (75%). Of the 27 breast cases FNS yielded diagnostic material in 70.38% cases while FNA was diagnostic in 85.19%, thus establishing definite superiority. However FNS seemed to be better for diagnosing malignant lesions while FNA appeared better for diagnosing benign ones. In the 5 salivary gland lesions and 5 miscellaneous lesions both FNS and FNA fared equally well. On the whole FNS technique was much more patient friendly and gave high class "text book" quality smears while FNA smears gave quantitatively more adequate material. Both the techniques therefore would be complementary to each other.

Topical phenytoin in diabetic ulcers: a double blind controlled trial.

Data of 57 patients who completed the trial and 13 who did not, were analysed. With phenytoin, there was a marginal: increase in the reduction of mean ulcer area and acceleration of effect 3rd on 4th week. With control: the number completing the trial was larger: response to treatment was better in grade II ulcers, Table IV. This study has the hall marks of a real clinical trial, has raised the possibility of wound healing properties of phenytoin and confirms the results of others.

Coronary atherosclerosis in Mangalore--a random post mortem study.

A study was undertaken in Mangalore, South Kanara District of Karnataka, India to evaluate the rising prevalence of coronary artery diseases in our country. Seventy hearts were analysed, at post-mortem, between December 1996 and December 1997. The coronary arteries and the myocardium were examined, both grossly and histologically, to relate them with regard to the age and gender of the deceased. Fifty five hearts were from males and 15 were from females. Forty eight (68.59%) hearts were proven to be afflicted with coronary atherosclerosis. Twenty seven of these had three or four vessel disease. A total of 192 sections from the four major epicardial arteries of the 48 hearts were examined. Of these, 124 showed atherosclerosis (with 37 in advanced stages), of which 103 were occlusive lesions while the remaining 21 were fatty streaks. Severe stenosis (grade III or IV) was commonest in the left anterior descending artery. Twenty one (30%) of the 70 hearts showed histological evidence of myocardial ischaemia. Of these 6 were from females and 15 were males. Myocardial ischaemia was found to have no correlation to the severity of stenosis.

FNAC diagnosis of mucinous carcinoma of male breast--a case report.

Mucinous carcinoma of the male breast is a very rare tumour. So far only about 8 cases have been reported in the literature most of which were diagnosed after surgical resection. Fine-needles aspiration biopsy even though a well established procedure for the evaluation of breast masses in female there are only occasional reports of aspirates form male breast masses. We herein-present one case of mucinous carcinoma of breast in a 65 year old male diagnosed by fine needle and confirmed by histopathology.

Fine needle aspiration cytology in systemic lupus erythematosus lymphadenopathy. A case report.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology characterized by inflammation in various organ systems, including lymph nodes, due to the production of antinuclear antibodies. The onset of disease is between ages 13 and 40 years, with a female preponderance. CASE: A 30-year-old female presented with right cervical lymphadenopathy and gave a history of intermittent fever and swollen joints of 2.5 years' duration. The patient was on intermittent corticosteroids. With a suggestion of tuberculous lymphadenitis, the patient underwent fine needle aspiration (FNA). The diagnosis of lupus adenopathy was established by FNA of enlarged right cervical lymph nodes. Smears showed predominantly typical and atypical immunoblasts, plasma cells, occasional Reed-Sternberg-like cells and dispersed hematoxylin bodies. Smears were negative for acid-fast bacilli. CONCLUSION: When SLE patients develop lymphadenopathy, FNA cytology helps differentiate lupus adenopathy from infectious conditions, such as tuberculous adenitis, and from Kikuchi's lymphadenitis.

Neurogenic appendicopathy--role of enterochromaffin cells in its pathogenesis.

One hundred cases of neurogenic appendicopathy were histochemically studied for schwann cells and enterochromaffin cells. The early phase, labelled as neuro-appendicopathy (29 cases) showed minimum to moderate number of extraepithelial enterochromaffin cells without neurogenous hyperplasia. In 53 cases, there was intra and submucosal neural hyperplasia with increase in the extraepithelial enterochromaffin cells, representing the active phase. The late phase known as obliterative neurogenic appendicopathy, showed extraepithelial enterochromaffin cells and schwann cell proliferation of variable grades (18 cases). The origin of extraepithelial enterochromaffin cells is related to proliferating nerve plexus, rather than epithelial enterochromaffin cells.

Connective tissue stromal changes in tumours and tumour-like lesions of the breast.

Between June 1994 and December 1995, one hundred and fifteen tumours and tumour-like lesions of the breast were studied in the Department of Pathology, Kasturba Medical College, Mangalore. Neoplasms constituted 80.9% and tumour like lesions accounted for 19.13%. Among the tumours, 51.6% were benign and 48.4% were malignant. Tumour-like lesions included the entire spectrum of fibrocystic disease. Tumours were common between 2nd and 8th decades while tumour-like lesions were uncommon above 6th decade. Whereas benign tumours exhibited ground substance, collagen and reticulin fibres in varying amounts, tumour-like lesions and carcinoma showed more of collagen fibres and less of ground substance. Elastosis and lymphoplasmacytic infiltrate were prominent features in carcinomas rather than in benign lesions.

Paneth cell metaplasia in colonic adenocarcinoms.

The junctional mucosa of 49 colorectal carcinomas were studied for Paneth cell metaplasia. Twenty two cases (44.89%) showed Paneth cells in the junctional mucosa. The carcinomas were seen mainly in the age range of 51 to 60 years (38.4%) The occurrence of Paneth cell metaplasia was higher in the vicinity of tumours of ascending colon and in well differentiated grades of adenocarcinomas. This probably indicates the reactive host response in the junctional mucosa which is of better prognostic significance.