Can anti-Helicobacter pylori and anti-CagA antibodies be used to select patients with dyspepsia for gastroscopy?

BACKGROUND: agA IgG antibody in sera may indicate presence of peptic ulcer disease among dyspeptic patients and therefore may be used as a serological marker to identify high risk patients for peptic ulcer who can be subjected to endoscopy. Present study was performed to identify association of CagA IgG antibody in patients with peptic ulcer. METHODS: Consecutive patients with dyspepsia were subjected to endoscopy and sera was collected from each. Rapid urease test in antral tissue collected from each patient by endoscopic biopsy was performed. Antral tissue was also examined histologically. IgG Antibody against H. Pylori and CagA IgG antibody was tested in each patients sera. RESULTS: Out of 82 patients with dyspepsia included in the study 28 had peptic ulcer. Of whom 26 were positive for anti IgG H. Pylori antibody. More than 80% patients with peptic ulcer patients had detectable anti Cag A antibody in contrast to 33% patients with non ulcer dyspepsia (P < 0.001). CONCLUSION: Anti-Cag A antibody may be used as a screening test in patients with dyspepsia to select high risk patients for peptic ulcer for upper gastrointestinal endoscopy.

Celiac disease in osteoporotic Indians.

OBJECTIVE: 1) The aim of the study was to identify the atypical celiac disease (CD) in a cohort of symptomatic osteoporotic patients, younger than 55 years of age and 2) To study associated clinical and laboratory features and outcome with gluten-free diet. MATERIAL AND METHODS: We studied 33 patients (F:M = 28:5), mean age 29 years (range 15-52 years) with osteoporosis (WHO diagnostic criteria, T-score less than -2.5 on DEXA scan) from January 2000 - June 2002. Serological screening for CD was done by detecting circulating IgA antibodies to tissue transglutaminase by ELISA. Patients with presence of antibodies to transglutaminase were subjected to biopsy from the 2nd part of the duodenum by upper GI endoscopy. The biopsies were reported independently by two pathologists who were blinded for the serology report. Measurement of mucosal thickness, crypts and villi were done with an ocular micrometer. Other parameters like complete hemogram, serum iron, total iron binding capacity (TIBC), calcium profile, 25-OH-D, parathyroid hormone (PTH) were evaluated. Assessment of clinical and laboratory parameters was performed within 4-12 weeks of starting gluten-free diet (GFD). RESULTS: Thirteen patients had circulating IgA antibodies to transglutaminase. Intestinal biopsies were performed on 11 patients and were consistent with the diagnosis of CD (total villous atrophy--two, subtotal villous atrophy with crypt hyperplasia--nine). Patients with CD had significant anaemia when compared with non-CD osteoporotic patients. Other important observations in these 11 patients were low serum calcium and phosphorus, low 25-OH-D, high PTH. Significant improvement in clinical and laboratory parameters was noted in all patients within 6-12 weeks of starting GFD. CONCLUSION: Symptomatic osteoporotic patients (younger than 55 years of age) especially with associated anaemia should be investigated for CD. Simple measures like omission of wheat from diet (GFD) lead to significant improvement in symptoms within weeks.

A comparison of robot-assisted versus manually constructed endoscopic coronary anastomosis.

BACKGROUND: New technology has enabled surgeons to attempt totally endoscopic coronary artery bypass grafting. Our purpose was to compare three different techniques of totally endoscopic anastomosis using a porcine animal model. METHODS: Porcine hearts were excised and the right coronary artery was dissected free for use as an arterial graft. The hearts were placed in a human thoracic model and an endoscopic arterial anastomosis between the free right coronary artery and the left anterior descending coronary artery was performed using one of the following: (1) two-dimensional visualization with straight endoscopic instruments (n = 8); (2) three-dimensional head-mounted visualization with curved endoscopic instruments (n = 7); or (3) three-dimensional visualization with robotic telemanipulation (n = 8). Pathologic analysis of suture placement, vessel trauma, and patency was performed. Anastomoses were graded according to quality, ease, and patency using a seven-point Likert scale (1 = excellent, 7 = very poor). RESULTS: Endoscopic anastomotic ease and quality were significantly improved when three-dimensional visualization and curved endoscopic instruments were employed. Telemanipulation enhanced the process and provided the best operative results with regard to time required to construct the anastomosis, as well as ease and quality. CONCLUSIONS: Totally endoscopic anastomosis is feasible using currently available technology. Three-dimensional visualization and robotic telemanipulation significantly facilitate anastomosis construction and will likely benefit clinical operative outcome.

Off-pump surgery decreases postoperative complications and resource utilization in the elderly.

BACKGROUND: Bypass surgery in the elderly (age >70 years) has increased mortality and morbidity, which may be a consequence of cardiopulmonary bypass. We compare the outcomes of a cohort of elderly off-pump coronary artery bypass (OPCAB) patients with elderly conventional coronary artery bypass grafting (CABG) patients. METHODS: Chart and provincial cardiac care registry data were reviewed for 30 consecutive elderly OPCAB patients (age 74.7 +/- 4.2 years) and 60 consecutive CABG patients (age 74.9 +/- 4.1 years, p = 0.82) with similar risk factor profiles: Parsonnet score 17.2 +/- 8.1 (OPCAB) versus 15.6 +/- 6.5 (CABG), p = 0.31; and Ontario provincial acuity index 4.5 +/- 1.9 (OPCAB) versus 4.3 +/- 2.0 (CABG), p = 0.65. RESULTS: Mean hospital stay was 6.3 +/- 1.8 days for OPCAB patients and 7.7 +/- 3.9 days for CABG patients (p < 0.05). Average intensive care unit stay was 24.0 +/- 10.9 h for OPCAB patients versus 36.6 +/- 33.5 h for CABG patients (p < 0.05). Atrial fibrillation occurred in 10.0% of OPCAB patients and 28.3% of CABG patients (p < 0.05). Low output syndrome was observed in 10% of OPCAB patients and 31.7% of CABG patients (p < 0.05). Cost was reduced by $1,082 (Canadian) per patient in the OPCAB group. Postoperative OPCAB graft analysis showed 100% patency. CONCLUSIONS: OPCAB is safe in the geriatric population and significantly reduces postoperative morbidity and cost.

Comparative bioequivalence study of rifampicin and isoniazid combinations in healthy volunteers.

OBJECTIVE: To assess the bioavailability of rifampicin (RMP) in three brands of combination formulations of anti-tuberculosis drugs. DESIGN: A three-way double-blind, cross-over bioavailability study of RMP and isoniazid (INH), consisting of a comparison of a two-drug combination of tablets of RMP and INH each separately (reference brand R) and a tablet of RMP + INH (brand N), and a capsule of RMP + INH (brand L) was carried out in 12 healthy male volunteers. Coded plasma samples were analysed for levels of RMP as well as INH and acetylisoniazid (ACINH) by two high performance liquid chromatography (HPLC) methods. RESULTS: The mean values of RMP in brand N (Cmax 6.49+/-0.52 microg/mL, Tmax 2.33+/-0.18 h, AUC(0-24h) 39.83+/-3.44 microg/mL.h) were comparable with those obtained with brand R (Cmax 5.22+/-0.59 microg/mL, Tmax 2.50+/-0.12 h, AUC(0-24h) 33.33+/-3.47 microg/mL.h). The mean values of RMP in brand L (Cmax 3.05+/-0.52 microg/ mL, Tmax 3.79+/-0.57 h and AUC(0-24h) 21.78+/-3.67 microg/ mL.h) were significantly different from those in brand R. Nevertheless, all of the pharmacokinetic parameters obtained for INH and ACINH in all three brands were comparable. CONCLUSION: Using brand R as a comparison, brand N was bioequivalent and brand L was not bioequivalent.

Comparison of absorption rate and bioavailability of two brands of carbamazepine.

OBJECTIVE: To assess the bioavailability of carbamazepine from two brands of carbamazepine--Tegretol 200 and Zen-200. METHODS: A two-way randomised cross-over bioavailability of carbamazepine was carried out in twelve healthy male volunteers. Coded plasma samples were analysed for levels of carbamazepine by high performance liquid chromatography (HPLC) method. Tegretol 200 and Zen-200 were tested for in-vitro dissolution profiles. RESULTS: The mean Cmax, Tmax and t1/2a for Tegretol 200 were: 2.17 +/- 0.42 mcg/mL, 11.67 +/- 6.37 h and 2.72 +/- 1.87 h; for Zen-200 were 3.10 +/- 0.05 mcg/mL, 3.50 +/- 2.11 h and 0.76 +/- 0.76 h respectively. These values were statistically significant. However AUC (0-96 h) value of 150.16 +/- 27.13 mcg/ml.h after Zen-200 was not statistically significant as compared to 128.68 +/- 20.22 mcg/ml.h after Tegretol 200. The in-vitro dissolution profiles of the two formulations were dissimilar. The fluctuations in CBZ levels after Tegretol 200 was significantly less as compared to Zen-200. The absorption profile as judged by parameter 'A' was 50.44 +/- 10.95 for Tegretol 200 and 42.49 +/- 18.89 for Zen-200. CONCLUSION: Based on parameter 'A' and other pharmacokinetic parameters, the marketed generic carbamazepine product, Zen-200 is not bioequivalent to Tegretol 200.

Comparative bioavailability study of a conventional and two controlled release oral formulations of Tegretol (carbamazepine)--200 mg.

OBJECTIVES: To assess the bioquivalence of carbamazepine (CBZ) controlled release formulation A (Tegretol CR, local) vs formulation B (Tegretol CR, Basel) and confirm their controlled release characteristics by comparing with conventional formulation (Tegretol). METHODS: A three-way randomized cross-over bioavailability study was carried out using CBZ 200 mg tablets of conventional and two controlled release formulations in twelve healthy volunteers. Coded plasma samples were analysed for levels of CBZ by HPLC method. RESULTS: The mean Cmax, Tmax, t1/2 and AUC for formulation A were: 1.67 +/- 0.26 mcg/mL, 24 +/- 0 hr, 47.8 +/- 9.7 hr and 136.7 +/- 25.4 mcg/ml. h; for formulation B were 1.41 +/- 0.31 mcg/mL, 25 +/- 8 hr, 46.9 +/- 7.9 and 119 +/- 32.3 mcg/ml.h and for conventional formulation were 2.43 +/- 3.6 mcg/mL, 9.5 +/- 7.4 hr, 44.6 +/- 9.8 hr and 178.8 +/- 41.9 mcg/ml.h respectively. The fluctuation in plasma concentration within 24 h (peak:trough) were 11.7 +/- 8.14% with conventional formulation as compared to 0% and 1.2 +/- 3.98% with formulation A and B respectively. The mean Tmax for both the controlled release formulations was not statistically significant. On the basis of 90% confidence interval, mean AUC and Cmax values obtained after controlled release formulation A, though statistically significant (P < 0.05) lie well within the prescribed limits of 80-120% as compared to formulation B. Thus both the controlled release formulations were bioequivalent. In comparison to conventional formulation, both controlled release formulations gave lower Cmax, lower AUCs, higher Tmax values, less fluctuation in CBZ plasma concentrations, reduction in ratio of Cmax/AUC values, thus demonstrating controlled release characteristics of the formulation. CONCLUSIONS: Based on the above mentioned parameters both controlled release formulations are bioequivalent and demonstrate controlled release characteristics.

Safety and cost-effectiveness of MIDCABG in high-risk CABG patients.

BACKGROUND: Myocardial revascularization without cardiopulmonary bypass has been proposed as a potential therapeutic alternative in high-risk patients undergoing coronary artery bypass grafting. To evaluate this possibility we compared 15 high-risk (HR) patients in whom minimally invasive direct coronary artery bypass grafting was used as the method of revascularization with 41 consecutive patients who underwent conventional coronary artery bypass grafting during 1 month. METHODS: Patients undergoing myocardial revascularization without cardiopulmonary bypass were significantly older than their low-risk (LR) counterparts (72.2 +/- 11.6 versus 63.3 +/- 9.7 years, p = 0.006). The demographic profile for HR versus LR patients was as follows: female patients, 60.0% versus 26.8%, p = 0.02; diabetes, 20.0% versus 24.4%, p = 0.7; prior stroke, 33.3% versus 7.4%, p = 0.03; chronic obstructive pulmonary disease, 60.0% versus 9.8%, p < 0.0001; peripheral vascular disease, 33.3% versus 12.2%, p = 0.03, congestive heart failure, 26.6% versus 9.8%, p = 0.09; impaired left ventricular (ejection fraction < 0.40), 40.0% versus 17.0%, p = 0.07; urgent operation, 86.6% versus 46.3%, p < 0.0001; and redo operation, 20.0% versus 0%, p = 0.003. RESULTS: There were no deaths in the HR group and one death in the LR group. The average intensive care unit stay was 1.1 +/- 0.5 days in HR patients versus 1.6 +/- 1.6 days in LR individuals (p = 0.2), and the average hospital stay was 6.1 +/- 1.8 versus 7.3 +/- 4.4 days, respectively (p = 0.3). We used an acuity risk score index developed by the Adult Cardiac Care Network of Ontario to predict outcome in the HR group. The expected intensive care unit stay in HR patients was 4.1 +/- 1.2 days (versus the observed stay of 1.1 +/- 0.5 days, p < 0.0001), and the expected hospital stay was 12.5 +/- 1.5 days (versus the observed stay of 6.1 +/- 1.8 days, p < 0.0001). The expected mortality in the HR group was 6.1% versus 0%, p = 0.3. A cost regression model was used to examine predicted versus actual cost (in Canadian dollars) for the HR patient cohort (based on Ontario Ministry of Health funding). The expected cost for the HR cohort would have been $11,997 per patient. In contrast, the average cost for these 15 patients was $5,997 per patient, an estimated cost saving of 50%. CONCLUSIONS: Myocardial revascularization without cardiopulmonary bypass appears to be a safe and cost-effective therapeutic modality for HR patients requiring myocardial revascularization.

Neuroleptic malignant syndrome: an experience of four cases.

We report four cases of neuroleptic malignant syndrome occurring after administration of a typical antipsychotic haloperidol and a newer atypical antipsychotic clozapine. The management of these patients is discussed.

Determination of pyrazinamide in human by high performance liquid chromatography.

A facile and sensitive high performance liquid chromatographic (HPLC) technique has been developed for the determination pyrazinamide (PZA) in human plasma. Nicotinamide(NIA) is used as internal standard(IS). Plasma is deproteinized with 0.7 M perchloric acid; clear supernatant is neutralized with 1M NaOH and injected onto HPLC. The separation of pyrazinamide and the internal standard is carried out on a Supelco LC-18 (DB) column with a basic mobile phase. Pyrazinoic acid, the major metabolite, other anti-tuberculous drugs and endogenous components do not interfere with measurement of pyrazinamide. The limit of detection of pyrazinamide with this method is 0.2 mg/0.2 ml plasma (CV 8.2%).

Pharmacokinetics of primaquine in patients with P. vivax malaria.

The pharmacokinetics of primaquine (PQ) and its major carboxylic acid metabolite (PQC) have been studied in seven Indian patients with P. vivax malaria following PQ 15 mg/day p.o. for 14 days. After a single oral dose on Day 1, a mean peak blood concentration of 50.7 ng/ml PQ was attained after 2.3 h, which declined monoexponentially with a half-life of 5.6 h. The mean total body clearance was 37.6 l/h and the volume of distribution was 292 l. The mean renal excretion (0-24 h) of the drug was only 0.54% of the dose and renal clearance was 0.189 l/h. Following chronic administration, none of the pharmacokinetic parameters was affected, and a steady state blood concentration of 2.5-4.2 ng/ml PQ was attained. After the first dose of PQ, PQC had a mean area under the blood concentration - time curve 11-fold higher than that of the parent drug. In contrast to the rapid distribution and elimination of PQ, the metabolite showed a longer mean residence time and accumulation in the body. The mean Cmax and AUC of the metabolite on Day 14 were 48 and 40% higher than the corresponding Day 1 values. The metabolite could not be detected in urine at any time in any patient. PQ and its metabolite did not show any accumulation in blood cells.