CDRI compound no. 99/411 is a potent 1,2,4-trioxane antimalarial candidate drug under development at our Institute. An HPLC method for determination of CDRI 99/411 with its starting material and intermediates has been developed and validated for in process quality control and stability studies. The analytical performance parameters such as linearity, precision, accuracy, specificity, limit of detection (LOD) and lower limit of quantification (LLOQ) were determined according to International Conference on Harmonization ICH Q2(R1) guidelines. HPLC separation was achieved on a RP-select B Lichrospheres column (250 mm ? 4 mm, 5μm, Merck) using water containing 0.1%glacial acetic acid and acetonitrile as the mobile phase in a gradient elution. The eluents were monitored by a photo diode array detector at 245 and 275 nm. Based on signal to noise ratio of 3 and 10 the LOD of CDRI 99/411 was 0.55 mg/mL, while the LLOQ was 1.05 mg/mL. The calibration curves were linear in the range of 1.05-68 mg/mL. Precision of the method was determined by inter- and intra-assay variations within the acceptable range.

The pharmacokinetics and dosage regimen of cefotaxime following its single subcutaneous administration (10 mg/ kg) were investigated in buffalo calves. Plasma and urine samples were collected over 10 and 24 h post administration, respectively. Cefotaxime in plasma and urine was estimated by microbiological assay technique using E. coli as test organism. The pharmacokinetic profiles fitted one-compartment open model. The peak plasma levels of cefotaxime were 6.48 +/- 0.52 microgram/ml at 30 min and the drug was detected upto 10 h. The absorption half-life and elimination halflife were 0.173 +/- 0.033 h and 1.77 +/- 0.02 h, respectively. The apparent volume of distribution and total body clearance were 1.17 +/- 0.10 l/kg and 0.45 +/- 0.03 l/kg/h, respectively. The urinary excretion of cefotaxime in 24 h, was 5.36 +/- 1.19 percent of total administrated dose. A satisfactory subcutaneous dosage regimen for cefotaxime in buffalo calves would be 13 mg/kg repeated at 12 h intervals.
Animals ; Anti-Bacterial Agents/*administration&dosage/blood/*pharmacokinetics/urine ; Area Under Curve ; *Buffaloes ; Cefotaxime/*administration&dosage/blood/*pharmacokinetics/urine ; Drug Administration Schedule ; Half-Life ; Male ; Tissue Distribution

OBJECTIVETo describe the epidemiology and severity of illness of children hospitalized with respiratory syncytial virus (RSV) infection, including those who received palivizumab prophylaxis, at Royal University Hospital (RUH), Saskatoon and Regina General Hospital (RGH) from July 2002 to June 2005.

METHODSChildren hospitalized for ≥ 24 hours with laboratory-confirmed RSV infection were enrolled, and their health records were retrospectively reviewed for patient demographics and referral patterns, use of palivizumab prophylaxis, severity of infection (length of hospitalization, need for and duration of pediatric intensive care and mechanical ventilation) and outcome of infection.

RESULTSA total of 590 children (324 males) were hospitalized over the three years. The median chronological age at admission was 5.3 months, and median hospital stay was 4.0 days. Gestational age at birth was ≥ 36 weeks in 82.4% of patients. RSV disease severity was mild to moderate in 478 patients (81.0%) and severe in 110 (18.6%). Thirty-nine patients (6.6%) required pediatric intensive care unit admission, for a median of 5.0 days. Twenty-two of these patients (56%) were mechanically ventilated for a median of 6.0 days. Two children died, not attributed to RSV infection. Twenty-two patients had received palivizumab prophylaxis before hospital admission, with 18 completing at least 2 of the monthly doses. Most of these children (17/22) had mild to moderate illness.

CONCLUSIONSRSV causes significant morbidity in Saskatchewan, affecting predominantly term infants. The majority of illness is mild to moderate. Some patients who have received palivizumab may still develop significant RSV disease.

Adolescent ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Child ; Child, Preschool ; Female ; Hospitalization ; Humans ; Infant ; Infant, Newborn ; Male ; Palivizumab ; Respiratory Syncytial Virus Infections ; epidemiology ; prevention & control ; Saskatchewan ; epidemiology ; Tertiary Care Centers ; Time Factors

The present study was planned to investigate the pharmacokinetics of ceftriaxone in experimentally induced febrile buffalo calves (n = 5). The fever was induced by intravenous injection of E.coli lipopolysaccaride (1 microgram/kg). To study the pharmacokinetics, ceftriaxone was administered at the dose rate of 10 mg/kg body wt. in all animals. At 1 min, the peak concentration of ceftriaxone was 79.4 +/- 2.37 microgram/ml and the drug was detected up to 6 h. The elimination rate constant was 0.35 +/- 0.02 /h and elimination half-life was 2.04 +/- 0.14 h. The apparent volume of distribution (Vd(area)) and total body clearance (ClB) were 1.21 +/- 0.15 l/kg and 0.41 +/- 0.03 l/kg/h, respectively. To maintain a minimum therapeutic concentration of 1 microgram/kg, a satisfactory dosage regimen of cefriaxone in febrile buffalo calves is 19 mg/kg followed by 18 mg/kg at 8 h intervals.
Animals ; Anti-Bacterial Agents/administration&dosage/*pharmacokinetics ; Area Under Curve ; Buffaloes/*metabolism ; Ceftriaxone/administration&dosage/*pharmacokinetics ; Drug Administration Schedule/veterinary ; Fever/drug therapy/*metabolism/*veterinary ; Half-Life ; Lipopolysaccharides/administration&dosage ; Male ; Metabolic Clearance Rate

Severe alcoholic hepatitis has very high short term mortality and corticosteroids have been the mainstay of treatment for decades. Patients with Lille score >0.45 are considered non-responders to steroids and have poor outcome. Recently Orthotopic Liver Transplantation (OLT) is being increasingly used as rescue treatment for these patients, without waiting for 6 months of abstinence. Liver transplant is the only rescue treatment which can potentially provide long term benefit for patients who are steroid non-responders. However, with scarcity of organs being a concern, all patients of severe alcoholic hepatitis cannot be chosen for transplantation in an arbitrary way. There is a need for development of predictive tools and objective protocols to select patients who can justify the use of precious liver grafts. With a stringent criteria for selection of patients receiving the graft, liver transplantation in severe alcoholic hepatitis can become a viable rescue therapeutic option conferring significant survival advantage of both short- and long-term basis. The optimal criteria for selection will also prevent misuse of the liver donor pool as well as to prevent mortality in salvageable patients. Further research needs to be done to identify subset of patients which are at low risk of recidivism and also cannot be managed with pharmacotherapy alone. We reviewed the current knowledge on role of OLT in patient with acute severe alcoholic hepatitis in the present review.
Adrenal Cortex Hormones ; Alcoholics* ; Drug Therapy ; Fibrosis ; Hepatitis, Alcoholic* ; Humans ; Liver Diseases, Alcoholic ; Liver Transplantation* ; Liver* ; Mortality ; Steroids ; Tissue Donors ; Transplants

Purpose: Intensity-modulated radiotherapy (IMRT) provides higher dose to target volumes and limits the dose to normal tissues. IMRT may be applied using either simultaneous integrated boost (SIB-IMRT) or sequential boost (SEQ-IMRT) technique. The objectives of this study were to compare acute toxicity and objective response rates between SIB-IMRT and SEQ-IMRT in patients with locally advanced head and neck cancer. Materials and Methods: Total 110 patients with locally advanced carcinoma of oropharynx, hypopharynx, and larynx were randomized equally into the two arms (SIB-IMRT vs. SEQ-IMRT). Patients in SIB-IMRT arm received dose of 66 Gy in 30 fractions, 5 days a week, over 6 weeks. SEQ-IMRT arm’s patients received 70 Gy in 35 fractions over 7 weeks. Weekly concurrent cisplatin chemotherapy was given in both arms. Patients were assessed for acute toxicities during the treatment and for objective response at 3 months after the radiotherapy. Results: Grade 3 dysphagia was significantly more with SIB-IMRT compared to SEQ-IMRT (72% vs. 41.2%; p = 0.006) but other toxicities including mucositis, dermatitis, xerostomia, weight-loss, incidence of nasogastric tube intubation and hospitalization for supportive management were similar in both the arms. Patients in SIB-IMRT arm showed better treatment-compliance and had significantly less treatment-interruption compared to SEQ-IMRT arm (p = 0.028). Objective response rates were similar in both the arms (p = 0.783). Conclusion Concurrent chemoradiation with SIB-IMRT for locally advanced head and neck cancer is well-tolerated and results in better treatment-compliance, similar objective response rates, comparable incidence of mucositis and higher incidence of grade 3 dysphagia compared to SEQ-IMRT.

Purpose: Intensity-modulated radiotherapy (IMRT) provides higher dose to target volumes and limits the dose to normal tissues. IMRT may be applied using either simultaneous integrated boost (SIB-IMRT) or sequential boost (SEQ-IMRT) technique. The objectives of this study were to compare acute toxicity and objective response rates between SIB-IMRT and SEQ-IMRT in patients with locally advanced head and neck cancer. Materials and Methods: Total 110 patients with locally advanced carcinoma of oropharynx, hypopharynx, and larynx were randomized equally into the two arms (SIB-IMRT vs. SEQ-IMRT). Patients in SIB-IMRT arm received dose of 66 Gy in 30 fractions, 5 days a week, over 6 weeks. SEQ-IMRT arm’s patients received 70 Gy in 35 fractions over 7 weeks. Weekly concurrent cisplatin chemotherapy was given in both arms. Patients were assessed for acute toxicities during the treatment and for objective response at 3 months after the radiotherapy. Results: Grade 3 dysphagia was significantly more with SIB-IMRT compared to SEQ-IMRT (72% vs. 41.2%; p = 0.006) but other toxicities including mucositis, dermatitis, xerostomia, weight-loss, incidence of nasogastric tube intubation and hospitalization for supportive management were similar in both the arms. Patients in SIB-IMRT arm showed better treatment-compliance and had significantly less treatment-interruption compared to SEQ-IMRT arm (p = 0.028). Objective response rates were similar in both the arms (p = 0.783). Conclusion Concurrent chemoradiation with SIB-IMRT for locally advanced head and neck cancer is well-tolerated and results in better treatment-compliance, similar objective response rates, comparable incidence of mucositis and higher incidence of grade 3 dysphagia compared to SEQ-IMRT.

PURPOSE: Shoulder dislocation comprises 60% of all major joint dislocations worldwide and a number of reduction techniques are described in the literature with varying degrees of success. The description of a large number of techniques speaks for itself that no method is effective all the times and one should be acquainted with more than one technique. An ideal method of reduction should be simple, easily reproducible, relatively painless that can be performed unassisted without sedation or anaesthesia with minimal or no further complications. We report our results of using a novel method of anterior shoulder reduction described recently in the literature that claims to fulfil most of the characteristics of an ideal method if not all. METHODS: This prospective study was conducted in a tertiary care centre. All the cases of primary anterior shoulder dislocation presenting within three days of injury without any associated fracture or spine trauma with or without greater tuberosity fracture were included. The reduction was done using a novel method by orthopaedic residents in all cases. The need for a second reduction attempt or anaesthesia was considered a treatment failure. Time taken for reduction, pain felt during reduction and complications if any were noted. RESULTS: There were 47 (77.04%) males and 14 (22.95%) females with a mean age of (37.04 ± 12.63) years. The new technique was effective in locating a shoulder dislocation on the first attempt in 58 of the 61 dislocated shoulders (95.08%). The remaining three shoulders were reduced on second attempt by the same technique. Sedative, pre-medication or anaesthesia was not used in any case. The average time taken for the shoulder reduction was (130.5 ± 25.8) seconds and confidence interval (95%) 124-137 s. Iatrogenic complications were not seen in any of the patients. CONCLUSION This relatively painless technique of shoulder reduction is easy to acquire and practice in emergency department. The advantages of this manoeuvre and its associated safety may justly lead surgeons to select it as their primary method for reduction of anterior shoulder dislocations.

BACKGROUND/AIMS: To evaluate the ability of the recently proposed albumin, international normalized ratio (INR), mental status, systolic blood pressure, age >65 years (AIMS65) score to predict mortality in patients with acute upper gastrointestinal bleeding (UGIB). METHODS: AIMS65 scores were calculated in 251 consecutive patients presenting with acute UGIB by allotting 1 point each for albumin level <30 g/L, INR >1.5, alteration in mental status, systolic blood pressure < or =90 mm Hg, and age > or =65 years. Risk stratification was done during the initial 12 hours of hospital admission. RESULTS: Intensive care unit (ICU) admission, endoscopic therapy, or surgery were required in 51 patients (20.3%), 64 (25.5%), and 12 (4.8%), respectively. The predictive accuracy of AIMS65 scores > or =2 was high for blood transfusion (area under the receiver operator characteristic curve [AUROC], 0.59), ICU admission (AUROC, 0.61), and mortality (AUROC, 0.74). The overall mortality was 10.3% (n=26), and was 3%, 7.8%, 20%, 36%, and 40% for AIMS65 scores of 0, 1, 2, 3, and 4, respectively; these values were significantly higher in those with scores > or =2 (30.9%) than in those with scores <2 (4.5%, p<0.001). CONCLUSIONS: AIMS65 is a simple, accurate, non-endoscopic risk score that can be applied early (within 12 hours of hospital admission) in patients with acute UGIB. AIMS65 scores > or =2 predict high in-hospital mortality.
Blood Pressure ; Blood Transfusion ; Endoscopy ; Gastrointestinal Hemorrhage* ; Hemorrhage ; Hospital Mortality ; Humans ; Intensive Care Units ; International Normalized Ratio ; Mortality

Background: and Purpose Mechanical thrombectomy (MT) is an effective treatment for patients with basilar artery occlusion (BAO) acute ischemic stroke. It remains unclear whether bridging intravenous thrombolysis (IVT) prior to MT confers any benefit. This study compared the outcomes of acute BAO patients who were treated with direct MT versus combined IVT plus MT. Methods: This multicenter retrospective cohort study included patients who were treated for acute BAO from eight comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale 0–3 measured at 90 days. Secondary outcome measures included mortality and symptomatic intracranial hemorrhage (sICH). Results: Among 322 patients, 127 (39.4%) patients underwent bridging IVT followed by MT and 195 (60.6%) underwent direct MT. The mean±standard deviation age was 67.5±14.1 years, 64.0% were male and median National Institutes of Health Stroke Scale was 16 (interquartile range, 8 to 25). At 90-day, the rate of favorable functional outcome was similar between the bridging IVT and direct MT groups (39.4% vs. 34.4%, P=0.361). On multivariable analyses, bridging IVT was not asComorbidisociated with favorable functional outcome, mortality or sICH. In subgroup analyses, patients with underlying atherosclerosis treated with bridging IVT compared to direct MT had a higher rate of favorable functional outcome at 90 days (37.2% vs. 15.5%, P=0.013). Conclusions Functional outcomes were similar in BAO patients treated with bridging IVT versus direct MT. In the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT may potentially confer benefit and this warrants further investigation.