Objective:To determine the potential drug-drug interactions between anti-malarial candidate 97/78 and anti-tubercular drug rifabutin in-vivo in rats followed byin-vitro investigation of the underlying mechanisms of drug interaction.Methods: Single oral dose study was conducted in male and female rats at 40 mg/kg and 70 mg/kg for 97/78 and rifabutin respectively. Results:It was reported that rifabutin co-administration altered pharmacokinetics of 97/63 (active metabolite of 97/78). A significant decrease was reported in the systemic exposure of 97/63 by a factor of 3-4. The AUC0-last values were (4.03 ± 0.60) and (5.44 ± 1.15) μg?h?mL-1 upon 97/78 administration alone, while the values were decreased to (1.13 ± 0.10) and (1.23 ± 1.13) μg?h?mL-1 upon rifabutin co-administration in male and female rats respectively. Statistically significant differences were also reported in Cmaxand Tmax values upon rifabutin co-administration.In-vitro drug metabolism study in rat liver microsomes has shown that the metabolism of 97/63 was increased by 10%-12% upon rifabutin co-incubation. The extent of plasma protein binding of 97/63 was found to be decreased from 54%-55% to 6%-8% upon rifabutin addition.Conclusions:It was concluded that rifabutin co-administration altered PK parameters of 97/63 in SD rats. However, no intersex influences were reported in the interaction pattern. The results obtained in the in-vivo study were well correlated with thein-vitro findings and can further be applied to explore other aspects of potential drug interactions between these two drugs.

Introduction: Isolated Hoffa fracture is an infrequent injury and little research has been done on this subject. The purpose of this study was to evaluate the functional outcome and complications of surgically managed Hoffa fractures with cannulated cancellous screw. Materials and Methods: Between 2011 and 2014, eight isolated Hoffa fractures in seven adult patients with mean age 39.8±11.9 years (range 25-60 years) were managed with cannulated cancellous screw of 6.5mm diameter applied in anterior to posterior direction using swashbuckler and medial parapatellar approach for lateral and medial Hoffa fractures respectively. All patients were evaluated using knee evaluation score after two years or longer. Mean follow up was 28±3.8 months (range 24-36 months). Results: All fractures in the eight patients healed clinicoradiologically by the 16th week with excellent result in 87.5% cases and good in 12.5% cases. By the end of union, the range of motion (ROM) of the knee was 0° to 110° except in two patients. One patient had ROM 10°-100° and other had 15°-90°. Mean knee evaluation score was 87.5±10.4. There was no incidence of non-union, infection or avascular changes in the patients or loss of reduction till final follow up. Conclusion: Open reduction and fixation with two 6.5 mm cannulated cancellous screws with early mobilization yielded good functional outcome in isolated Hoffa fractures.

Objective: To determine the potential drug-drug interactions between anti-malarial candidate 97/78 and anti-tubercular drug rifabutin in-vivo in rats followed by in-vitro investigation of the underlying mechanisms of drug interaction. Methods: Single oral dose study was conducted in male and female rats at 40 mg/kg and 70 mg/kg for 97/78 and rifabutin respectively. Results: It was reported that rifabutin co-administration altered pharmacokinetics of 97/63 (active metabolite of 97/78). A significant decrease was reported in the systemic exposure of 97/63 by a factor of 3-4. The AUC0-last values were (4.03 ± 0.60) and (5.44 ± 1.15) μg h mL^-1 upon 97/78 administration alone, while the values were decreased to (1.13 ± 0.10) and (1.23 ± 1.13) μg h mL^-1 upon rifabutin co-administration in male and female rats respectively. Statistically significant differences were also reported in Cmax and Tmax values upon rifabutin co-administration. In-vitro drug metabolism study in rat liver microsomes has shown that the metabolism of 97/63 was increased by 10%-12% upon rifabutin co-incubation. The extent of plasma protein binding of 97/63 was found to be decreased from 54%-55% to 6%-8% upon rifabutin addition. Conclusions: It was concluded that rifabutin co-administration altered PK parameters of 97/63 in SD rats. However, no intersex influences were reported in the interaction pattern. The results obtained in the in-vivo study were well correlated with the in-vitro findings and can further be applied to explore other aspects of potential drug interactions between these two drugs.

PURPOSE: To compare the efficacy and safety of latanoprost, bimatoprost, travoprost and timolol in reducing intraocular pressure (IOP) in patients with primary open angle glaucoma. METHODS: This was a prospective study conducted at a tertiary-care centre. One hundred and forty patients with newly diagnosed primary open angle glaucoma were randomly assigned to treatment with latanoprost (0.005%), bimatoprost (0.03%), travoprost (0.004%) or timolol gel (0.5%); 35 patients were assigned to each group. All patients were followed for 2, 6, and 12 weeks. The main outcome measure studied was the change in IOP at week 12 from the baseline values. Safety measures included recording of adverse events. RESULTS: The mean IOP reduction from baseline at week 12 was significantly more with bimatoprost (8.8 mmHg, 35.9%) than with latanoprost (7.3 mmHg, 29.9%), travoprost (7.6 mmHg, 30.8%) or timolol (6.7 mmHg, 26.6%) (ANOVA and Student's t-tests, p < 0.001). Among the prostaglandins studied, bimatoprost produced a maximum reduction in IOP (-2.71; 95% confidence interval [CI], -2.25 to -3.18) followed by travoprost (-1.27; 95% CI, -0.81 to -1.27) and latanoprost (-1.25; 95% CI, -0.79 to -1.71); these values were significant when compared to timolol at week 12 (Bonferroni test, p < 0.001). Latanoprost and travoprost were comparable in their ability to reduce IOP at each patient visit. Ocular adverse-events were found in almost equal proportion in patients treated with bimatoprost (41.3%) and travoprost (41.9%), with a higher incidence of conjunctival hyperemia (24.1%) seen in the bimatoprost group. Timolol produced a significant drop in heart rate (p < 0.001) at week 12 when compared to the baseline measurements. CONCLUSIONS: Bimatoprost showed greater efficacy when compared to the other prostaglandins, and timolol was the most efficacious at lowering the IOP. Conjunctional hyperemia was mainly seen with bimatoprost. However, the drug was tolerated well and found to be safe.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antihypertensive Agents/adverse effects/*therapeutic use ; Bimatoprost/adverse effects/therapeutic use ; Blood Pressure/drug effects ; Female ; Glaucoma, Open-Angle/*drug therapy/physiopathology ; Heart Rate/drug effects ; Humans ; Intraocular Pressure/drug effects ; Male ; Middle Aged ; Prostaglandins F, Synthetic/adverse effects/therapeutic use ; Timolol/adverse effects/therapeutic use ; Tonometry, Ocular ; Travoprost/adverse effects/therapeutic use ; Treatment Outcome ; Visual Acuity/drug effects ; Visual Field Tests ; Visual Fields/drug effects

Sudden ascent to high altitudes beyond 2,438 m can cause life-threatening complications such as acute mountain sickness and high altitude cerebral and pulmonary oedema. We present a case of pituitary apoplexy in a young man who ascended to high altitude gradually, after proper acclimatisation. He developed headache, nausea, vomiting and persistent hypotension. Magnetic resonance imaging revealed an enlarged pituitary gland with haemorrhage. His hormonal estimation showed acute adrenal insufficiency due to corticotropin deficiency. The patient responded well to conservative medical management with hormonal replacement therapy. This is most likely the first reported case of high altitude-induced pituitary apoplexy in the literature.
Acclimatization ; Adrenal Insufficiency ; complications ; Adrenocorticotropic Hormone ; deficiency ; Adult ; Altitude ; Altitude Sickness ; complications ; Brain ; pathology ; Hormone Replacement Therapy ; methods ; Humans ; Hypotension ; physiopathology ; Intracranial Hemorrhages ; physiopathology ; Magnetic Resonance Imaging ; methods ; Male ; Pituitary Apoplexy ; diagnosis ; etiology ; Pituitary Gland ; physiopathology

Background/Aims: Gluten-free diet has an excess of fats and simple sugars and puts patients with celiac disease at risk of metabolic complications including metabolic syndrome and fatty liver. We assessed prevalence of metabolic syndrome and fatty liver in two cohorts of celiac disease. Methods: Study was done in 2 groups. In group 1, 54 treatment naïve patients with celiac disease were recruited. Of them, 44 returned after 1-year of gluten-free diet and were reassessed. In group 2, 130 celiac disease patients on gluten-free diet for ≥1 year were recruited. All patients were assessed for anthropometric and metabolic parameters and fatty liver. Metabolic syndrome was defined as per consensus definition for Asian Indians. Fatty liver was defined as controlled attenuation parameter value >263 decibels by FibroScan. Results: In group 1, of 44 treatment naïve patients with celiac disease, metabolic syndrome was present in 5 patients (11.4%) at baseline and 9 (18.2%) after 1 year of gluten-free diet. Patients having fatty liver increased from 6 patients (14.3%) at baseline to 13 (29.5%) after 1year of gluten-free diet (P=0.002). In group 2, of 130 patients with celiac disease on gluten-free diet for a median duration of 4 years, 30 out of 114 (26.3%) and 30 out of 130 patients (23%) had metabolic syndrome and fatty liver, respectively. Conclusions Patients with celiac disease are at high risk of developing metabolic syndrome and fatty liver, which increases further with gluten-free diet. These patients should be assessed for nutritional and metabolic features and counseled about balanced diet and physical activity regularly.

Aged ; Bendamustine Hydrochloride ; therapeutic use ; Humans ; Lymphadenopathy ; diagnosis ; Lymphoma ; diagnosis ; drug therapy ; Male ; Rituximab ; therapeutic use

STUDY DESIGN: Retrospective study. PURPOSE: To evaluate the clinico-radiological efficacy of stand-alone minimally invasive transarticular screw (MIS-TAS) fixation without supplemental Gallie fixation in the management of mobile C1–C2 instability. OVERVIEW OF LITERATURE: Data evaluating the efficacy and feasibility of MIS-TAS in the literature is scanty. METHODS: Patients with mobile atlantoaxial instability and >2 years follow-up were included and managed by stand-alone TAS fixation using the Magerl technique and morselized allograft without additional fixation. Patient demographics and intra-operative parameters were noted. Clinical parameters (Visual Analog Scale [VAS] and Oswestry Disability Index [ODI]), neurology (modified Japanese Orthopaedic Association [mJOA]), and radiological factors (anterior atlanto-dens interval and space available for cord) were evaluated pre and postoperatively. Computed tomography (CT) was performed in patients who did not show interspinous fusion on X-ray at 1 year, to verify intra-articular fusion. Statistical analysis was performed using IBM SPSS ver. 20.0 (IBM Corp., Armonk, NY, USA); the Student t-test and analysis of variance were used to assess statistical significance (p <0.05). RESULTS: A total of 82 consecutive cases (three males, one female; mean age, 36.26±5.78 years) were evaluated. In total, 163 TASs were placed. Significant improvement was noticed in clinical (mean preoperative VAS=7.2±2.19, postoperative VAS=3.3±1.12; mean preoperative ODI=78.3±4.83, postoperative ODI=34.05±3.26) and neurological features (mean preoperative mJOA=14.73±2.68, postoperative mJOA=17.5±2.21). Radiological evidence of fusion was noted in 97.5% cases at final follow-up. Seventeen patients were found to have no interspinous fusions upon X-rays, but CT revealed facet fusion in all patients except in two. Inadvertent vertebral artery injury was noted in three cases. CONCLUSIONS: Stand-alone TAS fixation with morselized allograft provides excellent radiological and clinical outcomes. The addition of a supplementary tension band and structural graft are not essential. This provides the opportunity to avoid the complications associated with graft harvesting and wiring.
Allografts ; Asian Continental Ancestry Group ; Atlanto-Axial Joint ; Bone Wires ; Demography ; Female ; Follow-Up Studies ; Humans ; Joint Instability ; Male ; Neurology ; Retrospective Studies ; Transplants ; Vertebral Artery