Management of intrapulmonary hemorrhage in patients undergoing pulmonary thrombo-endarterectomy.

Massive pulmonary hemorrhage during pulmonary thromboendarterectomy (PTE) can be managed by a conservative approach with mechanical ventilatory support, positive end-expiratory pressure, lung isolation, reversal of heparin, and correct of coagulopathy. We present three challenging cases that developed intrapulmonary hemorrhage during/after PTE and managed successfully. The first patient had bleeding from the bronchial artery and right internal mammary collaterals, which was managed by coil-embolization. The second patient had a breach in the blood airway barrier in the right upper lobar segment of the lung, and the repair was done using a surgical absorbable hemostat. The third patient developed reperfusion injury, he was instituted on veno-venous extracorporeal membranous oxygenation, a week later, the patient recovered completely. An algorithm was adopted and modified to our requirements; all the 3 challenging intrapulmonary hemorrhage cases were successfully managed. This algorithm can be used for satisfactory outcomes in patients who suffer intrapulmonary hemorrhage during PTE.

Methemoglobinemia Unmasked by Use of Sodium Nitroprusside and Hypothermia in a Case of Chronic Thromboembolic Pulmonary Hypertension During Pulmonary Endarterectomy: A Case Report.

In performing pulmonary endarterectomy (PEA) for a patient with chronic thromboembolic pulmonary hypertension (CTEPH), we encountered methemoglobinemia that was unmasked by hypothermia while on cardiopulmonary bypass (CPB). The patient on dapsone therapy for antiphospholipid antibody syndrome had developed acquired methemoglobinemia that went undiagnosed because her cyanosis was believed to be due to CTEPH and the resulting ventilation-perfusion (V/Q) mismatch. Although pharmacological triggers for methemoglobin are well known, causation by hypothermia is not described. Monitoring saturation while on CPB was challenging because of nonpulsatile blood flow but was overcome using cerebral oximetry.

Gaining Insights on Nasopharyngeal Carcinoma Treatment Outcome Using Clinical Data Mining Techniques.

The analysis of Electronic Health Records (EHRs) is attracting a lot of research attention in the medical informatics domain. Hospitals and medical institutes started to use data mining techniques to gain new insights from the massive amounts of data that can be made available through EHRs. Researchers in the medical field have often used descriptive statistics and classical statistical methods to prove assumed medical hypotheses. However, discovering new insights from large amounts of data solely based on experts' observations is difficult. Using data mining techniques and visualizations, practitioners can find hidden knowledge, identify interesting patterns, or formulate new hypotheses to be further investigated. This paper describes a work in progress on using data mining methods to analyze clinical data of Nasopharyngeal Carcinoma (NPC) cancer patients. NPC is the fifth most common cancer among Malaysians, and the data analyzed in this study was collected from three states in Malaysia (Kuala Lumpur, Sabah and Sarawak), and is considered to be the largest up-to-date dataset of its kind. This research is addressing the issue of cancer recurrence after the completion of radiotherapy and chemotherapy treatment. We describe the procedure, problems, and insights gained during the process.

Does Restrictive Fluid Strategy during Robotic Pelvic Surgeries Obtund Intraoperative Rise in Intraocular Pressure?

BACKGROUND: Robotic pelvic surgeries require steep Trendelenburg position which may result in rise in intraocular pressure (IOP). AIM: The aim of this study was to compare the changes that occur in IOP during robotic pelvic surgeries in steep Trendelenburg position with a restrictive intravenous fluid administration. SETTINGS AND DESIGN: This prospective observational study was conducted in a tertiary care institution. SUBJECTS AND METHODS: Twenty consenting patients scheduled for pelvic robotic gynecological surgeries were enrolled. All patients received general anesthesia following a standardized protocol. IOP was measured before induction of anesthesia, immediately after induction and intubation, at the end of surgery immediately after making the patient supine and immediately after extubation. Ringer's lactate was administered intravenously at a rate of 4 mL/kg/h targeting a mean arterial pressure of >65 mmHg and urine output of >0.5 mL/kg/h. STATISTICAL ANALYSIS USED: Paired t-test was used in this study. RESULTS: There was a fall in IOP soon after induction from baseline which was not significant. Immediately, following intubation, there was a significant rise in IOP. At the end of surgery, though IOP remained high, it was not statistically significant. However, following extubation, IOP rose further and the difference from the baseline became statistically significant. Although there was a moderate increase in peak airway pressure and highest EtCO2 levels during Trendelenburg from baseline values, the differences were statistically insignificant. CONCLUSION: During robotic pelvic surgeries, adopting a restrictive intravenous fluid strategy with the maintenance of normal end-tidal carbon dioxide levels could abate effects of steep Trendelenburg position on IOP.

Efficacy of alpha2 agonists in obtunding rise in intraocular pressure after succinylcholine and that following laryngoscopy and intubation.

CONTEXT: Elevation of intraocular pressure (IOP) is an inherent and inadvertent association with the use of succinylcholine and alpha2 agonists can be used to obtund this effect. AIMS: The study was aimed to assess the efficacy of intravenous dexmedetomidine and clonidine premedication in attenuating rise in IOP during laryngoscopy and intubation following administration of succinylcholine. SETTINGS AND DESIGN: This prospective, observational study was conducted in 40 patients aged 20-60 years undergoing non ophthalmic surgical procedures. SUBJECTS AND METHODS: For patients in Group D, dexmedetomidine 0.4 mcg/kg and in Group C clonidine 1 µg/kg over 10 min was administered before induction. All patients were induced with propofol. Laryngoscopy and intubation were performed 1 min after administration of succinylcholine 2 mg/kg. STATISTICAL ANALYSIS USED: Mann-Whitney, Chi-square and Wilcoxon tests. RESULTS: Mean baseline IOP of both groups were comparable (15.4 ± 2.6 vs. 14.7 ± 2.3). Following premedication and induction, IOP decreased in both groups and the reduction was significantly more in Group D. Following administration of succinylcholine and 1 min after intubation IOP raised and exceeded the baseline value in Group C (16.0 ± 1.6 and 18.6 ± 2.2). Though there was an increase in IOP in Group D (12.0 ± 1.9 and 14.0 ± 2.1), it did not reach up to baseline values. Then there was a gradual reduction in IOP in both groups at 3, 5, and 10 min and Group D continued to have a significantly low IOP than Group C up to 10 min. CONCLUSIONS: Dexmedetomidine 0.4 µg/kg resulted in a reduction of IOP and blunted the increase in IOP, which followed administration of succinylcholine, laryngoscopy, and intubation. Though clonidine 1 µg/kg reduced IOP, it did not prevent rise in IOP following succinylcholine, laryngoscopy, and intubation.

A novel treatment for pulmonary hemorrhage during thromboendarterectomy surgery.

Injury to the pulmonary artery during thromboendarterectomy is a rare but potentially fatal complication with no reported surgical techniques to combat it. Treatment is only supportive and morbidity is high. We report the intraoperative diagnosis and surgical management of pulmonary hemorrhage in 3 patients after pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension.

Hydrochemical assessment of tropical springs--a case study from SW India.

The paper deals with the hydrochemical characterization and water quality assessment of springs emerging from the Archaean crystalline basements at the foothills of Western Ghat mountains in the highlands and Neogene sedimentary formations in the coastal lowlands of Kerala in south west India. A total of 19 springs from two important river basins of southern Kerala such as Ithikkara and Kallada river basins were studied for 18 physico-chemical (temperature, pH, electrical conductivity (EC), total dissolved solids (TDS), dissolved oxygen (DO), total hardness (TH), Na(+), K(+), Ca(2+), Mg(2+), CO3 (2-), HCO3 (-), Cl(-), SO4 (2-) , NO3 (-), SiO2, Fe(2+), and F(-) ) as well as bacteriological parameters. The discharge computations show that free-falling type of springs in the area discharge about 256.23 million liters of water a year. A comparative study between the spring water samples of highland and lowland regions reveal that the quality of spring water, except pH and bacteriological contents, satisfies the standards set by the Bureau of Indian Standards and World Health Organization for drinking water. Spring water samples collected from the lowlands register high value of Na(+) and Cl(-) compared with the highlands. Bicarbonate, Ca(2+), Mg(2+), and K(+) values are high in highland than lowland springs. The present study reveals that the spring water sources in the region can be developed as an alternate source for drinking water, provided pH correction and proper disinfection are done prior to its end use.

Formulation and evaluation of thermosensitive biogels for nose to brain delivery of doxepin.

Thermoreversible biogels can serve as effective systems for delivery of drugs through nose with increased nasal residence time. The objective of this study was to use chitosan and glycerophosphate based thermoreversible systems for delivery of doxepin to brain through intranasal administration. Formulations were prepared by admixture of suitable dilutions of chitosan and glycerophosphate with or without polyethylene glycol, followed by addition of the antidepressant doxepin hydrochloride. Both systems were evaluated for gelling characteristics, rheology, mucoadhesion, in vitro release, and ex vivo permeation through sheep nasal mucosa. In vivo efficacy was evaluated in Swiss albino mice through the forced swim test. Nasal tissues of mice subjected to repeated exposure to formulation were evaluated histopathologically. Both formulations gelled rapidly at 37°C, returned to sol state on cooling, and exhibited thixotropy. Addition of polyethylene glycol decreased the glycerophosphate content required for gelation and rendered the formulation isotonic. Both gels showed good mucoadhesion, enhanced drug permeation, and provided prolonged in vitro release at 37°C. Efficacy of the formulation in treated groups was inferred from the measured pharmacodynamic parameter and histopathological reports of formulation treated groups showed no significant local toxicity. The biogels could be potential systems for effective drug delivery to brain via nose.

Development and evaluation of buccoadhesive tablet for selegiline hydrochloride based on thiolated polycarbophil.

Selegiline hydrochloride (SHCl), a monoamine oxidase B inhibitor, is used as an adjunct in the therapy of Parkinson's disease. This study is concerned with the preparation and evaluation of mucoadhesive buccal tablet for controlled systemic delivery of SHCl. Buccal absorption of selegiline can bypass its first-pass metabolism and improve bioavailability accompanied by greatly reduced metabolite formation, which is potentially of enhanced therapeutic value in patients with Parkinson's disease. Polycarbophil-cysteine (PCP-cys) conjugate, which is a thiolated derivative of the mucoadhesive polymer polycarbophil, was synthesized by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride-mediated amide bond coupling. Tablets of SHCl based on native and thiolated polycarbophil were prepared. The prepared tablets were evaluated for drug content, swelling behavior, mucoadhesive strength, in vitro drug release, ex vivo permeation and in vitro cytotoxicity. PCP-cys tablets showed enhanced mucoadhesion and retarded drug release compared to polycarbophil tablets. Permeation data of SHCl from matrices prepared using the PCP-cys polymer revealed a significantly higher value of apparent permeability in comparison to polycarbophil, which supported the information in literature that thiolation imparts permeation enhancing properties to mucoadhesive polymers. In vitro cytotoxicity studies on PCP-cys using L-929 mouse fibroblast cell line indicated that conjugation with cysteine does not impart any apparent toxicity to polycarbophil. The results from the study indicate that the buccal delivery of SHCl using thiolated polycarbophil tablet could provide a way for improved therapy of Parkinson's disease.

Bilayered films based on novel polymer derivative for improved ocular therapy of gatifloxacin.

CONTEXT: Thiomers could prove to be suitable mucoadhesives for fabrication of ocular inserts. OBJECTIVE: The study intends to explore the application of thiolated sodium alginate (TSA) to the preparation of bilayered ocular inserts of gatifloxacin. METHODS: Cysteine moieties were grafted onto sodium alginate (SA) and the resultant thiomer was characterized for relevant physicochemical properties. Bilayered inserts were fabricated with a mucoadhesive immediate release layer composed of either SA or TSA and a sustained release layer composed of acrylates. Films were prepared by solvent evaporation and evaluated for mechanical properties, drug content, and in vitro release. RESULTS AND DISCUSSION: The synthesized TSA possessed 248.80 ± 49.7 µ mol thiol groups/gm and its solutions thickened on standing due to disulphide bridging. Its films showed improved mucoadhesion and also a strikingly beneficial property of resisting erosion and remaining as a hydrated adhesive layer for the duration of drug release. The bilayered films were found to be flexible, with good folding endurance, uniform thickness, and appropriate drug content, and showed a release of about 80% of loaded gatifloxacin in 12 h. CONCLUSION: The study demonstrates promise in employing thiolated polymer in conjunction with acrylates for the design of ocular inserts for twice a day therapy with gatifloxacin.

Design and characterization of chitosan-alginate microspheres for ocular delivery of azelastine.

The use of mucoadhesive biopolymers is one of the best approaches to prolong the drug residence inside the cul-de-sac, consequently increasing the bioavailability. Thus, the focus of this work was to develop mucoadhesive microspheres to overcome the limitations of ocular drug delivery. The chitosan-sodium alginate microspheres of azelastine hydrochloride were fabricated using modified ionotropic gelation technique. The particle size, zeta potential, entrapment efficiency and drug release kinetics were evaluated and characterized by SEM, FT-IR, DSC, in vitro mucoadhesion and in vivo study. The microspheres had average particle size in the range of 3.55 to 6.70 µm and zeta potential +24.55 to +49.56 mV. The fabricated microspheres possess maximum drug entrapment of 73.05% with 65% mucin binding efficiency and revealed a controlled release over the 8-h period following a non-Fickian diffusion. SEM showed that microspheres were distinct solid with irregular shape. FT-IR and DSC results concluded the drug entrapment into microspheres. In vivo studies on ocular rat model revealed that azelastine microspheres had better efficacy. Chitosan sodium alginate microspheres prepared were in particle size range suitable for ocular purpose. In vitro release and in vivo efficacy studies revealed that the microspheres were effective in prolonging the drug's presence in cul de sac with improved therapeutic efficacy.

Preparation and evaluation of chitosan based thermoreversible gels for intraperitoneal delivery of 5-fluorouracil (5-FU).

Sterile thermoreversibly gelling systems based on chitosan- glycerol phosphate were developed for intraperitoneal delivery of the antineoplastic agent 5-FU. The formulation was evaluated for gelling characteristics and in vitro drug release. Drug free gels were evaluated for in vitro cytotoxicity in L-929 mouse fibroblast cells. Drug loaded gels were subjected to acute toxicity studies in Swiss albino mice via intraperitoneal route and efficacy studies via intratumoral injections in subcutaneous colon carcinoma bearing BALB/c mice. The formulations gelled reversibly in 8 min at 37 °C and provided prolonged release of the drug. Drug free systems showed dose dependent cytotoxicity in fibroblast cells, while in vivo studies revealed a 2.8-fold increase in LD50 of 5-FU administered intraperitoneally as the developed system. Tumor volume measurements showed comparable efficacy of 5-FU administered as gel and commercial injection with a greatly improved safety profile of the former as adjudged from mortality and body weight measurements.

Entrapped central venous catheter after mitral valve replacement and its surgical retrieval.

Central venous pressure monitoring line insertion is routine prior to the conduct of cardiac surgery, and in rare instances, malposition can contribute to operative complications. We describe here how a central venous line lying in the right atrium became caught in a left atrial (LA) closure suture during a mitral valve replacement. The opening of the LA suture line is highly unsafe without cardiopulmonary bypass (CPB) because of the possibility of systemic air embolism, but by employing an ingenious method of suturing over and unravelling the continuous sutures closing the left atrium, it was possible to surgically retrieve it without the use of a CPB.

Eudragit RL100 based microspheres for ocular administration of azelastine hydrochloride.

In the present study, potential of polymeric microspheres for treatment of allergic conjunctivitis was investigated. Azelastine hydrochloride loaded Eudragit RL100 microspheres were prepared by solvent evaporation technique. The change in drug-polymer ratio on the particle size, zeta potential, entrapment efficiency and in vitro drug release was investigated. As Eudragit concentration ranged from 40 to 80 mg/ml the size range obtained was 4.18-7.36 µm with positive zeta potential. With the increase in drug polymer ratio, the entrapment efficiency was increased with maximum 14.56%. In vitro release studies demonstrated prolonged release of the drug over the period of 6 hr. Scanning electron micrographs showed that microspheres were spherical with distinct solid dense structure. Fourier transform infrared and differential scanning calorimetry studies concluded slight change in peak intensities of drug in microspheres. In vivo studies in rat model indicated that reduction in eosinophil count number was more pronounced in azelastine hydrochloride microspheres than marketed formulation, Azelast®.

Haemodynamic response to endotracheal intubation in coronary artery disease: Direct versus video laryngoscopy.

Endotracheal intubation involving conventional laryngoscopy elicits a haemodynamic response associated with increased heart and blood pressure. The study was aimed to see if video laryngoscopy and endotracheal intubation has any advantages over conventional laryngoscopy and endotracheal intubation in patients with coronary artery disease. Thirty patients suffering from coronary artery disease scheduled for elective coronary artery bypass grafting (CABG) were studied. The patients were randomly allocated to undergo either conventional laryngoscopy (group A) or video laryngoscopy (group B). The time taken to perform endotracheal intubation and haemodynamic changes associated with intubation were noted in both the groups at different time points. The duration of laryngoscopy and intubation was significantly longer in group B (video laryngoscopy) when compared to group A patients. However, haemodynamic changes were no different between the groups. There were no events of myocardial ischaemia as monitored by surface electrocardiography during the study period in either of the groups. In conclusion, video laryngoscopy did not provide any benefit in terms of haemodynamic response to laryngoscopy and intubation in patients undergoing primary CABG with a Mallampatti grade of <2.

Transesophageal echocardiaography evaluation of thoracic aorta.

Trans-esophageal echocardiaography is a sensitive, minimally invasive, diagnostic tool which gives real time functional image of the aorta. It helps in the diagnosis of pathologies of aorta like atherosclerosis, aneurysm and aortic dissection.

Synthesis of thiolated alginate and evaluation of mucoadhesiveness, cytotoxicity and release retardant properties.

Modification of polymers by covalent attachment of thiol bearing pendant groups is reported to impart many beneficial properties to them. Hence in the present study, sodium alginate-cysteine conjugate was synthesized by carbodiimide mediated coupling under varying reaction conditions and the derivatives characterized for thiol content. The thiolated alginate species synthesized had bound thiol content ranging from 247.8±11.03-324.54±10.107 ΅mol/g of polymer depending on the reaction conditions. Matrix tablets based on sodium alginate-cysteine conjugate and native sodium alginate containing tramadol hydrochloride as a model drug were prepared and mucoadhesive strength and in vitro drug release from the tablets were compared. Tablets containing 75 mg sodium alginate-cysteine conjugate could sustain release of 10 mg of model drug for 3 h, whereas 90% of the drug was released within 1 h from corresponding tablets prepared using native sodium alginate. An approximately 2-fold increase in the minimal detachment force of the tablets from an artificial mucin film was observed for sodium alginate-cysteine conjugate as compared to native sodium alginate. In vitro cytotoxicity studies in L-929 mouse fibroblast cells studied using an MTT assay revealed that at low concentrations of polymer, sodium alginate-cysteine conjugate was less toxic to L-929 mouse fibroblast cell line when compared to native sodium alginate. Hence, thiolation is found to be a simple route to improving polymer performance. The combination of improved controlled drug release and mucoadhesive properties coupled with the low toxicity of these new excipients builds up immense scope for the use of thiolated polymers in mucoadhesive drug delivery systems.

Development and characterization of self-microemulsifying drug delivery system of tacrolimus for intravenous administration.

Tacrolimus (FK 506), a poorly soluble immunosuppressant is currently formulated in nonaqueous vehicle containing hydrogenated castor oil derivative for intravenous administration. Hydrogenated castor oil derivatives are associated with acute anaphylactic reactions. This proposes to overcome the problems of poor aqueous solubility of the drug and the toxicity associated with currently used excipients by the development of a new parenterally acceptable formulation using self-microemulsifying drug delivery system (SMEDDS). Solubility of FK 506 in various oils, surfactants, and cosurfactants was determined to identify SMEDDS components. Phase diagrams were constructed at different ratios of surfactants:cosurfactant (K(m)) to determine microemulsion existence area. Influence of oily phase content, K(m), aqueous phase composition, dilution, and incorporation of drug on mean globule size of microemulsions was studied. SMEDDSs were developed using ethyl oleate as oily phase and Solutol HS 15 as surfactant. Glycofurol was used successfully as a cosurfactant. Developed SMEDDS could solubilize 0.8% (wt/wt) FK 506 and on addition to aqueous phase could form spontaneous microemulsion with mean globule size < 30 nm. The resulting microemulsion was iso-osmotic, did not show any phase separation or drug precipitation even after 24 h, and exhibited negligible hemolytic potential to red blood cells.

Development and validation of HPTLC method for estimation of tacrolimus in formulations.

A new, simple, and rapid high-performance thin-layer chromatographic method with a derivatization procedure was developed and validated for quantitative determination of tacrolimus. Tacrolimus was chromatographed on silica gel 60 F(254) TLC plate using toluene-acetonitrile-glacial acetic acid (6:4:0.1, by volume) as mobile phase. Tacrolimus was visualized using a derivatization reagent containing anisaldehyde-sulfuric acid in absolute alcohol and quantified by densitometric analysis in the reflectance mode at 675 nm. The method was found to give compact spots for the drug (R(f) = 0.40 +/- 0.03). The linear regression analysis data for the calibration plots showed good linear relationship with r(2) = .9989 in the concentration range 100-800 ng/spot. The method was validated for precision, recovery, repeatability, and robustness as per the International Conference on Harmonization guidelines. The minimum detectable amount was found to be 28.90 ng, whereas the limit of quantitation was found to be 97.04 ng. Statistical analysis of the data showed that the method is precise, accurate, reproducible, and selective for the analysis of tacrolimus. The method was successfully employed for the estimation of equilibrium solubility and quantification of tacrolimus as a bulk drug and in commercially available capsules and in-house developed self-microemulsifying formulations.