Distal Revascularization and Interval Ligation as a Useful Option for Steal Syndrome.

Distal revascularization and interval ligation (DRIL) is considered a useful option to relieve haemodialysis access-related steal syndrome. The results of this procedure are not known in the local setup. This is a case series of patients who underwent DRIL between January 2005 and December 2015. A total of ten patients (9 females) were included in the study. All the patients presented with grade 3 steal syndrome. Seven patients had rest pain while three had tissue loss. Polytetrafluoroethylene was used in all patients as the brachio-brachial bypass graft. All patients had smooth recovery except one patient who had postoperative brachio-brachial graft thrombosis and required thrombectomy. In all the cases, access was preserved. Steal symptoms resolved completely in all patients except for two, who had partial relief of rest pain and neurological symptoms. DRIL is a safe and effective procedure for resolution of steal syndrome and in preserving access at the same time.

Sequential scapholunate and volar beak ligament reconstructions with flexor carpi radialis tendon grafts.

The flexor carpi radialis tendon is considered by many the workhorse tendon in hand and wrist surgery. Some have expressed concerns about altering the mechanics of the wrist by sacrificing part or all of the flexor carpi radialis tendon. We present an interesting case of sequential scapholunate and volar beak ligament reconstructions using a flexor carpi radialis tendon autograft where a slip of tendon was harvested twice within three years, achieving a satisfactory clinical outcome at five years following the initial surgery.

Formulation and process considerations for beads containing Carbopol 974P, NF resin made by extrusion-spheronization.

Preliminary studies revealed that Carbopol 974P, NF resin could be incorporated into beads manufactured by extrusion and spheronization, and can slow the release of a highly water soluble drug if calcium chloride was included in the granulating fluid to reduce the tack of the wetted polymer. In this study, the same approach was used to produce high quality chlorpheniramine maleate beads with a prolonged release duration. Because of the complex nature of the extrusion and spheronization process and the various components in the bead formulations, a statistically sound factorial experiment was considered for this study. A one-half fraction of a two level factorial design with three center points was employed to estimate the effects of simultaneously modifying multiple process and formulation variables, including the Carbopol concentration, calcium chloride concentration, water content, and the spheronization speed and time. Product yield, average bead roundness, and the drug release profile were selected as responses. Increasing the Carbopol content across the experimental range resulted in a significant (P<0.05) reduction in the percentage drug released at 25, 40, and 60 min. Results suggest that combining the conditions of high Carbopol, high water, and low calcium chloride levels with low spheronization speeds at long spheronization times produce the highest quality bead with the longest drug release duration.

Intravenous chloroprocaine attenuates hemodynamic changes associated with direct laryngoscopy and tracheal intubation.

We compared the effects of an IV administration of chloroprocaine and lidocaine on circulatory responses associated with endotracheal intubation. Thirty patients were randomly allocated to receive normal saline (placebo), lidocaine (1.5 mg/kg), or preservative-free chloroprocaine (4.5 mg/kg) 45 s before endotracheal intubation. Blood pressures and heart rate and rhythm were recorded before laryngoscopy and at 0.5, 1, 1.5, 2, 3, and 5 min after intubation. Blood samples were analyzed for catecholamine and chloroprocaine concentrations. Chloroprocaine reduced increases in blood pressure in response to intubation when compared with patients receiving normal saline and lidocaine. Systolic blood pressures at 0.5 and 1 min after intubation were significantly lower in the chloroprocaine group when compared with both the control and lidocaine groups (P < 0.05). Diastolic and mean blood pressures were significantly lower in the chloroprocaine group at all time points until 5 min after intubation (P < 0.05). Chloroprocaine and, to a lesser degree, lidocaine, produced marked attenuation of intubation-induced increases in plasma concentration of epinephrine and norepinephrine. Plasma concentrations of norepinephrine were significantly smaller in the chloroprocaine group at 0.5, 1, and 1.5 min, and plasma concentrations of epinephrine were significantly smaller at 0.5 after intubation when compared with control and lidocaine groups (P < 0.05). Measurable concentrations of chloroprocaine were recorded in plasma samples for 2 min after its administration. No adverse chloroprocaine effects (i.e., circulatory disturbances, venous irritation) were detected. The IV administration of chloroprocaine effectively blunted cardiovascular response produced by laryngoscopy and endotracheal intubation, and this effect was more pronounced when compared with IV lidocaine.

Cataplasm-based controlled drug delivery: development and optimization of a novel formulation.

The objective of the present study was to study the formulation variables involved in the development of a novel plasterlike preparation (cataplasm) and to optimize important formulation variables with an aim to maximize the in vitro release of the drug with minimum lag time. Cataplasm was prepared by dispersing a model drug (ibuprofen), humectant (glycerol), adhesive (Indopol H100), polymer (Carbopol C934P) with other formulation ingredients in a beaker with an open-blade impeller. The paste was cast on a nonocclusive backing membrane and dried overnight. The diffusion of the model drug was studied across a cellulosic membrane using Franz's diffusion cells. The amounts of three formulation variables, carbopol (X1), glycerol (X2), and indopol (X3) were studied at three levels, and a face-centered cubic design was used to maximize the flux. An optimization procedure for maximum flux and minimum lag time predicted a flux of 97.22 mcg/cm2/hr at X1 (2% w/w), X2 (11.75% w/w), and X3 (6%, w/w). An experimental patch prepared with the above concentrations yielded a flux of 90.7 mcg/cm2/hr.

Solid-state stability assessment of controlled release tablets containing Carbopol 971P.

A tablet formulation containing dyphylline, Carbomer, magnesium stearate, talc and lactose was prepared by the direct compression method. The objective of the study was to assess the stability of these tablets after subjecting them to exaggerated conditions of temperature (4, 25, 37, 45 and 55 degrees C) and humidity (37 degrees/11%RH, 37 degrees/51%RH and 37 degrees C/91%RH). The samples were analyzed for crystalline, thermal and dissolution changes with time for a period of 12 months using X-ray diffractometry (XRD), differential scanning calorimetry (DSC) and U.S.P. Dissolution Apparatus 2. Moisture sorption studies of all tablets indicated sorption of large amounts of moisture at 37 degrees C/91%RH. The fit factors, f1 andf2, were calculated and used to compare the dissolution profiles. The results showed increased f1 and decreased f2 values at higher humidity, while the samples were fairly stable at lower humidity and at all temperatures studied. Powder XRD patterns of tablets showed a change in crystallinity at higher humidity. The thermal and crystalline data indicated that the change in dissolution behavior at higher humidity may be due to the conversion of dyphylline to its hydrate form.

Effect of permeation enhancers on the release of ketoprofen through transdermal drug delivery systems.

Feasibility studies were performed to prepare membrane controlled transdermal drug delivery system of ketoprofen containing Carbopol 934p gels. The ability of permeation enhancers such as oleic acid, polyethylene glycol 400 and propylene glycol to provide improved performance has been investigated. The variables studied were drug loading, type of the permeation enhancers, and their concentration. Diffusion studies across Spectra/por 1 membranes were performed using Franz diffusion cells. The medium employed was pH 7.4 phosphate buffer. The permeation parameters such as flux, enhancement ratio, permeation and diffusion coefficients have been evaluated. The results indicated a zero or near zero-order release kinetics. The studies indicated that oleic acid in a concentration of 35% w/w provided the maximum permeation when the ketoprofen concentration in the patches was 5%. Corresponding values of flux,enhancement ratio, permeability and diffusion coefficients were 6.22 micrograms/cm2/h, 8.57, 1.09 x 10(-3) cm/h, and 3.13 x 10(-6) cm3/h respectively. Further, an increase in ketoprofen loading from 5 to 10% increased the permeation.

Tissue engineering science: consequences of cell traction force.

Blood and tissue cells mechanically interact with soft tissues and tissue-equivalent reconstituted collagen gels in a variety of situations relevant to biomedicine and biotechnology. A key phenomenon in these interactions is the exertion of traction force by cells on local collagen fibers which typically constitute the solid network of these tissues and gels and impart gross mechanical integrity. Two important consequences of cells exerting traction on such collagen networks are first, when the cells co-ordinate their traction, resulting in cell migration, and second, when their traction is sufficient to deform the network. Such cell-collagen network interactions are coupled in a number of ways. Network deformation, for example, can result in net alignment of collagen fibers, eliciting contact guidance, wherein cells move with bidirectional bias along an axis of fiber alignment, potentially leading to a nonuniform cell distribution. This may govern cell accumulation in wounds and be exploited to control cell infiltration of bioartificial tissues and organs. Another consequence of cell traction is the resultant stress and strain in the network which modulate cell protein and DNA synthesis and differentiation. We summarize, here, relevant mathematical theories which we have used to describe the inherent coupling of cell dynamics and tissue mechanics in cell-populated collagen gels via traction. The development of appropriate models based on these theories, in an effort to understand how events in wound healing govern the rate and extent of wound contraction, and to measure cell traction forces in vitro, are described. Relevant observations and speculation from cell biology and medicine that motivate or serve to critique the assumptions made in the theories and models are also summarized.

Design of 9-beta-D-arabinofuranosyladenine (ara-A) transdermal delivery system for animal studies: regulation of drug concentration in vivo.

Transdermal delivery systems of 9-beta-D-arabinofuranosyladenine (ara-A), having controlling membranes of various permeabilities, were developed and applied to Azone-pretreated hairless mouse abdominal skin. It was confirmed that the blood concentrations of ara-A and its metabolite 9-beta-D-arabinofuranosylhypoxanthine (ara-H) in hairless mice are controlled by the permeability of the controlling membrane in the transdermal patch. Furthermore, these blood concentrations were found to closely agree with the values obtained from theoretical model calculations. Finally, but importantly, the "micropharmacokinetic" behavior of ara-A in cutaneous tissue could also be predicted. These results suggest that the transdermal patch may be employed in dermal and transdermal ara-A efficacy studies in the treatment of cutaneous herpes virus infections in hairless mice.

Bioavailability of N-acetylprocainamide from mixed diet in rats.

The purpose of this study was to determine the bioavailability of N-Acetylprocainamide (NAPA) from mixed diet in rats. Six groups of 8 male Charles River CD rats received NAPA-HCl as follows: Group I, an intravenous dose (mean 21 mg) of 14C-labelled drug. Group II, in a solution given by oral gavage with and without feed (50 mg) in a two-way crossover fashion. Groups III-VI, incorporated in diet (42-68 mg). Urine and feces were collected for 48 hours and assayed for NAPA and procainamide by a specific HPLC method. On the average, 73% of the drug was eliminated unchanged in urine. Only a small percentage (3-4%) of the intact drug was recovered in feces after intravenous or oral administration. There were no detectable levels of procainamide in urine and feces. The absolute bioavailability of NAPA from oral solution with and without feed was 87 and 90%, respectively, and from the mixed diet was 84-92%. There was no statistically significant difference between the bioavailability of NAPA from solution in fasted and fed rats or from NAPA-mixed diet, indicating that the absorption of the drug in rats was not affected by food. The relative bioavailability of the drug from mixed diet ranged from 94-103%.

Pharmacokinetics of procainamide and N-acetylprocainamide in rats.

The pharmacokinetics of distribution and elimination of procainamide and its major metabolite, N-actylprocainamide, were studied in rats. Eight rats were selected randomly, and each received intravenously 14C-labeled procainamide hydrochloride (75 mg/kg) or 14C-labeled N-acetylprocainamide hydrochloride (86 mg/kg) according to a two-way crossover design. Serial blood samples were withdrawn for 8 hr, and cumulative urine and feces were collected for 48 hr. The plasma concentration-time relationships of procainamide and N-acetylprocainamide were characterized by one- and two-compartment open models, respectively. A pseudo-three-compartment model was necessary to characterize the time course of N-acetylprocainamide in plasma formed after administration of procainamide. The biological half-lives of procainamide and N-acetylprocainamide averaged 0.66 and 2.1 hr, respectively. The urinary excretion profiles of these drugs and the ratio of their biological half-lives in rats were similar to those in humans.