Stapedotomy: does prosthesis diameter affect outcome?

Two hundred ears with otosclerosis have been operated upon using a 0.4-mm diameter Teflon platinum piston in 100 ears and a 0.6-mm diameter Teflon piston in the other 100 ears. The postoperative air-bone gap, calculated as the difference between the postoperative air and bone conduction levels, was smaller in the 0.6 mm group for all frequencies except at 2000 Hz, the differences were statistically insignificant except at 4000 Hz. The mean postoperative air-bone gap was 8.6 dB and 7.4 dB for the 0.4 and 0.6 mm groups, respectively, which is statistically insignificant. We found no postoperative loss of bone conduction exceeding 15 dB, there was a deterioration of more than 10 dB in three ears, one in the 0.4 mm group and two in the 0.6 mm group. According to our results, we conclude that the 0.4 mm and the 0.6 mm Teflon prostheses produce the same hearing improvement in stapes surgery for otosclerosis.     

The association between hospital readmission and insurance provider among adults with asthma.

CONTEXT: Asthma is ranked as the ninth most common chronic condition in the U.S., and its annual direct costs from hospital services alone are estimated at $3.1 billion. Hospitalization rates due to asthma reveal several disparities and may be attributed to recent changes in the healthcare delivery system, including the penetration of managed care. OBJECTIVE: To examine the relationship between 7-day hospital readmission and insurance provider among adults with asthma. DDESIGN: A retrospective cohort study that included patients aged 18-64 with a principal diagnosis of asthma, who were discharged from acute nonfederal hospitals in New Jersey between 1 January 1993 and 31 December 1996. In the absence of unique patient identifiers, a linkage system was used to match subsequent readmissions for the same patient to the first admission. MMAIN OUTCOME MEASURE: Seven-day readmission. RESULTS: Results showed a significantly increased risk of 7-day readmission for managed care patients as compared to indemnity patients (OR= 1.67, 1.10-2.53). Shorter lengths of stay were associated with greater odds of readmission (LOS=0: OR=5.17, 2.49-10.75, LOS=1: OR=2.30, 1.30-4.07). CONCLUSIONS: Managed care patients have shorter lengths of stay as compared to indemnity patients, which leads to an increased risk of returning to the hospital within a short period of time. In trying to provide cost-effective patient care, we may be discharging patients prematurely.     

Experimental studies of tumor radioimmunodetection using antibody mixtures against carcinoembryonic antigen (CEA) and colon-specific antigen-p (CSAp)

Experiments with the GW-39 human colonic carcinoma growing in hamsters showed that injection of radioactive antibody to a colorectal-specific, tumor-associated antigen, CSAp, results in better tumor radiolocalization than was seen previously with radioantibodies to carcinoembryonic antigen (CEA). However, a mixture of both radioactive antibodies resulted in potentiation of CEA-tumor radioimmunodetection without affecting CSAp-tumor radiolocalization. Hence, multi-marker antibody mixtures may be the method of choice in cancer radioimmunodetection.     

Change in velocity and energy dissipation on impact in motor vehicle crashes as a function of the direction of crash: key factors in the production of thoracic aortic injuries, their pattern of associated injuries and patient survival. A Crash Injury Research Engineering Network (CIREN) study

OBJECTIVE: To examine the effect of change in velocity (MV) and energy dissipation (IE) on impact, above and below the test levels for federal motor vehicle crash (MVC) safety standards, on the incidence of aortic injury (AI) and its mortality and associated injury patterns in frontal (F) and lateral (L) MVCs. Comparison of 80 AI and 796 non-AI patients of AIS=3. METHODS: Eight hundred seventy-six MVC adult drivers or front-seat passengers (552 F and 324 L) evaluated by 10 Level I CIREN study Trauma Centers together with vehicle and crash scene engineering reconstruction. Patient seatbelt and/or airbag use correlated with clinical or autopsy findings. RESULTS: In AI, 63% of cases were dead at the scene and only 16% survived to leave hospital. The relation between IE dissipated in the MVC and the DeltaV on impact was exponential as DeltaV increased, but the rise in IE for a given DeltaV was greater in LMVC than in FMVC (p <0.05). A more rapid rise in IE/DeltaV occurred above the mean DeltaV of 48 +/- 19.7 kph (30 mph) in FMVC and above the mean DeltaV of 36 +/- 16.2 kph (23 mph) in LMVC. As DeltaV increased above these means, 65% of 46 FMVC aortic injuries (AIs) and 64% of 34 LMVC AIs occurred. In AI patients there was evidence of focusing of the point of IE impact on the upper chest with a higher incidence of rib1-4 fractures than in non-AI (p <0.01) and more brain, heart, lung and spleen injuries (p <0.01) consequent to lower seatbelt use (p <0.01), but LMVC also had more pelvic fx (p <0.05). Airbags + seatbelts in FMVC and seatbelts in LMVC reduced mortality (p <0.05) Comparison of AI incidence in three successive 4-year vehicle model year periods showed a progressive decrease as new safety devices were introduced (p < 0.05). CONCLUSIONS: The implications for AI of the focused IE at the upper chest suggest a probable mechanism for MVC AI with the pressurized aortic arch acting as the long arm of a lever system with the fulcrum at the subclavian artery, producing maximum torsional strain at the short arm of the isthmus where 75% of the AIs occurred. AI mortality is also influenced by the associated injuries. To develop more effective safety systems to prevent AI, MVC safety testing with airbags and seatbelts should be carried out at DeltaVs of 1 SD above means for FMVC and LMVC.     

Effect of monensin liposomes on the cytotoxicity of anti-My9-bR immunotoxin

The purpose of the study was to evaluate the utility of monensin liposomes in the enhancement of in-vitro cytotoxicity, apoptosis and in-vivo antitumour activity of anti-My9-bR immunotoxin. Monensin liposomes were prepared and studied for the enhancement of in-vitro cytotoxicity and apoptotic response of anti-My9-bR immunotoxin against both sensitive and resistant human promyelocytic leukemia HL-60 cells by MTS/PES method and acridine orange staining, respectively. Further, the in-vivo cytotoxicity enhancement of anti-My9-bR immunotoxin by monensin liposomes was studied in a survival model of severe combined immunodeficient (SCID) mice bearing intraperitoneal HL-60 tumours. The in-vitro cytotoxicity of anti-My9-bR immunotoxin was enhanced 580 fold and 4.7 fold against sensitive and resistant HL-60 cells, respectively, by monensin liposomes (5 x 10(-8) M). The combination of anti-My9-bR immunotoxin (50ng mL(-1)) with monensin liposomes (5 x 10(-8) M) produced apoptosis in 40% of cells, whereas the apoptotic response was minimal (< 10%) in anti-My9-bR immunotoxin- or monensin liposome (alone)-treated HL-60 (resistant) cells. In SCID mice bearing HL-60 tumours, anti-My9-bR immunotoxin (75 microg kg(-1) administered intravenously every other day for a total of five courses) showed a median survival time of 20 days, which was no different than that of vehicle control- or monensin liposome-treated mice. However, anti-My9-bR immunotoxin (75 microg kg(-1)) in combination with monensin liposomes (4 microg kg(-1) monensin), administered every other day for a total of five courses, was found to prolong the survival of 20% of mice for more than 46 days. Our results indicate that, despite anti-My9-bR immunotoxin being ineffective in the HL-60 tumour model, its combination with monensin liposomes could improve the antitumour response.     

Effect of pendimethalin on growth and photosynthetic activity of Protosiphon botryoides in different nutrient states

The effect of pendimethalin on the green alga Protosiphon botryoides was investigated. Results indicate that specific growth rate, cell number, chlorophyll a level, and dry weight yield significantly decrease with increasing pendimethalin concentrations, while protein and carbohydrate contents increase significantly. On the other hand, photosynthetic activity decreases whereas dark respiration increases with high pendimethalin concentrations. High doses of pendimethalin exhibited no clear trend with 77 K fluorescence (Fv/Fm). Increasing nitrate and phosphate levels led to a decrease in cell number, chlorophyll a, and dry weight as compared with the control at high doses of pendimethalin. The results obtained revealed that N:P < 1 increases the inhibitory effect of high doses of the herbicide.     

Synthesis,biological evaluation,and molecular modeling of (<Emphasis Type="Italic">E</Emphasis>)-2-aryl-5-styryl-1,3,4-oxadiazole derivatives as acetylcholine esterase inhibitors

A library of 2,5-disubstituted 1,3,4-oxadiazole derivatives of (E)-2-aryl-5-(3,4,5-trimethoxystyryl)-1,3,4-oxadiazoles 4(a–o) and (E)-2-aryl-5-(2-benzo[d][1,3]dioxol-5-yl)vinyl)-1,3,4-oxadiazoles 5(a–q) were synthesized and evaluated for their in vitro acetylcholinesterase (AChE) inhibitory activity. All the synthesized compounds exhibited moderate to good inhibitory activity toward the AChE enzyme. Among the oxadiazole derivatives examined, compounds 4a, 4g, 5c, and 5m (IC₅₀ values of 24.89, 13.72, 37.65, and 19.63 μM, respectively) were found to be promising inhibitors of AChE. Molecular protein–ligand docking studies were examined for these compounds using GOLD docking software and their binding conformations were determined and the simultaneous interactions mode was also established for the potent derivatives.     

Population pharmacokinetics of gliclazide in normal and diabetic rabbits

Gliclazide is a second‐generation sulphonylurea drug widely used in the treatment of type 2 diabetes. However, there is no single report to describe the population pharmacokinetics of gliclazide in animal models. This study was aimed to evaluate the population pharmacokinetics (PK) of gliclazide in normal and alloxan‐induced diabetic rabbits using nonlinear mixed effects modeling. A total of 90 New Zealand white rabbits were administered with three doses (4.13, 8.27 and 16.53 mg/kg b.wt) of gliclazide by an oral route. Blood samples were collected up to 24 hr and the gliclazide concentrations in rabbit were determined using the HPLC method. The non‐compartmental and classical compartmental PK analyses were performed using Phoenix WinNonlin. Population PK analysis of gliclazide was performed using nonlinear mixed‐effects model software NONMEM and Phoenix NLME considering the weight, age, sex, health and dose as covariates. The final population values for clearance (CL), volume of distribution (V) and the absorption rate constant (k_a) were 5270 ml/hr, 55700 ml and 0.708 hr^?1, respectively. The inter‐individual variability in gliclazide CL, V and k_a was 16.3%, 14.9% and 26.5%, respectively. There was no significant difference between NONMEM and Phoenix NLME pharmacokinetic results. The visual predictive check and bootstrap analysis confirmed the predictive ability, model stability and precision of the parameter estimates from this model. This population PK model demonstrated that gliclazide pharmacokinetics is best described by one‐compartment model with first‐order absorption in rabbits. Body weight is a covariate that significantly influences gliclazide kinetic disposition in rabbits.     

Effects of Hepatic Ischemia-Reperfusion Injury on the P-Glycoprotein Activity at the Liver Canalicular Membrane and Blood–Brain Barrier Determined by In Vivo Administration of Rhodamine 123 in Rats

Purpose

To investigate the effects of normothermic hepatic ischemia-reperfusion (IR) injury on the activity of P-glycoprotein (P-gp) in the liver and at the blood–brain barrier (BBB) of rats using rhodamine 123 (RH-123) as an in vivo marker.

Methods

Rats were subjected to 90 min of partial ischemia or sham surgery, followed by 12 or 24 h of reperfusion. Following intravenous injection, the concentrations of RH-123 in blood, bile, brain, and liver were used for pharmacokinetic calculations. The protein levels of P-gp and some other transporters in the liver and brain were also determined by Western blot analysis.

Results

P-gp protein levels at the liver canalicular membrane were increased by twofold after 24 h of reperfusion. However, the biliary excretion of RH-123 was reduced in these rats by 26%, presumably due to IR-induced reductions in the liver uptake of the marker and hepatic ATP concentrations. At the BBB, a 24% overexpression of P-gp in the 24-h IR animals was associated with a 30% decrease in the apparent brain uptake clearance of RH-123. The pharmacokinetics or brain distribution of RH-123 was not affected by the 12-h IR injury.

Conclusions

Hepatic IR injury may alter the peripheral pharmacokinetics and brain distribution of drugs that are transported by P-gp and possibly other transporters.