Inositol 1,4,5-trisphosphate turnover enzymes--activities and subcellular distribution in hepatocarcinogenesis

The metabolism of inositol 1,4,5-trisphosphate and inositol 1,3,4,5- tetrakisphosphate in homogenates and sub-fractions from normal rat liver and premalignant liver nodules was investigated. The activities of 5-phosphatase, expressed as pmol converted substrate per minute and mg protein, were equal when using the two substrates, and did not differ between normal and nodular homogenates. Subcellular fractions were purified by sequential steps of differential centrifugation and density gradient fractionation procedures. The total phosphatase activity was found to be distributed between cytosol (15%) and membraneous fractions (75%), with most of the enzyme activity residing in the plasma membranes. A doubling of phosphatase specific activity was seen in the nodular low density membrane fraction, containing Golgi apparatus and endosomes, as compared with normal liver. Inositol 1,4,5- trisphosphate 3-kinase activity was found to be exclusively cytosolic. No difference in this enzyme was seen between the two tissue types studied. Vasopressin (0.2 or 2 microM) had no effect either on phosphatase or kinase activity. The compartmentalization of inositol polyphosphate 5-phosphatase activity presents a possible explanation of earlier findings that premalignant liver tissue was able to respond with inositol 1,4,5-trisphosphate, but not inositol 1,3,4,5- tetrakisphosphate formation after agonist stimulation.      

A BPA survey of recently appointed consultants

A postal survey of recently appointed consultant paediatricians was undertaken to determine whether they perceived their training had adequately equipped them for their current job. The response rate was 69% (207/299). After excluding replies from consultants trained outside the UK the analysis was carried out on 167 replies. Trainees held a mean 5.2 posts during general and higher professional training, necessitating a mean 1.8 house moves. Altogether 82% felt moves were beneficial to training but 46% found moves 'very disruptive' to family life. Only 12% of district general hospital and 22% of teaching hospital senior registrars took two research sessions a week. Supervision and training in research was absent or poor for more than 60%; 24% felt major changes and 55% moderate changes were needed to current training. Training in non-clinical skills was particularly in demand and a curriculum for both trainers and trainees with regular appraisals is required. Research at senior registrar level needs review and educational methods improved to achieve better training in a shorter period.     

Clonidine added to a continuous interscalene ropivacaine perineural infusion to improve postoperative analgesia: a randomized, double-blind, controlled study

Although clonidine has been shown to increase the duration of local anesthetic action and prolong postoperative analgesia when included in single-injection nerve blocks, the only controlled investigation of the efficacy of this practice to improve analgesia for continuous perineural local anesthetic infusion failed to discern any clinically relevant benefits. For this study, we used a larger dose of clonidine in an attempt to improve analgesia. Patients (n = 20) undergoing moderately painful orthopedic surgery of the shoulder received an interscalene brachial plexus block (40 mL of mepivacaine 1.5%, epinephrine 2.5 microg/mL, and clonidine 50 microg) and a perineural catheter before surgery. After surgery, ropivacaine 0.2% or ropivacaine 0.2% plus clonidine 2 microg/mL was delivered via the catheter for 3 days (basal rate, 5 mL/h; patient-controlled bolus, 5 mL; lockout, 1 h). Investigators and patients were blind to random group assignment. The primary outcome variable was designated as the most intense pain during the day after surgery. Secondary end-points included additional pain scores, patient-controlled bolus doses, oral analgesic use, sleep quality, and catheter- or infusion-related complications. There were no statistically significant differences between groups for any of the variables investigated. We conclude that adding clonidine 2 microg/mL to a ropivacaine interscalene perineural infusion does not decrease breakthrough pain intensity the day after surgery. For the additional end-points, our negative findings are only suggestive of a lack of effect and require further study for verification.     

Gelatin matrix treatment of complex renal injuries in a porcine model

PURPOSE: We developed a complex porcine renal laceration model at our laboratory to test the efficacy of an abbreviated, sutureless treatment regimen using FloSeal gelatin matrix hemostatic sealant (Baxter Healthcare Corp., Fremont, California). We evaluated the influence of preliminary renal arterial occlusion on hemostatic efficacy and assessed the risk of delayed hematoma or urinoma formation after treatment. MATERIALS AND METHODS: A total of 21 commercial swine underwent celiotomy with creation of a complex upper pole renal injury using a 4 x 4 cm cruciate press instrument. The injury was uniformly produced at the caudal extent of the upper third portion of the left kidney. Subjects were prospectively randomized into 3 treatment groups. Experimental animals were treated with the application of gelatin matrix with (7 in group 1) or without (7 in group 2) preliminary renal arterial occlusion. Control subjects (7 in group 3) were treated with conventional horizontal mattress sutured gelatin sponge bolsters over the capsular injury. Operative blood loss, time to hemostasis and volume of gelatin matrix required for hemostasis were compared among the groups. Abdominal computerized tomography with intravenous contrast medium was performed in each animal 7 days postoperatively. RESULTS: Gelatin matrix use resulted in significantly less mean blood loss (80.7 and 99.0 ml in groups 1 and 2, respectively) vs conventional suture treatment (191.8 ml in group 3, p = 0.036). Time to hemostasis was similarly decreased (1.1, 2 to 2.5 and 5.8 minutes in groups 1 to 3, respectively, p = 0.009). Followup abdominal computerized tomography with contrast medium revealed no clinically significant perinephric fluid collections (greater than 2 cm). CONCLUSIONS: FloSeal gelatin matrix hemostatic sealant provided effective hemostasis after complex renal injury with and without preliminary vascular control. No delayed bleeding or clinically significant urinoma formation was noted. These findings suggest a possible increased role for FloSeal gelatin matrix in renal salvage surgery.     

Role of weight history on functional limitations and disability in late adulthood: the ARIC study

OBJECTIVE: To examine associations of weight history with functional limitations and disability in white and African-American men and women. RESEARCH METHODS AND PROCEDURES: Data were from the Atherosclerosis Risk in Communities study (n = 11,177). Associations of recalled weight status at age 25 and weight change from age 25 to ages 45 to 64 with functional limitations, activities of daily living (ADLs), and instrumental activities of daily living (IADLs) at follow-up (ages 52 to 75) were examined using logistic regression. RESULTS: Obesity (BMI > or = 30 kg/m2) at age 25 was associated with functional limitations and ADL and IADL impairment at follow-up in white and African-American men and women. For example, obese compared with normal weight (BMI, 18.5 to 24.9 kg/m(2)) white women had higher odds of mild [odds ratio (95% confidence interval), 1.97 (1.18 to 3.29)] and severe [9.81 (5.92 to 16.27)] functional limitations and ADL [3.48 (2.36 to 5.13)] and IADL [2.95 (2.00 to 4.33)] impairment. In African-American women, obesity was associated with higher odds of mild [2.71 (1.14 to 6.41)] and severe [6.01 (2.53 to 14.26)] functional limitations and ADL [1.82 (1.10 to 3.00)] and IADL [2.39 (1.47 to 3.90)] impairment. Similar associations were found in men. Compared with weight maintenance (+/-10 lbs), large weight gain (>30 lbs) from age 25 to ages 45 to 64 was also associated with functional limitations and ADL and IADL impairment in white and African-American men and women. DISCUSSION: Maintenance of a healthy body weight throughout adulthood may play a role in preventing or delaying the onset of functional limitations and disability, resulting in increased quality of life and decreased health care costs.