The different effect of pioglitazone as compared to insulin on expression of hepatic and intestinal genes regulating post-prandial lipoproteins in diabetes.

This study investigates lipoprotein composition in diabetes before and after treatment with insulin or pioglitazone and its relationship to gene expression of five genes found in liver and intestine which are involved in cholesterol homeostasis. Thirty zucker diabetic fatty fa/fa and 10 lean rats were examined. mRNA for 3-hydroxy3-methylglutaryl coenzyme A reductase (HMGCoA), microsomal triglyceride transfer protein (MTTP), Niemann Pick C1-like 1 (NPC1L1) and ATP binding cassette transporters (ABC) G5 and G8 was determined using real-time, reverse transcriptase (RT-PCR). Cholesterol, triglyceride, apo B48 and apo B100 were elevated in chylomicrons and very low density lipoproteins (VLDL) of untreated diabetic animals (p<0.02). For similar blood glucose pioglitazone was more effective than insulin in normalising the lipoproteins. In diabetic animals, HMGCoA reductase, MTTP and NPC1L1 mRNA were significantly elevated (p<0.02) and ABCG5 and ABCG8 were significantly reduced (p<0.02) in the liver. Pioglitazone significantly reduced hepatic MTTP and NPC1L1 mRNA (p<0.0001) and significantly increased ABCG5 and G8 mRNA (p<0.0001) as compared to insulin. In conclusion diabetes was associated with major changes in mRNA levels of proteins involved in the regulation of post-prandial lipoproteins. Pioglitazone and insulin have different effects on post-prandial lipoprotein metabolism in part due their effect on genes regulating cholesterol synthesis and lipoprotein assembly.

Messenger RNA levels of genes involved in dysregulation of postprandial lipoproteins in type 2 diabetes: the role of Niemann-Pick C1-like 1, ATP-binding cassette, transporters G5 and G8, and of microsomal triglyceride transfer protein.

AIMS/HYPOTHESIS: The aim of the present study was to examine the relationship between chylomicron composition and expression of genes that regulate chylomicron production in the intestine. We examined expression of the following: (1) Niemann-Pick C1-like 1 (NPC1L1), which regulates cholesterol absorption; (2) ATP-binding cassette transporters G5 and G8 (ABCG5, ABCG8), which regulate cholesterol homeostasis through their ability to excrete enterocyte cholesterol back into the lumen of the intestine; and (3) microsomal triglyceride transfer protein (MTTP), which packages the chylomicron particle by assembling cholesterol, triglyceride, phospholipids and apolipoprotein B48. SUBJECTS, MATERIALS AND METHODS: Type 2 diabetic (26) and non-diabetic (21) patients were examined. Levels of NPC1L1, ABCG5 and ABCG8 and MTTP mRNA were measured in duodenal biopsies by real-time PCR. Lipoproteins were isolated by sequential ultracentrifugation. RESULTS: Diabetic patients had more NPC1L1 mRNA than the control subjects (p<0.02). Expression of ABCG5 and ABCG8 mRNA was lower in the diabetic patients (p<0.05) and MTTP expression was increased (p<0.05). There was a positive correlation between NPLC1L1 and MTTP mRNA (p<0.01) and a negative correlation between NPC1L1 and ABCG5 mRNA (p<0.001). Diabetic patients on statin therapy had increased ABCG5 and ABCG8 mRNA compared to those not on statin (p<0.02 and p<0.05) and less MTTP mRNA than those not on statin (p<0.05). CONCLUSIONS/INTERPRETATION: This study demonstrates that in type 2 diabetes there are important alterations to the expression of intestinal genes that regulate cholesterol absorption and chylomicron synthesis. In diabetic patients statin therapy is associated with reduced MTTP expression and increased ABCG5 and ABCG8 mRNA. The study suggests new mechanisms to explain postprandial diabetic dyslipidaemia and the beneficial effect of statins.

Should human figure drawings be admitted into court?

In recent years, there has been debate about the validity of figure drawings, although surveys of clinicians in both general and forensic practice still find them to be one of the most widely used tests of personality functioning. Using both Heilbrun's (1992) guidelines for the use of psychological tests in a forensic evaluation and the U.S. Supreme Court's Daubert v. Merrell Dow Pharmaceuticals, Inc. (1993) criteria for the admission of scientific evidence, I examine the admissibility of human figure drawings in court. The results suggest that the most commonly used methods for interpreting human figure drawings fall short of meeting the standards for admissibility. The use of overall rating scales, although weak in validity, appear to minimally meet these standards.

An investigation into the functions of nurses' communication at the inter-shift handover.

AIMS: This study set out to investigate the functions of nurses' communication at the inter-shift handover. BACKGROUND: The inter-shift handover should facilitate continuity in care by transferring patient information between shifts. However, nurses may also use this time for team building. METHODS: An observational study was conducted during six inter-shift handovers occurring on one ward in a general hospital in the UK. The data was transcribed and a thematic analysis applied. FINDINGS: The main themes related to the transfer of patient information and team building, the strongest theme being team building. Nurses were found to communicate goals and values relating to nursing practice so facilitating cohesiveness of the nursing team. CONCLUSIONS: The nursing ritual of inter-shift handover serves the purpose of enhancing a shared value system amongst nurses. It should therefore not be regarded as an outdated means of communication.

Preemptive epidural analgesia and recovery from radical prostatectomy: a randomized controlled trial.

CONTEXT: Preemptive analgesia can decrease the sensitization of the central nervous system that would ordinarily amplify subsequent nociceptive input, but a clear demonstration of its clinical efficacy is necessary for it to become a routine component of acute pain therapy. OBJECTIVE: To determine the impact of preemptive epidural analgesia on postoperative pain and other clinically important outcome variables after radical retropubic prostatectomy. DESIGN AND SETTING: A block randomized double-blind clinical trial lasting 20 months at a single academic medical center. PATIENTS: A total of 100 generally healthy and neurologically intact patients scheduled for radical retropubic prostatectomy for the treatment of prostate cancer in whom an epidural catheter for treating postoperative pain was to be placed prior to the induction of general anesthesia. INTERVENTIONS: Epidural bupivacaine, epidural fentanyl, or no epidural drug was administered prior to induction of anesthesia and throughout the entire operation, followed by aggressive postoperative epidural analgesia for all patients. MAIN OUTCOME MEASURES: Daily pain scores during hospitalization and pain scores obtained 3.5, 5.5, and 9.5 weeks after hospital discharge. RESULTS: The patients who received epidural fentanyl or bupivacaine prior to surgical incision (preemptive analgesia) experienced 33% less pain while hospitalized (P=.007). Pain scores in those receiving preemptive analgesia were significantly lower at 9.5 weeks (P=.02), but were not significantly different at 3.5 or 5.5 weeks. At 9.5 weeks, 32 (86%) of 37 patients receiving preemptive analgesia were pain-free compared with 9 (47%) of 19 control patients (P=.004). Patients receiving preemptive analgesia were more active 3.5 weeks after surgery (P=.01), but not at 5.5 or 9.5 weeks. CONCLUSIONS: Even in the presence of aggressive postoperative pain management, preemptive epidural analgesia significantly decreases postoperative pain during hospitalization and long after discharge, and is associated with increased activity levels after discharge.

Survey of 520 eyes with uveal metastases.

OBJECTIVE: The purpose of this investigation is to report the clinical features of patients with uveal metastases seen at a major ocular oncology center. DESIGN/PARTICIPANTS: A retrospective chart review was performed on all patients with uveal metastases evaluated at an ocular oncology outpatient facility over a 20-year period. MAIN OUTCOME MEASURE: To assess the systemic and ophthalmic features of uveal metastases. RESULTS: A total of 950 uveal metastases were diagnosed in 520 eyes of 420 consecutive patients. Of the 950 metastatic foci, the uveal involvement included iris in 90 (9%), ciliary body in 22 (2%), and choroid in 838 (88%). The total number of uveal metastases per eye was 1 (71%) in 370 eyes, 2 (12%) in 63 eyes, and 3 or more (17%) in 87 eyes. The mean number of uveal metastases per eye was two (median, one). Iris metastases presented most often as a yellow-to-white solitary nodule in the inferior quadrant. Ciliary body metastases typically presented as a solitary, sessile, or dome-shaped yellow mass in the inferior quadrant, but were difficult to visualize directly. The choroidal metastases typically were yellow in color, plateau shaped, and associated with subretinal fluid. In the 479 eyes with choroidal metastases, the epicenter of the main tumor was found in the macular area in 59 eyes (12%), between the macula and equator in 383 eyes (80%), and anterior to the equator in 37 eyes (8%). The mean size of the main (largest) choroidal tumor in each eye was 9 mm in base and 3 mm in thickness. At the time of ocular diagnosis, 278 patients (66%) reported a history of a primary cancer and 142 patients (34%) had no history of a cancer. Subsequent evaluation of these 142 patients after the ocular diagnosis of uveal metastasis showed a primary tumor in the lung in 50 patients (35%), breast in 10 (7%), others in 9 (6%), and no primary site was found in 73 patients (51%). Nearly half of the patients with no known primary site eventually died of diffuse metastatic disease. In the entire group of 420 patients, the uveal metastasis came from a primary cancer of the breast in 196 (47%), lung in 90 (21%), gastrointestinal tract in 18 (4%), kidney in 9 (2%), skin in 9 (2%), prostate in 9 (2%), and other cancers in 16 (4%). In 73 cases (17%), the primary site was never established despite systemic evaluation by medical oncologists. CONCLUSIONS: Iris, ciliary body, and choroidal metastases have typical clinical features that should suggest the diagnosis. The choroid is the most common site for uveal metastases, and the tumors occur most often in the posterior pole of the eye with an average of two tumors per eye. Approximately one third of patients have no history of primary cancer at the time of ocular diagnosis. Breast and lung cancers represent more than two thirds of the primary tumor sites.

"Does being in here mean there is something wrong with me"?

Much of what has been written about how psychiatric hospitals change a patient's self-image has been written from the perspective of the hospital and related social forces. Little has been done to explain the patient's perspective and role in this process. This study examines the process from that essential perspective, using both qualitative and quantitative methods. The results suggest that both frequency and duration of exposure to psychiatric hospitals, as well as a past history of hallucinations, are important variables in determining engulfment in the patient role. The process of engulfment appears to be a developmental sequence with important transitional events (e.g., hallucinations, Supplemental Security Income, repeated hospitalizations) demarcating and pushing forward the process, and shifting beliefs and definitions associated with each developmental stage. What seems to underlie this process is patients' need to maintain a positive view of themselves as competent.