Molecular evolution of the HoxA cluster in the three major gnathostome lineages

The duplication of Hox clusters and their maintenance in a lineage has a prominent but little understood role in chordate evolution. Here we examined how Hox cluster duplication may influence changes in cluster architecture and patterns of noncoding sequence evolution. We sequenced the entire duplicated HoxAa and HoxAb clusters of zebrafish (Danio rerio) and extended the 5' (posterior) part of the HoxM (HoxA-like) cluster of horn shark (Heterodontus francisci) containing the hoxa11 and hoxa13 orthologs as well as intergenic and flanking noncoding sequences. The duplicated HoxA clusters in zebrafish each house considerably fewer genes and are dramatically shorter than the single HoxA clusters of human and horn shark. We compared the intergenic sequences of the HoxA clusters of human, horn shark, zebrafish (Aa, Ab), and striped bass and found extensive conservation of noncoding sequence motifs, i.e., phylogenetic footprints, between the human and horn shark, representing two of the three gnathostome lineages. These are putative cis-regulatory elements that may play a role in the regulation of the ancestral HoxA cluster. In contrast, homologous regions of the duplicated HoxAa and HoxAb clusters of zebrafish and the HoxA cluster of striped bass revealed a striking loss of conservation of these putative cis-regulatory sequences in the 3' (anterior) segment of the cluster, where zebrafish only retains single representatives of group 1, 3, 4, and 5 (HoxAa) and group 2 (HoxAb) genes and in the 5' part of the clusters, where zebrafish retains two copies of the group 13, 11, and 9 genes, i.e., AbdB-like genes. In analyzing patterns of cis-sequence evolution in the 5' part of the clusters, we explicitly looked for evidence of complementary loss of conserved noncoding sequences, as predicted by the duplication-degeneration-complementation model in which genetic redundancy after gene duplication is resolved because of the fixation of complementary degenerative mutations. Our data did not yield evidence supporting this prediction. We conclude that changes in the pattern of cis-sequence conservation after Hox cluster duplication are more consistent with being the outcome of adaptive modification rather than passive mechanisms that erode redundancy created by the duplication event. These results support the view that genome duplications may provide a mechanism whereby master control genes undergo radical modifications conducive to major alterations in body plan. Such genomic revolutions may contribute significantly to the evolutionary process.     

Chronic pancreatitis and maldigestion

Patients with chronic pancreatitis may suffer from maldigestion and malnutrition. Longstanding inflammation and fibrosis in the gland can destroy exocrine tissue, leading to inadequate delivery of digestive enzymes to the duodenum in the prandial and postprandial period and subsequent maldigestion. Maldigestion is augmented by inadequate bicarbonate delivery to the duodenum, with secondary inactivation of enzymes and bile acids by gastric acid. Abdominal pain, sitophobia, nausea, vomiting, postprandial satiety, and on-going alcohol abuse may contribute to poor oral intake. Gastric dysmotility and mechanical gastric outlet obstruction from fibrosis in the pancreatic head may contribute to malnutrition and clinical decline. Patients with chronic pancreatitis may at times experience profound steatorrhea and weight loss. In this article, we examine the natural history of exocrine insufficiency in chronic pancreatitis, outline the important nutritional issues in these patients, review the methods of diagnosis of maldigestion, and discuss the approach to therapy.     

A comparison of once-daily tramadol with normal release tramadol in the treatment of pain in osteoarthritis

OBJECTIVE: To compare the efficacy and tolerability of once daily (OD) tramadol tablets with normal release tramadol capsules (50 mg) taken 3 or 4 times daily in a multicenter, double blind, double dummy parallel study. METHODS: Patients with moderate to severe pain due to osteoarthritis (OA) were recruited from general practice. Following a titration period of a week, patients were assessed over one month for the analgesic efficacy and tolerability of the test medications. RESULTS: Both treatments were shown to be effective. There was no difference between treatments and both produced good pain control as shown by clinically relevant decreases from baseline pain scores, low escape medication use, and sleep disturbance. The efficacy of the OD tramadol over the 24 h dosing interval was confirmed by the low sleep disturbance, absence of "end of dose" effects in morning pain scores, and low escape medication use. Of the 279 patients recruited, 140 withdrew, mostly because of adverse events. The adverse event profiles were typical of opioids and were similar for both treatments. CONCLUSION: Tramadol OD was at least as effective and well tolerated as normal release tramadol in the management of OA pain. However, OD tramadol offers the advantage of a reduced dosing regimen, which is especially valuable in the elderly population.     

Association of neural tube defects and folic acid food fortification in Canada

Many women do not receive folic acid supplements before conception. In response, most of Canada's cereal grain products were being fortified with folic acid by January, 1998, thereby providing an additional 0·1–0·2 mg per day of dietary folate to the Canadian population. We assessed the effect of supplementation on prevalence of open neural tube defects in the province of Ontario. Among 336 963 women who underwent maternal serum screening over 77 months, the prevalence of open neural tube defects declined from 1·13 per 1000 pregnancies before fortification to 0·58 per 1000 pregnancies thereafter (prevalence ratio 0·52, 95% Cl 0·40–0·67, p<0·0001). At a population level, folic acid food fortification is associated with a pronounced reduction in open neural tube defects.     

Sharps injury recordkeeping activities and safety product use in California health care facilities: pilot study results from the sharps injury control program

BACKGROUND: In 1999, licensed health care facilities in California (N = 2532) were invited to participate in a survey about occupational bloodborne pathogens exposure surveillance activities, recordkeeping methods, and use of safety-enhanced sharps devices. RESULTS: A total of 1274 facilities responded to the survey from January 1999 through August 1999 (response rate = 50%). Sharps-related injuries were recorded for multiple departments on various forms in diverse manners. Only 66% of hospitals, 37% of home health agencies, and 33% of skilled nursing facilities reported sharps injuries on a mandated sharps injury log. More than 70% of facilities stated that they used some type of safety device or needleless system, but this figure varied by type of device and facility type. Eighty-four percent of general acute care hospitals, 28% of home health agencies and skilled nursing facilities each had evaluated at least 1 safety-enhanced device. Almost 90% of all facilities expressed a need for educational materials on topics such as device selection and evaluation. CONCLUSIONS: Standardization of surveillance and recordkeeping activities does not exist across facility types. Standards and regulations demand complex recordkeeping activities. Increased funding for distribution of educational materials and on-site training should accompany changes in mandated reporting activities when appropriate. Increased testing and evaluation of devices across facility types are necessary to ensure that safety-enhanced devices are protective of health care workers and patients.     

MRI-guided thermal therapy of transplanted tumors in the canine prostate using a directional transurethral ultrasound applicator

PURPOSE: To evaluate MRI-based techniques for visual guidance, thermal monitoring, and assessment during transurethral ultrasound thermal therapy of implanted tumors in an in vivo canine prostate model. MATERIALS AND METHODS: Transmissible venereal tumors (TVT) were grown in the right lobe of the prostate in four dogs. High-temperature thermal therapy was selectively applied to the tumor-bearing lobe using a transurethral ultrasound applicator with a 180 degrees directional heating pattern. Temperature-sensitive MRI (MRTI) using a fast interleaved gradient-echo echo-planar (iGE-EPI) imaging sequence was used for cumulative thermal dose calculations in multiple image planes during the treatment. The results from MRTI-based dose maps and post-treatment MRI were compared to those from histologic analysis. RESULTS: MRTI monitoring in multiple planes across the prostate guided the use and control of a directive ultrasound applicator for the selective ablation of the sections of the prostate that contained implanted tumors. Findings in gadolinium enhanced MRI obtained immediately after thermal therapy slightly underestimated the size of tissue necrosis after treatment, as verified by histopathologic analysis. CONCLUSION: The use of multiplanar MRTI with a transurethral ultrasound applicator shows significant potential for selective thermal ablation of prostate tumor and tissue.     

Development and evaluation of an interactive Web-based breast imaging game for medical students

RATIONALE AND OBJECTIVES: The purpose of this study was to develop and evaluate by student survey an interactive computer tool for teaching breast imaging to 4th-year medical students. MATERIALS AND METHODS: An interactive computer game was designed for competitive play between two students or between one student and one of two cyber players. Content was determined from a survey of faculty members in breast imaging, and the survey results were grouped into 10 learning objectives. Pre-existing knowledge of these objectives in 16 4th-year medical students was tested by a quiz. On the basis of the learning objectives, case scenarios and questions were incorporated into the game, which was programmed in JavaScript and available on a Web site. Preliminary and final versions of the game were used for teaching 55 4th-year medical students. A subgroup of 42 students received an informational handout. Student surveys were performed. RESULTS: Mean quiz score for pre-existing knowledge of the learning objectives was 45% (range, 13%-67%). Survey results showed that images contributed to educational value (92%), the Web site was more interesting to students than the handout (93.6%), and the Web site provided additional reinforcement of learning beyond that of the handout or lecture (88.8%). Students liked the Web site accessibility (96%), and more than 70% agreed the Web site was also appropriate for other medical specialties. An Internet search identified no other Web-based computer games for medical students. CONCLUSION: Students surveyed found the Web site to be worthwhile, convenient, and applicable to other specialties.     

Traumatic hip dislocation in athletes

Sports injuries are increasingly prevalent. Dislocations of the hip are rare; however, they are seen in high-velocity sports such as football and rugby. The injuries may be described as anterior or posterior, and classified according to severity of injury. It is critical to the sports medicine practitioner to promptly recognize and manage this complex injury. This article presents a functional management algorithm including reduction techniques for the simple hip dislocation. Early reduction minimizes complications in all studies. Immediate on-field reduction has been performed successfully and safely in a limited number of cases. An aggressive rehabilitation protocol is proposed to assist the athlete back to sporting activity as soon as possible. The potential benefits of early reduction limit the risk of avascular necrosis of the femoral head and sciatic neuropathy; therefore, further investigation into the standard use of this immediate reduction technique is warranted.