Insulin activates the hepatitis B virus X gene through the activating protein-1 binding site in HepG2 cells

OBJECTIVES: To study the turnaround time (TAT) for rendering diagnoses on routine biopsy specimens, to examine pathology practice variables that influence TAT, and to assess the level of surgeons' satisfaction with biopsy TAT. DESIGN: Over a 3-month period, voluntary participants in the College of American Pathologists Q-Probes laboratory quality improvement program prospectively collected TAT data on up to 20 biopsy specimens performed on elective surgical cases, completed questionnaires profiling their institution's practice characteristics, and had surgeons complete questionnaires indicating their satisfaction with biopsy report TAT. SETTING AND PARTICIPANTS: One hundred fifty-seven private and public small hospitals located in 43 American states (n = 153), Canada (n = 1), and Australia (n = 3). MAIN OUTCOME MEASURES: The routine surgical biopsy report TATs for 2 testing intervals, each commencing when surgeons acquired the biopsy specimens. One interval concluded when pathologists signed off the biopsy diagnoses, and the other concluded when surgeons received the hard-copy reports. RESULTS: Pathologists signed off 85.9% of 5384 biopsy diagnoses by the second working day, and surgeons received 88.3% of the hard-copy reports by the fourth working day. In 90% of hospitals participating in this study, pathologists signed off half their biopsy diagnoses between the second and third postcollection days, and 90% of surgeons received half their final hard-copy reports by the fourth postcollection day. Institutional practice variables associated with fewer sign-off and/or hard-copy receipt TATs exceeding the institutional 90th percentile performance benchmarks included yearly surgical caseloads greater than 2000 cases per full-time equivalent pathologist, provision of pathology support services on site, and accreditation of the hospital by the Joint Commission on Accreditation of Healthcare Organizations and of the laboratory by the College of American Pathologists. Most (96.4%) surgeons indicated that they were satisfied with hard-copy TATs and that they believed most (98.1%) of the hard-copy TATs had no effect on the lengths of their patients' hospital stays. CONCLUSIONS: Pathologists are capable of signing off most routine biopsy diagnoses within 2 working days and delivering the final hard-copy reports to surgeons within 4 working days (both intervals measured from the time that surgeons collect biopsy specimens). Most surgeons report they are satisfied with this level of performance.     

Coupling protein stability and protein function in Escherichia coli CspA

Idiopathic thrombocytopenic purpura (ITP, also known as immune thrombocytopenic purpura) in adults is principally a disease of young women. Although in some patients the onset is acute and complete resolution occurs, in most patients, the onset is insidious and the course is chronic. In spite of the relative frequency of ITP, there are important unresolved issues in its diagnosis and management. For this reason, the American Society of Hematology (ASH) chose ITP as the disease topic for its initial sponsored practice guideline in 1993. A major conclusion of the published guideline was the lack of firm evidence on which to base diagnostic procedures and management strategies. This review describes the clinical features of ITP in adults, emphasizes the principal unresolved issues in diagnosis and management, and outlines the critical areas for future research.     

Tailored written invitations for second round breast cancer screening: a randomised controlled trial

OBJECTIVES: Firstly, to determine if attendance for second round mammography screening in those sent a tailored letter (that is, making reference to their screening history) is increased compared with those sent a standard letter; secondly, to investigate the acceptability of tailored letters. SETTING: North West Glasgow Breast Screening Centre. METHODS: A randomised controlled trial. RESULTS: Overall attendance was unrelated to whether the women were sent a tailored or standard letter; 60% of those sent the standard letter attended (922/1531) compared with 62% of those sent the tailored letter (956/1552) (chi 2 = 0.61, P = 0.4) (difference 2%; 95% confidence interval -2% to 5%). There were no significant differences in percentage attendance within each of the study subgroups: women who attended previously and received an all clear result, women who attended previously and received a false positive result, women who were invited previously and failed to attend, and women who were previously too young to be invited for screening. However, there was a statistically significant difference in percentage attendance between these four groups, independent of letter type (chi 2 = 510, P < 0.00001). Although women found the letters acceptable and understandable, they did not seem to pay close attention to the content. CONCLUSIONS: Tailoring invitation letters does not have a significant effect on uptake rates for breast screening and does not justify the additional workload required.     

Evidence that bacteria prefer to adhere to thrombus

This study was undertaken to investigate the possible association between thrombosis and infection using an in vitro test model in which fresh bovine blood was recirculated through test conduits (3.5 mm inner diameter) containing stent-like devices. Anticoagulation was adjusted so that the recirculating blood deposited thrombi on the stent to cause gradual occlusion, thus impeding the flow. Four stent-like devices were placed in separate conduits in each experiment, and blood was recirculated with the help of pneumatically driven ventricles. Flow through these conduits was monitored by ultrasonic flow detection. To quantitate bacterial interaction with thrombi, Staphylococcus epidermidis (15E10(9)) was labeled with 111Indium-oxine and added to the blood. Experiments lasted until the flow in the test conduits dropped to 10% of the starting flow. During this recirculation, as flow gradually decreased, one stent was taken out when flow was still at 100%, the second at 75%, the third at 50%, and the fourth at 10% of the starting flow. The number of bacteria associated with the thrombus was measured by gamma counting. The following observations were made: 1) the amount of thrombus increased with time in all experiments (this was confirmed in separate experiments by using autologous 111Indium labeled platelets); 2) bacterial adhesion showed a concomitant increase as thrombus size increased (this was confirmed by using 111Indium labeled bacteria), and 3) bacterial incorporation into the thrombus occurred regardless of whether they were viable or pretreated with the antibiotic rifampin. These observations suggest that as thrombi develop, they may preferentially attract micro-organisms. This suggests that devices with adherent thrombi may have greater susceptibility for infection.     

Induced luteolysis in the primate: rapid loss of luteinizing hormone receptors

The molecular mechanisms involved in luteolysis are still unclear in the primate. This study aimed to investigate the effect of induced luteolysis on the ovarian luteinizing hormone (LH) receptor and the steroidogenic enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the marmoset monkey. Luteolysis was induced in the mid-luteal phase either directly by systemic prostaglandin F2alpha (PGF2alpha), or indirectly by LH withdrawal using systemic gonadotrophin releasing hormone antagonist (GnRHant) treatment. The LH receptor was studied by isotopic mRNA in-situ hybridization and in-situ ligand binding and 3beta-HSD expression was studied using isotopic mRNA in-situ hybridization and immunohistochemistry. Induced luteolysis was associated with a reduction in the expression of LH receptor (P < 0.0001) and 3beta-HSD mRNA, closely followed by a reduction in the LH receptor (P < 0.05) and 3beta-HSD protein concentrations within 24 h. There were no differences in the findings whether luteolysis was induced with PGF2alpha or GnRHant. This study shows that disparate mechanisms to induce luteolysis in the primate result in an identical rapid loss of the LH receptor and 3beta-HSD. In conclusion, induced luteolysis leads to rapid loss of the steroidogenic pathway in luteal cells.     

Completed suicide among adolescents with no diagnosable psychiatric disorder

The characteristics of male adolescent suicide victims with (n = 84) and without (n = 8) a diagnosable psychiatric disorder were compared. Using psychological autopsy methods--interviews with victims' family members and health care professionals, and review of records (e.g., medical, school, police)-data were collected on all adolescent suicides in Finland during a 12-month period. Compared with adolescents with a psychiatric disorder, those with no disorder tended to come from less disturbed families, had shown less antisocial behavior, and had less frequently utilized health care and social services. Adolescents with no disorder more often communicated suicidal thoughts for the first time just before the suicide, and difficulties with the law (discipline problems) were more common precipitants than among those with a disorder. It was concluded that the process leading to suicide seems to be relatively short among male adolescents with no diagnosable psychiatric disorder. Communication of suicidal intent and problems with discipline are among the few clinical warning signs.     

Range of motion and complications after postburn heterotopic bone excision about the elbow

OBJECTIVE: To review the results of surgical management of heterotopic ossification about the elbow in burned patients. DESIGN: Retrospective analysis with long-term patient follow-up. MATERIALS AND METHODS: Eleven patients with 16 elbows requiring surgery were admitted between January 1, 1982 and December 31, 1993. A posterior approach to the elbow with release of the encased ulnar nerve +/- anterior transposition and transolecranon osteotomy to access extensive bone formation in the olecranon fossa was employed. Eight patients (11 elbows) were available for long-term follow-up conducted at mean 50 +/- 13 months after surgery. Long-term follow-up consisted of measurement of range of elbow motion, as well as clinical assessment of ulnar nerve function. MAIN RESULTS: For the 11 elbows examined postoperatively, the mean range of motion preoperatively in flexion-extension was 11 degrees +/- 5 degrees compared to 89 degrees +/- 12 degrees postoperatively (p < 0.001). Three patients with poor long-term results had ankylosis of the joint preoperatively. Of four patients with ulnar nerve paresis preoperatively, none had ulnar nerve dysfunction at follow-up. Of 16 elbows operated on, four (25%) had postoperative complications. Two suffered soft-tissue breakdown with hardware exposure requiring abdominal flap closure, one early failure of olecranon fixation, and one late infected hardware. CONCLUSIONS: Surgery for both limited range of motion as well as ulnar nerve compression is effective in cases of heterotopic ossification about the elbows of burned patients. Early operative intervention is indicated in progressive disease, particularly ulnar nerve palsy, if soft-tissue quality is adequate. Complications with 25% of elbows suggest that use of olecranon osteotomy for joint access may warrant review.     

Nucleic acid crystallography: a view from the nucleic acid database

What are the future directions of the field of nucleic acid crystallography? Although there have been many duplex structures determined, the sample is still relatively small. This is especially true if one wants to derive enough information about the relationships between sequence and structure. Indeed, there are data for all the possible 10 dimer steps, but for some steps it is very limited. If the structural code resides in trimers or tetrad steps then there is simply not enough data to do meaningful statistical analyses. So the first direction that needs to be explored is the determination of more structures with more varied sequences. The other noticeable thing about the data is the shortness of the strands. While it is probably true that attempts to crystallize very long sequences will not meet with success, the idea of crystallizing sequences engineered to fit together via sticky ends such as has been done for the CAP-DNA complex (Schultz et al., 1990) should give data about the behavior of much longer stretches of DNA. The question of the effects of environment on the structure of DNA continues to be a very important one to address since DNA is rarely alone. The preliminary data we have analysed from the current sample shows that the conformation of some steps are very sensitive to packing type. Numerous studies of the hydration around DNA shows that there is a real synergy between the hydration structure and the base conformation. More data will allow further quantitation of these observations. RNA structure is the next very exciting frontier. The emerging structures of duplexes with internal loops, the two hammerhead ribozyme structures and the group I intron ribozyme have given us a glimpse of the complexity and elegance of this class of molecules. With the technology now in place to allow the determination of the structures of these molecules, the expectation is that now we will see a large increase in the number of these structures in the NDB.