Pelvic inflammatory disease in adolescents

PURPOSE OF REVIEW: We discuss the epidemiology, risk factors, microbiology, diagnosis, treatment and prevention of pelvic inflammatory disease in adolescents. RECENT FINDINGS: Young age is one of the most important risk factors for sexually transmitted diseases and pelvic inflammatory disease. Sexually active adolescents have the highest incidence of Chlamydia trachomatis, Neisseria gonorrhoeae, and pelvic inflammatory disease of any sexually active age group. Long-term sequelae of pelvic inflammatory disease include ectopic pregnancy, tubal factor infertility, tubo-ovarian abscesses and chronic pelvic pain. Subclinical pelvic inflammatory disease is responsible for a significant portion of these long-term sequelae. New (2006) Centers for Disease Control and Prevention treatment guidelines for pelvic inflammatory disease are available. One of the best methods of prevention of pelvic inflammatory disease is to screen and treat sexually active adolescents for chlamydial infection. Implementation of nucleic acid amplification assays allows screening of adolescents via self-collected urine or vaginal swab samples. SUMMARY: Pelvic inflammatory disease is a highly preventable source of reproductive morbidity for adolescents. It is prudent that clinicians provide counseling regarding healthy sexual behaviors, STD prevention, and contraception whenever an adolescent presents in need of STD screening or evaluation for pelvic inflammatory disease.     

Mixing rapid-acting insulin analogues with insulin glargine in children with type 1 diabetes mellitus

OBJECTIVE: To determine whether mixing insulin glargine (IG) with a rapid-acting insulin (RAI) analogue in the same syringe had any deleterious effects on glycemic control in children with type 1 diabetes mellitus. STUDY DESIGN: Data from 55 children mixing the IG with a RAI analogue was collected for 6 months before and 6 months after the insulin mixing began. Data from a control group of 55 children not mixing the insulins was collected at similar intervals. Parameters evaluated included hemoglobin A1c (HbA1c) values, number of non-severe and severe hypoglycemic events, number of diabetic ketoacidosis (DKA) events, and blood glucose distribution patterns. RESULTS: After 6 months of study, HbA1c values were equivalent for the control and test groups (8.54+/-1.14 vs 8.61+/-1.14, respectively; P=1.0000). Percentages of blood glucose values in, above, and below the target range did not vary significantly in the groups. There were no significant differences in the groups in the occurrence of non-severe or severe hypoglycemic events or of DKA events. CONCLUSION: There were no significant differences in glycemic control between children who mixed IG in the same syringe with a RAI analogue compared with children who took separate injections.     

Increased oxidative-related mechanisms in the spinal cord injury in old rats

In the present study, we evaluated the effect of age, in a model of spinal cord injury that was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy. Spinal cord injury in old rats resulted in severe trauma characterized by edema and neutrophil infiltration. Immunohistochemical examination demonstrated an increase in immunoreactivity for nitrotyrosine. In contrast, the degree of: (a) spinal cord inflammation and tissue injury (histological score), (b) nitrotyrosine, (c) PARS, and (d) neutrophils infiltration was markedly reduced in spinal cord tissue obtained from young rats. We have also demonstrated that ageing significantly worsened the recovery of limb function and caused an increase in mortality rate when compared with young rats.     

Characterizing substance abuse programs that treat adolescents

Few systematic studies have examined the characteristics of substance abuse treatment programs serving adolescents. An expert panel recently identified nine key elements of effective adolescent substance abuse treatment. We measured the percentage of treatment programs in the United States with at least 10 adolescent clients on a given day that reported these elements using data from the 2003 National Survey of Substance Abuse Treatment Services. This first look into the characteristics of facilities serving significant numbers of adolescents indicates that many facilities may be lacking in components considered important. The most significant measured potential areas for improvement occurred in the areas of including mental health as well as medical issues in comprehensive assessments and developing curricula to meet the developmental and cultural needs of clients. On a more encouraging note, many facilities were conducting discharge planning and providing aftercare, although the specifics of these services were not determined.     

3-(1,1-dioxo-2H-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones, potent inhibitors of hepatitis C virus RNA-dependent RNA polymerase

Recently, we disclosed a new class of HCV polymerase inhibitors discovered through high-throughput screening (HTS) of the GlaxoSmithKline proprietary compound collection. This interesting class of 3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones potently inhibits HCV polymerase enzymatic activity and inhibits the ability of the subgenomic HCV replicon to replicate in Huh-7 cells. This report will focus on the structure-activity relationships (SAR) of substituents on the quinolinone ring, culminating in the discovery of 1-(2-cyclopropylethyl)-3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-6-fluoro-4-hydroxy-2(1H)-quinolinone (130), an inhibitor with excellent potency in biochemical and cellular assays possessing attractive molecular properties for advancement as a clinical candidate. The potential for development and safety assessment profile of compound 130 will also be discussed.     

N, N' (4,5-dihydro-1h-imidazol-2-yl)3-aza-1,10-decane-diamine and N, N'(4,5-dihydro-1H-imidazol-2-yl)3-aza-1, 10-dodecane-diamine antagonize cell proliferation as selective ligands towards topoisomerase II

New alkyl imidazoline derivatives have been synthesized as potential anti-cancer agents. The anti-proliferative activity of these compounds, evaluated against representative human haematological and solid neoplastic cell lines, showed that N, N'-di (4,5-dihydro-1H-imidazol-2-yl)3-aza-1,10-decane-diamine (8) and N, N'-di (4,5-dihydro-1H-imidazol-2-yl)3-aza-1,10-dodecane-diamine (9) were the most active compounds; in fact, they inhibited the cell proliferation at submicromolar concentrations. In enzyme assays, compound 9 turned out to be an inhibitor of topoisomerase II at concentrations comparable with those of the reference topoisomerase II inhibitor, etoposide.     

Imino-tetrahydro-benzothiazole derivatives as p53 inhibitors: discovery of a highly potent in vivo inhibitor and its action mechanism

Several neurological disorders manifest symptoms that result from the degeneration and death of specific neurons. p53 is an important modulator of cell death, and its inhibition could be a therapeutic approach to several neuropathologies. Here, we report the design, synthesis, and biological evaluation of novel p53 inhibitors based on the imino-tetrahydrobenzothiazole scaffold. By performing studies on their mechanism of action, we find that cyclic analogue 4b and its open precursor 2b are more potent than pifithrin-alpha (PFT-alpha), which is known to block p53 pro-apoptotic activity in vitro and in vivo without acting on other pro-apoptotic pathways. Using spectroscopic methods, we also demonstrate that open form 2b is more stable than 4b in biological media. Compound 2b is converted into its corresponding active cyclic form through an intramolecular dehydration process and was found two log values more active in vivo than PFT-alpha. Thus, 2b can be considered as a new prodrug prototype that prevents in vivo p53-triggered cell death in several neuropathologies and possibly reduces cancer therapy side effects.     

Chest physical therapy in patients with acute exacerbation of chronic bronchitis: effectiveness of three methods

OBJECTIVE: To compare the short-term effects of postural drainage (PD), oscillating positive expiratory pressure (using the FLUTTER device), and expiration with the glottis open in the lateral posture (ELTGOL) on oxygen saturation, pulmonary function, and sputum production in patients with an acute exacerbation of chronic bronchitis. DESIGN: A prospective, randomized study. SETTING: A clinical ward. PATIENTS: Ten patients with chronic bronchitis exacerbation received PD, FLUTTER, and ELTGOL by the same respiratory therapist at about the same time of day on separate days and in random order. MAIN OUTCOME MEASURES: Oxygen saturation and pulmonary function were measured before, immediately after, and 15 minutes and 1 hour after each treatment. Improvement in sputum production was measured by total sputum wet weight immediately after and for 1 hour after treatment. INTERVENTIONS: PD consisted of positioning the patients in a posture that allows bronchial drainage by gravity. FLUTTER is a device that is claimed to combine oscillating positive expiratory pressure with oscillations of the airflow. ELTGOL is an airway clearance technique that uses lateral posture and different lung volumes to control expiratory flow rate to avoid airway compression. The total time spent for treatments was 30 minutes. RESULTS: All techniques were well tolerated, and oxygen saturation and pulmonary function did not change significantly during and after treatments. Thirty minutes after the beginning of treatment, sputum production increased significantly with all techniques, but during the 1 hour after the end of treatment, it was significantly larger with FLUTTER (from 15.0 +/- 8.6g to 19.0 +/- 9.3g, p < .01) and ELTGOL (from 17.0 +/- 7.0g to 20.6 +/- 6.9g, p < .02) than with PD (from 15.5 +/- 4.0g to 17.5 +/- 3.7g, NS). CONCLUSIONS: All three treatments were safe and effective in removing secretions without causing undesirable effects on oxygen saturation, but FLUTTER and ELTGOL techniques were more effective in prolonging secretion removal in chronic bronchitis exacerbation than was the PD method.     

Nursing students' experiences with and strategic approaches to case-based instruction: a replication and comparison study between two disciplines

In the classroom and in clinical areas, knowing how to learn, reason, reflect, think creatively, generate and evaluate ideas, make decisions, and solve problems have been identified as key elements of critical thinking. However, to be successful in the current health care arena, caregivers cannot be satisfied with possessing the ability to solve problems and simply meet preestablished "outcomes" (Alfaro-LeFevre, 1998). It is necessary to improve knowledge and practice applications and to explore the best ways to do things within a work group. This qualitative study evaluated the experiences of senior-level nursing students using case-based instruction in a course titled, Leading and Managing in Nursing. It is a replication and extension (Phase II) of an original case-based instruction study, completed with senior physical therapy students (Phase I). Phase III of this study trajectory is the creation of an interdisciplinary case-based course that addresses either or both clinical collaborative care issues or leadership and management issues for health care profession students. From this Phase II study, six thematic groupings emerged as distinct student experiences in case-based instruction-motivation, real world, learning, knowledge development, emerging from within, and group dynamic issues.     

Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-gamma, reduces acute pancreatitis induced by cerulein

OBJECTIVE: In the present study, we investigated the effects of rosiglitazone (10 mg/kg, i.p.), a PPAR-gamma agonist, on the development of acute pancreatitis. DESIGN: Intraperitoneal injection of cerulein in mice induced an acute pancreatitis characterized by edema, neutrophil infiltration elevated serum levels of amylase and lipase. This experimental model was performed to test the anti-inflammatory activity of rosiglitazone. SETTING. University research laboratory. INTERVENTIONS: Male CD mice (20-22 g) were allocated into four groups (n=10 for each group): (a) Cerulein+vehicle group. Mice were treated hourly (x 5) with cerulein (50 microg/kg, in saline solution, i.p.); (b) Rosiglitazone group (same as the Cerulein+vehicle group but were administered rosiglitazone, 10 mg/kg bolus, 30 min prior to cerulein); (c) Sham+saline group. Mice were treated with saline instead of cerulein; (d) Sham+Rosiglitazone. Identical to Rosiglitazone group except that the saline was administered instead of cerulein. Mice were killed at 6 h after the induction of pancreatitis. Blood samples, pancreas, and lungs were collected. MEASUREMENTS AND RESULTS: Infiltration of pancreatic and lung tissue with neutrophils was associated with enhanced lipid peroxidation. Immunohistochemical examination demonstrated a marked increase in immunoreactivity for nitrotyrosine and for ICAM-1 in the pancreas of cerulein-treated mice. In contrast, the degree of (a) pancreatic inflammation and tissue injury, (b) upregulation/formation of ICAM-1 and nitrotyrosine, and (c) neutrophils infiltration was markedly reduced in pancreatic tissue obtained from rosiglitazone-treated mice. CONCLUSION: These findings support the view that rosiglitazone and other potent PPAR-gamma agonists may be useful in the therapy of acute pancreatitis.