Risk profile of walk-in triage compared with an appointment-based phone-triage evening clinic.

The aim of this study is to compare risk factors in new clients attending the walk-in triage-based day clinic (WITS) to those attending a telephone-triage appointment-based evening clinic of a sexual health service. The method involves an audit of computerized medical records of new clients attending between July 2002 and December 2007. There were 37,833 new clients of which 37,223 (98.4%) attended WITS and 610 (1.6%) attended the evening clinic. WITS clients were significantly older (31% vs. 30%, P < 0.041), more likely to be male (58% vs. 43%, P < 0.001), sex workers (6% vs. 3%, P < 0.001), not employed (34% vs. 10%, P < 0.001), diagnosed with gonorrhoea (1.7% vs. 0.7%, P < 0.041), herpes (4% vs. 2%, P < 0.000), non-specific urethritis (6% vs. 2%, P < 0.000) and less likely asymptomatic (35.1% vs. 53.4%, P < 0.001). Men attending WITS had significantly more female partners in the 12 months (3.9 vs. 3.0, P < 0.001), but other risks were similar in both clinics. A telephone-triage appointment-based evening clinic is important for asymptomatic high-risk individuals.

E2-induced degradation of uterine insulin receptor substrate-2: requirement for an IGF-I-stimulated, proteasome-dependent pathway.

The insulin receptor substrates are docking proteins that bind various receptor tyrosine kinases and signaling proteins. Previous studies have shown that E2 or progesterone can regulate the relative abundance of insulin receptor substrate-1 and -2 in cells and tissues. For instance, uterine insulin receptor substrate-2 was decreased markedly at 24 h after E2 treatment of mice. In the present study we used various in vivo experimental approaches to examine the mechanism by which E2 influences uterine insulin receptor substrate-2 expression. Uterine insulin receptor substrate-2 mRNA levels were diminished after E2 treatment, but this diminution did not account for the total reduction in insulin receptor substrate-2 protein, suggesting that the E2-induced decrease in insulin receptor substrate-2 is not regulated solely at the mRNA level. Cotreatment with progesterone prevented the E2-stimulated reduction in insulin receptor substrate-2 protein at 24 h after hormone exposure. In addition, MG-132 and epoxomicin, inhibitors of proteasomal protease activity, inhibited the E2-induced decrease in uterine insulin receptor substrate-2 protein levels, and this correlated to an increase in uterine protein ubiquitination. Insulin receptor substrate-2 protein was diminished in uteri of E2-treated insulin receptor substrate-1-null mutant mice, but not in E2-treated IGF-I-null mutant mice. Furthermore, E2-induced diminution of uterine insulin receptor substrate-2 protein was only partially inhibited in the presence of wortmannin, a PI3K inhibitor. Collectively, these data suggest that the E2-induced decrease in uterine insulin receptor substrate-2 requires IGF-I signaling, is not dependent solely on insulin receptor substrate-1 and PI3K, and is blocked by progesterone as well as by pharmacological inhibition of proteasomal protease activity. We speculate that the IGF-I-activated IGF-I receptor, in response to E2, directly or indirectly modifies insulin receptor substrate-2, probably through phosphorylation, leading to ubiquitination and subsequent degradation of this docking protein by the proteasome. This degradation could be a regulatory step to inhibit insulin receptor substrate-2-dependent signaling in the uterus.

Evidence of juxtacrine signaling for transforming growth factor alpha in human endometrium.

To determine the mechanism of signaling for transforming growth factor alpha (TGFalpha) in human endometrium, uterine luminal fluid proteins were retrieved by lavage followed by collection of the adjacent endometrium at hysterectomy. In the endometrium we observed the presence of the full-length transmembrane TGFalpha protein and the phosphorylation of its only known receptor, the epidermal growth factor receptor (EGFR), by immunoprecipitation-Western blot; TGFalpha mRNA via reverse transcription-polymerase chain reaction; and immunolocalization of TGFalpha to the surface endometrium adjacent to the uterine lumen. Despite this demonstration of TGFalpha in functional endometrium, we could not detect measurable amounts of TGFalpha in any of the 16 endometrial washings by either immunoprecipitation-Western blot or by ELISA. Recovery rate for intraluminal fluid spiked with TGFalpha control peptide was 93.4-97%. The inability to detect TGFalpha in intraluminal fluid despite its high concentration in cells directly adjacent to the uterine lumen, along with the absence of any cleaved TGFalpha species identified in the endometrium, suggests that TGFalpha signals its receptor as a transmembrane ligand. Since the EGFR is present in the endometrium and on the surface of embryos, these data are consistent with a juxtacrine mode of signaling for TGFalpha between endometrial cells, and between the luminal surface epithelium and preimplantation embryos.

Evaluation of the postcoital test in cycles involving exogenous gonadotropins.

OBJECTIVE: To evaluate the hypothesis that a postcoital test, optimally performed in the periovulatory period of cycles in which gonadotropin-induced superovulation was used, correlates with cycle fecundity. METHODS: Of 1135 total consecutive cycles, 367 first cycles were analyzed from the reproductive endocrinology and infertility service of a university medical center. This referral population had a mean age of 34.6 years for the female partner, a nulliparity rate of 81%, and a mean length of infertility of 4.8 years. Postcoital tests were performed 36-40 hours after hCG administration in gonadotropin-stimulated cycles. Clinical pregnancy was defined as fetal cardiac activity as seen on transvaginal ultrasound examination. RESULTS: Couples with no sperm observed per high-power field in the cervical mucus achieved a 16% fecundity rate (21 pregnancies in 129 cycles), one to ten sperm a 18% fecundity rate (28 pregnancies in 154 cycles), and more than ten sperm a 15% fecundity rate (13 pregnancies in 84 cycles). There was no significant difference between groups (n = 367, P = .85); the power to detect a statistically significant difference was .82. As validation of optimal cervical mucus, fecundity rates were compared with these postcoital test values across the entire range of peak periovulatory serum estrogen levels, and no correlation was seen (P = .61, .86, and .96 for estrogen levels of 201-500, 501-1500, and 1501-3433 pg/mL, respectively). CONCLUSION: With precise periovulatory timing and supraphysiologic estrogen levels optimizing qualitative cervical mucus characteristics in gonadotropin-induced cycles, the number of sperm observed per high-power field does not correlate with cycle fecundity.

Influence of health locus of control and parental health perceptions on follow-through with school nurse referral.

The health perceptions and health locus of control of 50 parents of students in a school district in New Jersey were investigated in this comparative descriptive study. The study was based on the Health Belief Model and Roger's Science of Unitary Human Beings. Subjects were categorized into two groups, depending on whether or not they followed through with school nurse referrals for their children. Data were collected from each subject to measure levels of health locus of control and health perceptions. The hypothesis stated that parents who do not follow up on health referrals for their children will score lower on health perceptions and health locus of control than parents who schedule referrals for their children. Results revealed no significant differences between compliant and noncompliant parents in health perceptions and health locus of control. Chi-square analyses were used to determine the relationships between sample characteristics and participants' responses to the Health Locus of Control scale and the Health Perceptions Questionnaire.

Hematosalpinx with pelvic pain after endometrial ablation confirms the postablation-tubal sterilization syndrome.

Complications after endometrial ablation are uncommon, and published series show that the majority of women who are treated by this technique remain symptom free in the postoperative period. A 39-year-old woman with previous tubal ligation underwent laparoscopic-assisted vaginal hysterectomy for debilitating pelvic pain 1 year after endometrial ablation. Pathologic assessment of the surgical specimen showed bilateral hematosalpinges from continued cyclic occult bleeding. The symptoms and findings in this case confirm the postablation-tubal sterilization syndrome.

Azithromycin and erythromycin in the treatment of cervical chlamydial infection during pregnancy.

OBJECTIVE: To compare azithromycin and erythromycin in regard to side effects, intolerance, and cure rate in a pregnant population with chlamydial cervicitis. METHODS: Thirty women were randomized to receive either erythromycin, 500 mg orally four times a day for 7 days, or azithromycin, 1 g orally as one dose. All subjects completed questionnaires identifying the incidence of nausea, vomiting, diarrhea, abdominal pain, and anorexia. Post-treatment cultures were taken from all subjects. RESULTS: All subjects receiving erythromycin reported two or more gastrointestinal side effects, versus none in the azithromycin group (P < .001). Five of 15 subjects in the erythromycin treatment arm were intolerant to the 500-mg dose given four times a day, compared to none in the azithromycin group (P < .025), so the dosage was lowered to 250 mg four times a day to complete the course. Repeat cervical testing demonstrated similar cure rates for both medications: 100 and 93% (14 of 15) for azithromycin and erythromycin, respectively. CONCLUSION: These data suggest that azithromycin is a valid treatment option in pregnant patients who cannot tolerate erythromycin because of side effects.

Characterization of antigen receptor response elements within the interleukin-2 enhancer.

T-cell activation and induction of interleukin-2 (IL-2) expression in human T lymphocytes require both interaction of foreign antigen with the T-cell antigen receptor and protein kinase C (PKC) stimulation. Agents such as phorbol 12-myristate 13-acetate (PMA) that stimulate PKC augment the effects of antigen but are not sufficient for IL-2 activation. By analysis of deletion mutants, we identified three DNA sequences extending from -73 to -89, -217 to -255, and -263 to -279, designated IL-2 sites A, D, and E, respectively, that are required for maximal induction of IL-2 expression. One of these regions, site E, interacted with a protein (NF-IL-2E) present only in the nuclei of cells which have been stimulated. The other two sequences interacted with a protein (NF-IL-2A) that is constitutively expressed in T cells. When multiple tandem copies of either the E site or the A site were placed upstream of the gamma-fibrinogen promoter, they activated expression via this promoter in response to signals initiated at the antigen receptor but not following PMA stimulation. For this reason, we denoted them antigen receptor response elements. The uncoupling of antigen receptor and PKC requirements in these studies indicates that these signal pathways are, at least in part, distinct and integrated at the level of the gene.

A 275 basepair fragment at the 5' end of the interleukin 2 gene enhances expression from a heterologous promoter in response to signals from the T cell antigen receptor.

Using a transient transfection assay, we have defined the sequences required for the activation of the IL-2 gene in response to signals from the T cell antigen receptor. To do so we have transfected the human T cell line Jurkat with hybrid DNA constructs in which fragments from the IL-2 gene are linked to an indicator gene. The indicator gene product, as well as IL-2 production from the endogenous IL-2 gene were assayed after activation of the transfected Jurkat cells by various stimuli. We have demonstrated that a 275 bp fragment stretching from 52 to 326 bp upstream of the IL-2 gene transcription initiation site is required for expression of the linked indicator gene. This IL-2 gene fragment has several of the characteristics of a transcriptional enhancer element, in that it functions in both orientations and will enhance the expression from the promoter of an unrelated gene. Such enhancement occurred only after activation of Jurkat cells through the T cell antigen receptor. More specifically, this 275 bp fragment activated the expression of a linked gene after binding of a monoclonal antibody to the Jurkat T cell antigen receptor in the presence of PMA. In addition, calcium ionophore, which circumvents antigen receptor binding in T cell activation, induced the expression of the linked gene through this 275 bp sequence, in the presence of PMA. Finally, in a mutant Jurkat cell line lacking T3/antigen receptor complexes at the cell surface, no expression due to the IL-2 5' flanking region was seen after exposure to antibody to the T cell antigen receptor plus PMA or to PHA plus PMA. In contrast, calcium ionophore plus PMA did induce the expression of a linked gene through the IL-2 5' flanking region in the mutant Jurkat cell line. The responsiveness of the transfected hybrid genes containing the IL-2 regulatory region paralleled the expression of the endogenous IL-2 gene, as determined by IL-2 bioassays. We conclude that the 275 bp IL-2 sequence (-326 to -52 bp) is a target for the signal pathway originating at the T cell antigen receptor. Definition of this 275 bp target sequence should now permit the isolation of the molecules that bind to and activate the IL-2 gene.