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Biomedical subjects

E L Wong

Publications and source records attributed to E L Wong.

At least 19 recordsLinked to original sources

A prospective study assessing the effects of introducing the female condom in a sex worker population in Mombasa, Kenya.

OBJECTIVE: To assess the impact and costs of adding female condoms to a male condom promotion and distribution peer education programme for sex workers in Mombasa, Kenya. DESIGN: A 12 month, prospective study of 210 female sex workers. METHODS: We interviewed participants about their sexual behaviour every 2 months for a total of seven times and introduced female condoms after the third interview. We also collected cost data and calculated the cost and cost effectiveness of adding the female condom component to the existing programme. RESULTS: Introduction of the female condom in an HIV/AIDS prevention project targeting sex workers led to small, but significant, increases in consistent condom use with all sexual partners. However, there was a high degree of substitution of the female condom for male condoms. The cost per additional consistent condom user at a programme level is estimated to be 2160 dollars (1169 pounds sterling, 1711 euros) (95% CI: 1338 to 11 179). CONCLUSIONS: The female condom has some potential for reducing unprotected sex among sex workers. However, given its high cost, and the marginal improvements seen here, governments should limit promotion of the female condom in populations that are already successfully using the male condom. More research is needed to identify effective methods of encouraging sex workers to practise safer sex with their boyfriends.

Single-Use Internal Condom↗

Female condom introduction and sexually transmitted infection prevalence: results of a community intervention trial in Kenya.

OBJECTIVE: To measure the impact on sexually transmitted infection (STI) prevalence of a female condom introduction and risk-reduction program at Kenyan agricultural sites. DESIGN: We conducted a cluster-randomized trial to determine whether a replicable, community-level intervention would reduce STI prevalence. METHODS: Six matched pairs of tea, coffee and flower plantations were identified. The six intervention sites received an information/motivation program with free distribution of female and male condoms, and six control sites received only male condoms and related information. Participants were tested for cervical gonorrhea and chlamydia by ligase chain reaction on urine specimens, and vaginal trichomoniasis by culture, at baseline, 6 and 12 months. RESULTS: Participants at intervention (n = 969) and control sites (n = 960) were similar; baseline STI prevalence was 23.9%. Consistent male condom use was more than 20% at 12 months. Consistent female condom use was reported by 11 and 7% of intervention site women at 6 and 12 months. Unadjusted STI prevalence was 16.5 and 17.4% at 6 months, and 18.3 and 18.5% at 12 months, at the intervention and control sites, respectively. Logistic regression models confirmed the null effect of the female condom intervention. CONCLUSIONS: Female condom introduction did not enhance STI prevention at these sites. It is unclear which aspects of the intervention -- STI education, condom promotion, case management -- were associated with decreased STI prevalence from baseline to follow-up.

Adult↗

Prospective evaluation of patients refused admission to an intensive care unit: triage, futility and outcome.

OBJECTIVES: To evaluate factors associated with decisions to refuse ICU admission and to assess the outcome of refused patients. DESIGN AND SETTING: Prospective, descriptive evaluation in a multi-disciplinary intensive care unit, university referral hospital. PATIENTS AND PARTICIPANTS: All adult emergency referrals over a 7-month period. INTERVENTIONS: The number of beds available at the time of referral, the patient's age, gender, diagnosis, mortality probability model score and hospital survival were documented. The outcome of the referral and the reason for refusal were recorded. MEASUREMENTS AND RESULTS: Of 624 patients 388 were admitted and 236 (38%) refused. Reasons for refusal were triage (n=104), futility (n=82) and inappropriate referral (too well; n=50). The standardised mortality ratio (SMR) for refused and admitted groups was 1.24 (95% CI 1.05-1.46) and 0.93 (0.78-1.09) respectively. The SMR ratio (refused SMR/admitted SMR) was highest in the middle range of illness (1.95, 1.19-3.20). Inappropriate referrals had a better than expected outcome despite refusal, with a SMR ratio of 0.39 (0.11-0.99). Excluding inappropriate referrals, multivariate analysis demonstrated that refusal was associated with older age, diagnostic group and severity of illness. Triage decisions were associated with a diagnosis of sepsis, and futility decisions with greater severity of illness and recent cardiac arrest. CONCLUSIONS: Refusal of admission to our ICU is common. Excess mortality of patients refused is most marked in the middle range of severity of illness. Age, diagnostic group, and severity of illness are important in decision making. Strategies should be developed to create admission criteria that would identify patients in the middle range of severity of illness who should benefit most from ICU care.

Adolescent↗

The pharmacokinetics of once-daily dosing of ceftriaxone in critically ill patients.

The aim of this study was to determine the pharmacokinetic profile of the normal recommended dose of ceftriaxone in critically ill patients and to establish whether the current daily dosing recommendation maintains plasma concentrations adequate for antibacterial efficacy. Ceftriaxone at a recommended dose of 2 g iv was administered od to 12 critically ill patients with severe sepsis and normal serum creatinine concentrations. Blood samples were taken at pre-determined intervals over the first 24 h and on day 3 for measurement of ceftriaxone concentrations. There was wide variability in drug disposition, explained by the presence of variable renal function and identified by the measurement of creatinine clearance. In nine patients with normal renal function, there was a high level of creatinine clearance (mean +/- S.D., 41 +/- 12 mL/min) and volume of distribution (20 +/- 3.3 L), which resulted in an elimination half-life of 6.4 +/- 1.1 h. In comparison with normal subjects, ceftriaxone clearance was increased 100%, volume of distribution increased 90% and the elimination half-life was similar. Three patients had substantially suboptimal plasma ceftriaxone concentrations. We confirm previous findings that ceftriaxone clearance in critically ill patients correlates with renal clearance by glomerular filtration. The elimination half-life is prolonged (21.4 +/- 9.8 h) in critically ill patients with renal failure when compared with previously published data in non-critically ill patients with renal failure. We conclude that in critically ill patients with normal renal function, inadequate plasma concentrations may result following od bolus dosing of ceftriaxone. Drug accumulation may occur in critically ill patients with renal failure.

Adolescent↗

Dose-response study of epidural ropivacaine for labor analgesia.

BACKGROUND: Ropivacaine has been introduced for use in epidural analgesia in labor. However, there have been few formal dose-response studies of ropivacaine in this setting. METHODS: The authors performed a prospective, randomized, double-blind study examining the effectiveness of five different doses of ropivacaine (10, 20, 30, 40, and 50 mg) administered epidurally in a volume of 10 ml to establish analgesia in 66 parturients who were in active labor with cervical dilatation less than 4 cm. A dose was considered effective when the visual analog scale pain score decreased by 50% or more from baseline. RESULTS: A sigmoid dose-response curve and a probit log dose-response plot (linear regression coefficient, r = 0.84; coefficient of determination, r2 = 0.71) were obtained. The ED50 (median effective dose) obtained based on the maximum likelihood estimation was 18.4 mg (95% confidence interval, 13.4-25.4 mg). Time to onset of analgesia, duration of analgesia, time to two-segment regression of sensory block level, and incidence of motor block were not affected by the dosage of ropivacaine administered (P = 0.93, 0.12, 0.55, and 0.39, respectively). However, the upper level of sensory block was dose-related (P < 0.01). CONCLUSION: In a traditional dose-response study, the ED50 of ropivacaine required to initiate epidural analgesia in early labor was found to be 18.4 mg (95% confidence interval, 13.4-25.4 mg).

Adult↗

Spinal ropivacaine for cesarean section: a dose-finding study.

BACKGROUND: The dose-response relation for spinal ropivacaine is undetermined, and there are few data available for obstetric patients. METHODS: In a prospective, randomized, double-blind investigation, the authors studied 72 patients undergoing elective cesarean delivery. An epidural catheter was placed at the L2-L3 vertebral interspace. Lumbar puncture was then performed at the L3-L4 vertebral interspace, and patients were randomized to receive a dose of spinal ropivacaine diluted to 3 ml with normal saline: 10 mg (n = 12), 15 mg (n = 20), 20 mg (n = 20), or 25 mg (n = 20). Sensory changes assessed by ice and pin prick and motor changes assessed by modified Bromage score were recorded at timed intervals. A dose was considered effective if an upper sensory level to pin prick of T7 or above was achieved and epidural supplementation was not required intraoperatively. RESULTS: Anesthesia was successful in 8.3, 45, 70, and 90% of the 10-, 15-, 20-, and 25-mg groups, respectively. A sigmoid dose-response curve and a probit log dose-response plot were obtained, and the authors determined the ED50 (95% confidence interval) to be 16.7 (14.1-18.8) mg and the ED95 (95% confidence interval) to be 26.8 (23.6-34.1) mg. Duration of sensory and motor block and degree of motor block, but not onset of anesthesia, were positively related to dose. CONCLUSIONS: The ED50 and estimated ED95 for spinal ropivacaine were 16.7 and 26.8 mg, respectively. Ropivacaine is a suitable agent for spinal anesthesia for cesarean delivery.

Adult↗

Measuring women's psychological well-being in Indonesia.

This paper describes the development of a set of measures of women's psychological well-being in Indonesia, identifies meaningful clusters of women based on the well-being measures, and explores the sociodemographic factors associated with these well-being clusters. This is the first published study to measure psychological well-being among a large sample of Indonesians and the first to focus on women in that country. Rather than use standard measures of psychological well-being developed in Western nations and untested among Asian women, focus groups were conducted to develop an understanding of Indonesian women's perceptions of their own well-being. The focus group findings were used to develop 41 questionnaire items to measure psychological well-being, and the questionnaire was administered to 796 women in Sumatra and Lampung. Factor analysis reduced the well-being variables into five factors accounting for 45% of the total variance: (1) general negative feelings; (2) satisfaction with relationships and ability to control fertility; (3) satisfaction with economic, family and personal conditions; (4) negative feelings regarding marital and domestic issues; and (5) ability to pursue activities outside the home. We constructed five scales based on these factors. Based on their scores on these scales, women grouped into three clusters differentiated by their scores on four of the five scales. Low levels of psychological well-being were associated in bivariate analyses with: (1) rural residence; (2) young age (under age 30); (3) marriage before age 20; (4) low socioeconomic status; and (5) lower educational attainment.

Adult↗

A survey of undergraduate teaching in anaesthesia.

Currently, no well accepted and clearly defined 'core' curriculum for undergraduate anaesthesia, teaching exists. To address this deficiency, we surveyed 73 university departments of anaesthesia and intensive care. Sixty-five replied from South-east Asia (12), Australasia (13), the UK and Ireland (28) and Canada (12). A questionnaire containing 37 items ranging from departmental structure to curriculum content was used. We found significant regional differences. Overall, most departments taught pharmacology of anaesthetic drugs (83%), pre-operative assessment (92%) and care of the unconscious patient (77%). Ninety-seven per cent taught airway management and intubation and 80% taught intravenous cannulation. Basic life support was taught by 92% and advanced life support by 71%. Fewer than half taught advanced trauma life support principles (44%). Critical care teaching was less well defined, but a consensus of schools taught respiratory failure and ventilation, management of circulatory shock and principles of sepsis and multi-organ system failure. Practical clinical skills were taught mainly using patients and simulators, 46% had a skills laboratory and six employed a resuscitation officer. However, it should be noted that we did not assess the quality and outcome of teaching.

Anesthesiology↗

Randomised double-blind comparison of morphine vs. a morphine-alfentanil combination for patient-controlled analgesia.

In a randomised, double-blind study, we compared a combination of morphine and alfentanil with morphine alone for patient-controlled analgesia (PCA) after Caesarean section under spinal anaesthesia. After surgery, patients were randomly allocated to receive PCA with a bolus dose of either morphine 0.75 mg plus alfentanil 0.125 mg (Group MA, n = 40) or morphine 1.5 mg alone (Group M, n = 37) with a lockout interval of 8 min and no hourly dose limit. Clinical assessments were made in the first 24 h, after which patients completed a written questionnaire. There were no differences between groups in PCA usage or visual analogue scale pain scores measured at 2, 4, 6 and 24 h. There was a low incidence of side-effects in both groups. In the questionnaire, patients in Group MA scored higher compared with Group M when asked to grade speed of onset and effectiveness of analgesia after a PCA bolus; there were no differences in grading for duration of analgesia or overall patient satisfaction. Addition of alfentanil to morphine may have advantages for PCA.

Adult↗

Combined spinal-epidural analgesia in labour: comparison of two doses of intrathecal bupivacaine with fentanyl.

We have compared intrathecal bupivacaine 1.25 mg and fentanyl 25 micrograms (group A) with bupivacaine 2.5 mg and fentanyl 25 micrograms (group B), for combined spinal-epidural analgesia in 49 labouring parturients in a prospective, randomized, double-blind study. Onset and quality of analgesia were similar in both groups, with median visual analogue scale pain scores of 0 achieved in 5-10 min. Median duration of analgesia was longer in group B (median 120 (range 90-120) min) compared with group A (75 (75-105) min) (P = 0.013). Median upper sensory level was higher in group B compared with group A at 15 min (T6-7 vs T11, P = 0.003) and at 30 min (T6 vs T11-12; P = 0.001). Motor block was greater in group B: seven patients had a modified Bromage score > or = 1 compared with none in group A at 15 min (P = 0.017). Group B also had a greater decrease in arterial pressure. Patient-midwife satisfaction scores and other side effects were similar. We conclude that intrathecal bupivacaine 1.25 mg with fentanyl 25 micrograms provided analgesia of similar onset and quality compared with bupivacaine 2.5 mg and fentanyl 25 micrograms. Although the duration of analgesia was shorter, the incidences of motor block and hypotension were less with the smaller dose.

Adult↗

A controlled trial of nonoxynol 9 film to reduce male-to-female transmission of sexually transmitted diseases.

BACKGROUND: Nonoxynol 9 is a proved spermicide, but whether it is also a microbicide is uncertain. A truly effective vaginal microbicide would reduce the susceptibility of women to sexually transmitted diseases, including infection with the human immunodeficiency virus (HIV). METHODS: We enrolled 1292 HIV-negative female sex workers in Cameroon and enrolled them in a double-blind, placebo-controlled study in which the participants were randomly assigned to use either a film containing 70 mg of nonoxynol 9 or a placebo film, inserted into the vagina before intercourse. All of the women were provided with latex condoms and were instructed to have their male sexual partners use them. At monthly follow-up visits, we examined the women with a colposcope for genital lesions, tested endocervical specimens for gonorrhea and chlamydia infection with DNA probes, tested for HIV infection, and treated the women for curable sexually transmitted diseases. RESULTS: The rates of HIV infection (cases per 100 woman-years) were 6.7 in the nonoxynol 9 group and 6.6 in the placebo group (rate ratio, 1.0; 95 percent confidence interval, 0.7 to 1.5). The rates of genital lesions were 42.2 cases per 100 woman-years in the nonoxynol 9 group and 33.5 in the placebo group (rate ratio, 1.3; 95 percent confidence interval, 1.0 to 1.6). The rates of gonorrhea were 33.3 and 31.1 cases per 100 woman-years in the nonoxynol 9 and placebo groups, respectively (rate ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4). The corresponding rates of chlamydia infection in the nonoxynol 9 group and the placebo group were 20.6 and 22.2 per 100 woman-years (rate ratio, 0.9; 95 percent confidence interval, 0.7 to 1.3). The women reported that condoms were used during 90 percent of sexual acts. CONCLUSIONS: The use of a nonoxynol 9 vaginal film did not reduce the rate of new HIV, gonorrhea, or chlamydia infection in this group of sex workers who used condoms and received treatment for sexually transmitted diseases.

Adult↗

Long-term use of the female condom among couples at high risk of human immunodeficiency virus infection in Zambia.

BACKGROUND: Few studies have measured female condom use for more than a 6-month period or among persons at high risk of STD. OBJECTIVE: To measure long-term use of the female condom among couples at high risk of HIV infection and to evaluate the effect of female condom use on unprotected coital acts. STUDY DESIGN: Ninety-nine Zambian couples with symptomatic sexually transmitted diseases (STD) received female condoms, male condoms, and spermicides and were counseled to use either condom plus spermicide for each coital act. Couples were followed up at 3-, 6-, and 12-month visits. Barrier contraceptive use was measured prospectively by coital log. RESULTS: Among the 99 couples enrolled, 51, 38, and 30 couples were successfully followed up for 3, 6, and 12 months, respectively. Female condoms were reportedly used in 24%, 27%, and 23% of coital acts and by 86%, 79%, and 67% of the returning couples during each time interval. Higher-level female condom users used male condoms less often but had fewer unprotected coital acts (5% vs. 14%; p < 0.05) than lower-level female condom users. CONCLUSION: A majority of couples at high risk of HIV infection used the female condom in conjunction with other barrier methods over a 1-year period. The addition of female condoms accompanied by appropriate counseling to the barrier method mix may reduce unprotected sex among couples at high-risk of HIV infection.

Adult↗

Measuring condom use: asking "do you or don't you" isn't enough.

This article compares cross-sectional measures of condom use among 2,269 female sex workers in Cameroon randomly assigned to receive one of five different questionnaires measuring condom use. We found that the level of reported condom use varied depending on the type of survey questions used. Measures based on 2-week coital logs or the past 10 acts categorized more women as "100%" or "0%" users than always-to-never scales categorized women as "always" or "never" users. Consistency of use also varied by type of partner. Internal consistency of responses was high. Future studies should assess differences in prospective measures of condom use and the level of association between various measures and infection with sexually transmitted disease.

Adolescent↗

Identification of a viral kinase that phosphorylates specific E2Fs and pocket proteins.

The transcription factor E2F and its regulation by pRB and related pocket proteins are central to cell cycle control in higher eukaryotes. Much of our knowledge of this regulation has come from studies using immediate-early proteins of DNA tumor viruses. Previously, we reported that the 72-kDa immediate-early region 1 gene product of the human cytomegalovirus, IE72, transactivates the dihydrofolate reductase promoter through the E2F site and that it physically interacts with E2F1 (M. J. Margolis, S. Pajovic, E. L. Wong, M. Wade, R. Jupp, J. A. Nelson, and J. C. Azizkhan, J. Virol. 69:7759-7767, 1995). In this study, we further characterized the mechanism by which IE72 modulates E2F-dependent transcription. In vitro phosphorylation reactions using gel-purified bacterially expressed proteins revealed that IE72 is a kinase that autophosphorylates and phosphorylates E2F1, -2, and -3 (but not E2F4 or -5) and the RB-related pocket proteins p130 and p107 (but not pRB). The region of IE72 spanning amino acids 173 to 197 shows a high level of homology to the ATP binding sites in over 500 kinases. The kinase-negative protein IE72deltaATP, from which this region has been deleted, cannot activate E2F-dependent transcription. The kinase activity of IE72 is also required for its ability to reduce the association of E2F4 with p107 and p130. Taken together, these data suggest that the kinase activity of IE72 is required for E2F-dependent transcriptional activation and that this is likely to result from phosphorylation of specific members of the E2F and pocket protein families by IE72.

Amino Acid Sequence↗

Expression and characterization of CD4-IgG2, a novel heterotetramer that neutralizes primary HIV type 1 isolates.

CD4-IgG2 is a novel fusion protein comprising human IgG2 in which the Fv portions of both heavy and light chains have been replaced by the V1 and V2 domains of human CD4. This tetrameric protein is being developed as an immunoprophylactic agent to reduce the probability of infection following HIV-1 exposure, in settings such as occupational or perinatal exposure to the virus. CD4-IgG2 has been expressed in Chinese hamster ovary cells and is secreted as a fully assembled heterotetramer. The protein binds with nanomolar affinity to purified gp120 from both a laboratory-adapted strain and a primary isolate of HIV-1. Pharmacokinetic studies in rabbits demonstrated that CD4-IgG2 has a plasma terminal half-life greater than 1 day, compared with 15 min for soluble CD4 (sCD4). CD4-IgG2 does not bind to Fc receptors on the surface of U937 monocyte/macrophage cells. Compared to molecules that incorporate the Fc portion of IgG1, CD4-IgG2 has less potential to mediate functions such as antibody-dependent enhancement of infection or transplacental transmission of HIV-1. When tested in a virus-free HIV-1 envelope glycoprotein-mediated cell fusion assay, the tetrameric CD4-IgG2 molecule inhibited syncytium formation more effectively than monomeric sCD4 or a dimeric CD4-gamma 2 fusion protein. This suggests the protein will block cell-to-cell transmission of HIV-1. Moreover, CD4-IgG2 effectively neutralized a panel of laboratory-adapted strains and primary isolates of HIV-1, including strains with different tropisms and isolated from different stages of the disease, at concentrations that should be readily achieved in vivo.

Animals↗

Interaction of the 72-kilodalton human cytomegalovirus IE1 gene product with E2F1 coincides with E2F-dependent activation of dihydrofolate reductase transcription.

Three polypeptides are produced from the major immediate-early (IE) region of human cytomegalovirus by alternative splicing. The IE gene products regulate subsequent viral and cellular gene expression. We previously reported that cotransfection of a genomic clone of the major IE region stimulated transient expression of chloramphenicol acetyltransferase driven by the dihydrofolate reductase (DHFR) promoter and that an intact E2F site was required for the trans activation (M. Wade, T. F. Kowalik, M. Mudryj, E.-S. Huang, and J. C. Azizkhan, Mol. Cell. Biol. 12:4364-4374, 1992). With the availability of cDNA clones for the individual major IE proteins, we sought to determine which of these proteins exerted this effect and whether the IE protein(s) interacted with E2F. In this study, we use cotransfection to demonstrate that the 55- and 86-kDa major IE proteins from the IE2 region can each moderately trans activate the DHFR promoter and that the 72-kDa IE1 protein stimulates DHFR transcription to a much higher level. Furthermore, trans activation through the 72-kDa IE1 protein is in part E2F dependent, while activation by the 55- and 86-kDa IE proteins is E2F independent. We also demonstrate by in vitro pull-down assays that the 72-kDa IE1 protein can specifically interact with the DNA binding domain of E2F1 (amino acids 88 to 191) in the presence of nuclear extract. Moreover, antibodies to either E2F1 or IE72 will immunoprecipitate both E2F and IE72 from cells that stably express IE72, and antibody to E2F1 will immunoprecipitate IE72 from normal human fibroblast cells infected with human cytomegalovirus.

Base Sequence↗

Allelic loss on chromosome 11 in hereditary and sporadic tumors related to familial multiple endocrine neoplasia type 1.

Familial multiple endocrine neoplasia type 1 (FMEN1) is an autosomal dominant disorder characterized by tumors of the parathyroid glands, pancreatic islets, and anterior pituitary. The gene for this disease maps to chromosome 11q12-11q13, and allelic loss in this region has been shown in both sporadic and FMEN1-related parathyroid tumors. FMEN1-related pancreatic islet tumors, and rarely in sporadic anterior pituitary tumors. We tested for allelic loss at 7 loci on chromosome 11 in 17 tumors outside the parathyroid. We found loss of heterozygosity in 2 of 2 FMEN1-related benign pancreatic islet tumors but in none of 8 informative sporadic islet tumors (P = 0.02) including 5 malignant gastrinomas. Of 3 islet tumors from patients who had some but not all features of FMEN1, one showed allelic loss for 5 of 5 informative restriction fragment length polymorphisms, and the other 2 retained heterozygosity for all informative markers. A bronchial carcinoid from an FMEN1 patient and 3 sporadic anterior pituitary tumors showed no allelic loss. These data provide new evidence that many sporadic pancreatic islet neoplasms, even when malignant, do not develop through homozygous inactivation of the MEN1 gene.

Adenoma, Islet Cell↗