Socioecological differences in factors associated with inconsistent condom use with female sex workers and casual partners: an observational study of heterosexual men attending an anonymous HIV testing clinic in Singapore.

Sexual practices among heterosexual men may differ between female sex workers (FSWs) and casual partners. We surveyed 203 heterosexual men and investigated the attributes associated with inconsistent condom use among them. Lower educational attainment was positively associated with inconsistent condom use with FSWs (adjusted prevalence ratio (aPR) 2.63; P = 0.018) and casual partners (aPR 1.55; P = 0.022), whereas early age of sexual debut (aPR 3.00; P = 0.012) and alcohol use during sex (aPR 7.95; P < 0.001) were positively associated with inconsistent condom use with FSWs. Socioecological factors may explain such differences.

Parental preferences with regards to disclosure following adverse events occurring in relation to medication use or diagnosis in the care of their children - perspectives from Malaysia.

INTRODUCTION: Open disclosure is poorly understood in Malaysia but is an ethical and professional responsibility. The objectives of this study were to determine: (1) the perception of parents regarding the severity of medical error in relation to medication use or diagnosis; (2) the preference of parents for information following the medical error and its relation to severity; and (3) the preference of parents with regards to disciplinary action, reporting, and legal action. METHODS: We translated and contextualised a questionnaire developed from a previous study. The questionnaire consisted of four case vignettes that described the following: medication error with a lifelong complication; diagnostic error with a lifelong complication; diagnostic error without lifelong effect; and medication error without lifelong effect. Each case vignette was followed by a series of questions examining the subject's perception on the above areas. We also determined the content validity of the questionnaire. We invited parents of Malaysian children admitted to the paediatric wards of Tuanku Jaafar Hospital to participate in the study. RESULTS: One hundred and twenty-three parents participated in the study. The majority of parents wanted to be told regarding the event. As the severity of the case vignettes increased, the desire for information, remedial action, acknowledgement of responsibility, compensation, punishment, legal action, and reporting to a higher agency also increased. The findings did not have strong evidence of a relationship with subject's demographics. CONCLUSION: This study gives insights into previously unexplored perspectives and preferences of parents in Malaysia regarding open disclosure. It also highlights the opportunity for more research in this area with potentially broad applications.

Microarray analysis of differentially expressed genes in preeclamptic and normal placental tissues.

PURPOSE OF INVESTIGATION: To detect the candidate genes for preeclampsia (PE). MATERIALS AND METHODS: The gene expression profiles in preeclamptic and normal placental tissues were analyzed using cDNA microarray approach and the altered expression of important genes were further confirmed by real-time RT-PCR (reverse transcription polymerase chain reaction) technique. Total RNA was extracted from placental tissues of three cases with severe PE and from three cases with normal pregnancy. After scanning, differentially expressed genes were detected by software. RESULTS: In two experiments (the fluorescent labels were exchanged), a total of 111 differentially expressed genes were detected. In placental tissue ofpreeclamptic pregnancy, 68 differentially expressed genes were up-regulated, and 44 differentially expressed genes were down-regulated. Of these genes, 16 highly differentially expressed genes were confirmed by real-time fluorescent quantitative RT-PCR, and the result showed that the ratio of gene expression differences was comparable to that detected by cDNA microarray. CONCLUSION: The results of bioinformatic analysis showed that encoding products of differentially expressed genes were correlated to infiltration of placenta trophoblastic cells, immunomodulatory factors, pregnancy-associated plasma protein, signal transduction pathway, and cell adhesion. Further studies on the biological function and regulating mechanism of these genes will provide new clues for better understanding of etiology and pathogenesis of PE.

ABL fusion oncogene transformation and inhibitor sensitivity are mediated by the cellular regulator RIN1.

ABL gene translocations create constitutively active tyrosine kinases that are causative in chronic myeloid leukemia, acute lymphocytic leukemia and other hematopoietic malignancies. Consistent retention of ABL SH3/SH2 autoinhibitory domains, however, suggests that these leukemogenic tyrosine kinase fusion proteins remain subject to regulation. We resolve this paradox, demonstrating that BCR-ABL1 kinase activity is regulated by RIN1, an ABL SH3/SH2 binding protein. BCR-ABL1 activity was increased by RIN1 overexpression and decreased by RIN1 silencing. Moreover, Rin1(-/-) bone marrow cells were not transformed by BCR-ABL1, ETV6-ABL1 or BCR-ABL1(T315I), a patient-derived drug-resistant mutant, as judged by growth factor independence. Rescue by ectopic RIN1 verified a cell autonomous mechanism of collaboration with BCR-ABL1 during transformation. Sensitivity to the ABL kinase inhibitor imatinib was increased by RIN1 silencing, consistent with RIN1 stabilization of an activated BCR-ABL1 conformation having reduced drug affinity. The dependence on activation by RIN1 to unleash full catalytic and cell transformation potential reveals a previously unknown vulnerability that could be exploited for treatment of leukemic cases driven by ABL translocations. The findings suggest that RIN1 targeting could be efficacious for imatinib-resistant disease and might complement ABL kinase inhibitors in first-line therapy.

Measuring the geographic coverage of methadone maintenance programme in Hong Kong by using geographic information system (GIS).

OBJECTIVE: While access and utilization form core components in assessing the effectiveness of a health service, the concept of coverage is often neglected. In this study we propose to develop a GIS-based methodological framework for the measurement of district-based geographic coverage to examine the service effectiveness of methadone treatment programme (MTP) in Hong Kong on a regular basis. METHODS: To overcome the incompatibility of spatial units, population data and data of heroin addiction of the year 2001 are interpolated by population-weighted and area-weighted algorithms. Standard overlay and proximity analytical functions are used to delineate altogether 20 accessible zones around each methadone clinic at a fixed 1.5 km Euclidean distance. Geographic coverage here is defined as the percentage of heroin addicts covered by a methadone clinic within the accessible zone by district. RESULTS: A total of 6413 out of 11000 reported heroin addicts are found geographically covered. The average geographic coverage in Hong Kong is 44.6%, with the figure varying from 0% to 96% by district. One district having no clinic results in 0% coverage whereas another without a clinic yields 15.3% coverage from the clinic in adjacent district. Maps illustrating district-based geographic coverage are generated. CONCLUSION: As continuous data collection is required for a monitoring system, the simplified approach facilitates the handling of large volume data and relevant data analysis. It is concluded that the number of methadone clinics is as important as their locations. Geographic coverage could become an important consideration for monitoring harm reduction.

Electrocardiographical case. Asymptomatic patient with deep T-wave inversions.

A 45-year-old man was found to have an abnormal myocardial perfusion scan. He was asymptomatic, with no chest pain, breathlessness or palpitations. Clinical examination was unremarkable. The 12-lead electrocardiography (ECG) showed increased QRS voltage in leads V3-V6, and deep T-wave inversions noted in leads V3-V6, with an absence of septal Q waves. These ECG features were characteristic of apical variant hypertrophic cardiomyopathy (HCM). He underwent a coronary angiogram that revealed normal coronary arteries, and a left ventriculogram which showed apical HCM. Transthoracic echocardiography further confirmed the diagnosis. No drug therapy was instituted as he was asymptomatic. Apical HCM is discussed.

Inadvertent intrathecal injection of labetalol in a patient undergoing post-partum tubal ligation.

After receiving a continuous spinal anesthetic for labor following an inadvertent dural puncture with a 17-gauge epidural needle, a morbidly obese parturient underwent post-partum tubal ligation 12 h after vaginal delivery. The patient received a total of 2 mL of 0.75% hyperbaric bupivacaine for the surgery. In response to moderate hypertension the patient received intravenous labetalol hydrochloride 20 mg. She subsequently was inadvertently administered approximately 15 mg of labetalol through the spinal catheter. The spinal catheter was removed immediately after the procedure. She suffered no apparent adverse neurologic effects.

First case series on the use of imiquimod for morphoea.

BACKGROUND: Morphoea is characterized by fibrosis, which is mediated by cytokines including transforming growth factor (TGF)-beta. OBJECTIVE: Our objective was to use imiquimod 5% cream (Aldara), an inducer of interferon-gamma, known to inhibit TGF-beta, to treat morphoea. METHODS: Patients with morphoea were treated with imiquimod and evaluated during their follow-up visits to 6 months. RESULTS: The dyspigmentation, induration and erythema of 12 patients with morphoea lesions improved. The histology of the skin also showed a decrease in dermal thickness. CONCLUSION: This is the first case series describing the successful application of imiquimod in the management of morphoea.

Psoriasis treatment: traditional therapy.

Even before the recent development of biological agents, a long list of effective treatments has been available for patients with psoriasis. Topical therapies such as corticosteroids, vitamin D analogues, and retinoids are used for localised disease. Phototherapy including broadband ultraviolet B (UVB), narrowband UVB, PUVA, and climatotherapy are effective for more extensive disease. Systemic therapies such as methotrexate, retinoids, and ciclosporin are effective for patients with refractory or extensive cutaneous disease.

Bioartificial liver treatment prolongs survival and lowers intracranial pressure in pigs with fulminant hepatic failure.

Intracranial hypertension leading to brainstem coning is a major cause of death in fulminant hepatic failure (FHF). We have developed a bioartificial liver (BAL) utilizing plasma perfusion through a bioreactor loaded with porcine hepatocytes and a column with activated charcoal. In a Phase I clinical trial, we observed a decrease in intracranial pressure (ICP) in FHF patients. However, these patients received BAL therapy together with other measures. We therefore examined whether BAL therapy alone could prevent development of intracranial hypertension in pigs with surgically induced FHF. Pigs (40-60 kg) underwent end-to-side portacaval shunt, transection of all hepatic ligaments, and placement of slings around the hepatic artery and bile duct. After 3 days, the slings were tightened to induce liver necrosis. After 4 h, Group 1 pigs (n = 6) underwent a 6 h treatment with the BAL utilizing 10 billion cryopreserved pig hepatocytes and a charcoal column, Group 2 pigs (n = 6) with the BAL containing charcoal but no cells, and Group 3 pigs (n = 6) with the BAL containing neither cells nor charcoal. Group 1 pigs maintained a normal ICP during BAL treatment and for 14 h afterward and because of this effect they survived longer than Groups 2 and 3 animals. In contrast, Groups 2 and 3 pigs showed an early (6-8 h) rise in ICP.

Synthesis of substituted 4(Z)-(methoxyimino)pentyl-1-piperidines as dual NK1/NK2 inhibitors.

The NK1 and NK2 receptor activity of a series of 5-[(3,5-bis(trifluoromethyl)phenyl)methoxy]-3-(3,4-dichlorophenyl)-4(Z)-(methoxyimino)pentyl-1-piperidines was evaluated. Compounds 11d, 11e, 11f, 12a, and 12k were found to be our most potent inhibitors.

Clinical experience with artificial liver support systems.

Fulminant hepatic failure is a devastating disease that, despite recent therapeutic advances, continues to be associated with high morbidity and mortality. Orthotopic liver transplantation has emerged as the sole modality of treatment that significantly improves survival. However, the critical shortage of donors precludes timely transplantation for all patients. Consequently, almost half of all patients with fulminant hepatic failure die before a graft becomes available. This has generated interest in developing a system that would support patients until either native liver regeneration occurs or an optimal donor liver can be found. Investigators have used biological, artificial and bioartificial techniques in an attempt to improve survival in liver failure. This article reviews the history, the current state of the art and future directions of artificial liver support.

Synthesis and NK1/NK2 receptor activity of substituted-4(Z)-(methoxyimino)pentyl-1-piperazines.

A series of 5-[(3,5-bis(trifluoromethyl)phenyl)methoxy]-3-(3,4-dichlorophenyl)-4(Z)- (methoxyimino)pentyl-1-piperazines was prepared and their affinity for the NK1 and NK2 receptors investigated. Compounds 7f, 10o, 10r, and 10s were found to be our most potent inhibitors.

Extraprostatic biopsy improves the staging of localized prostate cancer.

OBJECTIVE: To evaluate the role and safety of biopsy of the seminal vesicles and neurovascular bundles in determining the pathologic stage of prostatic carcinoma. METHODS: Eighty-one consecutive patients were enrolled in a comprehensive cryosurgical biopsy protocol that included sextant intraprostatic plus extraprostatic biopsy. The pathologic stage, determined after biopsy, was compared with the clinical stage, determined by digital rectal examination (DRE) and transrectal ultrasonographic (TRUS) evaluation. As well, complication rates for these patients were compared with rates for a separate group that underwent sextant intraprostatic biopsy alone. RESULTS: Of the 81 patients, 61 (75%) were confirmed to have cancer by biopsy. None of these patients was considered to have extraprostatic extension by clinical evaluation (DRE and TRUS), but 16 of 61 (26%) were identified to have extraprostatic cancer in the seminal vesicles (8 of 61, 13%) or in the neurovascular bundles (8 of 61, 13%) by extraprostatic biopsy. There was no significant difference in the complication rates between sextant intraprostatic biopsy and sextant intraprostatic plus extraprostatic biopsy (p>0.97). CONCLUSIONS: Extraprostatic biopsy identifies extension of carcinoma in a large proportion of patients in whom clinical evaluation by DRE and TRUS indicates organ-confined disease. Extraprostatic biopsy is therefore warranted as routine evaluation before surgery in order to correctly stage prostatic carcinoma and select appropriate therapy.

Clinical use of a bioartificial liver in the treatment of acetaminophen-induced fulminant hepatic failure.

Patients with acetaminophen-induced fulminant hepatic failure (FHF) who meet the King's College Hospital criteria have a high mortality risk (>90%) if they do not undergo liver transplantation. We have developed a treatment strategy for these patients based on the use of an extracorporeal bioartificial liver (BAL) support system. In this study, we report the results of the clinical application of BAL support in patients with acetaminophen-induced FHF. All patients were admitted to a dedicated surgical intensive care unit. They were evaluated for urgent liver transplantation and received the standard medical measures, including N-acetylcysteine administration and intracranial pressure monitoring. Moreover, they underwent daily 6-hour BAL treatments. Eight patients were treated. Three patients were bridged to liver transplantation, and five patients recovered without a transplant. All patients experienced neurological and metabolic improvement after treatments with the BAL support system. The BAL support system seems to improve the outcome of high-risk patients with acetaminophen-induced FHF, even in the absence of liver transplantation. Avoiding liver transplantation is particularly important in an era of organ shortage and high cost of transplants.

Intracranial pressure during liver transplantation for fulminant hepatic failure.

During orthotopic liver transplantation (OLT) for fulminant hepatic failure (FHF), some patients develop cerebral injury secondary to intracranial hypertension. We monitored intracranial pressure (ICP) and cerebral perfusion pressure (CPP) before and during OLT in 12 FHF patients undergoing transplantation. All four patients who had normal ICP preoperatively maintained normal ICP/CPP throughout OLT. During OLT, four of the eight patients with pretransplant intracranial hypertension had six episodes of ICP increase. These episodes of intracranial hypertension occurred during failing liver dissection (n=3) and graft reperfusion (n=3). At the end of the anhepatic phase, the ICP was lower than the preoperative ICP in all patients, and was below 15 mmHg in all but one patient. These data suggest that in FHF patients who develop intracranial hypertension before OLT, dissection of the native liver and graft reperfusion are associated with a risk of brain injury resulting from intracranial hypertension and cerebral hypoperfusion.