Burden of blood transmitted infections in substance users admitted for inpatient treatment in Singapore and the associated factors

INTRODUCTION

There is a paucity of local data on the prevalence of blood transmitted infections (BTIs), such as hepatitis B, hepatitis C and human immunodeficiency virus (HIV) infections, among illicit drug users. This study aimed to examine the prevalence of BTIs among substance-dependent inpatients and identify the factors associated with BTIs.

METHODS

We conducted a retrospective case note analysis of 170 inpatients who had a history of substance dependence and were seen at the National Addictions Management Service, Singapore, between 1 June 2009 and 31 May 2010.

RESULTS

The majority of the 170 inpatients were male (88.2%) and Chinese (58.2%). The mean age of the patients was 43.1 years, and the main drug of abuse was opioids (86.5%). BTIs were found in 70 (41.2%) inpatients; the prevalence of hepatitis B, hepatitis C and HIV infections was 3.7%, 39.6% and 0%, respectively. Lifetime intravenous drug use, but not needle-sharing, was more common among inpatients who were positive for BTIs (p < 0.01). Logistic regression analysis showed that lifetime intravenous drug use (OR 4.3, 95% CI 1.7–10.8, p < 0.01) was the only significant predictor of BTI.

CONCLUSION

41.2% of the substance users seeking help were positive for at least one BTI. Lifetime intravenous drug users were found to be more than four times more likely to have a BTI. Early detection and prevention is essential to improve prognosis.     

Partially circumventing peripheral tolerance for oncogene-specific prostate cancer immunotherapy

BACKGROUND: Failure of cancer immunotherapy is essentially due to immunological tolerance to tumor-associated antigens (TAAs), as these antigens are also expressed in healthy tissues. METHODS: Here, we used transgenic adenocarcinoma of mouse prostate (TRAMP) mice, which develop lethal prostate cancer due to prostate-specific expression of SV40 T antigen (Tag), to evaluate effects of prostatic transformation on oncogene TAA-specific tolerance and to test the possibility of breaking such tolerance using a modified recombinant vaccinia virus. RESULTS: We showed that Tag expression in TRAMP mice is uniquely extra-thymic, and levels of prostatic Tag expression positively correlate with malignant transformation of the prostate. Yet, young tumor-free TRAMP mice were tolerant to Tag antigen. We therefore attempted overcoming such peripheral oncogene-specific T cell tolerance through immunization with a vaccinia construct encoding Tag immunogenic epitopes. This vaccination modality showed that oncogene-specific tolerance was successfully overcome by effective in vivo priming of Tag-specific cytotoxic T cells (CTLs). However, this was restricted to young TRAMP mice. Tag-specific CTL from "tumor na?ve" young TRAMP mice showed significant anti-tumor efficacy in vivo by eliminating established heterotopic prostate tumors and prolonging survival in SCID mice harboring Tag-expressing tumors. In contrast, older TRAMP mice with established prostate tumors exhibited oncogene-specific tolerance as evidenced by failure to generate Tag-specific CTL following Tag-specific immunization. CONCLUSIONS: Peripheral tolerance can be overcome for effective anti-tumor therapy following oncogene-specific immunization. However, this ability to elicit oncogene-specific CTL is impeded in the tumor-bearing host, in the context of increased oncogene expression associated with tumor progression.     

Cure, continence and quality of life after treatment for fistula-in-ano

Background: The best operation for high anal fistulas is difficult to nominate because they have varying cure and incontinence rates. The objective of this study was to quantify the relative importance of the outcomes of cure, continence and other quality‐of‐life (QOL) factors. Methods: A questionnaire was sent in October 2006 to patients with anal fistulas and to colorectal surgeons. Participants were asked to nominate up to five QOL domains. They were also asked to choose between two treatment options (with different cure and continence rates). Results: Seventy‐five of 134 (56%) surgeons and 28 of 199 (14%) patients replied. Comparing draining and cutting setons, surgeons (57 of 71, six neutral) favoured the former and patients (15 of 27, four neutral) preferred the latter. Comparing mucosal advancement flap with cutting seton, both surgeons (71 of 75, four neutral) and patients (13 of 26, two neutral) preferred the former. There was greater uncertainty among surgeons when comparing draining seton (23) and mucosal advancement flap (33), with 18 neutral. Patients preferred the mucosal advancement flap (19) to draining seton (three) and four were neutral. In direct questioning of objectives, surgeons nominated continence, leakage, pain, cure and sepsis as the five most important QOL factors. Patients nominated independent activity, pain, continence, psychological health and leakage as their five factors. Conclusion: Functional impairment and QOL do not necessarily correlate. The development of a validated specific QOL scale for patients with anal fistulas would be important to compare the results of different treatment options. This scale should include social and psychological factors in addition to the physical outcomes.     

The reaction of posttransplant denervated liver on the hemorrhagic shock in rats

OBJECTIVE: The aims of the study were to determine the effects of denervation on the function of the liver transplantation as a blood reservoir and to define its vulnerability to ischemic-reperfusion (I/R) injury after hemorrhagic shock. MATERIALS AND METHODS: Hemorrhagic shock with a mean arterial blood pressure (MAP) of 40 to 50 mm Hg was induced by withdrawing blood at a rate of approximately 1 mL/min among 10 posttransplant denervated rats and 10 sham rats for 1 hour. The rats were then resuscitated by retransfusing the drawn blood with sacrifice under deep anesthesia at 1 hour after resuscitation. The total amount of blood required to achieve hemorrhagic shock was compared between groups as well as the vulnerability and reactions of the posttransplant denervated liver to I/R injury after hemorrhagic shock as assessed by gene expressions of c-jun, c-fos, tumor necrosis factor (TNF)-alpha, interleukin (IL)6, IL-10, and heat-shock protein 70 (HSP70). RESULTS: The volume of blood that had to be drawn to reach a MAP of 40 to 50 mm Hg was not significantly different between the groups. One hour of hemorrhagic shock followed by resuscitation resulted in significant increases in the genes expression of c-fos, TNF-alpha, IL-6, IL-10, and HSP70 in comparison to the control values, but no difference was observed between experimental and sham groups. CONCLUSION: We suggest that the function of the liver as a blood reservoir and the gene expressions of c-fos and pro- and anti-inflammatory cytokines, as well as the protective protein HSP70 in response to I/R injury, were not altered by liver transplantation.     

Fluorescence Dilution Technique for Measurement of Cardiac Output and Circulating Blood Volume in Healthy Human Subjects

Background: The authors previously validated in an animal model a new indicator dilution technique for measuring cardiac output and circulating blood volume by recording transcutaneously the fluorescence of circulating indocyanine green with an optical probe placed on the skin surface. The current study compared fluorescence dilution recordings recorded from several locations on the human face in terms of signal intensity and stability and estimated the subjects' cardiac output and circulating blood volume from the recordings.

Methods: Fluorescence dilution traces were recorded transcutaneously in six healthy human volunteers after rapid intravenous injection of 1 mg indocyanine green. Three placements of the optical probe were tested: the nose ala, the ear lobe, and the temple area. In three subjects, the recordings were calibrated in terms of circulating indocyanine green concentration to estimate cardiac output and circulating blood volume.

Results: Fluorescence dilution traces had the same duration for the three locations, but the recordings obtained from the nose ala and the ear lobe were twice as intense as those from the temple. The fluorescence intensity at each site was linearly related to the local laser Doppler perfusion index. The coefficient of variation for the area under the first pass curve (inversely proportional to cardiac output) was approximately 6% for triplicate measurements at the same location. Cardiac output and circulating blood volume derived from the fluorescence recordings were in the normal range.     

Muscle weakness,spasticity and disuse contribute to demineralization and geometric changes in the radius following chronic stroke

Summary Bone health status of the radius in individuals with chronic stroke was evaluated using peripheral quantitative computed tomography. Bone mineral density and cortical thickness on the affected side were compromised when compared with the unaffected side. Muscle weakness, spasticity, and disuse were identified as contributing factors to such changes. Introduction Following a stroke, demineralization and geometric changes occur in bone as a result of disuse and residual impairments, and these can contribute to an increased risk of fragility fractures. Methods This study used peripheral quantitative computed tomography (pQCT) to evaluate volumetric bone mineral density and geometry at the midshaft radius in people living with chronic stroke. Older individuals with chronic stroke were recruited. Each subject underwent a pQCT scan of the midshaft radius at the 30% site on both upper limbs. Muscle strength, motor function, spasticity, and chronic disuse were also evaluated. Data from 47 subjects (19 women) were assessed. Results A significant difference was found between the two limbs for cortical bone mineral content, cortical bone mineral density, cortical thickness, and polar stress-strain index. There was no significant side-to-side difference in total bone area. Percent side-to-side difference in muscle strength, spasticity, and chronic disuse were significant determinants of percent side-to-side difference in cortical bone mineral content and cortical thickness. Conclusions The findings suggest that following chronic stroke, endosteal resorption of the midshaft radius occurred with a preservation of total bone area. Muscle weakness, spasticity, chronic disuse significantly contributed to demineralization and geometric changes in the radius following chronic stroke.     

Downregulation of matrix metalloproteinase-9 and attenuation of edema via inhibition of ERK mitogen activated protein kinase in traumatic brain injury

Emerging data suggest that matrix metalloproteinase-9 (MMP-9) plays a critical role in the pathophysiology of brain injury. However, the regulatory mechanisms involved in vivo remain unclear. In this study, we focus on a mitogen activated protein kinase (MAPK) pathway that may trigger MMP-9 after traumatic brain injury. We aim to show that inhibition of the extracellular signal regulated kinase (ERK) would attenuate MMP-9 levels, reduce blood-brain barrier damage, and attenuate edema after trauma induced by controlled cortical impact in mouse brain. Western blots showed that phospho-ERK was rapidly upregulated after trauma. Treatment with U0126, which inhibits MEK, the kinase upstream of ERK, effectively prevented the activation of ERK. After trauma, gelatin zymography showed an increase in MMP-9. U0126 significantly reduced trauma-induced MMP-9 levels. Correspondingly, U0126 ameliorated the degradation of the tight junction protein ZO-1, which is an MMP-9 substrate, and significantly attenuated tissue edema. At 7 days after trauma, traumatic lesion volumes were significantly reduced by U0126 compared with saline-treated controls. These data indicate that the ERK MAPK pathway triggers the upregulation in MMP-9 after trauma, and further suggest that targeting the upstream signaling mechanisms that regulate deleterious MMP-9 activity may reveal new therapeutic opportunities for traumatic brain injury.     

Vascular complications of allograft nephrectomy.

OBJECTIVES: To identify risk factors that predisposes patients to vascular complications from allograft nephrectomy and to determine the safe management of this group of patients. DESIGN: This is a retrospective review of 1543 renal transplants performed in our institution between January 1990 and January 2002. PATIENTS AND METHODS: During this period, 161 (10.4%) transplant nephrectomies were performed, of which we identified nine patients (5.6%) who sustained significant vascular complications. RESULTS: Seven patients required ligation of external iliac artery for control of haemorrhage. Immediate vascular reconstructions (femoral-femoral cross-over bypass in two cases and one vein patch to an external iliac artery defect) were performed in three patients. Two patients had endovascular stenting of their external iliac artery pseudoaneurysm. No patient suffered limb loss. However, three patients died-two died from overwhelming sepsis and one patient died of an intra-cerebral haemorrhage. CONCLUSIONS: While vascular complications associated with transplant nephrectomy are relatively rare, they are associated with a significantly poor outcome. Immediate attempts to reconstruct the vascular supply to the lower limb are associated with a high complication rate. We advocate that where possible, vascular reconstruction should be deferred and that external iliac artery ligation can be performed safely with surprisingly low limb ischaemia rate.     

Effectiveness of near-peer simulation for managing the acutely deteriorating patient among residents of an internal medicine junior residency programme

INTRODUCTIONNear-peer teaching is gaining popularity as a teaching modality, as it improves the learner’s understanding, is targeted at an appropriate level and promotes familiarisation. This study was initiated to evaluate the effectiveness of incorporating near-peer instruction into simulation-based training within a junior residency programme.METHODS42 first-year residents from an internal medicine junior residency programme were recruited. Participants underwent a simulation-based training programme conducted over five weeks. Each week involved either an emergency or acute clinical scenario. A structured questionnaire was administered prior to and after the course to compare participants’ perceived knowledge, experience and confidence in managing the clinical scenarios.RESULTSIn our study, 83% of participants agreed/strongly agreed that the scenarios were realistic. There were improvements in perceived knowledge, experience and confidence after the course. The greatest improvement was seen for experience (post-simulation: median 7.00 [interquartile range (IQR) 6.00‒8.00] vs. pre-simulation: median 5.00 [IQR 3.00–6.25]). 65% of participants were keen to help with future training.CONCLUSIONNear-peer simulation training was found to be a viable and valuable method of instruction for first-year residents for increasing experience, instilling confidence and improving perceived knowledge. Integration of such programmes within medical education curricula shows good promise of continuity, with many first-year residents inspired to organise subsequent sessions.     

A thromboxane synthetase antagonist ameliorates progressive renal disease of Dahl-S rats

Recent studies have suggested a role for thromboxane in the progression of renal disease. The current study evaluated the role of this arachidonic acid metabolite in a model of renal disease which bears many biologic similarities to that in the kidneys of patients with chronic progressive renal failure. The model is that induced by ferritin-anti-ferritin immune complex nephritis in Dahl-salt sensitive rats rendered hypertensive by a high salt intake. Rats with this model of renal disease were chronically given a thromboxane synthetase antagonist OKY-046 or a placebo treatment from 16 to 29 weeks of age. Sequential observations of serum creatinine and 24-hour urinary protein excretion showed an ameliorating effect of OKY-046 on these renal parameters. Histologic examination of the kidneys also showed significantly less glomerular sclerosis in OKY-046 treated animals. The efficacy of OKY-046 was monitored by measurements of serum TXB2 levels and of glomerular production of TXB2 (and other prostaglandins); amounts of TXB2 were significantly reduced in the OKY-046 group. It is concluded that blockade of thromboxane generation has been successful in ameliorating the functional and structural lesions in this model of renal disease, providing further support to the thesis that thromboxane is an important mediator in events leading to eventual chronic renal failure and sclerosis.