A polymorphism in TIM1 is associated with susceptibility to severe hepatitis A virus infection in humans

During infection with the hepatitis A virus (HAV), most patients develop mild or asymptomatic disease. However, a small number of patients develop serious, life-threatening hepatitis. We investigated this variability in disease severity by examining 30 Argentinean patients with HAV-induced acute liver failure in a case-control, cross-sectional, observational study. We found that HAV-induced severe liver disease was associated with a 6-amino-acid insertion in TIM1/HAVCR1 (157insMTTTVP), the gene encoding the HAV receptor. This polymorphism was previously shown to be associated with protection against asthma and allergic diseases and with HIV progression. In binding assays, the TIM-1 protein containing the 157insMTTTVP insertion polymorphism bound HAV more efficiently. When expressed by human natural killer T (NKT) cells, this long form resulted in greater NKT cell cytolytic activity against HAV-infected liver cells, compared with the shorter TIM-1 protein without the polymorphism. To our knowledge, the 157insMTTTVP polymorphism in TIM1 is the first genetic susceptibility factor shown to predispose to HAV-induced acute liver failure. Furthermore, these results suggest that HAV infection has driven the natural selection of shorter forms of the TIM-1 protein, which binds HAV less efficiently, thereby protecting against severe HAV-induced disease, but which may predispose toward inflammation associated with asthma and allergy.     

Pain coping profiles in adolescents with chronic pain

This study sought to evaluate the extent to which the pain coping profiles observed by Walker and colleagues in a sample of patients with chronic abdominal pain also were evident in a sample of adolescent patients who presented to a tertiary care clinic for evaluation of a variety of diverse pain conditions. In addition, we aimed to evaluate the relation of these pain coping profiles to patients' emotional and physical functioning. Participants (n=254) were adolescent patients aged 12-17 years. Patients completed the Pain Response Inventory (PRI) as well as measures of pain, somatic symptoms, anxiety and depressive symptoms, and functional disability. Using the PRI classification algorithm developed by Walker and colleagues, we successfully classified all the patients in our sample. We also found that the pain coping profiles successfully differentiated among patients with different levels of symptoms, disability, and emotional distress, further demonstrating the external validity of these profiles. Results have implications for tailoring pain treatment interventions to patients' particular coping profiles.     

Adverse outcomes of endoscopic retrograde cholangiopancreatography

Endoscopic retrograde cholangiopancreatography (ERCP) has evolved from a diagnostic tool into a primarily therapeutic procedure for a variety of biliary and pancreatic problems. ERCP can, however, cause a wide range of short-term complications, including pancreatitis, hemorrhage, and perforation. In general, complications appear to be associated primarily with patient-related factors and the technical skill of the endoscopist. Overall, the risk factors for complications include suspected sphincter of Oddi dysfunction and technique-related variables, such as difficult cannulation, precut sphincterotomy in inexperienced hands, failure to achieve drainage, and percutaneous transhepatic biliary access. Reviewed here are specific risk factors for post-ERCP pancreatitis and hemorrhage. A risk-factor assessment may be useful to help the endoscopist decide whether or not to perform ERCP and aids in making decisions regarding the techniques to be used. The principal strategies to reduce complications of ERCP include improving the training and education of endoscopists regarding risk factors; avoiding marginally indicated ERCP and preferentially using alternative imaging techniques; making referrals to advanced centers for complex or high-risk cases; and, in due course, concentrating ERCP practices among fewer endoscopists performing more ERCPs.     

Improved outcome of cervical neoplasia in HIV-infected women in the era of highly active antiretroviral therapy

Cervical neoplasia has been associated with human immunodeficiency virus (HIV) infection. Both preinvasive disease and invasive cervical cancer have been reported to have a much poorer outcome in HIV-infected women than in the general population. The use of highly active antiretroviral therapy (HAART) has resulted in significant improvements in the treatment of HIV infection, including a decrease in the incidence and severity of several acquired immune deficiency syndrome (AIDS)-related malignancies. Two cases of cervical dysplasia in HIV-infected women are presented, one from the pre-HAART era, who subsequently developed invasive cervical cancer and died, and one in whom HAART was used with good outcome. Data from several reports of the use of HAART in HIV-infected women indicates that the prognosis for cervical neoplasia is improved. Possible reasons for this improvement include better immune function seen in HAART-treated women, as well as increased surveillance for cervical neoplasia in HIV-infected women in recent years. However, the future impact of improved HIV care, including HAART, on cervical neoplasia is unclear.     

Use of saline contrast echo timing to distinguish intracardiac and extracardiac shunts: failure of the 3- to 5-beat rule

Patent foramen ovale (PFO) is thought to be associated with cryptogenic stroke and migraine headache. Saline contrast echocardiography (SCE) is the gold standard for identifying the presence of right-to-left shunt, whether from PFO or pulmonary arteriovenous malformation (PAVM). The timing of left heart contrast entry during SCE is used to distinguish a PFO from a PAVM, a method that is not as specific as previously thought. In this report, we describe a patient with a SCE demonstrating the early appearance of left heart bubbles during good effort Valsalva injections that is ultimately proven to be due to a PAVM. The case illustrates the limited specificity of left heart contrast timing during SCE as the sole criteria for differentiating intracardiac and extracardiac shunts.     

“Melanosis” in the small and large intestine

Deposition of pigment in the intestinal mucosa is commonly observed by the endoscopist, especially within the colon, and particularly during investigations for constipation. Pigment may also be detected in the small intestine. Although labeled as melanosis, electron microscopy and X-ray analytical methods have provided evidence that this pigment is not melanin at all, but lipofuscin. Often, herbal remedies or anthracene containing laxatives are often historically implicated, and experimental studies in both humans and animal models have also confirmed the intimate relationship with these pharmacological or pseudo-pharmacological remedies. The appearance of melanosis coli during colonoscopy is largely due to pigment granule deposition in macrophages located in the colonic mucosa. The pigment intensity is not uniform, being more intense in the cecum and proximal colon compared to the distal colon. Possibly, this reflects higher luminal concentrations of an offending agent in the proximal compared to distal colon, differential absorption along the length of the colon, or finally, differences in macrophage distribution within the colon. Mucosal lymphoid aggregates normally display a distinct absence of pigment producing a ＂starry sky＂ appearance, especially in the rectosigmoid region. Interestingly, some focal, usually sessile, colonic mucosal neoplastic lesions, rather than submucosal lesions, may be better appreciated as pigment deposition may be absent or limited. If detected, removal and further histopathologic analysis of the polyp may be facilitated.     

Management strategies for gastrointestinal,erectile, bladder,and sudomotor dysfunction in patients with diabetes

There are substantial advances in understanding disordered gastrointestinal autonomic dysfunction in diabetes. It occurs frequently. The underlying pathogenesis is complex involving defects in multiple interacting cell types of the myenteric plexus as well. These defects may be irreversible or reversible. Gastrointestinal symptoms represent a major and generally underestimated source of morbidity for escalating health care costs in diabetes. Acute changes in glycaemia are both determinants and consequences of altered gastrointestinal motility. 35–90% of diabetic men have moderate‐to‐severe erectile dysfunction (ED). ED shares common risk factors with CVD. Diagnosis is based on medical/sexual history, including validated questionnaires. Physical examination and laboratory testing must be tailored to patient's complaints and risk factors. Treatment is based on PDE5‐inhibitors (PDE5‐I). Other explorations may be useful in patients who do not respond to PDE5‐I. Patients at high cardiovascular risk should be stabilized by their cardiologists before sexual activity is considered or ED treatment is recommended. Estimates on bladder dysfunction prevalence are 43–87% of type 1 and 25% of type 2 diabetic patients, respectively. Common symptoms include dysuria, frequency, urgency, nocturia and incomplete bladder emptying. Diagnosis should use validated questionnaire for lower urinary tract symptoms. The type of bladder dysfunction is readily characterized with complete urodynamic testing. Sudomotor dysfunction is a cause of dry skin and is associated with foot ulcerations. Sudomotor function can be assessed by thermoregulatory sweat testing, quantitative sudomotor axon reflex test, sympathetic skin response, quantitative direct/indirect axon reflex testing and the indicator plaster. Copyright © 2011 John Wiley & Sons, Ltd.     

Methods of investigation for cardiac autonomic dysfunction in human research studies

This consensus document provides evidence‐based guidelines regarding the evaluation of diabetic cardiovascular autonomic neuropathy (CAN) for human research studies; the guidelines are the result of the work of the CAN Subcommittee of the Toronto Diabetic Neuropathy Expert Group. The subcommittee critically reviewed the limitations and strengths of the available diagnostic approaches for CAN and the need for developing new tests for autonomic function. It was concluded that the most sensitive and specific approaches currently available to evaluate CAN in clinical research are: (1) heart rate variability, (2) baroreflex sensitivity, (3) muscle sympathetic nerve activity, (4) plasma catecholamines, and (5) heart sympathetic imaging. It was also recommended that efforts should be undertaken to develop new non‐invasive and safe CAN tests to be used in clinical research, with higher sensitivity and specificity, for studying the pathophysiology of CAN and evaluating new therapeutic approaches. Copyright © 2011 John Wiley & Sons, Ltd.