Search

Substance use disorders are nearly twice as common among sexual minority youth (SMY) as among their heterosexual peers. Most applied literature about this population suggests interventions on eithe...

Suicide is a growing public health issue among adolescents. While the majority of transgender and gender diverse (TGD) youth are healthy, many experience suicidal thoughts and behavior (STB). Due to discrimination and stigma, TGD youth attempt suicide at higher rates then heterosexual, cisgender and even cisgender, LGBQ youth. Despite this vulnerability to suicide, few treatments have been developed and tested for this population. One treatment, attachment-based family therapy (ABFT) has been adapted to work with LGBQ youth and may be promising for TGD adolescents at risk for suicide. This article provides an overview of our ABFT modifications for TGD youth with thoughts of suicide. Specifically, we illustrate how treatment outcomes, in a single case study, relate to processes within clinical treatment tasks. The case study demonstrates the application of these ABFT modifications with a self-identified, gender nonconforming adolescent (who had recently attempted suicide) and his caregivers. Treatment evaluation measures were collected over the course of 24 weeks to illustrate the youth's clinical progress. The youth's suicidal symptoms diminished markedly by the end of treatment. Further, the family reported an increased ability for problem solving and more open communication by treatment conclusion.El suicidio es un problema de salud pública cada vez mayor entre los adolescentes. Si bien la mayoría de los jóvenes transgénero y de géneros diversos (TGD) son saludables, muchos tienen pensamientos y conductas suicidas. Debido a la discriminación y al estigma, los índices de intento de suicidio en los jóvenes TGD son más altos que en los jóvenes heterosexuales, cisgénero e incluso LGBQ cisgénero. A pesar de esta vulnerabilidad al suicidio, se han desarrollado y se han evaluado pocos tratamientos para esta población. Un tratamiento, la terapia familiar basada en el apego (TFBA), se ha adaptado para trabajar con jóvenes LGBQ y puede ser prometedor para adolescentes TGD en riesgo de suicidio. Este artículo ofrece un resumen de nuestras modificaciones a la TFBA para los jóvenes TGD con pensamientos de suicidio. Específicamente, ilustramos cómo los resultados del tratamiento, en un solo caso práctico, se relacionan con los procesos dentro de las tareas del tratamiento clínico. El caso práctico demuestra la aplicación de estas modificaciones de la TFBA con un adolescente que se identificó como de género no conforme (y que recientemente había intentado suicidarse) y sus cuidadores. Se recopilaron las valoraciones de una evaluación del tratamiento durante el transcurso de 24 semanas para ilustrar el avance clínico del joven. Los síntomas de suicidio del joven disminuyeron notablemente al final del tratamiento. Además, la familia informó una mayor capacidad para resolver problemas y una comunicación más abierta al concluir el tratamiento.自杀是青少年中一个日益严重的公共卫生问题。虽然大多数变性和性别多样化（TGD）的青少年是健康的，但许多人经历过有自杀的念头和有自杀行为（STB）出现的时候。由于歧视和感到被污名化，TGD青少年试图自杀的比例高于异性恋、双性恋，还有双性恋的LGBQ青少年。尽管这类人群很容易有自杀的可能性，但针对这一人群的治疗方法很少被开发和试验出来。有一种治疗方法，即基于依恋的家庭治疗（ABFT）已被应用于针对LGBQ青少年的治疗方法，并可能对有自杀风险的TGD青少年有帮助。本文概述了我们对有自杀想法的TGD青少年进行干预的ABFT的实践。具体来说，我们在一个单一的案例研究中，说明了治疗结果与临床治疗任务的过程之间的关系。该案例研究展示了这些ABFT调适之后的应用，对象是一个自我认同的、性别不一致的青少年（他最近曾试图自杀）和他的照顾者。在24周的时间里，治疗评估措施都被汇总，以说明该青少年的临床进展。在治疗结束时，该青少年的自杀症状明显减少了。此外，家庭报告说，在治疗结束时，其解决问题的能力有所提高，沟通也更加开放。.

Paracetamol overdose (POD) is a major clinical problem as the commonest cause of fulminant hepatic failure (FHF) in the UK and the USA. While the main loss of liver mass occurs following hepatocyte necrosis, hepatocyte apoptosis has also been reported to occur during paracetamol toxicity in murine liver. Hepatocyte apoptosis has not previously been identified in human liver and the significance of apoptosis in paracetamol toxicity is not known. In this study of paracetamol toxicity in human liver after POD, hepatocyte apoptosis was identified at time of liver transplantation or death and was associated with striking regenerative activity. The biological significance of apoptosis is unclear but the rates of apoptosis found (0.6%) could account for a significant loss of hepatic parenchyma. The stimulus for apoptosis is not known but it is unlikely to be induced directly by paracetamol since it is absent from serum at this time. The possibility that apoptosis may be induced by Kupffer cell activation with cytokine production is raised. Patients who develop FHF after POD have a poor prognosis, with few therapeutic options apart from liver transplantation; an understanding of the dynamics of liver regeneration and ongoing cell loss by apoptosis may allow the development of new therapies in these patients.

Chronic alcohol misuse is the most common cause of hepatic steatosis. The accumulation of lipid is reversible with abstinence, but some workers have suggested that the severity of hepatic steatosis predicts the progression with time to alcoholic cirrhosis. Triacylglycerol is the major accumulating lipid and subcellular fractionation and electron microscopy studies have shown accumulation of lipid droplets within the golgi fraction. This is consistent with the reports in both experimental animals and man of reduced hepatic secretion of very low density lipoprotein triacylglycerol which may be secondary to acetaldehyde-induced disruption of the cytoskeletal elements. In addition, hepatic production of triacylglycerol increases, but most studies in animal models suggest that increased triacylglycerol synthesis becomes less important as hepatic lipid accumulates.

The systemic inflammatory response syndrome (SIRS) and sequential organ failure assessment (SOFA) scores are widely used as prognostic markers in critical care settings and could improve triage of high-risk paracetamol (acetaminophen) overdose patients.To evaluate the prognostic accuracy of the SIRS and SOFA scores following single time point paracetamol overdose.Analysis of 100 single time point paracetamol overdoses admitted to a tertiary liver centre, with subsequent prospective validation of identified thresholds. Individual laboratory samples were correlated with the corresponding clinical parameters in relation to time post-overdose, and the daily SOFA and SIRS scores calculated.A total of 74 (74%) patients developed the SIRS, which occurred significantly earlier in patients who died (n=21) compared with spontaneous survivors (n=53, P=0.05). The SIRS occurred in 70 (70%) patients by 96h post-overdose, with a 30% mortality rate; compared with 0% mortality in the 30 non-SIRS patients (P=0.001). Median SOFA scores were significantly higher in nonsurvivors at 48 (P=0.009), 72 (P0.001), and 96h (P0.001). A SOFA score7 during the first 96h post-overdose predicted death/transplantation with a sensitivity of 95.0 (95% CI 78.5-99.1) and specificity of 70.5 (95% CI 66.3-71.6). A validation cohort of 38 single time point paracetamol overdoses confirmed the extremely high negative predictive value of both the SIRS and SOFA thresholds.The absence of either a SOFA score7 or a SIRS response during the first 96 h following paracetamol overdose could improve triage and reduce transfers of lower risk patients to tertiary liver centres.

Anorexia nervosa is currently considered a disorder confined to Western culture. Its recent identification in non-Western societies and different subcultures within the Western world has provoked a theory that Western cultural ideals of slimness and beauty have infiltrated these societies. The biomedical definition of anorexia nervosa emphasizes fat-phobia in the presentation of anorexia nervosa. However, evidence exists that suggests anorexia nevosa can exist without the Western fear of fatness and that this culturally biased view of anorexia nervosa may obscure health care professionals' understanding of a patient's own cultural reasons for self-starvation, and even hinder their recovery.

Chemokines are small protein inflammatory mediators that were classically known for their elicitation of inflammatory cells out of the vasculature. However, more contemporary studies show that these ubiquitous factors impinge on many facets of biology, including hematopoiesis, angiogenesis, and mitogeneis. The elucidation of mechanisms involved in the immunopathogenesis of liver disease has magnified the importance of chemokines in this organ. Accordingly, a number of in vitro and in vivo studies have highlighted the importance of chemokine biology in both acute and chronic liver disease, and a variety of liver diseases have been shown to involve chemokines and their receptors during the initiation and main tenance of liver pathology. A greater understanding of the role chemokines play during liver disease may permit the employment of therapies that target or enhance chemokines in the liver. This review will highlight the current clinical and experimental research in the immunopathogenesis of acute and chronic liver diseases.

Aims —To investigate the associations between the Rsa I, Dra I, and Taq I genetic polymorphisms of cytochrome p4502E1 and susceptibility to alcoholic liver disease or to hepatocellular carcinoma. Methods —DNA samples isolated from 61 patients with alcoholic liver disease, 46 patients with hepatocellular carcinoma, and 375 healthy controls were subjected to polymerase chain reaction amplification followed by digestion with the endonucleases Rsa I, Dra I, or Taq I. Meta-analysis was performed using data from previous studies of Rsa I polymorphism and the risk of alcoholic liver disease. Results —No association was found between any of the three polymorphisms and susceptibility to hepatocellular carcinoma. The distributions of Rsa I and Dra I alleles among the patients with alcoholic liver disease were not significantly different from those among the control group. Meta-analysis of this data and previous data concerning Rsa I polymorphism and alcoholic liver disease risk failed to demonstrate any significant association between the two. However, the alcoholic liver disease group in this study showed a significantly lower frequency of the less common Taq I allele compared with the healthy control group (odds ratio, 0.33; 95% confidence interval, 0.12 to 0.78). Conclusions —Possession of the less common Taq I cytochrome p4502E1 allele is associated with reduced susceptibility to alcoholic liver disease. There is no existing evidence that the Taq I polymorphism is directly associated with altered alcohol metabolism, but it might be in linkage disequilibrium with as yet unidentified protective factors.

Paracetamol-induced hepatic necrosis is the most common form of toxic liver injury experienced in clinical practice in the UK and USA. Recently, reports have described prevention of hepatic necrosis, induced by other hepato-toxins, by inhibiting tumour necrosis factor alpha (TNFalpha). The aim of the present study was to determine the role of TNFalpha in paracetamol-induced hepatic necrosis. Six-week-old CBA/J female mice were given 300 mg/kg paracetamol by intraperitoneal (IP) injection after an 8-h fast. Hepatic expression of TNFalpha was measured by enzyme-linked immunoassay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR). Serum TNFalpha was measured by ELISA. One hour prior to paracetamol injection, mice were also given blocking anti-TNFalpha antibodies, soluble TNFalpha receptor, interleukin 10 (IL-10), and dexamethasone. Hepatic injury was measured by serum aspartate aminotransferase and histological assessment on haematoxylin and eosin (HE)-stained liver sections. There was a significant increase in serum TNFalpha at 6 h (control 0.002+/-0.002 ng/ml, n=7; paracetamol-treated 0.022+/-0.007 ng/ml, n=5, p0.05), but hepatic TNFalpha expression did not change up to 24 h following paracetamol injection. Histologically severe centrilobular hepatic necrosis was noted at 3 h and progressed for 24 h after paracetamol poisoning. Death rate, serum aspartate aminotransferase, and hepatic histology were not significantly different between the groups treated with blocking anti-TNFalpha antibodies, soluble TNFalpha receptor, IL-10, and dexamethasone, compared with controls. In conclusion, there is no evidence to suggest that modulation of TNFalpha expression affects hepatic injury following experimental paracetamol poisoning; anti-TNFalpha therapies are therefore unlikely to be effective in the corresponding clinical situation.

The social use of ecstasy (methylenedioxymethampheta-mine, MDMA) and amphetamines is widespread in the UK and Europe, and they are popularly considered as 'safe'. However, deaths have occurred and hepatotoxicity has featured in many cases of intoxication with amphetamine or its methylenedioxy analogues such as ecstasy. Recreational use of these drugs presents an important but often concealed cause of hepatitis or acute liver failure, particularly in young people. The patterns of liver damage and multiple putative mechanisms of injury are discussed. Recognition of the aetiological agent requires a high index of suspicion. Optimum management of the resultant liver damage, including the controversial role of liver transplantation for fulminant hepatic failure, is also discussed.

The clinical history and examination is essential in the evaluation of patients with liver disease. This chapter details important points in the clinical history and examination allowing the physician to identify likely causes of liver damage and their investigation. The evaluation should allow the physician to differentiate acute and chronic liver diseases, and in the latter case separate those with obstructive or chronic parenchymal liver disease. It should also allow identification of important complications such as encephalopathy, ascites and portal hypertension. Identification of these main features or complications of liver disease by the clinical evaluation leads to a logical plan of investigation and prompt diagnosis and management of the liver disease.

Transjugular intrahepatic portosystemic stent-shunts (TIPSS) have been shown to reduce portal hypertension consistently and have recently been reported to arrest active variceal hemorrhage. This retrospective and nonrandomized study compares the results of TIPSS with esophageal transection (ET) and devascularization in patients with uncontrolled variceal hemorrhage admitted to a single center with an interest in variceal bleeding.Two hundred and sixty cirrhotic patients have been referred with variceal bleeding over the past 7 yr. In 41 patients (15.8%), hemorrhage was uncontrolled despite two treatments with sclerotherapy. Thirty-eight patients were eligible for analysis. Nineteen were considered for ET and 19 for TIPSS. Patients in the two groups were well matched for age, sex, etiology of liver disease, and its severity and complications. They have been followed for 13 patient years (TIPSS-7, longest 20 months; ET-6, longest 23 months). Data for survival and rebleeding were analyzed by the Kaplan-Meier method on an intention-to-treat basis.Seven of the 19 were considered unfit for surgery, and 12 underwent esophageal transection and devascularization. TIPSS was undertaken successfully in 17 patients, the Palmaz stent being used in 4 and the Wallstent in 13. Successful TIPSS reduced the mean portal pressure gradient from 22.2 (SE 1.2) to 9.7 (SE 0.7) mm Hg (p0.001). Mortality within 30 days of the initial bleed was 42% in the TIPSS group compared with 79% in the ET group (p0.05). Rebleeding occurred in 15.6% patients with TIPSS, compared with 26.2% in the ET group. Encephalopathy in the two groups of patients was not significantly different (TIPSS 25% and ET 22%). TIPSS was followed by active infection in 20% compared with 36% after ET.This study shows that the overall mortality in this group of patients is high whatever the type of treatment used. TIPSS can be performed successfully on these patients who are often not suitable for surgery. Mortality rates were significantly lower in patients treated by TIPSS. Compared with ET, TIPSS should be regarded as the preferred mode of treatment for uncontrolled variceal hemorrhage in patients with cirrhosis.

A micromethod was developed to assay the hepatic activity and subcellular distribution of phosphatidate phosphohydrolase (PAH, EC 3.1.3.4), an important regulatory enzyme in triacylglycerol synthesis, in human needle biopsy specimens. In normal liver PAH is predominantly cytosolic in distribution, but on treatment with oleic acid it shifts to the membranous compartments of the cell, its physiologically active site. The hepatic specific activity of PAH was similar in controls and patients with fatty liver but significantly more of the enzyme was associated with the membranous compartments in patients with severe alcoholic fatty liver. These observations may explain the enhanced rates of triacylglycerol synthesis observed in these patients and may be implicated in the pathogenesis of alcoholic fatty liver.

Variceal haemorrhage is a common and frequently fatal presentation of cirrhosis. There have been several recent developments in endoscopic therapy, pharmacological therapy and portal shunting, offering new therapeutic options. These are reviewed and followed by a management strategy incorporating these developments with established therapies.

We assessed the long-term efficacy of transjugular intrahepatic portasystemic stent-shunt (TIPSS) in 64 patients. Insertion was successful in 56 patients (87.5%). The reasons for its use were: variceal bleeding (49); ascites (6); portal hypertensive gastropathy (6); hypersplenism (2); and embolization of a spontaneous shunt (1). Fourteen patients were Childs A, 20 Childs B and 28 Childs C cirrhotics. Two patients were non-cirrhotic; one with amyloidosis and one with non-cirrhotic portal fibrosis. Patients were followed clinically and radiologically (Doppler ultrasonography and routine portography at 6 months). During 33 patient-years of follow-up, 22 died, 12 during index admission (two were procedure-related) and nine were transplanted. Twenty-five patients are alive, with a mean survival of 7.1 (SD 7) months. Variceal rebleeding occurred in 10 patients (22.7%), one of whom died, and was always associated with shunt insufficiency (shunt thrombosis 2, hepatic vein stenosis (HVS) 1, intimal hyperplasia (IH) 4, dislocated stent 1, inadequate stent 2). Clinical encephalopathy was induced in seven patients (17.1%) following TIPSS. All responded to medical therapy, but two required reduction in shunt size. Ascites improved after TIPSS in 36 patients (87.8%), but reaccumulated in seven (17.5%), associated with shunt dysfunction in five (SBP 2, IH 3, HVS 2). Fatal sepsis occurred in two patients, and 14 other episodes of infection required antibiotics. TIPSS is a useful treatment for variceal bleeding, resistant ascites and portal hypertensive gastropathy. Shunt dysfunction and sepsis occur frequently, and regular surveillance is necessary.

Transjugular intrahepatic portosystemic stent shunt (TIPSS) is a new percutaneous technique for reducing portal venous pressure. We attempted TIPSS in six patients with recurrent bleeding for oesophageal or gastric varices between July 1991 and January 1992 with success in five. There have been no deaths. One patient re-bled after TIPSS. His portal pressure was found to be elevated persistently indicating an inadequate shunt. Following further dilatation of the shunt, portal pressure fell to a satisfactory level and bleeding has not recurred. No bleeding episodes have occurred in the other patients following successful TIPSS. Our series contributes to the growing body of experience which suggests that TIPSS is a safe and effective treatment for recurrent variceal bleeding.

Understanding the morphological, movement, and biomechanical characteristics that influence rearfoot motion during lateral movements is necessary for footwear design and for the determination of injury mechanisms. The purpose of this study was to identify factors related to rearfoot kinematics during a lateral braking movement. Seven highly skilled male tennis players performed 24 trials of side shuffle movements at various speeds. A rear view of the right leg performing a braking step onto a force platform was filmed. The neutral-O landing style was most commonly demonstrated. Average movement velocity, foot velocity at touchdown, and body mass were variables demonstrating weak or nonsignificant correlations with the rearfoot parameters. Although structural inversion was correlated significantly with the maximum rearfoot angle and velocity (r = -0.52 and -0.69), the results were affected by movement speed and sample size. The biomechanical characteristics displayed the greatest influence on the various rearfoot kinematic parameters. The magnitude of the significant (P less than 0.0001) correlations generally decreased in the following order: maximum horizontal and vertical force gradients, corresponding times to the maximum gradient values, maximum horizontal and vertical forces, and the corresponding times to maximum forces. In conclusion, the gradient-associated parameters were the most useful biomechanical parameters for predicting changes in rearfoot kinematics.

In experimentally produced alcoholic fatty liver microsomal fatty acid composition was measured using gas chromatography. The results showed an increase in linoleic acid (18:2, n-6) and hexadecaenoic acid (22:6, n-3) and a decrease in arachidonic acid (20:4, n-6) in alcohol-fed rats. Using high performance liquid chromatographic separation of radiolabelled substrate and products, delta 9, delta 6 and delta 5 desaturase enzymes were assayed. The activity of delta 9 and delta 5 desaturase was decreased in alcohol-fed rats and delta 6 desaturase activity was similar in control and alcohol-fed groups. These results indicated there was no causal relationship between desaturase activity and membrane fatty acid changes. Increased amounts of eicosatrienoic acid (20:3, n-9) in rats fed less than 5% fat were observed in both control and alcohol-fed rats. The results indicated that essential fatty acid deficiency was not due to alcohol consumption.