Autophagy: highlighting a novel player in the autoimmunity scenario

Autophagy is a physiological cellular mechanism that degrades and recycles proteins and other molecules to maintain an adequate amino acid level during nutritional starvation of the cell. Autophagy is involved in cellular homeostasis and differentiation, as well as in tissue remodeling, aging, cancer, and other diseases. Under particular environmental conditions, autophagy can also be a contributor to programmed cell death, or can act as a defense mechanism for the elimination of intracellular bacteria and viruses. According to recent experimental data, autophagy may be implicated in autoimmunity by promotion of major histocompatibility complex (MHC) class II presentation of cytosolic antigens and control of T lymphocyte homeostasis, and its induction by Th1 cytokines and perhaps by specific serum autoantibodies. We review herein the role of autophagy in immune function and its possible contribution to breakdown of tolerance and development of autoimmunity.     

Les kystes du ligament croisé antérieur : à propos de 24 cas

The purpose of this study is to present clinical and magnetic resonance imaging (MRI) features of ganglion cysts of the anterior cruciate ligament (ACL). Such cysts are rare and often unsuspected. We reviewed a series of 24 ganglion cysts of the ACL (7 females, 17 males) between 1998 and 2004. The mean age was 45 years old (25–74). All patients presented with knee pain. The mean follow-up was 25 months (6–48). All patients had a preoperative MRI, which confirmed the diagnosis. Seventeen patients had an arthroscopic treatment and 7 were treated with percutaneous aspiration and steroid injection under. Fourteen patients were evaluated with the International knee Documentation Committee (IKDC) subjective score. Computed tomography or ultrasound guidance. MRI demonstrated 16 mucoid degenerative cysts of the ACL and 8 well circumscribed ganglion cysts with a fluid collection. The surgical pathology confirmed 13 mucoid cysts and 4 ganglion cysts; 2 recurrences were observed after surgical treatment. After percutaneous aspiration, we observed 3 recurrences, 2 failures and one vascular complication. We observed two types of ACL cysts, which could be differentiated on the MRI. Percutaneous treatment was less reliable than surgical treatment. The percutaneous aspiration should be reserved to the ganglion cysts with fluid collection, while arthroscopy is indicated for the failure cases. We recommend resection for the mucoid cysts. An aggressive resection of the ACL may compromise the knee stability so that the patient must be informed preoperatively. In theses cases, aspiration was often inefficient.     

Transcranial US of preterm neonates: High risk gestational age and birth weight for perinatal asphyxia

Objective

The study aims to determine the high risk gestational week (GW) and/or birth weight (BW) of the preterm neonate, below which perinatal hypoxic cerebral injuries are expected to occur.

Material and methods

Eighty preterm neonates, born at or before 37 GW, were included. Twenty-three of them were <32 GW and 57 >32 GW. Also, 28 of them were <1500 g and 52 >1500 g. Imaging was done by transcranial ultrasound with 4–9 MHz curvilinear probe. CT scan was additionally performed for only 18 candidates. The study protocol was approved by the ethics committee in Al-Mana General Hospital (AGH).

Results

Intraventricular hemorrhage (IVH) was diagnosed in six preterm neonates <32 GW and two >32 GW. Three <32 GW and one >32 GW presented with hypoxic ischemic encephalopathy (HIE) with no hemorrhage. Two preterm neonates <32 GW had both IVH & HIE. All positive cases were below 1500 g BW.

Conclusion

Preterm neonates <32 GW and/or <1500 g are highly susceptible for HIE and/or IVH. Thus, special medical care, including post-labor hospitalization in well equipped special baby care units (SCBU) and routine transcranial ultrasound (TCUS) screening is recommended for those preterm neonates.     

From bases to basis: linking genetics to causation in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a multifactorial autoimmune disease with inherited and environmental components in pathogenesis. It is exceptional among autoimmune diseases in showing strong heritability according to familial occurrence and monozygotic twins concordance, yet with weak associations with the usual genetic risk elements for autoimmunity, such as the HLA alleles. Among the latter, there is risk (at least in some populations) conferred by HLA DRB1*08 and possibly some protection by DRB1*11. However, the inconsistency among studies on HLA is surprising, given that PBC is a relatively homogenous disease entity. Among non-HLA genes, some studies implicate polymorphisms of genes for cytotoxic T-lymphocyte antigen-4, interleukin-2, or interleukin-10; polymorphisms of the vitamin D receptor could synergize with low sunlight exposure to create deficiency of the immunoregulatory factor, activated vitamin D. A new lead is available from the finding in female subjects with PBC of an increase in the degree of monosomy of the X chromosome that is presumed to carry immune response genes. A further suggested source of inquiry is the apparent protection of African-American women from PBC. Finally, data on inheritance should be sought in PBC by descent methodology, rather than by cross-sectional association studies in cases and control subjects, and based on analysis of a large number of families with an affected member through a worldwide effort.     

Liver abnormalities in connective tissue diseases

The liver is a lymphoid organ involved in the immune response and in the maintenance of tolerance to self molecules, but it is also a target of autoimmune reactions, as observed in primary liver autoimmune diseases (AILD) such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. Further, the liver is frequently involved in connective tissue diseases (CTD), most commonly in the form of liver function test biochemical changes with predominant cholestatic or hepatocellular patterns. CTD commonly affecting the liver include systemic lupus erythematosus, antiphospholypid syndrome, primary Sjögren's syndrome, systemic sclerosis, dermatomyositis, polimyositis, and anti-synthetase syndrome, while overlap syndromes between AILD and CTD may also be diagnosed. Although liver cirrhosis and failure are extremely rare in patients with CTD, unusual liver conditions such as nodular regenerative hyperplasia or Budd–Chiari syndrome have been reported with increasing frequency in patients with CTD. Acute or progressing liver involvement is generally related to viral hepatitis reactivation or to a concomitant AILD, so it appears to be fundamental to screen patients for HBV and HCV infection, in order to provide the ideal therapeutic regimen and avoid life-threatening reactivations. Finally, it is important to remember that the main cause of biochemical liver abnormalities in patients with CTD is a drug-induced alteration or coexisting viral hepatitis. The present article will provide a general overview of the liver involvement in CTD to allow rheumatologists to discriminate the most common clinical scenarios.     

Computer-administered cognitive-behavioral therapy for depression

The authors evaluated a six-session interactive computer cognitive-behavioral treatment program given to volunteer patients who met Research Diagnostic Criteria (RDC) for major or minor depressive disorder. Patients were randomly assigned to computer-administered cognitive-behavioral treatment, to therapist-administered cognitive-behavioral treatment, or to a waiting-list control condition. After treatment and at 2-month follow-up, both treatment groups had improved significantly more than control subjects in their scores on the Beck Depression Inventory, SCL-90-R depression and global scales, Hamilton Rating Scale for Depression, and Automatic Thoughts Questionnaire. The treatment groups did not differ from each other at either time.     

Aicardi syndrome with favorable outcome]

BACKGROUND: Aicardi syndrome is usually associated with a very poor outcome. CASE REPORT: We report a particular case of Aicardi syndrome characterised by a partial agenesis of the corpus callosum associated with an arachnoidal interhemispheric cystic formation, and by a complete control of epilepsy and a favorable outcome regarding visual and psychomotor performances. CONCLUSION: A better prognosis could be expected in Aicardi syndrome when spasms occur lately and are not preceded by partial seizures, when agenesis of corpus callosum is partial and especially when chorioretinal lacunae are small, isolated, few and spare the macula.     

The importance of a home care program for patients with advanced cancer pain

At the Pain Clinic of the National Cancer Institute of Milan, a special Home Care Program has been set up to assist advanced cancer patients with pain and their families during their remaining survival. The Home Care Unit comprises a team of physician, nurse clinicians, psychologists and many volunteers who are active both in the hospital and at the patient's home. This entire operation provides a continuous relationship between the family, the patient and the Home Care Unit. This Home Care Program, which is one of a kind with other forms of treatment for advanced cancer patients (i.e. hospices), has produced interesting results. Out of a sample group of 50 patients, 33 were monitored at home by the Home Care Unit while 17 had their families to do the monitoring. Over a six-week period the following results were reported: a) Improvement of psycho-emotional factors such as anxiety, weakness and mood for both patients and their families who entered the Home Care Program. b) The Quality of Life Index remained unchanged for the sample group that entered the Home Care Program whereas it deteriorated for patients monitored by their families. c) A decrease in the Integrated Pain Score for both groups; however, results showed a statistically significant difference in favor of patients on the Home Care Program. d) The Performance Status decreased by very little over the study period, and there was little difference between the two groups. These results confirm the need for a Home Care Program which must go hand in hand with the Pain Clinic as an effective way to control Total Pain.