Musculoskeletal involvement in systemic sclerosis

Musculoskeletal involvement is more frequent than expected in patients with systemic sclerosis (SSc) and is a major cause of disability, even if the prognosis of the disease largely depends on visceral involvement. The most common clinical feature of musculoskeletal involvement is arthralgia; less frequent features are arthritis, flexion contractures, stiffness (affecting predominantly fingers, wrists and ankles), proximal muscle weakness (mainly of the shoulder and hip) and tendon sheath involvement. Tendon friction rubs are predictive of poor prognosis. If musculoskeletal involvement is suspected, serum creatinine phosphokinase, aldolase, lactate dehydrogenase, alkaline phosphate, rheumatoid factor and anticyclic citrullinated peptide autoantibodies should be checked routinely. Treatment for muscle involvement has not yet been considered adequately and, in the future, it is to be hoped that clinical trials will identify new drugs to control this aspect of SSc, which seriously compromises patients' quality of life.     

The Autism Impact Measure (AIM): Initial Development of a New Tool for Treatment Outcome Measurement

The current study describes the development and psychometric properties of a new measure targeting sensitivity to change of core autism spectrum disorder (ASD) symptoms, the Autism Impact Measure (AIM). The AIM uses a 2-week recall period with items rated on two corresponding 5-point scales (frequency and impact). Psychometric properties were examined using a large sample (n = 440) of children with ASD enrolled in the Autism Treatment Network. The exploratory factor analysis indicated four factors and resulted in a 25-item questionnaire with excellent overall model fit. Test–retest reliability, cross-informant reliability, and convergent validity with other measures of ASD symptoms and overall functioning were strong. The AIM is a reliable and valid measure of frequency and impact of core ASD symptoms.     

Increased production of cytokines and growth factors by aortic allografts: A possible explanation for myointimal hyperplasia formation.

Accelerated myointimal hyperplasia is a major complication of arterial allografts. The aim of our study was to analyze the role of growth factors in the genesis of myointimal hyperplasia in arterial allografts. Two groups of experiments were performed: Isografts and Allografts. The Isograft group consisted of 18 inbred Lewis rats in which a 1-cm long segment of aorta was inserted as abdominal aortic interposition graft. The aortic segments were obtained from syngeneic Lewis rats. The Allograft group consisted of 18 inbred Lewis rats, in which a 1-cm long segment of aorta was interposed at the level of the abdominal aorta. The aortic segments were obtained from allogeneic Brown-Norway rats. No immunosuppression was used. The animals were sacrificed 4 weeks after surgery and the aortic grafts were analyzed by light, electron microscopy (n = 3 for each group) and immunohistochemistry (n = 3 for each group). In addition, aortic segments (n = 12 for each group) were put in an organ culture to assess production of growth factors. All allografts showed evidence of severe myointimal hyperplasia, which was minimal in isografts. PDGF, bFGF and TGF-beta(1) production, generally considered to be the cause of myointimal hyperplasia, was not increased in allografts, whereas IL-1, TNF-alpha and GM-CSF production was increased in allografts and probably lymphocytes were the source of these cytokines (p < 0.001). We conclude that myointimal hyperplasia in aortic allografts is associated with an increase of IL-1, TNF-alpha and GM-CSF produced by lymphocytes.     

Median Arcuate Ligament in Orthotopic Liver Transplantation: Relevance to Arterial Reconstruction

Median arcuate ligament (MAL) syndrome results from luminal narrowing of the celiac artery by the insertion of the diaphragmatic muscle fibers or by fibrous bands of the celiac nervous plexus. In 10% to 50% of cases it is responsible for significant angiographic celiac trunk compression. In orthotopic liver transplantation (OLT), the presence of celiac compression by MAL is considered to be a risk factor for hepatic arterial thrombosis (HAT); it may lead to graft loss. Various surgical procedures have been proposed to overcome the impact of MAL in OLT, but their impact is still ill defined. The aim of our study was to compare standard hepatic artery reconstruction and graft reconstruction (aortohepatic bypass) in terms of HAT among patients with MAL undergoing OLT. We retrospectively reviewed 168 adult recipients of OLT performed from January 1991 to December 1998. Ten cases (5.6%) of celiac compression by MAL were identified after celiomesenteric arteriography. There was no significant difference in terms of HAT incidence when aortohepatic bypass was performed compared to a standard anastomosis; moreover, this was greater in the graft reconstruction group (25% vs 17%; P = .67). In our opinion, the presence of an arcuate ligament should not contraindicate a routine hepatic artery reconstruction.     

Hypnosis, attention and concentration: reflections on the possibilities of hypnosis outside the hypnotic setting

The authors define the concepts of attention, concentration and hypnosis. Starting from these theses they examine the possible existence of a continuum of states of consciousness, from wakefulness to the so-called hypnosis, with an increasing number of correlations of neurophysiological plasticity. The authors point out that, in those cases in which the requirements needed for the hypnotic phenomenon to take place are lacking, it is possible to exploit the patient's 'concentration' by using a kind of ideoplastia which goes with it. The final question is whether or not the concepts of concentration and hypnosis are synonymous - whether or not concentration is hypnosis or vice versa. The authors offer some personal and original reflections on these questions.     

Quantitative analysis of wild-type and HBeAg minus hepatitis B viruses by a sequence-dependent primer extension assay

The ratio between wild-type hepatitis B virus (HBV) and HBV mutant, unable to secrete “e” antigen (HBeAg minus HBV) appears to be an important determinant of the outcome of chronic hepatitis B. Quantitative analysis of wild-type and HBeAg minus HBVs in the blood could be useful to monitor chronic hepatitis B patients. We developed a solid-phase minisequencing assay for both viruses using a primer-guided incorporation of a single labeled nucleotide on an affinity captured biotinylated amplified HBV-DNA template. A standard curve was constructed by mixing increasing quantities of wild type and mutant virus DNAs. The detection of wild-type and HBeAg minus sequences, ranging from 10% to 90% of overall viremia, was linear and reproducible till 0.1 pg/μl of serum HBV-DNA. The assay yields numerical values and the ratio of incorporated nucleotides defines the relative proportions (%) of the two viral sequences with accuracy. We tested the sensitivity and accuracy of the minisequencing on mixed end point dilutions of wild-type and HBeAg minus reference sera and amplified products. The feasibility and reproducibility of the assay were tested in 35 sera from 21 HBsAg positive patients with chronic hepatitis B using both minisequencing and oligo-hybridization assays. A high correlation was found between the two assays (r = 0.957 P < 0.0001). In conclusion, the minisequencing assay provides a precise and reproducible quantitative analysis of wild-type and HBeAg minus HBVs in clinical specimens. It is proposed to study the relations between HBV heterogeneity and the course of hepatitis B and its response to therapy. © 1994 Wiley-Liss, Inc.     

A new hepatitis C virus-like flavivirus in patients with cryptogenic liver disease associated with elevated GGT and alkaline phosphatase serum levels

Summary. The intriguing co-infection of two flaviviruses (GBV-A and GBV-B) in tamarins and the recent discovery of another flavivirus (GBV-C/HGV) in humans raises the question of the relations between hepatitis C virus (HCV) and GBV-C/HGV. To address this issue the sera of 285 patients with liver disease (102 patients with cryptogenic and 183 with known forms of chronic liver disease) and 19 patients without liver disease were tested for HGV-RNA. GBV-C/HGV-RNA was detected by RT-PCR using primers encompassing 5'NC and NS5 regions and hybridization with specific biotinilated and radiolabelled probes. GBV-C/HGV RNA was found in 11 of 20 (55%) acute hepatitis C patients, in 13 of 117 (11.1%) patients with chronic hepatitis C, in 11 of 27 patients with a liver transplant (40.7%), one of 19 (5.3%) patients with chronic HBV infection, 15 out of 102 (14.7%) patients with cryptogenic liver disease and two out of 19 patients with inflammatory bowel disease. In cryptogenic patients, elevated serum gammaglutamyl transpeptidase (GGT, higher than twice the normal values) and alkaline phosphatase (ALP, above normal values) levels were significantly associated with GBV-C/HGV-RNA infection ( P <0.001). In conclusion GBV-C/HGV appears to be transmitted in humans by blood exposure and to be associated with liver disease in HCV co-infected patients and in a minority of patients with cryptogenic disease. The virus is only occasionally pathogenic for the liver and when liver damage is present; the association with the combined elevation of GGT and APH serum levels might represent a specific feature of the liver tropism of the agent.