Interferon-alpha reduces insulin resistance and beta-cell secretion in responders among patients with chronic hepatitis B and C

This study aimed at elucidating the effects of interferon (IFN)-alpha on glucose metabolism in patients with chronic hepatitis B and C infections. Twenty-eight biopsy-proven patients with chronic hepatitis B (ten cases) and hepatitis C (18 cases) were given IFN-alpha for a total of 24 weeks. The patients received a 75 g oral glucose tolerance test (OGTT), glucagon stimulation test, tests for type 1 diabetes-related autoantibodies and an insulin suppression test before and after IFN-alpha therapy. Ten of the 28 patients responded to IFN-alpha therapy. Steady-state plasma glucose of the insulin suppression test decreased significantly in responders (13.32+/-1.48 (S.E.M.) vs 11.33+/-1.19 mmol/l, P=0.0501) but not in non-responders (12.29+/-1.24 vs 11.11+/-0.99 mmol/l, P=0.2110) immediately after completion of IFN-alpha treatment. In the oral glucose tolerance test, no significant difference was observed in plasma glucose in either responders (10.17+/-0.23 vs 10.03+/-0.22 mmol/l) or non-responders (10.11+/-0.22 vs 9.97+/-0.21 mmol/l) 3 Months after completion of IFN-alpha treatment. However, significant differences were noted in C-peptide in both responders (2.90+/-0.13 vs 2.20+/-0.09 nmol/l, P=0.0040) and non-responders (2.45+/-0.11 vs 2.22+/-0.08 nmol/l, P=0.0287) before vs after treatment. The changes of C-peptide in an OGTT between responders and non-responders were also significantly different (P=0.0028), with responders reporting a greater reduction in C-peptide. No case developed autoantibodies during the treatment. In patients who were successfully treated with IFN-alpha, insulin sensitivity improved and their plasma glucose stayed at the same level without secreting as much insulin from islet beta-cells.     

Relaxin-3 in GABA projection neurons of nucleus incertus suggests widespread influence on forebrain circuits via G-protein-coupled receptor-135 in the rat

Relaxin-3 (RLX3) is a newly identified member of the relaxin/insulin peptide family that is highly conserved across a range of species from fish to mammals and is highly expressed in rat, mouse and human brain. Extensive pharmacological studies have demonstrated that RLX3 is a high affinity, selective ligand for G-protein-coupled receptor-135 (GPCR135, now classified as relaxin family peptide-3 receptor; RXFP3). In ongoing studies to understand the physiological functions of RLX3, the distribution of RLX3-containing neuronal elements in rat brain was determined by immunohistochemistry, using an affinity-purified polyclonal antiserum raised against a conserved segment of the RLX3 C-peptide (AS-R3(85-101)). Consistent with the distribution of RLX3 mRNA, neurons containing RLX3-like immunoreactivity (LI) were observed in the pontine nucleus incertus and the majority of these cells, which are known to express corticotropin-releasing factor receptor-1, were shown to express glutamic acid decarboxylase-65-immunoreactivity, suggesting a GABA phenotype. Nerve fibers and terminals containing RLX3-LI were observed adjacent to cells in the nucleus incertus and in various forebrain regions known to receive afferents from the nucleus incertus, including cortex, septum, hippocampus, thalamus, hypothalamus and midbrain. Regions that contained highest densities of RLX3-positive fibers included the medial septum, lateral preoptic area, lateral hypothalamus/medial forebrain bundle and ventral hippocampus; and additional fibers were observed in olfactory bulb and olfactory and frontal/cingulate cortices, bed nucleus of the stria terminalis, dorsal endopiriform, intergeniculate, and supramammillary nuclei, and the periaqueductal gray and dorsal raphe. The RLX3-positive network overlapped the regional distribution of GPCR135 mRNA and specific binding sites for an [125I]-GPCR135-selective, chimeric peptide. These anatomical findings further support the proposition that RLX3 is the endogenous ligand for GPCR135 in rat brain and provide evidence for broad modulatory activity of RLX3 in behavioral activation relating to autonomic and neuroendocrine control of metabolism and reproduction and higher-order processes such as stress and cognition.     

Difficult diagnosis of fever of unknown origin related to an infraclinic liposarcoma: "small tumor and fever of unknown origin"

INTRODUCTION: Palpation of soft tissues constitutes part of the physical examination when faced with a patient with fever of unknown origin. Our case highlights the difficulty of diagnosis when the tumor still remains impalpable ten months after onset of fever and severe biological inflammatory process. EXEGESIS: A 49-year-old woman was admitted for fever of unknown origin associated with important biological inflammatory process. In view of her past medical history of breast carcinoma, a search for a relapse was performed and remained negative. Despite multiple investigations and repeated physical examinations, no diagnosis was obtained. Finally, [18F] fluorodoexyglucose positron emission tomography led to a diagnosis showing a high fixation located in the right thigh, related to a myxoid liposarcoma after surgical resection. CONCLUSION: Dramatic regression of fever and biological inflammatory process after surgical treatment illustrates the concept of "small tumor and fever of unknown origin", an exceptional entity but which physicians should be aware of. The role of new technical imaging with [18F] fluorodoexyglucose positron emission tomography has however to be clarified in the evaluation of fever of unknown origin.     

Oral lichenoid reactions related to mercury sensitivity

Lichen planus is a common disorder of unknown aetiology. It has been proposed that in some cases it represents a form of allergic reaction to the metals contained in dental amalgam, particularly mercury. Twenty-nine consecutive dentate patients who had lichen planus of the oral mucosa were patch-tested to the range of metals contained in dental amalgam. Ten out of 29 (34%) showed an allergic reaction to mercury and all of these patients had amalgams greater than 5 years old. The amalgams were poorly contoured and had corroded, resulting in continued release of mercury ions. Six patients had their amalgams replaced with composite or glass ionomer materials resulting in resolution of ulcerated lesions. In a follow-up of 3-24 months, one patient had a recurrence of ulcerated areas and another, despite resolution of the oral lesions had persistent discomfort.     

Jejunal perforation by a fish bone diagnosed by CT-Scan: report of two cases

The authors relate two cases of peritonitis secondary to jejunal perforation by a fish bone. Clinically, the first patient presented signs and symptoms of acute diverticulitis and the second had signs of duodenal perforation. In both cases, the diagnosis was made by the CT-scan revealing a linear radio-opaque object suggestive of a fish bone perforating the jejunum. At laparotomy of the first case, we found a perforation located above several loops of small bowel densely adhered to the nonabsorbable intra-abdominal mesh. Removal of the fish bone, suture of the jejunal perforation, washing and drainage of the abdominal cavity were performed. The mesh was removed and replaced by a polyglycolic acid mesh. In the second case, jejunal perforation occurred in an unaltered small bowel loop and a short intestinal resection was performed. The postoperative course was uneventful for both patients. These clinical cases allow us to discuss the several fish bone perforation site and our patients precipitating factors.     

Periodontal healing after mandibular third molar surgery--A comparison of distolingual alveolectomy and tooth division techniques

The purpose of this study was to compare the periodontal healing of mandibular second molars after the removal of impacted mandibular third molars using distolingual alveolectomy and tooth division techniques. A total of 120 consecutive healthy patients who presented with bilaterally impacted mandibular third molars were included in this study. The same operator removed the impacted third molars on both sides in all patients. The third molar on one side was removed by distolingual alveolectomy using a chisel, whereas the contralateral tooth was removed by the tooth division technique using burs. Attachment level, periodontal pocket depth and bone healing distal to the mandibular second molars were assessed at 7 days, 3 months and 6 months after surgery. The results showed better periodontal healing and bone healing when distolingual alveolectomy was employed, especially in the removal of deeply impacted mandibular third molars.     

Sjögren's syndrome: a condition with features of chronic graft-versus-host disease: does duct cell adhesion or permeability play a role in pathogenesis?

Primary and Secondary Sj?gren's syndrome are disease complexes characterized by periductal inflammatory cell infiltration of the salivary and lacrimal glands and manifest as dry mouth and dry eyes. Secondary Sj?gren's syndrome may be associated with a connective tissue disorder. Additional extraglandular features in Sj?gren's syndrome include a generalized inflammatory exocrinopathy that might be associated with abnormalities of both humoral and cellular mediated immunity. Similar inflammatory changes and extraglandular features, including an altered immune response, have been reported in patients developing graft-versus-host disease after bone-marrow transplantation and in patients with primary biliary cirrhosis. The periductal nature of the inflammatory response involving minor salivary and other glands raises the possibility of altered duct cell adhesion or permeability in playing a role in the aetiopathogenesis of Sj?gren's syndrome. The paper pulls together evidence that could be interpreted in this light. Evidence for bacterial or viral factor(s) altering the antigenicity of the histocompartibility (HC) complex on ductal cells in Sj?gren's syndrome patients is also described. A hypothesis is proposed for Sj?gren's syndrome in which the principal feature is an alteration in salivary gland duct cell adhesion or permeability. A re-evaluation of current knowledge of these two conditions from a clinical and experimental context are interpreted in this light.     

On the nature of Mycobacterium tuberculosis-latent bacilli.

Mycobacterium tuberculosis-latent bacilli are microorganisms that adapt to stressful conditions generated by the infected host against them. By slowing metabolism or becoming dormant, they may counterbalance these conditions and appear as silent to the immune system. Moreover, the dynamic turnover of the infected cells provokes a constant reactivation of the latent bacilli when the environmental conditions are favourable, or an activation after being dormant in necrotic and fibrotic lesions for a long period of time. Since there is no in vivo nor in vitro evidence for quick resuscitation of dormant bacilli, the current authors strongly favour the possibility that latent tuberculosis infection can be maintained for no longer than approximately 10 yrs, which is, nowadays, a time period very close to that considered for "primary" tuberculosis. This concept may also be helpful for newer epidemiological considerations regarding the real impact of reinfection in tuberculosis.