Caffeine-induced Ca(2+) signaling as an index of cardiac progenitor cells differentiation.

Cardiac progenitor cells (CPCs), migrating from heart tissue, in culture aggregate to form cardiospheres (CSs) in which replication and cardiogenic differentiation occur. However, the frequency of functional differentiation in CSs and the role of cell clustering in supporting it remain to be established. The aim of our study is to quantify differentiation of a muscle-type Ca(2+) release mechanism in CS-derived cells, correlate it with cardiac differentiation markers and test its dependency on CS formation. CPCs migrating from murine cardiac explants were studied prior and after CSs formation (Pre-CS and Post-CS). Inducibility of RyR- and IP3-R-mediated Ca(2+) transients in individual cells was tested by exposure to caffeine and ATP, respectively; expression of cardiac and non-cardiac lineage markers was assessed. Caffeine responsiveness was negligible in Pre-CS cells and increased by 7.5 fold in Post-CS cells (3.6 vs. 26.9%; p < 0.05), and was closely correlated with activation of the cardiac TnI gene promoter. ATP-induced responses, frequent in Pre-CS (86%), were slightly increased in Post-CS cells (94%; p < 0.05). Expression of cardiac-specific Ca(2+)-handling proteins (Cav1.2, NCX1, RyR2, SERCA2a) was either limited to the Post-CS stage, or markedly enhanced. CS beating was infrequent, but its pharmacology was compatible with cardiac excitation-contraction coupling. Expression of non-cardiac lineage was low in general, and similar between Pre- and Post-CS cells. Culture conditions inhibiting CSs formation prevented the increase in caffeine responders. In conclusion, clustering in CSs leads to the induction of a muscle-specific functional response in about 30% of CPCs; this is accompanied by development of a cardiac-specific expression pattern.

Rapid multifocal chondrolysis after liver transplantation in four patients.

BACKGROUND: Favourable clinical outcomes achieved with liver transplantation may be jeopardised by corticosteroid-induced osteoarticular complications, such as osteoporosis or aseptic osteonecrosis. CASE REPORT: A previously unreported joint complication in liver transplant recipients is described. METHODS: Retrospective study of liver transplant recipients in whom destructive joint disease developed, identified among 330 symptomatic patients out of a total of 1260 managed over a 15 year period (November 1984-January 2000) in a university based liver transplantation centre. RESULTS: In four patients (23-56 years), rapid chondrolysis developed 2-12 years after transplantation in more than three weightbearing or non-weightbearing joints free of radiological features of avascular osteonecrosis, evidence of infection, or defined inflammatory arthritis. Pathological examination of five hip joints and one knee joint found no evidence of infection or inflammation. Six joint replacement procedures were performed successfully in three patients. CONCLUSION: Clinicians managing liver transplant recipients, and perhaps recipients of other organs, should be aware that rapid chondrolysis may develop. The pathogenesis of this rare complication is unclear.

Normocomplementemic urticarial vasculitis inaugurating destructive polyarthritis.

Urticarial vasculitis is an entity characterized by recurrent bouts of urticaria and histological evidence of leukocytoclastic vasculitis. An underlying systemic disease is often present. Joint manifestations occur mainly in cases with hypocomplementemia. We report a case of destructive polyarthritis preceded by urticarial vasculitis without hypocomplementemia.

A comparison of fluconazole oral suspension and amphotericin B oral suspension in older patients with oropharyngeal candidosis. Multicentre Study Group.

BACKGROUND: the optimum treatment for oropharyngeal candidosis, particularly in older patients, has not been established. Local treatment with nystatin and amphotericin B can be problematic. The oral suspension formulation of fluconazole may offer a good alternative to these conventional agents. OBJECTIVE: to compare the safety and efficacy of fluconazole oral suspension with amphotericin B oral suspension in the treatment of older patients with oropharyngeal candidosis. DESIGN: randomized open-label study. PATIENTS: three hundred and five patients, aged 62 or older, with at least one sign or symptom of oropharyngeal candidosis. METHODS: we evaluated patients for the signs and symptoms of candidosis before receiving the study drug and on days 4, 7 and 14. We assessed patients who were cured or improved after 7-14 days of treatment 2 weeks after the end of treatment (follow-up). We obtained specimens from buccal lesions for microscopic examination (baseline only) and culture at baseline and on days 7 and 14. Patients were evaluated for adverse events on days 4, 7 and 14. RESULTS: one hundred and fifty patients received fluconazole and 155 received amphotericin B. There were no statistically significant differences in clinical or mycological response between fluconazole and amphotericin B at the end of treatment or at follow-up. At the end of treatment, 122 (81%) of 150 fluconazole-treated and 135 (87%) of 155 amphotericin B-treated patients were clinically cured or improved. Mycological cure rates were 35% and 46% for fluconazole and amphotericin B, respectively. The symptoms of burning sensation and buccal pain resolved significantly sooner (P < 0.05) in fluconazole-treated patients. The presence of dentures did not affect the response to antifungal therapy. The incidence of adverse events was 46% in the fluconazole group and 50% in the amphotericin B group (not statistically significant). CONCLUSION: fluconazole oral suspension is a good therapeutic alternative to amphotericin B oral suspension in the treatment of older patients with oropharyngeal candidosis.

Hepatic hypertrophic osteoarthropathy: the value of liver transplantation.

We describe 4 cases of hepatic hypertrophic osteoarthropathy treated successfully by liver transplantation. Hepatic hypertrophic osteoarthropathy is a rare and disabling condition associated with severe liver diseases. It responds poorly to conservative management, and liver transplantation is the only radical treatment option.

Arthralgias and cryoglobulinemia during protease inhibitor therapy in a patient infected with human immunodeficiency virus and hepatitis C virus.

We present the case of a woman who had a chronic infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). She developed severe polyarthralgias associated with type II mixed cryoglobulinemia during therapy with an HIV-1 protease inhibitor. This therapy resulted in a dramatic increase in her CD4+ T cell count, from 70/mm3 to 567/mm3, which was composed of a high proportion (88%) of naive CD45RA+ CD62L+ cells, together with a recovery of her CD4+ T cell reactivity to antigenic stimulation. This may suggest that rapid recovery of immune competence in the CD4+ T helper subset might participate in the development of immunopathologic events such as this patient's cryoglobulinemia.

Aspergillus osteomyelitis after heart-lung transplantation.

Aspergillus osteomyelitis is a severe complication of invasive aspergillosis. Fewer than 15 cases have been observed after solid organ transplantation. We describe a case of Aspergillus osteomyelitis of the ilium after heart-lung transplantation with favorable outcome after medical treatment.

[Giant hemangioma of the liver disclosed by fever and an inflammatory syndrome. Apropos of 3 cases]. / Angiomes géants du foie révélés par de la fiévre et un syndrome inflammatoire. A propos de 3 cas.

Three cases of giant liver haemangioma were revealed by fever and biological inflammatory changes, which disappeared after resection of the haemangioma. These rare symptoms accompanying liver haemangioma may lead to misdiagnosis. Resection whenever possible results in the disappearance of symptoms. Anatomic necrotic changes inside the angioma seem to be the cause of these inflammatory patterns.

[Osteonecrosis, metastases and bronchial carcinoid]. / Ostéonécrose, métastases et carcinoïde bronchique.

The authors report the case of a 35-year-old woman undergoing surgery in 1976 for a bronchial carcinoid tumour, considered to be benign. Twelve years later, diagnostic evaluation of liver metastases led to the discovery of an asymptomatic lesion of D10, the CT scan and NMR appearances of which were suggestive of osteonecrosis, a diagnosis confirmed histologically. Investigations were repeated 2 years later because of spinal pain. While NMR and CT scan remained compatible with bone necrosis, biopsy on this occasion confirmed the presence of carcinoid tumour. These rare tumours metastasise little. Secondary bone deposits, essentially axial, are of an osteoblastic nature. The lesion seen in our patient was closer to idiopathic bone infarcts or those associated with Gaucher's or sickle cell diseases than to classical vertebral osteonecrosis. The relationship between vertebral necrosis and metastasis remains obscure.

[Osteoarticular complications after hepatic transplantation]. / Complications ostéoarticulaires après transplantation hépatique.

Between January and December 1989, among 396 patients receiving liver transplantation, 27 have developed 33 post-transplantation osteoarticular complications (27 non septic and 6 septic episodes). After liver transplantation, non septic complications are distinct from the pattern observed after kidney transplantation with a lower prevalence of avascular bone necrosis (n = 4) but a higher prevalence of new vertebral fractures (n = 18) and presence of stress fracture (n = 3). This difference is probably caused by the lower steroids dosage in liver transplantation and by the preexisting bone status which is different in kidney and liver graft recipients. These complications are essentially observed in cirrhosis (n = 12) and primary biliary cirrhosis (n = 10). Staphylococcus aureus is found in 5/6 osteoarticular infections whereas extra-osteoarticular (essentially intra-abdominal) infections are mainly due to Gram negative bacteria and candidiasis. Finally, 2 patients presented hypertrophic osteoarthropathy associated with chronic graft rejection, reversible after liver retransplantation.