Le traitement médical de l’arthrose digitale

Medical treatment of osteoarthritis of the fingers includes preventive measures, physiotherapy, including orthesis techniques and treatment with drugs.     

Phase I targeted combination trial of sorafenib and erlotinib in patients with advanced solid tumors.

PURPOSE: Sorafenib and erlotinib are potent, orally administered receptor tyrosine kinase inhibitors with antiproliferative and antiangiogenic activities. Given their inhibitory target profile and efficacy as single agents, the combination of these drugs is of considerable interest in solid malignancies. This study aimed to determine the recommended phase II dose of this targeted combination, their toxicity profile, pharmacokinetic interaction, and preliminary clinical activities. EXPERIMENTAL DESIGN: Sorafenib was administered alone for a 1-week run-in period, and then both drugs were given together continuously, with every 28 days considered as a cycle. Three dose levels were assessed. RESULTS: Seventeen patients with advanced solid tumors received 75 cycles of treatment. The most frequent adverse events of all grades were constitutional and gastrointestinal in nature followed by electrolytes and dermatologic toxicities. Fatigue was the most common adverse event (17 patients; 100%) followed by diarrhea (15 patients; 88%), hypophosphatemia (13 patients; 76%), and acneiform rash (12 patients; 71%). These adverse events were predominantly mild to moderate. The recommended phase II dose of this combination was determined as 400 mg twice daily sorafenib and 150 mg daily erlotinib. Pharmacokinetic analysis revealed no significant effect of erlotinib on the pharmacokinetic profile of sorafenib. Among 15 evaluable patients, 3 (20%) achieved a confirmed partial response and 9 (60%) had stable disease as best response. CONCLUSIONS: Sorafenib and erlotinib are well tolerated and seem to have no pharmacokinetic interactions when administered in combination at their full single-agent recommended doses. This well tolerated combination resulted in promising activity that needs further validation in phase II studies.     

Diminished concentrations of insulin-like growth factor I in cystic fibrosis

Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data on IGF-I in cystic fibrosis are sparse and conflicting. From 1990-3, 235 of our 240 patients (114 males, 121 females, median age 16.2 years, ranged 0.1-44.0 years) had IGF-I measured once by radioimmunoassay. IGF-I was significantly reduced compared with a healthy Scandinavian control population: mean (-2 SD to +2 SD) IGF-I SD score was -0.97 (-3.7 to 1.7) in males and -0.67 (-3.2 to 1.9) in females. Height SD score was -0.95 (-3.3 to 1.4) in males and -0.81 (-3.2 to 1.6) in females. In patients who were still in the growth period a significant correlation of IGF-I SD score to height SD score (r = 0.28, p < 0.001) was found. The low IGF-I concentrations may reflect the catabolic state of many patients with cystic fibrosis and play a part in their abnormal growth pattern.     

Sudden child death and 'healthy' affected family members with medium-chain acyl-coenzyme A dehydrogenase deficiency

A family is described in which the father and three (and probably all four) of his children had a decreased capacity for the oxidation of medium-chain fatty acids. One of the children suddenly died at the age of 16 months following an episode of a rapidly deteriorating Reye syndrome-like illness with hypoketotic hypoglycemia and dicarboxylic aciduria, but without any previous alarming symptoms. The eldest sibling had died at the age of 19 months under similar conditions. The other family members had always been healthy. On fasting, all affected family members accumulated in their plasma the medium-chain fatty acids octanoic, decanoic, and cis-4-decenoic acids. Their urinary organic acid excretion profile could be characterized as "dicarboxylic aciduria." A deficiency of medium-chain acyl-coenzyme A dehydrogenase was demonstrated in a postmortem liver sample of the index patient. Cultured fibroblasts from the father and the two healthy children had a decreased rate of [14C]octanoate oxidation. It is suggested that a deficiency of medium-chain acyl-coenzyme A dehydrogenase may lead to a life-threatening illness when other complicating factors such as diarrhea and vomiting result in an abnormal depletion of the body's glycogen stores. Careful monitoring of at-risk patients during a minor illness is necessary.     

Nephrocalcinosis in preterm infants: a single center experience

The risk of nephrocalcinosis in preterm infants is considerable, but conflicting numbers are given for the actual incidence (10–65%). Furosemide induced hypercalciuria is said to be the main risk factor. We examined retrospectively the incidence, causes and outcome of nephrocalcinosis in preterm infants born in our hospital from 1988 to 1998 (n=2190). An abnormal renal echogenicity or nephrocalcinosis was seen in 31 infants (29.7±3.3 weeks gestational age; 1307±690 g birth weight). Nephrocalcinosis was diagnosed in 16, hyperechoic kidneys (HK) in 10 and Tamm-Horsfall kidneys in 5 infants. Main risk factors were low gestation age and birth weight, length of hospitalization, variations in acid-base status, length of assistant ventilation and hypercalciuria at diagnosis. The incidence of nephrocalcinosis was 0.73% [1.7% for low birth weight infants (VLBW)]. Taking the cases of nephrocalcinosis and HK together, incidence was calculated to be 1.2% overall and 2.5% for VLBW infants, but increased to 7% in 1998. The follow-up showed persisting nephrocalcinosis or hyperechoic kidneys in 8/26 preterm infants. In conclusion, the incidence of nephrocalcinosis was lower in our population than is usually reported. The numbers have, however, increased over the past few years. From the follow-up it was obvious that long-term observation of preterm infants is necessary and that complications might arise in the long run. Received: 9 July 2001 / Revised: 14 November 2001 / Accepted: 18 November 2001