A prognostic index as diagnostic strategy in children suspected of mitochondriocytopathy

The aim of this study was to assess an optimal screening for paediatric patients suspected of mitochondriocytopathy to justify a muscle biopsy. Forty-five patients were included. Medical history, physical examination, cardiac and ophthalmologic evaluation, clinical chemical investigations, in vivo function tests, neuroimaging and a skeletal muscle biopsy were performed in all patients. The results of the biochemical muscle studies were compared with the results of the other investigations. First, parameters with a statistical relationship with the result in muscle, normal or deficient, were selected. Secondly, a prognostic index was constructed using these parameters. Five parameters were selected: age <4 years, elevated fasting lactate to pyruvate ratio, elevated thrombocyte count, elevated lactate, and elevated alanine. Each parameter was scored 0 (not present) or 1 (present). The chance of a normal biopsy with a given value of this index (sum of the scores) was calculated: logit (Pr) = alpha + beta x index; alpha: -0.8167 and beta: 0.8331. (Pr: probability of normal biopsy.) The chance of a normal biopsy with an index value of 5 is 0.03, 4 is 0.07, 3 is 0.16, 2 is 0.30, 1 is 0.50 and 0 is 0.69. This prognostic index is a valuable instrument in deciding whether the suspicion of mitochondriocytopathy is strong enough to merit a muscle biopsy.     

Multiple intracranial juvenile xanthogranulomas. Case report

The authors report on an 11-year-old boy in whom proptosis of the eye caused by a benign intraosseous xanthofibroma of the left orbital wall became clinically apparent at the age of 4 years. Two years later he developed bilateral papilledema, at which time computerized tomography and magnetic resonance studies revealed multiple enhancing intracranial lesions. The largest mass was located in the left middle fossa; other lesions were located at the tentorium cerebelli, in both lateral ventricles, near the superior sagittal sinus, and extracranially near the left jugular vein. The mass in the left middle fossa was resected and diagnosed as juvenile xanthogranuloma (JXG). Thirty months later, the patient again became symptomatic, exhibiting behavioral abnormalities and a decrease in mental powers. At that time, the two remaining lesions in both lateral ventricles had grown enough to cause trapping of the temporal horns and raised intracranial pressure. These lesions were successively resected and histopathologically confirmed to be JXGs. However, resection of the second intraventricular lesion was complicated by postoperative bilateral amaurosis, presumably caused by postdecompression optic neuropathy. According to a review of the literature, fewer than 20 patients with JXG involving the central nervous system have been reported. The patient described in this report is the first in whom multiple intracranial JXGs developed in the absence of cutaneous manifestations. Although JXGs are biologically benign lesions, the treatment of patients with multifocal and/or progressive intracranial manifestations is problematic.     

Gastrointestinal effects and acute toxicity of suprofen.

The acute effects of orally administered, high doses of alpha-methyl-4-(2-thienylcarbonyl)benzeneacetic acid (suprofen) were studied in various tests, related to gastrointestinal functions. A decrease of the diarrheal stools in the castor oil test in rats was the first effect noted; the ED50 in this test was 40 mg/kg. This dose is 540 times higher than the ED50 of suprofen in the acetic acid-induced writhing test in rats (ED50 = 0.074 mg/kg). Temporarily decreased food consumption in rats was first noted after administration of 80 mg/kg. This is more than 1000 times the ED50 in the rat anti-writhing test. The appearance of gastrointestinal lesions was also studied in rats and a direct quantitative comparison was made with indometacin, acetyl-salicylic acid and ketoprofen. The dose of suprofen that produced lesions in 50% of the rats was 200 mg/kg, viz. 2700 times the ED50 in the rat anti-writhing test. Similarly obtained safety margins are 9.0 for indometacin, 78 for acetyl-salicylic acid and 102 for ketoprofen. The mortality after a single oral administration of suprofen was studied in mice, rats, guinea-pigs and dogs. LD50-values, based on mortality 7 days after administration, were 590 mg/kg, 353 mg/kg, 280 mg/kg and more than 160 mg/kg, respectively. Comparative LD50's in mice and rats were 14 and 19 mg/kg for indometacin, 280 and 70 mg/kg for ketoprofen. Therefore the safety margin in rats, with respect to the ED50 in the acetic acid-induced writhing test, is 4770 for suprofen, 156 for ketoprofen and 17.3 for indometacin. In guinea-pigs the safety margin of suprofen is 1470 with respect to the ED50 in UV-erythema and in dogs more than 250 with respect to the ED50 in urate-induced arthritis. From these data we may conclude that suprofen is comparatively safer than the reference compounds studied and that its effects on the gastrointestinal tract appear at doses far above those required for effectiveness in tests related to pain, fever and inflammation.     

Orthostatic stress response during the menstrual cycle is unaltered in formerly preeclamptic women with low plasma volume

Plasma volume (PV) varies with the menstrual cycle not only in healthy parous controls (CON) but also in formerly preeclamptic women with a subnormal PV (LPV). It is unknown whether formerly preeclamptic women with LPV are more susceptible to orthostatic stress than healthy controls. In this study, the authors compared autonomic responses to acute (standing from supine position) and gradual (menstrual cycle) orthostatic stress between LPV and CON. In 11 LPV (PV相似文献   

Vitamin D and Muscle Function: Is There a Threshold in the Relation?

ObjectivesFirst, to determine the association between serum 25 hydroxyvitamin D (25OHD) concentration and muscle mass, strength, and performance. Second, to explore if there is a threshold in the association.DesignCross-sectional, single-center study.SettingThe central part of the Netherlands (52° Northern latitude).ParticipantsA total of 802 independently living men and postmenopausal women 40 to 80 years of age.MeasurementsHealth-related and lifestyle factors, including physical activity, 25OHD concentration, lean mass, handgrip strength, knee extension strength, and physical performance were determined.ResultsOverall, higher 25OHD level was significantly associated with higher lean mass (22.6 g per nmol/L, 95% CI 7.3–37.9), handgrip strength (0.020 kg per nmol/L, 95% CI 0.001–0.038), and physical performance (0.006 points per nmol/L, 95% CI 0.001–0.012), after adjustment for various confounders. This association was most pronounced below a 25OHD level of 60 nmol/L, with lean mass increase 79.6 g per nmol/L (95% CI 40.8–118.4, P < .01), handgrip strength 0.09 kg per nmol/L (95% CI 0.045–0.141, P < .01), and physical performance 0.02 points per nmol/L (95% CI 0.005–0.032, P < .01), and these significant associations attenuated to null above this threshold.ConclusionIn middle-aged men and (postmenopausal) women, a higher 25OHD level was significantly associated with higher lean mass, muscle strength, and performance. These associations were most pronounced below 60 nmol/L and absent above 60 nmol/L, indicating a ceiling effect.     

AIDS-related B-cell lymphoma (ARL): correlation of prognosis with differentiation profiles assessed by immunophenotyping

This study was undertaken to analyze the differentiation profiles assessed by immunophenotyping in AIDS-related B-cell lymphoma (ARL) and their relation to the clinical course. Paraffin-embedded sections of 89 ARL cases during 1989 to 2004 were stained immunohistochemically with antibodies to CD3, CD10, CD20, CD38, CD138/Syndecan-1 (Syn-1), multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF4), B-cell lymphoma protein-2 (BCL-2), BCL-6, latent membrane protein-1 (LMP-1), and Ki-67. Expression of CD10 and CD20 were associated with better overall survival (OS; P = .009 and P = .04, respectively). Expression of CD20 was associated with longer disease-free survival (DFS; P = .03), whereas expression of CD138/Syn-1 was associated with shorter DFS (P = .03). OS and DFS were worse in patients with immunophenotypic profiles related to post-germinal center (GC) differentiation (BCL-6 and CD10 negative, MUM1/IRF4 and/or CD138/Syn-1 positive) when compared with GC differentiation (P = .01). When controlled for age-adjusted International Prognostic Index (IPI), prior AIDS-defining illness (ADI), and year of ARL diagnosis, a post-GC differentiation remained significantly associated with poor OS and DFS. Expression of CD10 was associated with a preserved immunocompetence, whereas CD20 was less frequent in patients developing ARL while on highly active antiretroviral therapy (P = .04). In summary, lack of CD20 or CD10 expression and a post-germinal center signature are associated with a worse prognosis in ARL.