Age-dependent adaptation of the liver thyroid status and recovery of serum levels and hepatic insulin-like growth factor-I expression in neonatal and adult diabetic rats

The effect of treatment with thyroxine (T(4)) on the hepatic deiodinase (5'D-I) activity and triiodothyronine (T(3)) content and on insulin-like growth factor-I (IGF-I) secretion and mRNA hepatic expression were studied in neonatal and adult diabetic (D) rats and compared with 4 thyroidectomized (Tx) groups: neonatal and adult Tx rats treated or not with T(4). Serum T(3) and T(4) decreased by 92% in both Tx populations and by 80% to 70% in D adults according to the severity of diabetes: -70 mg/kg body weight (BW) (D(70)) or 50 mg/kg BW (D(50)) of streptozotocin (STZ) injected, whereas only a 30% to 33% decrease was found in D neonates. A similar decrease of liver 5'D-I activity and T(3) concentrations was found in neonatal and adult Tx rats, whereas a significant reduction in those parameters was observed only in adult diabetics, either D(70) or D(50), but not in D neonates. Serum levels and liver mRNA expression of IGF-I determined by ribonuclease protection assay, plasma and pituitary growth hormone (GH), plasma insulin, and glycemia were also measured in both D populations. A decrease in circulating IGF-I, previously reported for Tx adult rats, was also found in both D populations. T(4) treatment recovered IGF-I and liver T(3) in both Tx groups and D neonates, but not in D adults. These results show an age-dependent adaptation of the liver thyroid economy in diabetes, as hepatic 5'D-I does not respond to diabetes in neonates and IGF-I is insensitive to T(4) treatment in adult diabetics and suggest a positive correlation between hepatic T(3) content and IGF-I expression in conditions of diabetes and Tx.     

Outcome of protease inhibitor substitution with nevirapine in HIV-1 infected children

Background  

Protease inhibitors (PIs) have been associated with metabolic complications. There is a trend to switch to simpler therapy to improve these disturbances. We report a case-series describing the effects in metabolic abnormalities in seven HIV-infected children, previously treated with protease inhibitor (PI) after switching to nevirapine.     

Erythroid failure in Diamond-Blackfan anemia is characterized by apoptosis

Programmed cell death, also known as apoptosis, is frequently initiated when cells are deprived of specific trophic factors. To investigate if accelerated apoptosis contributes to the pathogenesis of Diamond- Blackfan anemia (DBA), a rare pure red blood cell aplasia of childhood, we studied the effect of erythropoietin (epo) deprivation on erythroid progenitors and precursors from the bone marrow of DBA patients as compared with hematologically normal controls. Apoptosis in response to epo deprivation was evaluated by enumeration of colony-forming unit- erythroid (CFU-E)- and burst-forming unit-erythroid (BFU-E)-derived colonies in plasma clot semisolid culture and by the identification of typical DNA oligosomes by gel electrophoresis from marrow mononuclear cells in liquid culture. In all DBA patients there was a marked decrease in CFU-E- and BFU-E-derived colony formation compared with normal controls at comparable time points of epo deprivation, with a complete loss of CFU-E-derived colonies in semisolid culture by 9 hours of epo deprivation versus 48 hours in controls. The BFU-E-derived colony response to epo deprivation displayed a similar pattern of decrement. Apoptotic changes assessed by the presence of characteristic DNA fragmentation began in the absence of epo deprivation and were readily detected within 3 hours of epo deprivation in DBA cultures versus 9 hours in controls. We conclude that DBA is characterized by accelerated apoptosis as measured by the loss of erythroid progenitor clonogenicity and increased progenitor and precursor DNA fragmentation leading to the formation of characteristic oligosomes, consistent with an intrinsic erythroid-progenitor defect in which increased sensitivity to epo deprivation results in erythroid failure.     

Defaecography in patients with irritable bowel syndrome and healthy volunteers

Background: In patients with IBS, many symptoms have their origin in the recto-anal segment, with motility changes in the rectum and in the internal anal sphincter, and alterations in rectal sensitivity. However, up to now, it is not known if these clinical and physiological changes are equated with morphological changes in the recto-anal segment. Methods: Sixteen consecutive patients with IBS (mean age 22, range 18–33 years; 13 females) and 10 healthy volunteers (mean age 34.5, range 19–50 yr.; 6 males) were evaluated prospectively with defaecography. Results: 1) Anorectal angle: No significant differences were observed in the anorectal angle during rest (91.6 ± 3.5° vs 92.6 ± 2.5°) and during defaecation (92 ± 5.5° vs 98.7 ± 2.6°) between patients with IBS and healthy volunteers. However, patients wih IBS were unable to widen the angle during defaecation, remaining the same at rest (91.6 ± 3.5°) as during defaecation (92 ± 5.5°). IBS patients with constipation (n = 2) compared to those with normal frequency defaecation (n = 13) showed no significant differences at rest (95 ± 6 vs 89.8 ± 4.1°) and during defaecation (100 ± 8 vs 88.9 ± 6.4°). Healthy volunteers widened the angle by more than 5° during defaecation. 2) Perineometry: although not significant, patients with IBS had less perineal descent during the simulated defaecation (1.98 ± 0.37 cm) than healthy subjects (2.1 ± 0.3 cm). Nevertheless, during squeeze there was significantly less mobility or perineal descent in patients with IBS than in control subjects (0.21 ± 0.17 vs 0.95 ± 0.21 cm; P = 0.01). Conclusions: The findings of this study suggest that patients with IBS as a whole, whether constipation predominant or not, showed changes in pelvic-floor mobility.

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Résumé. La défécographie chez des patients porteurs d'un syndrome du c?lon irritable et chez des volontaires sains. Chez des patients atteints d'un syndrome du c?lon irritable, de nombreux sympt?mes trouvent leur origine dans le segment recto-anal avec des modifications de la motilité du rectum et du sphincter interne ainsi que des altérations dans la sensibilité rectale. On ne sait toutefois pas jusqu'à présent si ces modifications cliniques et physiologiques sont corrélées avec des changements morphologiques dans le segment recto-anal. Methode: Seize patients consécutifs atteints d'un syndrome du c?lon irritable (age de 18 à 33 ans; M = 22 ans; 13 femmes) et 10 volontaires sains (age de 19 à 50 ans; M = 34,5 ans; 6 hommes) ont étéévalués prospectivement avec une défécographie. Resultats: 1. L'angle ano-rectal: aucune différence significative n'a été observée quant à la valeur de l'angle ano-rectal au repos (91,6 ± 3,5° versus 92,6 ± 2,5°) et l'angle de défécation (92 ± 5,5° versus 98,7 ± 2,6° entre les patients atteints d'un syndrome du c?lon irritable et les volontaires sains. Les patients porteurs d'un syndrome du c?lon irritable étaient toutefois incapables d'ouvrir leur angle durant la défécation, la valeur restant la même au repos (91,6 ± 3,5°) et durant la défécation (92 ± 5,5°). Les patients porteurs d'un syndrome du c?lon irritable avec constipation (n = 2) en comparaison à ceux dont la fréquence de défécation était normale (n = 13) ne démontraient aucune différence significative au repos (95 ± 6 versus 89,8 ± 4,1°) et durant la défécation (100 ± 8 versus 88,9 ± 6,4°). Les voluntaires sans ouvraient leur angle ano-rectal de plus de 5° durant la défécation; 2. bien que non significative, la périnéométrie montrait que les patient porteurs d'un syndrome du c?lon irritable avaient une descente périnéale moins importante durant une défécation simulée (1,98 ± 0,37 cm) que les sujets sains (2,1 ± 0,3 cm). Néanmoins, durant les efforts d'exonération, il y avait une mobilité nettement moindre ou une descente périnéale de moindre importance chez des patients avec d'un syndrome du c?lon irritable que des sujets de contr?le (0,21 ± 0,17 versus 0,95 ± 0,21 cm; P = 0,01). Conclusion: Les constatations de cette étude suggèrent que les patients porteurs d'un syndrome du c?lon irritable montrent dans leur ensemble des modifications de la mobilité du plancher pelvien que la constipation soit prédominante ou pas.

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Accepted: 10 February 1997     

New HIV type 1 CRF01_AE/B recombinants displaying unique distribution of breakpoints from incident infections among injecting drug users in Thailand

The goals of this study were to identify and characterize recombinant human immunodeficiency virus type 1 (HIV-1) genomes among incident infections in a prospective cohort study of injecting drug users (IDUs) in Bangkok, Thailand. Through cross-sectional, comparative phylogenetic analysis of the protease and env (C2-V4) gene regions, subtype discordance was observed in HIV-1 sequences from 4 of 111 IDUs (3.5%). Near-full-length HIV-1 genome sequences of the four strains revealed that in all four, the gp120 sequences clustered with a CRF01_AE prototype, while the remainder of the genomes displayed distinct mosaic patterns, with multiple breakpoints between HIV-1 CRF01_AE and subtype B-like regions. Two of the four HIV-1 recombinant strains displayed a nearly identical mosaic structure, suggesting the possible emergence and spread of a potentially new circulating recombinant form of HIV-1. Further characterization of these and other recombinant genomes through long-term follow-up will be important in understanding the generation of viral diversity and escape from the hosts immune responses. This information will be especially important for vaccine development.     

An outbreak of mumps in the Province of Leon Spain 1995-1996

In Spain mumps vaccine is given at the age of 15 months together with measles and rubella vaccines since 1982. Increased numbers of cases and outbreaks of mumps appeared in several autonomous communities in 1995. An outbreak of mumps in the province of -