The ultrastructure of nasal mucosa in children with asthma

Nasal brushing has sometimes been used to characterize some affections of the respiratory tract, but seldom employed in chronic diseases such as asthma, for the possible presence of cellular inflammation in the small specimens used for electron microscopy. The present study evaluated the ultrastructure of epithelial cells obtained by nasal brushing in 11 allergic children with asthma, before and after staying in an environment free of allergens, usually implicated in the genesis of inflammatory events. The ultrastructural alterations of the nasal mucosa have been graded on the basis of their severity. Grade I lesions were characterized by well-differentiated mucous and ciliated cells. The ciliated cells appeared usually well preserved but decreased in number. In grade II lesions, most of the epithelial surface was covered by mucous cells. A further phenotype composed of poorly differentiated ciliated or mucous cells was detected. Grade III lesions showed aspects of depletion of the ciliated and mucous cells. The epithelium was largely composed of undifferentiated cells. Furthermore, the comparison of specimens at 2 different times of sampling did not differ. The data demonstrate that in allergic children with asthma, the nasal mucosa showed ultrastructural changes, which appeared to be unmodifiable during a prolonged stay in an environment free of allergens. Moreover, the nasal epithelium may provide a convenient sampling site, allowing grade of mucosal damage, with the benefit that the brush method is minimally invasive and avoids complications related to bronchoscopic examination.     

Effects of deferiprone on immune status and cytokine pattern in thalassaemia major

OBJECTIVE: The present study was undertaken to evaluate the possible occurrence of immunological abnormalities in thalassaemia major patients treated with deferiprone (L1). METHODS: Longitudinal observational cohort study. RESULTS: The absolute number of CD8+ lymphocytes was high and the CD4/CD8 ratio low before L1 treatment; these parameters returned to normal after 3 months of L1 treatment. TNF-alpha, IL-2 and IL-2sRalpha were elevated before L1 treatment (11.83 +/- 1.75, 11.75 +/- 3.91, 1,409 +/- 621 pg/ml, respectively), while IL-6 was normal (2.58 +/- 0.79 pg/ml). After 12 months of treatment, IL-10 was higher than in previous periods, although always within the normal range. TNF-alpha, IL-2 and IL-2sRalpha returned to normal after 12, 6, and 3 months of L1 treatment, respectively.     

Cardiopulmonary perfomances in young children and adolescents born with large abdominal wall defects

Background/Purpose: As long as the survival rate of patients with abdominal wall defects (AWD) increases, information about long-term follow-up is becoming necessary. Even though quality of life in these patients, in absence of associated anomalies, appears to be unaffected, respiratory impairment soon after birth has been documented; therefore, participation in sports rarely is addressed. Methods: Eighteen patients, ranging in age from 7 to 18 years, operated on at birth for large abdominal wall defects ([gt ] 4 cm for gastroschisis; [gt ]6 cm for omphalocele) were asked to come for a stress test on a treadmill, with measurements of time of exercise (TE), maximal oxygen consumption (VO₂ max) and continuous recording of vital parameters. Respiratory function also was assessed by Forced Vital Capacity (FVC). Results: Ergometric data were compared with those of a normal pediatric population. All patients were able to perform the stress test with no cardiovascular abnormalities detected at rest or on exertion. Maximum heart rate was reached after a significantly shorter TE, and VO₂ max was significantly reduced when comparing normal subjects with AWD subjects and AWD subjects in sports with those sedentary. FVC was only slightly reduced in AWD patients without reaching statistical significance. Conclusions: These findings indicate that patients operated on for AWD at birth exhibit a normal cardiorespiratory function; decreased TE and VO₂ max are likely to reflect a lack of physical activity with a lower degree of fitness. Therefore, no limitations to motor performances should exist for these patients. Well-being may be greatly improved by regular exercise. J Pediatr Surg 38:478-481.     

Genetic control of postoperative systemic inflammatory reaction and pulmonary and renal complications after coronary artery surgery

BACKGROUND: Although some data suggest that the individual genetic predisposition for developing major or minor degrees of postoperative systemic inflammatory reaction may influence postoperative morbidity, this hypothesis has not been clinically tested to date.Methods and results The -174 G/C polymorphism of the promoter of the interleukin 6 gene was determined preoperatively in 111 consecutive patients submitted to primary isolated coronary artery bypass. The results of the genetic analysis were then correlated with the postoperative interleukin 6 levels and the development of postoperative renal and pulmonary complications. G homozygotes had significantly higher interleukin 6 levels postoperatively (P <.0001 for the difference between areas under the curve). These patients also had worse postoperative pulmonary and renal function. The mean perioperative difference in serum creatinine, potassium, and nitrogen was 0.82 +/- 0.34, 0.99 +/- 0.44, and 10.1 +/- 7.8 mg/dL versus 0.18 +/- 0.14, 0.15 +/- 0.48, and 2.6 +/- 4.1 mg/dL for GG versus non-GG carriers (P <.0001), respectively. The mean respiratory index at 6 and 12 hours was 2.9 +/- 0.8 and 2.8 +/- 0.3 versus 2.1 +/- 0.5 and 1.3 +/- 0.1, respectively (P <.0001). The mean duration of mechanical ventilation was 22.5 +/- 2.1 versus 12.7 +/- 6.7 hours (P <.01). A correlation was found between postoperative interleukin 6 levels and renal and pulmonary complications. CONCLUSION: The interleukin 6 -174 G/C polymorphism modulates postoperative interleukin 6 levels and is associated with the degree of postoperative renal and pulmonary dysfunction and in-hospital stay after coronary surgery.     

Hepatocyte transplantation in the treatment of acute liver failure: microencapsulated hepatocytes versus hepatocytes attached to an autologous biomatrix

A liver transplant is considered today to be the only effective therapeutic solution for many otherwise intractable hepatic disorders. However, liver transplantation is beset by shortage of donors. Over the years, many liver support systems have been developed to supply the liver functions, mostly as a bridge to transplantation. Transplantation of isolated hepatocytes (HcTx) instead of whole liver has constituted one of the most appealing possibilities to treat several diseases. We compared two different models of HcTx in a surgical model of acute liver failure in pigs, using microencapsulated hepatocytes (MHcTx) and hepatocytes attached to a porcine biomatrix (PBMHcTx), both transplanted into peritoneum. The collected data were survival, laboratory findings, hemodynamic parameters, light microscopy, histology, MTT, and glycogen content. The group with PBMHcTx has a better outcome than the group with MHcTx (p < 0.05). Histology showed normal morphology of the hepatocytes, high glycogen content, 75% viability, positive MTT, and 95% adhesion of the hepatocytes to the biomatrix. Our biomatrix (PBM) provides cell-to-cell contact and interaction with extracellular matrix, which have been shown to play major roles in hepatocyte survival and physiologic regulation of gene expression, and guarantee a prompt engraftment and an adequate neovascularization. PBMHcTx is a useful method to treat acute liver failure and it indicates a possible liver-direct gene therapy in the treatment of inherited and acquired disorders.     

Sustained-release diltiazem reduces myocardial ischemic episodes in end-stage renal disease: a double-blind,randomized, crossover,placebo-controlled trial

End-stage renal disease (ESRD) patients receiving maintenance hemodialysis and suffering from coronary artery disease (CAD) often receive doses of calcium channel antagonists that are too low. This may be the result of physician's desire to avoid adverse side effects during hemodialysis. The aim of this study was the assessment of the safety and efficacy of incremental doses of diltiazem for the treatment of myocardial ischemia in ERSD patients with CAD to identify the optimal dose of the drug. A total of 196 chronic hemodialysis patients were enrolled with CAD showing more than 5 min of transient myocardial ischemia during a 48-h Holter ECG monitoring. A double-blind, randomized, crossover, placebo-controlled trial design was used. Incremental doses of diltiazem (120 to 240 mg/d) were administered in 4 mo. With a dose of 120 and 180 mg/d, a significant reduction in the number and duration of total and symptomatic ischemic episodes was observed (P < 0.001), but the number and the duration of silent ischemic episodes were not reduced. Conversely, the efficacy on silent myocardial ischemia was obtained with a dosage of diltiazem of 240 mg/d (P < 0.001). In addition, with a sustained-release formulation (120 mg twice daily), the efficacy was similar to that obtained with four 60-mg tablets, but the safety was improved, especially during hemodialytic session. The circadian variations analysis of transient ischemic episodes showed a significant reduction in both ischemic peaks observed at baseline only with 240 mg/d of diltiazem. The findings emphasize that sustained-release diltiazem (120 mg twice daily) can be largely useful in uremic patients with CAD on maintenance dialysis. Diltiazem reduces the number and the duration of silent ischemic episodes, has a good tolerability, and positively modifies the circadian pattern of ischemic episodes.     

IX Antonio Arrigo Award. Clinical neurophysiology in neuromuscular disorders: usefulness and limitations

This lecture focuses on the impact of classic and modern electrophysiological techniques on the diagnostic approach to patients with neuromuscular disorders, placing emphasis on the limitations of currently used techniques and on the future prospects of clinical neurophysiology. The refinement of old techniques together with the development of new ones will hopefully improve the diagnostic capability of neurophysiology, improve understanding of the complex pathogenic mechanisms underlying neuromuscular disorders and help further the research of new therapeutic strategies.