Potential risk factors for the development of acute renal failure in preterm newborn infants: a case-control study

AIMS: To determine in a case-control study possible associations between the development of acute renal failure in preterm newborns and therapeutic interventions, particularly drug treatments. METHODS: The study population was 172 preterm infants of <38 weeks gestation; 71 had acute renal failure and 101 were controls closely matched for gestational age and birth weight. Maternal and neonatal information was collected for both groups through questionnaires and interviews. Routine data on renal variables were also collected. Univariate and multivariate logistic regression analyses were performed. RESULTS: Very low birthweight infants were at high risk of acute renal failure (79% of cases were <1500 g). However, the acute renal failure was transient. Mothers of infants with acute renal failure received more drugs during pregnancy and delivery (mainly antibiotics and non-steroidal anti-inflammatory drugs). Of the possible therapeutic interventions, intubation, catheterisation, and phototherapy were mainly applied to case subjects. A low Apgar score and patent ductus arteriosus were diagnosed in a greater percentage of neonates with acute renal failure. Moreover, in the first few days of life and before diagnosis of acute renal failure, case subjects received more drugs (antibiotics, non-steroidal anti-inflammatory drugs, and diuretics) and for a longer time. In the multivariate logistic analysis, medullary hyperechogenicity (odds ratio (OR) 4.491; 95% confidence interval (CI) 1.879 to 10.731) and ceftazidime administration (OR 5.082; 95% CI 1.493 to 17.297) were associated with a greater risk of acute renal failure. CONCLUSIONS: The results suggest the need for careful monitoring of very low birthweight infants and attention to drug treatments, as it is difficult to differentiate between normality and renal failure in the first few days of life.     

The glycopeptide CSF114(Glc) detects serum antibodies in multiple sclerosis

Synthetic glycopeptides have the potential to detect antibodies in multiple sclerosis (MS). In the present study, we analyzed the antibodies (IgM class, IgG class and IgG subclasses) to the synthetic glycopeptide CSF114(Glc) in the serum of 186 MS patients, 166 blood donors (BDs), 25 patients affected by meningitis/encephalitis, 41 affected by systemic lupus erythematosus (SLE) and 49 affected by rheumatoid arthritis (RA). The IgM antibody level to CSF114(Glc) was significantly increased in MS patients versus BDs (p<0.001) or versus other autoimmune diseases (SLE or RA, p<0.001). The IgG response was restricted to the subclass IgG2. IgM antibodies to CSF114(Glc) were found in 30% of relapsing/remitting MS patients and, at lower levels, in subjects affected by meningitis/encephalitis. The study of antibodies to CSF114(Glc) is a new, potential immunological marker of MS.     

Effects of vitamin E supplementation on intracellular antioxidant enzyme production in adolescents with type 1 diabetes and early microangiopathy

Defective intracellular antioxidant enzyme production (IAP) has been demonstrated in adults with diabetic nephropathy. To evaluate the effects on IAP of vitamin E administration in adolescents with type 1 diabetes and early signs of microangiopathy, 12 adolescents (aged 11-21 y; diabetes duration 10-18) were studied. Eight had retinopathy [background (four), preproliferative (three), or proliferative (one)], four had persistent microalbuminuria, and seven had both. Skin fibroblasts were obtained by biopsies and cultured in Dulbecco's modified Eagle's medium. CuZn superoxide dismutase (SOD), MnSOD, catalase (CAT), and glutathione-peroxidase (GPX) activity and mRNA expression were measured before and after 3 mo of synthetic vitamin E supplementation (600 mg twice daily); on both occasions, IAP was evaluated at different ex vivo glucose concentrations (5 and 22 mM). Ten adolescents with type 1 diabetes (aged 12-20 y) without angiopathy and eight healthy volunteers (aged 15-22 y) participated as control subjects. Vitamin E serum levels were measured throughout the study. In normal glucose concentrations, CuZnSOD, MnSOD, CAT, and GPX activity and mRNA expression were not different among the groups. In high glucose, CuZnSOD activity and mRNA increased similarly in all groups [angiopathics: 0.96 +/- 0.30 U/mg protein; 9.9 +/- 3.2 mRNA/glyceraldehyde-3-phosphate dehydrogenase). CAT and GPX activity and mRNA did not increase in high glucose only in adolescents with angiopathy (0.35 +/- 0.09; 4.2 +/- 0.1 and 0.52 +/- 0.14; 2.4 +/- 0.9, respectively). MnSOD did not change in any group. Vitamin E supplementation had no effect on any enzymatic activity and mRNA in both normal and hyperglycemic conditions. Adolescents with early signs of diabetic angiopathy have defective IAP and activity, which are not modified by vitamin E.     

Analysis of local T lymphocyte subsets upon stimulation with intravesical BCG: a model to study tuberculosis immunity

Cell-mediated immune response can control tuberculosis infection. A significant role for immune cells like CD4, CD8 and gammadelta T lymphocytes have been recognized, but little is known about the kinetics of activation and accumulation of these cells in course of Tuberculosis infection in humans. This is due to both the difficult to access to human lung and the fact that most subjects are examined in different periods of infection which may condition T cell changes. To overcome these problems, we have used intravesical BCG (Bacillus Calmette-Guerin) treatment for preventing the recurrences of bladder cancer as an in vivo experimental model of human tuberculosis infection. 20 male caucasian patients with proven bladder superficial transitional cell carcinoma treated with transurethral resection followed by six weekly intravesical instillations of BCG (T0-T6) were enrolled. Changes in T lymphocyte subsets were assessed by flow cytometry in the bladder wash recovered after each BCG instillation. Our study shows that the action of BCG appears to be T cell dependent. Lymphocytes increase at any new instillation and tend towards the reduction with the suspension of the stimulus. BCG induces a massive increase in the proportion of CD4 Th1 subset followed by an increase in gammadelta T cells, while no significant variation for CD8 and NK cells is found. Our results suggest that BCG infection model represents a valid experimental tool to study the immunological events evoked in vivo by Mycobacterium tuberculosis in humans at the site of infection.     

Infliximab downregulates basic fibroblast growth factor and vascular endothelial growth factor in Crohn's disease patients

BACKGROUND: The use of infliximab in the treatment of Crohn's disease patients with symptomatic stenosis is controversial. AIM: To explore the influence of this agent on intestinal fibrogenesis by measuring in infliximab-treated Crohn's disease patients the serum levels of basic fibroblast growth factor and vascular endothelial growth factor, two factors known to be involved in the process of intestinal wound healing and fibrosis in this condition. METHODS: Serum levels of basic fibroblast growth factor and vascular endothelial growth factor were determined by enzyme-linked immunosorbent assay in 22 patients with steroid refractory or fistulizing Crohn's disease before, during (2 weeks) and after 12 weeks of treatment with infliximab, administered at week 0, 2 and 6 in a dose of 5 mg/kg. RESULTS: A substantial improvement in 19 of the 22 Crohn's disease patients was accompanied by a rapid and durable reduction in basic fibroblast growth factor and vascular endothelial growth factor serum levels. CONCLUSIONS: The action of infliximab in reducing serum basic fibroblast growth factor and vascular endothelial growth factor would seem to suggest a role of this agent in down-regulating the process of intestinal fibrogenesis in Crohn's disease.     

Solid and papillary epithelial neoplasm of the pancreas in an 11-year-old girl: case report and literature review

An 11-year-old girl presented with episodic abdominal pain of 2 years' duration. CT scan of the abdomen showed a mass in the tail of the pancreas. A distal pancreatectomy was done and the tumor was excised. Macroscopic and immunohistochemical studies were compatable with a solid and papillary epithelial neoplasm. This is a rare neoplasm with a decidedly female predominance. It has a very low malignant potential with a good prognosis. Surgical removal of the tumor is usually curative.     

Is the low tri-iodothyronine state a crucial factor in determining the outcome of coronary artery bypass patients? Evidence from a clinical pilot study

The cardiovascular system is an important target for thyroid hormones. The present study evaluates the changes affecting thyroid hormone metabolism during and 6 days after coronary artery bypass and their relationship with the post-operative outcome of the patients. Thirty-three patients were enrolled in the study; their thyroid hormone profiles were determined at 13 sampling points during surgery and for 6 days afterwards. Serum total tri-iodothyronine (T3) and free T3 (FT3) concentrations decreased significantly after surgery (P<0.001) and they remained significantly low until the end of the study. Free thyroxine (FT4) and T4 declined significantly immediately after surgery (P<0.05 for FT4, P<0.001 for T4) but they returned to baseline values (24 h and 96 h post-surgery respectively). Serum reverse T3 increased remarkably 36 h after surgery (P<0.001) and remained significantly higher than the baseline value throughout the study. A relevant finding was that the days of post-operative hospitalization (10+/-3 days, means+/-S.D.) was inversely correlated with the slope of the recovery of T3 concentration (P<0.001) or with the area under the plasma curves of T3 (P=0.024, time range 72-144 h) and the FT3/FT4 ratio (P=0.037, time range 72-144 h) during the post-operative period. Our data suggest a prolonged reduction of T4 to T3 conversion in patients undergoing cardiac surgery and indicate that the recovery period is the most critical in the evaluation of a possibly successful approach for T3 substitutive therapy.     

Neurovascular and tendinous damage with placement of anteroposterior distal locking bolts in the tibia

OBJECTIVE: To determine the proximity of anteroposterior locking bolts inserted into the distal metaphyseal tibia to nearby neural, vascular, and tendinous structures. DESIGN: A cadaver study. SETTING: University trauma center. METHODS: Sixteen legs (8 matched pairs) were nailed in either neutral (Group 1) or 10 degrees of internal rotation (Group 2) and locked using one anteroposterior bolt. The anterior tibial and extensor hallucis longus tendons and neurovascular bundle were identified, and their respective locations in relation to the bolt head were measured. Average distances were calculated for each structure in each group and statistically compared. Damage to any structure was noted at final dissection. RESULTS: Average distances from the bolt head to the neurovascular bundle, extensor hallucis longus, and anterior tibial tendons were 0.6, 0.5, and 1.6 mm, respectively, for Group 1 and 1.0, 1.5, and 1.8 mm, respectively, for Group 2 legs. Statistical comparison of distances for each anatomic entity for the two groups revealed no detectable significant differences (P = 0.7, 0.4, 0.7, respectively). For all specimens, the rate of nerve, artery, extensor hallucis longus, and anterior tibial tendon injury was 25%, 19%, 0%, and 6%, respectively. However, the incidence of at least one structure damage in Group 1 legs was 63% versus 12% in Group 2 specimens (P = 0.2). CONCLUSION: Anteroposterior distal tibial locking bolts lie in close proximity to the neurovascular bundle. With standard percutaneous techniques, these structures can be damaged. Although 10 degrees of internal rotation does not statistically affect the measured distance of the locking bolt to the neurovascular bundle, it appears to decrease the incidence of neurovascular injury. This difference may best be explained by the necessary path the drill bit must take through the soft tissues to reach the underlying bone. Regardless of nail orientation, larger incisions with careful dissection and clear visualization of the anatomy are recommended to help prevent this complication.     

Epidermal growth factor receptor targeted therapy by ZD 1839 (Iressa) in patients with brain metastases from non-small cell lung cancer (NSCLC)

PURPOSE: We report four cases of Brain Metastases (BM) from non-small cell lung cancer (NSCLC) responding to ZD 1839 therapy after standard therapy failure. PATIENTS AND METHODS: Four patients with BM from NSCLC, pretreated with two or more lines of chemotherapy, received ZD 1839 (Iressa), on a compassionate use basis, at the daily dose of 250 mg until disease progression. Three patients received Iressa after whole brain radiotherapy (WBRT) failure. RESULTS: After 3 months of ZD 1839 therapy, one patient had complete response on the brain with stabilization of extracranial disease, while the other three patients had partial response both on the brain and on extracranial sites. At the time of this analysis, two patients discontinued the treatment after 5 and 7 months for disease progression, while two patients are still on treatment with no evidence of treatment failure after 3+ and 12+ months. ZD 1839 was generally well tolerated, with skin toxicity recorded in two patients. CONCLUSION: ZD 1839 may be effective in NSCLC patients with pretreated BM. Large and prospective trials need to clarify the role of ZD 1839 in the treatment of BM from NSCLC.     

Gefitinib in elderly and unfit patients affected by advanced non-small-cell lung cancer

Elderly and poor performance status advanced non-small-cell lung cancer (NSCLC) patients often tolerate chemotherapy poorly. Special approaches are needed for these patient populations. Gefitinib (Iressa) was used in 59 elderly and/or unfit NSCLC pretreated patients participating in a compassionate use programme showing some activity and good tolerability.