Vitamin E supplementation improves neutropenia and reduces the frequency of infections in patients with glycogen storage disease type 1b.

BACKGROUND: Neutropenia and/or neutrophil dysfunction are part of glycogen storage disease type 1b (GSD1b) phenotype. Recent studies indicated that activation of apoptosis and increased reactive oxygen species are implicated in the pathogenesis of neutropenia in GSD1b. METHODS: We studied seven GSD1b patients over a 2-year-period to evaluate the efficacy of vitamin E, a known antioxidant, in preventing or improving the clinical manifestations associated with neutropenia and neutrophil dysfunction. Frequency and severity of infections, neutrophil counts and function, ileocolonoscopy and intestinal histology, were monitored. During the first year, patients did not assume vitamin E; during the second year of the study, vitamin E supplementation was added to their therapeutic regimens. RESULTS: During vitamin E supplementation, the mean values of neutrophil counts were significantly higher (p < 0.05) and neutrophil counts lower than 500/mm(3) were found less frequently (p < 0.05); the frequency and severity of infections, mouth ulcers and perianal lesions, was reduced (p < 0.05); ileocolonoscopy and histology showed a mild improvement. Vitamin E supplementation did not result in changes in neutrophil function. CONCLUSIONS: These results suggest that vitamin E supplementation might be beneficial in GSD1b patients and may alleviate disease manifestations associated with neutropenia.

The increase of endothelial progenitor cells in the peripheral blood: a new parameter for detecting onset and severity of sepsis.

Sepsis is a clinical syndrome characterized by non-specific inflammatory response with evidence of profound changes in the function and structure of endothelium. Recent evidence suggests that vascular maintenance, repair and angiogenesis are in part mediated by recruitment from bone marrow (BM) of endothelial progenitor cells (EPCs). In this study we were interested in whether EPCs are increasingly mobilized during sepsis and if this mobilization is associated with sepsis severity. Our flow cytometry data demonstrate that in the CD34+ cell gate the number of EPCs in the blood of patients with sepsis had a four-fold increase (45 +/- 4.5% p < 0.001) compared to healthy controls (12 +/- 3.6%) and that this increase was already evident at 6 hours from diagnosis (40.6 +/- 4.2 percent), reaching its maximum at 72 hours. Also the percentage of cEPCs identified in the patients with sepsis (35 +/- 4.6% of the CD34+ cell) was statistically different (p < 0.001) compared to that found in the blood of patients with severe sepsis (75 +/- 4.9%). In addition, we proved that at six hours after sepsis diagnosis, VEGF, CXCL8 and CXCL12 serum levels were significantly higher in septic patients compared to healthy volunteers 559 +/- 82.14 pg/ml vs 2.9 +/- 0.6 (p < 0.0001), 189.8 +/- 67.3 pg/ml 15 vs 11.9 +/- 1.6 (p = 0.014) and 780.5 +/- 106.5 pg/ml; vs 190.2 +/- 71.4 (p < 0.001). Our data suggest that the cEPC evaluation in peripheral blood, even at early times of diagnosis, in patients with sepsis can be envisaged as a valuable parameter to confirm diagnosis and suggest further prognosis.

Antimicrobial prophylaxis in laparoscopic gynecologic surgery: a prospective randomized study comparing amoxicillin-clavulanic acid with cefazolin.

Numerous studies have been published in recent years about antimicrobial prophylaxis in gynecologic surgery, but the optimal drug and schedule for the different surgical procedures is still a matter of debate. The aim of the present study was to compare two ultra-short term antimicrobial prophylaxis regimens (amoxicillin-clavulanic acid and cefazolin) in preventing infections following laparoscopic gynecologic operations. Three hundred sixty women hospitalized for a laparoscopic gynecologic surgery procedure were included in the study between January 1999, and December 2001. Patients were randomly allocated to receive amoxicillin-clavulanic acid (2.2 g) [Group A] or cefazolin (2 g) [Group B] as a single dose 30 minutes before surgery. Each patient was assessed daily until discharge to evidence febrile status and the presence of infections at the operative site, urinary tract and respiratory tract. In the amoxicillin-clavulanic acid (Group A) and cefazolin (Group B) groups, overall 164 and 172 patients, respectively, were evaluable for prophylactic efficacy at hospital discharge. Infectious complications were infrequent in both groups with febrile morbidity occurring in only one patient (0.6%) in the amoxicillin-clavulanic group. No sign of infections at the surgical site, urinary tract and respiratory tract was observed in either group. No death due to sepsis was recorded. It is concluded that ultra-short term prophylaxis with both amoxicillin-clavulanic acid and cefazolin is safe and effective in elective laparoscopic gynecologic surgery.

Antimicrobial prophylaxis in laparotomic gynecologic surgery: a prospective randomized study comparing amoxicillin-clavulanic acid with cefazolin.

A prospective randomized study was conducted at the Department of Obstetrics and Gynecology, University of Bari to compare two antimicrobial regimens, amoxicillin-clavulanic acid with cefazolin as ultra-short term prophylaxis in laparotomic gynecologic surgery. Patients were randomly allocated to receive a single dose of amoxicillin-clavulanic acid (2.2 g) [Group A] or cefazolin (2 g) [Group B] 30 minutes before surgery. Each patient was assessed daily until discharge for fever and the presence of infection of the surgical wound, urinary tract and respiratory tract. In the amoxicillin-clavulanic acid (Group A) and cefazolin (Group B) groups, overall 258 and 253 patients, respectively were evaluable for prophylactic efficacy at hospital discharge. Infectious complications were infrequent in both arms. Febrile morbidity occurred in 16 (6.3%) and 21 (8.1%) patients respectively in the amoxicillin-clavulanic acid and cefazolin groups. Wound infection and urinary tract infection were also higher but not significantly in the cefazolin group (0.8% versus 0% and 2.7% versus 2.0% respectively). There was no respiratory tract infection or septic death in either group. It is concluded that ultra-short term prophylaxis with both amoxicillin-clavulanic acid and cefazolin is safe and effective in elective laparotomic gynecologic surgery.

Effects of wortmannin on human neutrophil respiratory burst and phagocytosis.

Modulation of neutrophil response to naturally occurring stimuli is important to avoid host tissue injure. Both soluble and particulate stimuli may induce superoxide anion generation in human polymorphonuclear leukocytes. Recently wortannin has been shown to inhibit the N-formyl-methionyl-leucyl-phenylalanine (fMLP) induced activation of respiratory burst via phosphatidylinositol 3-kinase. However no data are available about the effect of the inhibitor on the respiratory burst induced by a particulate stimulus. In this paper we studied the effect of wortmannin on E. coli induced respiratory burst and phagocytosis by flow cytometry, which allows the quantitation of both H2O2 production and ingested bacteria in whole blood samples without the need of purification and concomitant manipulation of the cells. The effects of worthmannin on fMLP-induced chemotaxis was also examined by the under agarose method. Neither the E. coli nor the fMLP-induced responses were blocked by wortmannin, suggesting that PI 3-kinase activity is not required to activate these neutrophil functions. Since it is known that the respiratory burst elicited by fMLP is blocked by wortmannin, our results suggest that the generation of oxygen radicals is controlled via different signal transduction pathways, depending on the agonist used.

HLADR5 and C4BQO high frequency and antinuclear antibodies positivity in patients with 21 hydroxylase deficiency from Campania region.

HLA haplotypes, complement C4 factor and factor B immunochemical concentrations and autoantibodies titer have been studied in six patients with mild congenital adrenal hyperplasia (MC-AH), in two patients with classical congenital adrenal hyperplasia (CCAH) and in their parents. A high frequency of DR5 and C4BQO alleles have been found in MCAH patients. Moreover, C4BQO allele is carried out in three out of four cases associated with DR5. In the two CCAH patients we found a B51 and a B14 allele, the last one usually described in the non classical form of the disease in population of different ethnic origin. Signs of autoimmunity in some patients and parents have been found. C4 null alleles were several-fold more frequent among our patients with respect to the same ethnic control group and the autoantibody positivity could be the result of an altered immune regulation. The presence of a positive correlation between cortisol basal levels and C4 and Bf concentrations in the six MC-AH patients suggests an interrelationship between hormonal factors and immunological findings in this disease. Our finding about HLA antigens not previously described in this syndrome may stimulate more profound studies by genomic and cDNA probes.