Oral and maxillofacial manifestations of Gardner's syndrome associated with growth hormone deficiency: case report and literature review.

Gardner's syndrome (GS) is a hereditary disorder inherited as autosomal dominant with complete penetrance and variable expression. GS is a variant of familial adenomatous polyposis characterized by extracolonic manifestations including osteomas, dental anomalies, and epidermoid cysts. The association between GS and endocrine abnormalities has been well documented but a direct pituitary involvement has never been reported. We present a case of oral and maxillofacial manifestations in an adult patient affected by GS associated with growth hormone deficiency, a hitherto unreported association. The possible pathogenic mechanisms are discussed.     

Different cytokine levels in thrombolysis patients as predictors for clinical outcome

Thrombolytic therapy not always improves clinical outcome in ischemic stroke patients. This could cause lymphomonocyte accumulation in the infarcted brain area. These produce an excessive amount of proinflammatory cytokines, such as IL-1 beta, IL-6 and TNF-alfa. The aim of our study was to determine ILs levels in fibrinolytic therapy treated patients, compared with healthy controls and to evaluate if the varying levels can predictors of neurological outcome. Eighteen patients underwent thrombolytic treatment with t-PA within 3 h. Plasma levels of IL-1 beta, IL-6, TNF-alfa and IL-10 were determined by ELISA method before and within 24 h after t-PA infusion and compared with controls. Significantly higher levels of IL-1 beta and Il-6 emerged in stroke patients before treatment compared with the control group (P < 0.05 and 0.04, respectively). Slightly higher plasma levels of TNF-alfa and lower plasma levels of IL-10 were also found at base line in stroke patients. After thrombolytic treatment no significant variations were observed in the levels of TNF-alfa and IL-6, whereas a trend toward lower values for IL-1 beta and higher levels for IL-10 was observed. Positive correlations among the values of IL-6, TNF-alfa and National Institute of Health Stroke Scale (NIHSS) at discharges were observed. A similar correlation with modified Rankin scale score at 3 month was found. Pre-treatment cytokine status seems to influence pre-and long-term clinical outcome. Therefore an investigation into the possible predictor of cytokines seem worthy.     

Neuropathy in children and adolescents with diabetes mellitus

Nerve conduction velocities were studied in the median, posterior tibial, radial and sural nerves of 50 juvenile diabetics, average age 13 +/- 1.3 years and mean duration of diabetes 2.3 +/- 1.4 years. Motor conduction velocity (MCV) in the median nerve was reduced in 10% of the subjects, and in the posterior tibial in 32%. Sensory conduction velocity (SCV) in the radial nerve was reduced in 30% of the subjects, and in the sural in 44%. No relationship was found between the reduction in conduction velocity and the duration of diabetes; nevertheless, a correlation was observed between this reduction and the degree of glycaemic control represented by the glycosylated haemoglobin concentration. The authors emphasize the importance of good glycaemic control for the prevention of diabetic neuropathy.     

Effectiveness of combined GnRH analogue plus raloxifene administration in the treatment of uterine leiomyomas: a prospective,randomized, single-blind,placebo-controlled clinical trial

BACKGROUND: Raloxifene hydrochloride is a synthetic non-steroidal drug used for the prevention and treatment of post-menopausal osteoporosis. Pre-clinical and clinical data have shown that raloxifene may have a beneficial effect on leiomyomas. The aim of this prospective single-blind, randomized, placebo-controlled clinical trial was to evaluate the effectiveness of the addition of raloxifene to GnRH analogues on uterine, leiomyoma, and non-leiomyoma sizes, and on the occurrence of leiomyoma-related symptoms. METHODS: After randomization using a computer-generated list, 100 pre-menopausal women with symptomatic uterine leiomyomas received either leuprolide acetate depot plus raloxifene 60 mg daily (group A) or leuprolide plus placebo tablet (group B) for six cycles of 28 days. At baseline and after treatment, uterine, leiomyoma and non-leiomyoma sizes, and leiomyoma-related symptoms were evaluated for each woman. Analysis was by intention-to-treat method. RESULTS: After six cycles of treatment, a significant decrease in uterine, leiomyoma, and non-leiomyoma sizes was detected in both groups in comparison with baseline. At the same time, no significant difference in uterine and non-leiomyoma sizes was observed between the groups. Leiomyoma sizes were significantly (P < 0.05) lower in group A than in group B. No difference was observed in leiomyoma-related symptoms between groups throughout the study period. CONCLUSIONS: In women treated with GnRH analogue, the raloxifene administration induces a higher reduction of leiomyoma sizes.     

Drug resistance mutations and newly recognized treatment-related substitutions in the HIV-1 protease gene: prevalence and associations with drug exposure and real or virtual phenotypic resistance to protease inhibitors in two clinical cohorts of antiretroviral experienced patients

This study aimed at identifying HIV-1 protease amino acid changes associated with protease inhibitor (PI) exposure and susceptibility. New amino acid substitutions were correlated with the number of experienced PIs, reaching statistical significance only for those at positions 3, 44, and 74. The correspondence multivariate model demonstrated that > or =3 experienced PIs and substitutions or mutations at positions 3, 46, 54, 73, 74, and 84 were correlated with PI cross-resistance, including resistance for lopinavir and amprenavir in this cohort of patients who were naive for these drugs.     

Sodium hypochlorite-, chlorine dioxide- and peracetic acid-induced genotoxicity detected by the Comet assay and Saccharomyces cerevisiae D7 tests

Mutagenicity of drinking water is due not only to industrial,agricultural and urban pollution but also to chlorine disinfectionby-products. Furthermore, residual disinfection is used to providea partial safeguard against low level contamination and bacterialre-growth within the distribution system. The aims of this studywere to further evaluate the genotoxic potential of the worldwide used disinfectants sodium hypochlorite and chlorine dioxidein human leukocytes by the Comet assay and in Saccharomycescerevisiae strain D7 (mitotic gene conversion, point mutationand mitochondrial DNA mutability, with and without endogenousmetabolic activation) and to compare their effects with thoseof peracetic acid, proposed as an alternative disinfectant.All three disinfectants are weakly genotoxic in human leukocytes(lowest effective dose 0.2 p.p.m. for chlorine dioxide, 0.5p.p.m. for sodium hypochlorite and peracetic acid). The resultsin S.cerevisiae show a genotoxic response on the end-pointsconsidered with an effect only at doses higher (5- to 10-fold)than the concentration normally used for water disinfection;sodium hypochlorite and peracetic acid are able to induce genotoxiceffects without endogenous metabolic activation (in stationaryphase cells) whereas chlorine dioxide is effective in growingcells. The Comet assay was more sensitive than the yeast tests,with effective doses in the range normally used for water disinfectionprocesses. The biological effectiveness of the three disinfectantson S.cerevisiae proved to be strictly dependent on cell-specificphysiological/biochemical conditions. All the compounds appearto act on the DNA and peracetic acid shows effectiveness similarto sodium hypochlorite and chlorine dioxide. ¹Author to whom correspondence should be addressed. Tel: +39 0521 905608; Fax: +39 0521 905604; Email: mutgen{at}unipr.it Received on September 22, 2003; revised and accepted on November 27, 2003