Effect of different therapeutic modalities on spontaneous GH secretion in acromegalic patients

OBJECTIVES: Three major therapeutic modalities (transsphenoidal surgery, radiotherapy and medical therapy) are currently available for acromegaly. Although surgery is regarded as the primary option, 50--60% of macroadenomas require further treatment in the form of radiotherapy and/or medical therapy. Recent studies have suggested that radiotherapy might damage the normal hypothalamic-pituitary axis and also rarely leads to IGF-I normalization. The aims of this study were: (1) to examine the effect of different therapeutic modalities (transsphenoidal surgery, TSS; radiotherapy, RT; medical treatment with somatostatin analogues, SSA) on the daily spontaneous GH secretory pattern (day curve); and (2) to determine the relationship between the characteristics of the GH secretory pattern and the circulating concentration of IGF-I, acid-labile subunit (ALS) and IGFBP-3. DESIGN AND MEASUREMENTS: Spontaneous GH secretion was evaluated at hourly intervals from 0800 to 1800 h. IGF-I, IGFBP-3 and ALS were measured in basal conditions. The mean and the minimum values obtained from the day curve profile and the coefficient of variation (CV) of single values, which are expressions of the magnitude of the spontaneous secretory pulses, were used for statistical analysis. PATIENTS: In a group of 45 acromegalic patients (28 women, mean age 51 years, range 26--83 years, and 17 men, mean age 57 years, range 37--78 years) treated with different protocols, including TSS, RT and SSA therapy, we evaluated GH secretion to determine the effect of single treatment options on the spontaneous secretory profile. Subjects were grouped on the basis of different therapeutic modalities: TSS+RT+SSA (group 1), TSS+SSA (group 2), SSA (group 3), TSS (group 4), TSS+RT (group 5). In patients treated with somatostatin analogues (SSA), tests were performed about midway between two injections. RESULTS: The number of deficiencies of the other pituitary functions (PD) was significantly higher in the groups that underwent RT (groups 1 and 5) than in the other groups; in both cases, P<0.01. No significant differences were observed with regard to the mean GH, IGF-I, ALS or IGFBP-3 among the different treatment groups. A significant difference in the GH nadir was found between groups 2 and 4 (P=0.042) and between groups 3 and 4 (P=0.015). GH CV showed lower values in subjects who underwent RT (groups 1 and 5) than in the other groups. The difference was statistically significant between group 5 and groups 2, 3 and 4 (P<0.05), between group 1 and groups 3 and 4 (P<0.05), and between groups 2 and 4 (P=0.007). CONCLUSIONS: Our data confirm that radiation therapy decreases GH variability, and that this effect is probably due to hypothalamic damage, as already reported by others. In irradiated patients, a single random sample should therefore be sufficient to evaluate spontaneous GH secretion.     

Distractive flexion injuries of the subaxial cervical spine treated with anterior plate alone

The clinical and radiographic effect of anterior plate fixation alone was evaluated in 36 consecutive patients with distractive flexion (DF) injuries in the lower cervical spine. Mean follow-up time was 15 months. The aim of the present study was to determine whether anterior plate fixation alone provides sufficient stability when treating DF injuries in the cervical spine. Solid union was seen in 6 of 6 patients with stage 1 injury and in 15 of 17 patients with stage 2 injury. In the patients with stage 3 injury, 7 of 13 of the anterior fixations failed. These failures occurred mainly among the patients with severe neurologic injuries. We believe these findings substantiate the use of anterior plate alone for DF injuries at stage 1 and 2 but disqualify anterior plate fixation alone for DF injuries at stage 3, with neurologic injury present.     

Biophysical characterization of gap-junction channels in HeLa cells

HeLa cells seem not to be junctionally coupled when probed with techniques such as Lucifer yellow spreading and/or ionic coupling measured with three inserted microelectrodes. When investigated with double whole-cell patch-clamp measurements, HeLa cells in monolayer cultures were electrically coupled in 39% of the cases with very low transjunctional conductances (average one to five open channels). These gapjunction channels had a single-channel conductance = 26±6 pS and were voltage-gated with an equivalent gating charge z=3.1±1.5 for a voltage of half-maximal inactivation U _o=49±10 mV. The voltage-dependent component represents only 31±8% of the total junctional conductance. The voltage-insensitive conductance is characterized by a residual open probability p _o()=0.34±0.12, which corresponds to a ratio G _min/G _max=0.50±0.12. Dissociation of monolayer cells into cell pairs yielded about 58% coupled cell pairs with no notably altered single-channel properties.     

The effects of GSTM1 and GSTT1 polymorphisms on micronucleus frequencies in human lymphocytes in vivo.

The influence of genetic polymorphisms in GSTM1 and GSTT1 genes on micronucleus frequencies in human peripheral blood lymphocytes was assessed through a pooled analysis of data from seven laboratories that did biomonitoring studies using the in vivo cytokinesis-block micronucleus assay. A total of 301 nonoccupationally exposed individuals (207 males and 94 females) and 343 workers (237 males and 106 females) occupationally exposed to known or suspected genotoxic substances were analyzed by Poisson regression. The results of the pooled analysis indicate that the GSTT1 null subjects had lower micronucleus frequencies than their positive counterparts in the total population (frequency ratio, 0.55; 95% confidence interval, 0.33-0.89). The protective effect of this genotype is reversed with increasing age, with a frequency ratio of 1.33 (95% confidence interval, 1.06-1.68) in subjects aged 60 years. A significant overall increase in micronucleus frequency with age and gender (P < 0.001 and P = 0.024, respectively) was observed, females having higher micronucleus frequencies than males, when occupationally exposed (P = 0.002). Nonoccupationally exposed smokers had lower micronucleus frequencies than nonsmokers (P = 0.001), whereas no significant difference in micronucleus level was observed between smokers and nonsmokers in the occupationally exposed group (P = 0.79). This study confirms that pooled analyses, by increasing the statistical power, are adequate for assessing the involvement of genetic variants on genome stability and for resolving discrepancies among individual studies.     

Enhancement of Endothelial Cell E-Selectin Expression by Sera from Patients with Active Behçet's Disease: Moderate Correlation with Anti-endothelial Cell Antibodies and Serum Myeloperoxidase Levels

We studied the in vitro E-selection expression of endothelial cells treated with sera from patients with Beh?et's disease (BD) and factors (anti-endothelial cell antibodies, anti-neutrophil cytoplasmic antibodies, cytokines, and myeloperoxidase (MPO) that may contribute to adhesion molecule expression. A total of 21 patients with BD and 27 healthy controls were studied. In vitro E-selectin endothelial cell expression was investigated by ELISA after HUVEC incubation with sera or purified IgG from patients with BD and controls. Increased E-selectin expression was observed when endothelial cells were incubated with sera from patients with active disease or from patients with circulating anti-endothelial cell antibodies and high levels of plasma myeloperoxidase. Abnormalities of endothelial cell function have been suggested to play a role in the occurrence of vascular damage in BD. Our findings suggest that anti-endothelial cell antibodies and neutrophil hyperactivity, as inferred from the high plasma MPO levels in patients with active disease, may explain endothelial cell activation and neutrophil accumulation in vascular lesions.     

Investigating the role of imprinted genes in pediatric sporadic brain arteriovenous malformations

Arteriovenous malformation AVM is a vascular congenital defect affecting microvasculatu re of both brain and peripheral o rga ns.Arteriovenous malformation of the brain(bAVM,OMIM#108010),in particular,affects up to 15 per100,000 persons with no sex predominance.Almost 50%of the patients manifest intracerebral hemorrhage and epileptic seizures,as main clinical symptoms.     

A factor secreted by human embryo stimulates cytokine release by uterine mast cell

The existence of a biochemical network of embryo-maternal communicationimplies that various secreted molecules constitute a signal-responsemechanism, important for the process of embryo implantationin mammals. Here we report the purification of a protein withan apparent molecular weight of 136 kDa, responsible for a 2000-foldincrease in embryo-derived histamine-releasing factor (EHRF)activity. This protein, purified from medium from the in-vitroculture of 2–8-cell human embryos, by means of affinitychromatography, was capable of binding immunoglobulin (lg)Eas demonstrated by immunoblotting and enzyme-linked immunosorbentassays. We found that EHRF was capable of inducing release ofhistamine and cytokines in vitro from rat uterine tissue, collectedon day 4 of pregnancy (preimplantation stage of embryo development).When EHRF was used as a secretagogue, granulocyte macrophage-colonystimulating factor (GM-CSF) release increased from 3 to 55 pg/g(P <0.01) and tumour necrosis factor-     

Endothelin-1 concentrations in cord blood of neonates with meconium-stained amniotic fluid

BACKGROUND: The effects of meconium-stained amniotic fluid (MSAF) on cord blood endothelin-1 (ET-1) concentrations have not been explored. OBJECTIVE: The aim of this study was to verify whether MSAF influences ET-1 cord blood concentrations in healthy term neonates. METHODS: Using an enzyme-linked immunosorbent assay, plasma ET-1 concentrations were determined in 30 healthy term neonates with MSAF, and in 15 healthy term neonates without MSAF. The two groups were of the same gestational age, weight, Apgar score, cord blood pH, base excess, and hematocrit values, as well as systolic and diastolic blood pressures. RESULTS: ET-1 plasma concentrations were not significantly different between the two groups and did not correlate with cord blood pH or base excess values. CONCLUSION: Our data demonstrate that meconium passage does not induce ET-1 secretion.