Sex differences in the effects of ethanol pre-exposure during adolescence on ethanol-induced conditioned taste aversion in adult rats

Alcohol use, which typically begins during adolescence and differs between males and females, is influenced by both the rewarding and aversive properties of the drug. One way adolescent alcohol use may modulate later consumption is by reducing alcohol's aversive properties. Here, we used a conditioned taste aversion (CTA) paradigm to determine if pre-exposure to alcohol (ethanol) during adolescence would attenuate ethanol-induced CTA assessed in adulthood in a sex-dependent manner. Male and female Long-Evans rats were given intraperitoneal (i.p.) injections of saline or 3.0 g/kg ethanol in a binge-like pattern during postnatal days (PD) 35-45. In adulthood (>PD 100), rats were given access to 0.1% saccharin, followed by saline or ethanol (1.0 or 1.5 g/kg, i.p.), over four conditioning sessions. We found sex differences in ethanol-induced CTA, with males developing a more robust aversion earlier in conditioning. Sex differences in the effects of pre-exposure were also evident: males, but not females, showed an attenuated CTA in adulthood following ethanol pre-exposure, which occurred approximately nine weeks earlier. Taken together, these findings indicate that males are more sensitive to the aversive properties of ethanol than females. In addition, the ability of pre-exposure to the ethanol US to attenuate CTA is enhanced in males compared to females.     

Neuroblastoma screening: arguments from retrospective analysis of three German neuroblastoma trials

The justification for a neuroblastoma screening program has been discussed controversially. The analysis of 701 patients of the German neuroblastoma trials NB 79, 82, and 85 provides additional information on this subject. The basis of our investigation was the good prognosis of stage I and II patients (92% survival 5-10 years after diagnosis) compared with 66% in stage III and 11% in metastatic disease. The correlation of age and stage (p less than 0.0001), a median progression time of 14.6 months (range 3.4-33.5 mo) from localized to metastatic disease as observed in 18 patients, the high incidence of asymptomatic diseases in stages I (49%) and II (30%) patients and the cost-benefit estimation arguments in favor of a screening program. The key problem for the lab part is the lower incidence of abnormal catecholamine metabolite excretion in stage I and II patients. The origin of 89% of metastatic disease from intraabdominal sites suggests that ultrasonography may be of additional value.     

Treatment of hypercholesterolemia in children and adolescents

In patients with severe genetic hypercholesterolemia, therapeutic reduction of elevated serum total cholesterol and LDL cholesterol should begin in early childhood to lower the risks of cardiovascular disease later in life. We evaluated the effects of outpatient therapy with diet alone and with combined diet and drug therapy in children and adolescents with hypercholesterolemia of apparent dominant inheritance. Serum lipid values before and during dietary treatment were available in 35 patients (mean age at start of treatment 7.9 years, range 2.0-17.6 years) followed for an average duration of 17.5 months (range 4-70 months). A comparison between untreated state and combined therapy with diet and cholestyramine was possible in 14 patients (mean age 8.6 years, range 2.4-17.0 years) followed for 27.9 months (range 4-97 months). Dietary modification achieved by repeated counseling and training lowered serum total cholesterol by mean (+/- SE) 11.7 +/- 1.9% (p < 0.0001) and LDL cholesterol by 17.3 +/- 3.5% (p < 0.0001). However, five of 35 patients did not show an appreciable effect of therapy (cholesterol reduction < 5%), possibly because of non-compliance. Diet combined with cholestyramine in an average dose of 0.36 g/kg body weight/day reduced total cholesterol by 33.0 +/- 2.4% (p < 0.0001) and LDL cholesterol by 37.5 +/- 4.3% (p < 0.0001) and was effective in all patients. Both forms of treatment had no effect on serum triglycerides and HLD cholesterol. No serious side effects were noted, and percentile values for weight and height remained unchanged in all but three obese children.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma Neurotensin: Lack of a Differentiation and Tumor Marker in Children with Neuroblastoma

Neurotensin is a tridecapeptide with changing receptor expression in central and peripheral neural cells during ontogeny suggesting its potential use as a differentiation and tumor marker in neuroectodermal malignancies. We investigated the neurotensin levels in plasma samples of 58 patients with neuroblastoma using a sensitive radioimmunoassay. Elevated levels were found only in one stage III and in one stage IVs patient, while the neurotensin concentrations of 56 patients were in the range of control children. We conclude that plasma neurotensin reflects neither the differentiation nor the tumor status in children with neuroblastoma.     

Three-axis ellipsoidal fitting of videokeratoscopic height data after penetrating keratoplasty

PURPOSE: After penetrating keratoplasty corneal topography tends to be irregular and the fitting of spectacle glasses or contact lenses may be difficult. The purpose of this study was to demonstrate a mathematical method for approximation of discrete corneal topography height data with an ellipsoid for better appreciation of the clinical outcome after PK. PATIENTS AND METHODS: In 50 eyes (30 keratoconus, 20 Fuchs' dystrophy) penetrating keratoplasty was performed using nonmechanical trephination with the excimer laser 193 nm. Main outcome measures were objective corneal astigmatism (regular keratometry, corneal topography (TMS-1)), subjective refraction and best-corrected visual acuity (VA) in a fixed postoperative gate 3 and 12 month postoperatively and after suture removal. An approximation algorithm was applied for fitting a general ellipsoidal surface (not rotationally symmetric) to raw corneal topography height data. A set of parameters (meridional power, axis and asphericity) were calculated. The root mean square error (RMS) was determined between raw topography power data and the ellipsoidal model surface within an apical distance of 3 mm. The cylinder of subjective refraction was correlated with the keratometric readings, the Simulated Keratometry (SimK) of the topography system and the respective parameters of the model surface. RESULTS: The amount of the SimK cylinder yielded higher values than keratometry and the ellipsoidal fit; subjective refraction yielded the lowest value at each follow-up interval. The ellipsoidal fit showed the best correlation to the refractive cylinder at all follow-up stages (p = 0.04 at 3, p = 0.01 at 12 months and p = 0.002 after suture removal). The axis of the best ellipsoidal fit showed a significant correlation with the axis of the refractive cylinder at all follow-up intervals (p = 0.02 at 3 months, p = 0.01 before suture removal and p = 0.002 after suture removal). The axis of the keratometric cylinder showed a mild correlation at all follow-up examinations (p = 0.05 at 3 months, p = 0.02 before suture removal and p = 0.04 after suture). The cylinder of the topographic modeling system, however, showed a significant correlation with the refractive cylinder axis only after suture removal (p = 0.04). The paracentral corneal power of SimK (45.9D at 3 months, 44.4D at 12 months and 43.0D after suture removal) exceeded the respective values of conventional keratometry (43.1D at 3 months, 42.9D at 12 months and 41.7D after suture removal) and the ellipsoidal fit (43.3D at 3 months, 43.0D at 12 months and 41.8D after suture removal). The corneal asphericity from the ellipsoidal fit reached an approximately spherical shape in radial direction (A = 1.0) in the initial time period after penetrating keratoplasty, remained stable before suture removal and decreased significantly (p = 0.02) to a final value of A = 0.86 indicating a (normal) prolate shape of the cornea. The approximation error between the raw corneal topography height data and the best ellipsoidal fit model surface was nearly unchanged before suture removal (1.8 +/- 0.7 microm at 3 months and 1.9 +/- 1.1 microm at 12 months, p = 0.30) and decreased significantly to the examination after suture removal (0.9 +/- 0.5 microm, p = 0.01). CONCLUSIONS: The approximation of corneal topography height data with an ellipsoidal model surface renders reconstruction of clinically relevant corneal topography parameters including corneal asphericity. Even in markedly irregular corneal surfaces, such as after PK, the correlation of amount/axis of refractive cylinder with the model surface parameters is more accurate than with respective SimK values of corneal topography analysis.     

Superficial corneal effects of experimental nonmechanical penetrating keratoplasty using a Q-switched Er:YAG laser

PURPOSE: To assess thermal effects of Q-switched Er:YAG laser trephination to corneal epithelium and superficial stroma using different mask types and materials for experimental penetrating keratoplasty. METHODS: Laser trephination was performed in 20 freshly-enucleated porcine eyes (repetition rate 5 Hz, pulse energy 65 mJ, spot size 0.7 mm). We used flat, open-metal and ceramic masks for donor and recipient trephination placed directly onto the corneal surface. Main outcome measures as assessed by light microscopy after PAS staining of 8-microm paraffin sections included: extension of tissue thermal damage at the cut edge in the superficial and basal epithelial layers, the basement membrane and subepithelial stroma, and depth and width of epithelial/stromal involvement in the area of the donor mask contact. RESULTS: The thermal damage in the superficial epithelium was more pronounced in donor (mean extension 61.6 +/- 15.6 microm) than in recipient (29.4 +/- 24.9 microm, p= 0.05) trephination. In donor trephination, thermal damage zone of the superficial epithelial layer was significantly smaller with ceramic than with metal masks (21.0 +/- 23.0 versus 61.6 +/- 15.6 microm, p= 0.014). In contrast, differences at basal epithelial layer (p= 0.44), basement membrane (p= 0.79), and subepithelial stroma (p= 0.2) were not statistically significant. Superficial donor involvement of the cornea adjacent to the paracentral donor mask contact zone was seen neither with ceramic nor with metal masks. CONCLUSION: Superficial corneal alterations adjacent to the mask-cornea contact zone may be minimized by using the Er:YAG laser in a Q-switched mode. Ceramic masks, in contrast to metal masks, further reduce superficial thermal alterations at the cut edge.