Non-metastatic prostate cancer treated with exclusive radiotherapy: prognosis of patients according to lymph node radiologic or surgical assessment method. Multivariate retrospective analysis

PURPOSE: To compare retrospectively the outcome of localized prostate cancers treated by curative external radiotherapy in which the negative lymphatic status was either surgically or radiologically assessed. METHODS AND MATERIALS: From January 1986 to December 1995, 112 patients with localized prostate cancers were found to have no evidence of lymphatic disease in the pelvis. N0 status was assessed either surgically (61 patients, group pN-) or after a CT scan procedure (51 patients, group cN0). The treatment consisted of conventional external radiotherapy using a four-fields box technique to a total dose of 65 Gy. The pelvis was never irradiated. RESULTS: The two groups did not statistically differ according to age, PSA level, Gleason score, T stage and hormonal therapy. Actuarial NED survival rates were 80% and 60% at five and ten years respectively. At ten years, the actuarial NED survival rates were 78% and 34% in the pN- and cN0 groups respectively (p = 0.003). The multivariate analysis corroborated the positive impact of lymphatic dissection before radiotherapy on disease free survival of T1-T2 patients, but not for T3 stages. CONCLUSIONS: This retrospective study suggests the inability of CT scan to accurately evaluate the lymph node status in carcinoma of the prostate. Systematic ilio-obturator nodal dissection is strongly recommended in early stages before curative radiotherapy. Only pN-patients should be included in high dose conformal irradiation trials.     

Heart transplantation: echocardiographic assessment of morphology and function after more than 10 years of follow-up

BACKGROUND: Over recent years, heart transplantation (HTX) developed into a successful option for long-term treatment of end-stage heart failure. Ten-year survival ranges between 40% and 50%. Little is known, however, about function and morphology of transplanted hearts during follow-up of more than 10 years. METHODS: In a consecutive cohort of 65 patients (55 male, 54.6 +/- 12.1 years at the time of transplantation), graft function was assessed by color Doppler echocardiography 12.5 +/- 1.4 years after heart transplantation (10 to 15 years). RESULTS: Left atrial and ventricular dimensions were found in a normal range (LA 37.7 +/- 8.9 mm, LV enddiastolic 45.6 +/- 6.4 mm, 30 to 71 mm). Ejection fraction (EF) of 71 +/- 11.7% and a fractional shortening of 35.3 +/- 10.3% presented with normal values. Left ventricular mass (male 263.8 +/- 111.4 g, female 373.0 +/- 181.1 g) was slightly increased resulting in mild hypertrophy in women. Focused on right ventricular morphology, enlargement of both the right atrium and the right ventricle (RA 40.7 +/- 11.8 mm, RV 37.4 +/- 8.3 mm) was observed in the majority of the patients. Tricuspid valve insufficiency (> grade II) was present in 46 of 65 patients; 5 patients had previously undergone tricuspid valve replacement. Atrial filling waves were detectable in only 47 of 65 patients, thus, 28% of patients showed signs of LA-dysfunction. CONCLUSIONS: More than 10 years post-HTX, cardiac grafts were characterized by normal left ventricular dimensions and ejection fraction. LA-dysfunction and RV-enlargement associated with tricuspid insufficiency were frequent findings, however, not associated with clinical signs of congestive heart failure in the majority of patients.     

Nutritional assessment of serum and hepatic vitamin A levels in patients with cirrhosis

BACKGROUND: Serum vitamin A (retinol) levels may not correlate with hepatic vitamin A stores in patients with cirrhosis; thus, supplementation of vitamin A based on serum levels may have a detrimental effect. Our aim was to determine whether serum levels correlate with hepatic stores in cirrhotic patients. METHODS: A prospective study of patients with cirrhosis undergoing orthotopic liver transplantation was completed. Serum and hepatic levels of vitamin A were measured by high-performance liquid chromatography. Statistical analysis was performed using rank sum tests and Spearman rank correlation coefficients. RESULTS: Fifty cirrhotic patients (33 men and 17 women, mean age 53 years) were compared with a control group (25 men and 25 women, mean age 47 years) of liver donors. Median serum levels of retinol were 259 microg/L in controls and 166 microg/L in cirrhotic patients (p < .001). Median hepatic levels of retinol were 25 microg/g in controls and 27.5 +/- g/g in cirrhotic patients (p not significant). Total hepatic vitamin A levels (retinol plus retinyl esters) were 471 microg/g in controls and 244 microg/g in cirrhotic patients (p = .028). Serum retinol did not correlate with total hepatic vitamin A stores in cirrhotic patients (rs = .10, p = .332). CONCLUSIONS: Serum retinol and total hepatic vitamin A stores are lower in cirrhotic patients than in controls. However, because levels of serum retinol do not correlate with hepatic vitamin A levels, the decision to prescribe vitamin A replacement for patients with cirrhosis should not be made solely on the basis of serum retinol levels.     

Genetic and pharmacological demonstration of a role for cyclic AMP-dependent protein kinase-mediated suppression of protein phosphatases in gating the expression of late LTP

Protein kinases and phosphatases play antagonistic roles in regulating hippocampal long-term potentiation (LTP), with kinase inhibition and phosphatase activation both impairing LTP. The late phase of LTP (L-LTP) requires activation of cAMP-dependent protein kinase (PKA) for its full expression. One way in which PKA may critically modulate L-LTP is by relieving an inhibitory constraint imposed by protein phosphatases. Using mutant PKA mice [R(AB) transgenic mice] that have genetically reduced hippocampal PKA activity, we show that deficient L-LTP in area CA1 of mutant hippocampal slices is rescued by acute application of two inhibitors of protein phosphatase-1 and protein phosphatase-2A (PP1/2A) (okadaic acid and calyculin A). Furthermore, synaptic facilitation induced by forskolin, an adenylyl cyclase activator, was impaired in R(AB) transgenics and was also rescued by a PP1/2A inhibitor in mutant slices. Inhibition of PP1/2A did not affect early LTP (E-LTP) or basal synaptic transmission in mutant and wildtype slices. Our data show that genetic inhibition of PKA impairs L-LTP by reducing PKA-mediated suppression of PP1/2A.     

Long term (24 months) follow-up of a hepatitis A and B vaccine,comparing a two and three dose schedule in adolescents aged 12-15 years

BACKGROUND: A two dose schedule (0 and 6 months) for a combined hepatitis A and B vaccine is currently being developed. METHODS: The present study compared the combined hepatitis A and B vaccines in 12-15-year-old: Twinrix paediatric (360 EL.U HAV antigen/10 microg HBs antigen) on a three dose schedule (0, 1 and 6 months) to the adult formulation (720 EL.U HAV antigen/20 microg HBs antigen) on a two dose schedule (0 and 6 months) and also reports on the follow-up until 24 months. RESULTS: Seroconversion (SC) rates to HAV in both regimens reached 100% by month 7 and remained 100% up to month 24. Anti-HAV, GMTs were slightly higher for the two dose than the three dose regimens at this time point. Seroprotection against hepatitis B was >99% in both groups by month 7 and 24, this was still 94 and 96%, respectively. Statistical non-inferiority of group 1 (two dose) versus group 2 (three dose) was demonstrated. All vaccines were well tolerated and the most frequently reported local and general symptoms were pain and fatigue. There were no vaccine-related serious adverse events reported during the study. CONCLUSION: The two dose regimen elicited similar immunogenicity to HAV and HBsAg and reactogenicity profiles as the three dose regimen in this group of healthy adolescents. The reduction in the number of doses from the current three dose schedule will make vaccination against hepatitis A and B more convenient to the vaccinee, reduce healthcare staff time required and may lower the overall costs associated with vaccination.     

Systemic and intestinal antibody secreting cell responses and protection in gnotobiotic pigs immunized orally with attenuated Wa human rotavirus and Wa 2/6-rotavirus-like-particles associated with immunostimulating complexes

The undesirable side effects and variable efficacy of some oral live rotavirus vaccines in infants have necessitated alternative vaccine approaches. We evaluated a recombinant RFVP2/WaVP6 rotavirus-like-particle (2/6VLP) oral vaccine, using an immunostimulating complex (ISCOM) matrix as adjuvant, in a gnotobiotic (Gn) pig model of human rotavirus (HRV) disease. The 2/6VLPs adhered to the ISCOM-matrix (2/6VLP-ISCOM ) and were antigenic, but they failed to induce protection. However, when combined with attenuated (Att) HRV for oral priming, the 2/6VLP-ISCOM vaccine was effective as a booster and induced partial protection against virulent Wa HRV. The 250 microg 2/6VLP dose was more effective than 100 microg. The highest mean numbers of IgA antibody secreting cells evaluated by ELISPOT in intestinal lymphoid tissues were in pigs receiving AttHRV+2/6VLP-ISCOM or three doses of AttHRV and were associated with the highest protection rates.     

Comparison of ingestive effects of brewer's yeast,casein, and soy protein on bioavailability of dietary iron

The effects of brewer's yeast, casein, and soy protein intakes on the absorption and retention as well as the incorporation into hemoglobin and systemic iron stores of dietary iron were examined in an animal experiment with growing rats. Relative biological values (RBV) of iron in the rats fed casein (C), soy protein (SP), and yeast (Y) diets were 1.00, 0.31, and 1.77, respectively. The apparent absorption of iron in Y-diet-fed rats was significantly higher than that in C- or SP-diet-fed rats. The hemoglobin regeneration efficiency (HRE) of iron in Y group was significantly higher than those in C and SP groups. As a result of search for iron-absorptive enhancers (IAE) in yeast, RBV and HRE of the yeast-cell-wall-including diet turned out to be significantly higher than those of its lacking diet. These results suggest that IAE occurring in the yeast cell wall may be effective for iron absorption.