New drug development in digestive neuroendocrine tumors.

The traditional cytotoxic agents are of limited efficacy in the treatment of neuroendocrine tumors of the gastrointestinal tract (NETs). Recent investigations have brought up a number of biological features in this family of neoplasms that could represent targets for anticancer treatment. NETs seem to have an extraordinary tumor vascularization with high expression of proangiogenic molecules such as the vascular endothelial growth factor along with overexpression of certain tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR), the insulin growth factor receptor (IGFR) and their downstream signaling pathway components (PI3K-AKT-mTOR). The rationale of an antiangiogenic approach in the treatment of NETs and the use of other pharmacological strategies such as EGFR, IGFR and mammalian target of rapamycin inhibitors are discussed. Additionally, the emerging results of recent clinical trials with these targeted drugs are presented.     

Validation of a Parent-Adolescent Communication Scale for use in STD/HIV prevention interventions.

This study reports on the validation of a scale to assess adolescent girls' frequency of sexual communication with their parents. The Parent-Adolescent Communication Scale (PACS) was administered to 522 African American female adolescents ranging in age from 14 to 18. The PACS demonstrated satisfactory internal consistency (across multiple administrations) and acceptable test-retest reliability over a 12-month follow-up period. Concurrently, scores on the PACS were correlated with frequency of sexual communication with partner, sexual communication self-efficacy (boyfriend), perceived parental knowledge, family support, depression, and condom use with steady male sex partners. Prospectively, baseline PACS scores were correlated with frequency of sexual communication with partner and condom use. The present investigation indicates that the PACS is a reliable and valid measure of frequency of sexual communication between female adolescents and their parents. Utility of the PACS for researchers and practitioners is discussed.     

The average cumulative risks of breast and ovarian cancer for carriers of mutations in BRCA1 and BRCA2 attending genetic counseling units in Spain.

PURPOSE: It is not clear that the published estimates of the breast and ovarian cancer penetrances of mutations in BRCA1 and BRCA2 can be used in genetic counseling in countries such as Spain, where the incidence of breast cancer in the general population is considerably lower, the prevalence of BRCA2 mutations seems to be higher, and a distinct spectrum of recurrent mutations exists for both genes. We aimed to estimate these penetrances for women attending genetic counseling units in Spain. EXPERIMENTAL DESIGN: We collected phenotype and genotype data on 155 BRCA1 and 164 BRCA2 mutation carrier families from 12 centers across the country. Average age-specific cumulative risks of breast cancer and ovarian cancer were estimated using a modified segregation analysis method. RESULTS: The estimated average cumulative risk of breast cancer to age 70 years was estimated to be 52% [95% confidence interval (95% CI), 26-69%] for BRCA1 mutation carriers and 47% (95% CI, 29-60%) for BRCA2 mutation carriers. The corresponding estimates for ovarian cancer were 22% (95% CI, 0-40%) and 18% (95% CI, 0-35%), respectively. There was some evidence (two-sided P = 0.09) that 330A>G (R71G) in BRCA1 may have lower breast cancer penetrance. CONCLUSIONS: These results are consistent with those from a recent meta-analysis of practically all previous penetrance studies, suggesting that women with BRCA1 and BRCA2 mutations attending genetic counseling services in Spain have similar risks of breast and ovarian cancer to those published for other Caucasian populations. Carriers should be fully informed of their mutation- and age-specific risks to make appropriate decisions regarding prophylactic interventions such as oophorectomy.     

Solid liver mass. Studies with nuclear medicine

We present the case of a 23 year old female with two incidentally detected hepatic mass that have not clinically o radiologically specific findings. Nuclear medicine tracers, including colloids and hepatobiliary agents showing the characteristic findings of focal nodular hyperplasia: Hypervascularization, normal uptake of colloids, accumulation of hepatobiliary tracer and hot spots due to the retention of this tracer during the clearance fhase. The patient was underwent hepatectomy. The examination of surgical specimen revealed focal nodular hyperplasia. The scintigraphic studies could be an useful tool in the noninvasive diagnosis of liver masses.     

Results of chromosomal studies in 270 couples with reproductive problems]

Cytogenetic study in couples with recurrent reproductive failure allows the detection of structural chromosome anomalies which don't have a phenotypic effect in carriers, but permit the explanation of the production of genetically unbalanced gametes. We present the investigation performed in 270 couples which demonstrated a chromosomal alteration in 9.2% of them. This allows genetic counselling in respect of the importance of the finding, recurrence risk and reproductive alternatives. In 8.6% we found some cellular lines with aneuploidies in sexual chromosomes, which don't represent a such concrete risk.     

Almost total absence of the left ventricular myocardium with dextro-transposition of the great arteries

The term parchment heart is used to describe partial to nearly complete loss of ventricular myocardium. We report the first case of transposition of the great arteries with almost total absence of left ventricular myocardium. The latter was not recognized and the child underwent Mustard's operation at four months of age. He died on the operating table. At necropsy, the left ventricular wall was 1 mm in thickness; microscopic examination revealed few myocardial fibers within edematous connective tissue.     

Reaction of rectal mucosa of celiac patients to direct contact with gluten

It is assumed that the colonic mucosa of celiac patients is not sensitive to gluten. This assumption has been supported by the absence of clinical manifestations of colonic involvement in patients with active celiac disease which, by itself, does not confirm insensitivity to gluten. Eight children, aged from 11 to 25 months, with an initial diagnosis of celiac disease were studied: in five children a definite diagnosis has already been confirmed. Rectal gluten challenge was done by means of retention enemas. A volume of 100 ml of a 10% gluten suspension in water was introduced into the rectum three times per day for 8 days; each enema was retained at least 1 h. Rectosigmoidoscopies and rectal biopsies were done before and at the end of the challenge period. The endoscopic appearance of rectal mucosa was normal in all the children either before or after gluten challenge. The means of total mucosal thickness, intraepithelial lymphocyte counts, mitotic crypt cell activity, and cellular infiltration of lamina propria increased after challenge; the mean of goblet cell/epithelial cell ratio in the surface epithelium decreased. The differences between each pair of means (before and after challenge), however, were not significant except for total mucosal thickness (p less than 0.05), the meaning of which is unclear. This study did not definitely demonstrate that the rectal mucosa of celiacs is insensitive to gluten. For practical clinical purposes, however, it behaves as such. This makes the rectal mucosa a useless tool for the final diagnosis of celiac disease.     

Valganciclovir: A new oral alternative for cytomegalovirus retinitis in human immunodeficiency virus-seropositive individuals

Oral valganciclovir recently was approved by the Food and Drug Administration for treatment of cytomegalovirus (CMV) retinitis. We performed MEDLINE (June 1998-May 2002) and AIDSLINE (June 1998-December 2000) searches of available information on valganciclovir, and the drug's prescribing information was used to identify relevant articles. Additional studies, case reports, reviews, and abstracts were identified from references in the reviewed literature. Most of the information was obtained from abstracts or product labeling, since few trials have been published in the medical literature. Valganciclovir is a prodrug of ganciclovir and has been shown to have significantly higher oral absorption than ganciclovir capsules. One short-term study found valganciclovir to be as effective as intravenous ganciclovir in treating CMV retinitis. Recommended dosages for patients with normal renal function are valganciclovir 900 mg twice/day for induction and 900 mg once/day for maintenance. Side effects are similar to those of intravenous ganciclovir and require periodic monitoring of complete blood count and renal function. Given the need for lifelong therapy for CMV retinitis in some human immunodeficiency virus-positive patients, valganciclovir is a welcome alternative to long-term administration of intravenous antivirals.     

The Rey 15-item recognition trial: a technique to enhance sensitivity of the Rey 15-item memorization test

Numerous publications on the Rey 15-item Memorization Test have cited limitations primarily in test sensitivity, as well as to some extent in specificity. In the current study, 49 patients with suspect effort, 36 neuropsychology clinic patients not in litigation or attempting to secure disability, 33 learning disabled college students, and 60 normal controls were administered the Rey Test in standard format followed by a recognition trial. A free recall score <9 was found to have excellent specificity (97-100%), although sensitivity was modest (47%). However, use of a combined recall and recognition score (i.e., free recall + [recognition - false positives] <20) substantially increased sensitivity (71%) while maintaining high specificity (> or=92%).