Guidelines for the appropriate use of genetic tests in infertile couples

Research on genetic causes of male and female infertility rapidly expanded in the last years, following the development of in vitro fertilising techniques. Genetic tests are now available to explore the cause of the infertility and assess the risk of a given couple to transmit its genetic characteristics. This allows at-risk couples to take an informed decision when electing for a medically assisted reproduction. It also allows the professionals to offer a prenatal diagnosis when appropriate. Thus, the genetic work-up of the infertile couple has become good practice for an appropriate diagnosis, treatment and prognostic assessment. The lack of national or international rules for the genetic approach to the infertile couple, prompted the Italian community of professionals in the field of reproductive medicine to join and set up guidelines for the genetic diagnosis of male and female infertility. The group of clinical and research experts is representative of 12 national scientific societies and was supported by external experts from four international societies. We examine the clinically relevant genetic causes of male and female infertility and suggest the category of patients for which each genetic test is recommended or optional, both for an accurate diagnosis and prior to ART.     

Efficacy and safety of sublingual immunotherapy.

OBJECTIVE: To review the available published data concerning the use of sublingual immunotherapy (SLIT) in respiratory allergy to primarily evaluate the clinical efficacy and safety of the treatment and to secondarily consider the mechanisms of action and any unresolved questions. DATA SOURCES: Articles in the medical literature (starting from 1986 up to November 2003) derived from searching the MEDLINE database with the keywords sublingual immunotherapy, respiratory allergy, asthma, and rhinitis. Sources included review articles, randomized controlled clinical trials, postmarketing surveillance studies, and relevant reports from meeting proceedings. STUDY SELECTION: Articles concerning safety, efficacy, and mechanisms of SLIT published in English-language, peer-reviewed journals. RESULTS: SLIT proved effective and safe in adults and children. As with traditional subcutaneous immunotherapy, SLIT has long-lasting efficacy and a preventive effect on new sensitizations. CONCLUSION: SLIT is a viable alternative to subcutaneous immunotherapy. Its use in pediatric patients seems to be particularly promising.     

Viral load,CD4 percentage,and delayed-type hypersensitivity in subjects receiving the HIY-1 Immunogen and antiviral drug therapy

Two trials of subjects inoculated with the inactivated, gp120-depleted HIV-1 Immunogen are reported. In one study, in which 19 subjects received ZDV and 8 subjects received ddI, treatment with the HIV-1 Immunogen did not affect the pharmacokinetic parameters of the antiviral drugs. In another study, 65 subjects who were previously immunized with the HIV-1 Immunogen over a mean period of 4.0 years (range, 1.2–5.4 years) received inoculations at 0 and 6 months. At some point during this 48-week study, 72% of the subjects (47/65) were receiving antiviral drug therapy. The HIV-1 DNA load in CD4 cells and CD4 percentage were found to be stable over the 48-week period. Delayed-type hypersensitivity to HIV-1 antigens increased after two inoculations with the HIV-1 Immunogen. In these two trials, no serious treatment-related adverse events were documented in the subjects. The two studies presented herein are the first to suggest that an immune-based therapy such as the HIV-1 Immunogen can be combined safely with antiviral drugs, supporting further study to evaluate the clinical utility of this approach.     

Adequacy and support of physiological functions in the acutely ill cirrhotic patient

The cirrhotic condition is characterized by a series of changes in physiological functions and of subclinical alterations that imply an abnormal and fragile adaptive pattern with reduced resistance to superimposed distress. In the care of the critically ill cirrhotic patient, the supportive measures aimed at maintaining physiological stability through the control of such debilitating factors have a key role and are not secondary in importance to the more obvious measures needed to treat clinically evident and specific alterations or complications. The relationship between hepatic malfunction and the development of these physiological abnormalities is not fully understood. Our knowledge of the problem, however, has been recently improved and the need for supportive measures motivated by a series of notions on cardiorespiratory and metabolic abnormalities and interactions in hepatic decompensation.

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Resumen La condición cirrótica se caracteriza por una serie de cambios en las funciones fisiológicas y por alteraciones subclinicas que implican un patrón de adaptación anormal y fragil de resistencia reducida al estrés. Estas incluyen disfunción respiratoria con tendencia a la hipoxemia arterial en presencia de elevados indices cardiacos, una situatión crónica de hiperdinamismo cardiovascular pero con precaria eficacia miocárdica y latente riesgo de falla de alto débito, y cambios metabólicos que se traducen en un estado de fallas multisistémicas interrelacionadas características del cirrótico. En el cuidado del paciente cirrótico en estado crítico, las medidas de soporte orientadas al mantenimiento de la estabilidad fisiológica mediante el control de tales factores debilitantes tienen una importancia capital y no son secundarias frente a aquellas muy obvias que se requieren para tratar alteraciones o complicaciones específicas y clínicamente evidentes. La relación entre la disfunción hepática y el desarrollo de las mencionadas anormalidades fisiológicas no está totalmente aclarada, sin embargo, el estado de nuestro conocimiento sobre el problema ha sido enriquecido recientemente y se ha fortalecido la necesidad de establecer medidas de soporte por una serie de nociones relativas a las anormalidades e interacciones cardiorrespiratorias y metabólicas de la descompensación hepática.

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Résumé La cirrhose est caractérisée par des séries de variations des fonctions physiologiques et de modifications cliniques qui impliquent des modalités d'adaptation anormale et fragile se traduisant par une résistance réduite à l'état de détresse ou peut se trouver le cirrhotique. Des mesures appropriées pour maintenir la stabilité physiologique ont un rôle principal en présence de ces facteurs défavorables. Elles ne doivent pas être considérées comme moins importantes que les mesures essentielles qui sont nécessaires pour traiter les complications et les modifications cliniques spécifiques. La relation entre l'altération des fonctions du foie et le développement des anomalies physiologiques précitées n'est pas parfaitement élucidée, cependant, nos connaissances de ce problème ont été récemment améliorées et le besoin de mesures adéquates de soutien est devenu manifeste en raison de séries acquises de notions concernant les anomalies cardio-respiratoires et métaboliques ainsi que les interactions de la décompensation hépatique.

     

Immunohistochemical detection of p140trkA and p75LNGFR neurotrophin receptors in neuroblastoma

In neuroblastoma, high levels of mRNA for p14h ^trkA and p75 ^LNGFR neurotrophin receptors are predictive of favorable outcome. Their evaluation by Northern blot, however, requires substantial amounts of tissue and this prevents their routine evaluation as well as the possibility for multicenter studies to be easily carried out. In an attempt to overcome these limitations, the feasibility and reliability of determining both neurotrophin receptors on cryostat sections by immunohistochemistry were assessed, and these findings were compared to those obtained from Northern blot analysis. Primary tumor samples from 28 untreated patients at all stages were evaluated by using H10 anti-p140 ^trkA and ME20.4 anti-p75 ^LNGFR mAbs. Although weak, positiveimmunostaining was found in 9 of 28 tumors for p140 ^trkA and in 5 of 28 tumors for p75 ^LNGFR . As compared to Northern blot, the concordance rate was 79% (22 of 28 cases) for p140 ^trkA (p < 0.05) and 71% (20 of 28 cases) for p75 ^LNGFR (p < 0.05). No case negative for Northern blot was found to be positive with immunohistochemistry. Since only high mRNA levels for both receptors have been shown to be clinically relevant, their immunohistochemical detection, although less sensitive than Northern blot, can be just as sufficient and reliable as a prognostic tool, and possibly with a better cost-benefit ratio.     

Mucoadhesion of Latexes. I. Analytical Methods and Kinetic Studies

A Fourier transform infrared spectroscopy/attenuated total reflection technique for direct quantification of adsorbed poly(styrene) latexes on rat intestinal mucosa was developed for deposited latex amounts up to 1.5 g/m². The method agreed well with another dosage assay of adsorbed particles by turbidimetry after denaturation of the mucus. Adsorption kinetics were made under static conditions at latex concentrations of 4 g/L in physiological saline. Ninety percent of equilibrium was reached after 10 min for a particle size of 230 nm, 20 min for a size of 320 nm, and 30 min for a size of 670 nm. The plateaus were between 0.6 and 0.9 g/m² (adsorbed mass per apparent surface of mucosa). The first phase of the kinetics was theoretically approached by a diffusion model in the suspension medium. Mucosa from rat jejunum and ileum could be considered as a homogeneous biological model for latex adsorption.     

Perioperative immunonutrition in patients undergoing cancer surgery: results of a randomized double-blind phase 3 trial

HYPOTHESIS: Perioperative administration of a supplemented enteral formula may reduce the rate of postoperative infections. DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: Department of surgery at a university hospital. PATIENTS: Two hundred six patients with neoplasm of colorectum, stomach, or pancreas. INTERVENTION: Patients were randomized to drink 1 L/d of either a control enteral formula (n = 104) or the same formula enriched with arginine, RNA, and omega3 fatty acids (n = 102) for 7 consecutive days before surgery. The 2 diets were isoenergetic and isonitrogenous. Jejunal infusion with the same formulas was started 6 hours after operation and continued until postoperative day 7. MAIN OUTCOME MEASURES: Rate of postoperative infectious complications and length of hospital stay. RESULTS: Both groups were comparable for age, sex, weight loss, Karnofsky scale score, nutritional status, hemoglobin level, duration of surgery, blood loss, and rate of homologous transfusion. Intent-to-treat analysis showed a 14% (14/102) infectious complication rate in the supplemented group vs 30% (31/104) in the control group (P = .009). In the eligible population, the postoperative infection rate was 11% (9/85) in the supplemented group vs. 24% (21/86) in the control group (P = .02). The mean +/- SD length of postoperative stay was 11.1+/-4.4 days in the supplemented group and 12.9+/-4.6 in the control group (P = .01). CONCLUSION: Perioperative administration of a supplemented enteral formula significantly reduced postoperative infections and length of stay in patients undergoing surgery for cancer.     

Lessons from in vitro perifusion of pancreatic islets isolated from 80 human pancreases

We report the average insulin response to acute glucose measured by in vitro perifusion of pancreatic islets isolated from 80 consecutive human organs. Different perifusion parameters were considered [basal release, stimulation index (SI), time to peak, incremental area under the curve delta-AUC alpha)], and the correlation among them was determined. SI positively correlated with delta-AUC alpha (p < 0.001, r = 0.80) while negatively with time to peak (p < 0.05, r = -0.23). We also evaluated several variables of the isolation procedure that might affect responsiveness to glucose by human islets. Sex and age of pancreas donors, cold ischemia time, duration of the digestion, collagenase concentration, and lot characteristics (collagenase, trypsin, clostripain, and proteases activity), and final islet yield were considered. Multivariate regression analysis showed only an independent association between SI and the concentration of collagenase (p = 0.01).