Trans rectus sheath extra-peritoneal procedure (TREPP) for inguinal hernia repair under local anesthesia with sedation in the outpatient clinic: a feasibility study.

BACKGROUND: The Trans Rectus Sheath Extra-Peritoneal Procedure (TREPP) is an open procedure in which the mesh is placed in the preperitoneal space and is therefore associated with less chronic post-operative inguinal pain. TREPP is primarily performed under general or spinal anesthesia, however, it is also possible to perform under sedation and local anesthesia with potentially advantages. This retrospective feasibility pilot study investigates the safety and efficiency of TREPP under local anesthesia in the outpatient clinic in comparison with Lichtenstein. METHODS: Between 2019 and 2022, all patients who underwent an elective inguinal hernia repair under local anesthesia in the outpatient clinic operation theatre were assessed. 34 patients in the TREPP group and 213 patients in the Lichtenstein group were included. Outcomes were complications, operating time, theatre time, and early inguinal hernia recurrence within 8 weeks and 6 months post-operatively. RESULTS: No significant differences in complications such as wound infection, hematoma, seroma, urine retention and early recurrence between TREPP and Lichtenstein were found. Post-operative pain at 8 weeks was not significantly higher after Lichtenstein (8.8% vs. 18.8%, P = 0.22). Operating time (21.0 (IQR: 16.0-27.3) minutes vs. 39.0 (IQR: 31.5-45.0) minutes, P < 0.001) and theatre time (37.5 (IQR: 30.8-42.5) minutes vs. 54.0 (IQR: 46.0-62.0) minutes, P < 0.001) was significantly shorter for TREPP. CONCLUSION: This pilot study showed that TREPP appears to be feasible to perform safely under local anesthesia with comparable complication rates and substantially shorter operation time than Lichtenstein. These results justify further research with a larger study population and a longer period of follow up in order to provide firm conclusions.

Screening, diagnosis and monitoring of sarcopenia: When to use which tool?

BACKGROUND & AIMS: Sarcopenia is a muscle disorder associated with loss of muscle mass, strength and function. Early screening, diagnosis and treatment may improve outcome in different disease conditions. A wide variety of tools for estimation of muscle mass is available and each tool has specific technical requirements. However, different investigational settings and lack of homogeneity of populations influence the definition of gold standards, proving it difficult to systematically adopt these tools. Recently, the European Working Group on Sarcopenia in Older People (EWGSOP) published a revised recommendation (EWGSOP-2) and algorithm for using tools for screening and diagnosing sarcopenia. However, agreement of the EWGSOP2 criteria with other classifications is poor and although an overview of available tools is valuable, for the purpose of clinical decision-making the reverse is useful; a given scenario asks for the most suitable tools. RESULTS: Tools were identified for screening, diagnostics and longitudinal monitoring of muscle mass. For each of these clinical scenarios the most appropriate tools were listed and for each technique their usability is specified based on sensitivity and specificity. Based on this information a specific recommendation is made for each clinical scenario. CONCLUSION: This narrative review provides an overview of currently available tools and future developments for different clinical scenarios such as screening, diagnosis and longitudinal monitoring of alterations in muscle status. It supports clinical decision-making in choosing the right tools for muscle mass quantification depending on the need within a given clinical scenario as well as the local availability and expertise.

Functional Compromise Cohort Study (FCCS): Sarcopenia is a Strong Predictor of Mortality in the Intensive Care Unit.

BACKGROUND: Functional compromise in elderly patients is considered to be a significant contributing factor in increased postoperative morbidity and mortality. It is described as a state of reduced physiologic reserves including, e.g., sarcopenia, cachexia, malnutrition and frailty with increased susceptibility to adverse health outcomes. Aim of this study was to investigate the association of sarcopenia with mortality in ICU patients. METHODS: A retrospective analysis of a total of 687 patients admitted to the ICU from January 2013 until December 2014 was performed. Indirect measurements of functional compromise in these patients were conducted. Sarcopenia was assessed using the L3 muscle index by using Osirix© on computed tomography scans. Groningen Frailty Indicator (GFI) and Short Nutritional Assessment Questionnaire (SNAQ) scores were extracted from the digital patient filing system and were used to assess frailty and nutritional status. These factors were analyzed using logistic regression analysis as predictor for in-hospital mortality and 6-month mortality, which was the primary endpoint along with other secondary outcome measures. RESULTS: Age was an independent predictor of in-hospital mortality, OR 1.043 (95% CI 1.030-1.057, p < 0.001). Analysis of sarcopenia showed OR 2.361 (95% CI 1.138-4.895, p = 0.021), for GFI OR 1.012 (95% CI 0.919-1.113, p = 0.811) and for SNAQ OR 1.262 (95% CI 1.091-1.460, p = 0.002). CONCLUSION: This study shows a promising role for the sarcopenia score as a predictor of mortality on the ICU, based upon CT imaging at L3 level and SNAQ score. Further research is necessary to test this in larger cohorts and to develop a possible instrument to predict mortality in the intensive care unit.

Doppler-guided goal-directed fluid therapy does not affect intestinal cell damage but increases global gastrointestinal perfusion in colorectal surgery: a randomized controlled trial.

AIM: Individualized, goal-directed fluid therapy (GDFT), based on Doppler measurements of stroke volume, has been proposed as a treatment strategy in terms of reducing complications, mortality and length of hospital stay in major bowel surgery. We studied the effect of Doppler-guided GDFT on intestinal damage as compared with standard postoperative fluid replacement. METHOD: Patients undergoing elective colorectal resection for malignancy were randomized either to standard intra- and postoperative fluid therapy or to standard fluid therapy with additional Doppler-guided GDFT. The primary outcome was intestinal epithelial cell damage measured by plasma levels of intestinal fatty acid-binding protein (I-FABP). Global gastrointestinal perfusion was measured by gastric tonometry, expressed as regional (gastric) minus arterial CO2 -gap (Pr-a CO2 -gap). RESULTS: I-FABP levels were not significantly different between the intervention group and the control group (respectively, 440.8 (251.6) pg/ml and 522.4 (759.9) pg/ml, P = 0.67). Mean areas under the curve (AUCs) of intra-operative Pr-a CO2 -gaps were significantly lower in the intervention group than in the control group (P = 0.01), indicating better global gastrointestinal perfusion in the intervention group. Moreover, the mean intra-operative Pr-a CO2 -gap peak in the intervention group was 0.5 (1.0) kPa, which was significantly lower than the mean peak in the control group, of 1.4 (1.4) kPa (P = 0.03). CONCLUSION: Doppler-guided GDFT during and in the first hours after elective colorectal surgery for malignancy increases global gastrointestinal perfusion, as measured by Pr-a CO2 -gap.

The Cosmetics Europe strategy for animal-free genotoxicity testing: project status up-date.

The Cosmetics Europe (formerly COLIPA) Genotoxicity Task Force has driven and funded three projects to help address the high rate of misleading positives in in vitro genotoxicity tests: The completed "False Positives" project optimized current mammalian cell assays and showed that the predictive capacity of the in vitro micronucleus assay was improved dramatically by selecting more relevant cells and more sensitive toxicity measures. The on-going "3D skin model" project has been developed and is now validating the use of human reconstructed skin (RS) models in combination with the micronucleus (MN) and Comet assays. These models better reflect the in use conditions of dermally applied products, such as cosmetics. Both assays have demonstrated good inter- and intra-laboratory reproducibility and are entering validation stages. The completed "Metabolism" project investigated enzyme capacities of human skin and RS models. The RS models were shown to have comparable metabolic capacity to native human skin, confirming their usefulness for testing of compounds with dermal exposure. The program has already helped to improve the initial test battery predictivity and the RS projects have provided sound support for their use as a follow-up test in the assessment of the genotoxic hazard of cosmetic ingredients in the absence of in vivo data.

A human hemi-cornea model for eye irritation testing: quality control of production, reliability and predictive capacity.

We have developed a 3-dimensional human hemi-cornea which comprises an immortalized epithelial cell line and keratocytes embedded in a collagen stroma. In the present study, we have used MTT reduction of the whole tissue to clarify whether the production of this complex 3-D-model is transferable into other laboratories and whether these tissues can be constructed reproducibly. Our results demonstrate the reproducible production of the hemi-cornea model according to standard operation procedures using 15 independent batches of reconstructed hemi-cornea models in two independent laboratories each. Furthermore, the hemi-cornea tissues have been treated with 20 chemicals of different eye-irritating potential under blind conditions to assess the performance and limitations of our test system comparing three different prediction models. The most suitable prediction model revealed an overall in vitro-in vivo concordance of 80% and 70% in the participating laboratories, respectively, and an inter-laboratory concordance of 80%. Sensitivity of the test was 77% and specificity was between 57% and 86% to discriminate classified from non-classified chemicals. We conclude that additional physiologically relevant endpoints in both epithelium and stroma have to be developed for the reliable prediction of all GHS classes of eye irritation in one stand alone test system.

Identifying and characterizing chemical skin sensitizers without animal testing: Colipa's research and method development program.

The sensitizing potential of chemicals is usually identified and characterized using one of the available animal test methods, such as the mouse local lymph node assay. Due to the increasing public and political concerns regarding the use of animals for the screening of new chemicals, the Colipa Skin Tolerance Task Force collaborates with and/or funds research groups to increase and apply our understanding of the events occurring during the acquisition of skin sensitization. Knowledge gained from this research is used to support the development and evaluation of novel alternative approaches for the identification and characterization of skin sensitizing chemicals. At present one in chemico (direct peptide reactivity assay (DPRA)) and two in vitro test methods (cell based assays (MUSST and h-CLAT)) have been evaluated within Colipa inter-laboratory ring trials and accepted by the European Centre for the Validation of Alternative Methods (ECVAM) for pre-validation. Data from all three test methods will be used to support the development of testing strategy approaches for skin sensitizer potency prediction. The replacement of the need for animal testing for skin sensitization risk assessment is viewed as ultimately achievable and the next couple of years should set the timeline for this milestone.

The gonadotropins: tissue-specific angiogenic factors?

The gonadotropins, whose members are human chorionic gonadotropin (hCG), lutenizing hormone (LH) and follicle-stimulating hormone (FSH) are a well characterized hormone family known to regulate reproductive functions in both females and males. Recent studies indicate that they can modulate the vascular system of reproductive organs. It was shown that gonadotropins not only influence the expression of vascular endothelial growth factor (VEGF) and both its receptors VEGFR-1 and -2, but also modulate other ubiquitously expressed angiogenic factors like the angiopoietins and their receptor Tie-2, basic fibroblast growth factor or placental-derived growth factor. Some recent data indicates a possible direct action of gonadotropins on endothelial cells. Thus, the gonadotropins act as tissue-specific angiogenic factors providing an optimal vascular supply during the menstrual cycle and early pregnancy in the female reproductive tract as well as in testis. In pathological conditions (e.g. preeclampsia, intrauterine growth restriction, ovarian hyperstimulation or endometriosis), these tightly regulated interactions between the gonadotropins and the ubiquitous angiogenic factors appear to be disturbed. The intent of this short manuscript is to review the current knowledge of the regulatory role of the gonadotropins in vasculo- and angiogenesis. We also review angiogenic actions of thyroid-stimulating hormone (TSH), a glycoprotein closely related to gonadotropins, which display strong gonodal actions.

HCG in the regulation of placental angiogenesis. Results of an in vitro study.

Placental vascular development is essential for fetal growth and development. Inadequate placental vascular development is associated with early pregnancy losses and other pregnancy related pathologies. In addition to the ubiquitous, well-characterized angiogenic factors like vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF), some pregnancy-specific factors (e.g. human chorionic gonadotropin (hCG), insulin-like growth factor-II (IGF-II) or alpha fetoprotein (AFP) were recently described to play a possible regulatory role in this process. In the present study we described an improved separation method for human placental microvascular endothelial cells (HPMVEC) and their functional characterization. Using the combination of enzymatic digestion and multistep immunomagnetic sorting with CD31 antibodies a model for villous vascularization was established. Isolated cells took up ac-dil-LDL, spontaneously formed capillary-like structures, and expressed common endothelial markers such as vascular endothelial growth factor receptor-2 (VEGFR-2), angiopoetin-1 and -2, Tie-2, CD144, thrombomodulin, and von Willebrand factor (vWF) as shown by RT-PCR, flow cytometry and Western blot analysis. The expression of the hCG/LH receptor in the placental vascular tree was verified both in vitro and in vivo. hCG stimulated proliferation of HPMVEC in a dose specific manner. While hCG alone had no significant effect on endothelial cell apoptosis, the combination of VEGF-A and hCG protected HPMVEC from staurosporine-induced apoptosis. hCG significantly stimulated sprout formation when compared to controls in a spheroid angiogenesis assay. Our results demonstrate a modified and reproducible method allowing studies of placental vascular development and provide new insights into the possible role of trophoblastic factors in this process.

A prospective, randomized, comparative US trial of a combination hepatitis A and B vaccine (Twinrix) with corresponding monovalent vaccines (Havrix and Engerix-B) in adults.

In an open, randomized, multicenter, controlled clinical trial in the US, 773 adults were administered either a combination hepatitis vaccine (Twinrix: 720 EL.U inactivated hepatitis A antigen and 20 mcg recombinant hepatitis B surface antigen per milliliter) on a 0, 1, 6 month schedule or corresponding monovalent vaccines concurrently (Havrix, 1440 EL.U/ml of hepatitis A antigen at 0, 6 months and Engerix-B, 20 mcg of hepatitis B surface antigen at 0, 1, 6 months). Non-inferiority testing for the primary endpoint, severe soreness, and equivalence testing for the secondary endpoints, anti-HAV seroconversion and anti-HBs seroprotection, showed that safety and immunogenicity were comparable in the two groups.

Antibody responses to bovine parainfluenza virus type 3 (PIV3) vaccination and human PIV3 infection in young infants.

A phase 2 clinical trial was conducted to evaluate the antibody responses to bovine parainfluenza virus type 3 (bPIV3) vaccination in young infants. Three groups were tested as follows: placebo (n=66) and 10(5) (n=64) or 10(6) (n=62) TCID(50) of bPIV3. The vaccine or placebo was administered intranasally at ages 2, 4, 6, and 12-15 months, and serum specimens were collected at ages 2, 6, 7, 12-15, and 13-16 months. Serum hemagglutination inhibition (HI) and IgA antibody titers against bPIV3 and human PIV3 (hPIV3) were measured. The results indicate that antibody responses to bPIV3 vaccination are more likely to be detected by the bPIV3 IgA and HI assays than by the hPIV3 IgA and HI assays, that bPIV3-induced antibody response can be differentiated from hPIV3-induced antibody response most reliably by comparing bPIV3 and hPIV3 HI titers, and that bPIV3 vaccine prevents vaccine recipients from developing antibody profiles of hPIV3 primary infection.

Fuzzy-control of a hand orthosis for restoring tip pinch, lateral pinch, and cylindrical prehensions to patients with elbow flexion intact.

This study examines, through simulation, the use of fuzzy logic as a feasible control scheme for a hand orthosis that can restore fingertip pinch, lateral pinch, and cylindrical grasps to individuals suffering from C5-C7 spinal cord injuries. A simplified hand orthosis model, consisting of four fingers and a thumb, was derived for the purpose of planning appropriate grasp trajectories and for validating the fuzzy logic control architecture. For comparison a proportional-plus-integral-plus-derivative (PID) controller was also designed. Fuzzy logic is advantageous for this system since it eliminates solving coupled nonlinear equations of motion. For the various grips, the fuzzy controller produced better performance than the PID controller.

Oral oseltamivir treatment of influenza in children.

BACKGROUND: Oral oseltamivir administration is effective treatment for influenza in adults. This study was conducted to determine the efficacy, safety and tolerability of oseltamivir in children with influenza. METHODS: In this randomized, double blind, placebo-controlled study, children 1 through 12 years with fever [> or =100 degrees F (> or =38 degrees C)] and a history of cough or coryza <48 h duration received oseltamivir 2 mg/kg/dose or placebo twice daily for 5 days. The primary efficacy endpoint was the time to resolution of illness including mild/absent cough and coryza mild/absent, return to normal activity and euthermia. RESULTS: Of 695 enrolled children 452 (65%) had influenza (placebo, n = 235; oseltamivir, n = 217). Among infected children the median duration of illness was reduced by 36 h (26%) in oseltamivir compared with placebo recipients (101 h; 95% confidence interval, 89 to 118 vs. 137 h; 95% confidence interval, 125 to 150; P < 0.0001). Oseltamivir treatment also reduced cough, coryza and duration of fever. New diagnoses of otitis media were reduced by 44% (12% vs. 21%). The incidence of physician-prescribed antibiotics was significantly lower in influenza-infected oseltamivir (68 of 217, 31%) than placebo (97 of 235, 41%; P = 0.03) recipients. Oseltamivir therapy was generally well-tolerated, although associated with an excess frequency of emesis (5.8%). Discontinuation because of adverse events was low in both groups (1.8% with oseltamivir vs. 1.1% with placebo). Oseltamivir treatment did not affect the influenza-specific antibody response. CONCLUSIONS: Oral oseltamivir administration is an efficacious and well-tolerated therapy for influenza in children when given within 48 h of onset of illness.

Safety and immunogenicity of four doses of Neisseria meningitidis group C vaccine conjugated to CRM197 in United States infants.

BACKGROUND: Following widespread use of conjugate pneumococcal vaccine, Neisseria meningitidis likely will become the leading cause of bacterial sepsis and meningitis in US children. This report describes the safety and immunogenicity in US children of four consecutive doses of a meningococcal group C vaccine conjugated to CRM197 via reductive amination (MnCC). METHODS: One hundred six healthy 2-month-old infants received MnCC at 2, 4 and 6 months of age in a randomized, controlled double blind study; children in the other treatment arm were given a 7-valent conjugate pneumococcal vaccine. Parents reenrolled 64 of these children at 12 to 15 months to receive a fourth dose of MnCC. Routine childhood vaccines, including DTP, were coadministered. Temperatures and symptoms were recorded for 3 days after each immunization. Serum enzyme-linked immunosorbent assay IgG and bactericidal antibodies were measured prevaccination and before and 1 month after Doses 3 and 4. RESULTS: Moderate to severe local reactions, defined as erythema or induration > or =2.4 cm or pain that interfered with limb movement was reported after 0 to 3.2% of MnCC injections, depending on the reaction and dose. Fever occurred in 23 to 37% of children, but the contribution of MnCC to the febrile reactions is unknown. Geometric mean concentrations of IgG antibody to group C meningococcal polysaccharide were 3.72 microg/ml after Dose 3 and 8.03 microg/ml after the booster. Geometric mean functional serum bactericidal antibody titers after Doses 3 and 4 were 1:463 and 1:2341, respectively. One hundred percent of children had a serum bactericidal antibody titer of > or =1:64 after three doses and > or = 1:128 after the booster. CONCLUSIONS: The MnCC vaccine had an acceptable safety profile and generated high titers of bactericidal antibody in immunized US infants and toddlers. It appears to be an attractive candidate vaccine for the prevention of serogroup C meningococcal disease in young children.

Decreased mRNA stability as a mechanism of glucocorticoid-mediated inhibition of vascular endothelial growth factor gene expression by cultured keratinocytes.

Epidermal keratinocyte-derived overexpression of vascular endothelial growth factor has been functionally linked to increased density of tortuous and hyperpermeable dermal microvessels, representing a characteristic component of cutaneous inflammation. We hypothesized that potent anti-inflammatory properties of synthetic glucocorticoids are attributed in part to their interference with the regulated vascular endothelial growth factor expression by keratinocytes. As vascular endothelial growth factor is markedly upregulated by autocrine transforming growth factor alpha and paracrine hepatocyte growth factor/scatter factor expression, the effect of glucocorticoids on growth-factor-induced vascular endothelial growth factor production by primary and immortalized keratinocytes was examined. Glucocorticoids were shown to suppress vascular endothelial growth factor protein and mRNA expression in a concentration- and time-dependent fashion. In transcriptional activation studies, however, common 5'-regulatory regions of the vascular endothelial growth factor gene failed to confer inhibitory glucocorticoid effects. Instead, glucocorticoids were shown to increase vascular endothelial growth factor mRNA turnover, indicating that post-transcriptional modes of glucocorticoid action are employed to negatively regulate induced vascular endothelial growth factor expression. Together, these studies identify vascular endothelial growth factor upregulation by epidermal keratinocytes as a putative target of glucocorticoid action in cutaneous inflammation. Our data provide strong evidence that mRNA destabilization may represent a mechanism by which glucocorticoids inhibit growth-factor-regulated vascular endothelial growth factor gene expression by keratinocytes.

Ultraviolet-A-induced transactivation of the vascular endothelial growth factor gene in HaCaT keratinocytes is conveyed by activator protein-2 transcription factor.

Ultraviolet-A radiation represents a significant proportion of the ultraviolet solar spectrum that was recently shown to affect gene expression of epidermal keratinocytes by molecular mechanisms distinct from ultraviolet-B radiation. As ultraviolet-A either alone or in combination with ultraviolet-B may contribute to photocarcinogenesis, we aimed to explore the biologic effects of ultraviolet-A radiation on vascular endothelial growth factor gene expression by the immortalized keratinocyte cell line HaCaT. As keratinocyte-derived vascular endothelial growth factor not only provides the major cutaneous angiogenic activity but may also augment the malignant phenotype of tumor cells, we studied the molecular mechanisms of ultraviolet-A-induced vascular endothelial growth factor expression in HaCaT cells, serving as a transformed preneoplastic epithelial cell line. Whereas ultraviolet-B-mediated vascular endothelial growth factor expression has been previously indicated to be conveyed by indirect mechanisms, ultraviolet-A rapidly induced vascular endothelial growth factor mRNA expression in a fashion comparable to that seen with the transforming growth factor alpha, representing a direct and potent activator of vascular endothelial growth factor gene transcription. Ultraviolet-A was found to readily induce vascular endothelial growth factor promoter-based reporter gene constructs through a consensus element for activator protein-2 transcription factor. The critical role of activator protein-2 was substantiated by demonstration of ultraviolet-A-induced activator-protein-2-dependent nuclear DNA binding activity to this site, and by inhibition of ultraviolet-A-mediated vascular endothelial growth factor gene transcription through insertion of a critical mutation within the activator protein-2 sequence. Together, our data further elucidate photobiologic aspects of ultraviolet-A-induced gene expression by characterizing mechanisms of vascular endothelial growth factor upregulation at the molecular level. In addition, our experiments support the concept of a more general importance of activator protein-2 in ultra- violet-A-mediated responses by keratinocytes or keratinocyte-derived cell lines.

Correlates of immune protection induced by live, attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine.

The authors conducted a 2-year, multicenter, double-blind, placebo-controlled efficacy field trial of live, attenuated, cold-adapted, trivalent influenza vaccine administered by nasal spray to children 15-71 months old. Overall, vaccine was 92% efficacious at preventing culture-confirmed infection by influenza A/H3N2 and influenza B. Because influenza A/H1N1 did not cause disease during the years in which this study was conducted, the authors sought to determine vaccine efficacy and correlates of immune protection against experimental challenge with 107 TCID50 of attenuated H1N1 (vaccine strain) by intranasal spray. Prechallenge assessments included serum hemaglutination-inhibiting (HAI) antibody and nasal wash IgA antibody to H1N1. Vaccine was 83% efficacious (95% confidence interval, 60%-93%) at preventing shedding of H1N1 virus after challenge. Any serum HAI antibody or any nasal wash IgA antibody was correlated with significant protection from H1N1 infection as indicated by vaccine-virus shedding, and high efficacy against H1N1 challenge was demonstrated.

Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine.

OBJECTIVE: To determine the safety, immunogenicity, and efficacy of revaccination of children with live attenuated influenza vaccine. STUDY DESIGN: A 2-year multicenter, double-blind, placebo-controlled, efficacy field trial of live attenuated, cold-adapted trivalent influenza vaccine administered by nasal spray to children. This report summarizes year 2 results, a year in which the epidemic strain of influenza A/Sydney was not well matched to the vaccine strains. Each year, vaccine strains were antigenically equivalent to the contemporary inactivated influenza vaccine. In year 2, a single intranasal revaccination was administered. Active surveillance for influenza was conducted during the influenza season by means of viral cultures. Influenza cases were defined as illnesses with wild-type influenza virus isolated from respiratory secretions. RESULTS: In year 2, 1358 (85%) children, 26 to 85 months of age, returned for revaccination. The intranasal vaccine was easily accepted, well tolerated, and immunogenic. Revaccination resulted in 82% to 100% of the vaccinated children in a subset studied for immunogenicity being seropositive as compared with 26% to 65% of placebo recipients, depending on the influenza strain tested. No serious adverse events were associated with the vaccine. In addition to the strains in the vaccine, antibody was induced to the variant strain A/Sydney/H3N2. In year 2, influenza A/Sydney/H3N2, a variant not contained in the vaccine, caused 66 of 70 cases of influenza A; nonetheless, intranasal vaccine was 86% efficacious in preventing A/Sydney influenza. Eight cases of lower respiratory tract disease were associated with A/Sydney influenza; all cases were in the placebo group. CONCLUSIONS: This live attenuated, cold-adapted influenza vaccine was safe, immunogenic, and efficacious against influenza A/H3N2 (including a variant, A/Sydney, not contained in the vaccine) and influenza B. The characteristics of this vaccine make it suitable for routine use in children to prevent influenza.

Randomized multicenter trial documenting the efficacy and safety of a lactose-free and a lactose-containing formula for term infants.

OBJECTIVE: To evaluate the efficacy and safety of a new lactose-free infant formula. DESIGN: Randomized, prospective, double-blind, controlled, outpatient, multicenter, parallel 12-week trial. SETTING: Ambulatory-care facilities of the participating centers. SUBJECTS: 137 healthy term infants (approximately 7 days old at the time of study enrollment). INTERVENTION: Healthy term infants, whose mothers had decided not to breast-feed, were randomly assigned 1 of the 2 study formulas. MAIN OUTCOME MEASURES: Weight, length, and occipitofrontal circumference measurements were obtained at baseline and when the infant was 2, 4, 8, and 12 weeks old. Formula acceptance and tolerance were also assessed at weeks 2, 4, 8, and 12. Serum albumin concentration, creatirune level, and blood urea nitrogen were determined at baseline and week 12. Adverse events were assessed throughout the study. STATISTICAL ANALYSES PERFORMED: Each baseline anthropometric and laboratory variable was analyzed for comparability between groups using the Student t test and was also analyzed using a repeated-measures analysis of variance method. Covariance analysis was applied to the final laboratory data using the respective baseline data as covariates. Decisions about equality of mean responses to formula effects were based on the .05 level of significance in all cases. RESULTS: One hundred four infants completed the study. No significant differences between the 2 formula groups were noted for any of the growth and blood parameters. APPLICATIONS: This new formula is an effective and safe lactose-free nutrition alternative for infants who require such a diet.