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OBJECTIVE: This study evaluates the 24 month follow up for the NICHD Neonatal Research Network (NRN) Inositol for Retinopathy Trial. STUDY DESIGN: Bayley Scales of Infants Development-III and a standardized neurosensory examination were performed in infants enrolled in the main trial. Moderate/severe NDI was defined as BSID-III Cognitive or Motor composite score

IMPORTANCE: Previous studies of myo-inositol in preterm infants with respiratory distress found reduced severity of retinopathy of prematurity (ROP) and less frequent ROP, death, and intraventricular hemorrhage. However, no large trials have tested its efficacy or safety. OBJECTIVE: To test the adverse events and efficacy of myo-inositol to reduce type 1 ROP among infants younger than 28 weeks’ gestational age. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial included 638 infants younger than 28 weeks’ gestational age enrolled from 18 neonatal intensive care centers throughout the United States from April 17, 2014, to September 4, 2015; final date of follow-up was February 12, 2016. The planned enrollment of 1760 participants would permit detection of an absolute reduction in death or type 1 ROP of 7% with 90% power. The trial was terminated early due to a statistically significantly higher mortality rate in the myo-inositol group. INTERVENTIONS: A 40-mg/kg dose of myo-inositol was given every 12 hours (initially intravenously, then enterally when feeding; n = 317) or placebo (n = 321) for up to 10 weeks. MAIN OUTCOMES AND MEASURES: Type 1 ROP or death before determination of ROP outcome was designated as unfavorable. The designated favorable outcome was survival without type 1 ROP. RESULTS: Among 638 infants (mean, 26 weeks’ gestational age; 50% male), 632 (99%) received the trial drug or placebo and 589 (92%) had a study outcome. Death or type 1 ROP occurred more often in the myo-inositol group vs the placebo group (29% vs 21%, respectively; adjusted risk difference, 7% [95% CI, 0%-13%]; adjusted relative risk, 1.41 [95% CI, 1.08-1.83], P = .01). All-cause death before 55 weeks’ postmenstrual age occurred in 18% of the myo-inositol group and in 11% of the placebo group (adjusted risk difference, 6% [95% CI, 0%-11%]; adjusted relative risk, 1.66 [95% CI, 1.14-2.43], P = .007). The most common serious adverse events up to 7 days of receiving the ending dose were necrotizing enterocolitis (6% for myo-inositol vs 4% for placebo), poor perfusion or hypotension (7% vs 4%, respectively), intraventricular hemorrhage (10% vs 9%), systemic infection (16% vs 11%), and respiratory distress (15% vs 13%). CONCLUSIONS AND RELEVANCE: Among premature infants younger than 28 weeks’ gestational age, treatment with myo-inositol for up to 10 weeks did not reduce the risk of type 1 ROP or death vs placebo. These findings do not support the use of myo-inositol among premature infants; however, the early termination of the trial limits definitive conclusions.

BACKGROUND: Hypercarbia and increased intraabdominal pressure during prolonged pneumoperitoneum can adversely affect cardiac function. This study compared the intraoperative hemodynamics of morbidly obese patients during laparoscopic and open gastric bypass (GBP). METHODS: Fifty-one patients with a body mass index (BMI) of 40-60 kg/m2 were randomly allocated to undergo laparoscopic (n = 25) or open (n = 26) GBP. Cardiac output (CO), mean pulmonary artery pressure (MPAP), pulmonary artery wedge pressure (PAWP), central venous pressure (CVP), heart rate (HR), and mean arterial pressure (MAP) were recorded at baseline, intraoperatively at 30-min intervals, and in the recovery room. Systemic vascular resistance (SVR) and stroke volume (SV) were also calculated. RESULTS: The two groups were similar in terms of age, weight, and BMI. Operative time was longer in the laparoscopic than in the open group (p < 0.05). The HR and MAP increased significantly from baseline intraoperatively, but there was no significant difference between the two groups. In the laparoscopic group, CO was unchanged after insufflation, but it increased by 5.3% at 2.5 h compared to baseline and by 43% compared to baseline in the recovery room. In contrast, during open GBP, CO increased significantly by 25% after surgical incision and remained elevated throughout the operation. CO was higher during open GBP than during laparoscopic GBP at 0.5 h and at 1 h after surgical incision (p < 0.05). During laparoscopic GBP, CVP, MPAP, and SVR increased transiently and PAWP remained unchanged. During open GBP, CVP, MPAP, and PAWP decreased transiently and SVR remained unchanged. There was no significant difference in the amount of intraoperative fluid administered during laparoscopic (5.5 +/- 1.6 L) and open (5.6 +/- 1.7 L) GBP. CONCLUSION: Prolonged pneumoperitoneum during laparoscopic gastric bypass does not impair cardiac function and is well tolerated by morbidly obese patients.

In response to community demand, The Office of the Coordinator of Health Sciences at the University of British Columbia in Canada developed a two-day Interprofessional Team Building workshop and piloted it twice. The workshops included faculty and students with clinical experience from nine different health and human service programmes. The design of the workshop was drawn from team-building theory and exercises used in business education. It was augmented by clinical examples and case-based discussions. The purposes of the workshop were: to expand a student's knowledge of other disciplines, to develop skills that enable optimal performance within a team, and to provide an opportunity for students from a variety of disciplines to learn from and about each other. The workshops were highly successful and provide a model for introducing interprofessional education into traditionally segregated university curricula.

Intelligent polymers exhibit sharp, reversible phase changes in response to small changes in environmental conditions. For example, a small temperature change can cause a sharp precipitation or gelation of a smart polymer solution. Conjugation of these unusual polymers to biomolecules such as enzymes, ligands, lipids, and drugs can lead to many new and exciting applications in medicine and biotechnology. (1-4) This presentation reviews the principles, methodolgies and applications of these smart polymer-biomolecule systems, with special focus on temperature-sensitive polymer-protein conjugates.

A room-temperature-precipitable, activated terpolymer consisting of N-isopropylacrylamide (NIPAAm)/N-n-butylacrylamide(nBAAm)/N-acryloxysuccinimide (NASI) (LCST = 7-13 degrees C) at a monomer feed ratio of 60:40:2.5, respectively, was prepared and conjugated to an antibody. The conjugate was evaluated in a novel cellulose acetate (CA) membrane-based immunoassay which utilizes the especially strong physical attachment of the polymer to CA to bind and concentrate the polymer attached protein onto the membrane. When compared in the CA membrane immunoassay to the antibody-poly(NIPAAm) conjugate prepared via anhydrous copolymerization of NIPAAm and NASI at the monomer feed ratio of 40:1, respectively, the performance of the NIPAAm/nBAAm/NASI terpolymer was superior to that of the NIPAAm/NASI copolymer (LCST = 32 degrees C) when the studies were carried out at room temperature. However, the terpolymer and copolymer gave equivalent performance when the assay mixture was heated to 45 degrees C. These results indicate the importance of the LCST of the polymer component of the Ab-polymer conjugate to its adsorption and binding on the CA membrane.

We have developed a novel method to immobilize antibodies onto a cellulose acetate membrane using a conjugate of an N-isopropylacrylamide polymer covalently bound to the antibody. When compared with the unconjugated antibody, over 30-fold increase in retention of the antibody on the membrane was observed when it was conjugated to poly (N-isopropylacrylamide). Studies of the polymer-membrane interaction suggest a combination of hydrophobic and ionic forces, especially the former, is responsible for the high retention. We applied this novel immobilization technology in the development of a membrane-based immunoassay.

Background. We previously reported that vancomycin in hyperalimentation solution reduces catheter-related infections in the neonatal intensive care unit. Since June 1993 vancomycin (25 μg/ml) was routinely added to central venous catheter solutions, primarily hyperalimentation solution. Because the prophylactic use of vancomycin could lead to the emergence of resistant organisms, the decision to discontinue this practice was made in April of 1999. The use of vancomycin was reserved for documented infections with vancomycin-susceptible organisms. Objective. To compare catheter longevity, rate of laboratory-confirmed blood stream infections and total vancomycin exposure between two 18-month periods before and after the cessation of prophylactic vancomycin use. Methods. Data were evaluated for every neonate in whom a percutaneous central venous catheter was placed. Results. There were 394 neonates enrolled. No statistically significant difference was identified between the two periods regarding the mean catheter days or number of catheters per patient. There was a higher rate of Gram-negative laboratory-confirmed blood stream infections during Period I in patients with percutaneous central venous catheters in place. There were more isolates of coagulase-negative staphylococci in Period II, resulting in more frequent vancomycin therapy institution and thus an overall increase in the amount of vancomycin used in that period Conclusion. Discontinuing the use of prophylactic vancomycin resulted in exposure of fewer neonates to vancomycin but a higher total amount of vancomycin used. The impact of low dose widespread exposure to vancomycin vs. high dose limited exposure on the microbiologic flora in the neonatal intensive care unit should be further examined.

Objective To compare outcomes, quality of life (QOL), and costs of laparoscopic and open gastric bypass (GBP). Background Data Laparoscopic GBP has been reported to be a safe and effective approach for the treatment of morbid obesity. The authors performed a prospective randomized trial to compare outcomes, QOL, and costs of laparoscopic GBP with those of open GBP. Methods From May 1999 to March 2001, 155 patients with a body mass index (BMI) of 40 to 60 kg/m 2 were randomly assigned to undergo laparoscopic (n = 79) or open (n = 76) GBP. The two groups were similar in age, sex ratio, mean BMI, and comorbidities. Main outcome measures included operative time, estimated blood loss, length of hospital stay, operative complications, percentage of excess body weight loss, and time to return to activities of daily living and work. Changes in QOL were assessed using the SF-36 Health Survey and the bariatric analysis of reporting outcome system (BAROS). Operative and hospital costs of the two operations were also compared. Results There were no deaths in either group. Mean operative time was longer for laparoscopic GBP than for open GBP, but operative blood loss was less. Two (2.5%) of the 79 patients in the laparoscopic group required conversion to laparotomy. Median length of hospital stay was shorter for laparoscopic GBP patients (3 vs 4 days). The rate of postoperative anastomotic leak was similar between groups. Wound-related complications such as infection (10.5 vs 1.3%) and incisional hernia (7.9 vs 0%) were more common after open GBP; late anastomotic stricture was less frequent after open GBP (2.6 vs 11.4%). Time to return to activities of daily living and work were shorter after laparoscopic GBP than after open GBP. Weight loss at 1 year was similar between groups. Preoperative SF-36 scores were similar between groups; however, at 1 month after surgery, laparoscopic patients had better physical conditioning, social functioning, general health, and less body pain than open GBP patients. At 6 months, the BAROS outcome was classified as good or better in 97% of laparoscopic GBP patients compared with 82% of open GBP patients. Operative costs were higher for laparoscopic GBP patients, but hospital costs were lower. Conclusions Laparoscopic GBP is a safe and cost-effective alternative to open GBP. Despite a longer operative time, patients undergoing laparoscopic GBP benefited from less blood loss, a shorter hospital stay, and faster convalescence. Laparoscopic GBP patients had comparable weight loss at 1 year but a more rapid improvement in QOL than open GBP patients. The higher initial operative costs for laparoscopic GBP were adequately offset by the lower hospital costs.

The self reported annual frequencies of colds were assessed for two groups of 37 students each who were either consistent or inconsistent in the use of their hands. These data indicated that the inconsistent hand use group reported significantly more colds than their consistent hand use peers.

The compound 2-acetamidofluorene is a potent hepatocarcinogen; its N-acetoxy derivative (2-NOAc-AAF), a model ultimate form of the carcinogen, is strongly mutagenic and is chemically reactive with nucleophiles. The isomeric 3-acetamidofluorene is a mammary carcinogen, but is not hepatocarcinogenic; its N-acetoxy derivative (3-NOAc-AAF) is not reactive with nucleophiles. Derivatives of 3-NOAc-AAF containing electron-donating groups in positions conjugated with the 3-position have been synthesized. These show increased electrophilicity and mutagenicity. Thus, by electronic manipulation of the leaving-group capacity of the -OAc group of 3-NOAc-AAF, we have obtained compounds with increased biological activity, as well as increased chemical reactivity. Future experiments could show whether in vivo effects of these derivatives of 3-NOAc-AAF are more like the effects of 2-NOAc-AAF or of 3-NOAc-AAF.

"HEALTH ... is a purchaseable commodity of which a community can possess, within limits, as much or as little as it cares to pay for. It can turn its resources in one direction and fifty thousand of its members will live who would otherwise have died; it can turn them in another and fifty thousand will die who would otherwise have lived. Though no individual, by taking thought, can add a cubit to his stature, a nation, by doing so, can add an inch to the height of some groups among its children and a pound to their weight."

On the evening of March 2, 1984 in Hawaii, a 3-year-old girl (we will call her Katie) complained to her mother that she had been burned on her leg. Katie’s mother, thinking it was a mosquito bite, did not inspect the leg. Later that evening, Katie seemed to be inexplicably upset; she refused to be alone with her father, had nightmares, and screamed during the night. The following morning, the child talked of mosquito bites on her legs, but, when questioned by her mother, she eventually said the “bites” were burns from a gunlike device. After probing, Katie described a man who had abducted her from her preschool the previous day, had taken her to a house and photographed her, hugged her, and kissed her while she was naked. The man, she said, also burned her with fire from a gunlike device. Katie mentioned that a girlfriend from her preschool may also have been at the house.

New 9-substituted 3-nitrofluorenes were prepared as potential intermediates in a study of modified electrophilicity and mutagenicity of the carcinogen 3-N,O-diacetylhydroxylaminofluorene. The reported derivatives, together with some already known 9-substituted 3-nitrofluorenes, were too unstable to survive the reducing conditions required to transform the nitro group to the corresponding hydroxylamine.