Q-factor measurements through injection locking of a semiconductor-glass hybrid laser with unknown intracavity losses.

The injection locking properties of a newly developed waveguide-based external cavity semiconductor laser have been investigated. Using the injection locking properties to measure the Q-factor of complex optical cavities with unknown internal losses, has been demonstrated for the first time.

High precision wavelength estimation method for integrated optics.

A novel and simple approach to optical wavelength measurement is presented in this paper. The working principle is demonstrated using a tunable waveguide micro ring resonator and single photodiode. The initial calibration is done with a set of known wavelengths and resonator tunings. The combined spectral sensitivity function of the resonator and photodiode at each tuning voltage was modeled by a neural network. For determining the unknown wavelengths, the resonator was tuned with a set of heating voltages and the corresponding photodiode signals were collected. The unknown wavelength was estimated, based on the collected photodiode signals, the calibrated neural networks, and an optimization algorithm. The wavelength estimate method provides a high spectral precision of about 8 pm (5 · 10(-6) at 1550 nm) in the wavelength range between 1549 nm to 1553 nm. A higher precision of 5 pm (3 · 10(-6)) is achieved in the range between 1550.3 nm to 1550.8 nm, which is a factor of five improved compared to a simple lookup of data. The importance of our approach is that it strongly simplifies the optical system and enables optical integration. The approach is also of general importance, because it may be applicable to all wavelength monitoring devices which show an adjustable wavelength response.

Effects of an 11ß-hydroxysteroid dehydrogenase type 1 inhibitor, MK-0916, in patients with type 2 diabetes mellitus and metabolic syndrome.

AIM: We examined the effects of the 11ß-hydroxysteroid dehydrogenase type 1 (HSD1) inhibitor, MK-0916, on the multiple components of the metabolic syndrome (MetS) in patients with type 2 diabetes (T2DM) and MetS. METHODS: This was a 12-week, multicentre, randomized, double-blind, placebo-controlled study. Patients with T2DM (mean baseline A1C: 7.3%) and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III)-defined MetS were randomized 1 : 1 : 1 : 1 to 0.5, 2 or 6 mg/day MK-0916 or placebo. The primary efficacy endpoint was a change from baseline at week 12 in fasting plasma glucose (FPG). Secondary endpoints included glycosylated haemoglobin A(1c) (A1C), 2-h postprandial glucose (2-h PPG), body weight, waist circumference, blood pressure and lipid profile. RESULTS: Treatment with MK-0916 had no significant effect relative to placebo on FPG at week 12. Compared to placebo, 6 mg MK-0916 produced a modest, significant (p = 0.049) reduction in A1C of 0.3% at week 12, but no significant difference was observed in 2-h PPG. Six milligram MK-0916 increased LDL-C relative to placebo by 10.4% (p = 0.041). Treatment with MK-0916 led to modest dose-dependent decreases in blood pressure and body weight. Overall, MK-0916 was generally well tolerated. MK-0916 produced mechanism-based activation of the hypothalamic-pituitary-adrenal axis, resulting in mean increases in adrenal androgen levels that remained within the normal range at all doses tested. CONCLUSIONS: Inhibition of HSD1 with MK-0916 was generally well tolerated in patients with T2DM and MetS. Although no significant improvement in FPG was observed with MK-0916 compared to placebo, modest improvements in A1C, body weight and blood pressure were observed.

Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes.

AIM: Exenatide, an incretin mimetic for the adjunct treatment of type 2 diabetes (DM2), reduced A1C and weight in 30-week placebo-controlled trials. This analysis examined the effects of exenatide on glycaemic control and weight over an 82-week period in patients with DM2 unable to achieve adequate glycaemic control with sulphonylurea (SU) and/or metformin (MET). METHODS: This interim analysis is of 314 patients who received exenatide in the 30-week placebo-controlled trials and subsequently in 52 weeks of open-label uncontrolled extension studies for 82 weeks of exenatide in total. Patients continued their SU and/or MET regimens throughout. RESULTS: Patients completed 82 weeks of exenatide treatment [n = 314, 63% M, age 56 +/- 10 years, weight 99 +/- 21 kg, body mass index 34 +/- 6 kg/m2, A1C 8.3 +/- 1.0% (mean +/- SD)]. Reduction in A1C from baseline to week 30 [-0.9 +/- 0.1% (mean +/- SE)] was sustained to week 82 (-1.1 +/- 0.1%), with 48% of patients achieving A1C < or = 7% at week 82. At week 30, exenatide reduced body weight (a secondary endpoint) from baseline (-2.1 +/- 0.2 kg), with progressive reduction at week 82 (-4.4 +/- 0.3 kg). Similar results were observed for the intent-to-treat population (n = 551), with reductions in A1C and weight at week 82 of -0.8 +/- 0.1% and -3.5 +/- 0.2 kg respectively. The 82-week completer cohort showed statistically significant improvement in some cardiovascular risk factors. The most frequent adverse events were generally mild-to-moderate nausea and hypoglycaemia. CONCLUSION: In summary, 82 weeks of adjunctive exenatide treatment in patients with DM2 treated with SU and/or MET resulted in sustained reduction in A1C and progressive reduction in weight, as well as improvement in some cardiovascular risk factors.

New-onset absence status epilepsy presenting as altered mental status in a pediatric patient.

Absence status epilepsy (ASE) is an uncommon seizure disorder in children. The primary presentation of new-onset ASE in a pediatric patient is an unusual cause of altered mental status in the emergency department. We describe a previously healthy 8-year-old child who presented with an acutely altered mental state. The patient was awake but confused, with a fluctuating level of alertness and an inability to perform simple routine tasks. The results of general physical and neurologic examination, with the exception of mental status, were normal. Head computed tomography and laboratory test results were normal. Electroencephalographic testing revealed seizure activity consistent with ASE. Administration of intravenous diazepam caused cessation of seizure activity and a return to the patient's baseline mental function. Although rare, ASE should be considered in the differential diagnosis of altered mental status in children.

Purified protein derivative anergy in Kawasaki disease.

It was previously reported from Italy that all patients with Kawasaki disease had a positive tuberculin intradermal test. In this study from Seattle, WA, nine patients with Kawasaki disease showed no reaction to intradermal tuberculin. The difference in results might be caused by the different tuberculin products.

Comparison of Escherichia coli O157:H7 antigen detection in stool and broth cultures to that in sorbitol-MacConkey agar stool cultures.

We evaluated the Meridian IC-STAT direct fecal and broth culture antigen detection methods with samples from children infected with Escherichia coli O157:H7 and correlated the antigen detection results with the culture results. Stools of 16 children who had recently had stool cultures positive for this pathogen (population A) and 102 children with diarrhea of unknown cause (population B) were tested with the IC-STAT device (direct testing). Fecal broth cultures were also tested with this device (broth testing). The results were correlated to a standard of the combined yield from direct culture of stools on sorbitol-MacConkey (SMAC) agar and culture of broth on SMAC agar. Eleven (69%) of the population A stool specimens yielded E. coli O157:H7 when plated directly on SMAC agar. Two more specimens yielded this pathogen when the broth culture was similarly plated. Of these 13 stool specimens, 8 and 13 were positive by direct and broth testing (respective sensitivities, 62 and 100%). Compared to the sensitivity of a simultaneously performed SMAC agar culture, the sensitivity of direct testing was 73%. Three (3%) of the population B stool specimens contained E. coli O157:H7 on SMAC agar culture; one and three of these stool specimens were positive by direct and broth testing, respectively. The direct and broth IC-STAT tests were 100% specific with samples from children from population B. Direct IC-STAT testing of stools is rapid, easily performed, and specific but is insufficiently sensitive to exclude the possibility of infection with E. coli O157:H7. Performing the IC-STAT test with a broth culture increases its sensitivity. However, attempts to recover E. coli O157:H7 by culture should not be abandoned but, rather, should be increased when the IC-STAT test result is positive.

The pediatric intern retreat: 20-year evolution of a continuing investment.

For the past 22 years the interns in pediatrics at the University of Washington and Children's Hospital and Regional Medical Center have been relieved of all clinical duties in order to participate in a five-day retreat. The retreat provides an opportunity for the interns to learn more about their classmates, build stronger bonds, and provide mutual support. This retreat has been supported by the hospital, the department of pediatrics, faculty, fellows, and community physicians. The authors describe the history of the Intern Retreat, present its goals, daily activities, and faculty, and discuss how the retreat is funded and supported by the hospital and the medical community.

Optimization of ion-exchange protein separations using a vector quantizing neural network.

In this work, a previously proposed methodology for the optimization of analytical scale protein separations using ion-exchange chromatography is subjected to two challenging case studies. The optimization methodology uses a Doehlert shell design for design of experiments and a novel criteria function to rank chromatograms in order of desirability. This chromatographic optimization function (COF) accounts for the separation between neighboring peaks, the total number of peaks eluted, and total analysis time. The COF is penalized when undesirable peak geometries (i.e., skewed and/or shouldered peaks) are present as determined by a vector quantizing neural network. Results of the COF analysis are fit to a quadratic response model, which is optimized with respect to the optimization variables using an advanced Nelder and Mead simplex algorithm. The optimization methodology is tested on two case study sample mixtures, the first of which is composed of equal parts of lysozyme, conalbumin, bovine serum albumin, and transferrin, and the second of which contains equal parts of conalbumin, bovine serum albumin, tranferrin, beta-lactoglobulin, insulin, and alpha -chymotrypsinogen A. Mobile-phase pH and gradient length are optimized to achieve baseline resolution of all solutes for both case studies in acceptably short analysis times, thus demonstrating the usefulness of the empirical optimization methodology.

Discordant radiograph interpretation between emergency physicians and radiologists in a pediatric emergency department.

OBJECTIVES: To describe the types of discrepancies in radiograph interpretation between emergency physicians and radiologists in a pediatric emergency department, and to determine the impact of discrepant interpretations on patient care. METHODS: Prospective cohort study of discordant radiographs from the period beginning March 1, 1995 and ending March 31, 1996. During this period, 2083 radiographs were coded by the radiologist as concordant or discordant. Three hundred forty-nine were coded as discordant, and 324 were eligible for the study. Charts were reviewed for relevant physical examination findings and emergency department management. Discrepancies that affected patient care were deemed clinically significant. RESULTS: Twenty-three (1.1%) of 2083 radiographs were interpreted differently by the emergency physician and the radiologist in a way that might have changed patient management. This represents 7% (23/324) of the radiographs originally coded by a radiologist as discrepant. The most common discrepancy was a patient with a normal chest examination and a radiograph interpreted as having an infiltrate by the emergency physician, but subsequently read as having no infiltrate by a radiologist (12/324). These patients may have received antibiotics unnecessarily. Two discrepant interpretations had the potential to have serious consequences to the patient if not identified. One patient with cardiomegaly and another patient with free air on abdominal radiograph were not noted by the emergency physician. CONCLUSIONS: Emergency physicians would benefit from more rigorous interpretation of chest x-rays to avoid unnecessary treatment with antibiotics. Emergency physicians do a good job interpreting plain radiographs, but occasionally miss significant findings that could lead to adverse outcomes. The presence of radiologists to immediately read radiographs 24 hours a day could prevent missed findings, but, given the small number of significant misinterpretations, is unlikely to be cost effective.

Pediatric wilderness recreational deaths in western Washington State.

STUDY OBJECTIVE: To determine the causes and characteristics of pediatric recreational wilderness deaths. METHODS: All deaths of children between 12 months and 20 years of age involving a wilderness recreational activity in 5 western Washington counties between 1987 and 1996 were identified by medical examiners' logs. Univariate analysis was used to examine variables such as age, gender, activity, mechanism of injury, adult presence, blood alcohol level, safety equipment, and mode of evacuation. RESULTS: Of 40 cases meeting inclusion criteria, 90% involved male subjects and 83% of victims were 13 to 19 years old. Hiking (33%), swimming (20%), and river rafting (10%) were the most common activities. Death was most often by drowning (55%) or closed head injury (26%). No victim was alone. All children younger than 10 years of age were accompanied by an adult, in contrast to only 26% of individuals 10 years or older. Only 4 victims had drugs or alcohol in their system. No victim wore a personal flotation device or helmet, and only 5% had foul weather gear. Although nearly one third of victims were transported by airlift, more than half of the victims were dead at the scene. CONCLUSION: Males and teenagers were the 2 major risk groups for recreational wilderness deaths. Traditional activities such as hiking and swimming were the most common causes of death. Children younger than 10 years died despite the presence of an adult, whereas teenagers were usually with groups of peers. The majority of victims were not prepared for adverse events with basic safety equipment.

Novel perfusion sleeve for use during balloon angioplasty: initial clinical experience.

The perfusion sleeve (PS) is an "over-the-balloon" catheter designed to add perfusion capability to standard PTCA catheters. To evaluate the clinical effectiveness of this device, eight patients underwent standard PTCA with the PS retracted in the guide (Inflation 1-Control) and after deployment of the PS (Inflation 3-Control). Between standard inflations the PS was advanced and aligned with the already positioned PTCA balloon which was inflated for up to 15 minutes (Inflation 2-Perfusion). TIMI III flow was present in 5/7 and TIMI II flow in 2/7 patients during Inflation 2-Perfusion. Absolute ST segment shift (mm) on the ECG was significantly less at 3 minutes and prior to balloon deflation with the PS in place (1.0 +/- 1.4 and 1.1 +/- 1.1 mm) compared to Inflation 1-Control and Inflation 3-Control (2.6 +/- 1.3 and 2.3 +/- 0.3 mm) respectively (P < or = 0.05). Use of the PS in conjunction with standard PTCA is feasible, provides perfusion during prolonged balloon inflations and reduces the magnitude of ischemia.

Intramural delivery of agent via a novel drug-delivery sleeve. Histological and functional evaluation.

BACKGROUND: The infusion sleeve is a novel drug-delivery catheter system designed to deliver an agent under controlled conditions into the arterial wall at the site of angioplasty. The purpose of the present study was to characterize the delivery agent via the infusion sleeve in ex vivo and in vivo models. METHODS AND RESULTS: The delivery of horseradish peroxidase via the infusion sleeve was studied in a porcine explanted heart model. Under physiological conditions, arteries underwent balloon injury (approximately 10% overstretch), after which horseradish peroxidase (2.5 mL) was delivered at specific pressures. Cross-sectional analysis demonstrated greater staining when the agent was delivered at increasing pressures. The infusion sleeve was evaluated in an in vivo canine coronary model. With an infusion sleeve loaded over a standard dilatation catheter through a 9F guide, overstretch balloon injury was performed, after which fluoresceinated heparin was delivered. Animals were killed 2 hours after delivery. Fluoresceinated heparin-treated segments demonstrated high fluorescence signals, localizing with smooth muscle cell nuclei with less activity in the interstitium. The functional significance of intramural heparin delivery was studied in a porcine carotid model. In the presence of 111In-labeled platelets, arteries underwent overstretch injury followed by delivery of heparin (50 or 100 units/kg) or vehicle. Platelet deposition was reduced at 30 minutes (57%, P < .01) and 12 hours (39%, P = .06) compared with saline controls. CONCLUSIONS: Agent delivery via the infusion sleeve is pressure dependent; transmural delivery is possible with minimal disruption of arterial wall architecture; the infusion sleeve is compatible with standard angioplasty equipment; and heparin delivery at the site of balloon injury significantly reduces platelet deposition in a porcine model for a minimum of 12 hours.

Buffered lidocaine: analgesia for intravenous line placement in children.

OBJECTIVES: To evaluate the effectiveness of intradermal buffered lidocaine as analgesia before intravenous line (i.v.) placement in children. METHODS: This was a randomized clinical trial undertaken in the emergency department (ED) of a regional children's hospital. Participants were children 8 to 15 years old, seen in the ED and in need of i.v. lines. They were enrolled by three ED nurses. Participants were randomized to receive either intradermal buffered lidocaine or no analgesia. Before placement of the i.v. line, patients recorded the amount of pain they were in (baseline pain) on a visual analog pain scale. The primary outcome measure was amount of pain caused by the initial i.v. attempt, even if that attempt was unsuccessful. This was recorded by the participant on a visual analog scale. Demographic characteristics, the number of attempts to successful placement, and the time required to place the i.v. line were also recorded. Differences in pain of initial i.v. attempt and time to place the i.v. line were evaluated with the Mann-Whitney U test. Differences in success of i.v. line placement were evaluated with the chi 2 test. RESULTS: Fifty-nine patients completed the study. Thirty received buffered lidocaine, and 29 received no analgesia before i.v. line placement. There was no significant difference between the two groups with regard to baseline pain or demographic characteristics. The median level of pain of the initial i.v. attempt as measured by the visual analog scale was 2.3 in the buffered-lidocaine group and 4.4 in the no-lidocaine group. Thirty-three percent of patients in the lidocaine group and 28% percent in the no-lidocaine group required more than one i.v. attempt. The median time to i.v. line placement was 10 minutes in the lidocaine group and 6 minutes in the no-lidocaine group. CONCLUSIONS: Use of intradermal buffered lidocaine is an effective way to diminish the pain of i.v. line placement in children 8 to 15 years of age. There was no difference in i.v. success rate in this study; however, larger numbers of patients would be required to detect statistically significant differences. We recommend the routine use of intradermal buffered lidocaine for analgesia before i.v. line placement in older children in all but emergent situations.

Therapeutic regimens for anorectal gonococcal infection in males.

Anorectal gonococcal infection is particularly prevalent in women and homosexual men. Although the currently recommended Public Health Service therapeutic regimens for uncomplicated gonorrhea appear to be effective also for anorectal gonorrhea in women, their efficacy for anorectal infection in men has not been adequately evaluated. We report a case of gonococcal proctitis in a homosexual man that did not respond to therapy with ampicillin plus probenecid and tetracycline, but subsequently responded to spectinomycin therapy. Currently available therapeutic regimens for anorectal gonococcal infection in males are reviewed.

Anorectal gonococcal infection.

Anorectal gonococcal infection is common in women and homosexual men. In women with uncomplicated gonorrhea, the mean prevalence rate of anorectal involvement is 44%, with lone involvement of the anorectum in 4%. Among homosexual men with gonorrhea, anorectal infection occurs in 45%, although more than 90% of all male patients with anorectal gonorrhea admit to homosexual rectal intercourse. This infection is usually asymptomatic but occasionally presents with acute or chronic symptoms that mimic other causes of proctitis. Whereas currently recommended regimens for uncomplicated gonorrhea appear effective for anorectal gonorrhea in women, results in men have not been adequately evaluated. Available data showed failure rates from 7% to 35%; however, only one study used a currently accepted regimen. Further controlled studies in male patients with anorectal gonorrhea are clearly needed to establish optimal therapeutic regimens. Diligent contact tracing of all male homose.xual cases appears to be the only effective means of control at present.