Functional outcome after selective dorsal rhizotomy: a retrospective case control study.

PURPOSE: This study examines long-term benefit on functional outcomes and quality of life after selective dorsal rhizotomy (SDR) in children with spastic diplegia in Hong Kong. METHOD: This is a case control study. Individuals with spastic diplegia who were at 6 to 12 years post-SDR were recruited. Age, gender, cognition, and Gross Motor Function Classification System level-matched individuals with spastic diplegia who had not undergone SDR were recruited as controls. Outcome measures included physical level, functional level, physiological level, and quality of life. All data were compared by independent t-test. RESULTS: Individuals post-SDR (n = 15) demonstrated a significantly better range of ankle dorsiflexion in knee extension by - 5.7 ± 10.9° than the control group (n = 12). No other significant differences were observed. CONCLUSION: SDR is a safe, one-off procedure and provides long-term reduction in spasticity with no major complications. With the heterogeneity, we did not demonstrate between-group differences in long-term functional outcomes.

Design and Synthesis of 56 Shape-Diverse 3D Fragments.

Fragment-based drug discovery is now widely adopted for lead generation in the pharmaceutical industry. However, fragment screening collections are often predominantly populated with flat, 2D molecules. Herein, we describe a workflow for the design and synthesis of 56 3D disubstituted pyrrolidine and piperidine fragments that occupy under-represented areas of fragment space (as demonstrated by a principal moments of inertia (PMI) analysis). A key, and unique, underpinning design feature of this fragment collection is that assessment of fragment shape and conformational diversity (by considering conformations up to 1.5 kcal mol-1 above the energy of the global minimum energy conformer) is carried out prior to synthesis and is also used to select targets for synthesis. The 3D fragments were designed to contain suitable synthetic handles for future fragment elaboration. Finally, by comparing our 3D fragments with six commercial libraries, it is clear that our collection has high three-dimensionality and shape diversity.

Completeness of Neisseria meningitidis reporting in New York City, 1989-2010.

Invasive meningococcal disease (IMD) completeness of reporting has never been assessed in New York City (NYC). We conducted a capture-recapture study to assess completeness of reporting, comparing IMD reports made to the NYC Department of Health and Mental Hygiene (DOHMH) and records identified in the New York State hospital discharge database [Statewide Planning and Research Cooperative System (SPARCS)] by ICD-9 codes from 1989 to 2010. Reporting completeness estimates were calculated for the entire study period, and stratified by year, age group, clinical syndrome, and reporting system. A chart review of hospital medical records from 2008 to 2010 was conducted to validate hospital coding and to adjust completeness estimates. Overall, 2194 unique patients were identified from DOHMH (n = 1300) and SPARCS (n = 1525); 631 (29%) were present in both. Completeness of IMD reporting was 41% [95% confidence interval (CI) 40-43]. Differences in completeness were found by age, clinical syndrome, and reporting system. The chart review found 33% of hospital records from 2008 to 2010 had no documentation of IMD. Removal of those records improved completeness of reporting to 51% (95% CI 49-53). Our data showed a low concordance between what is reported to DOHMH and what is coded by hospitals as IMD. Additional guidance to clinicians on IMD reporting criteria may improve completeness of IMD reporting.

Development and evaluation of a positive youth development course for university students in Hong Kong.

With higher education, university graduates are important elements of the labor force in knowledge-based economies. With reference to the mental health and developmental problems in university students, there is a need to review university's role in nurturing holistic development of students. Based on the positive youth development approach, it is argued that promoting intrapersonal competencies is an important strategy to facilitate holistic development of young people in Hong Kong. In The Hong Kong Polytechnic University, a course entitled Tomorrow's Leader focusing on positive youth development constructs to promote student well-being will be offered on a compulsory basis starting from 2012/13 academic year under the new undergraduate curriculum structure. The proposed course was piloted in 2010/11 school year. Different evaluation strategies, including objective outcome evaluation, subjective outcome evaluation, process evaluation, and qualitative evaluation, are being carried out to evaluate the developed course. Preliminary evaluation findings based on the piloting experience in 2010/11 academic year are presented in this paper.

Identification of hemopexin in tear film.

Human tear fluid is a complex mixture of aqueous lipids, proteins, enzymes, and other biochemical and cellular elements. By conventional comparative proteomic approaches, we investigated the proteome in human tear fluid and compared the tear protein profile of normal control subjects with that of patients suffering from the ocular inflammatory disease vernal keratoconjunctivitis (VKC). Collected tear samples were directed to two-dimensional polyacrylamide gel electrophoresis protein separation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry peptide identification. Six differentially expressed proteins-interleukin 4, phospholipase A2, albumin, lactoferrin, hemopexin, and lipocalin-were displayed. Hemopexin had not been reported previously in tear film. Enzyme-linked immunosorbent assay confirmed that hemopexin concentrations were significantly higher in VKC tear samples and increased with disease stages. The results implied clinical interest of hemopexin in the tear proteome and eye diseases.

Lysergic acid diethylamide: role in conversion of plasma tryptophan to brain serotonin (5-hydroxytryptamine).

Injections of D-lysergic acid diethylamide decrease the turnover rate of 5-hydroxytryptamine of rat brain, as measured from the conversion of (14)C-tryptophan into (14)C-5-hydroxytryptamine. The 2-bromolysergic acid diethylamide given in doses fivefold greater than those of lysergic acid diethylamide fails to change the rate of (14)C-tryptophan conversion into (14)C-5-hydroxytryptamine. The effect of D-lysergic acid diethylamide is discussed with regard to its action on brain serotonergic neurons and its psychotomimetic effects.

Nitrous oxide "analgesia": resemblance to opiate action.

Nitrous oxide produced a dose-related "analgesia" in mice (median effective dose, 55 percent). The analgesia was evaluated by means of a phenylquinone writhing test. Narcotic antagonists or chronic morphinization reduced nitrous oxide analgesia. Either nitrous oxide releases an endogenous analgesic or narcotic antagonists have analgesic antagonist properties heretofore unappreciated.

Carbide and nitride phase characterization in a transition metal carbo-nitride using x-ray spectroscopy and atom probe tomography.

A multi-phase hafnium carbo-nitride was investigated by various analytical methods. Incomplete homogenization between mixed HfC-HfN starting powders subjected to hot isostatic pressing resulted in both carbon-rich and nitrogen-rich phases. The compositions of these two phases were quantified in detail by wavelength dispersive spectroscopy and atom probe tomography, with the atom probe tips having either a small or a large shank angle geometry. For each of the two phases, an agreement of the compositions obtained by wavelength dispersive spectroscopy and atom probe tomography was found. However, the quality of the mass spectrum and hit multiplicity (single hits) were generally higher for the carbon-rich as compared to the nitrogen-rich carbo-nitride. Though the atom probe tip geometry does not appear to influence the composition, the mass resolving power did improve with the larger shank angle geometry while the hit multiplicity deteriorated slightly. Finally, our results demonstrate that hafnium carbide requires less thermal assistance to field evaporate than hafnium nitride.

Complex evaporation behavior of a transition metal carbo-nitride (Hf(C,N)) studied by atom probe tomography.

The use of pulsed lasers in atom probe tomography has enabled the analysis of lower conductivity materials such as hafnium carbo-nitrides. The variability of experimental parameters can have a profound effect on field evaporation behavior, data quality and compositional accuracy. This is especially challenging for materials such as hafnium carbo-nitride, where a mixture of covalent, ionic and metallic bonding types is present. Here we study the influence of laser pulse energy on how the field evaporation evolves in a hafnium carbo-nitride and how that impacts data quality and compositional accuracy. Changing the laser pulse energy, while keeping other parameters constant, alters the resulting composition. A gain in Hf concentration is observed for higher laser pulse energies while at the same time the N concentration decreases. At lower laser pulse energies, the obtained composition is in good agreement with the reference bulk composition of the material. Furthermore, our results demonstrate that assessing the quality of an APT experiment or dataset merely based on commonly used metrics such as quality of mass spectrum, hit distribution on the detector, hit multiplicity and mass resolving power, can be misleading and is not enough to ensure the most accurate compositional data. Moreover, it is shown that the complex evaporation behavior of transition metal carbo-nitrides and potential ion loss mechanisms are not well enough understood yet and further work is required to fully comprehend these complex behaviors in these types of ceramics.

Hyperintensity of the precentral gyral subcortical white matter and hypointensity of the precentral gyrus on fluid-attenuated inversion recovery: variation with age and implications for the diagnosis of amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Hyperintensity of the subcortical white matter (SWM) of the precentral gyrus and hypointensity of the precentral gyrus gray matter (PGGM) on fluid-attenuated inversion recovery (FLAIR) are described as potentially useful diagnostic findings in amyotrophic lateral sclerosis (ALS). A detailed study of the prevalence of these findings in various age groups has not been described. METHODS: One hundred twenty-two patients underwent axial FLAIR brain examinations as part of either hearing loss or tinnitus evaluation. Examinations were randomly selected to reflect an even spread through the decades from ages 15 to 78 years and were reviewed by 2 readers, blinded to patient's age and sex, for the presence/absence of the above 2 signs. If SWM hyperintensity was present, it was graded as intense as caudate nucleus (grade 1) or insula (grade 2). RESULTS: We identified 32 cases of grade 1 and 5 cases of grade 2 SWM hyperintensity, and 28 cases of PGGM hypointensity. Both signs showed significant Spearman correlation with increasing age (r = 0.55, P < .001 for grade 1, r = 0.45, P < .001 for grade 2 SWM hyperintensity, r = 0.45, P < .001 for PGGM hypointensity). Analysis of variance showed there was a significant difference between the different age groups (P < .001) for both signs. Grading of the SWM and PGGM signals were highly reproducible with very good interobserver agreement (r = 0.88, P < .001, and r = 0.97, P < .001, respectively). CONCLUSION: This study suggests a statistically significant relationship between increasing age and the frequency of precentral gyrus SWM hyperintensity and PGGM hypointensity on FLAIR, and reinforces previous reports that these signs can be seen in patients who do not have ALS.

Sonographic evaluation of diaphragmatic function during breathing control.

OBJECTIVE: To investigate the effect of "breathing control" on sonographic diaphragmatic excursion. METHOD: A prospective, randomized, assessor-blinded study design involving 20 physiotherapy students; ten with knowledge of the breathing control technique (Group BC) and ten without (Group CON). All participants were asked to perform a Chester step test. Group BC performed BC, while Group CON adopted their own breathing pattern during recovery after the step test. Respiratory rate and sonographic parameters of the diaphragm including diaphragmatic excursion, speed of diaphragmatic contraction (slope of contraction), and inspiratory time were recorded before and after the step test. RESULTS: All baseline data were similar for both groups except age. Respiratory rate at 1 min post-step test was higher in Group CON (24.6±4.9 bpm) compared to Group BC (15.6 ± 3.8 bpm) (p < 0.001). Post-step test sonographic evaluation demonstrated an increase in diaphragmatic excursion with a significant time and group interaction (F(4,72) = 5.499, p = 0.005). Post hoc analysis revealed that the diaphragmatic excursion was significantly higher in Group BC compared to Group CON at first, second and third minute post-step test. Time and group interactions were not significant in inspiration time (F(4,72) = 2.459, p = 0.082) nor the slope of contraction (F(4,72) = 0.655, p = 0.582)]. CONCLUSION: Post-exercise diaphragmatic excursion was higher in participants applying BC. Non-invasive ultrasonography is able to promote objective evaluation of the relationship between breathing techniques and diaphragmatic function.

Hyperintensity of the middle cerebellar peduncles on fluid-attenuated inversion recovery imaging: variation with age and implications for the diagnosis of multiple system atrophy.

BACKGROUND AND PURPOSE: T2 hyperintensity of the middle cerebellar peduncle (MCP) is described in a number of diseases, including multiple system atrophy (MSA). We hypothesize that mild MCP hyperintensity on fluid-attenuated inversion recovery (FLAIR) imaging can be a normal finding. To our knowledge, a detailed study of the prevalence of this finding in various age groups with the FLAIR sequence has not been described. METHODS: One hundred twenty-two patients underwent an axial FLAIR examination of the brain as part of either a hearing loss or tinnitus work-up (ie, to exclude an acoustic neuroma or a retrocochlear cause). Subjects aged 15-78 years were included to reflect an even spread through the decades and were divided into 6 age groups. A radiologist and an MR imaging fellow graded the examinations subjectively, blinded to age: 0 for normal or 1 for the presence of MCP hyperintensity if the increased signal intensity was greater than that of adjacent pons and cerebellar white matter. Spearman rank correlation test of MCP hyperintensity with age and analysis of variance (ANOVA) were performed. RESULTS: Of 122 patients, we identified 17 with MCP FLAIR hyperintensity. None of these patients had a clinical condition that could cause MCP hyperintensity. MCP hyperintensity did not show a statistically significant correlation with age (r = 0.05, P = .62). Patients were divided into 6 age groups, and ANOVA showed no statistically significant difference in the incidence of MCP hyperintensity between different age groups (P = .95). However, results were highly reproducible with excellent interobserver correlation (r = 0.97, P < .001). CONCLUSIONS: Mild MCP FLAIR hyperintensity can occur normally, and this finding shows no relationship with age.

The solitary enhancing cerebral lesion: can FLAIR aid the differentiation between glioma and metastasis?

BACKGROUND AND PURPOSE: The purpose of this study is to investigate the diagnostic utility of fluid-attenuated inversion recovery (FLAIR) in differentiating between glioma and metastasis by assessing for nonenhancing adjacent cortical signal intensity abnormality in patients who present with a solitary enhancing cerebral lesion. METHODS: After approval from the institutional ethics committee was obtained, the MR imaging studies of 70 patients with a solitary enhancing lesion, without previous surgery or treatment, were reviewed. The axial FLAIR studies were initially reviewed for cortical involvement. If cortex involvement was detected, comparison with the axial T1, with and without gadolinium enhancement, was made to determine whether the cortex involvement was in an area without enhancement. If this was the case, the study was considered positive for glioma. Statistical analysis consisted of binary logistic regression and a 2 x 2 contingency table. RESULTS: Involvement of the adjacent cortex with FLAIR signal intensity abnormality but without enhancement was seen in 19 of 70 patients; 16 were gliomas and 3 were solitary metastasis. The sensitivity and specificity of this finding were 44% and 91%, respectively. The positive predictive value for glioma was 84%. CONCLUSION: FLAIR, when interpreted in concert with pre- and postgadolinium T1-weighted images, may be useful in differentiating glioma from metastasis when a solitary enhancing cerebral lesion is present. The presence of nonenhancing adjacent cortical involvement in a solitary enhancing lesion is a frequent and relatively specific sign.

Effects of footwear on running economy in distance runners: A meta-analytical review.

OBJECTIVES: Previous studies reported inconsistent findings about the effects of footwear on running economy, which is a surrogate measure of running performance. This meta-analytical review compared the running economy between running in barefoot, minimalists, and standard running shoes. DESIGN: Meta-analysis. METHODS: Electronic searches on MEDLINE, CINAHL, SPORTDiscus, and Cochrane Library databases were performed and the reference lists of the screened articles were also scrutinized. Two reviewers screened clinical trials that measured the oxygen cost of runners in different footwear conditions. RESULTS: Thirteen studies were selected in this meta-analysis with a total of 168 runners included. Barefoot running was shown to be more economic than shod running (p<0.01; standardized mean difference=-0.43; 95% Confidence Interval=-0.21 to -0.64; Z=3.96). Similar pattern was found when comparing minimalist and shoe (p<0.01; standardized mean difference=-0.49; 95% Confidence Interval=-0.29 to -0.70; Z=4.64). The observed changes were of small effect. Conversely, no significant difference in the metabolic cost was found between running in minimalists and barefoot running (p=0.45). CONCLUSIONS: Barefoot running or running in minimalist may require lower utilization of oxygen than shod running. Theoretically, the lower oxygen cost may improve long distance running performance. However, more than half of the runners in the included studies had previous barefoot experience and the findings may not apply to those habitual shod runners who are undergoing the transition. In addition, high risk of bias was reported in the included studies and quality study in the future is still warranted.

The diposi tion of morphine in surgical patients.

The disposition of serum morphine following administration of 10 mg/70 kg was determined by a sensitive and specific radioimmunoassay in 31 anethetized surgical patients ranging in age from 23 to 75 yr. Following iv injection, 93 per cent of the morphine disappeared from the serum within 5 min. The early serum levels of the drug (2 min) correlated directly with the patients' ages (r equal to 0.63, p smaller than 0.01). Patient 23 to 50 yr of age averaged 0.29 mug/ml, whereas patients 51 to 75 ur of age averaged 70 percent higher, 0.49 mug/ml. The serum half-life between 10 and 240 min was independent of age and averaged about 2 hr after either iv or im administration. Following im admininstration, morphine was rapidly absorbed, with peak levels occurring within 10 to 20 min. The decline in morphine serum levels paralleled the decline in morphine analgesia and was coincident with the apperance of morphine glucuronide in the serum. These studies demonstrate the applicability and specificity of the radioimmunoassay for morphine and suggest that serum levels of morphine may be a useful and objective indicator of its pharmacologic activity.

Regulation of metaraminol efflux from rat heart and salivary gland.

1. The turnover rate of noradrenaline (NA) in heart and submaxillary salivary gland was studied in rats exposed to 4 degrees C or maintained at room temperature (22 degrees C). Cold exposure increased the turnover of the NA store in heart but not in salivary gland.2. In another series of experiments the decline of metaraminol (M) from heart and submaxillary salivary gland was studied in rats exposed to 4 degrees C or maintained at room temperature. Cold exposure accelerated the efflux of M from heart, but not from salivary gland. It is concluded that the accelerated decline of M from heart is the consequence of selective activation of the sympathetic nerves that innervate the heart.3. The turnover of NA was studied in rat heart after the administration of M (100 mug/kg intravenously) or its precursor alpha-methyl-meta-tyrosine (200 mg/kg intraperitoneally). Turnover remained essentially normal after these drugs.4. The administration of desipramine (DMI, 20 mg/kg intraperitoneally) 1 hr after M (100 mug/kg intravenously) induced a rapid sustained efflux of M from heart and salivary gland. The results of this study suggest that the slow decline of M from heart is the result of the great affinity of the amine retrieval mechanism in sympathetic nerve endings for M. DMI inhibits the retrieval mechanism, thus accelerating the efflux of M.

Cervical priming with oral misoprostol in pre-labor rupture of membranes at term.

OBJECTIVE: To investigate the effectiveness of oral misoprostol as a cervical priming agent for patients presenting with pre-labor rupture of membranes at term. METHODS: Eighty patients presenting with pre-labor rupture of membranes at term were randomized to receive either 200 micrograms of misoprostol or 50 mg of vitamin B6 orally 1 hour after admission. Labor was induced with intravenous oxytocin infusion 12 hours after oral medication if the patient did not go into labor. We compared the induction rate, duration of labor, mode of delivery, and leaking-to-delivery interval in the two groups. RESULTS: The cervical score was significantly improved and the induction rate was also reduced in the misoprostol group when compared with the control group. The interval from recruitment to onset of labor, duration of labor, and the interval from recruitment to delivery were significantly shorter in the misoprostol group. The mode of delivery and the perinatal outcome were similar for the two groups. CONCLUSION: Oral misoprostol is an effective agent for cervical priming and labor induction in patients with pre-labor rupture of membranes at term.

Vaginal misoprostol compared with oral misoprostol in termination of second-trimester pregnancy.

OBJECTIVE: To compare the efficacy of vaginal with oral misoprostol in termination of second-trimester pregnancy after pretreatment with mifepristone. METHODS: Women requesting termination of second-trimester pregnancy were randomized into two groups. Thirty-six to 48 hours after oral administration of 200 mg of mifepristone, women were given either oral or vaginal misoprostol 200 microg every 3 hours for a maximum of five doses in the first 24 hours. Women receiving oral misoprostol also were given a vaginal placebo (vitamin B6), whereas those receiving vaginal misoprostol were given an oral placebo. If they failed to abort, a second course was given by the same route. RESULTS: The median induction-abortion interval in the vaginal group (9 hours) was significantly shorter than that in the oral group (13 hours). The percentage of women aborting within 24 hours in the vaginal group (90%) was significantly higher than that in the oral group (69%). The median amount of misoprostol used in the vaginal group (600 microg) also was significantly less than that in the oral group (1000 microg). There was no significant difference in the incidence of side effects between the two groups except for fatigue and breast tenderness, which were more common in the oral group. Seventy-six percent of the women preferred the oral route, and 24.5% of the women preferred the vaginal route. CONCLUSION: Vaginal misoprostol is more effective than oral misoprostol in termination of second-trimester pregnancy after pretreatment with mifepristone, but more women preferred the oral route.

Disposition of propranolol isomers in mice.

l-Propranolol was found to protect mice from hyperbaric oxygen-induced seizures. The disposition of effective doses of propranolol isomers in mice was followed using stereospecific antibodies with a radioimmunoassay procedure. Serum and tissue concentrations were determined and correlated with the protective effect. Following racemic administration, there were no differences in serum disposition of d- and l-propranolol, although there was initially a preferential uptake of the 1-isomer both into cardiac and brain tissue. The d-isomer exerted synergistic action on the 1-isomer protective effect.