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PubMed2003

Performance analyses of flowing chemical oxygen-iodine laser.

A modified simplified rate-equation model that utilizes the Voigt profile function and another gain saturation model deduced from the kinetic equations are presented for performance analyses of a flowing chemical oxygen-iodine laser. Both models are adapted to both the condition of homogeneous broadening and that of inhomogeneous broadening being of importance and the condition of inhomogeneous broadening being predominant. Effects of temperature and iodine density on the output power and on variations of output power, optical intensity, and saturation intensity with flow distance are presented as well. There are differences between results of two models, but both qualitatively agree with known results.

Journal Article↗
PubMed2004

Explicit formulas for transmission characteristics of graded-index oval core fibers.

Transmission characteristics of graded-index oval (GIO) core fibers are theoretically analyzed, and basic equations representing the specific properties of the fiber are obtained. Formulas for the propagation constant, the field-profile function, the cutoff condition, and the total number of guided modes are derived in explicit forms. The formula for the change of the Gaussian beam radius as a function of the propagation distance is also given, and the numerical example agrees well with experimental data and agrees completely with that obtained by the beam-propagation method. These explicit expressions are useful for finding optimum structural parameters of GIO fibers to be used in practical fields.

Journal Article↗
PubMedDate not supplied

Diagnostic practices for attention deficit hyperactivity disorder: a national survey of primary care physicians.

BACKGROUND: The American Academy of Pediatrics (AAP) clinical practice guideline emphasizes the appropriate diagnosis of attention deficit hyperactivity disorder (ADHD) in school-aged children. Although previous studies have shown wide variation in diagnostic practices for ADHD, few recent studies have examined nationally representative samples. OBJECTIVE: To describe practice patterns of primary care physicians evaluating school-aged children for ADHD in the late 1990s and compare the patterns with subsequently published AAP guidelines. METHODS: We surveyed a national sample of 2000 primary care pediatricians and family physicians. Of the 1076 returned surveys, 861 (43%) met data quality criteria and were included in the analysis. We tabulated frequencies for each item and used a chi2 test to examine relationships between survey items and physician characteristics. RESULTS: Primary care physicians most commonly reported conducting 1-2 new evaluations for ADHD per month, the majority spending 15-45 minutes and at least 2 office visits to confirm a diagnosis of ADHD. Although 58% of physicians used formal diagnostic criteria, only 28% reported using criteria according to the Diagnostic and Statistical Manual of Mental Disorders. Eighty-three percent reported using any teacher or school information such as report cards and rating scales. Approximately 70% used ADHD-specific rating scales, and 60% used global behavior scales. A quarter of respondents obtained laboratory tests such as hematocrit, lead, and thyroid function profile. Most physicians reported routinely assessing for coexisting conditions, ranging from 74% for tic disorders to 91% for depression and conduct disorder. CONCLUSIONS: Before the publication of AAP guidelines, primary care physicians' evaluation practices for school-aged children with ADHD varied widely, especially with respect to use of Diagnostic and Statistical Manual of Mental Disorders diagnostic criteria and inappropriate diagnostic tests.

Attention Deficit Disorder with Hyperactivity↗
PubMed1994

Prognosis of severely hypoxemic patients receiving long-term oxygen therapy.

Two hundred seventy severely hypoxemic (PaO2 < or = 55 mm Hg: mean +/- SD = 48 +/- 6) COPD patients (232 men) were selected for long-term oxygen therapy (LTOT). They were old (mean = 66 +/- 8 years), with severe airflow limitation (FEV1 = 30 +/- 12 percent of predicted), some CO2 retention (PaCO2 = 47 +/- 9 mm Hg), and compensated respiratory acidosis. Eighteen percent of the patients presented some complicating pleuropulmonary diseases (pleural thickening, sequelae of tuberculosis, etc). Overall survival proportion was poor: 70, 50, and 43 percent at 1, 2, and 3 years, respectively. The Cox model showed that the factors which independently reduced survival were lower CO transfer coefficient, smaller intrathoracic gas volume, more severe bronchial obstruction, the fact that oxygen administration did not increase PaO2 above 65 mm Hg, increasing age, and the presence of chest wall abnormalities. When the patients were divided into three groups according to mortality risk, the mean clinical and functional profile of the high-mortality risk group was consistent with the prevalence of emphysematous lesions. Moreover, the best survivors fitted better into the "bronchitic" type; they showed a higher mean PaCO2, suggesting that some degree of hypoventilation could delay muscular fatigue and improve survival. The difference in the proportion of "emphysematous" and "bronchitic" patients is a possible explanation for the variability of the mortality rate reported in literature.

Acidosis, Respiratory↗
PubMed2005

Overactive bladder in the elderly: a guide to pharmacological management.

Overactive bladder (OAB) is a common condition characterised by the symptoms of urinary frequency and urgency, with or without urge incontinence and nocturia. The prevalence of OAB increases markedly with age in both men and women. OAB can have a detrimental effect on physical functioning and psychological well-being, as well as significantly reducing quality of life. Antimuscarinic therapy -- with or without behavioural therapy -- represents the most common treatment for patients with OAB. Several antimuscarinic agents are currently available for the treatment of OAB in adults, including oxybutynin, tolterodine, trospium chloride, darifenacin and solifenacin. The antimuscarinics all appear to exert their clinical effect through inhibition of the bladder muscarinic receptors, but they vary both in structure and in their functional profile. While efficacy has been demonstrated in adult populations (including patients >65 years of age), few studies have been reported specifically in a geriatric population, and antimuscarinics are often underutilised in the elderly despite the marked increase in the prevalence of OAB in this age group. One explanation for this apparent underuse of an effective treatment option may be concerns about the frequency of anticholinergic adverse events, such as dry mouth; the likelihood of detrimental CNS effects, including cognitive impairment and sleep disturbances; and the potential for harmful interactions with existing pharmacotherapy. When selecting an antimuscarinic agent for the management of an elderly patient presenting with OAB, in addition to considering evidence of clinical efficacy and tolerability, issues of safety specific to an older population should be borne in mind. In particular, the likelihood of detrimental CNS effects should be considered, including cognitive impairment and sleep disturbances, secondary to anticholinergic load. Oxybutynin and tolterodine have both been associated with cognitive adverse events and effects on sleep architecture and quality. In contrast, trospium chloride and darifenacin do not appear to be associated with cognitive adverse events and trospium chloride does not negatively affect sleep architecture or quality. Biotransformation by the cytochrome P450 (CYP450) system is an important step in the activation or elimination of a large number of drugs, including oxybutynin, tolterodine, darifenacin and solifenacin, raising the possibility of clinically relevant and potentially serious drug interactions. In elderly patients, such interactions are of particular relevance given the potential for declining activity of certain members of the CYP450 family combined with decreased hepatic blood flow, which can reduce first-pass metabolism and thus the bioavailability of drugs metabolised via this route. Of the antimuscarinic agents used to treat OAB, only trospium chloride is not extensively metabolised in the liver by the CYP450 system and is excreted largely as the active parent compound in the urine. This paper provides an overview of the pathophysiology of OAB and reviews current approaches to achieving a differential diagnosis and selecting appropriate treatment for the older patient. The pharmacology and clinical effects of current medication for the treatment of OAB symptoms in patients defined by the OAB pharmacology literature as 'elderly' are also reviewed.

Aged↗
PubMed2002

Muscle strength testing: use of normalisation for body size.

Assessment of muscle strength tests has been a popular form of testing muscle function in sports and exercises, as well as in other movement-related sciences for several decades. Although the relationship between muscle strength and body size has attracted considerable attention from researchers, this relationship has been often either neglected or incorrectly taken into account when presenting the results from muscle strength tests. Two specific problems have been identified. First, most of the studies have presented strength data either non-normalised for body size, or normalised using inappropriate methods, or even several different normalisations have been applied on the same sets of data. Second, the role of body size in various movement performances has been neglected when functional movement performance was assessed by muscle strength. As a consequence, muscle function, athletic profiles, or functional movement performance assessed by tested muscle strength have been often confounded by the effect of body size. Differences in the normalisation methods applied also do not allow for comparison of the data obtained in different studies. Using the following allometric formula for obtaining index of muscle strength, S, independent of body size (assessed by body mass, m) should be recommended in routine strength testing procedures: The allometric parameter should be either b = 0.67 for muscle force (recorded by a dynamometer), or b = 1 for muscle torque (recorded by an isokinetic apparatus). We also recommend using body-size-independent indices of both muscle strength and movement performance when assessing functional performance from recorded muscle strength or vice versa.

Adolescent↗
PubMed2004

Recent advances in small molecule microarrays: applications and technology.

The field of Small Molecule Microarray's (SMM's) is an ever-expanding part of the larger microarray field. SMM's are array based detection systems that use small molecules as probes immobilized on a variety of microarray surfaces that are screened against a number of targets for purposes including, but not limited to, protein-small molecule ligand recognition and protein function profiling. This review covers the recent advances in the field with particular emphasis on the successful applications of SMM's, as well as technical advances in platform optimization and novel small molecule immobilization strategies.

Animals↗
PubMed2006

Gene variants in noncoding regions and their possible consequences.

Human biodiversity or individual traits are not well explained by exonic mutations of all 20,000 known human genes. Accumulating evidence has demonstrated that not all noncoding regions are junk DNA sequences, and that some functionally important noncoding variants contribute significantly to altered gene expression, qualitatively or quantitatively. Thus, functional profiling or clinical relevance of noncoding variations should not be underestimated or ignored. To validate these concepts, some important examples are discussed further in this short review.

5' Untranslated Regions↗
PubMed1997

Improved human islet isolation using a new enzyme blend, liberase.

Enzymatic digestion of donor pancreases is a vital step in human and large mammalian islet isolation. The variable enzymatic activities of different batches of commercially available collagenase is a major obstacle in achieving reproducibility in islet isolation procedures. In the present work, the effectiveness of Liberase, a standardized mixture of highly purified enzymes recently developed for the separation of human islets, was compared with that of a traditional collagenase preparation (type P). The results of 50 islet isolations using Liberase enzyme were compared with those of 36 isolations with collagenase, type P. No significant differences in donor age, cold ischemia time, digestion time, or weight of the pancreases were observed between the two groups. Islet yield was significantly higher in the group where the Liberase enzyme was used. All parameters examined (islet number, islet number per gram of tissue, islet equivalent number, and islet equivalent number per gram of tissue) were significantly improved when Liberase enzyme was used. Different lots of Liberase enzyme were tested, and no difference was observed. Islets isolated with Liberase enzyme were also of larger size and were much less fragmented, suggesting a gentler enzymatic action and better preservation of anatomical integrity. Islets isolated with Liberase enzyme, assessed both in vitro and in vivo, revealed a functional profile similar to that of islets separated with collagenase. Liberase enzyme appears, therefore, to represent a new powerful tool for improving the quality of human islet isolation.

Adult↗
PubMed1999

NH2-terminally modified gastric inhibitory polypeptide exhibits amino-peptidase resistance and enhanced antihyperglycemic activity.

Gastric inhibitory polypeptide (GIP) is an important insulin-releasing hormone of the enteroinsular axis that, like glucagon-like peptide 1(7-36) amide (tGLP-1), has a functional profile of possible therapeutic value for type 2 diabetes. Both incretin hormones are rapidly inactivated in plasma by the exopeptidase dipeptidyl peptidase (DPP) IV. The present study examined the ability of NH2-terminal modification of human GIP to protect from plasma degradation and enhance insulin-releasing and antihyperglycemic activity. Degradation of GIP by incubation at 37 degrees C with purified DPP IV was clearly evident after 4 h (54% intact). After 12 h, >60% of GIP was converted to GIP(3-42), whereas >99% of NH2-terminally modified Tyr1-glucitol GIP remained intact. Tyr1-glucitol GIP was similarly resistant to serum degradation. The formation of GIP(3-42) was almost completely abolished by inhibition of plasma DPP IV with diprotin A. Effects of GIP and Tyr1-glucitol GIP were examined in Wistar rats after intraperitoneal injection of either peptide (10 nmol/kg) together with glucose (18 mmol/kg). Plasma glucose concentrations were significantly lower and insulin concentrations higher after both peptides compared with glucose alone. More importantly, individual glucose values at 15 and 30 min together with the areas under the curve (AUCs) for glucose were significantly lower after administration of Tyr1-glucitol GIP compared with GIP (AUC 255 +/- 33 vs. 368 +/- 8 mmol x l(-1) x min(-1), respectively; P < 0.01). This was associated with a significantly greater and more protracted insulin response after Tyr1-glucitol GIP than GIP (AUC 773 +/- 41 vs. 639 +/- 39 ng x ml(-1) x min(-1); P < 0.05). These data demonstrate that Tyr1-glucitol GIP displays resistance to plasma DPP IV degradation and exhibits enhanced antihyperglycemic activity and insulin-releasing action in vivo.

Aminopeptidases↗
PubMed2001

Results of cystometry and urethral pressure profilometry in dogs sedated with medetomidine or xylazine.

OBJECTIVE: To compare effects of medetomidine and xylazine hydrochloride on results of cystometry and micturition reflexes in healthy dogs and results of urethral pressure profilometry (UPP) in sedated and conscious dogs. ANIMALS: 20 dogs. PROCEDURES: Urodynamic testing was performed 6 times in each dog (3 times after administration of xylazine [1 mg/kg of body weight, IV] and 3 times after administration of medetomidine (30 microg/kg, IM). Before each episode of sedation, UPP was performed. Heart and respiratory rates and indirect blood pressures were recorded prior to and 5, 10, 20, and 30 minutes after injection of sedative. Cystometry measurements included threshold volume, threshold pressure, and tonus limb. The UPP measurements included maximal urethral closure pressure (MUCP), functional profile length, and, in male dogs, plateau pressure. RESULTS: Mean MUCP was decreased markedly in xylazine- and medetomidine-sedated dogs. Xylazine and medetomidine also decreased plateau pressure in male dogs. The MUCP measurements were consistent among days for conscious and xylazine-sedated dogs but were inconsistent for medetomidine-sedated female dogs. The proportion of valid cystometry measurements was greater for xylazine (39 of 60) than for medetomidine (27 of 60). Cystometry was considered invalid when bladder pressure reached 30 cm H2O without initiation of a micturition reflex. CONCLUSIONS AND CLINICAL RELEVANCE: Medetomidine and xylazine have similar effects on measurement of UPP and cystometry. Medetomidine was less consistent among days for UPP in female dogs and produced fewer valid cystometry tests, compared with xylazine. For urodynamic evaluations, medetomidine administered IM cannot be substituted for xylazine administered IV.

Animals↗
PubMed1987

Neuropsychological aspects of primary affective depression.

This study compared the neuropsychological functioning of 50 primary affective depressives and a like number of normals on the complete Halstead-Reitan Neuropsychological Battery. Psychiatric diagnosis was based on Research Diagnostic Criteria. Comparison of the Wechsler subtests seen to measure right and left hemispheric functioning revealed a relative deficit for depressives on those tasks shown to be most sensitive to right hemispheric functioning. Profile similarities (rp) between groups on the combined Wechsler and Halstead-Reitan variables indicated normal similarity on left hemispheric tests and a significant dissimilarity on right hemispheric measures. Impairment ratings for each Halstead-Reitan measure indicated that depressives were significantly impaired when compared to normals on right hemispheric tasks, while they were within normal limits and did not differ from normals on left hemisphere impairment ratings. The potential of neuropsychological measures as diagnostic markers of psychiatric illness was examined.

Adult↗
PubMed2026

A Real-Time Image-Based Co-Culture Assay to Quantify Tumor-Infiltrating Lymphocyte-Mediated Apoptotic Killing of Patient-Derived Tumor Organoids.

Understanding the functional capacity of tumor-infiltrating lymphocytes (TILs) to recognize and eliminate autologous tumor cells is central to advancing personalized immunotherapy. The goal of this method is to provide an image-based, live-cell imaging protocol that measures TIL-mediated, caspase-3-dependent apoptotic killing against patient-derived tumor organoids (PDTOs) in real time. This method integrates established procedures for isolation and expansion of PDTOs and TILs with a standardized three-dimensional co-culture system and automated fluorescence-based apoptosis detection. Tumor organoids are plated in imaging-compatible 96-well plates and labeled with a red tumor marker, while expanded TILs are added at defined effector-to-target ratios in the presence of a caspase-3 activated green fluorescent substrate. Co-cultures are imaged every 4 h using a live-cell analysis system to capture phase-contrast and dual-fluorescence channels. Quantitative image analysis identifies red-positive tumor structures and calculates the proportion of red/green double-positive apoptotic tumor objects over time. Appropriate technical and biological replicates are incorporated, along with baseline, spontaneous apoptosis, negative and positive killing controls to ensure assay rigor. By preserving tumor heterogeneity within the PDTOs' three-dimensional architecture while enabling longitudinal quantification, this protocol provides a physiologically relevant system for functionally profiling patient-specific tumor-TIL interactions and investigating immunomodulatory agents that augment anti-tumor immunity.

Humans↗
PubMed2002

Characterization of CD4(+) CTLs ex vivo.

The cytotoxic potential of CD8(+) T cells and NK cells plays a crucial role in the immune response to pathogens. Although in vitro studies have reported that CD4(+) T cells are also able to mediate perforin-mediated killing, the in vivo existence and relevance of cytotoxic CD4(+) T cells have been the subject of debate. Here we show that a population of CD4(+) perforin(+) T cells is present in the circulation at low numbers in healthy donors and is markedly expanded in donors with chronic viral infections, in particular HIV infection, at all stages of the disease, including early primary infection. Ex vivo analysis shows that these cells have cytotoxic potential mediated through the release of perforin. In comparison with more classical CD4(+) T cells, this subset displays a distinct surface phenotype and functional profile most consistent with end-stage differentiated T cells and include Ag experienced CD4(+) T cells. The existence of CD4(+) cytotoxic T cells in vivo at relatively high levels in chronic viral infection suggests a role in the immune response.

CD4 Antigens↗
PubMed2006

Different neurotropic pathogens elicit neurotoxic CCR9- or neurosupportive CXCR3-expressing microglia.

What mechanism that determines microglia accomplishing destructive or constructive role in CNS remains nebulous. We report here that intracranial priming and rechallenging with Toxoplasma gondii in mice elicit neurotoxic CCR9+ Irg1+ (immunoresponsive gene 1) microglia, which render resistance to apoptosis and produce a high level of TNF-alpha; priming and rechallenging with lymphocytic choriomeningitis virus elicit neurosupportive CXCR3+ Irg1- microglia, which are sensitive to apoptosis and produce a high level of IL-10 and TGF-beta. Administration of CCR9 and/or Irg1 small interfering RNA alters the frequency and functional profiles of neurotoxic CCR9+ Irg1+ and neurosupportive CXCR3+ Irg1- microglia in vivo. Moreover, by using a series of different neurotropic pathogens, including intracellular parasites, chronic virus, bacteria, toxic substances, and CNS injury to intracranially prime and subsequent rechallenge mice, the bi-directional elicitation of microglia has been confirmed as neurotoxic CCR9+ Irg1+ and neurosupportive CXCR3+ Irg1- cells in these mouse models. These data suggest that there exist two different types of microglia, providing with a novel insight into microglial involvement in neurodegenerative and neuroinflammatory pathogenesis such as Alzheimer's disease and AIDS dementia.

Animals↗
PubMed2005

[Development and cell dynamics of PLCbeta2 positive cells in mouse taste buds].

Taste buds, the sensory end organs for the sense of taste, consist of taste sensing cells, supportive cells and basel cells. Taste bud cells are heterogeneous in terms of morphology as well as functional profiles. Although the lineage of mammalian taste bud cells is largely unknown, it is generally accepted that undifferentiated epithelial basal cells surrounding taste buds enter the taste buds to form and maintain this specialized corpuscle. To analyze taste bud formation during development, we conducted morphological observations and examined differentiation marker expression. Thickening of epithelia starts at 13 dpc foetus and immunohistochemistry against a neural marker, PGP 9.5, revealed that the change of epithelial morphology precedes neural projection observed at 14 dpc foetus. Taste sensing cells appear 6 days after birth indicated by expression of the single transduction component phospholipase Cbeta2 (PLCbeta2) as differentiation marker. To further investigate the maintenance and cell lineage in the taste buds in adults, we injected 5'bromo-2'deoxyuridine (BrdU) solution to young growing mice for a week. BrdU label retaining cells (LRCs) could be observed even 8 weeks after injection. LRCs were examined the differentiation by PLCbeta2 and proliferative activity by Ki-67. The results suggested two possibilities. (1) Part of PLCbeta2 positive cells retain proliferative activity and multipotentiality, or (2) precursor cells (stem cells) stay in the taste buds and produce at least part of the taste sensing cells through proliferation and differentiation processes.

Animals↗
PubMed1989

[Clinical study of a modified Stamey's endoscopic bladder neck suspension procedure for one hundred female patients with stress incontinence].

One hundred female patients with stress incontinence have been operated on by means of modified stamey's endoscopic bladder neck suspension procedure, i.e. quantifying the thread tension for bladder neck suspension. Twelve patients had 1,000 grams in the nylon loop, 5,800 grams, 9,700 grams, 25,600 grams and 49,400 grams. A follow-up period varied from 10 to 32 months (mean: 20.5 months). A 60-min pad-weighing test revealed urinary loss of 1.0 to 196.0 grams/hour (mean: 36.0) prior to operation. 1. The modified Stamey's procedure was successful in 95 patients (95%). The appropriate thread tension for bladder neck suspension was 400 grams. 2. Various complications were encountered: removal of unilateral nylon suture was necessitated in 2 patients, bleeding from operative wound in 2, bladder tamponade in 2, and clean intermittent catheterization for more than one month in 4. 3. Micturition parameters, i.e. maximum and average flow rates, temporarily got worse post-operatively. Maximum urethral closure pressure decreased and functional profile length elongated which were significantly different from those of pre-operative values. 4. Questionnaire sent to the patients revealed that 89 percent of them were satisfied with the operative results but 11 percent were not. 5. The modified Stamey's procedure is simple to perform and prevents over-tightness of nylon loops. We conclude that this operative method is the treatment of choice for correction of stress incontinence.

Adult↗
PubMed1991

[The urodynamic effects of an alpha 1-adrenoceptor agonist on the bladder and urethra of female dogs].

It has been known that alpha 1-adrenoceptors play an important role in urethral contraction. The incompetence of the urethral contraction is a cause of stress incontinence. We studied the urodynamic effects of a selective alpha 1-adrenoceptor agonist (midodrine hydrochloride) on the bladder and urethra of female dogs. Under anesthesia with intravenous chloralose, four doses (0.03, 0.1, 0.3 and 1.0 mg/kg) of midodrine were administered intravenously and urodynamic studies including cystometry, urethral pressure profilometry and electromyography (EMG) of the external urethral sphincter were performed. The administration of midodrine induced a significant increase of the maximum closing pressure in the proximal portion of the urethra (p less than 0.05 at 0.03 mg/kg and p less than 0.01 at 0.1, 0.3, 1.0 mg/kg). There were no significant changes in the functional profile length, the closing pressure at the external sphincters, the maximum bladder pressure, bladder capacity and bladder compliance. The administration of 0.3 mg/kg or more of midodrine produced a significant increase in the mean arterial blood pressure. After midodrine administration, transient increases in the external sphincter EMG activities were recognized. The activities showed the synergistic pattern during the bladder contractions. In conclusion, lower dose administration of a selective alpha 1-adrenoceptor agonist (midodrine) specifically produced an increase of the closing pressure in the proximal portion of the urethra without affecting blood pressure. These results suggest that midodrine is useful for the treatment of stress incontinence in humans.

Animals↗