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PubMed2001

Diagnostic exercise tests on 4000 consecutive men.

OBJECTIVE: Our purpose was to report the prevalence of abnormal treadmill test responses and their association with mortality in a large consecutive series of patients referred for standard diagnostic exercise tests, with testing performed and reported in a standardized fashion. BACKGROUND: Exercise testing is widely performed, but an analysis of responses has not been presented for a large number of consecutive tests performed on patients referred for diagnosis of cardiac disease. METHODS: All patients referred for evaluation at 2 university-affiliated Veterans Affairs Medical Centers who underwent exercise treadmill tests for clinical indications between 1987 and 2000 were determined to be dead or alive according to the Social Security Death Index after a mean 5.9-year follow-up. Patients with established heart disease (ie, prior coronary bypass surgery, myocardial infarction, or congestive heart failure) were excluded from analyses. Clinical and exercise test variables were collected prospectively according to standard definitions; testing and data management were performed in a standardized fashion with a computer-assisted protocol. All-cause mortality was used as the end point for follow-up. Standard survival analysis was performed, including Kaplan-Meier curves and a Cox hazard model. RESULTS: After the exclusions, 3974 men (mean age 57.5 +/- 11 years) had standard diagnostic exercise testing over the study period with a mean of 5.9 (+/-3.7) years of follow-up (64% of all tested). There were no complications of testing in this clinically referred population, 82% of whom were referred for chest pain, risk factors, or signs and symptoms of ischemic heart disease. Five hundred forty-nine (14%) had a history of typical angina. Indications for testing were in accordance with published guidelines. A total of 545 died, yielding an annual mortality rate of 1.8%. The Cox hazard model chose the following variables in rank order as independently associated with time to death: change in rate pressure product, age greater than 65 years, METs less than 5, and electrocardiographic left ventricular hypertrophy. A score based on these variables classified patients into low-, medium-, and high-risk groups. The high-risk group with a score greater than 3 has a hazard ratio of 4 (95% confidence interval 3.82-4.27) and an annual mortality rate of 4%. CONCLUSION: This comprehensive analysis provides rates of various abnormal responses that can be expected in men referred for diagnostic exercise testing at typical Veterans Administration Medical Centers. Four simple variables combined as a score predict all-cause mortality after clinical decisions for therapy are prescribed.

Aged↗
PubMed1993

Automatic and accurate method for analysis of proteins that undergo hinge-mediated domain and loop movements.

BACKGROUND: The structures of proteins that undergo significant main-chain conformational change are reported with increasing frequency. Three-dimensional atomic models are often available for two alternative conformational states of the same molecule. Inspection has shown these states to be varied in nature, arising by mechanisms that include hinge-facilitated closure between domains and smaller-scale loop motions within domains; these movements are often induced by metal ion binding or ligand binding. Polypeptides that display flexible segments are also observed in different crystal conformations or as alternatively packed subunits. Although subjective visual inspection has been previously used to compare structures and analyze conformational changes, there is a need for an objective method. RESULTS: We have developed a straightforward, robust, and objective algorithm that can locate the residues that mediate and participate in the changes between the two conformational states. Our method does not require initial superpositioning. We illustrate the method by considering several test cases. The first example is maltose binding protein, a polypeptide that exhibits rigid-body domain closure involving multiple hinges. The second is lactate dehydrogenase, which undergoes both loop and subdomain movement; we accurately describe the location and relative magnitude of these deformations. Finally, in the example of aspartate transcarbamoylase, both hinge-mediated domain movement and functionally relevant loop rearrangements are described. In the instances in which domain closure occurs, the residues that serve as hinges between the domains involved are accurately predicted. In addition, our technique successfully identifies the exact residues that undergo intra-domain loop movements, even for movements that are accompanied by larger scale inter-domain rearrangements. CONCLUSIONS: Our algorithm is successful in its comprehensive analysis and description of complex hinge-mediated domain motion for all structures displaying rigid-body movement and is accurate in identifying the location of any independent intra-domain rearrangements.

Journal Article↗
PubMed1997

Spinal cord neuropathology in rat experimental autoimmune encephalomyelitis: modulation by oral administration of myelin basic protein.

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) in which clinical neurological signs and histopathologic changes of disease can be suppressed by feeding CNS myelin proteins. Using immunohistochemistry and image analysis, the cellular immune response was quantified over the rostral-caudal axis of the spinal cord in rats with EAE and in animals fed high- or low-dose myelin basic protein (MBP) prior to inducing EAE (tolerized animals). In a subset of rats, MBP was fed 9 days after MBP immunization to examine the effect of oral tolerance on the progression of CNS pathology. In unfed rats or rats fed vehicle only, activated microglia and macrophages were co-localized with T-lymphocytes throughout the spinal cord, but greater cellular reactions were evident in gray matter relative to white matter. In all tolerized animals, the CNS inflammatory response was reduced relative to controls. Subtle pathologic changes were occasionally observed in the CNS of MBP-fed animals, but the distribution of inflammatory cells in the dorso-ventral axis was more polarized in animals fed high-dose MBP. In this group, more T-cells and activated microglia were present in the dorsal spinal cord, specifically in the gray matter. In the group fed MBP after disease induction, clinical disease progressed as in control non-fed rats, but recovery from disease appeared to be accelerated. Thus, the results presented here provide a comprehensive analysis of the distribution and magnitude of inflammatory cells within the spinal cord in EAE and challenge the theory that MBP-induced EAE is only a white matter disease. These data also describe how the activation and distribution of immune effector cells is altered by oral tolerance and may help predict a range of neurological deficits not previously appreciated in EAE, particularly those effected by gray matter pathology.

Administration, Oral↗
PubMed2005

Acellular dermal matrix for mucogingival surgery: a meta-analysis.

BACKGROUND: Many clinical studies revealed the effectiveness of acellular dermal matrix (ADM) in the treatment of mucogingival defects. The purpose of this meta-analysis was to compare the efficacy of ADM-based root coverage (RC) and ADM-based increase in keratinized tissues to other commonly used mucogingival surgeries. METHODS: Meta-analysis was limited to randomized clinical trials (RCT). Articles from January 1, 1990 to October 2004 related to ADM were searched utilizing the MEDLINE database from the National Library of Medicine, the Cochrane Oral Health Group Specialized Trials Registry, and through hand searches of reviews and recent journals. Relevant studies were identified, ranked independently, and mean data from each were weighted accordingly. Selected outcomes were analyzed using a meta-analysis software program. The significant estimates of the treatment effects from different trials were assessed by means of Cochrane's test of heterogeneity. RESULTS: 1) Few RCT studies were found to compile the data. In summary, selection identified eight RCT that met the inclusion criteria. There were four studies comparing ADM versus a connective tissue graft for root coverage procedures, two studies comparing ADM versus coronally advanced flap (CAF) for root coverage procedures, and two studies comparing ADM to free gingival graft in augmentation of keratinized tissue. 2) There were no statistically significant differences between groups for any of the outcomes measured (recession coverage, keratinized tissue formation, probing depths, and clinical attachment levels). 3) The majority of the analyses demonstrated moderate to high levels of heterogeneity. 4) Considering the heterogeneity values found among the studies, certain trends could be found: a) three out of four studies favored the ADM-RC group for recession coverage; b) a connective tissue graft tended to increase keratinized tissue compared to ADM (0.52-mm difference; P = 0.11); c) there were trends of increased clinical attachment gains comparing ADM to CAF procedures (0.56-mm difference; P = 0.16). CONCLUSIONS: Differences in study design and lack of data precluded an adequate and complete pooling of data for a more comprehensive analysis. Therefore, considering the trends presented in this study, there is a need for further randomized clinical studies of ADM procedures in comparison to common mucogingival surgical procedures to confirm our findings. It is difficult to draw anything other than tentative conclusions from this meta-analysis of ADM for mucogingival surgery, primarily because of the weakness in the design and reporting of existing trials.

Biocompatible Materials↗
PubMed2002

Investigation of penetratin peptides. Part 1. The environment dependent conformational properties of penetratin and two of its derivatives.

The homeodomain, the DNA-binding domain of Antennapedia homeoprotein, is composed of three alpha-helices and one beta-turn between helices II and III. Its third helix from the N-terminal (helix III) can translocate through the cell membrane into the nucleus and can be used as an intracellular vehicle for the delivery of oligopeptides and oligonucleotides. To the best of our knowledge, this helix III, called penetratin, which consists of 16 amino acids, is internalized by cells in a specific, non-receptor-mediated manner. For a better understanding of the mechanism of the transfer, the structure of penetratin was examined in both extracellular matrix-mimetic and membrane-mimetic environments: 1H-NMR and CD spectroscopic measurements were performed in mixtures of TFE/water with different ratios. The molecular conformations of two analogue peptides [(6,14-Phe)-penetratin and a 12 amino acid penetratin derivative (peptide 3)] were also studied. An atomic level comprehensive analysis of penetratin and its two analogues was performed. In a membrane-mimetic solvent system (TFEd2/water = 9: 1), on the basis of 553 distance restraints, the 4-12 region of penetratin exhibits a bent, irregular helical structure on NMR examination. Interactions between hydrophobic amino acid residues in conjunction with H-bonds stabilize the secondary structure of the molecule. Thus, both derivatives adopt a helix-like conformation. However, while (6,14-Phe)-penetratin displays both alpha-helical and 310-helical features, the structure of peptide 3 is predominantly a 310-helix. Of the three peptides, surprisingly (6,14-Phe)-penetratin has the largest helical content. An increase in the polarity of the molecular environment gradually disintegrates these helix-like secondary structures. In a highly aqueous molecular system (TFEd2/water = 1 : 9), the fast exchange of multiple conformers leads to too few distance restraints being extracted, therefore the NMR structures can no longer be determined. The NMR data show that only short-range order can be traced in these peptides. Under these conditions, the molecules adopt nascent helix-like structures. On the other hand, CD spectra could be recorded at any TFE/water ratio and the conformational interconversion could therefore be monitored as a function of the polarity of the molecular environment. The CD data were analysed comprehensively by the quantitative deconvolution method (CCA+). All three penetratin peptides display helical conformational features in a low dielectric medium, with significant differences as a function of their amino acid composition. However, these conformational features are gradually lost during the shift from an apolar to a polar molecular environment.

Amino Acid Sequence↗
PubMed2004

First assessment of the PM10 and PM2.5 particulate level in the ambient air of Belgrade city.

INTENTION, GOAL, SCOPE, BACKGROUND: As the strong negative health effect of exposure to the inhalable particulate matter PM10 in the urban environment has been confirmed, the study of the mass concentrations, physico-chemical characteristics, sources, as well as spatial and temporal variation of atmospheric aerosol particles becomes very important. OBJECTIVE: This work is a pilot study to assess the concentration level of ambient suspended particulate matter, with an aerodynamic diameter of less than 10 microm, in the Belgrade central urban area. Average daily concentrations of PM10 and PM2.5 have been measured at three representative points in the city between June 2002 and December 2002. The influence of meteorological parameters on PM10 and PM2.5 concentrations was analyzed, and possible pollution sources were identified. METHODS: Suspended particles were collected on Pure Teflon filters by using a Mini-Vol low-volume air sampler (Airmetrics Co., Inc.; 5 l min(-1) flow rate). Particle mass was determined gravimetrically after 48 h of conditioning in a desiccator, in a Class 100 clean room at the temperature T = 20 degrees C and at about 50% constant relative humidity (RH). RESULTS AND DISCUSSION: Analysis of the PM10 data indicated a marked difference between season without heating--(summer; mean value 56 microg m(-3)) and heating season--(winter; mean value 96 microg m3); 62% of samples exceeded the level of 50 microg m(-3). The impact of meteorological factors on PM concentrations was not immediately apparent, but there was a significant negative correlation with the wind speed. CONCLUSIONS: The PM10 and PM2.5 mass concentrations in the Belgrade urban area had high average values (77 microg m(-3) and 61 microg m(-3)) in comparison with other European cities. The main sources of particulate matter were traffic emission, road dust resuspension, and individual heating emissions. When the air masses are coming from the SW direction, the contribution from the Obrenovac power plants is evident. During days of exceptionally severe pollution, in both summer and winter periods, high production of secondary aerosols occurred, as can be seen from an increase in PM2.5 in respect to PM10 mass concentration. RECOMMENDATION AND OUTLOOK: The results obtained gave us the first impression of the concentration level of particulate matter, with an aerodynamic diameter of less than 10 microm, in the Belgrade ambient air. Due to measured high PM mass concentrations, it is obvious that it would be very difficult to meet the EU standards (EEC 1999) by 2010. It is necessary to continue with PM10 and PM2.5 sampling; and after comprehensive analysis which includes the results of chemical and physical characterization of particles, we will be able to recommend effective control measures in order to improve air quality in Belgrade.

Aerosols↗
PubMed2001

Clinical and exercise test predictors of all-cause mortality: results from > 6,000 consecutive referred male patients.

OBJECTIVE: To report the prevalence of abnormal treadmill test responses and their association with mortality in a large consecutive series of patients referred for standard exercise tests, with testing performed and reported in a standardized fashion. BACKGROUND: Exercise testing is widely performed, but few databases exist of large numbers of consecutive tests performed on patients referred for routine clinical purposes using standardized methods. Even fewer of the available databases have information regarding all-cause mortality as an outcome. METHODS: All patients referred for evaluation at two university-affiliated Veterans Affairs medical centers who underwent exercise treadmill testing for clinical indications between 1987 and 2000 were determined to be dead or alive using the Social Security death index after a mean 6.2 years (median, 7 years) of follow-up. Clinical and exercise test variables were collected prospectively according to standard definitions; testing and data management were performed in a standardized fashion using a computer-assisted protocol. All-cause mortality was utilized as the end point for follow-up. Standard survival analysis was performed, including Kaplan-Meier curves and a Cox hazard model. RESULTS: There were 6,213 male patients (mean +/- SD age, 59 +/- 11 years) who underwent standard exercise ECG treadmill testing over the study period with a mean follow-up duration of 6.2 +/- 3.7 years. There were no complications of testing in this clinically referred population, 78% of whom were referred for chest pain, or risk factors or signs or symptoms of ischemic heart disease. Overlapping thirds had typical angina or history of myocardial infarction (MI). Five hundred seventy-nine patients had prior coronary artery bypass surgery, and 522 patients had a history of congestive heart failure (CHF). Indications for testing were in accordance with published guidelines. Twenty percent died over the follow-up period, for an average annual mortality rate of 2.6%. Cox hazard function chose the following variables in rank order as independently and significantly associated with time to death: exercise capacity (metabolic equivalents < 5, age > 65 years, history of CHF, and history of MI. A score based on these variables (summing up the four variables [if yes = 1 point]) classified patients into low-risk, medium-risk, and high-risk groups. The high-risk group (score > or = 3) has a hazard ratio of 5.0 (95% confidence interval, 4.7 to 5.3) and a 5-year mortality rate of 31%. CONCLUSION: This comprehensive analysis provides rates of various abnormal responses that can be expected in patients referred for exercise testing at a typical medical center. Four simple variables combined as a score powerfully stratified patients according to prognosis.

Aged↗
PubMed1997

Quantitative evaluation of regional myocardial perfusion using fast X-ray computed tomography.

Clinical quantitation of regional myocardial perfusion using a minimally invasive and easily applied technique could allow for ready quantitation of the functional significance of coronary disease, allow for further understanding of flow reserve in various cardiomyopathic and hemodynamic overload (pressure versus volume) conditions, and possibly provide basic information needed regarding the development and clinical significance of coronary collateral vessels and diseases of the myocardial microcirculation. Electron beam CT (EBCT) is a unique cardiac imaging modality that allows for rapid acquisition tomographic slices of the heart with excellent spatial resolution. It has been demonstrated to provide accurate measurements of cardiac anatomy, biventricular function, myocardial mass, and estimates of mural atherosclerotic plaque burden via quantification of coronary calcium. The application of classical indicator techniques for use by fast x-ray computed tomography techniques such as electron beam CT has been shown to allow quantitative analysis of regional myocardial perfusion throughout the myocardium. Initial studies using central intravenous contrast injection in experimental animals showed a close correlation of regional myocardial perfusion as quantitated by electron beam CT with measurements using radiolabeled microspheres at resting and moderately increased flow states. At high flow states, however, electron beam CT significantly underestimated absolute myocardial perfusion and thus myocardial flow reserve. Using another fast CT device, the Dynamic Spatial Reconstructor (DSR), concepts of intramyocardial vascular blood volume and its relation to myocardial flow have been established. By adapting these concepts to electron beam CT scanning and accounting for the increase in intramyocardial vascular blood volume at vasodilatation, the ability to correctly quantitate perfusion states up to approximately 400 mL.min-1. 100 g-1 using central intravenous contrast administration was demonstrated. This implies that studies can be done with intravenous injection methods for characterization of regional myocardial perfusion up to the normal flow reserve of approximately 4:1. Important physiologic and clinical abnormalities in flow reserve generally result in a ratio < 3:1. Electron beam CT offers the capability to quantitate regional myocardial perfusion in both the clinical and research setting. Of particular interest is the ability to provide quantitative regional myocardial perfusion which can be coupled to the evaluation of cardiac anatomy and function as well as mural coronary atherosclerotic calcium burden during the same scanning session. Thus, electron beam CT has the potential to become a valuable, minimally invasive clinical tool for comprehensive analysis of cardiac function and coronary status.

Cardiomyopathies↗
PubMed2006

Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomized trials.

CONTEXT: Adverse effects of selective cyclooxygenase 2 (COX-2) inhibitors on renal events and arrhythmia have been controversial, with suggestions of a class effect. OBJECTIVE: To quantitatively evaluate adverse risks of renal events (renal dysfunction, hypertension, and peripheral edema) and arrhythmia events and to explore drug class effects and temporal trends of apparent effects of the COX-2 inhibitors: rofecoxib, celecoxib, valdecoxib, parecoxib, etoricoxib, and lumiracoxib. DATA SOURCES: A systematic search of EMBASE and MEDLINE (through June 2006), bibliographies, US Food and Drug Administration reports, and pharmaceutical industry clinical trial databases. STUDY SELECTION: From relevant reports, 114 randomized double-blind clinical trials were included. DATA EXTRACTION: Information on publication year, participant characteristics, trial duration, drug, control, dose, and events were extracted using a standardized protocol. DATA SYNTHESIS: Results were pooled via random-effects models and meta-regressions. Of 116 094 participants from 114 trial reports including 127 trial populations (40 rofecoxib, 37 celecoxib, 29 valdecoxib + parecoxib, 15 etoricoxib, and 6 lumiracoxib), there were a total of 6394 composite renal events (2670 peripheral edema, 3489 hypertension, 235 renal dysfunction) and 286 arrhythmia events. Results indicated significant heterogeneity of renal effects across agents (P for interaction = .02), indicating no class effect. Compared with controls, rofecoxib was associated with increased risk of arrhythmia (relative risk [RR], 2.90; 95% confidence interval [CI], 1.07-7.88) and composite renal events (RR, 1.53; 95% CI, 1.33-1.76); adverse renal effects increased with greater dose and duration (both P< or =.05). For all individual renal end points, rofecoxib was associated with increased risk of peripheral edema (RR, 1.43; 95% CI, 1.23-1.66), hypertension (RR, 1.55; 95% CI, 1.29-1.85), and renal dysfunction (RR, 2.31; 95% CI, 1.05-5.07). In contrast, celecoxib was associated with lower risk of both renal dysfunction (RR, 0.61; 95% CI, 0.40-0.94) and hypertension (RR, 0.83; 95% CI, 0.71-0.97) compared with controls. Other agents were not significantly associated with risk. Time-cumulative analyses indicated that for rofecoxib the adverse risks for peripheral edema and hypertension were evident by the end of year 2000 and for risk of arrhythmia by 2004. CONCLUSIONS: In this comprehensive analysis of 114 randomized trials with 116,094 participants, rofecoxib was associated with increased renal and arrhythmia risks. A COX-2 inhibitor class effect was not evident. Future safety monitoring is warranted and may benefit from an active and continuous cumulative surveillance system.

Arrhythmias, Cardiac↗
PubMed2006

A new toxin from the sea anemone Condylactis gigantea with effect on sodium channel inactivation.

A new peptide toxin exhibiting a molecular weight of 5043Da (av.) and comprising 47 amino acid residues was isolated from the sea anemone Condylactis gigantea. Purification of the peptide was achieved by a multistep chromatographic procedure monitoring its strong paralytic activity on crustacea (LD(50) approx. 1microg/kg). Complete sequence analysis of the toxic peptide revealed the isolation of a new member of type I sea anemone sodium channel toxins containing the typical pattern of the six cysteine residues. From 11kg of wet starting material, approximately 1g of the peptide toxin was isolated. The physiological action of the new toxin from C. gigantea CgNa was investigated on sodium currents of rat dorsal root ganglion neurons in culture using whole-cell patch clamp technique (n=60). Under current clamp condition (CgNa) increased action potential duration. This effect is due to slowing down of the TTX-S sodium current inactivation, without modifying the activation process. CgNa prolonged the cardiac action potential duration and enhanced contractile force albeit at 100-fold higher concentrations than the Anemonia sulcata toxin ATXII. The action on sodium channel inactivation and on cardiac excitation-contraction coupling resemble previous results with compounds obtained from this and other sea anemones [Shapiro, B.I., 1968. Purification of a toxin from tentacles of the anemone C. gigantea. Toxicon 5, 253-259; Pelhate, M., Zlotkin, E., 1982. Actions of insect toxin and other toxins derived from the venom of scorpion Androtonus australis on isolated giant axons of the cockroach Periplaneta americana. J. Exp. Biol. 97, 67-77; Salgado, V., Kem, W., 1992. Actions of three structurally distinct sea anemone toxins on crustacean and insect sodium channels. Toxicon 30, 1365-1381; Bruhn, T., Schaller, C., Schulze, C., Sanchez-Rodriquez, J., Dannmeier, C., Ravens, U., Heubach, J.F., Eckhardt, K., Schmidtmayer, J., Schmidt, H., Aneiros, A., Wachter, E., Béress, L., 2001. Isolation and characterization of 5 neurotoxic and cardiotoxic polypeptides from the sea anemone Anthopleura elegantissima. Toxicon, 39, 693-702]. Comprehensive analysis of the purified active fractions suggests that CgNa may represent the main peptide toxin of this sea anemone species.

Amino Acid Sequence↗
PubMed2004

Moxifloxacin and glucose homeostasis: a pooled-analysis of the evidence from clinical and postmarketing studies.

BACKGROUND: Recently, clinical data has emerged suggesting that the fluoroquinolone, gatifloxacin, can affect glucose homeostosis through an unknown mechanism. In order to explore the potential effects of moxifloxacin on glucose metabolism in humans, a pooled analysis of phase II/III clinical trials and postmarketing studies was performed and compared with results from an investigation in laboratory animals. METHODS: A pooled analysis of 30 (26 controlled, 4 uncontrolled) oral and two intravenous/oral prospective, controlled phase II/III moxifloxacin studies was performed to evaluate the frequency of hyper- and hypoglycaemic episodes and glucose-related adverse events and adverse reactions (i.e. those considered to be drug related) versus comparator antimicrobials (penicillins, cephalosporins, macrolides, doxycycline, fluoroquinolones). Similar evaluations were conducted on data pooled from five postmarketing surveillance studies. In addition, potential effects of supratherapeutic doses of moxifloxacin on blood glucose and plasma insulin levels in fed and fasted rats were assessed in comparison with those of gatifloxacin, levofloxacin and glibenclamide (glyburide). RESULTS: The phase II/III database was comprised of 14,731 patients (8474 moxifloxacin, 6257 comparator antimicrobial). There were no drug-related hypoglycaemic adverse events reported for moxifloxacin in either the oral or intravenous/oral database. Two drug-related hypoglycaemic adverse events were reported in the oral comparator group, both following administration of levofloxacin and both of mild severity; one drug-related hypoglycaemic adverse event was reported in the intravenous/oral comparator group after trovafloxacin administration. Drug-related hyperglycaemic adverse events were reported in seven (<0.1%) moxifloxacin and 1 (<0.1%) comparator-treated patients in the oral study database, none of these cases were considered serious and six of the seven moxifloxacin cases were graded as mild and required no countermeasures. There were no cases of drug-related hyperglycaemic events in any patient enrolled in the intravenous/oral studies. Coadministration of oral antidiabetic drugs with moxifloxacin or comparator antimicrobials did not change the rate of blood glucose increases or decreases in diabetic patients. Data from five moxifloxacin postmarketing studies (46 130 subjects) reported no episodes of hypoglycaemia and two non-drug-related hyperglycaemic episodes. Data from animal studies revealed that supratherapeutic doses of moxifloxacin and levofloxacin did not affect blood glucose or plasma insulin levels in both fed and fasted rats, whereas gatifloxacin decreased both blood glucose and plasma insulin in a dose-dependent manner in fed rats only. The reference compound glibenclamide increased insulin and decreased glucose levels as expected. CONCLUSIONS: Hyperglycaemic or hypoglycaemic adverse reactions were reported rarely in studies with oral or sequential intravenous/oral moxifloxacin, and incidence was comparable in moxifloxacin and comparator groups. Changes in glucose metabolism were also similar in diabetic patients treated with moxifloxacin compared with those patients without diabetes mellitus. This comprehensive analysis of the datapool for moxifloxacin phase II/III clinical trials and postmarketing studies suggests that moxifloxacin administration has no clinically relevant effect on blood glucose homeostasis.

Animals↗
PubMed2004

Ocular emergencies.

OBJECTIVE: To describe clinical data about ocular emergencies (OE) and their management. DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: This study was conducted from 1st January, 2000 to 31st December, 2002 at the Department of Ophthalmology, Khyber institute of Ophthalmic Medical Sciences, Lady Reading Hospital, Peshawar. MATERIAL AND METHODS: A comprehensive analysis of the computer record available for admitted ocular emergencies was undertaken in terms of gender, age, etiology, procedure performed and hospital stay. RESULTS: Ocular emergencies (1961) were 18.49% of total admissions. Male to female ratio was 2:1. Non-traumatic ocular emergencies were 1058 (53.95%) with male to female ratio of 1.47:1. In the non-traumatic ocular emergencies, majority (67.2%) were 40 years or above. Traumatic ocular emergencies were 925 (47.16%) with male to female ratio of 2.77:1. Majority (83.78%) of traumatic ocular emergencies were below 40 years and 562 (60.75%) below 20 years of age. Only 150 (16.21%) cases were 40 years and above. Corneal ulcers (44.51%) and glaucoma (24.38%) were the most common non-traumatic ocular emergencies, whereas, open globe injuries (73.4%) were leading the traumatic ocular emergencies. Total surgical procedures performed were 1382 (13.7% of total major ophthalmic surgery). Average stay in hospital was 5.5 days. CONCLUSION: Ocular emergencies predominantly affected the males in this series. Trauma related OE are almost as common as non-traumatic. Majority of OE need surgical intervention and the average hospital stay is longer than routine admissions.

Adult↗
PubMed1994

The family physician and industrial hygiene.

Family physicians are increasingly being called on to become involved in the health care of workers in local industries. Many family physicians are the sole providers of occupational health care in their communities, yet their formal training is usually deficient in some of the more specialized aspects of occupational medicine. Treating work-related injuries and exposures to hazardous substances may require analyses of work sites that many family physicians have neither the time nor the expertise to perform adequately. Industrial hygienists are the consultants who are qualified to assess potential occupational hazards and are trained to perform a comprehensive analysis of the work environment as it relates to worker health. This analysis may include the measurement of potentially hazardous substances, such as ambient air concentrations of particulate matter and toxic gases, and recommendations for prevention of exposures. Two cases are presented to illustrate how valuable a consultation with an industrial hygienist can be to the family physician.

Agriculture↗
PubMed2000

Marked declines in human immunodeficiency virus-related mortality in Chicago in women, African Americans, Hispanics, young adults, and injection drug users, from 1995 through 1997.

BACKGROUND: Declines in human immunodeficiency virus (HIV)-related mortality between 1995 and 1996 were seen across the United States but were small to nonexistent among people in marginalized sectors who are most likely to contract HIV and die of its effects. No comprehensive analysis describing HIV-related mortality in 1997 was available. OBJECTIVE: To describe Chicago's HIV-related mortality trends up to and including 1997, with specific attention focused on marginalized populations. METHODS: An analysis of cross-sectional HIV-related mortality data with emphasis on the years 1995 through 1997 was conducted for Chicago, Ill. Numbers, proportions, and rates of declines in HIV-related deaths were examined for the city as a whole and also among those diagnosed at Cook County Hospital, as a proxy for people with very low socioeconomic status. RESULTS: Between 1995 and 1996 there was an overall decline of 19% in HIV-related mortality in Chicago but small or no declines among women, African Americans, Hispanics, injection drug users, and people aged 20 to 29 years and more than 50 years. Between 1995 and 1997 there was an overall decline of 61%. At that time the declines were spread more evenly across diverse groups. There were almost no significant differences between the declines for these groups at Cook County Hospital and in the rest of Chicago. CONCLUSIONS: The HIV-related mortality has fallen dramatically in Chicago since 1995, the year of its maximum. During 1997, declines were seen among all groups. Declines were also seen among the most disenfranchised of the city. Access to care and the new combination therapies are apparently sustaining life for many in Chicago.

Adult↗
PubMed1991

Clinical correlates of response to botulinum toxin injections.

We studied 242 patients with cervical dystonia who had adequate follow-up after botulinum toxin injections to determine which clinical variables had a predictive value in the treatment outcome. Twenty-one patients (16%) categorized as nonresponders were compared with 113 patients (47%) considered to be definite responders. On average, the nonresponders had symptoms for 14 years longer than responders. Seventy-eight of 100 patients with complications were female compared with 54% of 190 patients without complications. In addition, patients with complications weighed less than those without complications. Both findings suggest that the occurrence of complications is related to smaller mean neck muscle mass. Botulinum toxin antibodies were detected in 35.7% of the nonresponders tested and in none of the responders. This comprehensive analysis of outcome variables leads us to conclude that patients with a long duration of dystonia before their first botulinum toxin injection respond less well than those with a short duration of symptoms, that some patients lose their responsiveness because of the development of blocking antibodies, and that women are more likely to develop complications, such as dysphagia and neck weakness, than are men.

Adolescent↗
PubMed1999

Quality assurance in molecular genetic testing laboratories.

CONTEXT: Specific regulation of laboratories performing molecular genetic tests may be needed to ensure standards and quality assurance (QA) and safeguard patient rights to informed consent and confidentiality. However, comprehensive analysis of current practices of such laboratories, important for assessing the need for regulation and its impact on access to testing, has not been conducted. OBJECTIVE: To collect and analyze data regarding availability of clinical molecular genetic testing, including personnel standards and laboratory practices. DESIGN: A mail survey in June 1997 of molecular genetic testing laboratory directors and assignment of a QA score based on responses to genetic testing process items. SETTING: Hospital-based, independent, and research-based molecular genetic testing laboratories in the United States. PARTICIPANTS: Directors of molecular genetic testing laboratories (n = 245; response rate, 74.9%). MAIN OUTCOME MEASURE: Laboratory process QA score, using the American College of Medical Genetics Laboratory Practice Committee standards. RESULTS: The 245 responding laboratories reported availability of testing for 94 disorders. Personnel qualifications varied, although all directors had doctoral degrees. The mean QAscore was 90% (range, 44%-100%) with 36 laboratories (15%) scoring lower than 70%. Higher scores were associated with test menu size of more than 4 tests (P = .01), performance of more than 30 analyses annually (P = .01), director having a PhD vs MD degree (P = .002), director board certification (P = .03), independent (P <.001) and hospital (P = .01) laboratories vs research laboratory, participation in proficiency testing (P<.001), and Clinical Laboratory Improvement Amendment certification (P = .006). Seventy percent of laboratories provided access to genetic counseling, 69% had a confidentiality policy, and 45% required informed consent prior to testing. CONCLUSION: The finding that a number of laboratories had QA scores that may reflect suboptimal laboratory practices suggests that both personnel qualification and laboratory practice standards are most in need of improvement to ensure quality in clinical molecular genetic testing laboratories.

Certification↗
PubMed2000

Unique frequency of known mutations in Brazilian MPS I patients.

The frequency of 10 known mutations in the IDUA gene-Q70X, A75T, H82P, R89Q, 678-7 g-->a, L218P, A327P, R383H, W402X, and P533R-was estimated in a group of 24 index cases with mucopolysaccharidosis type I. Three affected relatives were also analysed. Six of the 10 mutations screened were present in our patients (Q70X, R89Q, A327P, R383H, W402X, and P533R). These mutations account for 54% of the alleles; 37% of the genotypes were defined. Frequencies of these mutations are markedly different from those in the literature. A novel combination Q70X/A327P is described. This was the first time Brazilian MPS I patients were analysed with molecular techniques. The low frequency of common mutations indicates that a more comprehensive analysis of the IDUA gene should be done to delineate the mutation profile of MPS I better in our population.

Brazil↗
PubMed1998

Entorhinal cortex of the rat: organization of intrinsic connections.

Two sets of experiments were carried out to examine the organization of associational connections within the rat entorhinal cortex. First, a comprehensive analysis of the areal and laminar distribution of intrinsic projections was performed by using the anterograde tracers Phaseolus vulgaris-leuocoagglutinin (PHA-L) and biotinylated dextran amine (BDA). Second, retrograde tracers were injected into the dentate gyrus and PHA-L and BDA were injected into the entorhinal cortex to determine the extent to which entorhinal neurons that project to different septotemporal levels of the dentate gyrus are linked by intrinsic connections. The regional distribution of intrinsic projections within the entorhinal cortex was related to the location of the cells of origin along the mediolateral axis of the entorhinal cortex. Cells located in the lateral regions of the entorhinal cortex gave rise to intrinsic connections that largely remained within the lateral reaches of the entorhinal cortex, i.e., within the rostrocaudally situated entorhinal band of cells that projected to septal levels of the dentate gyrus. Cells located in the medial regions of the entorhinal cortex gave rise to intrinsic projections confined to the medial portion of the entorhinal cortex. Injections made into mid-mediolateral regions of the entorhinal cortex mainly gave rise to projections to mid-mediolateral levels, although some fibers did enter either lateral or medial portions of the entorhinal cortex. These patterns were the same regardless of whether the projections originated from the superficial (II-III) or deep (V-VI) layers of the entorhinal cortex. This organizational scheme indicates, and our combined retrograde/anterograde labeling studies confirmed, that laterally situated entorhinal neurons that project to septal levels of the dentate gyrus are not in direct communication with neurons projecting to the temporal portions of the dentate gyrus. These results suggest that entorhinal intrinsic connections allow for both integration (within a band) and segregation (across bands) of entorhinal cortical information processing.

Amidines↗