Comparison of results of nocturnal penile tumescence and rigidity in a sleep laboratory versus a portable home monitor

OBJECTIVES: To validate the results of the home penile tumescence monitor versus the sleep laboratory studies of erectile function. METHODS: We used both methods to study 18 episodes of rigidity and 19 episodes of tumescence in 10 subjects with erectile dysfunction before and after the use of an experimental vasodilating medication. RESULTS: The tumescence measurement in the sleep laboratory compared favorably with the changes in tumescence with the RigiScan portable home monitor: at the base (r = 0.70; P < 0.001), and at the tip (r = 0.84; P < 0.001). In measuring rigidity, the buckling pressure in the sleep laboratory compared favorably with the RigiScan measurements of percent average rigidity at the base (r = 0.56; P = 0.017), at the tip (r = 0.62; P = 0.006), and mean rigidity of the base and tip (r = 0.64; P = 0.004). In a comparison of the buckling pressure with the new RigiScan Plus quantitative program, there was good correlation with the rigidity activity units at the base (r = 0.70; P = 0.001) and at the tip (r = 0.72; P < 0.001). A clinical estimate of penetrable rigidity correlates with the RigiScan base rigidity of 55% to 60% and tip rigidity of about 50%. CONCLUSIONS: The portable home monitor is a viable and cost-effective clinical tool to measure nocturnal penile activity.     

Poly(ADP-ribose) polymerase gene expression status and genomic instability in human breast cancer

OBJECTIVE: To compare point-of-care results obtained from an on-site hemocytometer with values provided by an institutional laboratory instrument. DESIGN: A prospective laboratory evaluation. SETTING: The central laboratory and cardiac surgical intensive care unit of a university-affiliated tertiary care center. PATIENTS: Normal range comparison was performed using blood specimens routinely obtained from 48 hospitalized patients for complete blood count analysis. The second evaluation was performed on blood specimens routinely obtained (in the intensive care unit) after cardiac surgery involving extracorporeal circulation in a series of 187 consecutive patients. MEASUREMENTS AND MAIN RESULTS: Hemoglobin concentration, platelet count, mean corpuscular volume, mean platelet volume, and red and white blood cell counts were measured with both on-site (MD 16, Coulter Electronics, Hialeah, FL) and laboratory (STKS, Coulter Electronics) instruments. Hematocrit and red cell distribution width were calculated using measured variables. Blood specimens were obtained from two distinct patients series. To evaluate measurement values within the normal range, a series of 48 routinely obtained blood specimens for complete blood count analysis in our institutional laboratory were utilized for concurrent analysis with the on-site hemocytometer. To evaluate measurement values out of the normal range, a second comparison involved measurements performed on blood specimens obtained in the cardiac surgical intensive care unit for complete blood count analysis. Linear regression demonstrated good correlations between on-site and laboratory hemoglobin concentration (r2 = .97), hematocrit (r2 = .95), platelet count (r2 = .97), mean corpuscular volume (r2 = .91), red cell distribution width (r2 = .80), and red (r2 = .95) and white (r2 = .96) blood cell count results. A marginal correlation was observed between mean platelet volume values (r2 = .47). Bias analysis (mean +/- 2 SD) demonstrated similar measurements between on-site and laboratory hemoglobin concentration, hematocrit, platelet count, red blood cell count, white blood cell count, mean platelet volume, mean corpuscular volume, and red cell distribution width. CONCLUSIONS: On-site hemoglobin concentration, hematocrit, white blood cell count, red blood cell count, red cell distribution width, and platelet count values compare well with those results obtained from the laboratory. The MD 16 hemocytometer (Coulter Electronics) provides on-site hematologic results that can provide an accurate and rapid quantitative assessment of platelets, and red and white blood cells. Rapid access to information obtained from this type of system may be clinically useful, especially in critically ill patients.     

Evaluation of the Cell-DYN 35))

The Cell-Dyn 3500 is an automated haematology analyzer which quantitatively measures and computes haematological quantities including a full "five-part" white cell differential. It measures 22 parameters for erythrocytes, white blood cells and platelets, also giving the respective histograms. Evaluation of the Cell-Dyn 3500 was performed according to the International Committee for Standardization in Haematology (ICSH) norms, for a period of 5 weeks. A total of 1,235 samples were studied by comparison with the Coulter MaxM. The five-part white cell differential and the flagging system were estimated and compared with the smear examination of 506 samples, by four clinical pathologists trained in cytology. Good correlation was obtained within, between batches, and day-to-day, for the following parameters: red blood cells (RBC), haemoglobin (HGB), mean cell volume (MCV), white blood cells (WBC) and platelets (PLT). The accuracy was estimated (RBC, HGB, VGM, WBC and PLT) each day with three different levels of titrated controls with good results. The linearity was established for RBC, HGB, WBC and PLT. The results obtained were good. Carry-over studies were performed according to the Broughton method for the same parameters and the results were also good. Stability studies for the automatic parameters including the differential white blood cell count showed that these parameters were stable at 4 degrees C for 48 hours. At room temperature the stability was reduced to 7 hours. Agreement was good between the Cell-Dyn 3500 and the Coulter MaxM, for the automatic haemocytometric values. The comparative studies between the five-part white cell differential of the haematologic analyzer and the manual differential showed excellent results for neutrophils and lymphocytes, very good for monocytes and eosinophils. For the flag estimation two criteria were established, one based on the clinical significance and the other based on the alarm detection described in the analyzer manual. The specificity was good for both criteria. In general the sensibility was better for the second criteria. The Cell-Dyn 3500 has thus shown to be a good haematology analyser which greatly reduces the morphological examination of smears.     

Lysine and glutamate transport in the erythrocytes of common brushtail possum, Tammar Wallaby and eastern grey, kangaroo

STUDY OBJECTIVE: To compare drug output from a vented nebulizer (Pari LC Jet Plus) with a traditional unvented nebulizer (Hudson 1730 T Up-Draft 11) using aerosolized tobramycin, which is frequently used in the treatment of cystic fibrosis. DESIGN: Six nebulizers of each type were filled with a 4 mL tobramycin (80 mg) solution and were driven by a compressor (Pulmo-Aide). Various inspiratory flows (VI) (0, 5, 10, 15, 20 L/min for the Pari LC Jet Plus and 0, 5, and 10 L/min for the Hudson 1730, all at 40% relative humidity) were directed through each nebulizer. Drug output was measured from changes in weight and concentration (assessed by changes in osmometry) within the nebulizer. Particle size distributions were determined by laser diffraction allowing the calculation of the amount of aerosol output in the respirable range (<5 microm). The nebulizers were first run until end-nebulization to establish total drug output and then for either 4 or 5 min to determine the rate of drug output (mg/min) before intermittent aerosol output. RESULTS: The total drug output without VI for both the unvented and the vented nebulizers was not significantly different, 55 (51, 60) mg for the Hudson 1730 vs 51 (49, 53) mg for the Pari LC Jet Plus (mean [95% confidence limits]). Inspiratory flow had no effect on the unvented Hudson 1730 nebulizer but significantly increased the rate of total drug output and the rate of drug output in the respirable range for the vented Pari LC Jet Plus nebulizer (VI=0, 3.35 [2.84, 3.85] and 1.72 [1.48, 1.96] compared with VI=20, 9.87 [9.03, 10.70] and 6.11 [5.33, 6.88] mg/min). CONCLUSIONS: These findings indicate that the increase in the rate of drug output with VI for the vented nebulizer would result in shorter nebulization times and a relative decrease in drug loss during the expiratory phase.     

Comparison of the rapid yeast plus panel with the API20C yeast system for identification of clinically significant isolates of Candida species

The RapID Yeast Plus system (Innovative Diagnostic Systems, Norcross, Ga.) is a qualitative micromethod employing conventional tests and single-substrate chromogenic tests and having a 4-h incubation period. This system was compared with the API20C (bioMerieux Vitek, Hazelwood, Mo.) system, a 24- to 72-h carbohydrate assimilation method. One hundred thirty-three clinical yeast isolates, including 57 of Candida albicans, 26 of Candida tropicalis, 23 of Candida glabrata, and 27 of other yeasts, were tested by both methods. When discrepancies occurred, isolates were further tested by the Automated Yeast Biochemical Card (bioMerieux Vitek). Germ tube production and microscopic morphology were used as needed to definitively identify yeast isolates. The RapID Yeast Plus system correctly identified 125 yeast isolates, with an overall accuracy of 94% (125 of 133). Excellent correlation was found in the recognition of the three yeasts most commonly isolated from human sources. The test was 99% (105 of 106 isolates) accurate with C. albicans, C. tropicalis, and C. glabrata. The RapID Yeast Plus system compares favorably with the API20C system and provides a simple, accurate alternative to conventional assimilation methods for the rapid identification of the most commonly encountered isolates of Candida species.     

Bounds on null functions of linear digital imaging systems

OBJECTIVE: The purpose of this investigation was to quantitatively assess abnormally low attenuation of the lung by use of three-dimensional volumetric reconstructions from routine helical CT and to assess their correlation with pulmonary function tests. MATERIALS AND METHODS: Helical CT was performed in 100 patients in full inspiration. Examination was also performed in full expiration in 53 of these patients. Three-dimensional volumetric reconstructions were performed for total lung volumes at inspiration and at expiration, with a threshold of -896 H on inspiratory CT and -790 H on expiratory CT, to quantify emphysematous change. Correlation was made with pulmonary function tests in 79 patients. RESULTS: CT volumetric assessments of abnormally low attenuation of the lung at inspiration and expiration had a high correlation (r2 = .84, p < or = .0001). In comparison with pulmonary function tests, both inspiratory low attenuation of the lung and expiratory low attenuation of the lung correlated well with the logarithm of the ratio of the forced expiratory volume in 1 sec (FEV1) to the forced vital capacity (r2 = .74, p < or = .0001 and r2 = .74, p < or = .0001, respectively) and with the percentage of predicted ratio of the FEV1 to the forced vital capacity (r2 = .69, p < or = .0001 and r2 = .69, p < or = .0001, respectively). Linear correlations were also seen with FEV1, residual volume, and forced residual capacity. CONCLUSION: Three-dimensional volumetric reconstructions of hypoattenuating lung correlate well with pulmonary function tests. In addition, inspiratory and expiratory data are also correlative, suggesting that a dedicated expiratory examination is not needed. This easily obtainable information will prove useful for patients with obstructive lung disease from emphysema, providing a measure of pulmonary function status in this population.     

The automation of sediment urinalysis using a new urine flow cytometer (UF-100)

The UF-100 analyser is a fully automated instrument that stains the DNA and the membranes of the formed elements in native urine. The sample then passes as a laminar flow through a laser beam and light scattering, fluorescence and impedance are measured. The main purpose of the present work was to assess the analytical performance and the accuracy of the measurements of the UF-100 analyser. No carryover was observed, while the linearity was higher then the upper limit (40000 total particles microl(-1)) suggested by the manufacturer. The within-run imprecision was low, ranging from 17.7 % to 2.4% and was up to threefold better than manual microscopy. Comparison of results obtained by sediment microscopy (performed according to National Committee for Clinical Laboratory Standards (NCCLS) recommendations) and by the UF-100 analyser showed a linear correlation with r = 0.833 for erythrocytes, r = 0.934 for leukocytes, r = 0.880 for epithelial cells and r = 0.40 for casts. To evaluate the reliability of the UF-100 analyser in detecting bacteria we compared the results with the microbial culture (n = 608). Using a cut-off value of bacterial count above 1800 degrees l(-1) and at leukocyte count above 45 microl(-1), the analyser detected positive cultures with a sensitivity of 87 % and a specificity of 80 %. In conclusion, the UF-100 analyser can improve the work flow, increasing the output of urinalysis by reducing the number of specimens submitted for microscopy. Also the method provides reliable information for the identification of urinary tract inflammation and bacterial infection.     

Itraconazole for treatment of oral candidosis in pediatric cancer patients

The objective of this study was to determine the frequency, degree of curvature, and the configuration of mesiobuccal and mesiolingual root canals of mandibular first molars. The degree of curvature and configuration of root canals creates some technical difficulties to the clinician during biomechanical preparation. Therefore this knowledge is essential for successful endodontic therapy. Six hundred and ninety-seven freshly extracted mandibular first molars were used in this study. After introducing 0.8 to 15 K reamers into the mesial root canals, the teeth were radiographed in buccolingual (clinical) and mesiodistal (proximal) directions. All samples showed curvatures at varying degrees in both views. There was a significant correlation between the degree of primary curvature of mesiobuccal and mesiolingual canals in clinical directions for total samples. When the primary curvature values of the mesial root canals were evaluated in Vertucci classification, the mesiobuccal and mesiolingual canals in Vertucci type VI were found as significantly correlated (r = 0.7173, p < 0.05). A significant correlation was seen between the secondary curvature values of clinical and proximal views of mesiolingual canal in Vertucci type VI (r = 0.9891, p < 0.05). The secondary curvature values in the clinical views of mesiobuccal and mesiolingual canals were found as significantly correlated in Vertucci type II.     

Identification and cloning of a brain autoantigen in neuro-behavioral SLE

METHODS: The study reports the analytical and diagnostic performances of Cell Dyn 3500 (Abbott), an automated haematology analyser that provides the electrical impedance and the optical detection of total leukocyte and a five population leukocyte differential count. The evaluation of complete blood count and differential leukocyte count parameters was performed following the guidelines of the International Council for Standardization in Haematology and those of the National Committee for Clinical Laboratory Standards document H20-A. RESULTS: The CD 3500 demonstrated a good linearity, minimal carry-over, as well as acceptable levels of within and between-batch imprecision and stability. An excellent correlation between CD 3500 and the routine systems used in our laboratory (Technicon H*2 and Coulter STKS) was found for the major haematological indices, though agreement was not as good for MCHC. There was a good correlation between CD 3500 and manual reference differential method for neutrophils, lymphocytes, eosinophils and basophils, with the exception of monocytes. CONCLUSIONS: Regarding clinical sensitivity, the CD 3500 showed a high specificity to detect morphological abnormalities, but low sensitivity especially for the identification of immature granulocytes and nucleated red blood cells; if we overall evaluate any qualitative flags, we found an appreciable increase in sensitivity.     

Maximum flow rate--the single uroflowmetric parameter in clinical trials for benign prostatic hyperplasia?

BACKGROUND: Uroflowmetry parameters should be examined for both reliability and optimal test conditions in patients with benign prostatic hyperplasia (BPH), since the difference between one pre- and one post-intervention uroflow rate is usually evaluated in clinical trials of BPH. PATIENTS AND METHODS: Reproducibility of maximum flow rate (Qmax) or its modified forms, and the effects of urinary volume on the reproducibility were examined in terms of Spearman's correlation coefficient (r) in 67 BPH patients. RESULTS: Qmax had a higher r (0.672) as compared to other uroflow rates, such as mathematically modified forms of Qmax and adjusted values of Qmax on nomograms. Reliability was improved by bladder instillation (r = 0.811) or when voided volume was > or = 150 ml or the ratio of volumes was < 2.0 (r = 0.690-0.736). CONCLUSION(S): Qmax, preferably performed with urinary volumes of more than 150 ml or the ratio of volumes less than 2.0, is the most practical single parameter at present in the comparison of two uroflowmetric tests in BPH treatment.     

Laser scattering instrument for real time in-vivo measurement of ciliary activity in human fallopian tubes

Based on a laser light scattering technique and fibre optic probe, we have developed and tested a simple and practical device for real time measurements of ciliary activity in human Fallopian tubes during laparoscopy and laparotomy. A further aim was to investigate the relationship between the ciliary beat frequency (CBF) and the morphology of the ciliary epithelium. The mean +/- SE of CBF in the fimbria and in the ampulla were 5.4 +/- 0.3 Hz and 5.0 +/- 0.1 Hz respectively. Small pieces of fimbria and ampulla epithelium were taken from the same sites at which the CBF was measured, and the percentage of ciliary cells was determined by scanning electron microscopy. A high positive correlation was found between CBF and the percentage of ciliary cells in the fimbria (r = 0.84) and in the ampulla (r = 0.88). The instrument presented in this study provided, for the first time, a quantitative examination of the CBF in intact human Fallopian tubes and may be used for the investigation of ciliary activity in patients with infertility.     

Evaluation of a Coulter Chemistry Unit

Seventeen channels of a Coulter Chemistry Unit were evaluated. The evaluation included within-run and day-to-day precision, recovery, dilution, carryover and interference studies; as well as correlation studies between the Coulter Chemistry Unit and the procedures currently used in the author's laboratory. Criteria for acceptance of a procedure are outlined. Five channels of the particular instrument studied were found acceptable by the author's criteria, six channels had correctable defects, and six channels had either reagent or instrumentation deficiencies.     

Factors affecting the respiratory ratio during cardiopulmonary by-pass

Despite the wide use of hypothermic cardiopulmonary bypass (CPB) during open heart surgery there is little information about the patient metabolism. In particular no complete studies addressed the assessment of the respiratory ratio (RR) during CPB at different core temperatures. Therefore a clinical study was performed in order to evaluate the oxygen consumption (VO2) and carbon dioxide production (VCO2) in adult patients with valvular or coronary heart disease undergoing CPB. Twenty-five patients (16 male, 9 female) aged between 26 and 76 (54.2+/-12.4 mean +/- SD) were the subjects of this study. Measurements (102) were taken at various perfusion flow rates (from 1.6 to 2.9 L/min(-1) x m(-2)) and temperatures (from 24 to 37 degrees C). Arterial and mixed venous gas analyses were performed and O2 and CO2 concentrations were calculated, including the carbamate contribute. We calculated VO2, VCO2 and then RR from artero-venous differences in O2 and CO2 contents. Both VO2 and VCO2 showed a positive linear correlation with temperature (r = 0.82 and r = 0.59 respectively) and with blood flow rate (r = 0.61 and r = 0.29 respectively). The mean RR was 0.78+/-0.28 and more than 84% of RR values fell in the range 0.5-1.2. No significant correlation between RR and temperature and blood flow rate was observed. VCO2 and RR showed a positive linear correlation with the gas to blood flow rate ratio (r = 0.37 and r = 0.49 respectively).     

Mild feline mucopolysaccharidosis type VI. Identification of an N-acetylgalactosamine-4-sulfatase mutation causing instability and increased specific activity

The missense mutation, L476P, in the N-acetylgalactosamine 4-sulfatase (4S) gene, has previously been shown to be associated with a severe feline mucopolysaccharidosis type VI (MPS VI) phenotype. The present study describes a second mutation, D520N, in the same MPS VI cat colony, which is inherited independently of L476P and is associated with a clinically mild MPS VI phenotype in D520N/L476P compound heterozygous cats. Biochemical and clinical assessment of L476P homozygous, D520N/L476P compound heterozygous, and D520N homozygous cats demonstrated that the entire range of clinical phenotypes, from severe MPS VI, to mild MPS VI, to normal are clustered within a narrow range of residual 4S activity from 0. 5% to 4.6% of normal levels. When overexpressed in CHO-KI cells, the secreted form of D520N 4S was inactivated in neutral pH conditions. In addition, intracellular D520N 4S protein was rapidly degraded and corresponded to 37%, 14.5%, and 0.67% of normal 4S protein levels in the microsomal, endosomal, and lysosomal compartments, respectively. However, the specific activity of lysosomal D520N 4S was elevated 22. 5-fold when compared with wild-type 4S. These results suggest that the D520N mutation causes a rapid degradation of 4S protein. The effect of this is partially ameliorated as a result of a significant elevation in the specific activity of mutant D520N 4S reaching the lysosomal compartment.     

Direct quantitation of RNA transcripts by competitive single-tube RT-PCR and capillary electrophoresis

BACKGROUND: Patients with congestive heart failure (CHF) have a reduced exercise capacity because of the early appearance of fatigue and dyspnea. Qualitative changes in the skeletal muscle composition and metabolism can be responsible for the origin of symptoms METHODS: We correlated the myosin heavy chain (MHC) composition of the gastrocnemius in 20 patients with different degrees of CHF to NYHA class, diuretic consumption, echocardiographic parameters, and expiratory gases measured during cardiopulmonary exercise testing. MHC composition was determined electrophoretically in skeletal muscle needle microbiopsies and the percent distribution was calculated by densitometry. Maximal cardiopulmonary exercise testing was performed on a treadmill with a modified Naughton protocol. A capnograph was used. RESULTS: There was no correlation between ejection fraction, left ventricular end systolic diameter, left ventricular end diastolic diameter, and MHC composition. We found a significant positive correlation between the percentage of MHC 1 (slow aerobic isoform) and NYHA class (r2 = 0.62, p < 0.0001), peak VO2 (r2 = 0.5, p < 0.0004), ventilatory threshold (VT) (r2 = 0.33, p = 0.008) and O2 pulse (peak VO2/HR) (r2 = 0.40, p = 0.003). There was a negative correlation between both MHC2a (fast oxidative) and MHC2b (fast glycolytic) with peak VO2 (r2 = 0.38, p = 0.004 and r2 = 0.37, p = 0.004, respectively), VT (r2 = 0.2, p = 0.046 and r2 = 0.34, p = 0.007, respectively), and O2 pulse (peak VO2/HR) (r2 = 0.39, p = 0.003 and r2 = 0.23, p = 0.03). NYHA class was also correlated positively with MHC2a and MHC2b (r2 = 0.46, p = 0.001 and r2 = 0.41, p < 0.006, respectively) and negatively with the same clinical and functional parameters. CONCLUSIONS: The correlation between the magnitude of the MHC shift from the slow aerobic to the fast glycolytic and fast oxidative with both functional and objective measurements of exercise capacity (peak VO2, VT, O2 pulse) seem to suggest that changes in skeletal muscle composition may play a determining role in exercise tolerance in patients with CHF.     

Steady-state bioavailability and day-to-day variability of a multiple-unit (CR/ZOK) and a single-unit (OROS) delivery system of metoprolol after once-daily dosing

Home blood pressure (BP) monitoring is useful in the clinical management of patients with hypertension and the identification of those with "white-coat" hypertension; i.e. high readings in the clinic but normal BP at home. In the process of evaluating this technique, we compared self-measured home BP with intra-arterial BP. Healthy white men (n = 40) of 20-40 years of age and body weight below 95 kg were recruited by advertising in the local newspaper. Following a standardized procedure, performed within 2-4 weeks of a response to the advertisement, BP was measured by a physician at a clinic screening, by the subject at home (14 readings in 7 days) and finally in the clinic concomitantly intra-arterially and oscillometrically. The correlation coefficient for mean (M) home BP (r = 0.73) and oscillometric BP (r = 0.74) against intra-arterial BP were slightly higher than for screening BP (r = 0.65). However, in plots of the differences for individual MBP between the methods against the average of the methods, it appears that at levels of average MBP above 100 mmHg, screening BP overestimates the BP level, while this was not the case for home BP or oscillometric BP. Thus, by using intra-arterial measurement as standard of comparison, subject self-measured home BP is a reliable method of estimating blood pressure level in young men. Home BP measured shortly after screening and recruitment provides useful information of resting BP in subjects who potentially may have initial anxiety about BP measurement.     

Prion protein immunohistochemical staining in the brains of monkeys with transmissible spongiform encephalopathy

BACKGROUND: Spirituality is receiving greater attention in the medical literature, especially in the family practice journals. A widely applicable instrument to assess spirituality has been lacking, however, and this has hampered research on the relationship between spirituality and health in the clinical setting. METHODS: A new instrument, called the Spiritual Involvement and Beliefs Scale, was designed to be widely applicable across religious traditions, to assess actions as well as beliefs to address key components not assessed in other available measures, and to be easily administered and scored. The instrument is a questionnaire containing 26 items in a modified Likert-type format. Following careful pretesting, the instrument was administered to 50 family practice patients and 33 family practice educators. The validity and reliability of the instrument were then evaluated. RESULTS: By several measures, instrument reliability and validity are very good, with high internal consistency (Cronbach's alpha = .92); strong test-retest reliability (r = .92); a clear four-factor structure; and a high correlation (r = .80) with another established measure of spirituality, the Spiritual Well-Being Scale. CONCLUSIONS: The Spiritual Involvement and Beliefs Scale (SIBS) appears to have good reliability and validity. Compared with other instruments that assess spirituality, the SIBS has several theoretical advantages, including broader scope, use of terms that avoid cultural-religious bias, and assessment of both beliefs and actions. More testing is underway to further assess its usefulness.     

Inhibitory activities of gatifloxacin (AM-1155), a newly developed fluoroquinolone, against bacterial and mammalian type II topoisomerases

We determined the inhibitory activities of gatifloxacin against Staphylococcus aureus topoisomerase IV, Escherichia coli DNA gyrase, and HeLa cell topoisomerase II and compared them with those of several quinolones. The inhibitory activities of quinolones against these type II topoisomerases significantly correlated with their antibacterial activities or cytotoxicities (correlation coefficient [r] = 0.926 for S. aureus, r = 0.972 for E. coli, and r = 0.648 for HeLa cells). Gatifloxacin possessed potent inhibitory activities against bacterial type II topoisomerases (50% inhibitory concentration [IC50] = 13.8 microg/ml for S. aureus topoisomerase IV; IC50 = 0.109 microg/ml for E. coli DNA gyrase) but the lowest activity against HeLa cell topoisomerase II (IC50 = 265 microg/ml) among the quinolones tested. There was also a significant correlation between the inhibitory activities of quinolones against S. aureus topoisomerase IV and those against E. coli DNA gyrase (r = 0.969). However, the inhibitory activity against HeLa cell topoisomerase II did not correlate with that against either bacterial enzyme. The IC50 of gatifloxacin for HeLa cell topoisomerase II was 19 and was more than 2,400 times higher than that for S. aureus topoisomerase IV and that for E. coli DNA gyrase. These ratios were higher than those for other quinolones, indicating that gatifloxacin possesses a higher selectivity for bacterial type II topoisomerases.     

Myosin isoforms in skeletal muscle in patients with chronic heart decompensation: distribution and correlation with with exercise tolerance

Chronic heart failure (CHF) is accompanied by a reduced exercise capacity, and the symptoms can be at least in part explained by qualitative and quantitative changes in the skeletal muscle composition and metabolism. We have correlated the myosin heavy chain (MHC) composition of the gastrocnemius in 20 patients with different degrees of CHF to expiratory gases measured during maximal cardiopulmonary exercise testing, NYHA functional class and echocardiographic parameters. MHC composition was determined electrophoretically in skeletal muscle needle microbiopsies and the percent distribution calculated by laser densitometry. There was no correlation between ejection fraction, left ventricular end-diastolic and end-systolic diameters and MHC composition. The percentage of MHC 1 (slow aerobic isoform) was positively correlated with peak VO2 (r2 = 0.5, p = 0.0004), ventilatory threshold (VT, r2 = 0.33, p = 0.008), and O2 pulse (peak VO2/HR, r2 = 0.40, p = 0.003). There was a negative correlation between MHC 2a and 2b (fast isoforms) and peak VO2 (r2 = 0.38 and 0.37, p = 0.004, respectively), VT (r2 = 0.2, p = 0.05; r2 = 0.34, p = 0.007, respectively) and O2 pulse (r2 = 0.39, p = 0.003; r2 = 0.23, p = 0.03, respectively). NYHA functional class was also negatively correlated with the same parameters (r2 = 0.2, p = 0.01; r2 = 0.4, p = 0.001; r2 = 0.34, p = 0.006, respectively) as well as with MHC 1 (r2 = 0.62, p = 0.0001). A positive correlation was found between NYHA functional class and MHC 2a and 2b (r2 = 0.46, p = 0.001; r2 = 0.41, p = 0.002, respectively). The severity of heart failure is paralleled by a shift of the MHC pattern toward the fast MHC 2b. The correlation between the magnitude of the MHCs shift, from the slow aerobic to the fast type, with both clinical parameters (NYHA functional class) and functional measurements (peak VO2, VT, O2 pulse) of exercise capacity seem to suggest that changes in skeletal muscle composition may play a key role in exercise tolerance in patients with CHF.