Treatment with sisomicin of complicated urinary tract infections in patients with varying degrees of renal function impairment

The efficacy, tolerance and pharmacokinetics of the new aminoglycoside antibiotic sisomicin, have been studied in 29 elderly male patients with varying degrees of renal function impairment and suffering from complicated urinary tract infections. The antibiotic was equally effective in patients with normal and impaired renal function and a cure (negative urine culture at one week follow-up) of 56% was obtained. There was little apparent toxicity with the dosage regimens used, although serum creatinine values were statistically but not clinically significantly increased in some patients following treatment. Serum half-lives of sisomicin were prolonged in cases of impaired renal function but accumulation of antibiotic could be prevented by varying dosing intervals between 8 and 24 hours based on serum creatinine values. There was good correlation between serum creatinine and sisomicin serum half-life values and a practical method is described for dose adjustment based on the relationship between serum half-lives and serum creatinine concentrations.     

Serum nitric oxide metabolites and disease activity in patients with systemic sclerosis

There is no surrogate marker in serum for defining disease activity in scleroderma (SSc). Nitric oxide (NO), which regulates vasodilation and possesses pro-inflammatory actions, has been implicated in the pathogenesis of SSc. We compared serum NO _x (total nitrate and nitrite) level in SSc patients to healthy controls and evaluated its correlation with detailed symptomatology and scoring systems for various organ involvement. Symptoms and physical findings that suggested disease activity in regard to various organs were documented. Lung function test, high-resolution computed tomographic (HRCT) scan of thorax and echocardiography were performed. Serum NO _x was measured by chemiluminescence. Serum NO _x levels in SSc (n = 43) were significantly higher (72.4 ± 47.8 μM) than age- and sex-matched controls (n = 41; 37.1 ± 13.5 μM; p < 0.001). Serum NO _x were not found to be associated with lung fibrosis defined by lung function parameters or inflammation and fibrosis scores on HRCT. Twenty-two patients were found to have elevated serum NO _x level defined as mean ± 2 SD of normal controls. Logistic regression analysis revealed that age (OR 1.12, p = 0.02) and elevated pulmonary arterial pressure (PAP) (n = 9; OR 145.3, p = 0.01) were predictive factors for elevated serum NO _x . Prednisolone use was associated with lower serum NO _x level (OR 0.06, p = 0.04). Elevated PAP of increasing severity was found to be associated with higher level of serum NO _x (p = 0.004 by trend). Serum NO _x in SSc patients were elevated compared to healthy controls. Serum NO _x level was determined by multiple factors including age, prednisolone use, and elevated PAP.     

Multiple Genetic Mutations Associated with Polymyxin Resistance in Acinetobacter baumannii

We studied polymyxin B resistance in 10 pairs of clinical Acinetobacter baumannii isolates, two of which had developed polymyxin B resistance in vivo. All polymyxin B-resistant isolates had lower growth rates than and substitution mutations in the lpx or pmrB gene compared to their parent isolates. There were significant differences in terms of antibiotic susceptibility and genetic determinants of resistance in A. baumannii isolates that had developed polymyxin B resistance in vivo compared to isolates that had developed polymyxin B resistance in vitro.     

Reliability and validity of the sideways step test and its correlation with motor function after stroke

[Purpose] This study investigated the intra-rater, inter-rater and test-retest reliability of the sideways step test (SST), its correlation with other indicators of stroke-specific impairment, and the cut-off count best discriminating subjects with stroke from their healthy counterparts. [Subjects and Methods] Forty-three subjects with chronic stroke and 41 healthy subjects older than 50 years participated in this study. The SST was administered along with the Fugl-Meyer motor assessment for the lower extremities (FMA-LE), the five-times sit to stand (5TSTS) test, the Berg Balance Scale (BBS), the movement velocity (MVL) by the limits of stability (LOS) test, the ten-metre walk (10mW) test, the timed “Up and Go” (TUG) test and the Activities-specific Balance Confidence (ABC) scale. [Results] The SST showed good to excellent intra-rater, inter-rater and test-retest reliability. The SST counts correlated with 5TSTS times, 10mW times, TUG times, and the FMA-LE and BBS scores. SST counts of 11 for the paretic leg and 14 for the non-paretic leg were found to distinguish the healthy adults from subjects with stroke. [Conclusion] The sideways step test is a reliable clinical test, which correlates with the functional strength, gait speed, and functional balance of people with chronic stroke.Key words: Balance, Stroke, Rehabilitation     

Effects of chemical denervation with 6-hydroxydopamine on myocardial responsiveness to isoproterenol in rabbits

This study examined the hypothesis that chemical denervation with 6-hydroxydopamine (6-OHDA) would increase myocardial responsiveness to isoproterenol. Five days previously, 15 New Zealand white rabbits were given 60 mg/kg 6-OHDA intravenously. Fifteen control rabbits received vehicle. Hemodynamic, coronary blood flow (CBF), and cardiac output measurements were obtained before and during isoproterenol infusion (0.5 g/kg/min for 15 min). Norepinephrine tissue content, -adrenoceptor number (Bmax) and affinity (Kd), cyclic AMP content and cyclic AMP-phosphodiesterase (PDE) activity were measured in the subepicardium (EPI) and subendocardium (ENDO). Myocardial norepinephrine content was significantly decreased from 1263±292 (EPI) and 874±221 ng/g tissue (ENDO) in the control to 148 ±33 (EPI) and 90±45 ng/g tissue (ENDO) in the denervated group. There were no significant changes in cyclic AMP-PDE activity of Bmax and Kd of -adrenoceptors. Cyclic AMP content was similar at baseline, but controls had a significantly larger increase (123–155 %) during isoproterenol infusion when compared to the denervated group (27–37%). The denervated animals showed a smaller increase in cardiac output during isoproterenol infusion (from 203±30 to 235±26 ml/min), when compared to the control animals (from 135±18 to 216±42 ml/min). Baseline CBF was significantly higher in the EPI but not ENDO of the denervated group (185±20 ml/ 100 g/min in EPI and 150±8 in ENDO) compared to the control group (108±13 in EPI and 133±17 in ENDO). The relative increase in CBF during isoproterenol infusion was smaller in the denervated group (44–45%) than the control group (107–109%). Isoproterenol infusions of 0.1 and 2.5 g/kg/min showed similarly depressed coronary blood flow responses in denervated animals. Thus, the chemically denervated animals did not have -adrenoceptor upregulation, exhibited a lesser increase in cyclic AMP with isoproterenol, and had a reduced functinal and coronary blood flow response to isoproterenol. This occurred without any significant change in -adrenoceptor number or affinity, or in cyclic AMP-phosphodiesterase activity, indicating there may be receptor uncoupling or other changes in the signal transduction pathway.