Intracochlear perfusion of pneumolysin, a pneumococcal protein, rapidly abolishes auditory potentials in the Guinea pig cochlea

OBJECTIVE: Bacterial meningitis and chronic suppurative otitis media caused by Streptococcus pneumoniae are associated with considerable otological morbidity. Specifically, sensorineural hearing loss is a permanent sequela in a third of those who contract pneumococcal meningitis. Pneumolysin, a pneumococcal protein, has been implicated as one of the main virulence/cytotoxic factors. Its pathogenicity is intimately dependent on an ability to form transmembrane pores on binding with cholesterol in target tissues. MATERIAL AND METHODS: We perfused wild-type pneumolysin, at a number of different concentrations, into the guinea pig cochlea and used electrocochleography to characterize the effects of this cytolytic exotoxin in the organ of Corti. RESULTS: Intracochlear perfusion of pneumolysin (10 microg/50 microl) reduced the compound action potential of the auditory nerve within seconds. The cochlear microphonics (f1=8 kHz, f2=9.68 kHz) and their distortion product (2f1-f2) were also reduced, albeit in a slightly less dramatic fashion. At lower concentrations (1 microg/50 microl), a selective and earlier effect on inner hair cells was observed. CONCLUSIONS: These results clearly show that significant ototoxicity ensues when sensory cells of the organ of Corti are exposed to pneumolysin (and complete cochlear death when the concentration is high enough). Toxicity is dose-dependent and appears to be site-sensitive. This may have implications for any possible future protective strategies against pneumococcal disease in the ear.     

Prenatal ultrasound: detection and diagnosis of limb abnormalities

Many cases of congenital limb abnormalities referred for orthopaedic treatment are not diagnosed prenatally, despite routine ultrasound scanning. The authors aimed to study the detection rate and diagnostic accuracy of prenatal scans. Data concerning two groups of patients were collected. First, the authors followed-up 26,203 babies that had been scanned prenatally. Sixty had limb abnormalities; 15 of the abnormalities were detected prenatally (sensitivity 25%, 95% confidence interval 14%-36%). Second, the authors studied 67 cases from the Wessex Antenatally Detected Anomalies Register that had been identified prenatally. The diagnosis was confirmed postnatally in 56 cases (positive predictive value 84%, 95% confidence interval 75%-93%).     

Effects of creatine on body composition and strength gains after 4 weeks of resistance training in previously nonresistance-trained humans

This study examined the effects of Cr supplementation on muscle strength in conjunction with resistance training in nonresistance-trained males utilizing strategies previously reported in the literature to help optimize muscle CR uptake. Nineteen nonresistance-trained males underwent 4 weeks of resistance training (3 days x week(-1)) while assigned to Cr (20 g x d(-1) Cr + 140 g x d(-1) glucose) for 7 days (loading), followed by 5 g x d(-1) Cr + 35 g x d(-1) glucose for 21 days (maintenance; n = 9) or placebo (160 g x d(-1) glucose [loading] followed by 40 g x d(-1) [maintenance; n = 10]). In subjects classified as "responders" to Cr on the basis of body mass changes (n = 7), the magnitude of change in 180 degrees x s(-1) isokinetic (p = .029) and isometric (p = .036) force was greater compared to the placebo group. A positive correlation was found between changes in body mass and 180 degrees x s(-1) isokinetic (loading: r = 0.68, p = .04; maintenance: r = 0.70, p = .037) and isometric (loading: r = 0.82, p < .01) force. Estimated Cr uptake was also positively correlated with changes in isometric force (r = 0.71, p = .033). These results indicate that Cr supplementation can increase muscle strength (allied with 4 weeks of strength training) but only in subjects whose estimated Cr uptake and body mass are significantly increased; the greater the Cr uptake and associated body mass changes, the greater the performance gains.     

Sympathetic nerve activity is inappropriately increased in chronic renal disease

The hypothesis that in hypertensive patients with renal parenchymal disease sympathetic activity is "inappropriately" elevated and that this overactivity is a feature of renal disease and not of a reduced number of nephrons per se is addressed. Fifty seven patients with renal disease (various causes, no diabetes, all on antihypertensive medication) were studied, age range 18 to 62, creatinine clearance 10 to 114 ml/min per 1.73 m(2). Antihypertensives were stopped, but diuretics were allowed, to prevent overhydration. Matched control subjects were also studied. The effect of changes in fluid status was examined in seven patients while on and after stopping diuretics and in eight control subjects while on low- and high-sodium diet. Seven kidney donors were studied before and after unilateral nephrectomy. Sympathetic activity was quantified as muscle sympathetic nerve activity (MSNA) in the peroneal nerve. Mean arterial pressure, MSNA, and plasma renin activity were higher in patients than in control subjects, respectively (115 +/- 12 and 88 +/- 11 mmHg, 31 +/- 15 and 18 +/- 10 bursts/min, and 500 [20 to 6940] and 220 [40 to 980] fmol/L per s; P < 0.01 for all items). Extracellular fluid volume (bromide distribution) did not differ. Seven patients were studied again after stopping diuretics. MSNA decreased from 34 +/- 18 to 19 +/- 18 bursts/min (P < 0.01). Eight healthy subjects were studied during low- and high-sodium diet. MSNA was 26 +/- 12 and 13 +/- 7 bursts/min (P < 0.01). The curves relating extracellular fluid volume to MSNA were parallel in the two groups but shifted to a higher level of MSNA in the patients. In the kidney donors, creatinine clearance reduced by 25%, but MSNA was identical before and after donation. It is concluded that in hypertensive patients with renal parenchymal disease, sympathetic activity is inappropriately high for the volume status and that reduction of nephron number in itself does not influence sympathetic activity.