The burden of pneumococcal meningitis in Austrian children between 2001 and 2008.

UNLABELLED: The present study was conducted to evaluate the burden of pneumococcal meningitis in Austrian children between 2001 and 2008. Clinical outcome was retrospectively analyzed both on discharge and on follow-up investigations. This study was based on a prospective multicentre surveillance study on hospitalized invasive pneumococcal infections in Austrian children with a total annual "study population" of about 399,000 children aged below 5 years per year. Between 2001 and 2008, 74 cases of pneumococcal meningitis were identified in children aged below 5 years. The mean annual incidence rate for pneumococcal meningitis was 2.3 per 100,000 children in this age group. In 57/74 children (mean age on admission 14.5 ± 13.3 months), outcome data on hospital discharge were available: 5 deaths (8.8%), 20 children (35.1%) with sequelae and 32 children (56.1%) without sequelae were observed. Sequelae on discharge included motor impairment in 8 children (14.0%), hearing impairment in 9 children (15.8%) and/or other complications in 14 children (24.6%). In 7/8 children with motor deficits, matching cerebral lesions were identified by neuroimaging: cerebral infarction in five children, cerebral vasculitis and cerebral abscess in one child each. In 40/57 children, long-term outcome (18.9 ± 20.2 months after discharge) could be assessed: 1 child (2.5%) died 9 months after hospital discharge, 11 children (27.5%) had one or two long-term sequelae and 28 children (70.0%) had no sequelae. Long-term sequelae included motor impairment in three children (7.5%), hearing impairment in nine children (22.5%) and other deficits in two children (5.0%). CONCLUSION: Our study confirms that pneumococcal meningitis causes high mortality and severe long-term sequelae. On long-term follow-up, we observed improvements of motor impairment, but not of hearing impairment.

Free Brownian motion of individual lipid molecules in biomembranes.

The mobility of phospholipids in free-standing and supported membranes was investigated on the level of individual molecules. For the analysis of trajectories a new statistical treatment was developed that permitted us to clearly distinguish different types of diffusional motion. A freely diffusing subfraction of lipids within supported membranes was identified. Its mobility was characterized by a mean lateral diffusion constant of D(supp) = 4.6 microm(2)/s. In comparison, the mobility of lipids embedded in "free-standing" planar membranes yielded an increase in the mean diffusion constant by a factor of 4.5, D(free) = 20.6 microm(2)/s. This increase is attributed to the ultrathin (

Gating of the skeletal calcium release channel by ATP is inhibited by protein phosphatase 1 but not by Mg2+.

We have previously found that dephosphorylation/phosphorylation of the calcium release channel (CRC) of skeletal muscle confers channel sensitivity/insensitivity to the block by physiological [Mg2+] (approximately 1 mM). These studies have now been extended to modulation by ATP. Terminal cisternae vesicles of sarcoplasmic reticulum were incorporated into planar lipid bilayers. CRC gating by ATP (0.67 mM), in the absence of Ca2+ (< 1nM), was studied by treatment with protein kinase A (PKA) or phosphatase 1 (PPT1) and assayed in the presence and absence of free Mg2+ (1 mM). PPT1, PKA, and Mg2+ were directly applied to the bilayer using the microsyringe method, which controls the environment of the CRC in the bilayer for phosphorylation/ dephosphorylation cycles and for assays. PKA treated channels were activated by ATP to high open probabilities, while PPT1 treated channels were not activatable by ATP. Opening and closing of channels during cycles of PKA and PPT1 applications, respectively, provided evidence that the change of CRC activity is due to cyclic phosphorylation/dephosphorylation. Free Mg2+ (1 mM) did not block channels activated by ATP. The new finding is that channel gating by ATP can be controlled by the state of phosphorylation without inhibition by free Mg2+.

[Retrospective analysis of results and complications following kidney transplantation in diabetic nephropathy--a challenge for the future]. / Retrospektive Analyse der Ergebnisse und Komplikationen nach Nierentransplantation bei diabetischer Nephropathie--Herausforderung für die Zukunft.

A retrospective analysis was undertaken of the renal transplantation results in diabetic nephropathy over the past 10 years. Out of 428 kidney transplants in 348 patients, 22 transplants were performed in 20 diabetic patients during the observation period. Patient survival for diabetics after 1, 2, and 3 years in contrast to non-diabetic controls was significantly different (70%, 50.9%, 50.9%, respectively versus 93.9%, 89.5%, 83.3% in the non-diabetic control group) (p less than 0.001). Transplant survival was 55%, 42%, 34.4%, versus 74.7%, 67.4%, 57.6% after 1, 2, and 3 years, respectively (p less than 0.08). During the posttransplant period the incidence of cardiovascular and infectious complications, as well as the rate of amputation was much higher than in the pretransplant phase. Main causes of death were cardiovascular or infectious complications. Improvement of the still poor results in diabetic transplant recipients is certainly a challenge for the future.

Functional properties of the ryanodine receptor type 3 (RyR3) Ca2+ release channel.

Single-channel analysis of sarcoplasmic reticulum vesicles prepared from diaphragm muscle, which contains both RyR1 and RyR3 isoforms, revealed the presence of two functionally distinct ryanodine receptor calcium release channels. In addition to channels with properties typical of RyR1 channels, a second population of ryanodine-sensitive channels with properties distinct from those of RyR1 channels was observed. The novel channels displayed close-to-zero open-probability at nanomolar Ca2+ concentrations in the presence of 1 mM ATP, but were shifted to the open conformation by increasing Ca2+ to micromolar levels and were not inhibited at higher Ca2+ concentrations. These novel channels were sensitive to the stimulatory effects of cyclic adenosine 5'-diphosphoribose (cADPR). Detection of this second population of RyR channels in lipid bilayers was always associated with the presence of the RyR3 isoform in muscle preparations used for single-channel measurements and was abrogated by the knockout of the RyR3 gene in mice. Based on the above, we associated the novel population of channels with the RyR3 isoform of Ca2+ release channels. The functional properties of the RyR3 channels are in agreement with a potential qualitative contribution of this channel to Ca2+ release in skeletal muscle and in other tissues.

Differential activation by Ca2+, ATP and caffeine of cardiac and skeletal muscle ryanodine receptors after block by Mg2+.

The block of rabbit skeletal ryanodine receptors (RyR1) and dog heart RyR2 by cytosolic [Mg2+], and its reversal by agonists Ca2+, ATP and caffeine was studied in planar bilayers. Mg2+ effects were tested at submaximal activating [Ca2+] (5 microM). Approximately one third of the RyR1s had low open probability ("LA channels") in the absence of Mg2+. All other RyR1s displayed higher activity ("HA channels"). Cytosolic Mg2+ (1 mM) blocked individual RyR1 channels to varying degrees (32 to 100%). LA channels had residual P(o) <0.005 in 1 mM Mg2+ and reactivated poorly with [Ca2+] (100 microM), caffeine (5 mM), or ATP (4 mM; all at constant 1 mM Mg2+). HA channels had variable activity in Mg2+ and variable degree of recovery from Mg2+ block with Ca2+, caffeine or ATP application. Nearly all cardiac RyR2s displayed high activity in 5 microM [Ca2+]. They also had variable sensitivity to Mg2+. However, the RyR2s consistently recovered from Mg2+ block with 100 microM [Ca2+] or caffeine application, but not when ATP was added. Thus, at physiological [Mg2+], RyR2s behaved as relatively homogeneous Ca2+/caffeine-gated HA channels. In contrast, RyR1s displayed functional heterogeneity that arises from differential modulatory actions of Ca2+ and ATP. These differences between RyR1 and RyR2 function may reflect their respective roles in muscle physiology and excitation-contraction coupling.