Mast cells detected in cultures of neonatal rat heart cells

Although the presence of mast cells in heart muscle is well documented, their possible presence in heart cell cultures has not yet been considered. In this paper we show for the first time that cultures from neonatal rat hearts contain mast cells in proportions which may exert physiological influences on heart muscle cells. Evidence is based on cytochemistry, immunocytochemistry with a monoclonal antibody (F2) specific for connective tissue mast cells of the rat, and direct estimations of both cellular histamine and histamine released into the culture medium. Since the number of nonmuscle cells immunoreactive with antibody F2 exceeded the number of cells reacting with conventional cytochemical stains for mast cells, a substantial proportion of the former may represent less differentiated (precursor) cells.     

Head of the caudate nucleus is most vulnerable in chorea-acanthocytosis: a voxel-based morphometry study.

Chorea-acanthocytosis (ChAc; OMIM 200150) is a rare autosomal recessive disease with dysfunction of the erythrocyte membrane, presenting with acanthocytes and neurological manifestations characterized by progressive hyperkinesias (chorea, dystonia) and neuropsychological impairment. Damage to the basal ganglia was described previously in neuropathological and neuroimaging investigations. We analyzed high-resolution MRI of six ChAc patients with mutations in the VPS13A gene (median age, 37 years; mean time since clinical onset, 13 years) with respect to regional atrophy by use of the observer-independent technique of voxel-based morphometry in comparison to 15 age-matched healthy controls. Additionally, global brain atrophy was determined using the standardized brain parenchymal fraction (BPF) method. A robust regional reduction of gray matter density was observed in the head of the caudate nucleus bilaterally and was nearly symmetrical (P < 0.001, corrected for small volumes). No additional gray matter changes were found. In the BPF analysis, there was no significant global brain atrophy. The predilection of atrophy in the head of the caudate nucleus, as suggested by our results, argues for a particular vulnerability of this part of the striatum in ChAc and is in agreement with pronounced neuropsychological disturbances that are thought to rely on these regions.     

Core-shell structure of Miglyol/poly(D,L-lactide)/Poloxamer nanocapsules studied by small-angle neutron scattering.

The contrast variation technique in small angle neutron scattering (SANS) was used to investigate the inner structure of nanocapsules on the example of poly(D,L-lactide) (PLA) nanocapsules. The determination of the PLA and Poloxamer shell thickness was the focus of this study. Highest sensitivity on the inner structure of the nanocapsules was obtained when the scattering length density of the solvent was varied between the one of the Miglyol core and the PLA shell. According to the fit data the PLA shell thickness was 9.8 nm. The z-averaged radius determined by SANS experiments correlated well with dynamic light scattering (DLS) results, although DLS values were systematically slightly higher than the ones measured by SANS. This could be explained by taking into account the influence of Poloxamer attached to the nanocapsules surface. For a refined fit model with a second shell consisting of Poloxamer, SANS values and DLS values fitted well with each other. The characterization method presented here is significant because detailed insights into the nanocapsule and the Poloxamer shell were gained for the first time. This method could be used to develop strategies for the optimization of the shell properties concerning controlled release and to study changes in the shell structure during degradation processes.     

Severe metformin intoxication with lactic acidosis in an adolescent

A 15-year-old healthy girl ingested 38.25 g (0.55 g/kg body weight) of metformin in a suicide attempt. Subsequently she developed lactic acidosis and moderate renal failure. An initial session of haemodialysis was able to treat the acidosis and reduce the toxic level of metformin. Nevertheless, a further increase in serum lactate was observed during and after the first dialysis treatment. A second session of haemodialysis was started 5 h after the end of the first session and resulted in a lowering of the lactate level and an almost total elimination of metformin. During the further clinical course, reversible acute renal failure with a maximum creatinine of 2.4 mg/dl was observed. Conclusion: Despite sufficient haemodialysis, the production of lactate can be greater than the elimination in the case of severe metformin intoxication. Therefore haemodialysis should be continued even in the situation of rising lactate levels during the treatment.     

Efficacy and safety outcomes among de novo renal transplant recipients managed by C2 monitoring of cyclosporine a microemulsion: results of a 12-month, randomized, multicenter study

BACKGROUND: The clinical benefits of C2 monitoring of cyclosporine microemulsion have been demonstrated, but C2 targets in renal transplant recipients during the first year require validation. METHODS: MO2ART was a prospective, multicenter study of renal transplant recipients managed by C2 monitoring of cyclosporine microemulsion with steroids and mycophenolate mofetil or azathioprine. Patients were randomized on day 3 to two groups, which were managed from month 3 with higher or lower C2 target ranges (months 4-6, 1,000-1,200 ng/mL vs. 800-1,000 ng/mL; months 7-12, 800-1,000 ng/mL vs. 600-800 ng/mL, respectively). The primary endpoint was the glomerular filtration rate (GFR) at month 12. RESULTS: A total of 296 patients were recruited, of whom 250 remained in the study at 3 months (higher-C2, n=131; lower-C2, n=119). GFR at 12 months did not differ between the higher- and lower-C2 groups (65+/-17 mL/min vs. 66+/-14 mL/min). When patients were regrouped according to C2 achieved by months 8 to 12, those with the lowest C2 (<700 ng/mL) showed the lowest GFR at month 3 and the most pronounced increase in GFR between month 3 and month 12 (P=0.04). Five episodes of biopsy-proven acute rejection occurred after month 3 (higher-C2 group, n=2; lower-C2 group, n=3). The overall 12-month Kaplan-Meier incidence of biopsy-proven acute rejection was 13.7%. Patient and graft survival were 93% and 89%, respectively, at 12 months. CONCLUSION: Both C2 target ranges investigated showed excellent and nearly equivalent outcomes at 12 months. The decision to target the higher or lower end of these C2 ranges should be made on an individual basis, taking into account patient and graft characteristics, and co-medication.     

Wrist stability after experimental traumatic triangular fibrocartilage complex lesions

PURPOSE: The aim of this study was to evaluate changes in stability of the wrist after experimental traumatic triangular fibrocartilage complex lesions. METHODS: Sixteen cadaver wrist specimens were included: 8 were fixed in neutral rotation of the forearm, 4 in maximal supination, and 4 in maximal pronation. The specimens were tested in a multiangle and torque measuring instrument. First the intact specimen was tested, second a dorsal arthrotomy was performed, and the third test was with 1 of 4 different experimental lesions according to Palmer's classification of traumatic triangular fibrocartilage complex lesions (1A-1D). Forced radioulnar deviation and internal/external rotation were recorded with a load of 0.75 Nm in the interval -60 degrees to +60 degrees of flexion. RESULTS: We found the 1C lesion to be highly significantly related to wrist stability. Forced radioulnar deviation and forced internal/external rotation were altered significantly in 35 degrees of wrist extension. The other lesions did not alter the stability of the wrist significantly and the rotation of the forearm had no influence on the outcome. CONCLUSIONS: The 1A lesion does not alter significantly wrist stability and hence the common treatment by a two-third excision of the central part of the disk will not affect wrist stability. A 1C lesion alters significantly the stability of the wrist. At 35 degrees of wrist extension forced radioulnar deviation and forced internal/external rotation were altered significantly; this might be used in a clinical test for a 1C lesion. The rotation of the forearm has no influence on the outcome.     

Theory and practice of waiting time data as a performance indicator in health care. A case study from The Netherlands

In this article we investigate the use of waiting time data as a performance indicator in health care in The Netherlands. We explain why the current publication of waiting time data fails to achieve one of the main goals: to have consumers and general practitioners act upon this information. The reason, we claim, is that even seemingly clear-cut, easily measurable and objective numbers such as waiting times need interpretation to become meaningful. Discussing four themes - the patient behind the number, the treatment behind the number, the strategy behind the number, and the specificity of the number - we will discuss just how deeply this need for interpretation affects the usability of 'waiting times' for purposes such as informing consumers. We will argue that this problem is due to not making a clear distinction between performance indicators for internal use and for external use. We conclude that the usefulness of the publication of waiting time data for consumers strongly increases when waiting times are guaranteed and related to treatment options like booking possibilities and other performance indicators such as patient satisfaction.