Lack of plasma interleukin-1 beta or tumor necrosis factor-alpha elevation during unfavorable hemodialysis conditions.

Plasma interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) were determined by ELISA in 17 healthy controls, 23 HD patients, 10 continuous ambulatory peritoneal dialysis patients, and 15 chronic renal failure patients, as well as in 2 HD patients experiencing pyrogenic reactions. Another group of 10 chronic HD patients were dialyzed for 2.5 h, 5 with first-use Cuprophan membranes and 5 with first-use high-flux cellulose triacetate membranes. The mean bacterial and endotoxin concentrations of the dialysate used for HD treatments during the study period were 18,440 +/- 530 CFU/mL (mean +/- SEM) and 976 +/- 205 pg/mL, respectively. Blood specimens were obtained intradialysis and postdialysis for cytokine assay and were incubated to augment cytokine production. There was no difference in plasma IL-1 beta or TNF-alpha concentrations among the healthy controls, continuous ambulatory peritoneal dialysis patients, chronic renal failure patients, or HD patients. Neither cytokine increased significantly during or after HD. Two patients experiencing pyrogenic reactions had plasma TNF-alpha concentrations of 537 and 413 pg/mL, compared with matched controls of 6 and 0 pg/mL. Il-1 beta concentration did not differ from controls. We conclude that: (1) plasma IL-1 beta and TNF-alpha are not chronically elevated in chronic renal failure, continuous ambulatory peritoneal dialysis, or HD patients; (2) HD with new Cuprophan or cellulose triacetate membranes and high concentrations of dialysate endotoxin and bacteria does not cause elevation of circulating IL-1 beta or TNF-alpha; and (3) pyrogenic reactions might be mediated by TNF-alpha.     

Albuterol extended-release products: a comparison of steady-state pharmacokinetics

A new extended-release formulation of albuterol, Volmax, was developed based on the oral osmotic drug delivery system. Proventil Repetabs, another extended-release formulation of albuterol, is a repeat-action tablet. The steady-state pharmacokinetic profile of Volmax 8 mg orally every 12 hours for 3 days was compared with that of Proventil Repetabs 8 mg orally every 12 hours for 3 days in a randomized, two-way, crossover study in 23 healthy men. Results were determined for both daytime and nighttime dosing intervals. Volmax demonstrated significantly less peak-trough fluctuation during both dosing intervals than Proventil Repetabs (p less than 0.05). Peak plasma concentrations were higher and occurred earlier with Proventil Repetabs. There were no significant differences between the two formulations with respect to reported adverse experiences. Volmax exhibited a more controlled release of albuterol during both daytime and nighttime dosing intervals than Proventil Repetabs.     

Sensitivity of coherent oscillations in rat hippocampus to AC electric fields

The sensitivity of brain tissue to weak extracellular electric fields is important in assessing potential public health risks of extremely low frequency (ELF) fields, and potential roles of endogenous fields in brain function. Here we determine the effect of applied electric fields on membrane potentials and coherent network oscillations. Applied DC electric fields change transmembrane potentials in CA3 pyramidal cell somata by 0.18 mV per V m⁻¹ applied. AC sinusoidal electric fields have smaller effects on transmembrane potentials: sensitivity drops as an exponential decay function of frequency. At 50 and 60 Hz it is ∼0.4 that for DC fields. Effects of fields of ≤ 16 V m⁻¹ peak-to-peak (p-p) did not outlast application. Kainic acid (100 n m ) induced coherent network oscillations in the beta and gamma bands (15–100 Hz). Applied fields of ≥ 6 V m⁻¹ p-p (2.1 V m⁻¹ r.m.s.) shifted the gamma peak in the power spectrum to centre on the applied field frequency or a subharmonic. Statistically significant effects on the timing of pyramidal cell firing within the oscillation appeared at distinct thresholds: at 50 Hz, 1 V m⁻¹ p-p (354 mV m⁻¹ r.m.s.) had statistically significant effects in 71% of slices, and 0.5 V m⁻¹ p-p (177 mV m⁻¹ r.m.s.) in 20%. These threshold fields are consistent with current environmental guidelines. They correspond to changes in somatic potential of ∼70 μV, below membrane potential noise levels for neurons, demonstrating the emergent properties of neuronal networks can be more sensitive than measurable effects in single neurons.     

Controlled release of nerve growth factor from a polymeric implant

Recent studies suggest that neurotrophic factors applied directly to brain tissue may enhance regeneration in the central nervous system. Biocompatible polymeric implants providing a controlled release of nerve growth factor (NGF) for over one month were developed. The released nerve growth factor stimulated neurite sprouting in cultured PC12 cells. While a model polymer with demonstrated biocompatibility was used for the present study, the methods can be extended to other polymer systems. Controlled release implants may be useful in the treatment of Alzheimer's disease.     

Reduced incidence of severe infection after heart transplantation with low-intensity immunosuppression.

Despite advances in immunosuppressive therapy and prolonged graft and patient survival, infection after heart transplantation remains problematic. From January 1987 through June 1989, 104 heart transplantations were performed in 100 patients. Immunosuppression induction was by antilymphocyte globulin for 7 days, with oral cyclosporine introduced on stabilization of kidney function (day 3). Steroid therapy was rapidly tapered, and azathioprine was added only in cases of positive donor crossmatch or steroid-resistant rejection. No reverse isolation was used. Twenty-two deaths occurred, one from sepsis. Actuarial survival at 6 months, at 1 year, and at 2 years was 85% +/- 4%, 81% +/- 3%, and 75% +/- 4%, respectively. Fifty-four patients had 81 infections, of which 21 were bacterial; 83% of these episodes were treated. Sixty infections were opportunistic (85% viral), and only 23% necessitated treatment. Actuarial infection-free rates (all types necessitating treatment) at 1 month, at 6 months, and at 2 years were 83% +/- 4%, 75% +/- 5%, and 75% +/- 5%, respectively. Of the 100 transplant recipients, 66% were treated with azathioprine; 47 patients (69%) had an infection, whereas only seven (19%) of the patients not receiving azathioprine became infected (p less than 0.00001). Rejection was noted in 66% of patients, with a median time to the first episode of 4 weeks. A low-intensity immunosuppressive regimen has resulted in fewer serious infections, with acceptable graft loss from rejection. Increased infection surveillance is required for the first 30 days postoperatively and after treatment of rejection episodes.     

Problems in magnetic resonance imaging of patients with severe brain injury and a solution to one of them

A number of difficulties have been encountered in carrying out MRI scans with severely brain-injured subjects. One of the problems is maintenance of head position for the 30 minutes' duration of the scan. The use of a vacuum cushion has proved a low-cost solution to this problem.     

A clinical evaluation of plaster-of-Paris and eight synthetic fracture splinting materials.

A number of new synthetic orthopaedic splinting materials, all claiming substantial advantages over the traditional plaster-of-Paris, have been introduced in recent years. However, although their properties have been extensively measured in the laboratory, little has been documented concerning their performance in clinical use. This study was therefore initiated as a comparative evaluation of the clinical characteristics and ease of use of these relatively expensive materials in the fabrication of below-knee weight-bearing casts. The study encompassed nine materials--seven based on water-activated polyurethanes, one thermoplastic and plaster-of-Paris, and involved a total of 203 patients. It was concluded that plaster-of-Paris should be used for all routine splinting applications, but that in cases in which cast weight, cast bulk, or the time to bearing weight is important, a synthetic material, chosen principally on the basis of cost, is indicated.