Hyperalgesia caused by nerve transection: long-lasting block prevents early hyperalgesia in the receptive field of the surviving nerve

The aim of our study was to test the hypothesis that a long-lasting N-butyl tetracaine nerve block (>2 wk) would be much more effective in the prevention of hyperalgesia caused by nerve transection than the short-lasting lidocaine block. The study was performed with the use of the saphenous nerve section model in rats. The saphenous nerve was exposed and injected with saline, lidocaine (37 mM), or N-butyl tetracaine (37 mM). Ten minutes later, the nerve was transected in some of the rats. The development of mechanical hyperalgesia (pressure threshold) of the hindpaw was assessed during a 5-wk period. In rats with saphenous nerve transection without nerve block (saline injection), 3 h after the transection, the pressure threshold decreased by approximately 30% (from 175+/-11 g to 122+/-23 g, P < 0.0001); the threshold increased somewhat the next day, then it remained stable for 2 wk, with a slow process of recovery afterward. N-butyl tetracaine block without nerve transection caused a slow-developing decrease in the pressure threshold with the first statistically significant change at the sixth day. The comparison of the preventive effects of lidocaine and N-butyl tetracaine blocks on early hyperalgesia caused by nerve transection demonstrated that both lidocaine and N-butyl tetracaine prevented hyperalgesia 3 h after the transection. However, the protective effect of lidocaine disappeared the next day. In contrast, N-butyl tetracaine prevented early hyperalgesia for almost a week. The slow-developing late hyperalgesia caused by long-lasting nerve block makes it impossible to study the protective effect of such a block on late hyperalgesia caused by axotomy. As far as early hyperalgesia is concerned, the preventive effect of the N-butyl tetracaine was much longer than that of lidocaine and continued for approximately 1 wk. IMPLICATIONS: A long-lasting nerve block can prevent early hyperalgesia caused by nerve transection.     

Phase I study of an engineered aglycosylated humanized CD3 antibody in renal transplant rejection

BACKGROUND: The potential therapeutic benefits of CD3 monoclonal antibodies, such as OKT3, have been limited by their immunogenicity and their propensity to activate a severe cytokine release syndrome. This has constrained the clinical use of OKT3 to the treatment of acute rejection episodes of organ allografts. METHODS: We have humanized a rat CD3 antibody and created a single amino acid substitution in position 297 of the IgG1 heavy chain to prevent glycosylation and, consequently, binding of the therapeutic antibody to Fc receptors and to complement. This antibody has been given as first line antirejection therapy in nine kidney transplant recipients with biopsy-proven acute rejection episodes. RESULTS: None of the patients demonstrated any antiglobulin response nor any significant cytokine release syndrome. Seven of the nine showed evidence of resolution of their rejection, although some patients experienced re-rejection. CONCLUSIONS: These findings suggest that CD3 antibodies can be engineered to lose their toxicity while retaining their potency as immunosuppressants. Nonactivating humanized CD3 monoclonal antibodies now merit further investigation in the management of transplant patients and in therapy of autoimmune diseases.     

Cortical evoked responses from the perineal nerve

PURPOSE: We characterize and determine normal reference latencies for the cortical evoked response from the perineal nerve. MATERIALS AND METHODS: A total of 15 healthy, potent men with a mean age of 31.3 +/- 6.8 years underwent genital electrophysiological testing. Square wave stimuli were applied to the perineal nerve at the ventral base of the penis and the perineal floor. Cortical evoked responses were recorded, and onset latencies were measured at baseline and after anesthetization of the dorsal nerve of the penis. RESULTS: In all 15 subjects a cortical evoked response was elicited after stimulation of the perineal nerve at the ventral base of the penis with a mean latency measured from the first positive deflection (P1) of 48.4 +/- 7.8 milliseconds. Penile block of the dorsal nerve of the penis did not change or abolish the cortical evoked response. A similar cortical evoked response was obtained, although less consistently, after stimulation of the perineal nerve through its course in the perineal floor. CONCLUSIONS: A cortical evoked response from the perineal nerve can be elicited reliably at the ventral penis. This neural pathway is independent of the dorsal nerve of the penis. The study of perineal somatic innervation may prove important in understanding the physiology of ejaculatory and erectile dysfunction.     

Campath IH allows low-dose cyclosporine monotherapy in 31 cadaveric renal allograft recipients

BACKGROUND: Campath 1H is a depleting, humanized anti-CD52 monoclonal antibody that has now been used in 31 renal allograft recipients. The results have been very encouraging and are presented herein. METHODS: Campath 1H was administered, intravenously, in a dose of 20 mg, on day 0 and day 1 after renal transplant. Low-dose cyclosporine (Neoral) was then initiated at 72 hr after transplant. These patients were maintained on low-dose monotherapy with cyclosporine. RESULTS: At present, the mean follow-up is 21 months (range: 15-28 months). All but one patient are alive and 29 have intact functioning grafts. There have been six separate episodes of steroid-responsive rejection. One patient has had a recurrence of her original disease. Two patients have suffered from opportunistic infections, which responded to therapy. One patient has died secondary to ischemic cardiac failure. CONCLUSIONS: Campath 1H has resulted in acceptable outcomes in this group of renal allograft recipients. This novel therapy is of equal efficacy compared to conventional triple therapy, but allows the patient to be steroid-free and to be maintained on very-low-dose immunosuppressive monotherapy.     

The monitoring of contaminated impervious planar surfaces.

The responses of several types of surface contamination monitor have been investigated for three typical working surfaces contaminated by three radionuclides commonly used in diagnostic or analytical biomedical applications. Of the three radionuclides, 99mTc is an intermediate-energy gamma emitter, 125I decays by electron capture, emitting low-energy x-rays, and 32P is a moderate-energy beta emitter. For each radionuclide monitored values have generally been found to be within 30% of projected response, this being based on calibrations which make use of standard radionuclide sources and conditions. The several types of contaminated non-absorbent surface that have been investigated produce monitored values which for a given type of monitor and radionuclide cannot be differentiated from each other.     

Rehabilitation of patients with chronic respiratory disease

The difficulties that face the patient with chronic respiratory disease are complex and interrelated. Caring for such patients requires a holistic approach, including psychologic support and education of patient and family, combined with physical therapy, administration of bronchodilators, and oxygen therapy.