Influence of active dendritic currents on input-output processing in spinal motoneurons in vivo

The extensive dendritic tree of the adult spinal motoneuron generates a powerful persistent inward current (PIC). We investigated how this dendritic PIC influenced conversion of synaptic input to rhythmic firing. A linearly increasing, predominantly excitatory synaptic input was generated in triceps ankle extensor motoneurons by slow stretch (duration: 2-10 s) of the Achilles tendon in the decerebrate cat preparation. The firing pattern evoked by stretch was measured by injecting a steady current to depolarize the cell to threshold for firing. The effective synaptic current (I(N), the net synaptic current reaching the soma of the cell) evoked by stretch was measured during voltage clamp. Hyperpolarized holding potentials were used to minimize the activation of the dendritic PIC and thus estimate stretch-evoked I(N) for a passive dendritic tree (I(N,PASS)). Depolarized holding potentials that approximated the average membrane potential during rhythmic firing allowed strong activation of the dendritic PIC and thus resulted in marked enhancement of the total stretch-evoked I(N) (I(N,TOT)). The net effect of the dendritic PIC on the generation of rhythmic firing was assessed by plotting stretch-evoked firing (strong PIC activation) versus stretch-evoked I(N,PASS) (minimal PIC activation). The gain of this input-output function for the neuron (I-O(N)) was found to be ~2.7 times as high as for the standard injected frequency current (F-I) function in low-input conductance neurons. However, about halfway through the stretch, firing rate tended to become constant, resulting in a sharp saturation in I-O(N) that was not present in F-I. In addition, the gain of I-O(N) decreased sharply with increasing input conductance, resulting in much lower stretch-evoked firing rates in high-input conductance cells. All three of these phenomena (high initial gain, saturation, and differences in low- and high-input conductance cells) were also readily apparent in the differences between stretch-evoked I(N,TOT) and I(N, PASS) and thus could be accounted for by the activation of the dendritic PIC. As a result, stretch-evoked I(N,TOT) and F-I provided an accurate prediction of the overall change in stretch-evoked firing. However, in about half of the low-input conductance cells, the rate of rise of firing in response to stretch was not smoothly graded but instead consisted of a rapid surge. Stretch-evoked I(N,TOT) was always smoothly graded. This suggests that although stretch-evoked I(N,TOT) can be used to predict the overall change in firing, prediction of the dynamics of firing may be less accurate.     

医联体慢病管理信息系统探析

介绍慢病管理现状,构建医联体慢病管理信息系统,分析系统架构,阐述系统功能及效果,通过重构慢病服务流程,推行合理有序分级诊疗模式,实现疾病管理与健康管理的有效衔接。     

N-Phenylethyl Amitriptyline in Rat Sciatic Nerve Blockade

Background: The antidepressant amitriptyline is commonly used orally for the treatment of chronic pain, particularly neuropathic pain, which is thought to be caused by high-frequency ectopic discharge. Among its many properties, amitriptyline is a potent Na+ channel blocker in vitro, has local anesthetic properties in vivo, and confers additional blockade at high stimulus-discharge rates (use-dependent blockade). As with other drug modifications, adding a phenylethyl group to obtain a permanently charged quaternary ammonium derivative may improve these advantageous properties.

Methods: The electrophysiologic properties of N-phenylethyl amitriptyline were assessed in cultured neuronal GH3 cells with the whole cell mode of the patch clamp technique, and the therapeutic range and toxicity were evaluated in the rat sciatic nerve model.

Results: In vitro, N-phenylethyl amitriptyline at 10 [mu]m elicits a greater block of Na+ channels than amitriptyline (resting block of approximately 90%vs. approximately 15%). This derivative also retains the attribute of amitriptyline in evoking high-degree use-dependent blockade during repetitive pulses. In vivo, duration to full recovery of nociception in the sciatic nerve model was 1,932 +/- 72 min for N-phenylethyl amitriptyline at 2.5 mm (n = 7) versus 72 +/- 3 min for lidocaine at 37 mm (n = 4; mean +/- SEM). However, there was evidence of neurotoxicity at 5 mm.     

Central nervous system effects in acute thallium poisoning

We report the central nervous system manifestations, neuropsychological studies and brain magnetic resonance image (MRI) findings of two patients with acute thallium intoxication. Neurologically the patients suffered from confusion, disorientation, and hallucination in the acute stage, followed by anxiety, depression, lack of attention, and memory impairment, in addition to peripheral neuropathy. Neuropsychological tests revealed an impairment of memory function, including reversed digital span, memory registration, memory recall, memory recognition, similarity, proverb reasoning, and verbal fluency. High concentrations of thallium were found in the urine, blood, and drinking water of these two patients. Brain MRI showed lesions in the corpus striatum in one patient. During the follow-up periods, the clinical manifestations and neuropsychological studies showed a slowly progressive improvement, and a follow-up brain MRI 1.5 months later demonstrated a resolution of the lesions. We conclude that thallium intoxication might induce encephalopathy, and brain MRI studies demonstrated the acute-stage brain lesions in a severe intoxicated patient. In addition, neuropsychological tests also confirmed memory deficits, although the brain lesions in the corpus striatum might resolve.     

Rebound intracranial hypertension after treatment of spontaneous intracranial hypotension

Spontaneous intracranial hypotension (SIH) is characterized by orthostatic headache and the cause is usually cerebrospinal fluid leaks in spine level. Most patients with SIH have a benign course. Epidural blood patch (EBP) is the treatment of choice when initial conservative managements are ineffective. We reported a patient with SIH diagnosed by using magnetic resonance imaging and radionuclide cisternography. Acute rebound intracranial hypertension developed after EBP and was successfully treated with intravenous osmotic agent.     

Resection of pulmonary metastases in pediatric patients with Ewing sarcoma improves survival

Background

Ewing sarcoma (ES) is the second most common bone tumor in children, and survival of those with metastatic ES has not improved. Previous studies have shown a survival benefit to whole lung irradiation in patients with pulmonary metastases and may be given either before, after, or instead of surgical pulmonary metastasectomy (PM). The contribution of surgery compared with irradiation in ES has not previously been studied.

Methods

A retrospective review of patients younger than 21 years (median age, 16 years) treated at a single institution (1990-2006) was performed. Kaplan-Meier survival curves were compared using log-rank test and a multivariate Cox proportional hazards model. P ≤ .05 was regarded as significant.

Results

Eighty patients with ES were identified. Of these, 31 (39%) had pulmonary metastases. Nine patients had incomplete details of their full treatment regimen, but the following groups could be defined from the remainder: resection alone (n = 5), radiation alone (n = 3), radiation and resection (n = 3), or chemotherapy alone (n = 11). There were 24 deaths overall, with a median overall survival (OS) of 2.7 (95% confidence interval [CI], 1.7-5.2) years. Patients who had PM had the best OS (80%), whereas those who underwent radiation to the lung without PM compared with chemotherapy only for pulmonary metastasis both had similar OS of 0% at 5 years (P = .002). Patients who had radiation followed by PM for lung metastasis had a 5-year OS of 65%. Patients with PM had a longer OS compared with those without lung resection (P < .0001).

Conclusion

These data suggest a possible benefit for ES patients who undergo surgical resection of lung metastases.     

Concomitant ipsilateral pedicled fibular transfer and free muscle flap for compound tibial defect reconstruction.

Three patients with compound injuries of the lower extremities were treated with pedicle fibular grafts and a free muscle flap concomitantly. There were 1 female and 2 male patients, all of whom sustained high-energy trauma in a motor vehicle accident. The bone defect of the tibia ranged from 8 to 12 cm. The size of the soft-tissue defect ranged from 24 x 15 cm to 28 x 15 cm. All patients underwent preoperative angiography to ensure the patency of the peroneal artery and to avoid its use by risking viability of the leg. All patients were treated with an antegrade-flow pedicle fibular graft. The fibular graft was inserted as a single strut in 2 patients and as a double-barrel strut in 1 patient. The pedicle of the free muscle flap was anastomosed to the distal runoff of the fibular bone flap. All free muscle flap transfers succeeded without complication. Bone scans performed on postoperative day 7 showed viability of transferred bone. The average time to radiological union was 9 months, and the average time to full weight bearing was 12 months. Screw loosening occurred in 2 patients and osteomyelitis was noted in another patient who was treated successfully with sequestrectomy and antibiotics. Indications for this technique are a large segmental bone defect with a huge soft-tissue defect, and patency of the peroneal artery and at least one other major artery. This method provides the advantages of one-stage reconstruction, avoidance of contralateral donor site morbidity, easy control of infection, and chance for early weight bearing. When selected carefully, this technique can be considered when one wants to avoid a two-stage, two free flap transfer.     

Comparison of video urodynamic results after the pubovaginal sling procedure using rectus fascia and polypropylene mesh for stress urinary incontinence

PURPOSE: Video urodynamic changes were compared after the pubovaginal sling procedure using rectus fascia or polypropylene mesh in women with stress urinary incontinence. MATERIALS AND METHODS: A total of 50 women with various types of stress urinary incontinence were treated with the pubovaginal sling procedure using randomly abdominal rectus fascia in 24 or polypropylene mesh in 26. The sling was placed at the level of the bladder neck and tied with sufficient tension to prevent urinary leakage without obstructing the bladder outlet. Video urodynamics were performed preoperatively, and 7 to 14 days and 3 to 6 months postoperatively in all cases. Surgical results and urodynamic changes after the pubovaginal sling procedure were compared in the 2 groups. Long-term results were evaluated at a mean followup of 2 years. RESULTS: Complete continence was achieved in 23 patients (95.8%) in the rectus fascia group and 26 (100%) in the polypropylene mesh group, including 1 initial failure with reoperation, at a median followup of 24 and 23 months, respectively. The subjective success rate was 91.6% for rectus fascia and 92.3% for polypropylene mesh. The main cause of dissatisfaction was persistent urge incontinence and dysuria in 2 cases each. In each group video urodynamics revealed a mild but nonsignificant decrease in maximum urinary flow and a significant increase in bladder neck opening time at 7 to 14 days versus baseline. However, these parameters returned to baseline within 3 to 6 months postoperatively. Voiding pressure, cystometric capacity and post-void residual urine also showed no significant change in either group after the pubovaginal sling procedure. Patients treated with a polypropylene mesh sling had a shorter operative time and hospital stay, a higher spontaneous voiding rate after catheter removal and a lower incidence of wound pain after surgery. One patient treated with polypropylene mesh had sling margin extrusion. The incidence of new onset detrusor instability and persistent dysuria was similar in the 2 groups. Transrectal sonography of the sling showed that it was located beneath the bladder neck and proximal urethra in all patients in each group. CONCLUSIONS: The results of this study show that the pubovaginal sling procedure using rectus fascia or polypropylene mesh as the sling material had similar effectiveness for treating female stress incontinence but the polypropylene group had more rapid recovery. Postoperatively video urodynamics demonstrated that the pubovaginal sling using either sling material did not cause bladder outlet obstruction with proper surgical technique.     

Virtual reality: current urologic applications and future developments

The concept of virtual reality (VR) involves the computer generation of environments with which a user can interact directly. Virtual reality is now being used for medical applications, especially in the area of surgical simulation. As technology advances, VR simulation will play an important training role for both residents and urologists already in practice. This paper examines the history of VR, current developments, and its future implications for the field of urology.