Endocannabinoid involvement in endometriosis

Endometriosis is a disease common in women that is defined by abnormal extrauteral growths of uterine endometrial tissue and associated with severe pain. Partly because how the abnormal growths become associated with pain is poorly understood, the pain is difficult to alleviate without resorting to hormones or surgery, which often produce intolerable side effects or fail to help. Recent studies in a rat model and women showed that sensory and sympathetic nerve fibers sprout branches to innervate the abnormal growths. This situation, together with knowledge that the endocannabinoid system is involved in uterine function and dysfunction and that exogenous cannabinoids were once used to alleviate endometriosis-associated pain, suggests that the endocannabinoid system is involved in both endometriosis and its associated pain. Herein, using a rat model, we found that CB1 cannabinoid receptors are expressed on both the somata and fibers of both the sensory and sympathetic neurons that innervate endometriosis’s abnormal growths. We further found that CB1 receptor agonists decrease, whereas CB1 receptor antagonists increase, endometriosis-associated hyperalgesia. Together these findings suggest that the endocannabinoid system contributes to mechanisms underlying both the peripheral innervation of the abnormal growths and the pain associated with endometriosis, thereby providing a novel approach for the development of badly-needed new treatments.     

Cytological and cytoarchitectural changes in the feline cerebral cortex during experimental infantile hydrocephalus

While many reports have documented the effects of hydrocephalus on the ependyma and periventricular white matter, primarily in adult animal models, little is known about alterations specific to neurons. The present study has evaluated qualitatively the effects of hydrocephalus on the neurons and vasculature of the cerebral cortex in a neonatal animal model. The cisterna magna of 4 to 11-day-old kittens was injected with a solution of 25% kaolin to induce hydrocephalus. Ultrasonographic evidence of hydrocephalus was noted within 3-5 days of injection. Hydrocephalus progressed until day 18-25 postinjection when the animals were sacrificed. The cytologic and cytoarchitectural changes within the cortical mantle of affected animals were compared with control age-matched counterparts who had undergone intracisternal saline injections. Areas 4 (primary motor), 22 (association) and 17 (primary visual sensory) were examined light microscopically. Neurons from hydrocephalic brains exhibited 3 types of pathological response. Pyknotic somata were shrunken, disoriented and so hyperchromatic that neither nuclei or nucleoli could be delineated. Reactive somata were also shrunken and hyperchromatic, but nuclei and nucleoli could still be observed. Many neurons contained an abundance of vacuoles, giving their somata a flocculent appearance; these cells were termed 'spongy' neurons. Both normal and pathological neurons were smaller and disoriented, with a considerable decrease in neurons noted in areas 22 and 17 from severely hydrocephalic animals. The deeper cortical layers were more affected than the more superficial laminae in that more reactive and pyknotic neurons were present in layers V and VI. As the ventriculomegaly became more severe, changes could be observed in neurons within layers II and III. Furthermore, the cerebral vasculature exhibited a decrease in the number of vessels and a preponderance of profiles oriented parallel to the meningeal surface. The severity of these effects followed a rostral to caudal gradient, such that the occipital cortex demonstrated the most damage. These results suggest that both the motor deficits and the subtle cognitive deficiencies seen with hydrocephalus may be attributed to perturbation of neuronal and vascular elements in the cerebral cortex.     

Iodine-I25 episcleral plaque therapy in uveal melanoma

Purpose : To assess the efficacy of iodine‐125 (I‐125) episcleral plaque therapy in the management of uveal melanoma with regard to local control, survival, globe preservation and visual outcome. Methods : Between January 1985 and January 1997, 50 patients with the diagnosis of uveal melanoma were treated with I‐125 episcleral plaques. The mean initial tumour height was 5.5 mm (range, 2.0–9.5 mm) and basal diameter 9.5 mm (range, 4.0–14.5 mm). I‐125 seeds with a mean activity of 1259.1 MBq were used. The mean apical dose was 80.5 Gy (range, 68.0–95.0 Gy). Scleral dose ranged from 225.0 to 940.0 Gy. Pretreatment visual acuity was 6/60 or better in 43 patients. Results : One patient was lost to follow up and excluded from analysis. The remaining 49 patients had a mean follow up of 39.5 months. There were seven local failures, with a mean duration to tumour progression of 16.7 months. All seven patients were successfully managed with enucleation. Five other enucleations were performed for treatment‐ related complications. At the time of analysis, 10 patients have died, five of metastatic melanoma. Of the patients with preserved globes, corrected visual acuity was 6/60 or better in 31 patients. Conclusions : Good local tumour control and survival can be achieved with episcleral plaque therapy. Globe preservation with useful vision was possible in the majority of cases. Our findings are in keeping with other reported series.     

Fractionated proton beam radiotherapy for acoustic neuroma

OBJECTIVE: This study evaluated proton beam irradiation in patients with acoustic neuroma. The aim was to provide maximal local tumor control while minimizing complications such as cranial nerve injuries. METHODS: Thirty-one acoustic neuromas in 30 patients were treated with proton beam therapy from March 1991 to June 1999. The mean tumor volume was 4.3 cm(3). All patients underwent pretreatment neurological evaluation, contrast enhanced magnetic resonance imaging, and audiometric evaluation. Standard fractionated proton radiotherapy was used at daily doses of 1.8 to 2.0 cobalt Gray equivalent: patients with useful hearing before treatment (Gardner-Robertson Grade I or II) received 54.0 cobalt Gray equivalent in 30 fractions; patients without useful hearing received 60.0 cobalt Gray equivalent in 30 to 33 fractions. RESULTS: Twenty-nine of 30 patients were assessable for tumor control and cranial nerve injury. Follow-up ranged from 7 to 98 months (mean, 34 mo), during which no patients demonstrated disease progression on magnetic resonance imaging scans. Eleven patients demonstrated radiographic regression. Of the 13 patients with pretreatment Gardner-Robertson Grade I or II hearing, 4 (31%) maintained useful hearing. No transient or permanent treatment-related trigeminal or facial nerve dysfunction was observed. CONCLUSION: Fractionated proton beam therapy provided excellent local control of acoustic neuromas when treatment was administered in moderate doses. No injuries to the Vth or VIIth cranial nerves were observed. A reduction in the tumor dose is being evaluated to increase the hearing preservation rate.     

Uterine balloon therapy for menorrhagia: a feasibility study of its use in the community setting

OBJECTIVES: To determine whether uterine balloon therapy (UBT) for menorrhagia can be performed safely in the community setting, obviating the need for hospital admission or general anaesthesia. DESIGN: Prospective case studies of 20 women undergoing Thermachoice endometrial ablation for menorrhagia. SETTING: Glasgow Centre for Family Planning and Reproductive Health Care, Greater Glasgow Primary Care NHS Trust, Glasgow, UK. PARTICIPANTS: Twenty women with menorrhagia unresponsive to medical therapy. MAIN OUTCOME MEASURES: Pain levels experienced by women during the procedure, measured by visual analogue scores and analgesia requirements postoperatively. RESULTS: Pain scores were in the range 0.1-6.6 (median 1.1) for outpatient hysteroscopy, compared to 0.1-9.8 (median 4.0) for uterine balloon therapy. No procedure was abandoned due to pain. CONCLUSION: UBT performed under local anaesthetic is tolerated well by patients. It is an effective treatment for menorrhagia, which is safe and easy to perform in the community setting.     

Influence of peak VO2 and muscle fiber type on the efficiency of moderate exercise

PURPOSE: The purpose of this study was to determine if %Type I fibers and/or aerobic fitness (as peak .VO(2)) would predict Delta efficiency (DeltaEff) and Delta.VO(2)/Deltawork rate (WR) for moderate (below lactate threshold 0.05). CONCLUSION: These results suggest that aerobic fitness affects the energetic response to changes in power output during moderate exercise, such that the more aerobically fit a subject, the greater the increase in oxygen cost (.VO(2)) (reduced efficiency) as work rate increases. Further, Delta.VO(2)/DeltaWR reflects the inverse of DeltaEff for moderate-intensity exercise in healthy fed subjects.