Intensity modulated radiation therapy with electrons using algorithm based energy/range selection methods.

BACKGROUND AND PURPOSE: In recent years photon intensity modulated radiation therapy (IMRT) has gained attention due to its ability to improve conformity of dose distributions. A potential advantage of electron-IMRT is that the dose fall off in the depth dose curve makes it possible to modulate the dose distribution in the direction of the beam by selecting different electron energies. This paper examines the use of a computer based energy selection in combination with the IMRT technique to optimise the electron dose distribution. MATERIALS AND METHODS: One centimetre square electron beamlets ranging from 2.5 to 50 MeV were pre-calculated in water using Monte Carlo methods. A modified IMRT optimisation tool was then used to find an optimum mix of electron energies and intensities. The main principles used are illustrated in some simple geometries and tested on two clinical cases of post-operated ca. mam. RESULTS: It is clearly illustrated that the energy optimisation procedure lowers the dose to lung and heart and makes the dose in the target more homogeneous. Increasing the energy at steep gradients compensates for lack of target coverage at beam edges and steep gradients. Comparison with a clinically acceptable four segment plan indicates the advantage of the used electron IMRT technique. CONCLUSIONS: Using an intensity optimised mix of computer selected electron energies has the potential to improve electron treatments for mastectomy patients with good target coverage and reduced dose to normal tissue such as lung and heart.     

Blast exposure causes redistribution of phosphorylated neurofilament subunits in neurons of the adult rat brain

There is little information on threshold levels and critical time factors for blast exposures, although brain damage after a blast has been established both clinically and experimentally. Moreover, the cellular pathophysiology of the brain response is poorly characterized. This study employs a rat model for blast exposure to investigate effects on the neuronal cytoskeleton. Exposure in the range of 154 kPa/198 dB or 240 kPa/202 dB has previously been shown neither to cause visual damage to the brain, nor to affect the neuronal populations, as revealed with routine histology. Here, the brains were investigated immunohistochemically from 2 h to 21 days after blast exposure. A monoclonal antibody was used which detects only the phosphorylated epitope of the heavy subunit of the neurofilament proteins (p-NFH). This epitope is normally restricted to axons, that is, not demonstrable in the perikarya. Eighteen hours after exposure in the 240-kPa/202-dB range, p-NFH immunoreactivity accumulated in neuronal perikarya in layers II-IV of the temporal cortex and of the cingulate and the piriform cortices, the dentate gyrus and the CA1 region of the hippocampus. At the same time, the p-NFH immunoreactivity disappeared from the axons and dendrites of cerebral cortex neurons. The most pronounced immunostaining of neuronal perikarya was found in the hemisphere, which faced the blast source. The perikaryal accumulation of p-NFH was present also at 7 days but the neuronal perikarya had become negative at 21 days, at which time the axons again displayed p-NFH immunoreactivity. Exposure in the range of 154 kPa/198 dB caused similar, although less marked accumulation of p-NFH immunoreactivity in the neuronal perikarya. The findings are interpreted to show a dephosphorylation of NFHs in axons and dendrites and a piling up of p-NFHs in the perikarya due to disturbed axonal transport.     

肠易激综合征和胶原性结肠炎患者粪便中炎性标志物的检测

目的：与腹痛及腹部不适症状相关的排便习惯改变的长期反复发作是肠易激综合征（IBS）和胶原性结肠炎（CC）的共有症状。该研究旨在明确IBS和CC患排泄物中能否检测到炎性标志物，并探讨此种检测能否作为一种无创性方式用于这些功能紊乱性疾病的鉴别。材料与方法：采集18例CC患、46例IBS患和20例健康对照（HC）的粪便，经处理后留取上清液，采用免疫法测定嗜酸粒细胞蛋白X（EPX）、髓过氧化物酶（MPO）、纤维蛋白溶酶、白介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）水平。结果：与IBS组（中位数0．44μg／g，95％CI0．25～1．8；P〈0．001）和HC组（中位数0．46μg／g，95％CI0．21～1．3；P〈0．001）相比，EPX水平在CC组中有所增加（中位数3．81μg／g，95％CI0．47～16．2）。另外，MPO水平在CC组中也有所增加（中位数11．7μg／g，95％CI2．0～124），显高于IBS患组（中位数1．7μg／g，95％CI0．81～5．2；P〈0．01）和HC组（中位数2．5μg／g，95％CI1．1～6．3；P〈0．05）。     

Effects of phencyclidine on acoustic startle and prepulse inhibition in neuronal nitric oxide synthase deficient mice.

Prepulse inhibition of acoustic startle is a behavioural response, which is used to estimate sensorimotor gating deficits in schizophrenia. Recent studies show that several behavioural effects of the psychotomimetic drug, phencyclidine (PCP), in rodents are blocked by nitric oxide synthase (NOS) inhibitors suggesting that NO plays an important role in the pharmacological effects of PCP. The present study was conducted to examine the effects of PCP on prepulse inhibition in neuronal NOS (nNOS) deficient mice. PCP treatment caused a significant and dose-related increase in prepulse inhibition in nNOS-/- mice whereas prepulse inhibition was not significantly affected in +/+ and +/- mice. Basal prepulse inhibition level did not differ significantly between the groups. Furthermore, PCP caused a dose-related decrease in startle response reactivity in +/+ mice but did not significantly affect this measure in +/- and -/- mice. Basal startle response level did not differ between +/+ and +/- but was significantly lower in -/- mice. It is concluded that nNOS plays a role in the NO-sensitive effects of PCP.     

Biallelic deletions in INK4 in cutaneous melanoma are common and associated with decreased survival.

PURPOSE: Both the retinoblastoma and p53 pathways are often genetically altered in human cancers and their complex regulation is in part mediated by the three gene products p16, p14(ARF), and p15 of the INK4 locus on chromosome 9p21. Partial or complete biallelic deletions of the INK4 locus have been recognized in a variety of malignant tumors, including malignant melanoma. We have in the present study measured the frequency of INK4 deletions in a large number of melanoma metastases and determined their association with clinicopathologic variables and survival data. EXPERIMENTAL DESIGN: Quantitative real-time PCR, as well as fluorescence-based fragment analysis, has been used to perform measurements of the relative allelic concentrations of the INK4 genes in 112 human melanoma tumor samples from 86 patients. RESULTS: Thirty-eight of 86 melanoma patients (44%) had metastases with biallelic losses in INK4. Ten of 20 patients with multiple metastases showed similar deletion patterns in all analyzed tumors. There was no significant association between any of the clinicopathologic variables and loss of INK4. However, loss of INK4 had an adverse effect on median survival from time of diagnosis. Patients with tumors with diploid INK4 had a median survival of 142 months, whereas those with monoallelic or biallelic loss in INK4 had a median survival of only 47 months (P = 0.006). CONCLUSIONS: Our results point to homozygous deletions in the INK4 region as being one of the most common genetic alterations in malignant cutaneous melanoma. INK4 deletions are associated with an adverse prognosis.     

Vitrectomy for retained lens fragments in the vitreous after phacoemulsification

PURPOSE: To assess the visual results, retinal detachment (RD) rate, incidence of glaucoma, and intraocular lens (IOL) placement after vitrectomy for removal of retained lens fragments in the vitreous after phacoemulsification. SETTING: Department of Ophthalmology, University Hospital of Lund, Lund, Sweden. METHODS: This retrospective noncomparative interventional case series included all cases of pars plana vitrectomy for removal of retained lens fragments from January 1997 through January 2000. RESULTS: Sixty-six eyes of 65 patients had pars plana vitrectomy with removal of the lens material over the 3-year period. Visual acuity on presentation was 0.1 or worse in 36 eyes (54%). Visual acuity after vitrectomy was 0.5 or better in 35 eyes (53%). The postoperative visual acuity was worse than 0.1 in 14 eyes (21%). Twenty-seven (56%) of the 48 eyes operated on within 1 week and 8 (44%) of the 18 eyes operated on later achieved a visual acuity of 0.5 or better. Twelve eyes (80%) that had secondary posterior chamber IOL implantation achieved an acuity of 0.5 or better. An RD occurred in 7 eyes (11%). CONCLUSIONS: There was no statistically significant difference in outcomes between those having vitrectomy the first few days after cataract surgery and those having it later, although there was a trend toward better results when the vitrectomy was done sooner. Secondary IOL implantation resulted in a good visual outcome. Retinal detachment was the most severe complication.     

Attenuation of renal ischaemic injury by felodipine

Summary Felodipine is a vasodilating calcium channel blocker of the dihydropyridine type. The effects of felodipine on post-ischaemic renal function were evaluated in rats subjected to bilateral renal artery occlusion for 30 or 60 min.In a first set of experiments the recovery of renal function after 30 or 60 min of renal artery occlusion was followed intermittently for 16 days by endogenous creatinine clearance. Renal function was better preserved in rats given felodipine (45 nmol/kg i.v.) during the occlusion period than in vehicle-treated control rats. The survival rate after 60-min occlusion was 11% in controls but 70% in the felodipine-treated rats. After occlusion for 30 min the survival rate was similar in the two groups, but renal function recovered faster in the felodipine group than in the controls.In a second series, acute renal damage was evaluated by the extent of erythrocytes trapped in the kidney after 30-min reperfusion following 60-min renal artery occlusion. Felodipine administration (45 nmol/kg) during the occlusion reduced renal damage compared with vehicle controls. Kidney weight and systemic haematocrit were also better maintained in the felodipine-treated rats. Furthermore, renal damage was reduced by the t-butyl analogue or felodipine, H 186/86, which is devoid of vasodilatory effects. The results demonstrate that treatment with the vasodilator calcium channel blocker felodipine protects the kidney from ischaemic/reperfusion injuries. The tissue protection is not related to the haemodynamic effects alone, since the haemodynamically inactive dihydropyridine H 186/86 also reduced the extent of renal damage. An additional antiperoxidant or scavanger-like effect inherent in the dihydropyridine molecule is suggested. Send offprint requests to M. Nordlander at the above address     

Endometrial expression of vasopressin, oxytocin and their receptors in patients with primary dysmenorrhoea and healthy volunteers at ovulation

OBJECTIVE: To investigate gene expressions for neurohypophyseal and ovarian hormones as well as their receptors in the endometrium of women with primary dysmenorrhoea and healthy subjects at ovulation. STUDY DESIGN: A group of eight women with moderate to severe dysmenorrhoea and eight healthy subjects were compared in parallel between 18 and 35 years of age, regularly menstruating, non-overweight and nulliparous. The study was performed at The Department of Obstetrics and Gynecology, University Hospital of Lund, Sweden. Endometrial biopsies were taken around the time of ovulation, which was determined by repeated ultrasound examinations. Receptor and gene expressions for oxytocin and vasopressin in the tissue were measured. RESULTS: The gene expression for oxytocin receptor was significantly lower in dysmenorrhoic than in healthy women, in median 1.21 and 3.44 oxytocin-receptor/actin, respectively (p=0.048). The expressions for oxytocin peptide, vasopressin V1a receptor, oestrogen receptor alpha, beta and progesterone receptor did not differ between the two groups. Expression of vasopressin peptide was not detectable. CONCLUSION: A lower oxytocin receptor gene expression at mid-cycle could be involved in the aetiology of primary dysmenorrhoea. However, the importance of a paracrine effect of oxytocin and its receptor at ovulation warrants further investigation.