Accuracy of brain imaging in the diagnosis of idiopathic intracranial hypertension.

AIM: To investigate the accuracy of individual and combinations of signs on brain magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) in the diagnosis of idiopathic intracranial hypertension (IIH). MATERIALS AND METHODS: This study was approved by the institutional research ethics board without informed consent. Forty-three patients and 43 control subjects were retrospectively identified. Each patient and control had undergone brain MRI and MRV. Images were anonymized and reviewed by three neuroradiologists, blinded to clinical data, for the presence or absence of findings associated with IIH. The severity of stenosis in each transverse sinus was graded and summed to generate a combined stenosis score (CSS). The sensitivity, specificity, and likelihood ratios (LR) were calculated for individual and combinations of signs. RESULTS: Partially empty sella (specificity 95.3%, p < 0.0001), flattening of the posterior globes (specificity 100%, p < 0.0001), and CSS <4 (specificity 100%, p < 0.0001) were highly specific for IIH. The presence of one sign, or any combination, significantly increased the odds of a diagnosis of IIH (LR+ 18.5 to 46, p < 0.0001). Their absence, however, did not rule out IIH. CONCLUSIONS: Brain MRI with venography significantly increased the diagnostic certainty for IIH if there was no evidence of a mass, hydrocephalus, or sinus thrombosis and one of the following signs was present: flattening of the posterior globes, partially empty sella, CSS <4. However, absence of these signs did not exclude a diagnosis of IIH.

Implementation of apertures in a proton pencil-beam dose algorithm.

The use of field-specific apertures, routine in scattered or uniform-scanned proton fields, are still a necessity in pencil-beam scanned (PBS) fields to sharpen the penumbral edge at low energies and in high fraction dose application beyond that achievable with small spot size. We describe a model implemented in our clinical pencil-beam algorithm that models the insertion of a shaped aperture, including shapes adapted per energy layer such as may be achieved with a multi-leaf collimator. The model decomposes the spot transport into discrete steps. The first step transport a uniform intensity field of high-resolution sub-pencil-beams at the layer energy through the medium. This transport only considers primary scattering in both the patient and an optional range-shifter. The second step models the aperture areas and edge penumbral transition as a modulation of the uniform intensity. The third step convolves individual steps over the uniform-transported field including the aperture-modified intensities. We also introduce an efficient model based on a Clarkson sector integration for nuclear scattered halo protons. This avoids the explicit modeling of long range halo protons to the detriment of computational efficiency in calculation and optimization. We demonstrate that the aperture effect is primarily due to in-patient and shifter scattering with a small contribution from the apparent beam source position. The model provides insight into the primary physics contributions to the penumbra and the nuclear halo. The model allowed us to fully deploy our PBS capacity at our two-gantry center without which PBS treatments would have been inferior compared to scattered fields with apertures. Finally, Monte Carlo calculations have (nearly) replaced phenomenological pencil-beam models for collimated fields. Phenomenological models do, however, allow exposition of underlying clinical phenomena and closer connection to representative clinical observables.

Field size dependence of the output factor in passively scattered proton therapy: influence of range, modulation, air gap, and machine settings.

At the Francis H. Burr Proton Therapy Center field specific output factors (i.e., dose per monitor unit) for patient treatments were modeled for all beamlines (two gantries, fixed stereotactic, and fixed eye beamline). The authors evaluated the accuracy of dose calculation and output model for small fields. Measurements in a water phantom were performed in three of our beamlines quantifying the dependency of the output factor on the field size for a variety of proton ranges. The influence of snout size, air gap, modulation, and second scatterer was investigated. The impact of field size on output depends strongly on the depth of interest. The air gap has a notable influence on small field outputs. A field size specific correction factor to the output is necessary if the latter was modeled or measured without the custom hardware in place. The output was shown to be field size dependent even for large fields, indicating an effect beyond charged particle disequilibrium caused by lateral scatter.

Characterization of a mini-multileaf collimator in a proton beamline.

A mini-multileaf collimator (MMLC) was mounted as a field shaping collimator in a proton beamline at the Massachusetts General Hospital. The purpose is to evaluate the device's dosimetric and mechanical properties for the use in a proton beamline. For this evaluation, the authors compared MMLC and brass aperture shaped dose distributions with regard to lateral and depth dose properties. The lateral fall off is generally broader with the MMLC, with difference varying with proton range from 0.2 to 1.2 mm. Central axis depth dose curves did not show a difference in peak-to-entrance ratio, peak width, distal fall off, or range. Two-dimensional dose distributions to investigate the conformity of MMLC shaped doses show that the physical leaf width of approximately 2.5 mm does not have a significant impact. All differences seen in dose distribution shaped by the MMLC versus brass apertures were shown to be clinically insignificant. Measured neutron doses of 0.03-0.13 mSv/Gy for a closed brass beam block (depending on range) are very low compared to the previously published data. Irradiation of the tungsten MMLC, however, produced 1.5-1.8 times more neutrons than brass apertures. Exposure of the staff resulting from activation of the device is below regulatory limits. The measurements established an equivalency between aperture and MMLC shaped dose distributions.

Commissioning a passive-scattering proton therapy nozzle for accurate SOBP delivery.

Proton radiotherapy centers that currently use passively scattered proton beams do field specific calibrations for a non-negligible fraction of treatment fields, which is time and resource consuming. Our improved understanding of the passive scattering mode of the IBA universal nozzle, especially of the current modulation function, allowed us to re-commission our treatment control system for accurate delivery of SOBPs of any range and modulation, and to predict the output for each of these fields. We moved away from individual field calibrations to a state where continued quality assurance of SOBP field delivery is ensured by limited system-wide measurements that only require one hour per week. This manuscript reports on a protocol for generation of desired SOBPs and prediction of dose output.

Monitoring sexual steroids and cortisol at different stages of the ovarian cycle from two capuchin monkey species: use of non- or less invasive methods than blood sampling.

Endocrine monitoring of non-human primates (NHP) via faecal metabolites of steroid hormones appears as a useful non-invasive alternative to evaluate the reproductive status of free living NHP, as well as of those kept in captivity but of difficult handling. However, validation is needed with plasma values before its application in the field. The aim of the present study was to monitor the different phases of the menstrual cycle from the new world NHP Sapajus apella and S. libidinosus. For this, hormonal and faecal plasma levels of E2, P4 and cortisol were assessed during different days of the menstrual cycle, together with colpocitology. The mean duration of the menstrual cycle according colpocitology was of 21.7 and 21.0 days for S. apella and S. libidinosus, respectively. These values were similar to those observed via plasma analysis, i.e. 22.7 and 20.3 days for S. apella and S. libidinosus, respectively. The day of plasmatic E2 peak was set as Day -1 and the estimated day of ovulation was set as Day 0 and occurred two days earlier in S. libidinosus than in S. apella females. In both species, it was observed a delay in faecal E2 peak of six days for S. apella and of 11 days for S. libidinosus when compared with the plasma peak. A maximum P4 plasma concentration was observed in the middle of luteal phase in S. apella and in S. libidinosus, both at around day 5. However, faecal P4 peaks were detected at days 9 and 8 in S. apella and S. libidinosus, respectively. Mean plasma and faecal cortisol levels were variable during all ovulatory cycle of S. apella and S. libidinosus females. Although no exact correlation was observed between plasmatic and faecal profile of steroid hormone, faecal samples were able to indicate ovarian cycle phase, being important to assess the reproductive status of the females applying a non-invasive method.

Acute stroke with hyperdense middle cerebral artery sign benefits from IV rtPA.

OBJECTIVES: The current management of acute ischemic stroke is intravenous (IV) recombinant tissue plasminogen activator (rtPA). The presence of a hyperdense middle cerebral artery sign (HMCAS) on pre-treatment head computed tomogram (CT) is considered a poor prognostic sign. We compared the clinical outcome in IV rtPA-treated patients with and without a HMCAS. DESIGN: Retrospective analysis of prospectively collected cases treated with IV rtPA within three hours. Inclusion criteria were the presence of: i) an anterior circulation stroke; ii) a pre-treatment CT available; iii) a pre-treatment National Institutes of Health (NIH) stroke scale (NIHSS) score; and iv) a modified Rankin Score (mRS) at three months. RESULTS: One hundred and thirty patients were eligible for the analysis, 64 (49%) had a HMCAS. The HMCAS group had a trend toward a higher mean (+/-SD) pre-treatment NIHSS score compared to the non-HMCAS group (13.9+/-6 vs. 12.2+/-6; p=0.12). Accordingly, there were more patients with severe strokes (NIHSS>10) in the HMCAS group compared to the non-HMCAS one (48/64=75% vs. 35/66=53%; p=0.009). The mean (+/-SD) NIHSS score 24 hours after treatment was 10.6 (+/-8) in the HMCAS group and 8.3 (+/-7) in the non-HMCAS group (p=0.08). In a multiple logistic regression analysis, the only independent predictor of poor outcome (mRS 3-6) was pre-treatment NIHSS score (p<0.001). CONCLUSION: Patients with a HMCAS receiving IV rtPA did not fare worse at three months despite a greater proportion of patients with more severe strokes. Based on the current knowledge, IV rtPA remains a good treatment for patients with a HMCAS within three hours of symptom onset.

l-arginine alters the proteome of frozen-thawed bovine sperm during in vitro capacitation.

The aim of this work was to evaluate the proteomic changes that occurred in the frozen-thawed bovine spermatozoa after the addition of l-arginine (L-arg) during in vitro sperm capacitation. Aspects related to the sperm capacitation pattern like membrane integrity, mitochondrial activity, sperm motility and vigor, and the sperm proteome were determined. These were respectively assessed by chlortetracycline staining, H342/PI, JC-1, light microscopy, and the proteomic abundance by nUPLC-MS/MS analysis. Frozen-thawed sperm from three Nellore bulls were capacitated in vitro for 3 h in sp-TALP medium supplemented with 20 µg/mL heparin (Control) or with 20 µg/mL heparin plus 1 mM L-arg (L-arg group). Data were subjected to analysis of variance and means compared by SNK test at 5% probability. When compared to Control, the percentage of sperm motility was higher in the L-arg group (P < 0.05). For test data after 3 h of incubation, sperm capacitated with L-arg showed higher membrane integrity and mitochondrial potential when compared to Control (P < 0.05). Moreover, we observed an increase in the percentage of capacitated sperm pattern (P < 0.05). Protein abundance analysis identified 367 proteins. Forty proteins were differentially abundant between Control and L-arg group (P < 0.05), of which 11 were up-regulated, and 29 were down-regulated in L-arg group. In addition, we observed that one protein was uniquely abundant in the L-arg group. Our findings indicate that the addition of L-arg to the culture medium presented a differential protein abundance pattern and increased the bovine frozen-thawed sperm quality and the percentage of capacitated sperm. The proteomic changes observed may be linked to the molecular mechanisms involved in the action of L-arg on the in vitro sperm capacitation of cattle.

Effect of sodium nitroprusside, a nitric oxide donor, on the in vitro maturation of bovine oocytes.

Nitric oxide (NO) is a highly reactive free radical involved in intra- and intercellular signaling in various stages of reproduction. The objective of the present study was to evaluate the effect of the addition of sodium nitroprusside (SNP), a NO donor, on nuclear and cytoplasmic in vitro maturation of bovine oocytes. Analysis of variance was conducted and the means were compared by t test at a level of 5%. Low (10(-7) and 10(-9)M) and intermediate (10(-5)M) concentrations of SNP had no significant effect on nuclear maturation, however, when a greater concentration of SNP (10(-3)M) was added, oocytes remained in metaphase I (MI) after 24 h culture (P<0.05) and did not show cumulus expansion. To evaluate if this effect was reversible and if a retardation or inhibition had occurred in the progression from MI to MII, oocytes were cultured in presence of 10(-3)M of SNP for 24 h followed by culture for an additional 24 h in medium with or without SNP. After 48 h, the oocytes remained in MI even when the medium was changed at 24 h with or without SNP. The kinetics of nuclear maturation was assessed to evaluate if there had been or not a retardation in the progression of meiosis with the concentration of 10(-3)M SNP. This concentration delayed germinal vesicle breakdown (VGBD) at 8 h of culture (P<0.05), and at 12 h there was no significant difference between the control and the treated group. The concentrations that did not induce alterations in nuclear maturation were evaluated for cytoplasmic maturation. The concentration of 10(-5)M improved the percentage of peripheral cortical granules (P<0.05), and significantly increased the percentage of blastocysts. These results demonstrate that SNP at greater concentrations (10(-3)M) has a cytotoxic effect, but at intermediate (10(-5)M) concentrations it increases blastocyst rates. NO exhibits a dual effect on bovine oocytes, inhibits (10(-3)M of SNP) nuclear and cytoplasmic maturation or stimulates (10(-5)M of SNP) cytoplasmic maturation, depending on concentration in the culture medium.

Ultrasonographic imaging of the reproductive tract and surgical recovery of oocytes in Cebus apella (capuchin monkeys).

Two-dimensional real-time and Doppler ultrasonography are valuable non-invasive methods to assess reproductive anatomy and physiology. In adult, postpubertal female Cebus apella (capuchin monkeys), the objectives were to determine (1) uterine and ovarian dimensions, ovarian follicular dynamics, day of ovulation, and arterial blood flow of uterus and utero-ovarian ligament during the follicular phase of the menstrual cycle and (2) the number of oocytes aspirated from antral follicles at laparotomy. Based on two-dimensional, transabdominal B-mode ultrasonography, mean (+/- S.E.M.) length, height, width, and volume of the uterus were 17.9+/-0.4, 12.4+/-0.3, 13.6+/-0.3 mm, and 1.55+/-0.08 mL, respectively, and of the ovary were 13.4+/-0.2, 8.2+/-0.1, 7.7+/-0.1 mm, and 4.5+/-0.2 mL. Ovarian follicles were monitored for 6 days before ovulation, which occurred on day 9.3+/-0.5 (range, days 7-11; day 1=start of menses), with 10 of 12 ovulations in the right ovary. Diameter and volume of the preovulatory follicle were 10.1+/-0.2 mm and 0.55+/-0.03 mL (on the estimated day of ovulation) and of the CL were 8.1+/-0.4 mm and 0.3+/-0.05 mL. Resistivity and pulsatility indices were 0.86+/-0.02 and 2.15+/-0.11 for uterine arteries, and were 0.69+/-0.04 and 1.63+/-0.15 for the utero-ovarian ligament (UOL) artery; just prior to ovulation, both indices peaked (P<0.05) in the uterine artery ipsilateral to the side of ovulation, but both reached a nadir (P<0.05) in the UOL artery. In the absence of ovarian stimulation, 31 oocytes (diameter, 137+/-10 microm) were aspirated (average of 2 oocytes/(female attempt)) on days 5, 7, and 9. In conclusion, transabdominal ultrasonography facilitated assessment of reproductive anatomy and physiology in C. apella adult females. Resistance and pulsatility indices of uterine and UOL arteries changed near the time of ovulation. Dominant follicles were easiest to aspirate at 8-9 mm in diameter ( approximately day 9), with intact cumulus-oocyte complexes recovered from ovarian follicles 2-9 mm in diameter.

L-arginine affects the IVM of cattle cumulus-oocyte complexes.

Nitric oxide (NO) is identified as a signaling molecule involved in many cellular or physiological functions, including meiotic maturation of cattle oocytes. This study aimed to evaluate the effect of supplementation of culture medium with the L-arginine (L-arg, NO synthesis precursor) in nuclear maturation of oocytes, concentrations of nitrate/nitrite, progesterone (P4), and 17ß-estradiol (E2) in the culture medium; and the cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) intracellular concentrations in the cumulus-oocyte complexes (COCs) during the first hours of maturation in the presence of hemisections (HSs) of the follicular wall (control -ve). The addition of 5.0-mM L-arg increased (P < 0.05) the percentage of oocytes at the germinal vesicle breakdown stage after 7 hours of cultivation compared with control -ve. All concentrations of L-arg (2.5, 5.0, and 10.0 mM) increased the percentage of oocytes that reached the metaphase I (MI) at 15 hours (P < 0.05) but do not affect the progression from MI to metaphase II (P > 0.05) at 22 hours. All concentrations of L-arg tested increased (P < 0.05) the percentage of cumulus cells with plasma membrane integrity at 22 hours of cultivation. L-arginine did not change (P > 0.05) the nitrate/nitrite, P4, and E2 concentrations in relation to control -ve at any of the times tested. In immature COCs, immediately after being removed from the follicles (0 hours), the intracellular concentration of cGMP in the control -ve and treatment with 5-mM L-arg progressively decreased (P < 0.05) after the first hour of cultivation; however, COCs treated with 5.0-mM L-arg had higher concentrations of cGMP at 1 hour of cultivation (P < 0.05). The cAMP concentration of COCs supplemented or not with 5.0-mM L-arg progressively increased until 3 hours of cultivation and at, 6 hours, decreased (P < 0.05). The results show, in using this system, that (1) the mechanisms that give the oocyte the ability to restart the meiosis until MI after adding 5.0-mM L-arg do not involve changes in the concentration of nitrate/nitrite, P4, and E2 in the culture medium and (2) L-arg acts on a pathway that involves changing the cGMP concentration but does not involve changing cAMP concentration. More studies are needed to assess whether the observed effects of L-arg during IVM using this system are via NO or not and what the role is in increasing the viability of cumulus cells in the resumption and progression of meiosis until MI.

Evaluating a formal evidence-based clinical practice curriculum in a neurology residency program.

BACKGROUND: Since 1998, the University of Western Ontario Evidence-Based Neurology Programme has been fostering life-long self-teaching, self-evaluation, and promoting improvement of the care of neurological patients by teaching neurology residents to practice Evidence-Based Clinical Practice (EBCP). DESIGN/METHODS: Using a questionnaire/survey we evaluated participation during EBCP sessions and the applicability of EBCP to current and future clinical practice. Also, using a rating scale we investigated how likely our residents' and graduates' clinical practice has been influenced by the EBCP knowledge; and, if they were teaching these concepts to residents or medical students. The questionnaire was sent to all neurology residents and neurologists that graduated after implementation of the programme. RESULTS: All residents (100%) returned the survey/questionnaire, indicating that they attended the sessions consistently. Even though all respondents believed that the EBCP concepts were useful during their training, the concepts were infrequently utilized because of time constraints. On a scale of 1 to 10, they rated the influence to include EBCP concepts in their daily clinical practice as high (average: 6.8, S.D. 1.5). They all had frequent contact with medical students and non-neurology residents, but did not teach EBCP concepts to them on a consistent basis, because of time limitations. 10 (77%) out of 13 graduates returned the survey/questionnaire. They also believed the EBCP concepts were useful, but only used them when time allowed. They also rated the influence to include EBCP concepts in their daily clinical practice as high (mean 8.5, S.D. 1.2). Most graduates had frequent contact with trainees, but did not teach EBCP concepts to them on a consistent basis because of time constraints. Finally, all expressed the need to continue having this formal curriculum during residency. CONCLUSION/RELEVANCE: Although EBCP incorporated into the curriculum of a neurology residency programme increased neurologists and neurology trainees' confidence in knowledge of existing evidence, and reinforced the EBCP principles, these concepts were not used in daily clinical practice and were not taught to more junior trainees due to time constraints.

Reciprocal regulation of choline acetyltransferase and choline kinase in sympathetic neurons during cholinergic differentiation.

The regulation of the synthesis of acetylcholine and phosphatidylcholine in rat sympathetic neurons was examined in the context of cholinergic differentiation. We demonstrate that the activities of choline acetyltransferase (ChAT) and choline kinase (CK) are inversely affected by treatment of sympathetic neurons with retinoic acid, utilized as an agent that induces cholinergic differentiation. Whereas ChAT specific activity increased 2- to 4-fold after 12 days of treatment with 5 microM retinoic acid, CK specific activity decreased by 25-30%. These changes in enzyme activities were essentially reflected in the incorporation of [methyl-3H]choline into ACh and the metabolites of the CDP-choline pathway for phosphatidylcholine synthesis. When sympathetic neurons were treated under high potassium conditions (50 mM) for 12 days, the specific activity of CK increased 1.3-fold whereas the activity of ChAT decreased by up to 90%. Furthermore, experiments in which the incorporation of [methyl-3H]choline into ACh and the metabolites of the CDP-choline pathway was measured in the absence of Na+ or in the presence of hemicholinium-3 (HC-3), demonstrate that CK has access to the same pool of choline utilized by ChAT. These results provide evidence that the activities of ChAT and CK may be inversely regulated during the process of cholinergic differentiation.

CTP: phosphocholine cytidylyltransferase is both a nuclear and cytoplasmic protein in primary hepatocytes.

CTP:phosphocholine cytidylyltransferase (CT) has recently been reported to be a predominantly intranuclear enzyme in several cell lines (Wang et al., J. Biol. Chem. 268, 5899-5904 (1993)). This contrasts with previous reports that CT was a cytosolic protein that translocated to the endoplasmic reticulum upon activation. The aim of the present study was to compare the localization of CT in CHO cells and in primary rat hepatocytes. Indirect immunofluorescence of CHO cells revealed a largely nuclear localization of the CT. On the other hand, immunogold electron microscopy and biochemical studies showed a similar density of distribution of CT between the nucleus and cytoplasm. In primary rat hepatocytes immunofluorescence studies indicated that CT was largely cytoplasmic. Studies by immunogold electron microscopy of rat hepatocytes demonstrated that the enzyme was homogeneously distributed throughout all cytoplasmic regions and the nucleoplasm. This result was confirmed by biochemical studies using digitonin and streptolysin O, which permeabilizes the plasma membrane of cells. Enucleation studies indicated that in CHO cells 76% of the CT activity was in the nuclear fraction, whereas in hepatocytes only 32% was recovered in this fraction. The data indicate that CT is found both in nuclear and cytoplasmic fractions of primary hepatocytes and is not predominantly a nuclear enzyme.

Analysis of prostate and seminal vesicle motion: implications for treatment planning.

PURPOSE: To quantify prostate and seminal vesicle positional changes (target motion) between treatment planning and delivery, and to identify the factors contributing to target motion. METHODS AND MATERIALS: Thirty patients with adenocarcinoma of the prostate were prospectively evaluated by analyzing two sequential planning computerized tomography (CT) scans (S1, obtained prior to treatment, and S2, obtained during the fourth week of treatment) for each patient. All anatomical volumes of interest (soft tissue and bony) were reconstructed from transverse CT images and projected onto anterior and lateral beam's-eye view projections. Positional changes between S1 and S2 were eliminated by applying a rigid body translation and rotation. Target motion was then measured by recording the positional change between S1 and S2 at the edges (right, left, superior, inferior). Potential correlation of target motion with bladder volume, rectal volume, and rectal diameter changes were evaluated by linear regression analysis. RESULTS: Neither the prostate nor seminal vesicles remained fixed with respect to bony anatomy between S1 and S2. The distribution of positional changes were generally small (< 0.5 cm), but maximum displacements of 1.5-2.2 cm did occur, particularly in the lateral view. In this study, bladder volume changes between the scans were small and did not correlate with target motion (P = 0.67). Both rectal volume and rectal diameter changes correlated with target motion for both the prostate (p = 0.004 and 0.005, respectively) and seminal vesicles (p < 0.001 and < 0.001, respectively). However, neither the initial rectal volume nor the initial rectal diameter could be used to predict subsequent target motion when evaluated either singly or as part of a multiple regression model. CONCLUSIONS: Target motion occurs during the course of treatment planning and delivery and should be considered when designing conformal radiation fields. Although the target position at the time of planning CT may differ substantially from the mean treatment position, target motion cannot be predicted by evaluating simply measured parameters from a single scan, or double scan sequence.

Dose-escalation with proton/photon irradiation for Daumas-Duport lower-grade glioma: results of an institutional phase I/II trial.

PURPOSE: The role of dose escalation with proton/photon radiotherapy in lower-grade gliomas was assessed in a prospective Phase I/II trial. We report the results in terms of local control, toxicity, and survival. MATERIALS AND METHODS: Twenty patients with Grade 2/4 (n = 7) and Grade 3/4 (n = 13) gliomas according to the Daumas-Duport classification were treated on a prospective institutional protocol at Massachusetts General Hospital/Harvard Cyclotron Laboratory between 1993 and 1996. Doses prescribed to the target volumes were 68.2 cobalt Gray equivalent (CGE, 1 proton Gray = 1.1 CGE) to gross tumor in Grade 2 lesions and 79.7 CGE in Grade 3 lesions. Fractionation was conventional, with 1.8 to 1.92 CGE once per day. Eligibility criteria included age between 18 and 70 years, biopsy-proven Daumas-Duport Grade 2/4 or 3/4 malignant glioma, Karnofsky performance score of 70 or greater, and supratentorial tumor. Median age of the patient population at diagnosis was 35.9 years (range 19-49). Ten tumors were mixed gliomas, one an oligodendroglioma. RESULTS: Five patients underwent biopsy, 12 a subtotal resection, and 3 a gross total resection. Median interval from surgery to first radiation treatment was 2.9 months. Actuarial 5-year survival rate for Grade 2 lesions was 71% as calculated from diagnosis (median survival not yet reached); actuarial 5-year survival for Grade 3 lesions was 23% (median 29 months). Median follow-up is 61 months and 55 months for 4 patients alive with Grade 2 and 3 patients alive with Grade 3 lesions, respectively. Three patients with Grade 2 lesions died from tumor recurrence, whereas 2 of the 4 survivors have evidence of radiation necrosis. Eight of 10 patients who have died with Grade 3 lesions died from tumor recurrence, 1 from pulmonary embolus, and 1 most likely from radiation necrosis. One of 3 survivors in this group has evidence of radiation necrosis. CONCLUSION: Tumor recurrence was neither prevented nor noticeably delayed in our patients relative to published series on photon irradiation. Dose escalation using this fractionation scheme and total dose delivered failed to improve outcome for patients with Grade 2 and 3 gliomas.

Compartmentalization of choline and acetylcholine metabolism in cultured sympathetic neurons.

To determine the relative contribution of cell bodies and distal axons to the production of acetylcholine, we used retinoic acid to induce a cholinergic phenotype in compartmented cultures of rat sympathetic neurons. When [3H]choline was given to cell bodies/proximal axons for 24 h, 98% of the radiolabel was recovered as choline, phosphocholine, CDP-choline and phosphatidylcholine, whereas only 1 to 2% of the radiolabel was incorporated into acetylcholine. Choline taken up by cell bodies and transported to axons is poorly utilized for acetylcholine biosynthesis. In contrast, when distal axons were supplied with [3H]choline, 11% of the radiolabel was recovered in acetylcholine after 24 h, the remainder being incorporated into precursors/metabolites of phosphatidylcholine. The lack of acetylcholine synthesis in cell bodies/proximal axons could not be ascribed to an absence of choline acetyltransferase activity in this region of the neurons, since the specific activity of this enzyme was similar in cell bodies/proximal axons and distal axons. The rate of choline uptake by distal axons (15.3 4.4 nmol/5 min/mg protein) was approximately 10-fold greater than by cell bodies/proximal axons (1.6 0.8 nmol/5 min/mg protein). Moreover, choline uptake into distal axons was inhibited by 74.5% by hemicholinium-3, and by 80.1% by removal of Na(+) from the medium. In contrast, choline uptake by cell bodies/proximal axons was not significantly inhibited by hemicholinium-3 or Na(+) removal. These results suggest that the majority of axonal acetylcholine is synthesized in distal axons/axon terminals from choline taken up by a high-affinity choline transporter in distal axons.

Predicting relapse: a meta-analysis of sexual offender recidivism studies.

Evidence from 61 follow-up studies was examined to identify the factors most strongly related to recidivism among sexual offenders. On average, the sexual offense recidivism rate was low (13.4%; n = 23,393). There were, however, subgroups of offenders who recidivated at high rates. Sexual offense recidivism was best predicted by measures of sexual deviancy (e.g., deviant sexual preferences, prior sexual offenses) and, to a lesser extent, by general criminological factors (e.g., age, total prior offenses). Those offenders who failed to complete treatment were at higher risk for reoffending than those who completed treatment. The predictors of nonsexual violent recidivism and general (any) recidivism were similar to those predictors found among nonsexual criminals (e.g., prior violent offenses, age, juvenile deliquency). Our results suggest that applied risk assessments of sexual offenders should consider separately the offender's risk for sexual and nonsexual recidivism.

Accelerated fractionated proton/photon irradiation to 90 cobalt gray equivalent for glioblastoma multiforme: results of a phase II prospective trial.

OBJECT: After conventional doses of 55 to 65 Gy of fractionated irradiation, glioblastoma multiforme (GBM) usually recurs at its original location. This institutional phase II study was designed to assess whether dose escalation to 90 cobalt gray equivalent (CGE) with conformal protons and photons in accelerated fractionation would improve local tumor control and patient survival. METHODS: Twenty-three patients were enrolled in this study. Eligibility criteria included age between 18 and 70 years, Karnofsky Performance Scale score of greater than or equal to 70, residual tumor volume of less than 60 ml, and a supratentorial, unilateral tumor. Actuarial survival rates at 2 and 3 years were 34% and 18%, respectively. The median survival time was 20 months, with four patients alive 22 to 60 months postdiagnosis. Analysis by Radiation Therapy Oncology Group prognostic criteria or Medical Research Council indices showed a 5- to 11-month increase in median survival time over those of comparable conventionally treated patients. All patients developed new areas of gadolinium enhancement during the follow-up period. Histological examination of tissues obtained at biopsy, resection, or autopsy was conducted in 15 of 23 patients. Radiation necrosis only was demonstrated in seven patients, and their survival was significantly longer than that of patients with recurrent tumor (p = 0.01). Tumor regrowth occurred most commonly in areas that received doses of 60 to 70 CGE or less; recurrent tumor was found in only one case in the 90-CGE volume. CONCLUSIONS: A dose of 90 CGE in accelerated fractionation prevented central recurrence in almost all cases. The median survival time was extended to 20 months, likely as a result of central control. Tumors will usually recur in areas immediately peripheral to this 90-CGE volume, but attempts to extend local control by enlarging the central volume are likely to be limited by difficulties with radiation necrosis.

Limiting values of backscatter factors for low-energy x-ray beams.

Models for the calculation of upper and lower limiting values to the backscatter factor (BSF) are presented. The upper limit is obtained from Monte Carlo simulations of infinite parallel beams incident on semi-infinite phantoms with the dose contributions from all orders of photon scatter considered. The lower limits are calculated using an analytical photon transport model which considers only the primary dose and the scatter dose from photons that have undergone single scattering interactions in the phantom. The limiting values can be used to evaluate measured and modelled BSF values for x-ray beams with photons of < or = 150 keV. A parametrization of the limiting values in terms of photon energy and irradiation field size is presented so that results determined for monoenergetic beams can be extended to polyenergetic spectra. The utility of the limits is illustrated by comparisons made with BSFs from the literature.