How many growing vestibular schwannomas tend to stop growing without any treatment?

OBJECTIVE: To determine the long-term, spontaneous growth arrest rates in a large cohort of vestibular schwannoma patients. METHODS: This paper describes a retrospective case series of 735 vestibular schwannoma patients organised into four groups: group A patients showed tumour growth which then stopped without any treatment; group B patients showed tumour growth which continued, but were managed conservatively; group C patients had a growing vestibular schwannoma and received active treatment; and group D patients had a stable, non-growing vestibular schwannoma. Demographics, tumour size and vestibular schwannoma growth rate (mm/month) were recorded. RESULTS: A total of 288 patients (39.2 per cent) had growing vestibular schwannomas. Of the patients, 103 (35.8 per cent) were managed conservatively, with 52 patients (50.5 per cent of the conservative management group, 18 per cent of the total growing vestibular schwannoma group) showing growth arrest, which occurred on average at four years following the diagnosis. Eighty-two per cent of vestibular schwannomas stopped growing within five years. Only differences between age (p = 0.016) and vestibular schwannoma size (p = 0.0008) were significant. CONCLUSION: Approximately 20 per cent of growing vestibular schwannomas spontaneously stop growing, predominantly within the first five years; this is important for long-term management.

Application of ion exchange and extraction chromatography to the separation of actinium from proton-irradiated thorium metal for analytical purposes.

Actinium-225 (t1/2=9.92d) is an α-emitting radionuclide with nuclear properties well-suited for use in targeted alpha therapy (TAT), a powerful treatment method for malignant tumors. Actinium-225 can also be utilized as a generator for (213)Bi (t1/2 45.6 min), which is another valuable candidate for TAT. Actinium-225 can be produced via proton irradiation of thorium metal; however, long-lived (227)Ac (t1/2=21.8a, 99% ß(-), 1% α) is co-produced during this process and will impact the quality of the final product. Thus, accurate assays are needed to determine the (225)Ac/(227)Ac ratio, which is dependent on beam energy, irradiation time and target design. Accurate actinium assays, in turn, require efficient separation of actinium isotopes from both the Th matrix and highly radioactive activation by-products, especially radiolanthanides formed from proton-induced fission. In this study, we introduce a novel, selective chromatographic technique for the recovery and purification of actinium isotopes from irradiated Th matrices. A two-step sequence of cation exchange and extraction chromatography was implemented. Radiolanthanides were quantitatively removed from Ac, and no non-Ac radionuclidic impurities were detected in the final Ac fraction. An (225)Ac spike added prior to separation was recovered at ≥ 98%, and Ac decontamination from Th was found to be ≥ 10(6). The purified actinium fraction allowed for highly accurate (227)Ac determination at analytical scales, i.e., at (227)Ac activities of 1-100 kBq (27 nCi to 2.7 µCi).

Selenium-72 formation via nat Br(p,x) induced by 100 MeV protons: steps towards a novel 72Se/72As generator system.

Selenium-72 production by the proton bombardment of a natural NaBr target has been successfully demonstrated at the Los Alamos National Laboratory Isotope Production Facility (LANL-IPF). Arsenic-72 (half life 26 h) is a medium-lived positron emitting radionuclide with the major advantage of being formed as the daughter of another "generator" radioisotope (Se-72, 8.5 d). A (72)Se/(72)As generator would be the preferred mechanism for clinical utilization of (72)As for positron emission tomography (PET). No portable (72)Se/(72)As generator system has been demonstrated for convenient, repeated (72)As elution ("milking"). In this work, we describe (72)Se production and recovery from irradiated NaBr targets using a 100 MeV proton beam. We also introduce an (72)As generator principle based on (72)Se chelation followed by liquid-liquid extraction, which will be transferred to a solid-phase sorption/elution system.

Intraosseous soft tissue perineurioma: report of a vertebral example.

OBJECTIVE: To describe a unique intraosseous perineurioma affecting the L2 vertebral body and pedicle of a 28-year-old female. MATERIAL: A lytic, expansive lesion virtually limited to bone was gross totally excised; only minimal epidural extension was noted. METHODS: Histologic, immunohistochemical and ultrastructural studies were performed. RESULTS: The tumor was partially encapsulated, moderately cellular, and showed classic features of benign soft tissue perineurioma, being composed of interlacing fascicles of spindle cells with undulating nuclei and long, very narrow, cytoplasmic processes. Immunohistochemistry showed reactivity for EMA, Glut-1, claudin, collagen-4 and CD34; no S-100 or neurofilament protein staining was seen to suggest an origin in nerve. CONCLUSION: Perineurioma, a tumor affecting soft tissue, and presumably nerve-unassociated, may affect bone. No prior entirely osseous examples have been reported. This tumor expands the differential diagnosis of spindle cell tumors of bone.

Helminths in sympatric populations of mountain reedbuck (Redunca fulvorufula) and gray rhebok (Pelea capreolus) in South Africa.

Helminths of mountain reedbuck (Redunca fulvorufula fulvorufula) and gray rhebok (Pelea capreolus) were investigated in South Africa between June 1999 and February 2002. Forty-one mountain reedbuck were culled at Sterkfontein Dam Nature Reserve over 8 different periods, and 25 mountain reedbuck were culled at Tussen die Riviere Nature Reserve over 3 different periods. A total of 17 kinds of helminths were found at the 2 sites, including 15 nematodes, 1 trematode, and 1 cestode. At Sterkfontein, the most prevalent and abundant species were Cooperia yoshidai, Longistrongylus schrenki, and Haemonchus contortus, with the latter 2 being more abundant during November/December than at other times of the year, probably because infective larvae increased on pasture at that time. No statistical differences were found in parasite loads between male and female mountain reedbuck. No correlation was found between fecal egg counts and adult worm counts or between parasite counts and body condition. At Tussen die Riviere, helminths in mountain reedbuck were less prevalent and abundant than at Sterkfontein. The most important species were Nematodirus spathiger, Trichostrongylus falculatus, and Cooperia rotundispiculum. Four gray rhebok died of natural causes at Sterkfontein, from which 5 kinds of helminths were recovered, including C. yoshidai and Paracooperioides peleae.

Parasites of South African wildlife. XVIII. Cooperia pigachei n. sp. (Nematoda: Cooperiidae) from the mountain reedbuck, Redunca fulvorufula (Afzelius, 1815).

A new species of Cooperia, for which the name Cooperia pigachei n. sp. is proposed, was recovered from a mountain reedbuck, Redunca fulvorufula, from the Sterkfontein Dam Nature Reserve, Free State Province, and is described and illustrated. It is close to Cooperia neitzi Mönnig, 1932 and the South African race of Cooperia rotundispiculum in having more than 14 longitudinal cuticular ridges and in that the lateral cervical synlophe is of the closed type. The new species differs from all the other species of the genus in that the lateral branches of the dorsal ray are large and T-shaped. The spicules are robust, over 0.3 mm long and have large, curved shoes on their tips.

The incidence of neurosurgical disease in patients who are referred to a neurosurgical centre for CT scanning: should district general hospital scanners be more active?

This study assessed the incidence of neurosurgical intervention in those patients who were referred to a neurosurgical unit for a CT scan in whom the diagnosis was unclear. A prospective consecutive patient survey was performed over a 29 week period in a regional neurosurgical unit. One hundred patients were included. Twenty-eight patients required neurosurgical management, of whom, nine required surgery within 24 hours. Twenty-three patients required ventilation, of whom 14 did not have a neurosurgical condition. In this group of patients, the majority did not have a neurosurgical condition. Increasing the availability of scanning services in district hospitals may avoid the unnecessary transfer of potentially unstable patients.

Differential effects of chloroquine on cardiolipin biosynthesis in hepatocytes and H9c2 cardiac cells.

Chloroquine is a potent lysomotropic therapeutic agent used in the treatment of malaria. The mechanism of the chloroquine-mediated modulation of new cardiolipin biosynthesis in isolated rat liver hepatocytes and H9c2 cardiac myoblast cells was addressed in this study. Hepatocytes or H9c2 cells were incubated with [1,3-(3)H]glycerol in the absence or presence of chloroquine and cardiolipin biosynthesis was examined. The presence of chloroquine in the incubation medium of hepatocytes resulted in a rapid accumulation of radioactivity in cardiolipin indicating an elevated de novo biosynthesis. In contrast, chloroquine caused a reduction in radioactivity incorporated into cardiolipin in H9c2 cells. The presence of brefeldin A, colchicine or 3-methyladenine did not effect radioactivity incorporated into cardiolipin nor the chloroquine-mediated stimulation of cardiolipin biosynthesis in hepatocytes indicating that vesicular transport, cytoskeletal elements or increased autophagy were not involved in de novo cardiolipin biosynthesis induced by chloroquine. The addition of chloroquine to isolated rat liver membrane fractions did not affect the activity of the enzymes of de novo cardiolipin biosynthesis but resulted in an inhibition of mitochondrial cytidine-5'-diphosphate-1,2-diacyl-sn-glycerol hydrolase activity. The mechanism for the reduction in cardiolipin biosynthesis in H9c2 cells was a chloroquine-mediated inhibition of glycerol uptake and this did not involve impairment of lysosomal function. The kinetics of the chloroquine-mediated inhibition of glycerol uptake indicated the presence of a glycerol transporter in H9c2 cells. The results of this study clearly indicate that chloroquine has markedly different effects on glycerol uptake and cardiolipin biosynthesis in hepatocytes and H9c2 cardiac cells.

Thyroxine regulation of monolysocardiolipin acyltransferase activity in rat heart.

Treatment of rats with thyroxine has been shown to elevate the biosynthesis and content of cardiolipin in the heart [Cao, Cheng, Angel and Hatch (1995) Biochim. Biophys. Acta 1256, 241-244]. Treatment with thyroxine resulted in a 1.8-fold increase (P<0.025) in [1-(14)C]linoleate and a 1.7-fold increase (P<0.025) in [1-(14)C]oleate incorporated into cardiolipin in perfused hearts, compared with controls. The mechanism for the elevation in incorporation of unsaturated fatty acids into cardiolipin was a 1. 6-fold (P<0.025) increase in mitochondrial monolysocardiolipin acyltransferase activity. The results demonstrate that the acylation of cardiac monolysocardiolipin is regulated by thyroid hormone. Thus an elevation in cardiolipin biosynthesis is accompanied by an elevation in monolysocardiolipin acyltransferase activity to maintain the appropriate molecular species composition of cardiolipin in the cardiac mitochondrial membrane. We postulate that monolysocardiolipin acyltransferase might be a rate-limiting enzyme for the molecular remodelling of cardiolipin in the heart.

Acylation of monolysocardiolipin in rat heart.

Cardiolipin is a major mitochondrial membrane glycerophospholipid in the mammalian heart. In this study, the ability of the isolated intact rat heart to remodel cardiolipin and the mitochondrial enzyme activities that reacylate monolysocardiolipin to cardiolipin in vitro were characterized. Adult rat heart cardiolipin was found to contain primarily linoleic and oleic acids. Perfusion of the isolated intact rat heart in the Langendorff mode with various radioactive fatty acids, followed by analysis of radioactivity incorporated into cardiolipin and its immediate precursor phosphatidylglycerol, indicated that unsaturated fatty acids entered into cardiolipin mainly by deacylation followed by reacylation. The in vitro mitochondrial acylation of monolysocardiolipin to cardiolipin was coenzyme A-dependent with a pH optimum in the alkaline range. Significant activity was also present at physiological pH. With oleoyl-coenzyme A as substrate, the apparent K(m) for oleoyl-coenzyme A and monolysocardiolipin were 12.5 microm and 138.9 microm, respectively. With linoleoyl-coenzyme A as substrate, the apparent K(m) for linoleoyl-coenzyme A and monolysocardiolipin were 6.7 microm and 59.9 microm, respectively. Pre-incubation at 50 degrees C resulted in different profiles of enzyme inactivation for the two activities. Both activities were affected similarly by phospholipids, triacsin C, and various lipid binding proteins but were affected differently by various detergents and myristoyl-coenzyme A. [(3)H]cardiolipin was not formed from monolyso[(3)H]cardiolipin in the absence of acyl-coenzyme A. Monolysocardiolipin acyltransferase activities were observed in mitochondria prepared from various other rat tissues. In summary, the data suggest that the isolated intact rat heart has the ability to rapidly remodel cardiolipin and that rat heart mitochondria contain coenzyme A-dependent acyltransferase(s) for the acylation of monolysocardiolipin to cardiolipin. A simple and reproducible in vitro assay for the determination of acyl-coenzyme A- dependent monolysocardiolipin acyltransferase activity in mammalian tissues with exogenous monolysocardiolipin substrate is also presented.

Anterior sacral meningocele associated with a rectal fistula. Case report and review of the literature.

The authors report a case of anterior sacral meningocele associated with a rectal fistula in a patient who had presented 20 years earlier with bacterial meningitis. To their knowledge, this is the first case in which a rectal fistula developed due to an anterior sacral meningocele. The clinical presentation, diagnosis, and treatment of this uncommon lesion is discussed.

On the mechanism of the phospholipase C-mediated attenuation of cardiolipin biosynthesis in H9c2 cardiac myoblast cells.

The effect of phospholipase C treatment on cardiolipin biosynthesis was investigated in intact H9c2 cardiac myoblasts. Treatment of cells with phosphatidylcholine-specific Clostridium welchii phospholipase C reduced the pool size of phosphatidylcholine compared with controls whereas the pool size of cardiolipin and phosphatidylglycerol were unaffected. Pulse labeling experiments with [1,3-3H]glycerol and pulse-chase labeling experiments with [1,3-3H]glycerol were performed in cells incubated or pre-incubated in the absence or presence of phospholipase C. In all experiments, radioactivity incorporated into cardiolipin and phosphatidylglycerol were reduced in phospholipase C-treated cells with time compared with controls indicating attenuated de novo biosynthesis of these phospholipids. Addition of 1,2-dioctanoyl-sn-glycerol, a cell permeable 1,2-diacyl-sn-glycerol analog, to cells mimicked the inhibitory effect of phospholipase C on cardiolipin and phosphatidylglycerol biosynthesis from [1,3-3H]glycerol indicating the involvement of 1,2-diacyl-sn glycerol. The mechanism for the reduction in cardiolipin and phosphatidylglycerol biosynthesis in phospholipase C-treated cells appeared to be a decrease in the activities of phosphatidic acid:cytidine-5'triphosphate cytidylyltransferase and phosphatidylglycerolphosphate synthase, mediated by elevated 1,2-diacylsn-glycerol levels. Upon removal of phospholipase C from the incubation medium, phosphatidylcholine biosynthesis from [methyl-3H]choline was markedly stimulated. These data suggest that de novo phosphatidylglycerol and cardiolipin biosynthesis may be regulated by 1,2-diacyl-sn-glycerol and support the notion that phosphatidylglycerol and cardiolipin biosynthesis may be coordinated with phosphatidylcholine biosynthesis in H9c2 cardiac myoblast cells.

Lysophosphatidylcholine inhibits cardiolipin biosynthesis in H9c2 cardiac myoblast cells.

The effect of phospholipase A2 treatment on cardiolipin biosynthesis was investigated in intact H9c2 cardiac myoblasts. Treatment of cells with Naja mocambique mocambique phospholipase A2 reduced the pool sizes of phosphatidylcholine and phosphatidylethanolamine compared with controls. The pool sizes of lysophosphatidylcholine and lysophosphatidylethanolamine were elevated, whereas the pool sizes of cardiolipin and other phospholipids were unaffected by phospholipase A2 treatment. Pulse labeling experiments with [1,3-3H]glycerol and pulse-chase labeling experiments with [1,3-3H]glycerol were performed in cells incubated or preincubated in the absence or presence of phospholipase A2. In all experiments, radioactivity incorporated into cardiolipin was reduced in phospholipase A2-treated cells with time compared with controls, indicating attenuated de novo biosynthesis of cardiolipin. The mechanism for the reduction in cardiolipin biosynthesis in phospholipase A2-treated cells was a decrease in the activity of phosphatidic acid:cytidine-5'-triphosphate cytidylyltransferase, the rate-limiting enzyme of cardiolipin biosynthesis, mediated by elevated cellular lysophosphatidylcholine levels. The results suggest that de novo cardiolipin biosynthesis in H9c2 cells may be regulated by the cellular level of lysophosphatidylcholine.

The long-term outlook for hydrocephalus in childhood. A ten-year cohort study of 155 patients.

Despite the fact that ventriculoperitoneal shunt insertion is the most commonly performed surgical operation in the pediatric neurosurgeon's repertoire, there is a surprising paucity of long-term outcome studies for these patients detailing either the complication rate over a predetermined time period or more importantly their intellectual outcome. The aims of this study, therefore, were to determine the 10-year outcome in a cohort of 155 children with shunted hydrocephalus, both in terms of the number and time sequence of shunt complications and also the long-term academic (schooling) outcome of these individuals. This was a cohort study of 155 hydrocephalic children who underwent first-time ventriculoperitoneal shunt insertion between the years 1978 and 1983, who were then followed up on an annual outpatient basis for a period of 10 years or until death. Their academic records and the surgical morbidity and mortality encountered over the 10-year study period were used as the main outcome measures. For those children surviving until schoolage, 59% were able to attend a normal school. The academic outlook for those children with hydrocephalus secondary to infection (postmeningitic) or intraventricular hemorrhage was less favorable with 52 and 60% requiring special schooling compared to those children with congenital hydrocephalus (29%; p = 0.036). 44% (68/155) of patients in this cohort did not require a shunt revision. The commonest reasons for shunt revision were blockage (49%) and infection (19%) which predominantly occurred within the first year of their original shunt procedure. Overall the infection rate was 12% (44/380 procedures). Furthermore an increased incidence of shunt infection was noted in those under 6 months old (p = 0.040). There was an 11 % mortality during the 10-year follow-up period for those with nontumor-related hydrocephalus.

Timing of postoperative intracranial hematoma development and implications for the best use of neurosurgical intensive care.

This study records the incidence and timing of postoperative hematomas in neurosurgical patients and analyzes the best use of neurosurgical intensive care. In 2305 patients undergoing freehand or stereotactic biopsy, elective or emergency craniotomy, or posterior fossa surgery, 50 (2.2%) developed a hematoma. Clinical deterioration as a result of postoperative hematoma occurred within 6 hours of surgery in 44 patients and more than 24 hours after surgery in six patients. Although patients undergoing posterior fossa surgery or emergency craniotomy warrant longer periods of intensive-care observation, patients having elective supratentorial operations can safely be transferred to a neurosurgical ward for observation, provided they have regained their preoperative neurological status by 6 hours postsurgery.

Multiple dural metastases from a pituitary adenoma. Case report.

Only 12 cases of pituitary tumors that metastasized within the central nervous system have been reported. A further case is presented in which the histology of the multiple dural metastases remained identical to that of the original tumor, a pituitary adenoma. The authors discuss management of these rare lesions that appear histologically benign.

Calcitonin gene-related peptide reduces brain injury in a rat model of focal cerebral ischemia.

BACKGROUND AND PURPOSE: Calcitonin gene-related peptide is an endogenous vasodilating neuropeptide with a dense concentration in the trigeminocerebrovascular system. It is hypothesized that depletion of this peptide contributes to delayed cerebral ischemia after subarachnoid hemorrhage and that an exogenous supply of calcitonin gene-related peptide will augment ischemic cerebral blood flow and reduce neuronal injury. METHODS: In this study we have investigated the effect of an intravenous infusion of calcitonin gene-related peptide (100 ng/kg per minute), started 1 hour before and continued throughout 4 hours of focal cerebral ischemia, on cerebral blood flow and the volume of brain injury in a rat model of middle cerebral artery occlusion. RESULTS: Calcitonin gene-related peptide produces a significant improvement in ischemic cerebral blood flow (32 +/- 2 compared with 13 +/- 2 mL/100 g per minute in the controls; t = 6.92, P < .0001) with a concomitant reduction in the volume of ischemic brain injury (102 +/- 22 compared with 234 +/- 19 mm3; t = 4.47, P < .001). CONCLUSIONS: These findings lend support for the potential use of this peptide in the prophylactic treatment of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

(R)-2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl] acetic acid (BAY x1005), a potent leukotriene synthesis inhibitor: effects on anti-IgE challenge in human airways.

Anti-IgE at a fixed dilution (1:1000) contracted human airways that had been pretreated with atropine (1 microM), indomethacin (3 microM) and chlorpheniramine (1 microM). This response was blocked by the potent leukotriene synthesis inhibitor BAY x 1005 ((R)-2-[4-(Quinolin-2-yl-methoxy)phenyl)-2-cyclopentyl acetic acid]. The leukotriene synthesis inhibitor MK-886 also blocked the contraction, but BAY x1005 was approximately 10-fold more potent than MK-886 (the IC50 values were 0.27 microM and 3.4 microM for BAY x1005 and MK-886, respectively). BAY x1005 (1 microM) did not alter LTD4 cumulative concentration-effect curves on human airways. Bronchial muscles derived from different levels of the respiratory tract released small quantities of LTE4 (proximal, 7.99 +/- 1.25 ng/g tissue wet wt.; distal, 13.12 +/- 4.46 ng/g tissue wet wt.). These basal levels were significantly increased when the preparations were challenged with a fixed dilution (1:1000) of anti-IgE (proximal, 21.84 +/- 5.33 ng/g tissue wet wt.; distal 72.13 +/- 30.70 ng/g tissue wet wt.). Indomethacin (3 microM) did not alter either the basal amounts or the levels of LTE4 measured during anti-IgE stimulation. However, BAY x1005 or MK-886 in the presence of indomethacin prevented the increase in LTE4 levels that were observed during anti-IgE challenge. In these protocols the IC50 values obtained were 0.18 microM and 1.42 microM for BAY x1005 and MK-886, respectively. These data demonstrate that BAY x1005 is a potent leukotriene synthesis inhibitor in human airways.

Subgaleal haematoma resulting in extradural compression following craniotomy. Report of two cases.

We describe two patients who underwent intracranial aneurysm surgery and developed postoperative subgaleal haematomas which, in the presence of an unfixed bone flap, resulted in significant extradural compression and a marked clinical deterioration. The application of a pressure dressing to tamponade a developing scalp haematoma is unwise unless the bone flap has been rigidly fixed in place.

Testicular and epididymal sperm content in grazing Cashmere bucks: seasonal variation and prediction from measurements in vivo.

Each month, for 15 months, the testes and epididymides were recovered from five Australian cashmere bucks selected at random from a group of mature bucks (initial n = 116) at pasture (location 29 degrees S, 153 degrees E). The extent of seasonal change in testicular and epididymal sperm reserves was determined and indirect methods for predicting these reserves were developed. Paired testicular weight exhibited clear seasonal variation from 137 g in August to 269 g in February. The total elongated spermatid content of the testes, determined by homogenization, showed a very similar seasonal pattern, ranging from 13.8 x 10(9) in September to 36.2 x 10(9) in March. Seasonal changes of similar timing were observed for paired epididymal weight and sperm content. Although changes in total testicular spermatid content were largely the result of change in testicular weight (R2 = 0.72, P < 0.001), the elongated spermatid content of testicular parenchyma (mean, 127 x 10(6) g-1) exhibited significant seasonal variation with elevated values between February and June, suggestive of an increase in the efficiency of spermatogenesis. Daily sperm production, calculated by means of a spermatogenic time divisor for sheep, ranged from 2.76 x 10(9) in September to 7.23 x 10(9) in February. Scrotal circumference, scrotal volume and testicular length x diameter2 were identified as accurate predictors of testicular weight (R2 > or = 0.87) and sperm content (R2 > or = 0.70). The results demonstrate that: (a) cashmere bucks exhibit considerable seasonal variation in spermatogenesis associated primarily with changes in testicular mass but also with changes in the efficiency of spermatogenesis; and (b) indirect measures of testicular size are good predictors of testicular elongated sperm content. When the correct spermatogenic time divisor for goats is determined, such indirect measures may be used to predict daily sperm production.