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BACKGROUND: Stroke symptoms noticed upon waking, wake-up stroke, account for up to a quarter of all acute ischemic strokes. Patients with wake-up stroke, however, are often excluded from thrombolytic therapy. METHODS: Using our prospectively collected stroke registry, wake-up stroke and known-onset morning strokes were identified. Wakeup stroke was defined as a patient who was asleep >3 hours and first noted stroke symptoms upon awakening between 0100 and 1100. Known-onset morning stroke was defined as a patient who had symptom onset while awake during the same time interval. We compared wake-up stoke to known-onset morning stroke with respect to patient demographics, stroke severity, etiology and outcomes. RESULTS: One-quarter of patients with acute ischemic strokes (391/1415) had documented time between 0100 and 1100 of symptom onset: 141 (36%) wake-up strokes and 250 (64%) known-onset morning strokes. No difference in baseline characteristics, stroke severity, stroke etiology, neurologic deterioration, discharge disposition or functional outcome was detected. Known-onset morning stroke patients were significantly more likely to get thrombolytic therapy and have higher risk of in-hospital mortality. Wake-up stroke patients tended to be older, have higher diastolic blood pressure and have longer length of hospital stay. DISCUSSION: While patients with wake-up stroke were similar to patients with known-onset morning stroke in many respects, patients with known onset morning stroke were significantly more likely to get treated with thrombolytic therapy and have higher in-hospital mortality.

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Introducción: Los gliomas de alto grado son los tumores malignos más frecuentes del sistema nervioso central. El tratamiento con quimiorradioterapia y quimioterapia adyuvante con temozolomida puede prolongar la supervivencia, pero algunos pacientes desarrollan complicaciones durante o poco después de acabar el tratamiento debido a radionecrosis, edema o progresión tumoral. Pacientes y métodos: Presentamos el uso de bevacizumab en 4 pacientes que desarrollaron edema cerebral en relación con radionecrosis o progresión tumoral durante la fase inicial del tratamiento, con respuesta inadecuada a los corticoides y que no eran subsidiarios de tratamiento quirúrgico por la localización de la lesión o la mala situación clínica. Resultados: Los cuatro pacientes presentaron una rápida respuesta al tratamiento con bevacizumab, lo cual permitió reducir la dosis de corticoides y continuar el tratamiento estándar. Conclusiones: Bevacizumab es efectivo en el control de algunas complicaciones neurológicas debidas a edema, radionecrosis o rápida progresión de tumores no extirpables durante el tratamiento inicial de los gliomas malignos (AU)

Introduction: High grade gliomas are the most common primary malignant brain tumours. Treatment with chemoradiation and adjuvant chemotherapy with Temozolomide may prolong survival but some patients develop complications during or soon after therapy due to radiation necrosis, oedema or tumour progression. Patients: We report the use of Bevacizumab in four patients with newly diagnosed high grade gliomas who developed cerebral oedema due to tumour progression or radiation necrosis that did not respond to corticosteroids, and who were not candidates for surgical debulking. Outcomes: All four patients had a rapid response to treatment with bevacizumab, tolerating a decrease of the dose of corticosteroids, and were able to continue their standard therapy.Conclusions: Bevacizumab is effective in controlling some of the neurological complications from oedema, radiation necrosis, or rapid tumour progression during the initial treatment of malignant gliomas (AU)

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INTRODUCTION: High grade gliomas are the most common primary malignant brain tumours. Treatment with chemoradiation and adjuvant chemotherapy with Temozolomide may prolong survival but some patients develop complications during or soon after therapy due to radiation necrosis, oedema or tumour progression. PATIENTS: We report the use of Bevacizumab in four patients with newly diagnosed high grade gliomas who developed cerebral oedema due to tumour progression or radiation necrosis that did not respond to corticosteroids, and who were not candidates for surgical debulking. OUTCOMES: All four patients had a rapid response to treatment with bevacizumab, tolerating a decrease of the dose of corticosteroids, and were able to continue their standard therapy. CONCLUSIONS: Bevacizumab is effective in controlling some of the neurological complications from oedema, radiation necrosis, or rapid tumour progression during the initial treatment of malignant gliomas.

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BACKGROUND: Patients with acute neurologic symptoms may have other causes simulating ischemic stroke, called stroke mimics (SM), but they may also have averted strokes that do not appear as infarcts on neuroimaging, which we call neuroimaging-negative cerebral ischemia (NNCI). We determined the safety and outcome of IV thrombolysis within 3 hours of symptom onset in patients with SM and NNCI. METHODS: Patients treated with IV tissue plasminogen activator (tPA) within 3 hours of symptom onset were identified from our stroke registry from June 2004 to October 2008. We collected admission NIH Stroke Scale (NIHSS) score, modified Rankin score (mRS), length of stay (LOS), symptomatic intracerebral hemorrhage (sICH), and discharge diagnosis. RESULTS: Among 512 treated patients, 21% were found not to have an infarct on follow-up imaging. In the SM group (14%), average age was 55 years, median admission NIHSS was 7, median discharge NIHSS was 0, median LOS was 3 days, and there were no instances of sICH. The most common etiologies were seizure, complicated migraine, and conversion disorder. In the NNCI group (7%), average age was 61 years, median admission NIHSS was 7, median discharge NIHSS was 0, median LOS was 3 days, and there were no instances of sICH. Nearly all SM (87%) and NNCI (91%) patients were functionally independent on discharge (mRS 0-1). CONCLUSIONS: Our data support the safety of administering IV tissue plasminogen activator to patients with suspected acute cerebral ischemia within 3 hours of symptom onset, even when the diagnosis ultimately is found not to be stroke or imaging does not show an infarct.

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BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is frequently associated with intraventricular hemorrhage (IVH), which is an independent predictor of poor outcome. The purpose of this study was to examine the relationship between ICH volume and anatomic location to IVH, and to determine if ICH decompression into the ventricle is truly beneficial. METHODS: We retrospectively analyzed the CT scans and charts of all patients with ICH admitted to our stroke center over a 3-year period. Outcome data were collected using our prospective stroke registry. RESULTS: We identified 406 patients with ICH. A total of 45% had IVH. Thalamic and caudate locations had the highest IVH frequency (69% and 100%). ICH volume and ICH location were predictors of IVH (p < 0.001). Within each location, decompression ranges (specific volume ranges where ventricular rupture tends to occur) were established. Patients with IVH were twice as likely to have a poor outcome (discharge modified Rankin scale of 4 to 6) (OR 2.25, p = 0.001) when compared to patients without IVH. Caudate location was associated with a good outcome despite 100% incidence of IVH. Spontaneous ventricular decompression was not associated with better outcome, regardless of parenchymal volume reduction (p = 0.72). CONCLUSIONS: Intraventricular hemorrhage (IVH) occurs in nearly half of patients with spontaneous intracerebral hemorrhage (ICH) and is related to ICH volume and location. IVH is likely to occur within the "decompression ranges" that take into account both ICH location and volume. Further, spontaneous ventricular decompression does not translate to better clinical outcome. This information may prove useful for future ICH trials, and to the clinician communicating with patients and families.

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Conjugated linoleic acid (CLA) has been shown to reduce body fat and increase lean body mass in mice, rats, and pigs. A recent human trial indicated that CLA may work more effectively if used for prevention of body fat deposition and weight gain. To test this hypothesis, we conducted 2 experiments using relatively old mice (older than 6 mo): experiment 1, supplementation of CLA during dietary restriction and experiment 2, supplementation during ad libitum feeding followed by restriction. In experiment 1, there were significant effects of diet restriction and CLA supplementation on body composition, while CLA decreased body fat content in ad libitum diet but not significantly during diet restriction. In experiment 2, CLA fed animals had body weights similar to restricted animals and CLA significantly reduced body fat (significantly lower than prior to and post restriction, or pair fed). This suggests that CLA exerted modulation of body fat independent of reduced food intake. Based on these results, we concluded that CLA may be more effective at protecting against fat mass regain following weight loss than as a weight loss treatment.

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Four different methods for methylating conjugated linoleic acid (CLA) were compared. The HCl/MeOH and BF(3)/MeOH methods were tested under different time and temperature combinations. Increasing temperature and/or incubation time for either method decreased the cis-9,trans-11 and trans-10,cis-12 isomers, but trans-9,trans-11/trans-10,trans-12 isomers and artifacts (allylic methoxide) were increased. In addition, the triacylglyceride form of CLA was tested using the above methods and NaOMe at various temperatures for 20 min. The NaOMe did not generate methoxy artifacts. However, there were impurities in GC after methylation with NaOMe as well as with BF(3)/MeOH. The (trimethylsilyl)diazomethane method, which is a mild and easy alternative, was tested. Free forms of fatty acids were easily, but not completely, methylated by this method. Also, the method generated artifacts (trimethylsilyl CLA esters) and impurities (trimethylsilyl) that would interfere with short-chain fatty-acid analysis by GC.

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Putting together a comprehensive telehealth program is similar to putting together a puzzle. You have to fit all of the pieces together to see the big picture. An important piece of that puzzle is medical devices for telemonitoring. The equipment used in a telehealth program can span from low end, such as simply using a telephone; to high end, in which two-way audio-video systems are used with computer documentation, outcome software, and various medical device options.

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Two experiments were conducted to determine the conjugated linoleic acid (CLA) content of milk from cows offered diets rich in linoleic and linolenic acid. In experiment 1, 36 cows were assigned to a control and five treatment groups. Cows in the control group received a diet containing 51% forage and 49% grain on a dry matter basis. In the treatment group, grain was partly replaced by either 18% raw cracked soybeans, 18% roasted cracked soybeans, 3.6% soybean oil, 2.2% linseed oil, or 4.4% linseed oil. Experimental diets were fed for 5 wk. Average CLA contents in milk fat from wk 2 through 5 were 0.39% in control and 0.37, 0.77, 2.10, 1.58, and 1.63% of total fatty acids in the raw soybean, roasted soybeans, soybean oil, 2.2% linseed oil, and 4.4% linseed oil treatments, respectively. In experiment 2, 36 cows were assigned to a control and 5 treatment groups. Cows in the control group received a diet containing 55% forage and 45% grain. In the treatment groups, grain was partly replaced by soybean oil at 0.5, 1.0, 2.0, 4.0, or by linseed oil at 1.0% of the dietary dry matter. Experimental diets were fed for 5 wk. Average CLA contents in milk fat from wk 2 through 5 were 0.50% in control and 0.75, 0.76, 1.45, 2.08, and 0.73% of total fatty acids in 0.5, 1.0, 2.0, 4.0 soybean oil and 1.0% linseed oil treatments, respectively. Diets rich in linoleic or linolenic acid can increase CLA content of milk when dietary oil is accessible to the rumen microorganisms.

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We investigated the effects of conjugated linoleic acid (CLA) preparations, which were enriched for the cis-9,trans-11 CLA isomer or the trans-10,cis-12 CLA isomer, on body composition in mice. Body composition changes (reduced body fat, enhanced body water, enhanced body protein, and enhanced body ash) were associated with feeding the trans-10,cis-12 CLA isomer. In cultured 3T3-L1 adipocytes, the trans-10,cis-12 isomer reduced lipoprotein lipase activity, intracellular triacylglycerol and glycerol, and enhanced glycerol release into the medium. By contrast, the cis-9,trans-11 and trans-9,trans-11 CLA isomers did not affect these biochemical activities. We conclude that CLA-associated body composition change results from feeding the trans-10,cis-12 isomer.

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Two experiments were conducted. In Experiment 1, 8-wk-old mice were fed control diet or diet supplemented with 0.5% conjugated linoleic acid (CLA) to study the effect of CLA on body composition (CLA: 40.8-41.1% c-9,t-11 isomer, 43.5-44.9% t-10,c-12 isomer). The data for CLA-fed mice vs. controls described parallel but significantly distinct responses for both absolute and relative changes in body fat mass (reduced in CLA-fed mice) and for relative changes in whole body protein and whole body water (both of which were increased in CLA-fed mice). In the CLA-fed mice, the effect on whole body protein appeared to precede the reduction in body fat mass. In Experiment 2, weanling mice were fed control diet or diet supplemented with 0.5% CLA for 4 wk (test group), at which time all mice were fed control diet devoid of added CLA. The test group exhibited significantly reduced body fat and significantly enhanced whole body water relative to controls at the time of diet change. Time trends for changes in relative body composition were described by parallel lines where the test group exhibited significantly less body fat but significantly more whole body protein, whole body water, and whole body ash than controls. Tissue CLA levels declined following the withdrawal of CLA from the diet. In skeletal muscle of mice fed CLA-supplemented diet, the t-10,c-12 isomer was cleared significantly faster than the c-9,t-11 CLA isomer.

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Amphibians provide an unparalleled opportunity to integrate studies of development and evolution through the investigation of the fossil record of larval stages. The pattern of vertebral development in modern frogs strongly resembles that of Paleozoic labyrinthodonts in the great delay in the ossification of the vertebrae, with the centra forming much later than the neural arches. Slow ossification of the trunk vertebrae in frogs and the absence of ossification in the tail facilitate the rapid loss of the tail during metamorphosis, and may reflect retention of the pattern in their specific Paleozoic ancestors. Salamanders and caecilians ossify their centra at a much earlier stage than frogs, which resembles the condition in Paleozoic lepospondyls. The clearly distinct patterns and rates of vertebral development may indicate phylogenetic separation between the ultimate ancestors of frogs and those of salamanders and caecilians within the early radiation of ancestral tetrapods. This divergence may date from the Lower Carboniferous. Comparison with the molecular regulation of vertebral development described in modern mammals and birds suggests that the rapid chondrification of the centra in salamanders relative to that of frogs may result from the earlier migration of sclerotomal cells expressing Pax1 to the area surrounding the notochord.

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In a recent paper a new technique was proposed for remote ranging and topographical mapping by using a system with a single-photon-counting detector and a low-power pulsed laser [Appl. Opt. 35, 441 (1996)]. We report on the results from the laboratory and the field demonstration of this literal three-dimensional imaging technique. Using a detector system developed at Los Alamos with a commercial pulsed laser and observing from a single remote vantage point, we demonstrate use of this technique in the literal mapping of three-dimensional topography and the probing of a complex scene. With a reasonably short exposure this system can resolve features with height variations as small as 5 cm.

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BACKGROUND: Early detection of hearing loss coupled with appropriate early intervention is critical to speech, language, and cognitive development. These competencies serve as the foundation for later academic skills. For these reasons, many states are undertaking aggressive efforts to screen all newborns before hospital discharge. Universal detection of hearing loss in newborns is a three-stage process composed of 1) the birth admission screen, 2) follow-up and diagnosis, and 3) intervention services. Breakdown at any stage jeopardizes the entire effort. The goals of this research are to examine the birth admission screen by reviewing outcome measurements for 54 228 Texas newborns and to evaluate factors that impact outcomes positively or negatively. METHODOLOGY: All newborns were screened for hearing loss using a physiologic test of auditory function; either screening auditory brainstem responses or transient evoked otoacoustic emissions. Screening occurred in the newborn and intensive care nurseries, before hospital discharge in 9 sites as part of the nursery protocol. Patients. A total of 54 228 newborns were available for screening. OUTCOME MEASURES: Four measures were evaluated and are reported: the number of births screened, the number of newborns who passed the screen before discharge, the number of infants who returned for follow-up, and the number of infants identified with hearing loss. A Birth Screening Performance Index is also calculated. RESULTS: Results are reported for calendar years 1994, 1995, 1996, and through June 1997. A total of 54 228 newborns were available for screening; 52 508 were screened before hospital discharge during their birth admission and 50 721 passed this screen. Infants returning for follow-up screen as outpatients numbered 1224. Over this 31/2-year span, 113 infants who failed the birth admission screening had hearing loss that was sensorineural in nature. From these data, the estimated incidence of hearing loss is 3.14/1000 infants. CONCLUSIONS: Screening in the nursery with low false-positive rates can be achieved when three elements are present: audiology involvement, hospital support, and automated data and information management. Follow-up measures need improvement. Better tracking methods may help assure that at-risk newborns are connected to services.

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Recent coccidioidomycosis outbreaks among military personnel have alarmed public health officials. We used computerized hospitalization records to identify risk factors for coccidioidomycosis hospitalizations among active-duty United States Navy and Marine Corps personnel for the years 1981 to 1994. Primary pulmonary disease was the most common form of disease, accounting for 82 (73%) of the 113 first admissions. Crude annual rates of primary pulmonary disease increased markedly in 1992 and 1993 in concert with an epidemic in the United States. Demographic data from the pulmonary admissions were combined with that of a 2% random sample of the entire Navy and Marine Corps population for multivariate risk factor modeling. Persons from junior paygrades, older age groups, and those reporting a race/ethnicity other than Caucasian or Hispanic were most likely to be hospitalized with this disease. These risk factor data should be considered in designing coccidioidomycosis surveillance and prevention programs.

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The effects of conjugated linoleic acid (CLA) on body composition were investigated. ICR mice were fed a control diet containing 5.5% corn oil or a CLA-supplemented diet (5.0% corn oil plus 0.5% CLA). Mice fed CLA-supplemented diet exhibited 57% and 60% lower body fat and 5% and 14% increased lean body mass relative to controls (P < 0.05). Total carnitine palmitoyltransferase activity was increased by dietary CLA supplementation in both fat pad and skeletal muscle; the differences were significant for fat pad of fed mice and skeletal muscle of fasted mice. In cultured 3T3-L1 adipocytes CLA treatment (1 x 10(-4)M) significantly reduced heparin-releasable lipoprotein lipase activity (-66%) and the intracellular concentrations of triacylglyceride (-8%) and glycerol (-15%), but significantly increased free glycerol in the culture medium (+22%) compared to control (P < 0.05). The effects of CLA on body composition appear to be due in part to reduced fat deposition and increased lipolysis in adipocytes, possibly coupled with enhanced fatty acid oxidation in both muscle cells and adipocytes.

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We have demonstrated previously that cisplatin (DDP) and tamoxifen (TAM) act synergistically to kill human melanoma T-289 cells, and that the observed synergy is lost in the 3-fold TAM-resistant subline, 289/TAM6. We have identified the intracellular antiestrogen-binding sites (AEBSs), defined by their ability to bind antiestrogens while having no affinity for estrogen, as a possible mediator of this synergy. We report here that [3H]TAM binds to AEBSs, as defined by the ability of N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine-HCl, an AEBS-specific ligand, to compete with [3H]TAM binding. Furthermore, we have characterized the number of binding sites and their affinity for [3H]TAM by Scatchard analysis in whole-cell lysates, microsomal fractions, and nuclear fractions of both cell lines by competing [3H]TAM binding with increasing concentrations of unlabeled TAM. These data demonstrate that the loss of a high-affinity AEBS from the nuclear fraction of the 289/TAM6 cell line correlates with the loss of synergy between DDP and TAM in these cells. This implicates AEBSs as a critical component of the mechanism that mediates the synergistic interaction of DDP and TAM in human melanoma cells.

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Buspirone is a nonbenzodiazepine anxiolytic that has been effective in uncontrolled trials for treating childhood anxiety disorders. A 4-year-old boy with a history of laryngomalacia (congenital structural abnormality with airway collapse and obstruction on inhalation), pharyngeal dysphagia (difficulty in swallowing), poor weight gain, delayed self-feeding skills, and anxiety symptoms is described. An open trial of buspirone, increased gradually to 12.5 mg daily in divided doses over a period of 22 weeks, was associated with decreased anxiety, improved self-feeding skills, and weight gain. Based on parental reports, buspirone appeared to decrease separation and social anxiety, as well as anxiety associated with eating. Drug discontinuation was associated with symptom relapse, whereas drug readministration lead to the same clinical benefits that had been observed previously. The medication was well tolerated, and its benefits have persisted for over 1 year. No new recommendations can be made regarding the use of buspirone in preschool children or in the treatment of anxious behaviors adversely affecting medical conditions in children and adolescents.

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Previously it was reported that 4-hydroxy-2 (or 5)-ethyl-5 (or 2)-methyl-3(2H)-furanone (HEMF), a characteristic flavour component of Japanese-style fermented soy sauce that exhibits antioxidant activity, inhibits benzo[a]pyrene-induced forestomach neoplasia in mice. The antioxidant and anticarcinogenic activities of other structurally similar soy sauce flavour components are now reported. 4-Hydroxy-5-methyl-3(2H)-furanone (HMF) and 4-hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) were found to be antioxidants. In particular, HMF and HDMF (as well as HEMF) reduced hydrogen peroxide concentration in human polymorphonuclear leucocytes stimulated by arachidonic acid or 12-O-tetradecanoylphorbol-13-acetate. HMF and HDMF were administered individually in semipurified diet to female ICR mice previously treated with benzo[a]pyrene (1.5 mg/wk, orally for 4 wk) to initiate forestomach neoplasia. The mice were killed at 30 wk of age. Both furanones reduced forestomach neoplasms, with HDMF exhibiting more potency. The data indicate that HDMF and HMF, like HEMF, inhibit carcinogenesis in this system by acting at the post-initiation stage.

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