bluuebunny/crossref_metadata_2025_split huggingface dataset:
KIT Pathway Alterations in Mucosal Melanomas of the Vulva and Other Sites
Authors: Omholt Katarina , Grafström Eva , Kanter-Lewensohn Lena , Hansson Johan , Ragnarsson-Olding Boel K. 
Published: June 2011

Abstract
Purpose: A significant proportion of mucosal melanomas contain alterations in KIT. The aim of this study was to characterize the pattern of KIT, NRAS, and BRAF mutations in mucosal melanomas at specific sites and to assess activation of the KIT downstream RAF/MEK/extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/AKT pathways in mucosal melanoma specimens.
Experimental Design: Seventy-one primary mucosal melanomas from various sites were studied. Mutation analysis was done by DNA sequencing. Expression of KIT, phosphorylated (p)-ERK, and p-AKT was evaluated by immunohistochemistry.
Results: KIT mutations were detected in 35% (8 of 23) of vulvar, 9% (2 of 22) of anorectal, 7% (1 of 14) of nasal cavity, and 20% (1 of 5) of penile melanomas. No KIT mutations were found in 7 vaginal melanomas. The difference in KIT mutation frequency between vulvar and nonvulvar cases was statistically significant (P = 0.014). The overall frequencies of NRAS and BRAF mutations were 10% and 6%, respectively. Notably, vaginal melanomas showed a NRAS mutation rate of 43%. KIT gene amplification (≥4 copies), as assessed by quantitative real-time PCR, was observed in 19% of cases. KIT expression was associated with KIT mutation status (P &lt; 0.001) and was more common in vulvar than nonvulvar tumors (P = 0.016). Expression of p-ERK and p-AKT was observed in 42% and 59% of tumors, respectively, and occurred irrespective of KIT/NRAS/BRAF mutation status. NRAS mutation was associated with worse overall survival in univariate analysis.
Conclusions: Results show that KIT mutations are more common in vulvar melanomas than other types of mucosal melanomas and that both the RAF/MEK/ERK and PI3K/AKT pathways are activated in mucosal melanoma specimens. Clin Cancer Res; 17(12); 3933–42. ©2011 AACR.
Translating Scientific Advancement into Clinical Benefit for Castration-Resistant Prostate Cancer Patients
Authors: Attard Gerhardt , de Bono Johann S. 
Published: June 2011

Abstract
In the past 12 months, three novel therapeutics—sipuleucel-T, cabazitaxel, and abiraterone acetate—were granted Food and Drug Administration regulatory approval for the treatment of metastatic castration-resistant prostate cancer (CRPC) patients based on phase III studies that showed a survival advantage. Other agents, including the novel antiandrogen MDV3100, are at an advanced stage of clinical phase III evaluation. The treatment paradigm for CRPC has now changed significantly, and this has introduced new challenges for physicians, including selecting patients for specific therapies, developing the best sequencing and combination regimens for the several new effective agents that have recently been approved or are in development, and dissecting mechanisms of resistance that will inform the development of a new generation of therapeutics. This Focus issue reviews the results obtained with immunotherapies, taxane cytotoxics, and androgen receptor targeting therapeutics for CRPC, as well as the postulated mechanisms of resistance to these protocols and proposed strategies for improvement. The use of biomarkers for patient selection, monitoring of treatment activity, and acceleration of drug approval will be critical for achieving further improvements in the treatment for CRPC, and is also discussed in detail. Clin Cancer Res; 17(12); 3867–75. ©2011 AACR.
Recurrent Atherosclerotic Obstruction of the Internal Carotid Artery Five Years After Endarterectomy
Authors: HEYMAN ALBERT , BROWN IVAN W. , CAMPLONG LINDA , UTLEY CAROL 
Published: June 2011

A patient is described in whom an obstructive atherosclerotic plaque recurred in the cervical portion of the internal carotid artery five years after endarterectomy. The lesion appeared to be a new formation of atheromatous material contiguous to the site of the previous arteriotomy and resulted in neurological symptoms almost identical to those experienced by the patient five years before.
This case suggests that the treatment of cerebral ischemia by surgical removal of stenotic lesions in the extracranial cerebral arteries may produce only temporary relief of symptoms and emphasizes the need, following endarterectomy, for medical therapy of the underlying atherosclerotic disease.
Death Statistics for Cerebrovascular Disease: A Review of Recent Findings
Authors: WYLIE CHARLES M. 
Published: June 2011

There is a large margin of error in death statistics. Mortality statistics for cerebrovascular disease show, however, the well-known rise in frequency with age, the higher frequency in men than women which is likely to affect all countries in the coming years, and the greater involvement of nonwhite Americans and Japanese than of white Americans and Japanese Americans. I believe that incidence figures, when they become available in future years, will confirm these findings. Environmental factors, such as a "water factor," also relate to cerebrovascular death rates. Possibly the biggest factor in the medical environment, causing artificial swings in both mortality and incidence figures, will be shown to be the changing diagnostic habits of physicians.
From the viewpoint of etiology, the coexistence of hypertension and cerebrovascular disease dominates the epidemiological picture. The geographic distribution of cerebrovascular mortality in the U.S.A., and the higher mortality in Negroes and in the elderly, particularly relate to underlying hypertension. Ongoing and future population studies, focusing on morbidity as well as mortality, are likely to contribute much in clarifying the relative importance of other causal factors whose harmful effects can be controlled.
A Method for Measuring Cerebral Hemispheric Blood Flow and Metabolism
Authors: MEYER JOHN STIRLING , SHINOHARA YUKITO 
Published: June 2011

A new method for measuring cerebral hemispheric blood flow together with metabolism using an injection of a 5 ml bolus of hydrogen-saturated saline into each internal carotid artery is described. This method was extensively evaluated in the monkey prior to being used in man.
Under fluoroscopic control, a catheter was inserted into each cerebral transverse sinus via the basilic veins. Hemispheric blood flow was calculated from the clearance curves of hydrogen from the transverse sinus following injection using a formula based upon the Stewart-Hamilton principle. Hemispheric metabolic index for oxygen was estimated using a new formula by assuming that the distribution of hydrogen into each transverse sinus following injection of the bolus indicates the distribution of the blood from each hemisphere into each transverse sinus.
This method has certain advantages over the conventional method for measuring cerebral blood flow, since the actual geometry of the brain in which the blood flow measured is known and simultaneous estimations of hemispheric metabolism are possible.
Abnormalities of hemispheric blood flow and metabolism have been measured in 30 patients suffering from various neurological disorders including occlusion of one internal carotid artery.
The new formula for estimating hemispheric metabolism is applicable to radioisotopic and other indicator injection methods in which blood is sampled from the cerebral transverse sinuses or internal jugular veins.
It was also shown that the transverse sinus distribution of blood derived from each cerebral hemisphere varies from one individual to another.
Age: Its Significance in Nonembolic Cerebral Infarction
Authors: LOUIS SYDNEY , MCDOWELL FLETCHER 
Published: June 2011

The frequency of occurrence of nonembolic cerebral infarction is linearly related to age.
The sexual frequency of nonembolic cerebral infarction is directly related to the age group of the sample studied.
The mortality of nonembolic cerebral infarction and its prognosis are most closely related to the age of the patient at the time of stroke. The older the patient, the higher is the mortality and the poorer the prognosis.
The cause of death in nonembolic cerebral infarction is as much a function of age-related concurrent diseases, especially cardiac disease, as it is of stroke itself. The natural history of stroke is more related to the natural history of cardiac disease than it is to cerebral vascular disease.
These data may be viewed as lending support to the thesis that nonembolic cerebral infarction and the diseases that are frequently found with it, such as diabetes, cardiac disease and hypertension, are related in their occurrence and mortality to aging and may truly be concurrent events and not etiologically related one to the other.
The Role of the Sympathetic Nervous System in Lipid Deposition. I. Increased Lipid Deposits in the Iris of the Sympathectomized Eye in Rabbits Fed an Atherogenic Diet
Authors: AUSTIN JAMES , ROBERTS WILLIAM , NEVILLE HANS , ARMSTRONG DONALD 
Published: June 2011

Rabbits on a high-cholesterol diet deposit more lipid in the iris of the sympathectomized eye.
Histologically, the lipid deposits are composed of sudanophilic staining droplets localized both in smooth muscle cell cytoplasm of the iris dilator muscle and in larger oval cells. Possible metabolic and vascular mechanisms are noted which may underlie these findings. Potential clinical implications of these findings are cited.
The Electrical Activity of the Heart and Brain Under Acute Experimental Anoxia: The Protective Effect of Polarizing Solutions
Authors: ARIZA-HERRERA DANIEL , SODI-PALLARES DEMETRIO , SAENZ-ARROYO LUIS , CISNEROS FERNANDO , BISTENI ABDO , DEL MERCADO JOSE VAZQUEZ 
Published: June 2011

Acute anoxia was produced in 80 dogs under anesthesia with sodium pentobarbital. Respiration was maintained with a Palmer's pump through an endotracheal tube. The anoxia was produced by stopping the pump and occluding the endotracheal tube. Polarizing solution (glucose-potassium-insulin) was perfused in 40 of the animals, starting three hours prior to the anoxia. The remaining 40 dogs comprised the control group. Peripheral electrocardiograms, as well as electroencephalograms, were simultaneously recorded before and during the period of anoxia. Recordings were continuously obtained until no more than one ventricular complex in a ten-second period was observed, even though the electrical brain activity had disappeared by this time.
Our present experimental work suggests the beneficial effect of polarizing solutions by delaying the anoxic degradation of the electrical phenomenon of the heart and the brain.
Factors Influencing Stroke Rehabilitation
Authors: STERN PETER HANS , MCDOWELL FLETCHER , MILLER JAMES M. , ROBINSON MARILYN 
Published: June 2011

Quantitative and semiquantitative methods have been used to evaluate the clinical improvement of 62 patients with completed stroke who were admitted to a rehabilitation hospital.
Improvement in motility and leg strength on the paretic side was minimal and was not influenced by facilitation exercise techniques. Observed changes in strength and motility occurred to about the same degree on both the nonparetic and paretic sides. Patients who had a short interval between onset of stroke and admission to the rehabilitation program improved significantly more on the paretic side than those with a longer interval. Practically no improvement in motility and leg strength was found two months following a stroke.
Hemiplegia and hemiparesis were defined quantitatively on the basis of motility test scores. Patients with hemiparesis showed greater improvement in motility and self-care status in about half the time of hospital stay when compared with patients with hemiplegia. In spite of relatively static neurological deficits, all patients showed evidence of functional improvement as assessed by a self-care rating scale. The poorest functional outcome was seen in patients who had hemisensory losses in addition to hemiplegia. The observations indicate that early, functionally oriented stroke rehabilitation programs offer the best chance of aiding patients. Behavioral and sociological influences on final outcome are important and must be carefully evaluated to insure maximum chances of successes in rehabilitation.
Improvement in Motor Performance in Paretic and Paralyzed Extremities Following Nonembolic Cerebral Infarction
Authors: MCDOWELL FLETCHER , LOUIS SYDNEY 
Published: June 2011

The problems involved in measuring improvement as well as the conceptual difficulties in considering this phenomenon were considered in general terms.
Data on 300 patients with nonembolic cerebral infarction followed from five to nine years are presented, indicating that improvement in function of a paralyzed extremity may occur in the early phase after stroke but was extremely unlikely to continue during long-term follow-up from three months to five years. It was concluded that improvement in function might be determined more by retraining of the nonaffected muscles and particularly of the unaffected side rather than by recovery of the area paralyzed.
A-Mode Echoencephalography in the Evaluation of Cerebrovascular Disease
Authors: SANDOK BURTON A. 
Published: June 2011

The value of A-mode echoencephalography was studied in a series of patients with Cerebrovascular disease of various types. The procedure proved to be restricted value limited to those situations in which (1) a midline shift was obtained, and (2) the midline shift was observed within 36 hours after the onset of symptoms.
Whereas after 36 hours some patients with cerebral infarction showed a midline shift (presumably due to edema), such a shift was not noted in patients with cerebral infarct who were examined within 36 hours after its occurrence. Those patients showing a midline shift before this interval should be suspected of having an intracerebral hemorrhage or other intracranial space-occupying process.
Cerebrovascular Disease in the Bi-Racial Population of Evans County, Georgia
Authors: HEYMAN A. , KARP H. R. , HEYDEN S. , BARTEL A. , CASSEL J. C. , TYROLER H. A. , CORNONI J. , HAMES C. G. , STUART W. 
Published: June 2011

An epidemiological study was made of cerebrovascular disease in a bi-racial Southern community. The study population comprised about 3,000 men and women aged 15 to 75 years at the time of entry into the study. During the 87-month period between the initial and second examinations, 94 persons developed their first cerebrovascular event.
The incidence of stroke among white men (4.77/1,000/year) was almost four times that in white women and more than twice that reported for white men in other sections of the country. The incidence rates of stroke in Negro men and women were equal (5.8/1,000/year).
The risk factors predisposing to stroke in white men appeared to be severe hypertension, obesity, high hematocrit levels, and antecedent electrocardiographical abnormalities These factors were not as prominent among the other race-sex groups.
The high incidence of cerebrovascular disease found in this semirural population of Georgia supports previous reports of increased mortality rates for stroke in this section of the country and represents a unique situation, the exact cause for which remains to be determined.
Computed tomographic-angiographic findings within the first five hours of cerebral infarction.
Authors: Horowitz S H , Zito J L , Donnarumma R , Patel M , Alvir J 
Published: June 2011

Modern management of acute stroke necessitates early diagnosis. To this end, we sought to delineate the radiographic features of focal hemispheric infarction within 5 hours of ictus.
Fifty patients, ages 54-79, with ischemic strokes productive of at least hemiparesis underwent computed tomographic scanning and cerebral angiography (n = 38) or carotid ultrasound (n = 12). Radiographic lesions were characterized for location, size, and pathophysiology.
Acute abnormalities, hypodensity, and mass effect were seen in 56% of scans and confirmed on a second scan 5-7 days later. Intracranial angiographic abnormalities occurred in 61% of patients: arterial occlusions in 45% and delayed arterial filling in 16%. Hemorrhagic infarctions occurred in 26% of second scans and were associated with mass effect (100%) and arterial occlusions (89%). Infarcts with hemorrhagic transformation were larger on both scans than those without (p = 0.001). Of four patients with infarctions in watershed territories on the scans, two had middle cerebral artery occlusions on angiography, thereby questioning the specificity of such scan lesions to low-flow states.
We conclude that cerebral infarctions are often visible on early scans, but their locations may not be etiologically determinative. The infarcts associated with intracranial arterial occlusions (45%) were of thromboembolic origin, but, given current controversies as to the pathophysiology of lacunar and watershed infarctions, we cannot ascertain the etiology in the remainder. These findings are relevant to the new stroke therapies that require administration in the first hours after infarction.
Determination of S-100 and glial fibrillary acidic protein concentrations in cerebrospinal fluid after brain infarction.
Authors: Aurell A , Rosengren L E , Karlsson B , Olsson J E , Zbornikova V , Haglid K G 
Published: June 2011

We initiated the present study to evaluate the clinical value of consecutive concentration determinations of S-100 and glial fibrillary acidic proteins in cerebrospinal fluid from patients with brain infarction.
We took sequential samples of cerebrospinal fluid from 28 patients within 48 hours, at 7 days, and at 18-21 days after the ictus. We measured astroglial protein concentrations using an enzyme-linked immunosorbent assay and also determined size of the infarction (computed tomography), clinical state of the patient (simplified activities of daily living test), blood-brain barrier dysfunction (cerebrospinal fluid/serum albumin ratio), and a myelin marker (myelin basic protein).
We found a transient increase of both proteins in the cerebrospinal fluid during the first week after the ischemic stroke (p less than 0.05). This increment was significantly correlated with the size of the infarction and the clinical state of the patients.
Transient release of astroglial proteins into the cerebrospinal fluid possibly reflects initial focal ischemic damage and, in the later phase, ongoing destruction of astroglial cells in the penumbra zone. We suggest that determinations of cerebrospinal fluid astroglial protein concentrations can be used to estimate ischemic brain damage, which should be of particular value in clinical trials of pharmacological agents, such as calcium antagonists, on stroke patients.
MK-801 does not protect against hypoxic-ischemic brain injury in piglets.
Authors: LeBlanc M H , Vig V , Smith B , Parker C C , Evans O B , Smith E E 
Published: June 2011

The excitatory amino acid inhibitor MK-801 has been shown in many animals species to protect against hypoxic-ischemic brain injury. We sought to determine whether hypoxic-ischemic injury to the newborn pig's brain could be prevented by the use of MK-801.
Hypoxic-ischemic injury to the brain was induced in forty 0-3-day-old piglets. They were randomized to receive either 3 mg/kg MK-801 (MK-801 group, n = 20) or vehicle (control group, n = 19) prior to insult. At time 0, the carotid arteries were ligated and the blood pressure was reduced by one third by hemorrhage. At 15 minutes, inspired oxygen was reduced from 50% to 6%. At 30 minutes, inspired oxygen was changed to 100%, carotid ligatures were released, and the withdrawn blood was reinfused. An additional 14 piglets received 3 mg/kg MK-801 but not hypoxic-ischemic injury (drug-only group), and a final group of 11 piglets were subjected to only a sham operation (sham group).
Neurological examination scores at 24, 48, and 72 hours showed that MK-801 and drug-only piglets were significantly worse than the controls. Pathological examination of the brains at 72 hours showed significantly greater damage in the brains of the MK-801 and control pigs relative to the sham and drug-only groups. No differences were found between the control and the MK-801 groups. No differences were found between the sham and drug-only groups.
MK-801, at a dose of 3 mg/kg, causes neurological dysfunction in piglets lasting at least 72 hours, but neither causes brain damage nor ameliorates the effects of hypoxic-ischemic injury to the brain of the newborn pig.
Central nervous system infarction related to cocaine abuse.
Authors: Daras M , Tuchman A J , Marks S 
Published: June 2011

Cocaine use in the United States has reached epidemic proportions, and increased availability of "crack" since 1983 has noticeably increased the incidence of neurovascular complications. In this report, we examine the relationship between cocaine use and ischemic infarct.
This study reports 18 cases of ischemic cerebrovascular events, which occurred among 15 men and three women aged 21-47 years who were evaluated in a 2-year period. Clinical presentations include thirteen cases with hemispheric infarcts, two brain stem strokes, two anterior spinal artery infarcts, and one with both hemispheric and cerebellar infarcts. Nine patients smoked crack, four snorted cocaine, and three injected it intravenously. In two cases, the route of administration could not be determined. Two patients died, but the other survived with various degrees of neurological deficit.
Traditional risk factors for strokes were identified in only six patients, suggesting that these factors are not necessary for the occurrence of a cocaine-related infarct. Multiple overlapping mechanisms may be responsible, including vasospasm, sudden onset of hypertension, myocardial infarction with cardiac arrhythmias, increased platelet aggregation, and vasculitis.
Dietary treatment of atherosclerosis abolishes hyperresponsiveness of retinal blood vessels to serotonin in monkeys.
Authors: Faraci F M , Armstrong M L , Heistad D D 
Published: June 2011

Atherosclerosis alters vascular responses of the eye to serotonin. Augmented vasoconstrictor responses in the retina to serotonin are associated with functional impairment and may contribute to amaurosis fugax. The goal of this study was to test the hypothesis that dietary treatment of atherosclerosis restores vascular responses of the eye toward normal.
We measured blood flow to the retina using microspheres in six normal monkeys, five atherosclerotic monkeys, and five atherosclerotic monkeys that were fed a normal (regression) diet for 18 months.
Infusion of 8 and 40 micrograms.min-1.kg-1 serotonin into the left atrium had little effect on blood flow to the retina in normal monkeys. In contrast, the high dose of serotonin reduced blood flow to the retina by a mean +/- SEM of 81 +/- 9% (p less than 0.05) in atherosclerotic monkeys. In monkeys that were fed the regression diet, serotonin had no effect on blood flow to the retina.
Regression of atherosclerosis abolishes augmented responses of the retinal circulation to serotonin.