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BACKGROUND AND PURPOSE: Novel stratagems to improve the efficacy of platinum coils in occluding cerebral aneurysms have primarily involved coating coils with materials thought likely to provoke more desirable histologic reactions. No investigations to date, however, have evaluated the utility of gold or vitronectin coatings, despite known endovascular histologic effects of these agents, which may be favorable for treating cerebral aneurysms. This study was conducted to evaluate the degree of endovascular histologic change associated with ultrathin gold- or vitronectin-coated platinum coils. It was hypothesized that such coatings would increase intra-aneurysmal intimal hyperplasia and the degree of luminal occlusion compared with standard platinum coils. MATERIALS AND METHODS: The ligated carotid artery rat model was used to study 4 different aneurysm coil conditions: no coil (sham-surgery controls), uncoated platinum coil, and gold- or vitronectin-coated platinum coil. Two weeks postimplantation, the aneurysms were harvested and stained with hematoxylin-eosin. Slides were evaluated for the degree of neointimal response by a pathologist blinded to treatment. Additional quantitative evaluation was performed blindly by using the ratio of intimal-to-luminal cross-sectional area. RESULTS: A gold- or vitronectin-coated platinum aneurysm coil produced a statistically significant increase in neointimal response compared with a sham (no coil). Arterial segments treated with gold-coated platinum coils also demonstrated a statistically significant 100% increase in neointimal response compared with those treated with bare platinum coils. CONCLUSIONS: In concordance with our hypothesis, ultrathin coatings of gold provoked a neointimal response and degree of luminal occlusion greater than that of plain platinum aneurysm coils in a rat arterial occlusion model.

Posterior cingulate cortex is the site of earliest reductions in glucose metabolism and qualitatively different laminar patterns of neurodegeneration in Alzheimer's disease (AD). This study used multivariate analyses of area 23 in 72 cases of definite AD to assess relationships between laminar patterns of neurodegeneration, neurofibrillary tangle (NFT) and senile plaque (SP) densities, age of disease onset and duration, and apolipoprotein E (ApoE) genotype. No age-related changes in neurons occurred over four decades in 17 controls and regression analysis of all AD cases showed no relationships between neuron, SP, and tau-immunoreactive NFT densities. Principal components analysis of neurons in layers III-Va and eigenvector projections showed five subgroups. The subgroups were independent because each had a full range of disease durations and qualitatively different laminar patterns in degeneration suggested disease subtypes (ST). Cases with most severe neuron losses (STSevere) had an early onset, most SP, and highest proportion of ApoE epsilon4 homozygotes. Changes in the distribution of NFT were similar over disease course in two subtypes and NFT did not account for most neurodegeneration. In STII-V with moderate neuron loss in most layers, cases with no NFT had a disease duration of 3.5 +/- 0.9 years (mean +/- SEM), those with most in layers IIIc or Va had a duration of 7.3 +/- 1 years, and those with most in layers II-IIIab had a duration of 12.1 +/- 1 years. In STSevere, cases with highest NFT densities in layers II-IIIab also were late stage. Finally, epsilon4 homozygotes were most frequent in STSevere, but four statistical tests showed that this risk is not directly involved in neurodegeneration. In conclusion, multivariate pattern recognition shows that AD is composed of independent neuropathological subtypes and NFT in area 23 do not account for most neuron losses.

Recent investigations have shown numerous fatty microemboli, which we previously termed small capillary and arteriolar dilatations (SCADs), in brain microvessels of patients who died after cardiac surgery assisted by cardiopulmonary bypass (CPB). The hypothesis of this study was that extraneous trace elements such as aluminum (Al) and silicon (Si) might be contaminating the blood and causing the formation of SCADs or coating the SCADs already formed in the extracorporeal circulation during CPB. Small capillary and arteriolar dilatations were identified in thick celloidin sections of the brains of 8 patients who died after cardiac surgery supported with a membrane oxygenator, and of 2 dogs that underwent CPB with a bubble oxygenator. The sections were infiltrated with Spurr's embedding medium for electron microscopy. Resin sections 0.5 microm thick were placed on 100-mesh copper grids and analyzed with laser microprobe mass spectrometry. Brain sections without SCADs from 3 patients (controls) whose deaths were not related to cardiac surgery were processed similarly. In SCADs and nearby neuropil sites of the 8 patients who had cardiac surgery, both Al and Si values were higher than in the neuropil, including vessels of the 3 controls. Si values were also high in the 2 dogs, in which a bubble oxygenator was used. Our results indicate that contamination with Al and Si continues to occur during cardiac surgery assisted by CPB. Our data also suggest that switching to membrane oxygenators from bubble oxygenators for CPB may have reduced Si contamination of blood. Further refinements of CPB aimed at eliminating microemboli formation and Al and Si entry into the circulation are warranted.

OBJECTIVE : We report a group of eight patients with a distinctive histological variant of meningioma that is associated with severe peritumoral edema. The clinical presentation, radiographic findings, and histology of this type of tumor may lead to misdiagnosis as an aggressive or malignant process. METHODS : We reviewed the histology from patients who had removal of meningiomas performed in our institution between 1978 and 1992. Tumors having abnormal proliferation of cells in the intramural vascular spaces were selected for study ; case histories and radiographs were reviewed. Tumor material was subjected to special stains, immunocytochemical examination, and electron microscopy. RESULTS : Several lesions were misread radiographically as being malignant. Patients underwent craniotomy with complete excision of the tumor. All lesions were small (≤3 cm), and no brain invasion, unusual tumor vascularity, or dural sinus involvement was noted in any case. Histologically, the meningioma pattern in each case was meningothelial and benign in appearance. The immunocytochemical and electron microscopic features of the unusual cells in the blood vessel walls are most consistent with their being of pericytic origin. All patients have remained asymptomatic and without evidence of tumor recurrence with follow-up from 3 to 12 years. CONCLUSION : These tumors showed proliferation of pericytes in blood vessel walls and represent a new subtype of meningothelial meningioma. The apparently benign nature of these lesions necessitates their recognition. Characteristic findings of pericytic proliferation associated with edema generation have led us to descriptively term this the PEG variant of meningioma.

To investigate the association between an age-related degenerative disease of subependymal veins and leukoaraiosis.Brains obtained at autopsy from 22 patients (average age, 73.2 years; range, 25-95 years) were examined with magnetic resonance (MR) imaging and neuropathologic methods with alkaline phosphatase microvascular staining. The degrees of leukoaraiosis shown on MR images and of deep venous occlusion were scored independently and results compared with logistic regression analysis.Noninflammatory collagenous thickening of venous walls resulting in severe periventricular venous stenosis was found in 13 (65%) of 20 patients over 60 years old. Advanced leukoaraiosis was found in 10 (77%) of these 13 patients. Greater venous disease was associated with more severe leukoaraiosis.Periventricular venous collagenosis, a commonly observed and previously ignored degenerative disease of elderly humans, is strongly associated with leukoaraiosis. Stenosis or occlusion of deep cerebral veins may promote development of leukoaraiosis.

Previous studies have shown tortuous arteries and arterioles in the brains of older people, but the effects of age and other factors have not been studied. To examine the effects of hypertension, age, race and sex on white matter (WM) arteriolar tortuosity (AT), we performed high-resolution microradiography and morphometry of human brains taken at autopsy from 44 subjects of various ages (range 30-96 years; 31 hypertensives/13 normotensives). About 70% of tortuosities in the WM were found at the gray-white interfaces of the insular region and adjacent subcortical-WM of the inferior frontal and superior temporal gyri. Six morphologic types of tortuous profiles were identified. The number of tortuous profiles increased with age, but not significantly. Hypertension, sex and race had no effect on tortuosity. Our findings also suggest that 1) WM AT is found mostly at the interfaces between gray matter and WM and, therefore, 2) the physical properties of the WM somehow predispose to the development of AT; 3) AT is not associated with tortuosity in the veins; and 4) the location of complex arteriolar coils supports a recent claim that they can be mistaken for the Charcôt-Bouchard microaneurysms if injection of contrast media and low-magnification radiography of the brain slices are employed for that purpose.

Various biologic and non-biologic materials may be embolized to the brain after the use of cardiopulmonary bypass (CPB) pumps during open heart surgery but their relative frequency and importance are uncertain. Among the nonbiologic materials, Antifoam A, which contains organosilicates and silicon, continues to be employed as an additive to prevent frothing. Recent improvements in filtration and oxygenation techniques have clearly reduced the incidence of large emboli and complications like stroke but other neurologic sequelae following open heart surgery are common and in many cases poorly explained. A recently developed histochemical technique for the demonstration of the endothelial alkaline phosphatase (AP) was employed in a post-mortem study of brains from 8 patients and 6 dogs dying within a few days after open heart surgery employing cardiopulmonary bypass perfusion. Brains from 38 patients and 6 dogs who were not subjected to heart surgery were studied as controls with the same technique. The AP-stained slides are suitable for both light microscopic examination of the thick celloidin sections as well as a subsequent processing for high-resolution microradiography. Small capillary and arteriolar dilatations (SCADs) were seen in the test subjects/animals but not controls. SCADs were seen in all parts of the brain. Approximately 50% of the SCADs showed birefringence when examined with polarized light. SCADs are putative embolic phenomena and the exact nature and source of the embolic material is under investigation. A glycolipid component is indicated by preliminary studies. SCADs are difficult to find in routine paraffin sections and most if not all of the offending material seems to be dissolved during processing.(ABSTRACT TRUNCATED AT 250 WORDS)

In the present work, artificial neural network (ANN) has been used to identify a servo-driven inverted pendulum system. The inverted pendulum is a benchmark problem of nonlinear multivariable system with inherent instability. The multi variable system has been considered with servomotor supply voltage as the input and four states of the system being the outputs. An LSVF controller has been used to stabilize the system for identification in closed loop. Here the non linear model of the inverted pendulum has been simulated. The Levenberg-Marquardt back-propagation method has been used for the non linear system identification via Feed-forward Neural Network (FNN). The neural network is trained using the error between the model's outputs and the plant's actual outputs. The results show good match between predicted and actual outputs.

String vessels are collagenous structures connected to capillaries. They have no endothelial cells or lumen. We assessed collagen IV-labeled string vessels in the white matter (WM) of subjects with Alzheimer's disease (AD) (n = 12) and non-AD controls (n = 11) using 100 microm celloidin sections. Ten standard fields were digitally captured and the number and length of normal vessels and string vessels were quantified by computerized image analysis. The WM of the AD-diagnosed individuals contained more strings per mm2 (3.95 +/- 0.49) than comparable WM from controls (1.36 +/- 0.39) (p = 0.0005) and had increased total string vessel length in mm/mm2 (AD = 0.29 +/- 0.04; control = 0.10 +/- 0.03; p = 0.0015). There was a 25% increase (not statistically significant) in vessel density in mm/mm2 in AD subjects (AD = 11.88 +/- 0.87; control = 9.53 +/- 0.78; p = 0.06), presumably due to brain atrophy in the white matter. Although vessel length was slightly increased in AD subjects, they still had more than double the string length per total vessel length (AD = 2.88 +/- 0.38) compared to controls (1.36 +/- 0.27) (p = 0.0057). This increase in string vessels in the white matter of AD subjects suggests a decrease in vascular supply in this disease.

The combination of 100 microm thick celloidin sections and alkaline phosphatase (AP) enzyme histochemistry of the vascular endothelium offers a greatly enhanced, 3D morphologic perspective and reveals intricate details of the vasculature of brain. A study of tumor specimens obtained at craniotomy from 6 patients with glioblastomas, 1 with anaplastic oligodendroglioma and 1 with juvenile pilocytic astrocytoma was undertaken using this technique. Five of the 6 glioblastomas, the anaplastic oligodendroglioma and the low-grade astrocytoma specimen showed uniform staining of afferent tumor blood vessels. In the glioblastomas, newly formed vessels formed dense, festooned networks at the advancing edges of the tumor. Feeding arteries entered the tumor at the junction between the edge of the tumor and adjacent brain or meninges and proceeded to form striking, coiled vessels and smaller branches. The density of both small arteries and veins was greatly increased within the tumor although there was much variability. Disordered arborization, arteriole to venous and arteriole to arteriole shunts were observed, leading to a situation where arteries connected directly to veins. In necrotic areas, there were often no AP-stained vessels. In many places, arterioles and capillaries were lacking. Numerous AP-negative veins of various sizes drained the tumors. Glomeruloid proliferations were presumptively identified as focal stain smudges or clusters of capillaries arising from nearby vascular channels. Increased alkaline phosphatase staining and/or focal new vessels were seen outside necrotic areas. The pilocytic astrocytoma and the oligodendroglioma showed less dense vascularity and no formation of the focal festoons of vessels shown by the glioblastomas. This technique may be useful for the study of tumor angiogenesis and to evaluate vascularity in experimental and human brain tumors after various therapies.

Background and Objectives The Pringle maneuver has been shown to increase ablation size during radiofrequency ablation (RFA). Efficacy of laparoscopic Pringle in proximity to major vasculature has not been well described. Laparoscopic RFA was performed in proximity to major hepatic vessels to examine effects of the Pringle on ablation size and vascular damage. Methods Laparoscopic RFA was performed in 10 pigs. Each underwent ablation of a peripheral site, and sites adjacent to the portal and hepatic veins. Ultrasound was used to position the RFA adjacent to vascular structures. US flow characteristics verified occlusion of blood flow. Five pigs underwent laparoscopic RFA with Pringle and five underwent laparoscopic RFA alone. Animals were then sacrificed for gross and microscopic evaluation. Results Peripheral, hepatic, and portal vein ablations showed no significant differences in volume between non-Pringle and Pringle lesions, though the median ablation volume for the peripheral site in the Pringle group was approximately twice that of the non-Pringle group. Pringle group overall median time to target temperature was significantly shorter (P = 0.047). Histologic examination revealed no evidence of endothelial damage or thermal-induced intravascular thrombosis of the hepatic or portal veins. Conclusions Laparoscopic RFA with Pringle in proximity to major vascular structures does not significantly increase ablation size, or cause acute vascular damage. Further studies are necessary to determine the utility of the Pringle in proximity to major intrahepatic blood vessels. J. Surg. Oncol. 2003;83:36–41. © 2003 Wiley-Liss, Inc.

The purpose of this study was to explain the morphology and significance of string vessels in human brains. Brain slices (1.5 cm thick) were embedded in celloidin, sections cut at 100 microm and stained with antibody to collagen IV. A second component of the study was a 3-D rotational study for which we used sections stained with propidium iodide for cell nuclei and anti-collagen stain for blood vessel basement membranes. The materials consisted of brain from two infants at 28 and 35 weeks gestation, two term infants at 20 days and 3 months, one 5 years old, and 3 adults aged 25, 57, and 84 years. String vessels were counted in at least six fields of deep white matter using a 10x objective and the counts averaged and expressed as string vessels per cubic mm. The 3-D rotational study using confocal microscopy was designed to find nuclei in string vessels. The least number of string vessels were present in the premature infant. All others had comparably similar numbers of string vessels except the two term-born infants in whom there was a 3-5-fold increase. However, the two brains had other pathologic lesions, which could affect the counts. In normal brains, string vessels appear as a singe line of stain and usually connect two arterioles or capillaries. They can form loops and occasionally a string vessel may continue into a normal capillary. String vessels have rare nuclei. Our study indicates that string vessels are present in utero, increase in number and are present throughout life. Their exact nature remains unexplained. They apparently do not represent age-related acquired atrophy of capillaries because they are present at all ages and do not progressively increase with normal aging. This technique appears suitable for the study of large number of string vessels.

The clinical, radiologic, and pathologic features of a case of solitary fibrous tumor of the meninges at the base of the brain are reported. The tumor caused clinical symptoms in a 42-year-old Caucasian male which were indicative of compression of hypothalamus, basal ganglia, and third ventricle. Radiologically it was a large extra-axial mass isointense to brain parenchyma on precontrast T1-weighted images that filled the suprasellar cistern and deformed the left cerebral peduncle. At surgery, the tumor was firm to hard and attached to dura. Histologically the tumor was composed of spindle-cell proliferation in a collagen-rich background but exhibited regional variations. CD34 immunoreactivity was a prominent histologic finding. Ultrastructural features of meningioma, such as complex interdigitation of cell processes and intercellular specialized junctions were absent. The cells showed the typical appearances of fibroblasts with proximity of banded collagen and precollagen and cytoplasmic rough-surfaced endoplasmic reticulum. DNA ploidy analysis showed diploid DNA content. Awareness of this neoplasm may lead to increasingly frequent recognition and the current WHO classification of brain neoplasms should be modified to include this new entity.

To examine the vascular supply and architecture of the germinal matrix in the preterm neonatal brain and to determine whether veins or arterioles are the source of germinal matrix hemorrhage.Brains from eight preterm neonates (24 to 35 weeks' gestation) and two full-term infants were fixed in alcohol, embedded in celloidin, sectioned at 100- and 500-micron thicknesses, stained for alkaline phosphatase, and examined with light microscopy. High-resolution contact radiographs of 500-micron-thick sections were also mounted on glass slides for microscopic examination.The upper and middle regions of the germinal matrix are supplied by branches of the lateral striate arteries, whereas the inferior part is supplied by branches of the recurrent artery of Heubner. In brain sections from four of the preterm infants, we found 15 circumscribed hemorrhagic foci within the germinal matrix. The largest was 5 mm in diameter; the smallest, 1 mm. All hemorrhages but one were closely associated with veins, with significant involvement of the perivenous space. The other hemorrhage appeared to be associated with an arteriole. In term and preterm infants, we found no arteriolar-to-arteriolar shunts, precapillary arteriolar-to-venules shunts, or vascular rete. At all gestational ages, the terminal vascular bed had only conventional branchings and connections.In preterm neonates, staining for endogenous alkaline phosphatase allows visual differentiation between afferent and efferent vessels. Germinal matrix hemorrhage in preterm neonates is primarily venous in origin. A hemorrhage can tunnel along the venous perivascular space, collapsing the vein and rupturing the tethered connecting tributaries. Extravasation of blood from the arterial circulation appears to be much less common.

Breast involvement with lupus panniculitis has been infrequently reported. We describe 2 cases with breast involvement proven by biopsy to be lupus panniculitis. Our review emphasizes the clinical presentation of lupus panniculitis with mastitis and its possible clinical similarity to malignancy. In addition, other connective tissue diseases and vasculitis with breast involvement are noted.

For over a century a controversy has existed about the prevalence and significance of Charcot-Bouchard (C-B) aneurysms, especially regarding their relationship to intracerebral hemorrhage (ICH) in man. We reassessed C-B aneurysms by staining thick brain sections from 35 hypertensives and 20 normotensives with the alkaline phosphatase (AP) endothelial stain followed by light microscopy and high-resolution microradiography. Charcot-Bouchard aneurysms were conspicuously absent in both groups which included four cases of hypertensive ICH. The three-dimensional perspective and enhanced ability to trace vessels with these techniques helped to identify arteriolar coils and twists that can be mistaken for aneurysms when demonstrated by injection methods. Routine brain pathologic sections from 2,800 autopsies over a decade showed rare examples of parenchymal aneurysms. We conclude that elimination in our study of a) injection artifacts and b) misinterpretations shows that C-B aneurysms are uncommon and have little relationship to ICH. Despite this, and in view of the original contribution of Charcot and Bouchard, the occasional examples of brain parenchymal aneurysms should continue to bear their names.

The decade of the 80's has seen the implementation of the problem-based curriculum (PC) (also called "parallel" or "student-centred" curriculum) in several medical schools in the United States. This new educational technique emphasizes active student participation and a hands-on learning process supplemented by judicious intervention by the faculty teachers. The students (often volunteers) are usually selected for their motivation rather than for highest intelligence or class ranking. For a period of two years, they meet twice or thrice-weekly in group sessions to explore problem cases developed by faculty for that special purpose. We describe the parallel curriculum here in some detail and suggest that medical educators in India give serious consideration to implementation of such a curriculum or its modification in their institutions. Medical graduates will benefit from the hands-on emphasis of this curriculum as well as the development of a disciplined approach in the handling of clinical problems. PC diminishes the stress levels associated with the traditional curriculum and lets the students play an active role in their education. PC will make them better prepared to face challenges during their clinical years and subsequent careers and should offset some of the weaknesses in the current educational system.

Cerebral capillary and arteriolar dilatations have been observed post mortem in humans and dogs following cardiopulmonary bypass. These dilatations often display an unexplained birefringence that facilitates their quick localization and identification.

The influence of the prenatal and postnatal maternal environment on stroke susceptibility was evaluated by reciprocally crossing the spontaneously hypertensive (SHR) and the Dahl salt-sensitive (SS/Jr) inbred rat strains to produce reciprocal F1 hybrids that were nurtured, respectively, during prenatal and postnatal life by SHR or SS/Jr mothers. Following placement on a high-salt diet containing 8% NaCl at 35 days of age, F1 rats reared by SHR mothers had shorter survival times and were more likely to die with cerebral hemorrhage than F1s reared by SS/Jrs. Across reciprocal F1 female groups, enhanced susceptibility to stroke was associated with greater elevations of systolic blood pressure, but this association was not seen across reciprocal F1 male groups. There was also an association between blood pressure and stroke within each F1/gender subgroup: Rats eventually suffering strokes developed higher blood pressure after placement on the high-salt diet than rats that did not suffer stroke. Lower day 35 body weights (before exposure to the high-salt diet) were associated with greater likelihood of stroke both across the reciprocal F1 groups, and within three of the four F1/gender subgroups. The differences in stroke susceptibility between the reciprocal F1 groupings may be due to systematic differences in the prenatal and/or postnatal environments of SHR and SS/Jr mothers and may be mediated by variations in the nutritive capacity of the two inbred mothers.

We have observed many focal dilatations or very small aneurysms in terminal arterioles and capillaries of 4 of 5 patients and 6 dogs who had recently undergone cardiopulmonary bypass. A smaller number of sausagelike dilatations distended medium-sized arterioles. Two other patients had a small number of the same microvascular changes following proximal aortography. Thirty-four patients and 6 dogs not undergoing cardiopulmonary bypass had none. (A 35th patient who had not undergone cardiopulmonary bypass or aortography showed a small number of dilatations; mediastinal air was a suggested source.) Some of the dilatations exhibited various forms of birefringence. Because most of the dilatations appear empty, we speculate that they are the sites of gas bubbles or fat emboli that have been removed by the solvents used in processing. These microvascular events, occurring only in conjunction with major arterial interventions, may be the anatomical correlate of the neurological deficits or moderate to severe intellectual dysfunction seen in at least 24% of patients after cardiac surgical procedures assisted by cardiopulmonary bypass.

Neurologic sequelae of Paget's disease of bone include involvement of the spinal cord or cauda equina due to mechanical compression by enlarged vertebrae, ischemia caused by a spinal artery, steal syndrome or neoplasm. We describe a patient with Paget's disease of bone who presented with acute cauda equina syndrome due to a spinal epidural hematoma. Clinicians need to recognize this entity since surgical intervention may result in a favorable outcome.

Lacunar infarcts (lacunes) are small, cystic lesions of the brain in patients with hypertension and/or diabetes. In order to improve our understanding of the relationship between lacunes and their blood vessels, the alkaline phosphatase (AP) technique of microvascular staining and high-resolution microradiography were employed in a three-dimensional study of 31 lacunes from 15 hypertensive subjects. A second aim was to compare the usefulness of the techniques with that of routine hematoxylin-eosin (HE) stain employed by previous investigators. Arteries were traced throughout their course. The lesions identified included intimal hyperplasia, hyalinization and atherosclerosis with variable narrowing and occasional occlusions. The small arterioles in the lacune cavities supplied adjacent intact brain. The AP technique clearly distinguished true lacunar infarcts from dilated perivascular spaces. AP and microradiography were superior to HE in showing the three dimensional details with far fewer sections. Four different types of relationships were observed between nutrient arteries and their lacunes, indicating that patterns of vascular involvement can be elucidated in brains of subjects dying with lacunar syndromes by using special techniques such as AP. Such patterns can be correlated with clinical risk factors such as hypercholesterolemia, hypertension etc., singly and in combination. Our data suggest that the natural history of lacunar infarcts may be changing in two ways--the number of lacunes per patient may be diminishing and white matter involvement may be increasing. Possible explanations for these changes are suggested.

In an ongoing study of brain microvasculature in humans at autopsy, we had the opportunity to analyze the overall scheme of this vascular supply. The native endothelial membrane enzyme, alkaline phosphatase, is used to precipitate black lead sulfide salt in the vessel wall, rendering the brain microvasculature visible by both light microscopy and microradiography. There are six distinct patterns of intraparenchymal afferent blood supply to the supratentorial brain: short arterioles from a single source (e.g., those in the cortex); short- to intermediate-length arterioles, single source (anterior two-thirds of the corpus callosum); short- to intermediate length arterioles and arteries, dual source (subcortical U fibers); intermediate-length arterioles and arteries, triple source (extreme/external capsule and claustrum); long arteries and arterioles, single source (centrum semiovale); and large, long muscular arteries, single source (thalamus and basal ganglia). The nature of this arrangement offers some protection to certain regions of the cerebrum from circulatory challenges such as hypotension, while leaving other areas vulnerable. The distal arterioles supplying two of these protected regions, the U-fiber area and the extreme/external capsule and claustrum area, also exhibit the feature of interdigitation, which can offer additional collateral potential from one arteriolar territory to the next. Aging, hypertension, diabetes mellitus, and atherosclerosis can have a significant impact on brain microcirculation. The way in which vascular patterns dictate the distribution of these effects is discussed. The ability to stain the cerebral microvessels and demonstrate the finer points of their patterns in sections and microradiographs has enabled us to resolve some long-standing questions about vascular connections and directions.(ABSTRACT TRUNCATED AT 250 WORDS)

The fine structure of 3 primitive neuroectodermal neoplasms of the cerebral hemispheres was studied. The predominant tumor cells were undifferentiated cells with prominent nuclei and scanty cytoplasm containing few organelles. Ultrastructural evidence suggesting differentiation into ependymal, neuronal and possibly astrocytic elements was also present. This study suggests that the cell of origin of this tumor is a primitive multipotential cell of the cerebrum.

The magnetic resonance (MR) appearances of 40 biopsy-proved meningiomas were blindly evaluated and correlated with their predominant histologic pattern--fibroblastic, transitional, syncytial, angioblastic, or mixed. T1-weighted images were not particularly useful in discriminating pathologic subtype, because most tumors were isointense with or hypointense to cortex regardless of histologic type. Signal intensity and features on T2-weighted images strongly correlated with histopathologic findings in over 75% of cases, however. Meningiomas markedly hypointense to cortex on T2-weighted images (seven of 40 cases) were composed predominantly of fibroblastic or transitional elements, while markedly hyperintense meningiomas (14 of 40 cases) demonstrated predominance of syncytial or angioblastic elements. Consideration of secondary features visible at MR imaging (degree of edema, cyst formation, presence of calcium aggregates) led to a more specific histologic prediction in over half of the remaining isointense tumors. The varied MR appearance of meningiomas has a clear histologic basis, and crude prediction of pathologic subtype is possible in over three-fourths of cases.

Giant cell tumors of synovium (pigmented villonodular synovitis) involving the vertebral column recently have been seen in two women: the third and fourth cases to be reported in the English-language literature. Unlike the previously reported cases, both these tumors grew outside the dura and produced symptoms of spinal cord compression. The first case involved lumbar vertebrae 5 and 6; the second, lumbar vertebrae 2 and 3. Even though initial resection of both tumors was incomplete, the patients improved postoperatively. One tumor was known to be unresectable at the time of surgery. In the other patient, a recurrence of symptoms required second and third resections 4 and 8 months after the first, respectively. Although synovial giant cell tumors rarely metastasize, the rate of local recurrence is high, especially if excision is incomplete. For this reason, close follow-up of patients with lesions in the spinal column is indicated. Increased physician awareness that synovial giant cell tumors can occur in the spine will help to ensure that these tumors are not misdiagnosed in this location.

The corpus callosum exhibits several unusual features: arteriole-venule pairs, perivascular fibrous alae, and recurrent companion arterioles. These and other anatomic aspects are compared and contrasted with those of the centrum semiovale. Vascular changes occurring with aging or hypertension, commonly seen in the centrum semiovale, rarely develop in the corpus callosum. The vascular supply to the central zone of the genu and body of the corpus callosum, via short penetrating arterioles, is similar to that of the cerebral cortex, whereas the vascular supply to the extreme lateral corpus callosum, centrum semiovale, and basal ganglia is substantially carried by long end-arteries. When observed critically, the anatomic features of the corpus callosum may explain such clinically observed phenomena as its relative resistance to flow of fluid masses, radiation injury, Binswanger disease, lacunar infarction, hypoxia, and hypoperfusion.

Myenteric plexuses and smooth muscle of the pylorus obtained by biopsy at pyloro myotomy in 5 infants with hypertrophic pyloric stenosis were studied by electron microscopy. Animal controls consisted of pyloruses from 2 infant and 2 adult rabbits and 2 adult rats. The principal findings in the plexuses of the patients were moderate numbers of variably sized, swollen degenerating axons that contained dense bodies, lamellated figures, vacuoles, granular or fibrillar material, and swollen mitochondria. The significance of this alteration in the etiology and pathogenesis of this disorder is not clear. Neurons in the plexuses showed no definite abnormalities. Although these findings do not confirm previous light microscopic observation of neuronal changes in the pyloric myenteric plexuses, they do not exclude a neurogenic mechanism for this disorder. The presence of small immature neurons and large mature neurons suggests that neuronal maturation and development in infantile hypertrophic pyloric stenosis are not impaired as previously reported. No ultrastructural changes were found in interstitial cells of the myenteric plexuses. Except for hypertrophy of the circular smooth muscle layers, no specific alterations were found in muscle fibers of the pylorus.

False positive and negative results can complicate the diagnosis of Hirschsprung's disease (HD) with the acetylcholinesterase (AChE) stain. To improve the diagnostic value of this test, the authors evaluated the concurrent hematoxylin and eosin (H and E) staining of extra sections after the AChE procedure. Flash-frozen (FF), cryostat-cut (CC) sections of rectal suction biopsies from 96 patients with constipation were evaluated by AChE together with H and E staining of additional unstained sections. In 13 of 15 cases of HD with a diagnostic (positive-A) AChE pattern, the H and E sections confirmed the diagnosis. In five cases with other AChE patterns, the H and E sections were instrumental when the diagnosis was made. Of the 76 non-HD subjects with positive-B (n = 8), equivocal (n = 6), and negative (n = 62) AChE patterns, the H and E sections eliminated the diagnosis in 62 (81%). Neuronal and nerve fiber morphologic characteristics were excellent. Rebiopsies were needed in 14 subjects (19%) when there was failure in finding neurons. Simplicity, quickness, and the high quality of the histologic preparations make this procedure a useful adjunct to the AChE stain.

The case history of a 28-year-old man who sustained a gunshot wound to the head and developed multiple pulmonary emboli composed of cerebral tissue is presented. The brain tissue fragments probably entered the severed end of a bridging vein, traveled along the superior sagittal sinus, and gained access to the internal jugular vein and systemic venous return.

Brain and cervical spinal cord removed at autopsy from hypertensive humans have been subjected to 4 levels of microscopic study, 3 being first histochemically prepared so as to stain the arterial and capillary system. Thick (100 microns) sections for light microscopy and thicker (500-1000 microns) for x-ray microscopy facilitate the study of long, complex anatomic units. Arterial and arteriolar microaneurysms have not been found. In addition to the usual age related vascular changes in normal people we have found: moniliform capillary dilatations, focal segments of arteriolar narrowing, état pre-criblé, and lacunar infarcts. Few changes have been encountered in the corpus callosum. While the segmental arteriolar narrowing occurs in the cortex as well as deep white matter, the effects of resultant poor perfusion might be expected to be more profound in the deep white matter.

Suppressive-B-cell factor (SBF) is an autoregulatory B-cell lymphokine produced by heat-aggregated-IgG stimulated B-lymphocytes which suppresses polyclonal immunoglobulin production. SBF production by rheumatoid arthritis (RA) patients' peripheral blood B-lymphocytes inversely correlates with disease activity and in vitro rheumatoid factor production. To further define the role of SBF in the pathogenesis of RA, the present study measured SBF production by surgically-obtained synovial membrane mononuclear leukocytes. SBF production by RA synovial leukocytes was similar to the levels previously described for RA peripheral blood leukocytes. Both RA and osteoarthritis (OA) synovial leukocytes produced significantly less SBF than leukocytes obtained from otherwise healthy patients with plica. OA patients produced less SBF than RA patients, but the difference was not statistically significant. SBF values for combined RA patients and controls with OA or plica correlated with the degree of histological plasma cell infiltration providing further evidence for SBF production by cells of the B-lymphocyte lineage. Depletion studies also demonstrated that synovial SBF was produced by B-lymphocytes. The molecular weight (34,000) of synovial SBF was similar to the molecular weight of peripheral blood SBF. Decreased SBF production by RA synovial B-lymphocytes is a functional abnormality in RA which may contribute to the perpetuation of synovial rheumatoid factor production and chronic synovial inflammation.

The pathologic changes in the brain of a five and a half month old male child who died of propionic acidemia are presented. Although previous pathologic reports of this disorder describe either no involvement of the central nervous system or focal myelin sheath vacuolization, the present case exhibited different pathology, namely, spongy degeneration of the white matter of Van Bogaert and Bertrand's type. Thus this case illustrates that the pathologic changes in the brain in propionic acidemia are variable. In addition, the cerebellum in this patient showed marked diffuse atrophy and early loss of the external granular layer, two changes that have not been emphasized by previous authors.

We report the first case of co-existing temporal arteritis and Sjögren's syndrome in the English language literature. Characteristic clinical and laboratory findings of both disorders were present. The combination of these two illnesses could be on the basis of chance alone or there may be a common etiology. Temporal arteritis could therefore be an addition to the spectrum of vasculitis diseases seen in Sjögren's syndrome.

Yersinia enterocolitica, a gram negative aerobic non-haemolytic bacillus, has been identified as a cause of meningitis only once before and the neuropathological features of Y. enterocolitica meningitis have not been reported in the literature. We describe the pathological features of a case of acute fatal meningitis caused by Y. enterocolitica, serotype 0:18, in a 47-year-old male alcoholic with cirrhosis. The organism presumably reached the meninges via the blood stream from the abdominal cavity. Intravascular fibrin thrombi, both recent and organising, were associated with multiple foci of necrosis in the brain. In spite of vigorous antibiotic therapy for three weeks the organism was cultured from the brain at autopsy. Among the various infections caused by Y. enterocolitica, meningitis appears to be the most difficult to eradicate.

A case of Crohn's colitis is described in a patient who demonstrated multiple extraintestinal complications, including erythema nodosum, pyoderma gangrenosum, and aphthous oral ulcerations. Our patient simultaneously developed an unusual vasculitis in muscle. Small vessels were affected by necrosis, and polymorphonuclear leukocyte infiltration was appreciated. Leukocytoclastic was suggested by these features and the additional finding of small amounts of nuclear debris. A strong immunofluorescence to antihuman C3 was demonstrated in the affected vessel walls. We did not find circulating IgG immune complexes in serum with the Raji cell assay. The implication of the finding of leukocytoclastic vasculitis in muscle, associated with Crohn's colitis, is discussed.

A histochemical staining technique for detection of acetylcholinesterase (AChE) in rectal suction biopsies was compared with the presence or absence of ganglion cells in full-thickness or suction biopsies for the diagnosis of Hirschsprung disease (HD) in infants and children. Biopsies from 55 of 58 children were adequate for both the AChE assay and routine pathologic examination for ganglion cells. Two patterns of AChE staining were noted. With pattern A, prominent nerve fibers staining for AChE were seen throughout the muscularis mucosa and the lamina propria. With pattern B, similar fibers were seen only in the muscularis mucosa and the areas of lamina propria that were immediately adjacent. No "false-negative" AChE staining reactions were found in patients with HD. No "false-positive" reactions showing pattern A were found. This pattern was diagnostic for HD. Three false-positive reactions were found showing pattern B in patients with conditions other than HD. Among 22 patients with HD, 19 were males and three were females. Pattern A occurred in all age groups and in both sexes. Pattern B in patients with HD was seen exclusively in male infants 1 month of age or less. Experience suggests that the AChE staining of rectal suction biopsies is an excellent screening test for HD in infants and children. If pattern B is encountered, however, the specimen should be examined by routine pathologic techniques for the presence of submucosal ganglion cells.

Conventional radiography and magnetic resonance imaging (MRI) of the craniovertebral junction were evaluated in 12 patients with longstanding rheumatoid arthritis (RA) and neck pain with or without other neurologic signs or symptoms of cervical myelopathy. MRI demonstrated abnormal soft tissue masses thought to represent pannus in 9 patients. Three patients showed cord or brainstem compression due to pannus or atlantoaxial subluxation. The 3 patients with MRI evidence of cord or brainstem compression had neurologic signs or symptoms of cervical myelopathy, and appropriate therapy was instituted based on these findings. This study indicates that MRI is able to detect abnormal soft tissue masses which probably represent pannus and their relationship to the spinal cord or brainstem, and confirms the utility of the procedure in the management of craniovertebral involvement in RA.

We studied two families in each of which three or more individuals were affected by brain tumors. In the first family, which had no evidence of neurofibromatosis or tuberous sclerosis, a man, his sister, and her son developed histologically proven gliomas; the man's great uncle was historically reported to have died from a brain tumor, but the exact nature of the tumor was not known. In this family two of the tumors were low grade astrocytomas of the cerebrum, whereas the third was a mixed glioma of the cerebellum. Karyotypic analysis of this tumor showed no marker chromosomes. A second family had a history of an unusual concentration of brain tumors. In one patient the tumor was a histologically verified glioma. Four other patients had historically reported brain tumors, the descriptions of which suggested gliomas. Both families showed involvement of individuals in adjacent generations, although in both instances there were skipped generations. Twins, siblings, or parents and children are the kindred groups affected in most other reported families with multiple brain tumors. The mode of inheritance of brain tumors in these two families and recent literature on the conditions associated with familial brain tumors are discussed.

A 57 year old white man with aortic insufficiency and previously undiagnosed ankylosing spondylitis, who developed subacute bacterial endocarditis (SBE), is described. Emergency aortic valve replacement was necessary, and the aortic valve pathology showed diffusely fibrosed and thickened valve leaflets with bacterial vegetations. This is the first recorded case of SBE in ankylosing spondylitis.