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V R Challa

Publications and source records attributed to V R Challa.

At least 19 recordsLinked to original sources
PubMed2004

Spontaneously remitting dermatomyositis.

Dermatomyositis (DM) is an inflammatory myopathy of skeletal muscle with characteristic cutaneous findings. It is a rare disorder with a bimodal age distribution that affects almost twice as many women as men. One category of DM, normal-enzyme DM, is characterized by cutaneous changes only at baseline, normal serum muscle enzyme levels and myositis demonstrated by electromyography (EMG) and/or muscle biopsy specimens. Typically, patients with normal-enzyme DM progress to severe muscle involvement and require systemic corticosteroid therapy. The patient we report has normal-enzyme DM confirmed by serial serum enzymes, EMG, and skin and muscle biopsies but is unique in that she never experienced progression of muscle weakness although muscle involvement was documented histologically and by EMG. Follow-up examination after 1 year revealed near-complete resolution of cutaneous involvement after topical therapy and no evidence of muscle weakness.

Aged↗
PubMed2002

A three-dimensional study of brain string vessels using celloidin sections stained with anti-collagen antibodies.

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.

Adult↗
PubMed2000

Cerebrovascular pathology in Alzheimer's disease and leukoaraiosis.

A high percentage of patients with Alzheimer's disease (AD) show evidence of white matter degeneration known as leukoaraiosis (LA), which is due to chronic ischemia. We found that the periventricular veins tend to become occluded by multiple layers of collagen in the vessel walls in the elderly. This collagen deposition is particularly excessive in LA lesions. Therefore, it is present in the brains of many AD patients, along with other ischemia-causing cerebrovascular pathology. We found evidence that there is severe loss of oligodendrocytes in LA, due to extensive apoptosis. No evidence of inflammation was found in the LA lesions. In thick celloidin sections of AD brain, we have obtained detailed 3D views of small (early) deposits of amyloid (stained with beta-amyloid antibody) around capillaries (stained with collagen IV antibody).

Aged↗
PubMed2000

Longer duration of cardiopulmonary bypass is associated with greater numbers of cerebral microemboli.

BACKGROUND AND PURPOSE: Many patients who undergo cardiac surgery assisted with cardiopulmonary bypass (CPB) experience cerebral injury, and microemboli are thought to play a role. Because an increased duration of CPB is associated with an increased risk of subsequent cerebral dysfunction, we investigated whether cerebral microemboli were also more numerous with a longer duration of CPB. METHODS: Brain specimens were obtained from 36 patients who died within 3 weeks after CPB. Specimens were embedded in celloidin, sectioned 100 microm thick, and stained for endogenous alkaline phosphatase, which outlines arterioles and capillaries. In such preparations, emboli can be seen as swellings in the vessels. Cerebral microemboli were counted in equal areas and scored as small, medium, or large to estimate the embolic load (volume of emboli). RESULTS: With increasing survival time after CPB, the embolic load declined (P<0.0001). (Lipid emboli are known to pump slowly through the brain.) Also with increasing time after CPB, the percentage of large and medium emboli became lower (P=0.0034). This decline is consistent with the concept that the emboli break into smaller globules as they pass through the capillary network. A longer duration of CPB was associated with increased embolic load (P=0. 0026). For each 1-hour increase in the duration of CPB, the embolic load increased by 90.5%. CONCLUSIONS: Thousands of microemboli were found in the brains of patients soon after CPB, and an increasing duration of CPB was associated with an increasing embolic load.

Adult↗
PubMed2000

Apoptosis in leukoaraiosis.

We report a case of leukoaraiosis that was studied for apoptosis. In the neuropil, the number of cells that showed DNA fragmentation was 2.5 times as great in the area of leukoaraiosis as in the adjacent white matter (P = .004) and 25 times as great as in the nearby cortex (P < .001). Our findings suggest that apoptosis, predominantly of oligodendrocytes, is involved in the pathogenesis of leukoaraiosis. Within the area of leukoaraiosis, we also found numerous small veins that were partially occluded by severe collagenous thickening of the vessel walls. This collagenosis may have contributed to or resulted from chronic ischemia in that area.

Aged↗
PubMed1998

Multivariate analysis of laminar patterns of neurodegeneration in posterior cingulate cortex in Alzheimer's disease.

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.

Aged↗
PubMed1998

Laser microprobe mass spectrometric study of aluminum and silicon in brain emboli related to cardiac surgery.

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.

Adult↗
PubMed1997

Cerebral microvascular alterations in aging, leukoaraiosis, and Alzheimer's disease.

We have been using alkaline phosphatase (AP) histochemical staining, formerly a research tool for the study of cerebral cortical vascular morphology, to examine pathological changes in the cortex and deep cerebral structures. Deep structures stain similarly to the cortex. The AP stain is found in the afferent vessels (small arteries, arterioles, and capillaries), but not in venules and veins. The stain is also present in leaky vessels, such as those in the area postrema. The vascular supply to the cerebrum is not homogeneous. Supply to the deep white matter, for instance, derives from the leptomeningeal border zone, and then medullary arterioles must wind their way for up to 4 cm before arriving at their ultimate destination. Adding to the difficulties, tortuosities develop in some of these vessels with aging. According to some calculations, hypertensive levels of blood pressure would be required to maintain irrigation through some of these vessels. We have identified a venous alteration that attends aging: periventricular venous collagenosis (PVC) is a previously unrecognized, noninflammatory, mural disease of the periventricular veins. In severe cases, examples can be found of veins that are completely occluded by this process. PVC is found in 65% of subjects over 60 years old, and it strongly correlates with leukoaraiosis. In addition to previously mentioned aging-related changes, we have found extreme tortuosity, multiplications, and aneurysms of the smallest arterioles and lumpy-bumpy capillaries in the deep structures of patients with Alzheimer's disease.

Adult↗
PubMed1997

Human germinal matrix: venous origin of hemorrhage and vascular characteristics.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Alkaline Phosphatase↗
PubMed1996

The histological effect of barrier vein wrapping of peripheral nerves.

Twenty-four Sprague-Dawley rats underwent exploration and exposure of the sciatic nerve, followed by sham isolation, irrigation, and subsequent wound closure (Group 1); barrier vein wrapping of the nerve using glutaraldehyde-preserved allograft inferior vena cava (Group 2); or barrier vein wrapping of the nerve with femoral vein autograft from the contralateral extremity (Group 3). Four months later, the rats were sacrificed and the nerves fixed in situ in buffered glutaraldehyde. Sections proximal, mid-portion, and distal to the barrier and vein wrap were fixed with osmium tetroxide, epon embedded, stained with toluidine blue, and studied under x200 and x400 light microscopy. Epineural scar formation increased 10 times in Group 2, compared to Group 3 (p < 0.0001). Epineural thickness and the number of degenerating axons did not differ significantly among all groups. Inflammatory cells in Group 2 increased 100 times, compared to Group 3 (p < 0.0001). Continuing with the underlying epineural layer was apparent grossly and microscopically with all allografts, but with no autografts. Thus, glutaraldehyde-preserved allograft vein wraps appear to incite a marked inflammatory response, with epineural scarring and adherence to the underlying nerve, while autograft vein wraps do not.

Animals↗
PubMed1996

Pericytosis and edema generation: a unique clinicopathological variant of meningioma.

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 election microscopy. RESULTS: Several lesions were misread radiographically as being malignant. Patients underwent craniotomy with complete excision of the tumor. All lesions were small (< or = 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.

Aged↗
PubMed1996

Neoplasms of the pineal region.

Tumors of the pineal region are rare but pose interesting diagnostic and therapeutic challenges. A diverse group of neoplasms may occur in the pineal region, and correct histologic diagnosis is critical to proper management of the disease. To emphasize the need for tissue diagnosis, we present five cases of pineal region tumors, including germinoma, pinealoblastoma, pinealoma, astrocytoma, and meningioma. In addition, we discuss the differential diagnosis of pineal region tumors, emphasizing the histologic, prognostic, and therapeutic differences between various tumor types.

Adult↗
PubMed1995

Brain microemboli associated with cardiopulmonary bypass: a histologic and magnetic resonance imaging study.

Emboli in brain tissue after cardiopulmonary bypass were reported in the literature 30 years ago, but there is little objective evidence confirming the presence of emboli in the brain after cardiopulmonary bypass with more modern equipment and techniques. Recently, with alkaline phosphatase vascular staining, we found an acellular fatty material in brain microvasculature from autopsy material of patients who died shortly after cardiopulmonary bypass. These fatty intravascular collections range in diameter from 10 to 70 microns, a size that lodges in the smallest vessels of the microvasculature. They have been found in numbers sufficient to cause detectable neurologic dysfunction and are believed, but not proved, to be emboli. By sequentially injecting colored microspheres, we can determine when emboli occur during experimental cardiopulmonary bypass. In ongoing related studies, magnetic resonance imaging was performed before cardiac valve replacement in 39 patients for whom preoperative and postoperative neurologic and neuropsychologic testing was available. Preliminary results suggest that magnetic resonance imaging evidence of prior stroke is not a significant risk factor for cognitive or motor decrement after cardiopulmonary bypass.

Animals↗
PubMed1995

Periventricular venous collagenosis: association with leukoaraiosis.

PURPOSE: To investigate the association between an age-related degenerative disease of subependymal veins and leukoaraiosis. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adult↗