Integrated web-based viewing and secure remote access to a clinical data repository and diverse clinical systems.

The advent of the World-Wide-Web protocols and client-server technology has made it easy to build low-cost, user-friendly, platform-independent graphical user interfaces to health information systems and to integrate the presentation of data from multiple systems. The authors describe a Web interface for a clinical data repository (CDR) that was moved from concept to production status in less than six months using a rapid prototyping approach, multi-disciplinary development team, and off-the-shelf hardware and software. The system has since been expanded to provide an integrated display of clinical data from nearly 20 disparate information systems.

Localization of amyloid P component in human brain: vascular staining patterns and association with Alzheimer's disease lesions.

Amyloid P component is a normal serum protein that is highly conserved across phylogeny. Although it resembles the classic acute-phase reactant C-reactive protein, and is considered to be a normal extracellular matrix component, its physiologic role in humans is unknown. Amyloid P component is also colocalized with accumulations of all recognized forms of amyloid. The present study uses light and electron microscopy to compare the cerebral localization of amyloid P component in cases with (n = 19) and without (n = 15) Alzheimer's disease (AD). In non-AD cases, amyloid P component was predominantly localized to the cerebrovasculature. Perivascular staining was observed in most cases, more so in the white than in the gray matter. In AD cases, amyloid P component was localized to all three characteristics histopathologic lesions, namely, neurofibrillary tangles, senile plaques, and amyloid angiopathy. Furthermore, in cases with prominent staining of gray matter parenchymal lesions, intravascular staining was decreased. Given the fixation and processing methods used, amyloid P component was never seen to be localized to the cerebrovascular basement membrane. These data argue against amyloid P component's postulated role as the anchor for vascular beta-amyloid deposition. Because there is no evidence for intrinsic amyloid P component production in brain, its perivascular and parenchymal distributions suggest either compromise of the blood-brain barrier or transport across vascular endothelium.

Association between vascular basement membrane components and the lesions of Alzheimer's disease.

A relationship between the microvasculature and Alzheimer senile plaques has been suggested by several lines of evidence. Besides close anatomic and biochemical relationships, both extrinsic (fibronectin) and intrinsic [heparan sulfate proteoglycan (HSPG)] components of the vascular basement membrane (VBM) have been colonized with amyloid plaques. The present study was designed to examine the association between three intrinsic components of the VBM [HSPG, collagen type IV (CIV), and laminin] and the histopathologic lesions of Alzheimer's disease (AD). Six cases with neuropathologically confirmed AD were immunocytochemically labeled for the presence of HSPG, CIV, laminin, or tau-2 (a marker for degenerating neurites) and examined at the light and electron microscopic levels. For light microscopic analyses, sections were counterstained with a fluorescent marker for amyloid. The present study illustrates an involvement of VBM components in the lesions associated with AD. First, we replicate our previous finding that HSPG antibodies immunolabel a subset of neurons; ultrastructural analyses indicate that at least some of these are actually extracellular neurofibrillary tangles. Second, we report that CIV and laminin immunoreaction product was not associated with neurons but did label several perivascular cells with the morphologic characteristics of microglia. Finally, we demonstrate that all three intrinsic VBM components, CIV and laminin as well as HSPG, are localized to senile plaques. Both light and electron microscopic studies indicate that the VBM components are associated with amyloid rather than degenerating neurites. These findings suggest that the VBM or its components may play a role in the AD pathogenetic cascade.

Microangiopathy and the colocalization of heparan sulfate proteoglycan with amyloid in senile plaques of Alzheimer's disease.

While the pathogenetic mechanisms responsible for Alzheimer's Disease (AD) remain unknown, blood vessel deformities, thickened vascular basement membrane (VBM), and amyloid fibrils emanating from the VBM all suggest vascular involvement. The present study immunocytochemically localized the VBM constituent heparan sulfate proteoglycan (HSPG), which is said to play a role in filtration of anionic and neutral proteins. In addition, thioflavine S was used to double-label each tissue section for the presence of amyloid. Samples were taken from frontal, temporal and parietal lobes of 8 patients who exhibited the neuropathologic lesions of AD and 6 patients who did not. HSPG immunolabeled the capillary bed in all samples. Tissue from patients with AD, however, exhibited severe microangiopathic changes: ragged and irregular outer capillary walls, both thickened and attenuated capillary diameters, and regionally increased capillary density. In addition, plaque-like extravascular accumulations of HSPG were seen in all patients with AD. These accumulations were found in the vicinity of capillaries, and were commonly colocalized with amyloid. Neither extravascular clouds of HSPG immunoreactivity nor fluorescing accumulations of amyloid were found in non-AD patients. The pattern of HSPG immunostaining confirms: (1) the high incidence of microangiopathy in AD; (2) the close anatomic relationship between plaque constituents and capillaries; and (3) the colocalization of HSPG with extravascular amyloid. The cerebral vasculature, and specifically the VBM, may thus be actively involved in the pathogenesis of AD.

Pyoderma gangrenosum and hairy cell leukemia.

Hairy cell leukemia (HCL) is an uncommon hematologic malignancy in which simultaneous cutaneous disturbances of various types have been reported. We report a case of a 62-year-old man with HCL who developed pyoderma gangrenosum (PG) at the site of incision for splenectomy. PG has been reported previously in a patient with HCL. Since splenectomy is important in the treatment of HCL, it is important for the clinician to know that surgical wound dehiscence may not be due to poor technique nor infection, but rather to pathergy.

Demonstration of elevated type I and type III procollagen mRNA levels in cutaneous wounds treated with helium-neon laser. Proposed mechanism for enhanced wound healing.

To assess laser modulation of wound healing, full-thickness cutaneous wounds were produced in the backs of pigs, and subjected to treatment with helium-neon laser. For comparison, some wounds were treated with non-laser energy source (a tungsten light) or left untreated as controls. Type I and type III procollagen mRNA levels were determined in the wounds by molecular hybridization with cDNA probes. The results indicated that type I and type III mRNA levels were markedly increased at days 17 and 28 of the healing in wounds treated with He-Ne laser, when compared to control or tungsten light-treated wounds. The results suggest that helium-neon laser stimulates wound healing by enhancing procollagen gene expression. These observations may have relevance to previous clinical studies suggesting that helium-neon laser stimulates wound healing.