Coherency image analysis to quantify collagen architecture: implications in scar assessment.

An important histological difference between normal, uninjured dermis and scar tissue such as that found in keloid scars is the pattern (morphological architecture) in which the collagen is deposited and arranged. In the uninjured dermis, collagen bundle architecture appears randomly organized (or in a basket weave formation), whereas in pathological conditions such as keloid scar tissue, collagen bundles are often found in whorls or in a hypotrophic scar collagen is more densely packed in a parallel configuration. In the case of skin, a scar disables the dermis, leaving it weaker, stiff and with a loss of optimal functionality. The absence of objective and quantifiable assessments of collagen orientation is a major bottleneck in monitoring progression of scar therapeutics. In this article, a novel quantitative approach for analyzing collagen orientation is reported. The methodology is demonstrated using collagen produced by cells in a model scar environment and examines collagen remodeling post-TGFß stimulation in vitro. The method is shown to be reliable and effective in identifying significant coherency differences in the collagen deposited by human keloid scar cells. The technique is also compared for analysing collagen architecture in rat sections of normal, scarred skin and tendon tissue. Results demonstrate that the proposed computational method provides a fast and robust way of analyzing collagen orientation in a manner surpassing existing methods. This study establishes this methodology as a preliminary means of monitoring in vitro and in tissue treatment modalities which are expected to alter collagen morphology.

Evidence for increased lipid peroxidation in multiple sclerosis.

Pentane and ethane are degradation products of unsaturated fatty acids which are released during lipid peroxidation. In order to assess whether multiple sclerosis is associated with lipid peroxidation, we measured pentane and ethane excretion by 16 patients with multiple sclerosis and compared them to healthy control subjects. Patients with acute exacerbation of multiple sclerosis had significantly higher concentrations of pentane (10.5 +/- 4.2 nmol/l)(p less than 0.01) compared to either patients in remission (4.5 +/- 1.7 nmol/l) or control subjects (4.9 +/- 1.1 nmol/l). The concentrations of ethane were not significantly different among these groups. Of the patients with acute exacerbation who later achieved remission, the pentane excretion also returned to normal (5.6 +/- 0.9 nmol/l). One patient who failed to reachieve clinical remission continued to excrete large amounts of pentane. We conclude that oxygen free radical activity is enhanced during exacerbation of multiple sclerosis.

Secretion of plasminogen activator by cerebral astrocytes and its modulation.

Plasminogen activator (PA) has been related to the neuron migration during brain development. PA has also been shown to degrade myelin basic protein. We present data to show that neonatal Balb/c astrocytes show PA activity on 125I-fibrin coated plates. Secreted and cell associated fibrinolytic activity is detected only in the presence of plasminogen. Modulants like concanavalin A and phorbol myristate acetate enhance PA production and this function involves a transcriptional event. Dexamethasone inhibits baseline as well as concanavalin A induced enhancement of PA activity. These results raise the possibility that astrocytes may have an active role in myelinoclastic disorders and CNS developmental defects.

Characterization of astrocyte plasminogen activator.

We have previously shown that astrocytes produce and secrete plasminogen activator (PA) and that this function is responsive to various modulating agents. When astrocyte conditioned medium (CM) is subjected to SDS-PAGE and PA activity localized by fibrin-agar gel overlay, the activity in the CM is found to comigrate with control t-PA. On affinity chromatography CM PA specifically binds to t-PA antibody. The latter also inhibits fibrinolytic activity of CM PA. When incubated with a fibrin clot, CM PA activity can be shown to bind to fibrin. These observations help identify the enzyme in astrocyte CM as t-PA. A possible role of astrocyte PA in myelin injury could provide an explanation for the previously observed correlation between fibrin deposition and demyelination as well as inhibition of demyelination by ancrod and heparin in experimental allergic encephalomyelitis.

Demyelinating optic neuropathy with Miller-Fisher syndrome. The case for overlap syndromes with central and peripheral demyelination.

The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barré syndrome with pathology restricted to the peripheral nervous system. A patient with Miller-Fisher syndrome and bilateral demyelinating optic neuropathy suggesting associated central nervous system pathology is presented. Clinical and experimental evidence regarding the association of central and peripheral nervous system demyelination is reviewed.

Spinal epidural lipomatosis: report of a case secondary to hypothyroidism and review of literature.

Epidural lipomatosis usually occurs as a complication of steroid therapy. This report includes the first description of a case secondary to hypothyroidism. Adults in all age groups can be affected and present with progressive signs and symptoms of spinal cord or cauda equina compression. The dorsal aspect of the thoracic spine is most commonly involved, usually in its total extent. Spine radiographs are normal and myelography poorly delineates the nature and extent of abnormality. While computed tomography can provide information about the nature of the spinal mass, magnetic resonance imaging is the investigation of choice. Extensive decompressive laminectomy is useful but the results are variable. Correction of underlying endocrine abnormality can reverse the process. The need for early diagnosis of this disorder is therefore emphasized.

Optic perineuritis with secondary syphilis.

Optic perineuritis is characterized by swollen optic discs in the absence of raised intracranial pressure and visual dysfunction. A patient with secondary syphilis who presented with these features is described. The need to recognize the spectrum of ocular and optic nerve involvement in secondary syphilis is emphasized.

Purtscher's retinopathy secondary to pancreatitis. Aspects of the topography of retinal abnormalities.

A 22-year-old man with acute pancreatitis developed sudden bilateral blindness with funduscopic features of Purtscher's retinopathy. The topography of retinal abnormalities has been ascribed to the properties of the retinal capillary network. However, the similarity between the distribution of the retinal abnormalities and the density of the nerve fiber layer suggests that the observed topography may, in fact, result from the anatomical characteristics of the nerve fiber layer.

Presentation of pinealoblastoma with ocular dipping and deafness.

Ocular dipping and deafness as presenting manifestations in a patient with pinealoblastoma are highly unusual. Presence of a discrete lesion allows us to postulate a mechanism to explain ocular dipping in light of the present understanding of vertical eye movement control. A mechanism for deafness, probably a false localizing sign of raised intracranial pressure, is proposed also.

Anterior ischaemic optic neuropathy secondary to cluster headache.

This report describes a patient with cluster headache who developed anterior ischaemic optic neuropathy during an attack of headache, an association not previously described. A possible pathophysiologic mechanism based upon the understanding of optic disc physiology and ocular vascular pathology in headache syndromes is proposed.