Surgical arthroscopy for anterior cruciate ligament reconstruction.
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Biomedical subjects
Publications and source records attributed to P M Moore.
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Vasculitis, or angiitis, affects both the central and peripheral nervous systems and is increasingly recognized as a cause of neurologic dysfunction. The vascular inflammation may be systemic or organ restricted. Recent work has expanded our knowledge on the pathogeneses of vasculitis. Historically, immune complex mediated vasculitis is best defined but studies now delineate cell mediated immune mechanisms including T cell and endothelial cell interactions. Additional factors in the genesis of vascular inflammatory diseases are also being explored. There are numerous underlying etiologies ranging from primary immunologic disturbances to infections, malignancies, and toxins. In order to plan rational therapies, clinicians need to be aware of current work on the pathogeneses of vascular inflammation as well as exploring specific etiologies in their individual patients.
Isolated angiitis of the central nervous system (IAC) is usually a fatal inflammatory disease with a predilection for small blood vessels. Recurrent cerebral infarction leading to death within a few years is the usual course, but this may be significantly altered by aggressive immunosuppressive therapy with prednisone and cyclophosphamide. Other diseases may, however, present with similar clinical and angiographic features. Because antemortem diagnosis suggests a therapy, establishing the criteria for diagnosis is important. This report describes clinical, angiographic, and biopsy features, and therapy of five successfully treated patients with IAC. The following specific criteria are recommended for establishing an antemortem diagnosis of IAC: (1) clinical pattern of headaches and multifocal neurologic deficits present for at least 6 months, unless the deficits are severe at onset or rapidly progressive; (2) cerebral angiography demonstrating segmental arterial narrowing; (3) exclusion of systemic inflammation or infection; and (4) leptomeningeal/parenchymal biopsy demonstrating vascular inflammation or exclusion of alternate diagnoses. Based upon the successful management of these five previously unreported patients, as well as others in the literature, the following treatment regimens are recommended for the initial 6 weeks of therapy: (1) prednisone 40 to 60 mg/day, and (2) cyclophosphamide 100 mg/day.
Plasma concentrations of LH, FSH and oestradiol-17 beta were measured in blood samples taken at 15 min intervals for 48 h during the follicular phase of four Merino ewes. The amplitude of pulses of LH and the mean concentration of LH were higher at the beginning of the follicular phase, 36-24 h before the preovulatory surge of LH (amplitude 2.4 ng ml-1, mean concentration 3.9 ng ml-1), than at the end, 24-0 h before the preovulatory surge (amplitude 1.2 +/- 0.1 ng ml-1; mean concentration 1.4 +/- 0.1 ng ml-1). There was no change in the inter-pulse interval during this time (mean 74 +/- 5 min). Over the same period, oestradiol levels increased from 7-8 pg ml-1 to a peak of 10-15 pg ml-1. Mean FSH concentrations declined (36-24 h: 3.6 ng ml-1 vs 24-0 h: 1.8 +/- 0.3 ng ml-1) before rising at the time of the preovulatory surge of LH and again 24 h later. It was concluded that the biphasic response of LH to oestrogen that is seen in ovariectomized ewes may also operate during the follicular phase of the oestrous cycle in entire ewes.
Despite the importance of neurologic manifestations of the collagen vascular diseases, it is clear that there are more questions than answers. The use of in vitro culture systems, in vivo models, and clinical and laboratory study of patients that attempt to correlate these findings with immunologic abnormalities, including parallels with animal models, should increase our understanding of these syndromes.
This study investigates a canine model of experimental brain tumor. Particularly addressed was the usefulness of gadolinium contrast-enhanced MRI for differentiating brain tumor tissue from cerebral edema. Cultured canine glioma cells were injected into the left hemispheres of six adult mongrel dogs. All dogs developed brain tumors. Serum samples drawn prior to and serially after tumor inoculation showed development of antibodies reactive to the tumor. All tumors were visualized with MRI. Contrast-enhanced T1-weighted imaging was the most sensitive with gadolinium producing tumor enhancement due to blood-brain barrier breakdown. Gross and microscopic autopsy findings correlated well with MRIs.
Three specific patterns of neurologic deficit were seen in a group of 52 patients with the idiopathic hypereosinophilic syndrome. Central nervous system dysfunction was seen in 7 patients (15%), 4 of whom had a distinctive encephalopathy characterized by behavioral disturbances and upper motor neuron signs. Peripheral neuropathy was found in 27 patients (52%), with a sensory polyneuropathy the commonest form (in 23 patients), although mononeuritis multiplex and radiculopathy were also seen. Central nervous system abnormalities from embolic disorders were seen in 6 patients (12%). Thus, a total of 65% of these patients had some neurologic dysfunction. Although the spectrum of neurologic disease is broad and includes very different manifestations, we conclude that distinct patterns of neurologic involvement are characteristic of this syndrome.
The vasculitides are a group of disorders that include the polyarteritis nodosa group of systemic necrotizing vasculitides, hypersensitivity vasculitis, Wegener's granulomatosis, lymphomatoid granulomatosis, giant cell arteritis, Behçet's disease, and isolated angiitis of the central nervous system. Classification is based on clinical, angiographic, and histological features. The frequency and distribution of neurological involvement vary with the underlying disorder and may provide the initial symptoms. Polyarteritis nodosa and Wegener's granulomatosis may affect both the central and peripheral nervous systems, whereas isolated angiitis of the central nervous system and Behçet's disease affect the central nervous system alone. Neurological dysfunction occurs in 80% of patients with polyarteritis nodosa and fewer than 10% of patients with hypersensitivity vasculitis. The mechanism of neurological dysfunction in the vasculitides is tissue ischemia. The clinical effects of ischemia vary, and symptoms may be transient or prolonged. Mononeuritis multiplex, polyneuropathy, and stroke are frequent complications, but encephalopathies, cranial neuropathies, and brachial plexopathies are seen as well. The occurrence of symptoms late in the course of a disease suggests ischemia resulting from healed, scarred vessels as well as from those that are acutely inflamed; this is the case in Takayasu's arteritis and possibly also in polyarteritis nodosa. Treatment is based on identifying and removing the sensitizing agent when possible. Wegener's granulomatosis requires therapy with cyclophosphamide; temporal arteritis, with corticosteroids. In other vasculitides a balance must be reached between the progression of the disease and the side effects of immunosuppression.
Isolated angiitis of the central nervous system is an uncommon clinicopathologic entity characterized by vasculitis restricted to the vessels of the central nervous system without other apparent systemic vasculitis. Experience with the diagnosis, treatment, and follow-up evaluation in four patients with this disease is presented. Early manifestations of disease include severe headaches, altered mental function, and focal neurologic deficits. The pattern of progression from headaches and altered mental status to multifocal neurologic deficits is particularly suggestive of the diagnosis of vasculitis of the central nervous system. Systemic symptoms such as fever, myalgia, arthralgia, and arthritis, which occur frequently in other vasculitic syndromes, are generally not present in patients with isolated angiitis of the central nervous system. No single laboratory study can firmly establish or completely exclude the diagnosis; consequently, tissue diagnosis with biopsy of the brain parenchyma and leptomeninges may be required. In two patients, recurrent disease developed despite treatment with corticosteroids alone. Sustained clinical remission was induced in all four patients with a regimen of daily cyclophosphamide and alternate-day prednisone therapy. Cyclophosphamide and alternate-day prednisone therapy are considered the treatment of choice in severe, progressive, or corticosteroid-resistant isolated angiitis of the central nervous system.
A combined retrospective and prospective study of a patient population with either or both biopsy and angiographic evidence of systemic necrotizing vasculitis was undertaken in order to delineate the neurologic manifestations of this syndrome. The type, extent and natural history of the lesions in the peripheral and central nervous system were evaluated, together with the response fo the nervous system disease to corticosteroids or cytotoxic agents or both. In 60 percent of the patients, there was involvement of the peripheral nervous system. Four patterns of neuropathy were seen: mononeuritis multiplex, extensive mononeuritis, cutaneous neuropathy and polyneuropathy. The central nervous system was involved in 40 percent of the patients, manifested predominantly by diffuse and focal disturbances of cerebral, cerebellar and brain stem function. This study demonstrates the complexity and heterogeneity of the neurologic complications of the systemic necrotizing vasculitides. With treatment of the vasculitic process and prevention of further insult, both the peripheral and central nervous system make significant, and at times, dramatic, recovery.
Transfer-proficient Flac mutants with reduced abilities to plate various F-specific phages were isolated, either by selection after mutagenesis, or as revertants of Flac traA mutants. In many of the mutants pilus-related properties were altered, including physical adsorption of R17 phage, the number of pili per cell and the outgrowth/retraction equilibrium. Complementation studies showed that the mutations were in traA, suggesting that specific alterations in the amino-acid sequence of the pilin subunit protein were responsible for the altered pilus properties. Complementation between the Flac traA mutants and the derepressed plasmid R100-1 restored phage sensitivity in some cases, suggesting that the incorporation of both mutant and R100-1 subunits into the pilus structure may result in conformational changes which increase the capacity of the pilus to interact with phages.
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Nucleocapsids in quantities approaching 1 mg were purified from 109 measles virus-infected cells. They contained one polypeptide species with a molecular weight of 59,000. Antiserum was raised in rabbits against purified nucleocapsids and used in a competitive radioimmunoassay. Because of their instability, purified nucleocapsids were not suitable for use in such an assay. Instead partially purified nucleocapsids from HEp-2 cells persistently infected with measles virus and labeled in vitro with [35S]methionine were used as the source of radioactive antigen. The radioimmunoassay thus developed measured less than 5 ng of nucleocapsids in infected cells.
Chitin synthase (ED 2.4.1.16) has been characterized in Aspergillus flavus. A K(m) value of 2.5 m(M) was obtained for the substrate UDPGlcNAc. The enzyme had a requirement for GlcNAc, and Mg2+ and activity was increased in the presence of soluble chitodextrins F1 and F2. The optimum activity was obtained using Tris--HCl buffer, pH 7.5, with a secondary peak at pH 6.2 and an incubation temperature of 29.5 degrees C. Distribution patterns of chitin synthase in protoplasts and mycelial material were very similar. The highest specific activity was found in a 200 000 X g fraction. Enzyme levels in growing mycelium increased during the exponential growth phase after which they declined. Activity also increased during the early stages of regeneration of both conidial and mycelial protoplasts, despite an initial lack in net protein synthesis. Chitin synthase levels were also dependent upon the carbon source available during regeneration.
Chitin synthase of Mortierella vinacea was present in the "microsomal' fraction (100 000 g precipitate), the 'cell-wall' fraction (2000 g precipitate) and the 'mitochondrial' fraction (10 000 g precipitate). The properties of the 'microsomal' enzyme were investigated. The pH optimum was between 5-8 and 6-2, and the temperature optimum was between 31 and 33 degrees C. The Km for UDP N-acetyl-D-glucosamine was 1.8 mM. The enzyme was stimulated by Mg2+ and a slight stimulation was also effected by N-acetyl-D-glucosamine. Soluble chitodextrins were inhibitory. A pH-dependent, heat-stable inhibitor of chitin synthase activity was present in the soluble cytoplasm from the mycelium. The effects of aeration and glucose concentration on enzyme production in growing cultures were also investigated; maximum specific activity of chitin synthase was associated with the cessation of exponential growth.
The enzyme chitin synthetase (UDP-acetylaminodeoxyglucosyl transferase, EC 2.4.1.16) in Cunninghamella elegans has been investigated. The enzyme was present in the microsomal, cell wall, mitochondrial and the soluble cytoplasmic fraction of the mycelium, with the former having the highest specific activity. The properties of the enzyme in this fraction were investigated; the Km for UDP GlcNAc was 1.23 mM and 2.08 mM GlcNAc in the presence of 1 mM UDP GlcNAc. The temperature optimum was between 26 degrees and 29 degrees C and maximal activity was at pH 6.25. Mg++ ions had no effect on chitin synthesis, but soluble chitodextrins inhibited the enzyme. The production of chitin synthetase was correlated with the growth of the fungus, maximum activity being found during the late exponential phase of growth. Chitin was confirmed as the sole product of enzyme action, by digestion with chitinase.
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