Biomedical subjects
Publications and source records attributed to T J Sullivan.
Multifocal fibrosclerosis is a condition of unknown aetiology, characterised by fibrous lesions occurring at a variety of sites. Clinical variants include retroperitoneal fibrosis, Riedel's thyroiditis, sclerosing cholangitis, and mediastinal fibrosis. Orbital pseudotumour has been reported as a manifestation of this condition. Three patients with multifocal fibrosclerosis in whom orbital involvement was the dominant feature are described.
Lewis x Buffalo F1 rat lymphocytes express both forms of the allelic marker RT7.1 (Lewis) and RT7.2 (Buffalo). We generated myelin basic protein (MBP)-specific encephalitogenic F1 T helper cell lines and adoptively transferred them into naive irradiated Lewis recipients, which enabled us to detect and isolate donor T cells (with RT7.2) within the recipients. The spinal cord and cerebrospinal fluid (CSF) were highly enriched for the donor T cells compared with the blood and spleen. The donor cell number peaked on the first day of disease in the spinal cord and CSF and decreased as the disease progressed. A high percentage of the donor T cells isolated from the spinal cord were positive for the T helper cell activation marker OX-40, whereas a (lower) percentage of CSF donor cells expressed OX-40. Donor cells isolated from blood or spleen were negative for OX-40 expression. In contrast, the IL-2 receptor (CD25) was positive on all the transferred T cells in all tissue sites examined. Cell-sorting experiments showed that the MBP-specific donor cells were enriched for IFN-gamma, IL-2, TNF-alpha, and IL-3 mRNA when compared with the host-recruited spinal cord cells, whereas similar amounts of IL-10 mRNA were produced by both populations. Lymphokine mRNA production was also enriched in donor T cells isolated from the spinal cord compared with donor T cells isolated from the spleen. The spinal cord donor cells produced higher levels of IL-2, IFN-gamma, and IL-3 mRNA, whereas similar amounts of IL-10 and TNF-alpha mRNA were produced from donor cells isolated from the spleen and the spinal cord. Our data suggest that the amount/percentage, activation state, and enhanced lymphokine production at the site of inflammation are all important factors in determining the autoimmune potential of Ag-specific effector T helper cells.
BACKGROUND: Sulfonamides undergo oxidative metabolism to yield reactive metabolites that haptenate proteins readily. Although it has been shown that sulfonamide metabolites bind covalently to murine microsomes, sulfonamide-conjugated serum proteins have not been analyzed in the peripheral blood of treated individuals. OBJECTIVE: We hypothesized that during treatment with sulfamethoxazole, intracellular proteins are haptenated by drug metabolites, and some of these are destined for secretion into the serum. METHODS: Using antibodies specific for sulfamethoxazole and an alkaline phosphatase immunoblotting technique, we attempted to demonstrate the presence of sulfamethoxazole-substituted proteins in the serum of individuals during a course of treatment. RESULTS: Five days into therapy, serum protein haptenation by sulfamethoxazole was demonstrated in two of the three individuals studied. In addition, Western blot analysis revealed that haptenation is not indiscriminate, but highly selective. A single 30 kd protein is the target of haptenation in all instances. A kinetic analysis revealed that substituted proteins can be detected early, within hours of administration. Moreover, haptenated proteins remain detectable in the serum 48 hours after discontinuation of the drug. CONCLUSION: The results presented here constitute the first direct evidence that sulfonamides, on being metabolized, covalently haptenate human serum proteins during a course of therapy.
PURPOSE: To describe, in three patients, the rare condition of spontaneous hemorrhage within the rectus muscle. METHODS: The records of three patients with a diagnosis of spontaneous hemorrhage within a rectus muscle were reviewed. RESULTS: Three adults had sudden unilateral painful proptosis with clinical and computed tomographic findings consistent with hemorrhage within a rectus muscle; in two patients, the presence of recent hemorrhage was confirmed on magnetic resonance imaging. In all three patients, the hemorrhage resolved spontaneously. CONCLUSIONS: Spontaneous hemorrhage within a rectus muscle may occur in otherwise healthy adults without any apparent underlying cause. In the absence of visual deterioration, no treatment is required, and complete clinical resolution may be anticipated.
1. Primary orbital amyloidosis is a rare form of localized amyloidosis in which the precursor protein has not previously been identified. We report here the first extraction of amyloid fibrils from a tissue biopsy containing orbital amyloid, and characterization of the fibril protein. 2. The N-terminal nine residues were identical with residues 278-286 and 275-283 of the third constant (CH3) domains of IgG1 and IgG4 gamma heavy chains, respectively. The mass of the fibril subunit protein was 6125Da by time-of-flight mass spectrometry, compared with the expected masses of 6169.9Da and 6214.9Da for the CH3 domains of gamma 1 from residue 278 and gamma 4 from residue 275, respectively. The fibril protein thus appeared to consist exclusively of an immunoglobulin heavy chain constant domain. 3. Only two examples of immunoglobulin heavy chain derived amyloid have been reported previously and both of these, as well as all published cases of the usual immunoglobulin light chain derived amyloid, contained variable domain sequence. The present case therefore represents a form of local, presumably clonal, B-cell/plasma-cell disorder characterized uniquely by deposition of an amyloidogenic immunoglobulin heavy chain constant domain fragment.
The influence of concomitant antacid administration on the relative bioavailability of the H2-receptor antagonists cimetidine, famotidine, nizatidine and ranitidine, was investigated in a panel of 21 healthy, adult male volunteers in an eight-way crossover trial. Administration with antacid reduced the bioavailability of all agents tested. The reduction in area under the serum concentration-time curve (AUC) was greatest for cimetidine (23%) and ranitidine (26%) and least for nizatidine (12%) and famotidine (19%). Reductions in peak serum concentration (Cmax) followed a similar pattern. The times of peak serum concentrations were not affected by antacid. Comparison of the relative bioavailability among all drugs tested showed no statistically significant differences in the effect of antacid administration on these agents. However, a high degree of intersubject variability was observed.
Of 258 cases of dacryocystorhinostomy performed on children in the period September 1981 to September 1991, 130 were for simple, unresolved congenital nasolacrimal duct obstruction. Other indications for surgery included punctal agenesis, lacrimal fistula, post-traumatic and post-inflammatory canalicular obstruction. Of 177 children without canalicular pathology, 171 (96%) were relieved of symptoms with one operation, without canalicular intubation. Of 81 cases with canalicular disease, 55 of 70 (79%) who underwent DCR plus canalicular intubation, and 10 of 11 who underwent DCR plus Lester-Jones tube, were substantially improved with one operation. No child required peroperative or postoperative blood transfusion. Dacryocystorhinostomy in childhood, in experienced surgical hands, is a safe procedure, achieving relief of symptoms in most cases, particularly in the absence of canalicular disease.
BACKGROUND: Capillary haemangiomas are vascular tumours of childhood characterised by proliferative and involutional phases and affecting 1% to 2% of newborns. Recently, recombinant interferons have been used in the treatment of life and sight threatening complications of these tumours. METHODS: The history, results of examination, investigations, management and outcome of two patients with sight-threatening orbital capillary haemangiomas treated with recombinant interferon alpha-2a and 2b respectively were reviewed. RESULTS: Orbital and systemic lesions displayed good response to interferons. Side effects noted were transient pyrexia and elevated serum aminotransferase levels. Disturbed liver function test results occurred in one case and normalised with temporary cessation of therapy. CONCLUSIONS: The interferons are a useful alternative treatment of orbital capillary haemangioma in selected cases.
PURPOSE: To present the ocular pathology of a three-year-old child with Leber's congenital amaurosis (LCA) who died from an unrelated episode of presumed viral meningitis. METHODS: Autopsy was performed, and in addition the globes were harvested for pathological examination. Before the child's death, known systemic disorders with infantile retinal dystrophy were excluded. RESULTS: The outer nuclear layer and photoreceptor layers are the primary site of retinal pathology in LCA. CONCLUSION: This report of the pathological findings in LCA, early in the natural history of the disease, indicates that process appears to be a degeneration rather than an agenesis.
We have produced, by using a sonicate of Borrelia burgdorferi, a monoclonal antibody (MAb), NYSP39H, that is specific for the P39 protein band. This MAb reacted with 13 isolates of B. burgdorferi but not with eight different spirochetes (four borrelias, two leptospiras, and two treponemas). Surface labeling of B. burgdorferi with biotin and subsequent treatment with Nonidet P-40 showed that P39 was not biotinylated but was extracted with Nonidet P-40, indicating that it is present within the outer membrane, but not on the surface of the spirochete. Immunoelectron microscopy revealed the immunogold probe primarily at the cytoplasmic membrane region of the spirochete. The MAb detected B. burgdorferi in the indirect fluorescent-antibody test only when the spirochetes from a culture or in a tick homogenate were fixed with polylysine and not with acetone. NYSP39H appears to be an appropriate probe for use in the specific detection of B. burgdorferi.
Three drug interactions of nizatidine and of other antisecretory agents were studied comparatively. First, the effects of nizatidine, cimetidine and ranitidine on the dispositional kinetics of theophylline were evaluated in chronic obstructive pulmonary disease (COPD) patients. Second, the effect of magnesium/aluminium hydroxide on the relative bioavailability of nizatidine, famotidine, cimetidine and ranitidine was evaluated in healthy volunteers. Finally, the effects of nizatidine and omeprazole on the dispositional kinetics of phenytoin were evaluated in healthy volunteers. Only cimetidine altered the steady-state kinetics of oral theophylline, slowing theophylline clearance by 25%. Each of the H2-receptor antagonists exhibited a modest decline in relative bioavailability when ingested with antacid. Antacid ingestion decreased the bioavailability of famotidine, ranitidine and cimetidine by 20-25%, and the bioavailability of nizatidine by 12%. Each of these effects was statistically significant. Finally, it was found that neither omeprazole nor nizatidine affected the single dose kinetics of phenytoin.
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The goal of this work is to develop a method for the functional analysis of malaria genes using the method of DNA transfection. We have developed a transient transfection vector by constructing a chimeric gene in which the firefly luciferase gene was inserted in frame into the coding region of the pgs28 gene of Plasmodium gallinaceum. This plasmid DNA was introduced into P. gallinaceum gametes and fertilized zygotes by electroporation, and luciferase expression was assayed after 24 hr. This report of successful introduction and expression of a foreign gene in a malaria parasite demonstrates the feasibility of this approach to developing methods for the functional analysis of parasite genes.
Steady-state theophylline pharmacokinetic parameters were studied in a panel of 14 patients with chronic obstructive pulmonary disease (COPD). Pharmacokinetic parameters were evaluated before, during, and after a 10-day regimen of the macrolide antibiotic, dirithromycin. The addition of dirithromycin (500 mg orally once daily at 7:00 AM) to a sustained-release theophylline dosing regimen (every 12 hours) elicited small changes in the steady-state pharmacokinetics of theophylline, which were not statistically significant. Mean steady-state plasma theophylline trough concentrations (Css,min) were invariant before, during, and after dirithromycin treatment. Mean average steady-state plasma theophylline concentrations (Cav) declined by 7% during dirithromycin treatment (NS), and mean peak plasma concentrations (Css,max) declined by 12% (NS). Theophylline clearance (CL/F) also remained relatively unchanged during dirithromycin treatment exhibiting an increase of only 11% (NS). Dirithromycin treatment does not significantly affect the steady-state pharmacokinetics of theophylline, and its use in COPD patients is not likely to modify treatment outcomes with theophylline.
Continuous infusions of any given H2-blocking drug have uniformly been found to be superior to intermittent infusions of the same H2-blocking drug in sustaining elevations in gastric pH. Comparisons of intermittent and continuous infusions among different H2-blocking drugs have heretofore not been made. Owing to its greater potency and longer half-life, the authors were interested in determining whether intermittent infusions of famotidine might be as effective as continuous infusions of ranitidine in sustaining elevations of gastric pH. The effectiveness of a continuous intravenous infusion of ranitidine (6.25 mg/hr) was compared with the effectiveness of intermittent intravenous infusions of famotidine (20 mg every 12 hours) in sustaining gastric pH above 4.0 in 18 young, healthy adult male subjects using a randomized two-way cross-over design. Gastric pH was continuously monitored for 24 hours. The intermittent famotidine regimen was determined to be as effective as the continuous ranitidine regimen with respect to the following parameters: (1) the percentage of the 24-hour dosing period during which gastric pH exceeded 4.0; (2) the area under the pH > or = 4 versus time curve; and (3) median gastric pH.
The effects of omeprazole (40 mg orally per day) and nizatidine (300 mg orally per day) on the disposition of phenytoin (4.5 mg kg(-1) p.o. single dose) were studied in 18 healthy, young adult males. Total and unbound plasma concentrations of phenytoin were measured for 48 h after each dose of phenytoin. Neither treatment altered the disposition kinetics of phenytoin, the hydroxylation of which is mediated specifically by cytochromes P450 of the 2C subfamily.
A case of anaerobic orbital cellulitis secondary to intraorbital wood and an approach to management are presented. Retained foreign bodies should be suspected in all penetrating orbital injuries involving wood. Computed tomography (CT) should be performed to delineate the location and size of any foreign body and to determine damage to adjacent structures. Magnetic resonance imaging (MRI) is useful in certain circumstances. Orbital infection should be anticipated and broad-spectrum antibiotic cover (including anaerobes) provided. Surgical intervention should be undertaken to remove any retained foreign bodies to prevent vision-threatening complications.
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