An anatomical explanation for good-prognosis rheumatoid arthritis.
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Biomedical subjects
Publications and source records attributed to J Ridgway.
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OBJECTIVE: The interrelationship between synovitis and bone damage in rheumatoid arthritis (RA) is a subject of controversy. Using magnetic resonance imaging (MRI), this study followed the bone changes in early RA and determined their relationship to synovitis. METHODS: Thirty-one patients with early RA who had swelling of the metacarpophalangeal (MCP) joints and 31 healthy control subjects with no clinical evidence of arthritis underwent MRI of the second through fifth MCP joints of the dominant hand by use of a 1.5T scanner. Coronal T1-weighted and T2-fat suppressed (FS) sequences were performed to evaluate bone edema, and gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) pulse sequences were obtained to evaluate synovitis. Bony abnormalities were described as bone edema (low signal on T1-weighted sequences and intermediate/high signal on T2 FS sequences adjacent to the bone cortex) or as bone cysts (circular juxtacortical abnormalities with low signal on T1-weighted images and with very high signal on T2 FS sequences). Contrast and noncontrast MRI films were scored in a blinded manner, and Fisher's exact probability test was used to determine differences between groups. RESULTS: Twenty-one of the 31 RA patients (68%) had bone edema, which was seen in 43 of 124 joints (35% of joints) and 3 of the 31 control subjects had bone edema seen in 3 of 124 joints (2% of joints) (P < 0.0001). Thirty RA patients (97%) had Gd-DTPA-confirmed MCP joint synovitis, and bone edema was seen in 40 of the 75 joints with Gd-DTPA-proven synovitis (53%), but in only 3 of 49 without (6%) (P < 0.0001). CONCLUSION: MCP joint bone edema is present in the majority of patients with RA at presentation, but is seen only occasionally in normal control subjects. The fact that bone edema occurred rarely in the absence of synovitis in patients with RA suggests that bony changes in RA are secondary to synovitis.
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OBJECTIVE: To determine whether cytologic examination of exfoliative specimens obtained during endoscopy was as useful as histologic examination of mucosal biopsy specimens for the diagnosis of gastrointestinal tract disease in dogs and cats and to compare the diagnostic accuracy of 2 techniques (brush or touch) in preparing specimens for cytologic examination. DESIGN: Prospective case series. ANIMALS: 85 dogs and 23 cats. PROCEDURE: Specimens for cytologic and histologic examination were obtained during routine endoscopic examination of the stomach, small intestine, and colon. A diagnosis was made on the basis of cytologic findings (graded objectively) and compared with the diagnosis on the basis of histologic findings. RESULTS: The diagnostic accuracy of cytologic examination was high for all 3 organs. Sensitivities, specificities, and predictive values of positive and negative results were > 90% in most instances. The diagnostic accuracy of the brush technique was equal or superior to that of the touch technique for 84% of specimens. The brush technique was most useful in detecting cellular infiltrates in the lamina propria, whereas the touch technique was more likely to detect acute mucosal inflammation. Percentages of false-positive (3.2%) and false-negative (6.9%) cytologic interpretations were low. CLINICAL IMPLICATIONS: Endoscopy is safe and requires little time to procure specimens for cytologic examination, which can be obtained concurrently with mucosal biopsy specimens. Cytologic examination of exfoliative specimens obtained during endoscopy is a useful and reliable adjunct to histologic examination of biopsy specimens in the diagnosis of gastrointestinal tract disease in dogs and cats.
Xenopus laevis eggs are surrounded by an extracellular matrix consisting of a vitelline envelope, and three jelly layers, J1, J2, and J3 (from egg surface outward). The jelly layers vary in thickness (about 150, 15 and 200 microns for J1, J2 and J3 respectively) but all are translucent allowing observation of sperm penetration. Video microscopy demonstrated that sperm are able to penetrate and traverse J3 at velocities approaching 30 microns/s. Sperm swim through jelly in a corkscrew-like manner with their rotational and forward velocities being tightly coupled at about 30 degrees/micron forward travel. They are propelled by whip-like power strokes involving hairpin bends in the flagellum that are generated every 180 degrees of rotation and which are propagated from base to tip. The overall trajectories of individual sperm are quite variable. Many sperm head directly for J2 but some do not, these swimming circumferentially, or even away from the egg surface. Most sperm (over 97%) that enter the jelly do not get to the egg surface but are stopped at a variety of positions within J3 or at the outer surface of J2. Efficient sperm penetration and passage through the jelly layers requires a low electrolyte concentration in the surrounding medium, and is inhibited by the lectin wheat germ agglutin (WGA) in a dose-dependent manner. WGA does not block sperm penetration of J3 but does block further progression towards the egg surface. This observation suggests that sperm motility within the jelly is dependent on the carbohydrate moieties of the large glycoconjugates present, and that their alteration by WGA binding accounts for the inability of sperm to reach the egg surface and fertilise the egg.
A small-scale study of the inter-rater and staff:client reliability of the Schalock & Keith (1993) Quality of Life Questionnaire (QOL-Q) was conducted. Whilst the sample size was small and the QOL-Q achieved an acceptable overall level of reliability, the study replicated the pattern of low staff:client concordance and staff overestimation of the independence and autonomy of clients reported by Reiter & Bendov (1996). The results are briefly discussed in the context of the ongoing debate about the utility of proxy response in the literature.
The clinical potential of bispecific antibodies (BsAb) has been hindered by the difficulty of obtaining clinical grade material, together with the immunogenicity of rodent-derived BsAb in patients. The supply issue is being directly addressed by recombinant methods for BsAb fragment production reviewed here. The immunogenicity issue will likely be overcome by the use of humanized or human antibodies. Currently, three technologies appear suitable for the production of BsAb fragments for clinical applications: BsF(ab')2 assembled from Fab' fragments expressed in Escherichia coli, BsF(ab')2 assembled using leucine zippers, and diabodies.
IgE antibodies are thought to play an important role in the induction of allergic inflammation of the bronchi. In this study we assessed the capacity of two inhibitors, FcERI-IgG, an immunoadhesin made up of the alpha chain of the high-affinity IgE receptor joined to a truncated IgG heavy chain, and MaE11, a humanized murine anti-human IgE antibody, to prevent allergen sensitization. Lung parenchyma strips from rhesus monkeys and human beings were passively sensitized for 20 hours with serum from a ragweed-sensitive patient in the presence of 0, 1-, 5-, or 10-fold concentrations of the inhibitors relative to IgE. The parenchymal strips were then suspended in a superfusion apparatus for measurement of isometric tone and collection of superfusate for histamine analysis in response to challenge with antigen E (AgE). Nonsensitized tissues did not react to AgE challenge, whereas AgE challenge of passively sensitized tissues resulted in a time-dependent parenchymal contraction and histamine release. Both FcERI-IgG and MaE11 completely abolished the AgE-induced contraction and histamine release in a dose-dependent manner. In addition, passively sensitized lung tissues failed to respond to direct challenge with either FcERI-IgG or MaE11. The results of this study suggest that FcERI-IgG and MaE11 may have important immunotherapeutic benefit for the amelioration of IgE-mediated diseases.
The purpose of this study was to measure signal enhancement over time in the normal pancreas after intravenous bolus infection of gadolinium-DTPA (Schering Health Care Ltd) (Gd-DTPA). Data was obtained from 25 patients with no evidence of pancreatic disease before, immediately after and over a 2 min period following injection of Gd-DTPA (Magnevist 0.2 ml per kg). Scans were obtained using a turboFLASH sequence which allows 11 slices to be acquired during a single breathhold period of 19 s. Five mm thick slices were acquired in the coronal/oblique plane at 0.5 mm intervals. A pre-contrast block of slices was obtained followed by dynamic post-contrast scanning with the first of four acquisitions beginning 12-15 s after bolus injection. A 10 s interval between each acquisition was selected to allow the patients to breathe. Signal intensity for each acquisition was measured for the pancreatic head and tail and also for the liver. All values were normalized to fat. Marked enhancement of the pancreas was seen in all cases with peak enhancement occurring in the first and second post-contrast acquisition. The pancreatic duct was more easily seen after contrast injection.
Cross-linking of the high affinity IgE receptor (Fc epsilon RI) expressed on mast cells and basophils is essential for triggering anaphylaxis in vivo. Previously, other investigators have tried to produce competitive inhibitors using IgE peptide analogues and anti-IgE antibodies with limited success. To create a novel specific inhibitor of IgE that can block binding of IgE to Fc epsilon RI without the capacity to stimulate degranulation, we made an Fc epsilon RI-IgG immunoadhesin. The Fc epsilon RI-IgG was constructed by gene fusion of the extracellular portion of the human alpha-chain of Fc epsilon RI, which contains the high affinity binding site for IgE, with a truncated human IgG1 H chain C region. The Fc epsilon RI-IgG recognizes both human and murine IgE. Coincubation of Fc epsilon RI-IgG with murine IgE prevented sensitization of RBL-2H3 cells and the subsequent histamine release in response to anti-IgE. Similarly, when the Fc epsilon RI-IgG was preincubated with equimolar concentrations of either hyperimmune mouse sera or purified mouse IgE, it completely blocked the passive cutaneous anaphylaxis reaction in rats. Furthermore, i.v. administration of Fc epsilon RI-IgG following intracutaneous injection of serum from DNP-immunized mice was able to block the passive cutaneous anaphylaxis reaction in a time-dependent fashion. These results demonstrate that Fc epsilon RI-IgG is a potent inhibitor of IgE binding to intracutaneous mast cells in vivo and may prove clinically useful for the treatment of IgE-mediated disease.
Magnetic resonance imaging was performed at 1.0 T in seven patients with severe acute pancreatitis. A T2-weighted spin echo sequence and a breath-hold multislice rapid gradient echo sequence (TurboFLASH) were used in each patient. TurboFLASH imaging was performed before and after intravenous gadopentetate-dimeglumine (Gd-DTPA). All MRI images were compared with a recent contrast-enhanced CT scan. Postgadolinium MRI was equivalent to contrast-enhanced CT in differentiating viable pancreatic parenchyma from areas of pancreatic necrosis. MRI identified the presence of gas in a case of pancreatic abscess but failed to identify small foci of pancreatic calcification demonstrated in one case by CT. MRI was also equivalent to CT in assessing the location and extent of peripancreatic inflammatory changes and fluid collections. However, MRI, particularly the T2-weighted spin echo, was superior to CT in characterizing the complex nature of such inflammatory changes in one case. Initial experience suggests that MRI is a valuable technique in assessing patients with severe acute pancreatitis.
The purpose of this study was firstly to show the diagnostic value of a rapid acquisition multislice sequence (TurboFLASH) during bolus injection of gadolinium-DTPA by comparing it with the pulse sequences currently used for abdominal studies and secondly to develop improved scanning protocols for the liver. Patients were referred for upper abdominal studies including portal vein assessment. 40 patients were imaged in the coronal plane using a multislice TurboFLASH (TF) sequence (TR = 100; TE = 4) acquired during a breath-hold period of 19 s. The short echo time allows up to 11 slices of 5 mm thickness to be acquired simultaneously. Images were obtained before, during and after bolus administration of Gd-DTPA. The slices from each acquisition were combined using a maximum intensity projection algorithm to include all the vessels on a single image. Initially each patient was scanned using a conventional axial T2 weighted spin-echo sequence (T2W-SE) (TR2000; TE = 45/90) and a coronal T1 weighted spin-echo sequence (TR450; TE = 15). The clarity of the demonstration of vascular anatomy was compared and scored for all sequences by two radiologists. Vessel patency, the conspicuity of mass lesions and the spread of tumour to adjacent structures were also scored. The anatomy of the main portal vein was significantly better shown by coronal TF images after bolus injection than on T2W-SE images or TF before Gd-DTPA. The right and left portal veins were equally well shown by coronal TF with Gd-DTPA and T2W-SE images. There was no significant difference between contrast enhanced TF and T2W-SE imaging in visualization of the hepatic veins. More lesions were demonstrated by post-contrast TF than by T2W-SE imaging. Portal venous occlusion was better appreciated by post-contrast TF. Our results demonstrate that Gd-DTPA TF imaging improves visualization of the main portal vein compared with SE sequences and provides a more accurate assessment of vessel patency. The segmental anatomy of the liver is better appreciated and the demonstration of focal liver lesions compared with T2W-SE images is improved during the non-equilibrium phase of enhancement. TF acquisitions before and after Gd-DTPA are obtained in approximately 5 min; thus a marked reduction in examination time can be achieved.
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A significant fall in brain T1 relaxation time, consistent with a reduction in brain water of approximately 0.3%, occurred in 19 chronic alcoholic patients admitted for detoxification. There was no correlation between T1 and the severity of withdrawal symptoms and hence no evidence that changes in brain water levels contributed to the abstinence syndrome.
Extraintestinal manifestations of inflammatory bowel disease (IBD) are commonly observed in humans but are poorly documented in companion animals. Thrombocytopenia is an uncommon but well-documented extraintestinal hematological abnormality in humans; however, there are no previous reports of IBD and concurrent thrombocytopenia in the veterinary literature. Seven dogs having idiopathic IBD and concurrent thrombocytopenia were identified and evaluated retrospectively (this represents an incidence of 2.5% in the authors' IBD population). Obvious known causes for thrombocytopenia were eliminated by diagnostic testing as deemed appropriate by the clinician of record. Thrombocytopenia resolved with treatment for the IBD in some but not all patients. This is similar to reports in humans. Thrombocytopenia typically appears to be subclinical, and the severity does not correlate with the degree of intestinal inflammation defined histopathologically. However, quantitative platelet counts should be monitored during IBD therapy, as additional immunosuppression may be required to treat thrombocytopenia, despite resolution of gastrointestinal signs. It is speculated that thrombocytopenia may be causally associated with canine IBD, possibly secondary to immune stimulation from lumenal bacterial antigens, altered immunological regulation, or both.
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