An introduction to glycosylation and rheumatic disease. What is the current state of play?
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Biomedical subjects
Publications and source records attributed to A Alavi.
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Two patients developed unilateral occipitotemporal infarcts that produced inferior quadrantic achromatopsia and an accompanying superior quadrantanopia. Magnetic resonance imaging and single-photon emission computed tomographic studies of both patients supported the current view that color vision is encoded in the lingual and fusiform gyri. Although the quadrantic defect in color processing was profound, neither patient was aware of it. Simple bedside testing of patients with superior quadrantanopia may disclose an unrecognized quadrantic achromatopsia.
To identify the source of inhibitory signals from the stomach or intestine that lead to satiation, the effects of 300-g tomato soup preloads on the gastric emptying of a solid meal and on hunger and fullness ratings were examined. Subjects were nine healthy women who each ingested an egg sandwich: 1) with no soup, 2) immediately after the soup, and 3) 20 min after the soup. Emptying of the sandwich was measured using radionuclide scintigraphy. Soup significantly prolonged the lag phase (period before significant emptying occurred, p < 0.05), and the half-emptying time (p < 0.01) of the sandwich, but only when ingested immediately before the sandwich. Thus, soup affected the emptying of the sandwich when the volume of soup in the stomach was at a maximum. Passage of soup into the duodenum over a 20-min period had no effect on emptying of the sandwich. Despite the different gastric/postgastric distributions of the soup and the sandwich in the two preload conditions, fullness ratings were not different.
Alveolar hypoxia is known to result in localized pulmonary arterial vasoconstriction. As a consequence, blood is diverted from poorly ventilated alveoli, maintaining ventilation-perfusion (V/Q) matching and thereby reducing the deleterious effects on gas exchange. An incomplete alveolar hypoxic vasoconstrictive response can be easily demonstrated by radionuclide V/Q lung scanning. A case of albuterol-induced inhibition of hypoxic pulmonary vasoconstriction is described in a patient with steroid-dependent asthma. The utility of V/Q lung scanning as a simple, noninvasive test to detect this phenomenon in patients with primary airway disorders who deteriorate despite appropriate therapy is also briefly discussed.
We assessed the relationship between temporal lobe metabolism measured quantitatively and qualitatively with PET using [18F]-fluorodeoxyglucose (FDG) and postoperative seizure frequency after anterior temporal lobectomy. Forty-three patients with refractory partial epilepsy had anterior temporal lobectomy and preoperative assessment with PET-FDG. Qualitative PET analysis was performed visually by two blinded observers, and quantitative PET analysis was performed using an anatomic template for six control and six temporal lobe subregions, deriving an asymmetry index for each region. Seizure outcome was assessed 1 year after surgery; patients were classified as being seizure-free or as having persistent seizures. Qualitative data were analyzed using Fisher's exact test and the t test, and quantitative data were analyzed using a repeated-measures ANOVA. Thirty-two patients (74%) were seizure-free at follow-up, and 11 had persistent seizures, although most improved. Twenty-nine of 35 patients (83%) with restricted temporal lobe hypometabolism by visual analysis were seizure-free, compared with three of eight patients (37.5%) with normal scans or multilobar hypometabolism. Quantitative analysis revealed that an asymmetry of mesial temporal lobe glucose consumption (uncal region) correlated with improved surgical outcome (p < 0.02). We developed a logistic regression model to predict individual outcome based on the asymmetry in uncal metabolism. Lateral temporal metabolism did not correlate with outcome. We conclude that both visual PET analysis and quantitative PET analysis predict outcome after temporal lobectomy, although quantitative measures offer more precise information.
Oligosaccharides can be of fundamental importance to glycoprotein function. Glycosylation abnormalities are present in rheumatoid arthritis (RA) and may be associated with disease pathogenesis. To determine whether similar disease mechanisms occur in the MRL-1pr/1pr autoimmune arthritic mouse, studies on B lymphocyte galactosyltransferase (GTase) have been carried out. In MRL mice, a significant reduction in peripheral blood lymphocyte (PBL) GTase activity was found when compared to their paired splenic (SP) GTase activity (-69%, p = 0.002) and histocompatible non-autoimmune control CBA/Ca mice (-67%; p = 0.002). The changes in PBL GTase activity are similar to those found in RA and on further analysis, using mixing experiments in the presence of purified human milk GTase, this reduction was shown not to be due to the presence of a soluble intracellular GTase inhibitor. Furthermore when examining MRL derived hybridoma cells producing IgG, significantly reduced GTase activity was detected in the rheumatoid factor (RF) producing hybridoma cells compared to those secreting an irrelevant antibody (-21%, p < 0.05). Together these findings suggest that the glycosylation changes observed in this study, and those reported previously in RA, are tissue-specific, may result from cells trafficking from centres of disease activity and are not the result of direct enzyme inhibition. It is now important to further understand the mechanisms controlling glycosylation and relate disease associated changes with those occurring as part of normal cellular physiology.
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Bile leaks are the most common biliary complication of laparoscopic cholecystectomy. Cholescintigraphy has been utilized in the past to diagnose postoperative bile leaks after open cholecystectomy. However, the sensitivity and specificity of this imaging technique has not been defined or compared to other clinical tests. We have retrospectively studied 30 patients over a 2-yr period who underwent cholescintigraphy for a possible postoperative bile leak. This study reviewed the cholescintigraphy images, clinical presentations, and abdominal ultrasonography/CT scanning. Using a gold standard that consisted of the findings of cholangiography and clinical outcome, we determined the diagnostic accuracy of these tests. Symptoms, laboratory testing, and physical examination were found to be poor predictors for the presence of postoperative bile leaks. Ultrasound and CT imaging were less sensitive and nonspecific. In contrast, cholescintigraphy was found to be quite accurate (83-87%) for predicting the presence of bile leaks after laparoscopic cholecystectomy, as well as other biliary surgeries.
UNLABELLED: In this paper we correlate the findings on 99mTc-HMPAO brain SPECT with the results of clinical examinations and electroencephalography to determine the utility of SPECT in the evaluation of patients with suspected status epilepticus. METHODS: Thirteen patients with suspected status epilepticus underwent serial neurologic examinations, serial electroencephalograms, CT/MRI scanning and 99mTc-HMPAO SPECT. Seven patients were diagnosed with status epilepticus and six patients received other neurological diagnoses. RESULTS: All patients with status epilepticus at the time of the brain SPECT scan demonstrated focal hyperperfusion on SPECT in an area concordant with that suggested by EEG. One patient with status epilepticus demonstrated a persistent area of hyperperfusion on SPECT 24 hr after the cessation of status with no evidence of breakdown in the blood-brain barrier demonstrated by 99mTc-DTPA SPECT. No patient in this study without a diagnosis of status epilepticus had focal areas of hyperperfusion on SPECT. CONCLUSION: We suggest that a 99mTc-HMPAO SPECT scan demonstrating focal hyperperfusion in a patient being evaluated for partial status epilepticus is nonspecific. Even in the absence of a structural lesion causing local breakdown in the blood-brain barrier, it may indicate either ongoing status epilepticus or recently terminated status. However, a SPECT scan demonstrating no area of focal hyperperfusion argues against the diagnosis of partial status.
UNLABELLED: The primary objective of this study was to characterize the effectiveness of 123I-metaiodobenzylguanidine (MIBG) as a screening test for pheochromocytoma in routine clinical practice. An attempt was made to determine why some tumors and some adrenal glands without pheochromocytoma minimally manifest increased uptake. METHODS: Planar images were obtained with a standardized protocol in a diverse group of patients. The intensity of uptake in each adrenal gland was graded on a 0-3-point scale by using the intensity of activity in the liver as a reference. Follow-up data were obtained from both the patients and the referring physicians. A final diagnosis was eventually established in 120 patients who had a total of 238 adrenal glands. RESULTS: There was an intramedullary pheochromocytoma in 24 of the 238 adrenal glands (10.1%). The uptake was very intense (Grade 3) in 21 of them (87.5%). The uptake was only mildly to moderately increased in the other three intra-adrenal tumors. There was no visible uptake in 148 of the 214 (69.2%) adrenals without a pheochromocytoma, but there was mildly to moderately increased activity in 66 (30.8%). There were no other features of the clinical data base which could differentiate between mildly increased uptake in a pheochromocytoma and mildly increased activity in a gland without a tumor, including the 24-hr urinary excretion of catecholamines. CONCLUSIONS: Since every intra- and extra-adrenal tumor was visualized, the findings suggest that 123I-MIBG may be the most sensitive screening test available for diagnosing pheochromocytoma. The test results should be definitive in most patients.
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UNLABELLED: The objective of this study was to define the sensitivity, specificity and accuracy of ventilation-perfusion (V/Q) lung scanning in distinguishing chronic thromboembolic pulmonary hypertension (PHT) from other nonembolic causes of PHT. METHODS: The V/Q lung scans from 75 patients in whom a confirmed cause of PHT was established were retrospectively reviewed. Twenty-five patients (33%) had chronic thromboembolic PHT, whereas 35 patients (47%) and 15 patients (20%) suffered from primary PHT and secondary nonthromboembolic PHT, respectively. RESULTS: A high-probability V/Q scan interpretation had a sensitivity of 96% and a specificity of 94% for detecting patients with thromboembolic PHT. The combination of high- and intermediate-probability V/Q scan interpretations had a sensitivity of 100% for detecting patients with thromboembolic PH; however, the specificity decreased to 86%. Of the 35 patients with primary PHT, all but one patient had low-probability V/Q scan interpretations. CONCLUSION: In this series, a low-probability V/Q scan interpretation effectively excluded the diagnosis of chronic thromboembolic PHT. In patients with an intermediate- or high-probability V/Q scan interpretation, pulmonary angiography was required to confirm the diagnosis of chronic thromboembolic PHT and determine whether surgical intervention was indicated. The V/Q lung scan appears to be a highly sensitive test for chronic thromboembolism in the diagnostic evaluation of patients with PHT. However, its role needs to be defined further by application to a prospectively recruited cohort of patients with PHT.
UNLABELLED: Standardized uptake values (SUVs) are widely used to measure 18F-fluorodeoxyglucose (FDG) uptake in various tumors. It has been reported that normalization of FDG uptake for patient body weight (SUVbw) overestimates FDG uptake in heavy patients, as their fraction of body fat (with low FDG uptake) is often increased. The objective of this study was to determine if "normalization of FDG uptake for the body surface area" (SUVbsa) is independent of the patient's body size and is more reliable than SUVbw. METHODS: FDG-PET images were acquired on 44 patients (body weight range: 45-115 kg) with cancer. SUVbw [(mCi/g of tissue)/(mCi injected/patient body weight in g)] and SUVbsa [(mCi/g of tissue)/(mCi injected/patient BSA in m2)] were determined for the liver. Since most observers are accustomed to using the SUVbw, the two values were compared by setting the mean SUVbsa equal to that of SUVbw. RESULTS: SUVbw and SUVbsa were 3.42 +/- 0.85 (mean +/- s.d.) and 3.42 +/- 0.60, respectively. The standard deviation of the SUVbsa was smaller than that of SUVbw. More importantly, there was a strong positive correlation between SUVbw and, not only body weight (r = 0.75) but also BSA (r = 0.68), whereas only a weak correlation between SUVbsa and body weight (r = 0.41) or BSA (r = 0.38) was found with a near flat regression line. CONCLUSION: SUVbw overestimates FDG uptake in large patients. SUVbsa appears preferable to SUVbw, since it is minimally affected by the body size.
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Eight subjects with late-life depression, eight subjects with probable Alzheimer disease, and eight healthy age-matched controls were studied using 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography in the resting state with their eyes open and ears unoccluded. The depressed subjects showed widespread reductions in the regional cerebral metabolic rate for glucose in most major neocortical, subcortical, and paralimbic regions that were significantly different from control values (P < 0.01). The metabolic decrements in the depressed group were comparable in magnitude to those seen in the Alzheimer disease group. These data demonstrate widespread nonfocal decline in glucose metabolism in late-life depression that is comparable to the hypometabolism seen in Alzheimer disease. These findings have pathophysiological implications in major depressive disorder in the elderly.
Abnormalities in the gastric pacemaker potentials occur in patients with impaired gastric emptying. It is unclear if treatment effects the underlying rhythm or if normalization of dysrhythmias is important. We examined the effect of cisapride using surface electrogastrograms and radionuclide gastric emptying studies of patients with idiopathic and diabetic gastroparesis. Twelve of 14 patients had abnormal baseline electrogastrograms. After six months of cisapride, four patients had normalization of their electrical activity and six had improvement. Patients with idiopathic gastroparesis had an increase in gastric emptying at 120 min from 48.9 +/- 3.8% (baseline) to 70.9 +/- 6.0% (six months), P = 0.009. Patients with diabetes mellitus had a similar improvement. Patients who had normalization of the electrogastrogram had a greater gastric emptying rate than patients with continued dysrhythmias. Thus, dysrhythmias are important in the etiology for gastroparesis, but other factors need to be examined.