Case records of the Massachusetts General Hospital. Case 39-2006. A 24-year-old woman with systemic lupus erythematosus, seizures, and right arm weakness.
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Acanthamoeba↗
Biomedical subjects
Jonathan Kay
Publications and source records attributed to Jonathan Kay.
Measurement of urinary metanephrines to screen for pheochromocytoma in an unselected hospital referral population.
BACKGROUND: Despite the rarity of pheochromocytoma, diagnosis is important because of the dangers of uncontrolled severe hypertension and the availability of very effective surgical treatment. Urinary or plasma catecholamines or catecholamine derivatives are commonly used to screen for pheochromocytomas before imaging, but data from 24-h urinary metanephrine results, patient age, and sex may better predict tumors in populations with a low pretest probability. METHODS: We retrospectively studied outcomes of an unselected population (1819 patients) referred to a tertiary hospital laboratory for urinary metanephrine testing and investigated the usefulness of some simple derivative measures for detecting pheochromocytoma. We normalized values for urinary 24-h excretion of metanephrine, normetanephrine, and 3-methoxytyramine by dividing by an age- and sex-specific reference range. We then compared pheochromocytoma prediction by the use of products of these normalized measures with the gold standard of biopsy-confirmed tumor. RESULTS: The product of the excretion of normalized metanephrine (nMAD) and normalized normetanephrine (nNMT) (nMAD.nNMT) was a highly sensitive (100%) and specific (99.1%) measure, yielding a positive predictive value of 82%. ROC curves were not improved by including the normalized 3-methoxytyramine concentrations in the product. The test for nMAD.nNMT gave higher sensitivity and specificity than the tests for either substance alone. CONCLUSION: The test for nMAD.nNMT is a useful measure for identifying pheochromocytoma in a population with a low pretest probability.
Adrenal Gland Neoplasms↗
Case records of the Massachusetts General Hospital. Case 4-2006. A 79-year-old woman with myalgias, fatigue, and shortness of breath.
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Aged↗
Wegener's granulomatosis: is biologic therapy useful?
Wegener's granulomatosis (WG) is a complex autoimmune disorder that has been transformed from a uniformly lethal process to a chronic disease with a relapsing-remitting course. In the setting of frequent relapses, the need to manage cumulative disease damage and drug toxicities has spurred the identification and development of new potent and directed therapies. Biologic agents, which offer the potential for remission-induction and drug-sparing approaches to treat WG, have been studied in several small, open-label clinical series and one large, randomized, placebo-controlled clinical trial. This article discusses the results of these trials and the potential of these biologic agents to treat WG.
Animals↗
End-to-end electronic control of the hospital transfusion process to increase the safety of blood transfusion: strengths and weaknesses.
BACKGROUND: Incorrect blood component transfused is a frequent serious incident associated with transfusion and often involves misidentification of the patient and/or the unit of blood. STUDY DESIGN AND METHODS: This study extended the evaluation of an electronic system involving bar code technology and handheld computers. Electronic control of collection of blood from blood refrigerators was incorporated into a previously described process for blood sample collection and blood administration. Practice was evaluated before and after its introduction in cardiac surgery. RESULTS: The baseline audits revealed poor practice. Significant improvements were found following the introduction of the electronic system, including from 8 percent to 100 percent in checking that the blood group and unit number on the blood pack matched the compatibility label and the pack was in date (p < or = 0.0001). Similar significant improvements were found in blood sample collection, the collection of blood from blood refrigerators, and the documentation of transfusion. Staff found the system easy to operate and preferred it to standard procedures. CONCLUSIONS: A bar code patient identification system improved transfusion practice, although areas for improvement were identified. These results provide support for further work on the development of such systems for both transfusion and other procedures requiring patient identification.
Blood Group Incompatibility↗
Technology to improve quality and accountability.
A body of evidence has been accumulated to demonstrate that current practice is not sufficiently safe for several stages of central laboratory testing. In particular, while analytical and perianalytical steps that take place within the laboratory are subjected to quality control procedures, this is not the case for several pre- and post-analytical steps. The ubiquitous application of auto-identification technology seems to represent a valuable tool for reducing error rates. A series of projects in Oxford has attempted to improve processes which support several areas of laboratory medicine, including point-of-care testing, blood transfusion, delivery and interpretation of reports, and support of decision-making by clinicians. The key tools are auto-identification, Internet communication technology, process re-engineering, and knowledge management.
Clinical Laboratory Techniques↗
Case records of the Massachusetts General Hospital. Case 31-2005. A 60-year-old man with skin lesions and renal insufficiency.
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Antibodies, Monoclonal↗
Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 35-2004. A 68-year-old man with end-stage renal disease and thickening of the skin.
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Aged↗
Advanced glycation endproducts and osteoarthritis.
Non-enzymatic glycation of proteins, such as collagen, results in the formation of advanced glycation endproducts (AGE). Advanced glycation endproducts result in pathologic stiffening of cartilage and extracellular matrix and accumulate with age. Pentosidine, an AGE, is present in serum, synovial fluid, and articular cartilage from patients with osteoarthritis (OA). However, AGE levels are not always increased, and may be decreased locally, in association with osteoarthritic pathology. The finding of pentosidine in articular cartilage of individuals with OA may not be specific for that disease, independent of chronologic age. Advanced glycation endproduct modification of normal articular cartilage increases its stiffness, increases chondrocyte-mediated proteoglycan degradation, reduces its susceptibility to matrix metalloproteinase-mediated degradation, and decreases proteoglycan synthesis by chondrocytes. These observations parallel findings in osteoarthritic cartilage, which suggests that AGE modification could contribute to the pathogenesis of OA. However, a causative link between AGEs and OA has not yet been established.
Aging↗
Regression of lymphoproliferative disorder after treatment for hepatitis C virus infection in a patient with partial trisomy 3, Bcl-2 overexpression, and type II cryoglobulinemia.
A patient with type II cryoglobulinemic vasculitis and hepatitis C virus (HCV) infection presented with a leukemiclike proliferation of B cells bearing marginal zone B-cell phenotypic markers. A partial trisomy 3 (bands 3q11-29) and overexpression of Bcl-2 without t(14;18) translocation was detected in the monoclonal B cells that were classic rheumatoid factor-producing B cells bearing the WA cross-idiotype. Treatment with interferon-alpha produced a complete clinical remission and synchronous marked decreases in viremia and monoclonal B-cell prevalence. This is the first report of partial trisomy 3 and Bcl-2 overexpression in type II cryoglobulinemic vasculitis associated with HCV infection. Further studies of HCV-infected patients with and without type II cryoglobulinemia are required to determine the prevalence and possible physiologic and/or pathophysiologic significance of these findings.
Chromosomes, Human, Pair 3↗
GTP cyclohydrolase I gene transfer augments intracellular tetrahydrobiopterin in human endothelial cells: effects on nitric oxide synthase activity, protein levels and dimerisation.
OBJECTIVES: Tetrahydrobiopterin (BH4) is an essential cofactor for endothelial nitric oxide synthase (eNOS) activity. BH4 levels are regulated by de novo biosynthesis; the rate-limiting enzyme is GTP cyclohydrolase I (GTPCH). BH4 activates and promotes homodimerisation of purified eNOS protein, but the intracellular mechanisms underlying BH4-mediated eNOS regulation in endothelial cells remain less clear. We aimed to investigate the role of BH4 levels in intracellular eNOS regulation, by targeting the BH4 synthetic pathway as a novel strategy to modulate intracellular BH4 levels. METHODS: We constructed a recombinant adenovirus, AdGCH, encoding human GTPCH. We infected human endothelial cells with AdGCH, investigated the changes in intracellular biopterin levels, and determined the effects on eNOS enzymatic activity, protein levels and dimerisation. RESULTS: GTPCH gene transfer in EAhy926 endothelial cells increased BH4 >10-fold compared with controls (cells alone or control adenovirus infection), and greatly enhanced NO production in a dose-dependent, eNOS-specific manner. We found that eNOS was principally monomeric in control cells, whereas GTPCH gene transfer resulted in a striking increase in eNOS homodimerisation. Furthermore, the total amounts of both native eNOS protein and a recombinant eNOS-GFP fusion protein were significantly increased following GTPCH gene transfer. CONCLUSIONS: These findings suggest that GTPCH gene transfer is a valid approach to increase BH4 levels in human endothelial cells, and provide new evidence for the relative importance of different mechanisms underlying BH4-mediated eNOS regulation in intact human endothelial cells. Additionally, these observations suggest that GTPCH may be a rational target to augment endothelial BH4 and normalise eNOS activity in endothelial dysfunction states.
3T3 Cells↗