摘要:

BackgroundThe HEIRS Study will evaluate the prevalence, genetic and environmental determinants, and potential clinical, personal, and societal impact of hemochromatosis and iron overload in a multiethnic, primary care-based sample of 100,000 adults over a 5-year period. Participants are recruited from 5 Field Centers. Laboratory testing and data management and analysis are performed in a Central Laboratory and Coordinating Center, respectively.MethodsParticipants undergo testing for serum iron measures and common mutations of the hemochromatosis gene (HFE) on chromosome 6p and answer questions on demographics, health, and genetic testing attitudes. Participants with elevated values of transferrin saturation and serum ferritin and/or C282Y homozygosity are invited to undergo a comprehensive clinical examination (CCE), as are frequency-matched control subjects. These examinations provide data on personal and family medical history, lifestyle characteristics, physical examination, genetic counseling, and assessment of ethical, legal, and social implications. Primary and secondary causes of iron overload will be distinguished by clinical criteria. Iron overload will be confirmed by quantification of iron stores. Recruiting family members of cases will permit DNA analysis for additional genetic factors that affect iron overload.ResultsOf the first 50,520 screened, 51% are white, 24% are African American, 11% are Asian, 11% are Hispanic, and 3% are of other, mixed, or unidentified race; 63% are female and 37% are male.ConclusionsInformation from the HEIRS Study will inform policy regarding the feasibility, optimal approach, and potential individual and public health benefits and risks of primary care-based screening for iron overload and hemochromatosis.

ISSN:0002-9629    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundOrthostatic intolerance (OI) is a syndrome characterized by lightheadedness, palpitations, fatigue, blurred vision, dizziness, chest discomfort, cognitive impairment, and occasionally syncope. These symptoms usually occur after upright posture and are associated with tachycardia and high plasma concentrations of norepinephrine. It has been proposed that a mutation in exon 9 of the norepinephrine transporter gene (Ala457Pro), resulting in more than 98% loss of function compared with the wild type, might provide a pathogenetic mechanism to explain the clinical symptoms of patients with OI.MethodsWe studied 46 young men from military service who had sought medical advice because of dizziness while standing. Every patient underwent a tilt-table test, with monitoring of blood pressure, heart rate, and plasma catecholamines in supine position and during 30 minutes of standing. Fourteen patients showing the full-blown OI syndrome (30 bpm increase in heart rate and 600 pg/mL plasma norepinephrine levels while standing) underwent direct DNA sequencing of exon 9 of the norepinephrine-transporter gene.Results and ConclusionsThe specific mutation (Ala457Pro) was not detected in any of the 14 OI patients. Based on these findings, we doubt that this specific genetic transport defect is a frequent cause of the impaired uptake of norepinephrine in OI patients. Its routine determination will therefore not be helpful to establish the clinical diagnosis of OI.

ISSN:0002-9629    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundType 2 diabetes mellitus is characterized by both insulin deficiency and insulin resistance. Effective treatment often requires therapy directed at both abnormalities. Patients on monotherapy might benefit from a combination agent such as glyburide/metformin, which increases insulin secretion and reduces insulin resistance.MethodsAll patients taking a glyburide/metformin preparation at the Carl T. Hayden VAMC were identified from pharmacy records. Patients with documented hemoglobin A1cvalues within 31 weeks prior and between 3 and 33 weeks after initiation of therapy (92 subjects) were examined.ResultsGlyburide/metformin combination therapy reduced hemoglobin A1clevels from 0.087 to 0.083 (P< 0.06). Significant reductions were seen in those patients with initial levels higher than 0.08 (0.094 to 0.087;P< 0.01). No significant reductions were seen in those patients with initial levels lower than 0.08.ConclusionsIn patients on monotherapy or on dual oral therapy with inadequate control, changing to a glyburide/metformin combination preparation may improve glucose control.

ISSN:0002-9629    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0002-9629    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The impressive anti-inflammatory effects of the tumor necrosis factor (TNF)&agr; blockers etanercept and infliximab have led to their use in multiple inflammatory diseases besides their original indication, rheumatoid arthritis (RA). The well-studied clinical effects of both agents in RA are the reduction of signs and symptoms of joint inflammation as well as the arrest of bone destruction. Infliximab has also been Food and Drug Administration-approved in the treatment of Crohn disease; etanercept is now FDA-approved for juvenile chronic arthritis and psoriatic arthritis. Favorable initial clinical trials have been reported in other rheumatic diseases, including ankylosing spondylitis and adult Still disease. In addition, TNF&agr; blockade is being studied in the treatment of uveitis, myelodysplastic syndromes, and graft-versus-host disease. Studies in sepsis and septic shock have identified small subsets of patients that may benefit from TNF&agr; blockade, but broader use in septic patients has not improved survival. The TNF&agr; blockers have had relatively infrequent serious side effects, especially compared with the immunosuppressive and cytotoxic agents otherwise employed to treat these diseases. Further studies of optimal dosing, combination with other therapies, and long-term benefits and side effects will emerge from future trials.

ISSN:0002-9629    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

A young man with salt-losing nephropathy had the unusual coexistence of hypokalemia caused by secondary hyperaldosteronism. When his NaCl intake was supplemented by 12 g/day (205 mmol), hyperaldosteronism was suppressed and so were his urinary K+wasting, hypokalemia, and episodic falling, during an extended follow-up. His findings are compared and contrasted with those in other reported patients with renal salt wasting, and also those in patients with Gitelman and Bartter syndromes.

ISSN:0002-9629    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundSpuriously low levels of plasma phosphate have been reported previously in patients with multiple myeloma and polyclonal gammopathy. We report 2 cases of spurious hypophosphatemia in patients with elevated concentrations of serum monoclonal immunoglobulins, 1 of whom had monoclonal gammopathy of undetermined significance and the other multiple myeloma.MethodsPlasma phosphate concentrations were measured using nondeproteinized and deproteinized plasma samples from patients with monoclonal gammopathies.ResultsIn 2 patients with monoclonal gammopathy, the levels of plasma inorganic phosphate were reported as <1.0 mg/dL when the phosphate concentration was determined using an analyzer that employs nondeproteinized plasma. When the samples were reanalyzed using a laboratory method that removes serum proteins, normal or elevated concentrations of phosphate were found. Plasma levels of phosphate in 4 other patients with monoclonal gammopathy were normal by both methods.ConclusionsThese data confirm previous reports that spurious hypophosphatemia occurs in some patients with increased levels of serum monoclonal immunoglobulins when laboratory methods using nondeproteinized samples are employed. The occurrence of unusually low plasma phosphate concentrations in patients without symptoms or clinically apparent causes of hypophosphatemia should alert physicians to search for monoclonal gammopathy.

ISSN:0002-9629    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

A 52-year-old woman with a history of chronic obstructive pulmonary disease presented with symmetrical polyarthritis involving her metacarpophalangeal and proximal interphalangeal joints, knees, ankles, and hips and with a purpuric rash involving her lower extremities. She had a history of recurrent episodes of purulent otitis often associated with myalgias and arthralgias. Laboratory studies at presentation included leukocytosis with 16% eosinophils, an elevated rheumatoid factor titer, and an elevated antineutrophil cytoplasmic antibody titer. Cultures from the right ear canal grewStaphylococcus aureus. Skin biopsy revealed leukocytoclastic vasculitis with pericapillary eosinophils. The patient was treated with prednisone and then with azathioprine after the rash relapsed during the tapering of prednisone. Four months after her initial presentation, she developed bilateral foot drop. A sural nerve biopsy revealed vasa nervosum vasculitis. The diagnosis of Churg-Strauss syndrome was established, and she was treated with an increased dose of azathioprine and a slowly tapering prednisone regimen. This case report suggests that patients with Churg-Strauss syndrome can present with a syndrome suggesting rheumatoid arthritis. In this particular patient, recurrent staphylococcal infections may have triggered the vasculitic process.

ISSN:0002-9629    

出版商:OVID    

年代:2003

数据来源: OVID