Pulmonary hypertension: clinical manifestations, classification and diagnosis.

Dyspnoea on exertion is the most common presenting symptom of pulmonary hypertension (PH), often a progressive and ultimately fatal condition. However, the presenting manifestations are protean, and more subtle features such hoarseness (caused by compression of the left recurrent laryngeal nerve) challenge master clinicians. Clinician scientists have refined the clinical classification in a manner that aids in accurate diagnosis and facilitates communication among healthcare providers and research investigators. Diagnostic algorithms emphasize confirmation and characterization of PH by catheterisation as well as differentiating between the current classes based upon essential and contingent diagnostic tests.

Evaluation of a rapid urine amylase test using post-ERCP hyperamylasemia as a model.

OBJECTIVE: The initial diagnosis of acute pancreatitis is often based on clinical criteria together with elevations of serum amylase and lipase. A reliable bedside urine test could facilitate the early diagnosis of pancreatitis. We evaluated a rapid urine amylase test (Rapignost) by using post-ERCP hyperamylasemia as a human model of acute development of hyperamylasemia suggestive of pancreatitis. METHODS: Seventy-five patients undergoing ERCP were prospectively evaluated. Patients with renal insufficiency, hyperlipidemia, or hyperglycemia were excluded. Before ERCP, patients had serum amylase and lipase measured, and urine amylase tested with the Rapignost test strip. At 4 and 16-24 h post-ERCP, a serum and urine (test strip) amylase were measured again; the adequacy of urine collection was verified by measuring a 2-h creatinine clearance. Patients were clinically assessed for the development of clinical pancreatitis. The concordance of the strip result with post-ERCP hyperamylasemia was assessed. RESULTS: The sensitivity of the test strip for the detection of hyperamylasemia was greatest at 16-24 h post-ERCP (78%). Specificity was uniformally high (100% specificity at 16-24 h post-procedure). The test strip was positive in all cases of clinical pancreatitis. Of three cases of clinically evident ERCP-induced pancreatitis, only one was urine test strip positive by 4 h post-procedure. CONCLUSIONS: Using post-ERCP hyperamylasemia as a model, the Rapignost rapid urine amylase test strip was only marginally sensitive but highly specific for hyperamylasemia. The urine test strip was positive in all cases of clinical pancreatitis and may be a useful bedside test for the diagnosis of acute pancreatitis.

Intraindividual peak flow variability.

OBJECTIVES: To quantify intraindividual variability in peak expiratory flow (PEF) measured with peak flow-meters and to define factors affecting PEF variability. METHODS: Three hundred one healthy subjects (aged 4 to 84 years) were recruited from sites at sea level (n = 220) and at 1,400 m altitude (n = 81). All testing was done with the same model peak flowmeter. Each subject was actively coached through five to eight successive PEF maneuvers. Three meters of the same model were tested using a mechanical waveform simulator at three different flows at both testing altitudes (sea level and at 1,400 m). RESULTS: Excluding outliers, the mean PEF was 523 L/min, mean standard deviation (SD) was 22 L/min, and mean coefficient of variation (CV) was 4.6%. The upper 95th percentile for CV was 8% for adults and 10% for youths. Analyzing only the three highest peak flows for each subject, the mean PEF was 539 L/min, mean SD was 12 L/min, and mean CV was 2.4%. The upper 95th percentile for CV was 6% for adults and 9% for youths. Linear regression analysis revealed a small but statistically significant correlation (p < 0.01) between mean peak flow and CV. In adults, SD correlated with sex (p < 0.01) but neither CV nor SD was correlated with age, height, weight, or altitude. Meter variability defined with the mechanical waveform simulator was small. Standard deviation varied from 1.5 to 4.2 L/min and CV from 0.4 to 1.6%. When the three largest peak flows for each subject were used, 5.5% of intraindividual variance was explained by meter variance. CONCLUSIONS: These estimates of intraindividual variability in healthy subjects are generally lower than those previously reported. Meter variability accounts for only a small part of total intraindividual variability. The 95th percentile data suggest that a fall in PEF of 6 to 8% in adults and 9 to 10% in youths would be statistically significant.

Increased specificity and sensitivity of insulin antibody measurements in autoimmune thyroid disease and type I diabetes.

Insulin autoantibodies (IAA), a marker for insulin-dependent diabetes mellitus (IDDM), have been reported in other diseases such as thyroid disease and after treatment with sulfhydryl containing medications. Reported prevalences of IAA in non-diabetics vary widely, probably due in part to methodological differences between laboratories. In addition, certain sera may have a high non-specific binding to insulin. We compared a radioimmunoassay (RIA) for IAA which included non-specific binding with an RIA that incorporated a competitive displacement with cold insulin to remove non-specific binding. Using the RIA which measured specific plus non-specific binding, IAA positivity was found in 22/92 (23.9%) of sera from thyroid disease patients, 16/124 (12.9%) of random masked sera from a hospital laboratory, 27/335 (8.1%) of first degree relatives of IDDM patients, 63/178 (35.4%) of subjects with newly diagnosed IDDM, and 0/92 (0%) of normal controls. Insulin antibodies (IA) were found in 80/99 (80.8%) of insulin-treated diabetic subjects. In contrast, using the displacement assay which allowed measurement of specific binding, the frequency of IAA positivity was lower for subjects with thyroid disease (7/92 (7.6%)), random hospital sera (12/124 (9.8%)), and for first degree relatives of IDDM patients (8/335 (2.4%)), while higher for subjects with newly diagnosed IDDM (71/178 (39.9%)). Subjects with insulin-treated diabetes (78/99 (78.8%)) and normal subjects (1/92 (1.1%)) showed little change. Strikingly, three of the eight (37.5%) relatives of IDDM patients that were positive in the RIA measuring specific binding were detected only because cold displacement was utilized. We conclude: (1) subjects with thyroid disease and first degree relatives of IDDM patients frequently have high non-specific binding for IAA in an RIA not employing a cold displacement step, (2) in some newly diagnosed IDDM patients and first degree relatives of IDDM patients, IAA may be missed by an assay not optimized to measure specific binding, and (3) displacement with cold insulin increases both the specificity and sensitivity of RIAs measuring insulin autoantibodies.