Delayed diagnosis of acute rheumatic fever in adults: a forgotten cause of febrile polyarthritis

Acute rheumatic fever is a nonsuppurative sequela of upper respiratory tract infection with group A streptococci. We describe our recent experience with the diagnosis and management of 3 cases of acute rheumatic fever to highlight the delays that may arise in the diagnosis of this condition. In adults, febrile polyarthritis is the most common presentation of acute rheumatic fever. Increased awareness on the part of the physician is necessary to ensure both prompt and accurate diagnosis of this cause of febrile polyarthritis.     

Distribution of thrombosis in patients with symptomatic deep vein thrombosis. Implications for simplifying the diagnostic process with compression ultrasound

BACKGROUND: Two different diagnostic strategies are used to perform compression (real-time) ultrasound for the diagnosis of clinically suspected deep-vein thrombosis. One is to examine the entire proximal venous system from common femoral to distal popliteal vein; the other is a limited examination of only the common femoral and the entire popliteal vein. The latter strategy, which is less time-consuming and requires less expensive equipment, is based on a strong impression from prospective studies using limited compression ultrasound that proximal vein thrombi always involve the common femoral or popliteal vein. This impression, which is supported by the demonstrated safety at long-term follow-up of not treating patients whose limited compression ultrasound is normal at presentation and then repeated within the next week, has not been tested in a formal study. Therefore, we reviewed a large series of venograms performed in consecutive patients with clinically suspected venous thrombosis to determine the distribution of venous thrombosis in symptomatic patients. METHODS: Venograms were performed using 150 mL of radiographic contrast material. Before the study, a panel of experts agreed on the standardized criteria for the assessment of venograms. Venograms were adjudicated blindly for the presence of deep vein thrombosis and to determine the distribution of proximal vein thrombosis and isolated calf-vein thrombosis, the size of proximal thrombi, and whether they were occlusive or nonocclusive. Subsequently, the duration of symptoms was related to the venographic findings. RESULTS: Five hundred sixty-two venograms from consecutive patients with a first episode of clinically suspected deep vein thrombosis were adjudicated. Of these, 20 (3.6%) were inadequate for interpretation. In the remaining 542, venous thrombosis was demonstrated in 189 instances (prevalence, 35%; 95% confidence interval, 31% to 39%) and were located in the proximal veins in 166 (88%; 95% confidence interval, 82% to 92%) venograms. Isolated calf-vein thrombosis was present in the remaining 23 (12%; 95% confidence interval, 8% to 18%) venograms. Proximal with concurrent calf thrombosis was detected in 164 (99%) of the 166 patients. Proximal thrombi involved only the popliteal vein in 16 (10%); the popliteal and superficial femoral veins in 70 (42%); and the popliteal, superficial, and common femoral vein in eight (5%); whereas thrombi involving the entire proximal deep venous system were detected in 58 (35%) venograms. Isolated thrombosis of the superficial femoral, common femoral, and iliac vein was not observed. Proximal venous thrombi were occlusive in 146 (88%) patients. No relation between the duration of symptoms and the extent or the occlusiveness of venous thrombi could be demonstrated. CONCLUSIONS: Most symptomatic patients have extensive occlusive proximal vein thrombosis at the time of presentation. Thrombi isolated to the superficial femoral or iliac vein were not observed in this large sample of consecutive patients. Our data support the use of the relatively simple, inexpensive, and rapid compression ultrasound method that limits the examination of the proximal veins to the common femoral and popliteal veins.     

Plasma marinobufagenin-like and ouabain-like immunoreactivity during saline volume expansion in anesthetized dogs

OBJECTIVES: This study investigated effects of acute plasma volume expansion on plasma levels and urinary output of two endogenous Na,K-ATPase inhibitors, marinobufagenin-like and ouabain-like immunoreactive substances. METHODS: Plasma volume was expanded for 3 h via intravenous saline infusion in three groups of anesthetized dogs--nontreated (n = 5); pretreated with rabbit antidigoxin (n = 5); and pretreated with rabbit antimouse (control) antibody (n = 4). RESULTS: Plasma marinobufagenin-like immunoreactivity increased to 11.87 +/- 3.16 nmol.l-1 (vs. 0.30 +/- 0.16 nmol.l-1) within 10 min of volume expansion, in parallel with a 15% increase in LVdP/dt, then decreased to 2.21 +/- 0.59 nmol.l-1, and in 90 min increased to 11.8 +/- 2.8 nmol.l-1, in parallel with the maximal natriuretic response. Plasma concentrations of ouabain-like immunoreactive material were increased after 90 min of saline infusion (0.019 +/- 0.004 nmol.l-1 vs. 0.139 +/- 0.056 nmol.l-1). Pretreatment of the animals with antidigoxin antibody blocked the positive inotropic and reduced natriuretic response to volume expansion, and decreased the urinary release of marinobufagenin-like, but not ouabain-like, material. CONCLUSIONS: These results show the presence of marinobufagenin-like immunoreactive substance in dog plasma and suggest that mammalian EDLF may have a bufodienolide nature. Endogenous marinobufagenin-like immunoreactive substance, which is likely to cross-react with antidigoxin antibody, is involved in the natriuretic and positive inotropic responses to plasma volume expansion.     

The chemorepulsive activity of secreted semaphorins is regulated by furin-dependent proteolytic processing

The semaphorins are a large group of cell surface and secreted proteins implicated in axonal pathfinding. Here we show that the secreted mouse semaphorin D (SemD) is synthesized as an inactive precursor (proSemD) and becomes repulsive for sensory and sympathetic neurites upon proteolytic cleavage. ProSemD processing can be blocked completely by an inhibitor selective for furin-like endoproteases or mutagenesis of three conserved dibasic cleavage sites. Its C-terminal pro-peptide contains a processing signal that is essential for SemD to acquire its full repulsive activity. SemD processing is regulated during the embryonic development of the mouse and determines the magnitude of its repulsive activity. Similarly to SemD, the secreted semaphorins SemA and SemE display repulsive properties that are regulated by processing. Our data suggest that differential proteolytic processing determines the repulsive potency of secreted semaphorins and implicate proteolysis as an important regulatory mechanism in axonal pathfinding.     

The combined dexamethasone/corticotropin-releasing hormone stimulation test is more closely associated with features of diurnal activity of the hypothalamo-pituitary-adrenocortical system than the dexamethasone suppression test

BACKGROUND: The dexamethasone suppression test (DST) is a widely used endocrine test in psychiatry, but was reported to not allow reliable inferences with regard to the basal activity of the hypothalamo-pituitary-adrenocortical (HPA) system. We compared the association of the standard DST and the combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) challenge with parameters of diurnal cortisol profiles. METHODS: We performed a DEX/CRH challenge and 24-hour cortisol profiles in 25 depressed patients (mean age: 47.4 +/- 16.0 years) and 33 age-matched healthy controls (mean age: 51.4 +/- 19.3 years). RESULTS: A path analysis showed cortisol area under the curve (AUC) after CRH (= DEX/CRH status) to be dependent upon minimal 24-hour cortisol and evening frequency of pulsatile cortisol release. In contrast, postdexamethasone cortisol (= DST status) was related to 24-hour mean cortisol. Simple linear regressions supported an association of cortisol AUC with several parameters of the diurnal cortisol profiles, which was not true for the standard DST. CONCLUSIONS: We conclude that the combined DEX/CRH challenge test is more closely associated with the activity of the HPA system than the standard DST in healthy and depressed subjects.