Dengue and dengue hemorrhagic fever among adults: clinical outcomes related to viremia, serotypes, and antibody response

BACKGROUND: Clinical manifestations of dengue vary in different areas of endemicity and between specific age groups, whereas predictors of outcome have remained controversial. In Brazil, the disease burden predominantly affects adults, with an increasing trend toward progression to dengue hemorrhagic fever (DHF) noted. METHODS: A cohort of adults with confirmed cases of dengue was recruited in central Brazil in 2005. Patients were classified according to the severity of their disease. Associations of antibody responses, viremia levels (as determined by real-time polymerase chain reaction [PCR]), and serotypes (as determined by multiplex PCR) with disease severity were evaluated. RESULTS: Of the 185 symptomatic patients >14 years of age who had a confirmed case of dengue, 26.5% and 23.2% were classified as having intermediate dengue fever (DF)/DHF (defined as internal hemorrhage, plasma leakage, manifested signs of shock, and/or thrombocytopenia [platelet count, < or =50,000 platelets/mm3]) and DHF, respectively. The onset of intermediate DF/DHF and DHF occurred at a late stage of disease, around the period of defervescence. Patients with DHF had abnormal liver enzyme levels, with a >3-fold increase in aspartate aminotransferase level, compared with the range of values considered to be normal. Overall, 65% of patients presented with secondary infections with dengue virus, with such infection occurring in similar proportions of patients in each of the 3 disease category groups. Dengue virus serotype 3 (DV3) was the predominant serotype, and viremia was detected during and after defervescence among patients with DHF or intermediate DF/DHF. CONCLUSIONS: Viremia was detected after defervescence in adult patients classified as having DHF or intermediate DF/DHF. Secondary infection was not a predictor of severe clinical manifestation in adults with infected with the DV3 serotype.     

Ability of myeloma cells to secrete macrophage inflammatory protein (MIP)-1alpha and MIP-1beta correlates with lytic bone lesions in patients with multiple myeloma

Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta have been identified as candidates for multiple myeloma (MM)-derived bone-resorbing factors. To validate the clinical relevance of these observations, we investigated correlations between the ability of MM cells to secrete these chemokines and the extent of MM bone lesions as well as levels of biochemical bone markers in patients with MM. Patients with multiple bone lesions exhibited higher MIP-1alpha and MIP-1beta secretion from MM cells along with elevated urinary deoxypyridinoline (Dpd), without significant elevation of serum bone-specific alkaline phosphatase (BALP) or osteocalcin compared with those with minimal bone lesions. MIP-1alpha and MIP-1beta levels correlated positively with urinary Dpd and serum BALP but not with serum osteocalcin. These results provide further evidence for a causal role of MIP-1alpha and MIP-1beta in the development of lytic bone lesions, and suggest that MM cells suppress osteoblastic bone formation to cause an imbalance of bone turnover and development of destructive bone lesions.     

Spontaneous echo contrast in descending aorta correlates with low blood-flow velocity in carotid arteries and hemostatic abnormalities.

Spontaneous echo contrast in the descending aorta (DA-SEC) was examined as a possible risk factor for cerebral thromboembolism. In 19 patients (10 males, 9 females) in the chronic stage of cerebral infarction, abnormal findings by transesophageal echocardiography, flow dynamics of the common carotid artery (CCA), and hemostatic factors including blood coagulation and fibrinolysis were investigated. In nine patients, DA-SEC was detected, and SEC in left atrium (LA-SEC) was detected in nine patients. The DA-SEC positive group showed decreased blood-flow velocity (BFV) in bilateral CCA, high levels of thrombin-antithrombin III complex (TAT) and prothrombin fragment 1.2 (F1+2), a decrease in platelet count and a slight increase in D-dimer, which means an activated state of thrombin generation and resulting fibrinolysis, compared to the DA-SEC negative group. On the other hand, the LA-SEC positive group showed normal BFV in CCA and only a slight increase in D-dimer. We conclude that the condition producing DA-SEC is a stronger risk factor for cerebral infarction than that producing LA-SEC.     

Radiofrequency catheter ablation within the coronary sinus eliminates a macro-reentrant atrial tachycardia: Importance of mapping in the coronary sinus

We describe a patient who underwent radiofrequency (RF) catheter ablation of symptomatic atrial fibrillation. After left atrial (LA) catheter ablation and pulmonary vein isolation, a macro-reentrant atrial tachycardia (AT) with a critical isthmus at the mitral isthmus was induced by incremental atrial pacing from the coronary sinus. Extensive RF energy applications from endocardial sites using ablation catheters with 4 mm- and 8 mm- tips resulted in no discrete potentials being recorded from the endocardial sites of the isthmus, but the tachycardia could not be terminated. However, discrete potentials were recorded within the CS, and epicardial RF energy applications from the CS eliminated the tachycardia. Thus, mapping in the CS is useful for detecting residual conduction at epicardial sites along the mitral isthmus. RF catheter ablation within the CS should be considered when no distinct electrograms are recorded after extensive ablation from the endocardial sites and when distinct electrograms are recorded within the CS.     

Increased plasma antigen levels of monocyte chemoattractant protein-1 in patients with restenosis after percutaneous transluminal coronary angioplasty

Monocyte chemoattractant protein-1 (MCP-1) plays an important role in the progression of atherosclerosis in coronary arteries. To examine whether or not plasma antigen levels of MCP-1 are related to restenosis after percutaneous transluminal coronary angioplasty (PTCA), the plasma antigen levels of MCP-1 were measured by enzyme-linked immunosorbent assay (pg/ml) before, 24 and 48 h, and 3 months after elective PTCA for stable exertional angina performed between June 1997 and March 1998. Restenosis was defined as recurrence of stenosis greater than 50% of the diameter in the dilated segment at 3-month follow-up angiography. There were no differences in plasma MCP-1 antigen levels before and at 24 h after PTCA between restenosis (R; n=27) and no-restenosis (N; n=43) groups (R vs N: 633+/-35 vs 589+/-34, and 669+/-41 vs 575+/-36 pg/ml before and at 24 h after PTCA, respectively), but plasma MCP-1 antigen levels were higher at 48 h and 3 months after PTCA in the R than in N group (R vs N: 678+/-41 vs 558+/-35, and 735+/-35 vs 571+/-32 pg/ml at 48 h and 3 months after PTCA, respectively). These data suggest that the MCP-1 production and macrophage accumulation in the balloon-injured site is partially associated with restenosis after PTCA.     

Successful catheter ablation of left ventricular epicardial tachycardia originating from the great cardiac vein: a case report and review of the literature.

A patient underwent radiofrequency (RF) catheter ablation for a drug-refractory ventricular tachycardia, but RF energy application at an endocardial site of the left ventricular outflow tract and at the left sinus of Valsalva could not eliminate the tachycardia. The earliest ventricular activation during the arrhythmia, which preceded the onset of the QRS complex by 32 ms, was found within the great cardiac vein and complete elimination of the tachycardia was finally achieved with RF application at that site.     

Pica during pregnancy among Mexican‐born women: a formative study

Although pica, the craving and purposive consumption of non‐food substances, is common among many populations, especially during pregnancy, the health consequences are not well understood. Further, very little is known about pica among Mexican populations in the United States and Mexico. Therefore, we conducted formative research to understand pica in this understudied population. Our objectives were to identify the frequency and types of pica behaviours, to understand perceived aetiologies and consequences of pica and to ascertain if the behaviour was common enough to warrant a larger study. We held nine focus group discussions (three in the Salinas Valley, California; six in Xoxocotla, Morelos, Mexico) with 76 Mexican‐born women who were currently pregnant or had delivered within the past 2 years. Earth, adobe, bean stones and ice were the most commonly reported pica substances. Twenty‐eight of the 76 participants (37%) reported ever engaging in pica; 22 participants (29%) reported doing so during pregnancy. The proportion of women reporting pica in the United States and Mexico was 43% and 34%, respectively. Women attributed pica to the overwhelming organoleptic appeal of pica substances (especially smell and texture) and to micronutrient deficiencies. Perceived consequences of unfulfilled pica cravings were birthmarks or fetal loss; fulfilled pica cravings were also thought to be generally harmful to the mother or child, with several women specifying toxic lead, pesticides or ‘worms’. In sum, pica among Mexican women is common enough to warrant a larger epidemiologic study of its sociodemographic correlates and physiological consequences.     

Abnormal platelet and lymphocyte calcium handling in prehypertensive rats

We have reported that the basal and stimulated cytosolic free calcium concentrations [( Ca2+]i) are elevated in platelets isolated from 12-14-week-old spontaneously hypertensive rats (SHR) as compared with normotensive Wistar-Kyoto (WKY) rats. To determine whether altered cell calcium metabolism precedes the development of overt hypertension, we measured [Ca2+]i under resting and stimulated conditions in blood platelets and thymic lymphocytes isolated from 4-week-old prehypertensive SHR and WKY rats. Blood pressure was similar in both groups (SHR 95 +/- 8 versus WKY rats 92 +/- 7 mm Hg). Basal [Ca2+]i in platelets was higher in SHR than WKY rats (63.4 +/- 3.9 versus 54.8 +/- 3.1 nM, p less than 0.003). Also the [Ca2+]i response to thrombin was greater in SHR than WKY rats in both the presence and absence of extracellular calcium. For lymphocytes, although no difference was detected in basal [Ca2+]i, the concanavalin A-induced peak [Ca2+]i was higher for SHR than WKY rats in both calcium-containing and calcium-free media. These results suggest that agonist-stimulated calcium influx and calcium discharge from intracellular stores are enhanced in both platelets and lymphocytes of 4-week-old SHR. We conclude that abnormalities in calcium metabolism in two different cell types precede the development of overt hypertension in the SHR.