A Comparative Study of Leptospirosis and Dengue in Thai Children

Two of the most common causes of acute febrile illnesses among children in the tropics are leptospirosis and dengue. Early in illness, these two conditions are often indistinguishable and rapid laboratory confirmation of the infecting pathogen is generally not available. An enhanced ability to distinguish leptospirosis from dengue in children would guide clinicians and public health personnel in the appropriate use of limited healthcare resources

Strategies for Diagnosis and Treatment of Suspected Leptospirosis: A Cost-Benefit Analysis

Symptoms and signs of leptospirosis are non-specific. A number of diagnostic tests for leptospirosis are available. We compared the cost-benefit of 5 management strategies: 1) no patients tested or given antibiotic treatment; 2) all patients given empirical doxycycline treatment; patients given doxycycline when a patient is tested positive for leptospirosis using: 3) lateral flow; 4) MCAT; 5) latex test. Outcomes were measured in duration of fever which is then converted to productivity losses to capture the full economic costs. Empirical doxycycline treatment was found to be the most efficient strategy, being both the least costly alternative and the one that resulted in the lowest average duration of fever. The significantly higher relative cost of using a diagnostic test as compared with presumptive treatment, and the limited sensitivity of all the diagnostic tests implied that only the latex test could be considered cost-effective when compared with the no-antibiotic-treatment option, and that all three tests were still inferior to empirical treatment

Phenotypic Characterization of Autoreactive B Cells—Checkpoints of B Cell Tolerance in Patients with Systemic Lupus Erythematosus

DNA-reactive B cells play a central role in systemic lupus erythematosus (SLE); DNA antibodies precede clinical disease and in established disease correlate with renal inflammation and contribute to dendritic cell activation and high levels of type 1 interferon. A number of central and peripheral B cell tolerance mechanisms designed to control the survival, differentiation and activation of autoreactive B cells are thought to be disturbed in patients with SLE. The characterization of DNA-reactive B cells has, however, been limited by their low frequency in peripheral blood. Using a tetrameric configuration of a peptide mimetope of DNA bound by pathogenic anti-DNA antibodies, we can identify B cells producing potentially pathogenic DNA-reactive antibodies. We, therefore, characterized the maturation and differentiation states of peptide, (ds) double stranded DNA cross-reactive B cells in the peripheral blood of lupus patients and correlated these with clinical disease activity. Flow cytometric analysis demonstrated a significantly higher frequency of tetramer-binding B cells in SLE patients compared to healthy controls. We demonstrated the existence of a novel tolerance checkpoint at the transition of antigen-naïve to antigen-experienced. We further demonstrate that patients with moderately active disease have more autoreactive B cells in both the antigen-naïve and antigen-experienced compartments consistent with greater impairment in B cell tolerance in both early and late checkpoints in these patients than in patients with quiescent disease. This methodology enables us to gain insight into the development and fate of DNA-reactive B cells in individual patients with SLE and paves the way ultimately to permit better and more customized therapies

Period-adding bifurcations and chaos in a periodically stimulated excitable neural relaxation oscillator

This is a pre-print. The definitive version: COOMBES, S. and OSBALDESTIN, A.H., 2000. Period-adding bifurcations and chaos in a periodically stimulated excitable neural relaxation oscillator. Physical Review E, 62(3), pp.4057-4066 Part B.The response of an excitable neuron to trains of electrical spikes is relevant to the understanding of the neural code. In this paper we study a neurobiologically motivated relaxation oscillator, with appropriately identified fast and slow coordinates, that admits an explicit mathematical analysis. An application of geometric singular perturbation theory shows the existence of an attracting invariant manifold which is used to construct the Fenichel normal form for the system. This facilitates the calculation of the response of the system to pulsatile stimulation and allows the construction of a so-called extended isochronal map. The isochronal map is shown to have a single discontinuity and be of a type that can admit three types of response: mode-locked, quasi-periodic and chaotic. The bifurcation structure of the system is seen to be extremely rich and supports period-adding bifurcations separated by windows of both chaos and periodicity. A bifurcation analysis of the isochronal map is presented in conjunction with a description of the various routes to chaos in this system

Respiratory functional characteristics of human leptospirosis

Introdução: O comprometimento respiratório da leptospirose humana pode ser sua principal manifestação clínica e comumente está associado a maior morbimortalidade. Métodos: Objetivando descrever aspectos funcionais respiratórios nessa doença, foram analisados 21 pacientes com oximetrias de pulso e espirometrias em dois momentos: em avaliação inicial e após cerca de 28 dias. Resultados: Dois (9,5%) doentes tinham saturação periférica de oxigênio menor que 95%. Padrões espirométricos normais foram observados em 8 (38,1%) casos; distúrbios ventilatórios restritivos foram inferidos em 7 (33,3%), obstrutivos com capacidade vital forçada reduzida em 4 (19%), e inespecíficos em 2 (9,5%). Espirometrias anormais se associaram a pior escore APACHE II (p=0,02) e anormalidades na radiografia de tórax (p=0,05). Após resolução clínica, verificou-se ganho funcional significativo (p<0,05) no grupo de pacientes com espirometria alterada. Conclusões: Alterações espirométricas foram detectadas no curso da enfermidade e estiveram associadas a pior gravidade clínica e maior freqüência de anormalidades radiológicas torácicas. _________________________________________________________________________________________ ABSTRACT: Introduction: Respiratory impairment may be the main clinical manifestation of human leptospirosis. Methods: With the aim of describing the respiratory functional characteristics of this disease, 21 patients were evaluated using pulse oximetry and spirometry at two times: an initial evaluation and after around 28 days. Results: Two (9.5%) patients presented peripheral oxygen saturation of less than 95%. Normal spirometric patterns were observed in eight (38.1%); cases restrictive ventilatory disorders were inferred in seven (33.3%), obstructive disorders with reduced forced vital capacity in four (19%), and nonspecific disorders in two (9.5%). Abnormal spirometry findings were associated with worse APACHE II scores (p = 0.02) and abnormalities on chest x-ray (p = 0.05). After clinical resolution, significant functional gain was observed (p < 0.05) in the group of patients with abnormal spirometry findings. Conclusions: It was concluded that respiratory functional abnormalities were detected during the course of the disease and were associated with greater clinical severity and higher frequency of chest radiographic abnormalities

Ophthalmic manifestations of Rochalimaea species

Rochalimaea henselae and R. quintana belong to the order Rickettsiales and are thought to be responsible for trench fever, bacillary angiomatosis, and cat scratch disease. We recently examined four patients with intraocular inflammation of unknown origin. Each patient had either unilateral or bilateral moderate loss of visual acuity ranging from 20/25 to counting fingers. Bilateral intraocular inflammation manifested by anterior and posterior segment cells, retinal lesions, macular exudate, and optic nerve head swelling was present to varying degrees. The R. henselae to R. quintana antibody titers were greater than or equal to 1:256 in each case. Marked improvement in vision occurred after treatment with either oral ciprofloxacin hydrochloride and prednisone or doxycycline hyclate. Rochalimaea species should be considered in the differential diagnosis of intraocular inflammation and inflammatory optic neuropathy. Appropriate treatment may result in marked improvement in visual acuity

Diagnosis of calcium pyrophosphate dihydrate crystal deposition disease: ultrasonographic criteria proposed

Methods: Three ultrasonographic patterns of CPPD calcification were identified and 11 patients enrolled. A control group comprised 13 patients with no evidence of CPPD deposits. Synovial fluid was aspirated from all patients and controls and examined for identification of crystals. All patients underwent a standard radiography examination at the same sites investigated by ultrasound. Results: In all patients with ultrasonographically defined CPPD deposits, CPPD crystals were found in the synovial fluid. In two cases, standard radiographic examination did not show evidence of the calcific deposits that were identified by ultrasonography. CPPD crystals were not found in the synovial fluid of controls. In four control group patients, ultrasonography identified calcifications defined as deposits of another nature. Conclusions: The ultrasonographic pattern used in this study for the diagnosis of CPPD disease demonstrated a very high correlation with the presence of CPPD crystals in synovial fluid. Ultrasonography demonstrated a sensitivity and specificity at least equal to that of radiography in identifying CPPD crystal calcifications

Reduced serum level of THDOC, an anticonvulsant steroid, in women with perimenstrual catamenial epilepsy

Purpose: Seizure exacerbation in catamenial epilepsy (CE) is associated with the decrease in progesterone secretion and increase in estradiol secretion during the premenstrual period. Moreover, experimental evidence suggests that tetrahydrodeoxycorticosterone (THDOC), a positive modulator of the type A receptor for γ - aminobutyric acid (GABA), and dehydroepiandrosterone sulfate (DHEAS), a negative modulator of this receptor, might play a crucial role in modulating seizure frequency during the menstrual cycle. Following these studies it seems of interest to investigate possible variations, among other hormonal parameters, of THDOC and DHEAS in CE patients. Methods: The serum concentrations of progesterone (P4), pregnenolone, allopregnanolone (AP), THDOC, DHEAS, cortisol, and DHEAS/cortisol ratio weremeasured throughout the menstrual cycle at the 7th, 11th, 15th, 19th, 23rd, and 27th day from the onset of spontaneous menstrual blood loss in young premenopausal women with CE (n = 17) and age-matched controls (n = 13). Results: At each time of the study, the serum concentration of THDOC and the DHEAS/cortisol ratio were lower (p < 0.05) in women with CE than in control women. The concentrations of P4, pregnenolone, and AP did not differ between the two groups of subjects. Conclusions: The reduced serum concentration of THDOCand the reduced DHEAS/cortisol ratio detected throughout the menstrual cycle in women with CE might play a role in CE. Moreover, the peculiar pattern of CE seizure exacerbation might suggest that these neuroendocrine variations are worth investigating in other epileptic syndromes, particularly in those characterized by relevant and uncontrolled variations in seizure frequency