Digital clubbing in tuberculosis – relationship to HIV infection, extent of disease and hypoalbuminemia

BACKGROUND: Digital clubbing is a sign of chest disease known since the time of Hippocrates. Its association with tuberculosis (TB) has not been well studied, particularly in Africa where TB is common. The prevalence of clubbing in patients with pulmonary TB and its association with Human Immunodeficiency Virus (HIV), severity of disease, and nutritional status was assessed. METHODS: A cross-sectional study was carried out among patients with smear-positive TB recruited consecutively from the medical and TB wards and outpatient clinics at a public hospital in Uganda. The presence of clubbing was assessed by clinical signs and measurement of the ratio of the distal and inter-phalangeal diameters (DPD/IPD) of both index fingers. Clubbing was defined as a ratio > 1.0. Chest radiograph, serum albumin and HIV testing were done. RESULTS: Two hundred patients (82% HIV-infected) participated; 34% had clubbing by clinical criteria whilst 30% had clubbing based on DPD/IPD ratio. Smear grade, extensive or cavitary disease, early versus late HIV disease, and hypoalbuminemia were not associated with clubbing. Clubbing was more common among patients with a lower Karnofsky performance scale score or with prior TB. CONCLUSION: Clubbing occurs in up to one-third of Ugandan patients with pulmonary TB. Clubbing was not associated with stage of HIV infection, extensive disease or hypoalbuminemia

The value of Doppler color flow mapping in determining pulmonary blood supply in infants with pulmonary atresia with ventricular septal defect

AbstractThirty-two neonates and infants with pulmonary atresia with ventricular septal defect were initially investigated with cross-sectional and spectral Doppler echocardiography and Doppler color flow mapping. All 32 had subsequent correlative angiography. This demonstrated that 24 infants had adequate-sized right and left pulmonary arteries (19 confluent, 5 nonconfluent). Of the five infants with nonconfluent pulmonary arteries, four had bilateral ductus arteriosus and one had a single left-sided ductus with anomalous origin of the right pulmonary artery from the ascending aorta. Nineteen infants had confluent pulmonary arteries, all of which were supplied by a single ductus. Eight infants had complete absence of or inadequate pulmonary arteries; all had multiple aortopulmonary collateral vessels arising from the descending aorta.The presence of adequate-sized right and left pulmonary arteries was correctly predicted in 21 of 24 infants by cross-sectional echocardiography alone and in all 24 by Doppler color flow mapping. Confluence of the right and left pulmonary arteries was predicted by cross-sectional imaging in 14 of the 19 infants in whom it occurred, and by Doppler color flow mapping in all 19 infants.The precise definition of the pulmonary blood supply was correctly predicted by Doppler color flow mapping in 16 of the 19 infants with confluent pulmonary arteries and a single ductus. However, in three infants in this group, Doppler color flow mapping made a false diagnosis of multiple aortopulmonary collateral vessels. In the eight infants with inadequate pulmonary arteries, Doppler color flow mapping correctly predicted the presence of two or more aortopulmonary collateral vessels, but it was unreliable in predicting the multifocal pulmonary blood supply in four of five patients with nonconfluent pulmonary arteries.In summary, Doppler color flow mapping improved the noninvasive evaluation of pulmonary atresia with ventricular septal defect. It consistently identified adequate-sized confluent pulmonary arteries supplied by a single ductus. In such cases, systemic pulmonary shunting can be performed without prior angiography. However, when Doppler color flow mapping suggested a multifocal pulmonary blood supply, the morphology was too complex to allow accurate ultrasound definition and angiography remained the essential diagnostic technique

Analysis of core circadian feedback loop in suprachiasmatic nucleus of mCry1-luc transgenic reporter mouse

The suprachiasmatic nucleus (SCN) coordinates circadian rhythms that adapt the individual to solar time. SCN pacemaking revolves around feedback loops in which expression of Period (Per) and Cryptochrome (Cry) genes is periodically suppressed by their protein products. Specifically, PER/CRY complexes act at E-box sequences in Per and Cry to inhibit their transactivation by CLOCK/BMAL1 heterodimers. To function effectively, these closed intracellular loops need to be synchronized between SCN cells and to the light/dark cycle. For Per expression, this is mediated by neuropeptidergic and glutamatergic extracellular cues acting via cAMP/calcium-responsive elements (CREs) in Per genes. Cry genes, however, carry no CREs, and how CRY-dependent SCN pacemaking is synchronized remains unclear. Furthermore, whereas reporter lines are available to explore Per circadian expression in real time, no Cry equivalent exists. We therefore created a mouse, B6.Cg-Tg(Cry1-luc)01Ld, carrying a transgene (mCry1-luc) consisting of mCry1 elements containing an E-box and E'-box driving firefly luciferase. mCry1-luc organotypic SCN slices exhibited stable circadian bioluminescence rhythms with appropriate phase, period, profile, and spatial organization. In SCN lacking vasoactive intestinal peptide or its receptor, mCry1 expression was damped and desynchronized between cells. Despite the absence of CREs, mCry1-luc expression was nevertheless (indirectly) sensitive to manipulation of cAMP-dependent signaling. In mPer1/2-null SCN, mCry1-luc bioluminescence was arrhythmic and no longer suppressed by elevation of cAMP. Finally, an SCN graft procedure showed that PER-independent as well as PER-dependent mechanisms could sustain circadian expression of mCry1. The mCry1-luc mouse therefore reports circadian mCry1 expression and its interactions with vasoactive intestinal peptide, cAMP, and PER at the heart of the SCN pacemaker