Antileukemic activity of substituted ureidothiazoles, ureidothiadiazoles, and related compounds.

A number of ureidothiazole and ureidothiadiazole derivatives related to ethyl 4-[[(2-thiazolylamino)carbonyl]-amino]benzoate were prepared and evaluated against the leukemia P-388 tumor system in mice. Preliminary structure-activity relationship study revealed that, among other considerations, active compounds of this series contain either an "isothioureido" [N-C(S-)=N-] or an "isothiosemicarbazono" [N-C(S-)=N-N=] structural unit.     

Flecainide acetate for treatment of bypass tract mediated reentrant tachycardia

Flecainide acetate was administered to 19 patients who had inducible sustained orthodromic atrioventricular reentrant tachycardia. Eleven of 18 patients had no inducible tachycardia and 7 patients continued to have inducible tachycardia while receiving flecainide. The effects of flecainide could not be evaluated because of hypotension during intravenous infusion in 1 patient. The main effect of the drug was a selective depression of retrograde conduction over the bypass tract, resulting in abolition of reentry or prolongation of tachycardia cycle length. The electrophysiologic effects of intravenous flecainide were concordant with those of oral flecainide in 5 patients who were studied during both regimens. Fifteen patients were discharged from the hospital on a regimen of flecainide. One patient received concomitant beta-blocking therapy. During an average follow-up of 18.5 months (range 2 to 48), 9 patients remained symptom free. Recurrences were observed in 5 patients, 3 of whom still had inducible tachycardia during electrophysiologic testing. Treatment had to be discontinued in 1 patient because of drug intolerance. Thus, flecainide is likely to be effective and well tolerated in the long-term treatment of at least 50% of patients who present with bypass tract mediated orthodromic reentrant tachycardia.     

Time course of inner ear degeneration and deafness in mice lacking the Kir4.1 potassium channel subunit

The Kir4.1 gene (KCNJ10) encodes an inwardly rectifying K(+) channel subunit abundantly expressed in the CNS. Its expression in the mammalian inner ear has been suggested but its function in vivo in the inner ear is unknown. Because diverse human hereditary deafness syndromes are associated with mutations in K(+) channels, we examined auditory function and inner ear structure in mice with a genetically inactivated Kir4.1 K(+) channel subunit. Startle response experiments suggest that Kir4.1-/- mice are profoundly deaf, whereas Kir4.1+/- mice react like wild-type mice to acoustic stimuli. In Kir4.1-/- mice, the Reissner membrane is collapsed, the tectorial membrane is swollen, and type I hair cells and spiral ganglion neurons as well as their central processes degenerate over the first postnatal weeks. In the vestibular ganglia, neuronal cell death with apoptotic features is also observed. Immunostaining reveals that Kir4.1 is strongly expressed in stria vascularis of wild-type but not Kir4.1-/- mice. Within the spiral ganglion, Kir4.1 labeling was detected on satellite cells surrounding spiral ganglion neurons and axons. We conclude that Kir4.1 is crucial for normal development of the cochlea and hearing, via two distinct aspects of extracellular K(+) homeostasis: (1). in stria vascularis, Kir4.1 helps to generate the cochlear endolymph; and (2). in spiral and vestibular ganglia, Kir4.1 in surrounding glial cells helps to support the spiral and vestibular ganglion neurons and their projecting axons.     

Structural modification study of mitoxantrone (DHAQ). Chloro-substituted mono- and bis[(aminoalkyl)amino]anthraquinones

A number of chloro-substituted [(aminoalkyl)amino]anthraquinones were synthesized and evaluated for their antineoplastic and cytotoxic activity. Treatment of 5,8-dichloroquinizarin with substituted amines in pyridine resulted in the replacement of one halogen atom by the amino group to yield mainly 1-chloro-5,8-dihydroxy-4-(substituted amino)anthraquinones. On the other hand, reaction between the dichloroquinizarin and the amines in butanol gave predominantly 1,4-dichloro-5-hydroxy-8-(substituted amino)anthraquinones. Other compounds in this series were prepared by displacement of chloro, nitro, or tosyl functions of the appropriate anthraquinone derivatives with various amines by conventional methods. 1,4-Dichloro-5-hydroxy-8-[[2-[(2-hydroxyethyl)amino]ethyl]amino] anthraquinone (6b) possesses the highest inhibitory activity against P388 leukemia. Its inhibitory action against B16 melanoma and against the in vitro L1210 screen is also significant. Several other chloro- and hydroxy-substituted aminoanthraquinones (5a, 5b, and 6a) also showed noticeable activity against P388 in vivo and L1210 in vitro. Structure-activity-relationship examination indicated that the hydroxyl group may contribute to the binding of certain chloroaminoanthraquinones for their biological activity and that the [2-[(2-hydroxyethyl)amino]ethyl]amino side chain seems to be the preferred substituent over other amino side chains.     

Live tweeting in medicine: ‘Tweeting the meeting’

Abstract

Medical conferences create an opportunity for lifelong learning for healthcare practitioners. The use of Twitter at such conferences continues to expand. This article focuses on how Twitter can be used by physicians and other healthcare providers at regional, national and international conferences, and also at local conferences, such as grand rounds. It also addresses the potential utility of Twitter chats and journal clubs in the promotion of lifelong learning. The impact of Twitter use in healthcare in general, and specifically at conferences, and how it can be measured, is discussed.     

Infective endocarditis of a bicuspid aortic valve caused by Hansenula anomala

Infective endocarditis due to Hansenula anomala developed on a bicuspid aortic valve in a 40-year-old man. H. anomala, an ascomycetous yeast, may be a member of the normal flora of the throat and alimentary tract in humans but has not been previously known to be pathogenic in humans. A past history of intravenous drug use may have contributed to the development of disease in this patient.     

Amino-substituted p-benzoquinones

Based on the observation of outstanding antineoplastic activity of a number of amino-substituted anthraquinones, thioxanthones, and N-(aminoethyl)-substituted naphthalimides, four types of amino-substituted p-benzoquinones were designed, synthesized, and their biological activity evaluated. Although none of these compounds exhibited inhibitory activity against P388 leukemia, 2,5-bis[[4-[(dimethylamino)methyl]phenyl]amino]-3,6-dibromo-1,4- benzoquinone and the corresponding dichloro compound demonstrated good inhibitory activity against the proliferating human colon adenocarcinoma in vitro. The dichloro compound was also found to be active against the leukemia L1210 screening in vitro. 2,5-Bis[[2-(dimethylamino)ethyl]amino]-1,4-benzoquinone possessed inhibitory activity against Neisseria catarrhali.     

Paradoxical ventricular septal motion with right ventricular dilatation as a manifestation of pure pressure overload due to pulmonary veno-occlusive disease

Paradoxical interventricular septal motion with right ventricular dilatation has been considered the hallmark of right ventricular volume overload. We report a 43-year-old woman with severe pulmonary hypertension due to pulmonary veno-occlusive disease who exhibited these echocardiographic abnormalities. Right ventricular volume overload was excluded by physical examination, echocardiography with saline contrast study and by cardiac catheterization, angiography, and shunt study. These echocardiographic findings are thus not pathognomonic of right ventricular volume overload and can be seen with pressure overload as well.