Findings 693 households of index patients with MDR tuberculosis were enrolled in the study. In 48 households, the Mycobacterium tuberculosis isolate from the index patient was XDR. Of the 4503 household contacts, 117 (2.60%) had active tuberculosis at the time the index patient began MDR tuberculosis treatment there was no difference in prevalence between XDR and MDR tuberculosis households. During the 4-year follow-up, 242 contacts developed active tuberculosis the frequency of active tuberculosis was nearly two times higher in contacts of patients with XDR tuberculosis
than it was in contacts of patients with MDR tuberculosis (hazard ratio 1.88, 95% CI 1.10-3.21). In the 359 contacts with active tuberculosis, 142 (40%) had had isolates tested for resistance Selleckchem RG-7388 against first-line drugs, of whom 129 (90.9%, 95% CI 85.0-94.6) had MDR tuberculosis.
Interpretation In view of the high risk of disease recorded in household contacts of patients with MDR or XDR tuberculosis, tuberculosis programmes should PI3K inhibitor implement systematic household contact investigations for all patients identified as having MDR or XDR tuberculosis. If shown to have active tuberculosis, these household contacts should be suspected as having MDR tuberculosis until proven otherwise.”
“Cholecystokinin modulates pain and anxiety via
its functions within brain regions such as the midbrain periaqueductal gray (PAG). The aim of this study was to examine the cellular actions of cholecystokinin on PAG neurons. Whole-cell patch clamp recordings were made from rat midbrain PAG slices in vitro to examine the postsynaptic effects of cholecystokinin and its effects on synaptic transmission. Sulfated cholecystokinin-(26-33) (CCK-S, 100-300 nM), but not non-sulfated cholecystokinin-(26-33) (CCK-NS, 100-300 nM) produced an inward current in a sub-population of opioid sensitive and insensitive PAG neurons, which did not reverse over a range of membrane potentials. The CCK-S-induced current was abolished by the CCK1 selective antagonist devazepide (100 nM), but not by the CCK2 selective antagonists CI988 (100 nM, 1
mu M) and LY225910 (1 mu M). CCK-S, but not CCK-NS produced a reduction in the amplitude of evoked GABA(A)-mediated inhibitory postsynaptic currents (IPSCs) and an increase in the evoked DNA ligase IPSC paired-pulse ratio. By contrast, CCK-S had little effect on the rate and amplitude of TTX-resistant miniature IPSCs under basal conditions and when external K(+) was elevated. The CCK-S-induced inhibition of evoked IPSCs was abolished by the cannabinoid CB1 receptor antagonist AM251 (3 mu M), the mGluR5 antagonist MPEP (10 mu M) and the 1, 2-diacylglycerol lipase (DAGL alpha) inhibitor tetrahydrolipstatin (10 mu M). In addition, CCK-S produced an increase in the rate of spontaneous non-NMDA-mediated, TTX-dependent excitatory postsynaptic currents (EPSCs).