Characteristics of Tuberculosis Cases that Started Outbreaks in the United States, 2002–2011

A review of 26 tuberculosis outbreaks in the United States (2002–2011) showed that initial source case-patients had long infectious periods (median 10 months) and were characterized by substance abuse, incarceration, and homelessness. Improved timeliness of diagnosis and thorough contact investigations for such cases may reduce the risk for outbreaks.     

Dilation of forearm blood vessels after angiotensin-converting-enzyme inhibition by captopril in hypertensive patients

In eight hypertensive patients, forearm vascular tone was assessed by water plethysmography following inhibition of angiotensin II-converting-enzyme (ACE) activity with captopril. Acute captopril administration increased venous distensibility (VV30) and decreased forearm vascular resistance (FVR), while it lowered systemic blood pressure (BP). Alpha-one adrenergic receptor blockade by prazosin did not prevent captopril from decreasing vascular tone or lowering blood pressure (BP). Thus, captopril dilated both veins and arterioles. The primary mechanism of captopril's acute antihypertensive action did not involve inhibition of alpha1-adrenergic receptor activity. Moreover, captopril and prazosin together produced a greater reduction in BP and peripheral resistance than occurred with either agent alone.     

A novel small molecule approach for the treatment of propionic and methylmalonic acidemias

Propionic Acidemia (PA) and Methylmalonic Acidemia (MMA) are inborn errors of metabolism affecting the catabolism of valine, isoleucine, methionine, threonine and odd-chain fatty acids. These are multi-organ disorders caused by the enzymatic deficiency of propionyl-CoA carboxylase (PCC) or methylmalonyl-CoA mutase (MUT), resulting in the accumulation of propionyl-coenzyme A (P-CoA) and methylmalonyl-CoA (M-CoA in MMA only). Primary metabolites of these CoA esters include 2-methylcitric acid (MCA), propionyl-carnitine (C3), and 3-hydroxypropionic acid, which are detectable in both PA and MMA, and methylmalonic acid, which is detectable in MMA patients only (Chapman et al., 2012). We deployed liver cell-based models that utilized PA and MMA patient-derived primary hepatocytes to validate a small molecule therapy for PA and MMA patients. The small molecule, HST5040, resulted in a dose-dependent reduction in the levels of P-CoA, M-CoA (in MMA) and the disease-relevant biomarkers C3, MCA, and methylmalonic acid (in MMA). A putative working model of how HST5040 reduces the P-CoA and its derived metabolites involves the conversion of HST5040 to HST5040-CoA driving the redistribution of free and conjugated CoA pools, resulting in the differential reduction of the aberrantly high P-CoA and M-CoA. The reduction of P-CoA and M-CoA, either by slowing production (due to increased demands on the free CoA (CoASH) pool) or enhancing clearance (to replenish the CoASH pool), results in a net decrease in the CoA-derived metabolites (C3, MCA and MMA (MMA only)). A Phase 2 study in PA and MMA patients will be initiated in the United States.     

Chemoradiation-induced changes in systemic inflammatory markers and their prognostic significance in oesophageal squamous cell carcinoma

Objective:Chemoradiation (CRT) may induce a change in systemic inflammatory state which could affect clinical outcomes in oesophageal cancer. We aimed to evaluate the changes and prognostic significance of systemic inflammatory markers following definitive CRT in oesophageal squamous cell carcinoma.Methods:A total of 53 patients treated with concurrent CRT were included in this retrospective analysis. We compared neutrophils, lymphocytes, platelets, neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) before and after CRT using Wilcoxon signed-rank test. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariable and multivariable survival analysis were performed using Cox regression analysis. Clinical univariable survival prognostic factors with p < 0.1 were included in a multivariable cox regression analysis for backward stepwise model selection.Results:Both NLR (median ∆+2.8 [IQR −0.11, 8.62], p < 001) and PLR (median ∆+227 [81.3–523.5], p < 0.001) increased significantly after CRT. Higher levels of pre-CRT, post-CRT and change (∆) in NLR and PLR were associated with inferior OS and PFS. Post-CRT NLR (HR 1.04, 95% CI 1.02–1.07, p < 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.005), cT-stage (HR 3.83, 95% CI 1.39–10.60, p = 0.01) and RT dose (HR 0.41, 95% CI 0.21–0.81, p = 0.01) were independent prognostic factors for OS in multivariable analysis. Change in NLR (HR 1.04, 95% CI 1.01–1.06, p = 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.002), cT-stage (HR 3.98, 95% CI 1.55–10.25, p = 0.004) and RT dose (HR 0.41, 95% CI 0.21–0.80, p = 0.009) were independent prognostic factors for PFS.Conclusion:Both NLR and PLR increased following definitive CRT. Post-CRT NLR and ∆NLR were associated with adverse survival in oesophageal SCC.Advances in knowledge:We showed that CRT increased PLR and NLR, possibly reflecting a systemic inflammatory state which were associated with poor clinical outcomes in oesophageal SCC.     

Steroid-eluting epicardial pacing leads in pediatric patients: encouraging early results.

OBJECTIVES. This study evaluated the pacing and sensing characteristics of a new porous-tipped steroid-eluting epicardial lead in a group of pediatric patients. BACKGROUND. Pacing in children may be complicated by small patient size, patient growth and the prevalence of structural congenital heart disease in children requiring pacing. Epicardial pacing has been associated with a high incidence of problems with sensing and capture, prompting the use of transvenous endocardial pacing when possible. In some children, epicardial pacing may still be desirable because of small patient size, potential for caval obstruction, previous cardiac surgery limiting transvenous access to the heart, or the need to repair congenital heart disease at the time of pacemaker insertion. METHODS. Twelve patients aged 3 weeks to 18 years underwent placement of 23 epicardial pacing leads (8 atrial, 15 ventricular). Pulse width thresholds, sensing thresholds and lead impedance were measured weekly for 6 weeks, then at 3, 6, 12 and 18 months after pacemaker implantation. The median duration of follow-up was 12 months. RESULTS. Ventricular pulse width thresholds did not change over time, whereas atrial pulse width thresholds improved significantly. At 6 months, the mean pulse width threshold at 2.5 V for the atrial and ventricular leads was 0.10 +/- 0.03 and 0.19 +/- 0.09 ms, respectively. The thresholds were slightly lower at 12 and 18 months. At the most recent follow-up, all atrial leads sensed appropriately at 2.5 mV and all ventricular leads at 5 mV. CONCLUSIONS. These encouraging early results suggest that steroid-eluting epicardial pacing leads may be an attractive option for children needing epicardial pacing. Their excellent pacing and sensing characteristics may allow reliable dual-chamber pacing in infants who are too small for transvenous pacing.     

Wound healing effect of methanolic leaf extract of Napoleona vogelii(Family:Lecythidaceae) in rats

Objective:To investigate the wound healing properly of Napoleona vogelii leaf extract in folkloric medicine.Methods:Roth sexes of adult albino rats(n=25) were used in this study and another group(n=30) were subjected to acute toxicity test(LD_(50)) of the plant extract.For the LD_(50),three randomized groups of 5 rats were first treated with 10,100,1 000 mg/kg body weight(bw),orally.This w as followed by a second treatment of 1500,3000,and 5 000 mg/kg bw of the leaf extract with continual monitoring of the animals for mortality or non-mortality.Incision wounds(1.3cm) were created on the skin of five groups of 5 rals using surgical blade under anesthesia.The first group was topically treated with petroleum jelly alone,group 2 was topically applied 400 mg/mL w/v of the reference drug,Neobaein,while group 3-5 were topically treated with 5-50 mg/mL w/v of the plant extract,respectively.Results:The percentage yield of the extract was 49.80%w/w dry matter.The phytochemical analysis revealed several bioactive constituents including glycosides,tannins,alkaloids,perpenoids.saponins,steroids,proteins,and carbohydrates.The LD_(50) was beyond our experimental limit and was not determined.Increased concentrations(5,20,and 50mg/mL w/v) of the extract had significant(ANOVA,P0.05) healing effect on the incision wounds giving rise to 125%-140% while treatmentawith Neobacin resulted in 150% healing effect on the third treatment regimen compared to the control(100%).Conclusions:These data indicate that Napoleona vogelii leaf extract contains potent bioactive compounds containing wound healing activity,substantiating its use as a wound healer in folkloric medicine.     

The development of a normalization method for comparing nerve regeneration effectiveness among different graft types

The inability to compare directly different nerve grafts has been a significant factor hindering the advance of nerve graft development. Due to the abundance of variables that exist in nerve graft construction and multiple assessment types, there has been limited success in comparing nerve graft effectiveness among experiments. Using mathematical techniques on nerve conduction velocity (NCV) autograft data, a normalization function was empirically derived that normalizes differences in gap lengths. Further analysis allowed for the development of the relative regeneration ratio (RRR). The RRR function allows researchers to directly compare nerve graft results based on the NCV data from their respective studies as long as the data was collected at the same post‐operation time. This function also allows for comparisons between grafts tested at different gap lengths. Initial testing of this RRR function provided confidence that the function is accurate for a continuum of gap lengths and different nerve graft types.     

Sociodemographic characteristics associated with parenthood amongst patients with a psychotic diagnosis: a cross-sectional study using patient clinical records

Social Psychiatry and Psychiatric Epidemiology - Estimates of parenthood in individuals with psychosis range from 27 to 63%. This number has likely increased due to the introduction of newer...