Citations

Pulmonic stenosis unassociated with a ventricular septal defect of significant size is often a complex abnormality. The stenosis may be valvular, infundibular, or both, and may be associated with an atrial septal defect or even with a small ventricular septal defect. Preoperative studies cannot accurately predict these variations. The surgical approach selected for such patients should permit the correction of each of the cardiac defects encountered. That this can be accomplished by means of extracorporeal circulation and open cardiotomy is demonstrated by the presented series of 10 cases without operative mortality.

A method based on the initial portion of indicator-dilution curves has been used to determine the proportion of blood from each lung which drains anomalously. The results obtained appear to substantiate the derivation and permit the expression, in numerical values, of the greater proportion of anomalous drainage of blood from the right lung in the usual case of atrial septal defect. The principal assumptions pertaining to the method are discussed in some detail.

AbstractBackgroundAmpullary and extensive periampullary lesions can be difficult to treat and often require pancreaticoduodenectomy (PD) for complete removal, even if benign. However, PD may be overtreatment for noninvasive lesions, and pancreas‐sparing total duodenectomy (PSTD) is an emerging valid surgical option for selected cases.MethodsWe reviewed patients undergoing PSTD at our institution over 16 months and a comparison group who had undergone PD for benign duodenal disease over the past 15 years. We also reviewed cases in the English‐language literature and performed a meta‐analysis of those patients who had undergone PSTD.ResultsPSTD had been performed in four patients, who had an average hospital length of stay (LOS) of 13 days; two of them experienced complications. None required conversion to PD, experienced a postoperative fistula or endocrine or exocrine insufficiency, or required intensive care. Two of the PSTDs were performed laparoscopically. Open PD for benign duodenal disease was performed in 22 patients, with overall morbidity and pancreas fistula rates of 82 and 27 %, respectively. The meta‐analysis found 128 unique cases of PSTD with morbidity and mortality rates of 46.4 and 2.3 %, respectively. Pancreaticobiliary leak was seen in 20 %, with an average LOS of 17 days.ConclusionsAlthough PSTD can be used to avoid PD and can be performed laparoscopically, it is technically challenging and still associated with morbidity.

AbstractProtein synthesis determines sensitivity of differentiating and malignant plasma cells to proteasome inhibitors by saturating cellular proteolytic capacity.A previously unsuspected, considerable proportion of newly synthesized polypeptides are hydrolyzed rapidly by proteasomes, possibly competing with endogenous substrates and altering proteostasis. In view of the anti-cancer effects of PIs, we set out to achieve a quantitative assessment of proteasome workload in cells hallmarked by different PI sensitivity, namely, a panel of MM cells, and in a dynamic model of plasma cell differentiation, a process that confers exquisite PI sensitivity. Our results suggest that protein synthesis is a key determinant of proteasomal proteolytic burden and PI sensitivity. In different MM cells and in differentiating plasma cells, the average proteolytic work accomplished per proteasome ranges over different orders of magnitude, an unexpected degree of variability, with increased workload invariably associated to increased PI sensitivity. The unfavorable load-versus-capacity balance found in highly PI-sensitive MM lines is accounted for by a decreased total number of immunoproteasomes/cell coupled to enhanced generation of RDPs. Moreover, indicative of cause-effect relationships, attenuating general protein synthesis by the otherwise toxic agent CHX reduces PI sensitivity in activated B and in MM cells. Our data support the view that in plasma cells protein synthesis contributes to determine PI sensitivity by saturating the proteasomal degradative capacity. Quantitating protein synthesis and proteasome workload may thus prove crucial to design novel negative proteostasis regulators against cancer.

Object Glomus tumors are rare skull base neoplasms that frequently involve critical cerebrovascular structures and lower cranial nerves. Complete resection is often difficult and may increase cranial nerve deficits. Stereotactic radiosurgery has gained an increasing role in the management of glomus tumors. The authors of this study examine the outcomes after radiosurgery in a large, multicenter patient population. Methods Under the auspices of the North American Gamma Knife Consortium, 8 Gamma Knife surgery centers that treat glomus tumors combined their outcome data retrospectively. One hundred thirty-four patient procedures were included in the study (134 procedures in 132 patients, with each procedure being analyzed separately). Prior resection was performed in 51 patients, and prior fractionated external beam radiotherapy was performed in 6 patients. The patients' median age at the time of radiosurgery was 59 years. Forty percent had pulsatile tinnitus at the time of radiosurgery. The median dose to the tumor margin was 15 Gy. The median duration of follow-up was 50.5 months (range 5–220 months). Results Overall tumor control was achieved in 93% of patients at last follow-up; actuarial tumor control was 88% at 5 years postradiosurgery. Absence of trigeminal nerve dysfunction at the time of radiosurgery (p = 0.001) and higher number of isocenters (p = 0.005) were statistically associated with tumor progression–free tumor survival. Patients demonstrating new or progressive cranial nerve deficits were also likely to demonstrate tumor progression (p = 0.002). Pulsatile tinnitus improved in 49% of patients who reported it at presentation. New or progressive cranial nerve deficits were noted in 15% of patients; improvement in preexisting cranial nerve deficits was observed in 11% of patients. No patient died as a result of tumor progression. Conclusions Gamma Knife surgery was a well-tolerated management strategy that provided a high rate of long-term glomus tumor control. Symptomatic tinnitus improved in almost one-half of the patients. Overall neurological status and cranial nerve function were preserved or improved in the vast majority of patients after radiosurgery.

Background— Alterations at the level of the coronary circulation with aging may play an important role in the evolution of age-associated changes in left ventricular (LV) fibrosis and function. However these age-associated changes in the coronary vasculature remain poorly defined primarily due to the lack of high resolution imaging technologies. The current study was designed to utilize cardiac micro–computed tomography (micro-CT) technology as a novel imaging strategy, to define the 3-dimensional coronary circulation in the young and aged heart and its relationship to LV fibrosis and function. Methods and Results— Young (2 months old; n=10) and aged (20 months old; n=10) Fischer rats underwent cardiac micro-CT imaging as well as echocardiography, blood pressure, and fibrosis analysis. Importantly, when indexed to LV mass, which increased with age, the total and intramyocardial vessel volumes were lower, whereas the epicardial vessel volume, with and without indexing to LV mass, was significantly higher in the aged hearts compared with the young hearts. Moreover, the aged hearts had a significantly lower percentage of intramyocardial vessel volume and a significantly higher percentage of epicardial vessel volume, when normalized to the total vessel volume, compared with the young hearts. Further, the aged hearts had significant LV fibrosis and mild LV dysfunction compared with the young hearts. Conclusions— This micro-CT imaging study reports the reduction in normalized intramyocardial vessel volume within the aged heart, in association with increased epicardial vessel volume, in the setting of increased LV fibrosis, and mild LV dysfunction.

Magnetic resonance elastography (MRE) is a MR imaging method capable of spatially resolving the intrinsic mechanical properties of normal lung parenchyma. We tested the hypothesis that the mechanical properties of edematous lung exhibit local properties similar to those of a fluid-filled lung at transpulmonary pressures (Ptp) up to 25 cm H2O. Pulmonary edema was induced in anesthetized female adult Sprague-Dawley rats by mechanical ventilation to a pressure of 40 cm H2O for ∼30 min. Prior to imaging the wet weight of each ex vivo lung set was measured. MRE, high-resolution T1-weighted spin echo and T2* gradient echo data were acquired at each Ptpfor both normal and injured ex vivo lungs. At Ptps of 6 cm H2O and greater, the shear stiffness of normal lungs was greater than injured lungs ( P ≤ 0.0003). For Ptps up to 12 cm H2O, shear stiffness was equal to 1.00, 1.07, 1.16, and 1.26 kPa for the injured and 1.31, 1.89, 2.41, and 2.93 kPa for normal lungs at 3, 6, 9, and 12 cm H2O, respectively. For injured lungs MRE magnitude signal and shear stiffness within regions of differing degrees of alveolar flooding were calculated as a function of Ptp. Differences in shear stiffness were statistically significant between groups ( P < 0.001) with regions of lower magnitude signal being stiffer than those of higher signal. These data demonstrate that when the alveolar space filling material is fluid, MRE-derived parenchymal shear stiffness of the lung decreases, and the lung becomes inherently softer compared with normal lung.

Objectives Chronic constipation in diabetes mellitus is associated with colonic motor dysfunction and is managed with laxatives. Cholinesterase inhibitors increase colonic motility. This study evaluated the effects of a cholinesterase inhibitor on gastrointestinal and colonic transit and bowel function in diabetic patients with constipation. Design After a 9-day baseline period, 30 patients (mean±SEM age 50±2 years) with diabetes mellitus (18 type 1, 12 type 2) and chronic constipation without defaecatory disorder were randomised to oral placebo or pyridostigmine, starting with 60 mg three times a day, increasing by 60 mg every third day up to the maximum tolerated dose or 120 mg three times a day; this dose was maintained for 7 days. Gastrointestinal and colonic transit (assessed by scintigraphy) and bowel function were evaluated at baseline and the final 3 and 7 days of treatment, respectively. Treatment effects were compared using analysis of covariance, with gender, body mass index and baseline colonic transit as covariates. Results 19 patients (63%) had moderate or severe autonomic dysfunction; 16 (53%) had diabetic retinopathy. 14 of 16 patients randomised to pyridostigmine tolerated 360 mg daily; two patients took 180 mg daily. Compared with placebo (mean±SEM 1.98±0.17 (baseline), 1.84±0.16 (treatment)), pyridostigmine accelerated (1.96±0.18 (baseline), 2.45±0.2 units (treatment), p<0.01) overall colonic transit at 24 h, but not gastric emptying or small-intestinal transit. Treatment effects on stool frequency, consistency and ease of passage were significant (p≤0.04). Cholinergic side effects were somewhat more common with pyridostigmine (p=0.14) than with placebo. Conclusions Cholinesterase inhibition with oral pyridostigmine accelerates colonic transit and improves bowel function in diabetic patients with chronic constipation. Clinical trial registration number TrialRegNo (NCT 00276406).