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Abstract Background An efficient method for the identification of medicinal plant products is now a priority as the global demand increases. This study aims to develop a DNA-based method for the identification and authentication of plant species that can be implemented in the industry to aid compliance with regulations, based upon the economically important Hypericum perforatum L. (St John’s Wort or Guan ye Lian Qiao). Methods The ITS regions of several Hypericum species were analysed to identify the most divergent regions and PCR primers were designed to anneal specifically to these regions in the different Hypericum species. Candidate primers were selected such that the amplicon produced by each species-specific reaction differed in size. The use of fluorescently labelled primers enabled these products to be resolved by capillary electrophoresis. Results Four closely related Hypericum species were detected simultaneously and independently in one reaction. Each species could be identified individually and in any combination. The introduction of three more closely related species to the test had no effect on the results. Highly processed commercial plant material was identified, despite the potential complications of DNA degradation in such samples. Conclusion This technique can detect the presence of an expected plant material and adulterant materials in one reaction. The method could be simply applied to other medicinal plants and their problem adulterants.

Having the ability to predict the protein-encoding gene content of an incomplete genome or metagenome-assembled genome is important for a variety of bioinformatic tasks. In this study, as a proof of concept, we built machine learning classifiers for predicting variable gene content in Escherichia coli genomes using only the nucleotide k-mers from a set of 100 conserved genes as features. Protein families were used to define orthologs , and a single classifier was built for predicting the presence or absence of each protein family occurring in 10%-90% of all E. coli genomes. The resulting set of 3,259 extreme gradient boosting classifiers had a per-genome average macro F1 score of 0.944 [0.943-0.945, 95% CI]. We show that the F1 scores are stable across multi-locus sequence types and that the trend can be recapitulated by sampling a smaller number of core genes or diverse input genomes. Surprisingly, the presence or absence of poorly annotated proteins, including "hypothetical proteins" was accurately predicted (F1 = 0.902 [0.898-0.906, 95% CI]). Models for proteins with horizontal gene transfer-related functions had slightly lower F1 scores but were still accurate (F1s = 0.895, 0.872, 0.824, and 0.841 for transposon, phage, plasmid, and antimicrobial resistance-related functions, respectively). Finally, using a holdout set of 419 diverse E. coli genomes that were isolated from freshwater environmental sources, we observed an average per-genome F1 score of 0.880 [0.876-0.883, 95% CI], demonstrating the extensibility of the models. Overall, this study provides a framework for predicting variable gene content using a limited amount of input sequence data. IMPORTANCE Having the ability to predict the protein-encoding gene content of a genome is important for assessing genome quality, binning genomes from shotgun metagenomic assemblies, and assessing risk due to the presence of antimicrobial resistance and other virulence genes. In this study, we built a set of binary classifiers for predicting the presence or absence of variable genes occurring in 10%-90% of all publicly available E. coli genomes. Overall, the results show that a large portion of the E. coli variable gene content can be predicted with high accuracy, including genes with functions relating to horizontal gene transfer. This study offers a strategy for predicting gene content using limited input sequence data., Competing Interests: The authors declare no conflict of interest.

Background: Lack of sustainable access to clean drinking water continues to be an issue of paramount global importance, leading to millions of preventable deaths annually. Best practices for providing sustainable access to clean drinking water, however, remain unclear. Widespread installation of low-cost, in-home, point of use water filtration systems is a promising strategy., Methods: We conducted a prospective, randomized, controlled trial whereby 16 villages were selected and randomly assigned to one of four treatment arms based on the installation location of Sawyer® PointONE™ filters (filter in both home and school; filter in home only; filter in school only; control group). Water samples and self-reported information on diarrhea were collected at multiple times throughout the study., Results: Self-reported household prevalence of diarrhea decreased from 25.6 to 9.76% from installation to follow-up (at least 7 days, and up to 200 days post-filter installation). These declines were also observed in diarrhea with economic or educational consequences (diarrhea which led to medical treatment and/or missing school or work) with baseline prevalence of 9.64% declining to 1.57%. Decreases in diarrhea prevalence were observed across age groups. There was no evidence of a loss of efficacy of filters up to 200 days post-filter installation. Installation of filters in schools was not associated with decreases in diarrhea prevalence in school-aged children or family members. Unfiltered water samples both at schools and homes contained potential waterborne bacterial pathogens, dissolved heavy metals and metals associated with particulates. All dissolved metals were detected at levels below World Health Organization action guidelines., Conclusions: This controlled trial provides strong evidence of the effectiveness of point-of-use, hollow fiber membrane filters at reducing diarrhea from bacterial sources up to 200 days post-installation when installed in homes. No statistically significant reduction in diarrhea was found when filters were installed in schools. Further research is needed in order to explore filter efficacy and utilization after 200 days post-installation., Trial Registration: ClinicalTrials.gov, NCT03972618 . Registered 3 June 2019-retrospectively registered.

Background: Meningitis is a very rare atypical presenting feature of anti-NMDA receptor encephalitis. In our case report, we describe an unusual clinical presentation of anti-NMDA receptor encephalitis with a biphasic pattern of meningitis followed by encephalitis and discuss potential mechanisms underlying this presentation. We aim to widen the differential diagnosis to be considered in a patient presenting with clinical meningitis and pyrexia., Case Presentation: This is a case of a 33-year old Caucasian woman who initially presented with a lymphocytic meningitis attributed to a viral infection. She subsequently developed fluctuating consciousness, agitation, visual hallucinations, dyskinetic movements, a generalized tonic-clonic seizure, and autonomic instability. Investigations revealed a diagnosis of anti-NMDA receptor encephalitis secondary to a previously unidentified ovarian teratoma. She made an excellent recovery with immunotherapy and removal of the teratoma., Conclusion: Clinicians should consider autoimmune encephalitides in individuals with meningitis, particularly where extensive investigations fail to identify a causative pathogen and there is rapid development of an encephalitic phenotype.

Purpose: This Food and Drug Administration-approved investigational device exempt trial assessed the safety and efficacy of a novel device for external left atrial appendage (LAA) exclusion., Description: Delivery tool and implant consisting of connectors imbedded in a compliant, soft silicone applied to the base of the LAA flush with the external wall was assessed., Evaluation: Patients in this prospective, multicenter trial were undergoing elective, nonendoscopic cardiac operations. A core laboratory independently assessed all intraprocedural and 90-day transesophageal echocardiograms. Sixty patients (37 men), aged 33 to 86 years, enrolled. The mean LAA application time was 27 seconds. Transesophageal echocardiograms at 90 days were available in 54 patients, and no leaks were detected. The residual LAA cavity exceeded 6 mm in 5 patients. One delivery device failed to close, and an adjunctive suture was required to complete LAA exclusion. One patient required adjunct sutures at a small tear site related to manual manipulation after fastener application., Conclusions: The study demonstrated safety and efficacy of this LAA exclusion device, offering an alternative to manual suturing or staples with or without reinforcement., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to compare retrograde with antegrade cerebral protection during acute aortic dissection repair using cerebral oximetry measurements. Fifty consecutive acute ascending aortic dissection repairs were analyzed. Cerebral oximetry data were collected for 41 of 50. Eight patients who had antegrade cerebral protection alone and 29 of 41 had retrograde cerebral protection alone. The per cent change in cerebral oximetry values during deep hypothermic circulatory arrest from baseline and from prearrest values was compared for the two groups using Student t test. The per cent change from baseline for the antegrade patients was: right 13.8 per cent and left -2.5 per cent; the per cent change from baseline for retrograde patients was: right 0.8 per cent and left 0.2 per cent (P values 0.216 and 0.725, respectively). The per cent change from the prearrest value for the antegrade patients was: right -12 per cent and left -15 per cent; the per cent change from prearrest for retrograde patients was: right -15 per cent and left -16 per cent (P values 0.514 and 0.956, respectively). No compelling evidence for an advantage to either antegrade or retrograde cerebral perfusion was detected. Further study with a focus on neurologic outcomes is warranted.

Inflammatory aortic aneurysms (IAAs) are rare and located mainly in the infra-renal abdominal aorta. The ascending aorta has been typically spared from this process. We report on two cases of ascending aortic inflammatory aneurysms and describe the available literature on this rare entity. , (© 2011 Wiley Periodicals, Inc.)

Background: Porcine bioprosthesis (bioroots) are an attractive surgical strategy for ascending aorta and arch replacement. This study evaluated the perioperative and late outcomes using this strategy for proximal aortic aneurysmal disease., Methods: Between March 1998 and November 2009, 170 patients (40% women; median age, 70 years) underwent proximal thoracic aortic replacement using the Freestyle (Medtronics Inc, Minneapolis, MN) bioroot, with graft extension in 149 (87.6%). Aneurysmal etiology included degenerative-atherosclerotic (91.2%), acute dissection (5.3%), and chronic dissection (3.5%); 78% had greater than moderate aortic insufficiency. Surgical procedures were bioroot alone or with aortoplasty (12.3%), bioroot with ascending aortic graft (38.2%), bioroot with hemiarch graft (44.1%), and bioroot with total arch (5.3%). Hypothermic circulatory arrest was required in 49%., Results: The 30-day mortality was 4.7% (n=8). The overall complication rate was 58% (n=100), including stroke (6.5%), renal failure (9.2%), respiratory failure (25.9%), and postoperative bleeding (7.6%). Mean hospitalization was 10.5±7.3 days; 38 were discharged to a rehabilitation facility (23.5%). Predictors of 30-day/hospital death were coronary artery disease (p=0.0003), renal insufficiency (p<0.0001), emergent/urgent procedure (p=0.02), and hypothermic circulatory arrest (p=0.002). The 1-year, 5-year, and 10-year survivals were 90%, 80%, and 35% respectively. Freedom from endocarditis and reoperation was 96% at 1 year and 94% and 95% at 5 years, respectively., Conclusions: Proximal thoracic aortic replacement using a porcine bioroot as part of the repair can be achieved with low perioperative mortality and acceptable late survival in a predominantly elderly population., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The diagnosis of thoracic aortic mobile thrombus (TAMT) is rare and is usually made after debilitating embolic events. The optimal treatment strategy is unknown. We report 14 patients with TAMT and aim to better define the role of early (less than 2 weeks) surgical thrombectomy., Methods: Between February 1996 and February 2010, we treated 14 patients (9 women; aged 32 to 84 years, mean age 51 years) with TAMT. Hypercoagulable disorders or a strong family history of vascular thrombosis, or both, occurred in 9 patients. Diagnosis was made by transesophageal echocardiogram in 6, computed tomography angiography in 7, and digital subtraction angiography in 1. Embolic locations were extremities (n=9), cerebral (n=6), and abdominal (n=6). Aortic thrombi (n=17) locations were ascending/arch (n=7), descending (n=8), and thoracoabdominal (n=2)., Results: All patients were initially treated with heparin and aspirin. Thoracic aortic thrombectomies were performed in 8 patients within 2 weeks of diagnosis: left thoracotomy (n=5), thoracoabdominal (n=1), and median sternotomy (n=2). Left atrial-femoral bypass was used in 5 patients, cardiopulmonary bypass in 2, and no support in 1. Additional procedures were celiac artery (n=1) and left subclavian artery (n=2) thrombectomies. Procedures for embolic complications were performed in 7 patients before aortic thrombectomy. Operative mortality was 0%, with no recurrent embolic events after 24±16 months. One patient had thrombectomy of the ascending aorta and medical therapy with warfarin and aspirin for a second concurrent small thrombus in the descending aorta. One patient presented with multiorgan failure and died shortly after admission. Six patients treated medically were discharged on a regimen of oral warfarin and aspirin (14±11 months follow-up), with 2 fatal recurrent embolic events within 6 weeks (p=0.09)., Conclusions: Thoracic aortic mobile thrombus is rare and is commonly associated with morbid thromboembolic events. In our experience, early surgical aortic thrombectomy had a low operative risk and may prevent fatal recurrent embolic events., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: A new device has been developed for occlusion of the left atrial appendage (LAA). Previous investigations have been in the canine model. The canine atrial appendage does not vary in size and shape as much as the human. The goal of this study was to investigate band occlusion of right atrial appendages in the pig model, which are more broad based., Methods: The right atrial appendages of six pigs were approached through a right thoracotomy. An expandable polyester fabric-covered silicone band was placed on the appendage. The animals were evaluated at the time of band placement with fluoroscopy, contrast injection, and in three animals, echocardiography. After one week, the animals were again evaluated with fluoroscopy. The animals were sacrificed at 12 weeks., Results: Bands were placed without complication at the base of all six appendages. All appendages were effectively occluded and all bands remained at the appendage base. The healed atrial surface was consistently smooth and devoid of thrombus., Conclusions: Occlusion of a broad-based appendage as seen with human LAA is feasible with this novel band technique.

We describe a case of acute cardiac failure in a patient involved in a motor vehicle accident. A diagnosis of acute mitral regurgitation and left atrioventricular disruption was made with transesophageal echocardiography. Successful repair was performed using the mitral valve leaflets to patch the disruption followed by valve replacement.

Background: The goal of this study was to obtain physiologically significant increases in peak left ventricular (LV) systolic pressure and stroke volume with latissimus dorsi muscle (LDM) stimulation in cardiomyoplasty (CMP). We hypothesized that preserving LDM integrity by vascular delay and intermittent stimulation would significantly increase LDM cardiac assistance., Methods: In 4 control dogs and 12 dogs that had undergone a vascular delay (VD) procedure, LV dysfunction was induced by intracoronary microsphere injections. Cardiomyoplasty surgery was performed 14 days later, followed by progressive LDM conditioning. In the control dogs and in 6 of the VD dogs, the LDM was stimulated 24 hours per day (VD plus constant stimulation [CS]). In the other 6 VD dogs, LDMs were stimulated on a daily schedule of 10 hours on and 14 hours off (VD plus interrupted stimulation [IS]). Latissimus dorsi muscle stimulated beats were compared with nonstimulated beats 9 weeks later., Results: In the control dogs, LDM stimulation had minimal effects. In VD + CS and VD + IS, LDM stimulation increased peak LV pressure, stroke volume, stroke work, and stroke power (p < 0.05). However, these changes were greater in the VD + IS group, in which LDM stimulation increased peak aortic pressure by 17.6 +/- 1.7 mm Hg, peak LV pressure by 19.7 +/- 1.1 mm Hg, peak positive LV dp/dt by 398 +/- 144 mm Hg per second, stroke volume by 5.1 +/- 0.7 mL, stroke work by 10.9 +/- 0.9 gm.m, and stroke power by 122.7 +/- 11.6 gm.m per second (p < 0.05 compared with VD + CS). Quantitative morphometric analysis showed minimal LDM degeneration in the VD + IS group (7.5% +/- 1.1%), and VD + CS group (10.5% +/- 4.5%) compared with the control group (29.5% +/- 4.5%, p < 0.05)., Conclusions: VD and IS considerably increased the LV assistance with LDM stimulation. Further studies of this combined approach to CMP should be planned.

A common concern in cardiomyoplasty is whether latissimus dorsi muscle (LDM) stimulation impairs diastolic function. This study determined the time course of left ventricular (LV) contraction and relaxation and their relationship to the diastolic function. Ten mongrel dogs underwent vascular delay of the left latissimus dorsi muscle 2 weeks before cardiomyoplasty. Fourteen to 18 days later, the effects of LDM stimulation were evaluated. Our study demonstrated that LDM stimulation significantly increased peak LV systolic pressure (131.3 +/- 7.5 to 152.0 +/- 7.5* mm Hg), +dP/dt (1585 +/- 151 to 2088 +/- 176 x mm Hg/s), stroke volume (10.8 +/- 1.5 to 13.8 +/- 1.9* ml), stroke work (17.2 +/- 2.7 to 25.6 +/- 3.8* gm x m), and peak aortic flow (4751 +/- 698 to 6712 +/- 926* ml/min), and significantly decreased the pre-ejection time (113.9 +/- 12.6 to 92.3 +/- 7.8* ms) and total systolic time (366.0 +/- 26.9 to 333.6 +/- 21.3* ms) (*p < 0.05). As for diastolic function, LDM stimulation decreased -dP/dt (-1462 +/- 116 to -1781 +/-116* mm Hg/s) and tau (64.0 +/- 6.1 to 52.1 +/- 2.9* ms). The diastolic filling time (Tdf) was significantly longer (177.9 +/- 17.6 to 213.7 +/- 18.7* ms) during the beat immediately after LDM stimulation. These changes reflected an overall stronger contraction and faster relaxation. Our results imply that with vascular delay, stimulation of LDM not only assists systolic function but also improves diastolic function in cardiomyoplasty.

Objectives: Dynamic cardiomyoplasty (CMP) as a surgical treatment for chronic heart failure improves functional class status for most patients. However, significant hemodynamic improvement with latissimus dorsi muscle (LDM) stimulation has not been consistent. The current protocols do not allow early LDM stimulation after CMP surgery. We hypothesized that vascular delay of LDM would increase myocardial assistance after CMP and allow early (48-h) LDM stimulation after CMP., Methods: Mongrel dogs (n = 24) were divided in four groups: 1) controls (n = 6), single-stage CMP; 2) Group ES (n = 6), single-stage CMP with early LDM stimulation beginning 48 h, postoperatively; 3) Group VD (n = 6), vascular delay of the LDM followed by CMP without early LDM stimulation, and 4) Group VDES (n = 6), vascular delay of LDM (14-18 days), followed by CMP with early stimulation (48 h postoperatively). Two weeks after CMP, global cardiac dysfunction was induced by injecting microspheres into the left coronary artery. LDM-assisted (S) beats were compared with nonstimulated beats (NS) by measuring aortic pressure (AoP), LV pressure, aortic flow, and by calculating first derivative of LV contraction (+/-dP/dt), stroke volume (SV), and stroke work (SW)., Results: In ES, LDM stimulation had no effect on the hemodynamic parameters. In the other groups, LDM stimulation significantly (p < 0.05) increased AoP, LVP, dP/dt, SV, and SW. However, these increases were much larger in VD and VDES. In VD, LDM stimulation increased peak AoP by 21.5+/-3.8 mm Hg, LVP by 22.1+/-4.1 mm Hg, dP/dt by 512+/-163 mm Hg/sec, SV by 10.4+/-2.3 mL, and SW by 22.1+/-5.4 g/m(-1). Similarly, in VDES, LDM stimulation increased peak AoP by 24.1+/-4.7 mm Hg, LVP by 26.2+/-4.3 mm Hg, dP/dt by 619+/-47 mm Hg/sec, SV by 6.5+/-0.7 mL, and SW by 16.7+/-4.1 g/m(-1)., Conclusions: In dogs with global LV dysfunction, CMP after vascular delay resulted in a significant improvement in hemodynamic function measured 2 weeks after surgery. This improvement was not provided by single-stage CMP with or without early stimulation. Vascular delay of the LDM before surgery may play an important role for early benefit after CMP, shorten the overall muscle training period, as well as increase hemodynamic response to LDM stimulation.

Objectives: In standard single stage cardiomyoplasty (CMP), the latissimus dorsi muscle (LDM) is not preconditioned prior to surgery. We hypothesized that latissimus dorsi preconditioning by vascular delay or by chronic electrical stimulation would result in an improved LV hemodynamic function early (14 days) after CMP., Methods: Mongrel dogs had preconditioning of the latissimus dorsi by a vascular delay procedure followed by CMP 14-18 days later (group I VD). Dogs in group II underwent 4 weeks of chronic stimulation (CS) of the latissimus dorsi (2 V/30 Hz, six bursts/min) followed by CMP. The latissimus dorsi muscle was fully stimulated from 48 h after cardiomyoplasty in both groups (2 V/30 Hz, three bursts/min). Two weeks after myoplasty, injecting 2.0-3.0 x 10(5) 90 microm latex microspheres in the left main coronary artery induced global cardiac dysfunction. Hemodynamic function was then evaluated for latissimus dorsi muscle assisted (S) beats and non-stimulated beats (NS) in each group by measuring peak systolic aortic pressure (AOP), left ventricular pressure (LVP) and end diastolic pressure (LVEDP), and by calculating maximum and minimum dP/dt., Results: Dogs with vascular delay of the latissimus dorsi showed a marked increase for all hemodynamic indices (AOP: 23.9+/-2.5%, LVP: 23.5+/-2.2%, max dP/dt: 49.4+/-3.3%) for LDM assisted (S) beats compared to non-stimulated beats (P < 0.001). Animals with chronic electrical training did not demonstrate a significant increase in any hemodynamic parameter with LDM stimulation., Conclusion: Preconditioning the LDM may play an important role in providing early cardiac assistance in CMP. Preconditioning the LDM with vascular delay resulted in improving performance of the LDM with consistent increases in LV hemodynamics. This was not observed after preconditioning with chronic electrical stimulation. Vascular delay of the latissimus dorsi can significantly improve muscle performance in CMP and could provide hemodynamic assistance early after surgery.

Cardiomyoplasty (CMP) has been considered as a possible treatment for patients with heart failure. Symptomatic improvements occur almost uniformly among survivors with CMP, but changes in left peak ventricular systolic pressure (PVSP) and stroke volume vary in patients. This study examined whether there is variability present shortly after cardiomyoplasty surgery. Cardiomyoplasty was performed in 11 mongrel dogs with normal ventricular function. Nine to twelve days after CMP, left ventricular (LV) function was evaluated by simultaneously measuring LV volume (conductance catheter) and pressure (Millar catheter). The latissimus dorsi muscle (LDM) was stimulated synchronously with ventricular systole in a ratio of 1:4 to 1:7 to avoid muscle fatigue. Data were analyzed on a beat by beat basis. The PVSP, and maximum dP/dt (+dP/dt) increased, but the absolute value of minimum dP/dt (-dP/dt) decreased in stimulated beats in 7 dogs while 4 dogs did not respond. The net changes in stimulated beats versus nonstimulated beats of PVSP were 6.1 +/- 1.8 mm Hg (4.3%), of stroke work was 4.5 +/- 1.9 gm x m (29.5%), of +dP/dt was 185 +/- 47 mm Hg/s (8%), and of -dP/dt was 168 +/- 43 mm Hg/s (7.8%) (p < 0.05) for all these net changes in the responding group while these variations were not significant in the nonresponding group. From the results of our study, active LDM assist improves left ventricular systolic function, occurring in only 7 of 11 experiments. This improvement is inconsistent and varied individually. The integrity of the LDM, tightness of wrapping, and adhesions might contribute to the variability which is present early after surgery and before the LDM is converted into a fatigue resistance muscle.

This study examined the effects of cardiomyoplasty with vascular delay on canine normal and depressed left ventricular (LV) function. To improve viability of the latissimus dorsi muscle (LDM), vascular delay was performed 2 weeks before cardiomyoplasty in 10 mongrel dogs. Two weeks after cardiomyoplasty, LV function was evaluated by simultaneously measuring LV and aortic pressure, and aortic flow. The LDM was stimulated at a ratio of 1:4-1:7 synchronously with ventricular systole. Microspheres (90 mu) were sequentially injected into the left coronary artery to depress LV function. Data were acquired and analyzed on a beat to beat basis. Results were as follows: LDM stimulation significantly augmented LV systolic pressure (LVSP) from 138 +/- 2 to 161 +/- 2* mmHg, the peak rate of change of LV pressure (+dP/dt) from 1888 +/- 46 to 2584 +/- 43* mmHg/sec, aortic systolic pressure (AoSP) from 140 +/- 2 to 159 +/- 2* mmHg, stroke volume (SV) from 11.2 +/- 0.3 to 13.3 +/- 0.3* ml, stroke work (SW) from 19 +/- 1 to 26 +/- 1* gm.m, peak aortic flow (P Qa) from 5542 +/- 142 to 7190 +/- 161* ml/min, and decreased -dP/dt from -1683 +/- 31 to -1689 +/- 49* mmHg/sec (* = p < 0.05). Microsphere injections depressed LV function, but did not affect the magnitude of the net changes between stimulated and nonstimulated beats. However, the percent changes significantly increased. Preconditioning of LDM with vascular delay augments cardiac function in LDM assisted beats. This improved performance was present in both normal as well as depressed LV function groups. Thus, investigations of cardiomyoplasty may not necessarily require a model of severe myocardial dysfunction. Vascular delay offers an important preconditioning method of LDM to augment cardiac function in cardiomyoplasty.

Cardiomyoplasty is a new surgical treatment for heart failure in which the patient's latissimus dorsi muscle (LDM) is isolated, wrapped around the heart, and electrically stimulated to provide cardiac assistance. At present, long term stimulation of the LDM is achieved with intramuscular electrodes, which produce minimal nerve damage. This study examined the use of epimysial electrodes by measuring the epimysial lead characteristics during a four-week LDM training. Lead resistance started at 463 +/- 41 omega after implantation, decreased during the following week (251 +/- 16 omega), and remained less than the initial value during the last three weeks (weeks two: 282 +/- 19 omega and week four: 341 +/- 28 omega). The recruitment properties were similar to nervecuff electrodes: low threshold voltages (week one: 0.75 +/- 0.12, week two: 0.90 +/- 0.33, week four: 0.52 +/- 0.10 V) and a very steep recruitment curve with low saturation voltages. Histological examination revealed normal muscle fibers with no inflammatory response. Epimysial leads may be more convenient for most surgeons because the design does not require any free-dissection of the nerve nor guiding a needle around the nerve with the risk of perforating vessels or nerve branches. These results indicate that epimysial leads are worthy of further investigation.

Interferons have multiple immunologic effects. One such effect is the activation of expression of cell surface antigens. Interferon alpha/beta enhance expression of class I but not class II histocompatibility antigens. Contradictory information has been published regarding the effect of interferon-alpha/beta administration in patients with kidney transplantation. In a model of rat heart transplantation we demonstrated that administration of interferon-alpha/beta accelerated rejection in a dose-dependent fashion in the absence of maintenance cyclosporine. Animals treated with maintenance cyclosporine had evidence of increased rejection at 20 days that was resolved completely at 45 days with cyclosporine alone.

We evaluated computerized quantitative electroencephalography for the intraoperative detection of cerebral dysfunction. The quantitative electroencephalogram was recorded continuously during 96 myocardial revascularizations involving hypothermic cardiopulmonary bypass using Cerebrovascular Intraoperative MONitor (CIMON) software. CIMON relies on an adaptive statistical approach to detect subtle, but clinically relevant, changes in electroencephalographic activity indicative of cerebrocortical dysfunction. Relative (percent of total) low-frequency (1.5 to 3.5 Hz) power was chosen as the single quantitative electroencephalographic descriptor because it is an established hallmark of cortical dysfunction and is surprisingly insensitive to moderate changes in body temperature and level of opioid anesthesia. Reference values for this measure were established for each patient after anesthetic induction before sternotomy. The large sample variance often seen in low-frequency power was dramatically decreased by using log-transformed data and allowing each patient to serve as his own control. Quantitative electroencephalographic changes in standard deviation units or z-scores were determined from the individualized reference self-norm. Prolonged (greater than 5 minutes) and statistically significant (greater than 3 standard deviation) focal increases in relative low-frequency power were temperature-corrected to determine a standardized cerebrocortical dysfunction time at 37 degrees C. (CDT37). In phase I (n = 48), this objective quantitative electroencephalogram-based numeric descriptor was used to predict neuropsychologic outcome. These CDT37 greater than 5-minute episodes occurred 38 times in 19 patients. The quantitative electroencephalogram-based descriptor predicted the occurrence of such disorientation (n = 14 or 29%) with a 68% false positive rate but only an 8% false negative rate. Since these intraoperative quantitative electroencephalographic episodes were often (19/38) associated with low (less than 50 mm Hg) pump pressures, phase II (n = 48) sought to correct the quantitative electroencephalographic abnormality and prevent postoperative disorientation by appropriate increases in cerebral perfusion. Although the number of episodes of quantitative electroencephalographic abnormality was similar (n = 31) in phase II, these ischemic events disappeared after prompt elevation of perfusion pressure. The phase II disorientation rate fell significantly (p less than 0.002) to 4%. Thus statistically significant increases in low-frequency electroencephalographic relative power persisting for a temperature-corrected duration of 5 minutes or more are a reliable means of alerting the surgical/anesthesia team to the presence of cerebrocortical dysfunction and provide a rational and objective basis for corrective intervention. This form of electroencephalographic monitoring appears to offer an opportunity for the timely correction of perfusion abnormalities or the administration of cerebroprotectant compounds.

Determination of defibrillation thresholds (DFTs) and implantable cardioverter defibrillator (ICD) testing requires repeated inductions of ventricular fibrillation (VF) and defibrillation attempts using known energy outputs. Little is known about the individual and cumulative effects of repetitive brief episodes of VF and hypoperfusion on cerebral function. The potential clinical utility of quantitative electroencephalographic (QEEG) monitoring during intraoperative ICD testing, by using processed 19-channel EEG (0.5-35 Hz bandwidth), was examined in ten anesthetized patients, five males and five females (mean age 62 +/- 10 years), who underwent ICD implantation and testing. Ischemic QEEG patterns were defined as those with a 3 standard deviation increase (P less than 0.01) in absolute delta (1.5-3.5 Hz) power persisting for greater than or equal to 2.5 minutes. The majority (80%) of the VF episodes (70) were accompanied by QEEG "slowing" (doubling of the pre-VF low frequency delta waves amplitude). All the patients (5/5) experiencing greater than 6 VF episodes showed a statistically significant increase in the low frequency amplitude. In contrast, this EEG abnormality was apparent in only one of five patients experiencing less than 6 VF episodes. These results suggest a cumulative QEEG depression associated with ICD testing. QEEG may provide an objective means for establishing an individualized upper safe limit of DFT testing and the total number of induced VF episodes.

In 51 patients who required automatic implantable cardioverter defibrillator implantation without additional cardiac procedures, the lead system was implanted using a lateral thoracotomy approach, with complete muscle sparing in the last 24 patients. Exposure was excellent and allowed repositioning of leads for optimal defibrillation thresholds in 18 patients. Five of 19 patients who had previously undergone intrapericardial procedures required intrapericardial dissection for lead placement to provide satisfactory defibrillation thresholds. There were no intraoperative deaths or infarctions. The 30-day mortality rate of 3.9% was comparable with those in other series, and the use of muscle-sparing techniques and supplemental epidural anesthesia prevented pulmonary complications or the need for prolonged ventilatory support. We favor a muscle-sparing lateral thoracotomy incision for automatic implantable cardioverter defibrillator insertion, particularly in patients with a history of previous intrapericardial procedures.

Continuous arteriovenous hemofiltration (CAVH) is a simple extracorporeal treatment for fluid overload, electrolyte imbalances, and removal of uremic toxins. The CAVH technique can be initiated rapidly and allows effective fluid removal without compromising cardiovascular status. This article describes two illustrative cases where CAVH was used to treat fluid overload accompanying in one case cardiogenic shock and in the other case septic shock. CAVH may have contributed to the removal of sepsis-related vasodilators as well as excess fluid. This therapy is an attractive alternative to hemodialysis in the critical care setting and may be the treatment of choice in hemodynamically unstable patients.

One thousand two hundred fourteen percutaneous transluminal coronary angioplasties were performed over a 38-month period. Sixty patients required immediate emergency coronary artery bypass grafting after angioplasty failure; 7 of these had evidence of acute myocardial infarction before angioplasty and were excluded from the study. Of the 53 patients remaining, 27 (51%) had electrocardiographic and enzyme evidence of postoperative myocardial infarction. Two patients died (4%), and 10 had postoperative complications (19%). No statistical significance was noted comparing age, sex, incidence of prior myocardial infarction or myocardial dysfunction, time for revascularization, or average number of grafts completed in those with single-vessel (n = 21) versus multiple-vessel (n = 32) coronary artery disease. Postoperatively, those with multiple-vessel disease required intraaortic balloon pump support (p = 0.06) and antiarrhythmic medications more frequently than single-vessel patients (p less than 0.01) and had a higher complication rate (p less than 0.05). Although not reaching statistical significance, the data also suggest a higher death and postoperative myocardial infarction rate in patients with multiple-vessel disease. Emergency coronary artery bypass grafting after failed percutaneous transluminal coronary angioplasty carries a higher morbidity and mortality than elective coronary artery bypass grafting, particularly for patients with multiple-vessel coronary artery disease.

Patients with recurrent ventricular tachycardia or a history of a sudden cardiac death episode and ventricular tachycardia inducible in the electrophysiology laboratory have a high incidence of recurrence and a high mortality despite medical therapy. Map-guided endocardial resection has improved treatment results, but is associated with a 10-30% failure rate. In our initial experience with endocardial resection (Group I) we incurred a 30% treatment failure rate. In the present study we have found the addition of sequential intraoperative mapping and routine use of cryotherapy (Group II) improved our results of ventricular tachycardia control without significant additional morbidity or mortality.

The internal mammary artery is the conduit of choice for coronary artery revascularization. Wide angulation between the left anterior descending coronary artery and obtuse marginal branches and the diseased segments of the coronary arteries can prevent optimal positioning of the left internal mammary artery for sequential anastomoses for revascularization. We describe a technique using a segment of the left internal mammary artery as a free graft sewn in an end-to-side fashion to the in situ left internal mammary artery. This approach has technical and physiological advantages over previously described techniques.

Most penetrating right ventricular injuries require simple suture repair, but more extensive injury or rupture of the right ventricle may not be amenable to this method. We have developed an approach to the problem and a technique for repair. Compression of the area with early institution of cardiopulmonary bypass will result in decompression of the right ventricle and preservation of perfusion, preventing profound hypotension. Coverage with an onlay autologous tissue patch provides hemostatic control of the defect without compromising ventricular function. Reinforcement with omentum or muscle flap can give additional protection when risk of infection is present. Application of these principles can be lifesaving and insure good cardiac function despite massive injury to the right ventricular myocardium.

Arterial wall infections are rare after orthotopic heart transplantation. An infected pseudoaneurysm developed in a patient at the site of aortic cannulation 6 months after his transplant procedure. Debridement of the infected tissue necessitated removal of a major portion of the aortic arch and reconstruction with in situ placement of a synthetic polyester (Dacron) graft. In situ placement of grafts is a controversial form of treatment of arterial wall infections in other portions of the aorta. Because of the extensive nature of the infection and its site, no other option was available. This patient represents the first reported case of successful aortic arch replacement for an infected pseudoaneurysm after orthotopic heart transplantation.

Repair of atrial septal defect (ASD) remains a high-benefit, low-risk procedure due to technologic improvements. From July 1981 to December 1986, 35 females (age, 7 months to 28 years) had repair of ASD; 20 by right thoracotomy and aortic cannulation (group 1) and fifteen by median sternotomy (group 2). In general, right thoracotomy was applied to patients with secundum ASD two years or older and without associated lesions, while median sternotomy was applied to patients with ostium primum lesions and/or associated lesions. Patients or their families perceived the cosmetic results superior to the right thoracotomy approach over the median sternotomy. We feel that a right thoracotomy and aortic cannulation is effective in females (2 years and older) with secundum ASD for a superior cosmetic result over median sternotomy. However, females with ostium primum and/or associated lesions should undergo median sternotomy for better cardiac access and safety.

From August 1984 to August 1986, 75 patients with end-stage heart disease and cardiac failure were evaluated. Twenty-five patients received orthotopic cardiac transplants from donors as far away as 1300 miles with an ischemic time of less than 4 hours. Seventeen of 25 patients are alive 3-24 months after transplantation. Evidence of rejection was seen in each patient. Twelve patients had mild, easily controlled rejection; 13 patients had severe rejection averaging 3.1 episodes per patient. The initial immunosuppressive regimen included cyclosporine and prednisone. To decrease complications related to high dose steroids, azathioprine has recently been added to our maintenance regimen to lessen steroid requirements. Acute rejection episodes were treated with 500-1000 mg of methylprednisolone for 3 days; antithymocyte globulin or the murine monoclonal antibody, OKT3, was added for severe or resistant rejection episodes. Three patients died of rejection, and two patients died of infection. Seventeen of 18 survivors are New York Heart Association (NYHA) Class I; 15 patients have returned to employment or full activity. Because of new developments in support of transplant candidates and treatment of complications, as well as the introduction of cyclosporine, orthotopic cardiac transplantation has become an effective treatment for end-stage heart disease.

The Pierce-Donachy ventricular assist device (VAD) was used as an attempted bridge to orthotopic cardiac transplantation in 12 patients aged 13 to 55 years. Ischemic (4 patients), dilated (4 patients), acute viral (1 patient), postpartum (1 patient), and hypertrophic cardiomyopathy (1 patient), along with a failed transplant (1 patient), were the causative factors of end-stage cardiomyopathy in these patients. All patients were candidates for orthotopic cardiac transplantation but sustained refractory cardiogenic shock (cardiac index less than 2 L/min/m2). Left VADs were placed in all patients; 7 also required right VADs. Four patients died of hemorrhagic complications less than 24 hours after VAD insertion. Ventricular assist device stabilization was successful in 8 patients and support ranged from eight hours to 64 days. Seven patients successfully underwent orthotopic cardiac transplantation. One died postoperatively of hemorrhagic complications, 6 were discharged from the hospital, and 1 patient died at 3 months of cytomegalovirus infection. Five patients are long-term survivors. The Pierce-Donachy VAD is an effective means for supporting critically ill patients with end-stage cardiomyopathy and cardiogenic shock before orthotopic cardiac transplantation. Death is related to hemorrhagic, rather than infectious or thromboembolic, complications. Patients successfully stabilized with the VAD can undergo orthotopic cardiac transplantation with acceptable mortality and morbidity rates.

The results of orthotopic cardiac transplantation have improved dramatically since the early experiences in the late 1960s. After almost 20 years of research and experience and the introduction of cyclosporine, 1 and 5 year survival rates are now 80 percent and 60 percent, respectively. The number of potential recipients far exceeds that of available donors, which is the limiting factor in cardiac transplantation. Complications related to immunosuppressive therapy remain significant, and despite decreased length of hospitalization, costs remain high. The majority of patients have good functional rehabilitation and are free of cardiac symptoms. Moreover, orthotopic cardiac transplantation has finally become a therapeutic treatment of end-stage heart disease.

Twenty-eight patients with malignant ventricular arrhythmias were treated with the automatic implantable cardioverter-defibrillator (AICD) in a 14-month period. Thirteen patients were resuscitated from a ventricular fibrillation (VF) episode. Fifteen patients presented with ventricular tachycardia (VT) refractory to medical therapy. The etiology was coronary artery disease in 23 of 28 patients (82%), dilated cardiomyopathy in 2 of 28 patients (7%), sarcoidosis in 2 of 28 patients, and 1 patient in 28 had lupus erythmatosis. The mean left ventricular ejection fraction was 29%. A total of 27 of 28 patients (96%) patients had inducible ventricular tachycardia using programmed stimulation. The patients considered for AICD implant failed a mean of 3.6 antiarrhythmic drugs. Rate counting and defibrillating leads were inserted through a lateral thoracotomy in 17 patients and a mediansternotomy incision in 11 patients in conjunction with another cardiac procedure in 10 patients. The generators were positioned in a subcutaneous pocket beneath the left costal margin. There were no operative deaths. The mean follow-up was 6.7 months (range 1 to 14) with no VT/VF deaths in patients with defibrillators. The study demonstrated that AICD is an effective device for prevention of sudden cardiac death.

Mechanical support of the failing heart is becoming an increasingly useful tool for bridging to cardiac transplantation and for recovery of the natural heart. Several options exist for cannulation sites during the implantation of the heterotopic prosthetic ventricles. These options include the left atrial appendage, the left ventricular apex, the interatrial groove, and the left atrial roof. The indications, contraindications, advantages, disadvantages, and surgical technique for each option are described. Operation of the drive console and postoperative care are also discussed.

In an experimental study, 26 mongrel dogs were treated with alloxan (50 mg per kilogram) to induce fasting hyperglycemia and diabetes. The animals were randomly subdivided into two groups, one of which received 100 mg of propranolol in divided doses for two weeks. The animals underwent sternotomy and were placed on total cardiopulmonary bypass. After aortic cross-clamping, each animal received 10 ml per kilogram of cardioplegic solution. Two different solutions were used, a standard hyperkalemic solution and a high-energy glucose-insulin-potassium (GIK) substrate. Baseline studies were made on the four groups of diabetic animals. Animals given potassium cardioplegia but no propranolol showed statistically significant decreases in cardiac index, heart rate, mean arterial pressure, and minute left ventricular stroke work index after bypass. In contrast, animals given GIK cardioplegia but no propranolol showed no changes in any of these measurements. Animals administered propranolol and potassium cardioplegia experienced decrease in mean arterial pressure from 77.5 +/- 14.1 mm Hg before bypass to 57.5 +/- 17.8 mm Hg after bypass. A similar reduction occurred in animals given propranolol and GIK cardioplegia. However, in this group, the cardiac index increased from 1.78 +/- 0.38 L/min/m2 before bypass to 2.96 +/- 0.73 L/min/m2 after bypass (p less than .006). Similarly, the minute left ventricular stroke work index increased after bypass in these animals. This study demonstrates the protective effect against myocardial ischemia of the addition of substrate to the cardioplegic solution in diabetic animals subjected to aortic cross-clamping during cardiopulmonary bypass, one group receiving propranolol and one group not receiving it.

The authors reviewed the postoperative frontal chest radiographs of 77 patients given aortic or mitral prostheses in one year and evaluated the criteria for distinguishing between the two: position (cephalocaudal or transverse), orientation (vertical or horizontal), orifice (en face or in profile), direction of flow through the valve (toward the cardiac apex or ascending aorta), and information given on the consultation form. 91% of patients had at least one form containing incomplete or incorrect information. Direction of flow appears to be the best criterion, being discernible in all Starr-Edwards and most Björk-Shiley prostheses; orifice and orientation are considerably less reliable, while position is totally unreliable.

OKT3 is a murine monoclonal antibody that recognizes the T3 surface antigen present on mature T cells, and it has been used to successfully treat renal allograft rejection. We report our experience with OKT3 in the treatment of cardiac allograft rejection. Eight patients with endomyocardial biopsy evidence of moderate or severe rejection were given fourteen daily intravenous treatments of OKT3. Six of the eight patients had complete recovery following OKT3 therapy; one required additional steroid therapy for recurrence and one patient failed to respond. Five of the six patients with a complete response have experienced no further rejection (mean follow-up 437 days). Adverse reactions to OKT3 were common early in the treatment course, but were well tolerated. We concluded that OKT3 is a safe and effective treatment of cardiac allograft rejection and that a majority of patients experience long-term rejection-free periods.