Effect of surrogate tolerogenesis on the vascular rejection of pig heart xenografts.

BACKGROUND: Organ xenografts are fulminantly rejected by antibody-mediated vascular rejection. Surrogate tolerogenesis (ST), the induction of tolerance within the donor, is effective with aorta xenografts. This preliminary study assesses the effect of ST on preformed antibodies and rejection of porcine heart xenografts. METHODS: Tolerance to the donor pig was induced by infusing recipient marrow into fetal pigs. Later, pig splenocytes were transfused and heterotopic pig hearts transplanted using chimeric or nonchimeric pigs. Anti-pig antibodies were assessed. RESULTS: With ST alone, xenografts developed cellular rejection at 4-6 days, whereas control grafts developed vascular rejection at 3-4 days (cellular vs. vascular, P<0.03). There was a reduction in preformed antibodies (P<0.03). ST combined with moderate cyclosporine prevented rejection at 9+ and 25 days in sensitized recipients compared with vascular rejection at 0.5-2 days for controls (P<0.07). CONCLUSIONS: ST seems to provide protection against vascular rejection. The cellular rejection seems sensitive to cyclosporine.

Facilitated coronary anastomosis using a nitinol U-Clip device: bovine model.

OBJECTIVE: The coronary anastomosis is the most difficult part of the coronary bypass procedure, particularly when using a minimally invasive technique. Methods to facilitate coronary anastomosis will make the minimally invasive approach to coronary bypass feasible. We sought preclinical validation and testing of the design and efficacy of a self-closing penetrating clip that can be used to facilitate the creation of graft-to-coronary end-to-side anastomosis. METHODS: The nitinol U-Clip device (Coalescent Surgical, Inc, Sunnyvale, Calif) was used in 13 consecutive calves (63-118 kg). In each animal, the device was (1) used to create an anastomosis of the right internal thoracic artery to a coronary artery with the heart beating and (2) compared to polypropylene suture when used to repair two carotid arteriotomies. Intraoperative, 1-week, 8-week, and 26-week postoperative angiograms and detailed histopathologic examinations were used to evaluate anastomotic patency and healing characteristics. RESULTS: The nitinol U-Clip device successfully created right internal thoracic artery-coronary artery anastomoses and repaired carotid arteriotomy sites in 13 consecutive calves. The clip was precisely placed by means of the integrated suture and needle in a fashion similar to that used for conventional suture. The clip met design specifications by reliable release and automatic closure, thereby eliminating knot tying and assisted suture management. At the time of harvest, angiography showed widely patent coronary anastomoses (FitzGibbon grade A criteria, n = 13) and carotid arteriotomy repair sites (n = 13). Histopathologic evaluation confirmed normal healing with smooth circumferential neointimal resurfacing at the anastomotic and repair sites. CONCLUSIONS: The nitinol U-Clip design and function was validated in the formation of bovine coronary anastomoses on the beating bovine heart with excellent graft patency and healing characteristics. The nitinol U-Clip device tests favorably when compared with conventional sutures in carotid artery repair.

Successful survival of primates receiving transplantation with "dead," nonbeating donor hearts.

A paucity of donor organs is the principal limitation in human heart transplantation. Prompted by our short-term studies of reanimating "dead" donor hearts in sheep, we applied the same reperfusion modifications in juvenile baboons to determine human applications in an anoxic arrest model (as occurs when non-brain-dead patients are extubated and allowed to die). Ten juvenile baboons (mean weight 3.6 kg) were studied. Five baboons were used as donors. After being anesthetized, donors were pretreated with methylprednisolone (Solu-Medrol), 50% dextrose, nifedipine, and prostaglandin E1 and then paralyzed and extubated. Donors became pulseless at 7 +/- 1 minutes and had electric arrest 9 to 18 minutes after paralysis. The five donors were left undisturbed and warm for 15, 22, 30, 30, and 31 minutes, respectively, after asystole. They were then given 250 ml of 4 degrees C Roe's crystalloid cardioplegic solution via the aortic root and the hearts were explanted into iced Euro-Collins solution. Five baboons served as recipients. After donor harvest, recipients were placed on cardiopulmonary bypass, given prostaglandin E1, and cooled to 18 degrees C; circulatory arrest was instituted and the recipient's heart excised. The donor heart was transplanted in an orthotopic position. Before reinstitution of bypass, 250 ml of terminal leukocyte-depleted blood cardioplegic solution was given, then bypass was restarted and the hearts were reperfused for 60 minutes. All animals were weaned from bypass without the use of inotropic agents. All animals were extubated within 2 to 4 hours after bypass and received standard immunosuppression. Peak creatine kinase MB/total creatine kinase ratio was 0.2% +/- 0.2%. Postoperative ejection fractions by echocardiography were 75% to 80% (mean 76%). Animals survived 1, 9, 13, 16, and 34 days, with three deaths caused by acute rejection and one each by stroke and diarrhea/dehydration. Pathologic findings showed no areas of fibrosis or ischemic damage. We conclude that successful reanimation and engraftment can be achieved with the use of the asystolic primate heart; this work suggests that human application is realistic and could greatly expand the donor pool.

Percutaneous transluminal coronary angioplasty failures in patients with multivessel disease. Is there an increased risk?

In recent years, there has been a nationwide trend toward performing percutaneous transluminal coronary angioplasty in patients with multivessel coronary artery disease. The clinical course of 57 consecutive patients who required emergency first-time coronary artery bypass grafting operations were reviewed to assess for difference in outcome between the 28 patients (49%) with single-vessel disease and the 29 patients (51%) with multivessel disease. The two groups were similar in preoperative characteristics except for a higher proportion of chronic obstructive pulmonary disease in the patients with multivessel disease (p = 0.03). Twice as many patients with multivessel disease were in shock (single-vessel disease = 4 [14%], multivessel disease = 8 [28%], p = not significant) en route to the operating room and significantly more patients with multivessel disease required on-going cardiopulmonary resuscitation (single-vessel disease = 0 [0%], multivessel disease = 5 [17%], p = 0.03). Significantly more coronary artery bypass grafts were placed in the patients with multivessel disease (single-vessel disease = 1.5 +/- 0.6, multivessel disease = 2.9 +/- 0.7, p < 0.01), which required longer aortic clamping time (p = 0.02) and cardiopulmonary bypass time (p < 0.01). There were seven postoperative deaths; all but one occurred in patients with multivessel disease (single-vessel disease = 1 [4%], multivessel disease = 6 [21%], p = 0.05). According to multivariate analysis, incremental risk factors of mortality were preoperative shock (p < 0.01), urgent or emergency percutaneous transluminal coronary angioplasty (p = 0.06), and multivessel disease (p = 0.12). Despite a similar incidence of myocardial infarction (single-vessel disease = 8 [29%], multivessel disease = 12 [41%], p = not significant), patients with multivessel disease had a higher incidence of cardiac morbidity (single-vessel disease = 4 [14%], multivessel disease = 11 [38%], p = 0.04) and noncardiac morbidity (single-vessel disease = 4 [14%], multivessel disease = 12 [41%], p = 0.02). By multivariate analysis, incremental risk factors of morbidity were preoperative shock (p < 0.01), multivessel disease (p = 0.02), and ejection fraction < 50% (p = 0.07). In the subset of patients with multivessel disease, preoperative shock, ejection fraction < 50, and an age of 60 years or greater were associated with higher morbidity and mortality. In conclusion, the risk of percutaneous transluminal coronary angioplasty failure is considerably higher in patients with multivessel disease. In certain subsets of patients with multivessel disease, coronary artery bypass grafting would be a safer procedure when compared with percutaneous transluminal coronary angioplasty for initial myocardial revascularization.

Delayed primary repair of intrathoracic esophageal perforation: is it safe?

The management of intrathoracic esophageal perforation with delayed diagnosis is a subject of controversy. Because of the obvious advantages of primary repair as a simple single-stage operation, this technique was preferentially used to treat 18 of 22 consecutive patients with esophageal perforation. These patients were stratified into three groups according to the time interval between perforation and repair: group A, less than 6 hours, five patients (28%); group B, 6 to 24 hours, six patients (33%); and group C, more than 24 hours, seven patients (39%). Group A patients were older (p < 0.05) and group B had fewer iatrogenic perforations (B, 17%; A, 80%; C, 57%, p < 0.1). Additional tissue was used to buttress the repair site in all three groups (A, 3/5 patients, 60%; B, 4/6 patients, 67%; C, 6/7 patients, 86%; p = not significant). In seven patients (39%), a fundic wrap was used to reinforce the site of primary repair. The outcomes of the three groups were analyzed. Group A had the lowest proportion of postoperative leaks (A, 0/4 patients, 0%; B, 4/6 patients, 67%; C, 5/6 patients, 83%; p < 0.05) and postoperative morbidity (A, 2/5 patients, 40%; B, 6/6 patients, 100%; C, 6/7 patients, 86%; p < 0.1). However the increased incidence of leak and morbidity did not lead to an increase in mortality. One death occurred in each group, with an overall mortality of 17% (A, 1/5 patients, 20%; B, 1/6 patients, 17%; C, 1/7 patients, 14%; p = not significant). We conclude that in the era of advanced intensive care capabilities, primary repair of intrathoracic esophageal perforation can be safely accomplished in most patients regardless of the time interval between perforation and operation. Leakage at the suture site is common unless primary repair is carried out without delay. Postoperative leakage, however, is usually inconsequential and does not necessarily result in an adverse outcome.

Current orientation induced by magnetic stimulation influences a cognitive task.

The direction of the current induced by transcranial magnetic stimulation (TMS) over the motor cortex has been observed to influence the threshold and latency of evoked muscle responses. This study investigates the effect of TMS-induced current orientation (ICO) over the prefrontal cortex, on a specific cognitive task (memory-guided saccade). TMS was applied with a figure-of-eight coil, placed at one of eight different orientations over the prefrontal cortex. The most effective ICO was antero-lateral, which is a different optimal ICO from that seen over the hand area of the motor cortex. This demonstrates that ICO can alter the effect of TMS on cognitive functions and that ICO is an independent variable that should not be ignored when designing TMS studies.

Fetal lamb pulmonary hypoplasia: pulmonary vascular and myocardial abnormalities.

Neonatal pulmonary hypoplasia resulting from a congenital diaphragmatic hernia (CDH) produces hemodynamic changes and morphologic abnormalities of the pulmonary vasculature. To characterize the myocardial and pulmonary vascular status of the fetus with pulmonary hypoplasia, we studied four chronically instrumented, near-term fetal lambs with pulmonary hypoplasia, induced by producing a diaphragmatic hernia. We found an elevation in the pulmonary arterial pressure (control, 43.8 +/- 5.9 mmHg; CDH, 58.8 +/- 9.1 mmHg; p < 0.05), an elevation in the systemic arterial pressure (control, 43.8 +/- 0.48 mmHg; CDH, 58.6 +/- 6.7 mmHg; p < 0.05), and an elevation in the pulmonary vascular resistance (control, 0.47 +/- 0.11; CDH, 3.87 +/- 1.9; p < 0.05). In addition, though the total pulmonary blood flow was reduced (control, 83.5 +/- 32.9 mL/min; CDH, 22.2 +/- 17.6 mL/min; p < 0.05), the blood flow reduction was proportional to the reduction in the lung mass (control, 79.8 +/- 28.1 [in flow per 100-g lung weight]; CDH, 85.4 +/- 71.7). The increase in the pulmonary vascular resistance in relation to the unit lung mass (control, 0.55 +/- 0.33; CDH, 0.99 +/- 0.5) was not as pronounced as its increase in relation to the total pulmonary blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiographic recognition of iatrogenic aortic valve leaflet perforation.

BACKGROUND: There is a paucity of literature regarding iatrogenic aortic valve perforation after cardiac operations performed in the vicinity of the aortic valve. This report describes the echocardiographic recognition of iatrogenic aortic valve perforation. METHODS: Among 6 patients who had previously under-gone non-aortic valve cardiac operations, a diagnosis of iatrogenic aortic regurgitation was made by transthoracic two-dimensional echocardiography and Doppler color flow imaging. RESULTS: The location of the aortic valve leaflet perforation varied and depended on the site of the previous intracardiac lesion repair. Repeat operations in 5 patients confirmed the echocardiographic findings. Aortic valve repair was confirmed in 2 patients by transesophageal echocardiography, whereas aortic valve replacement became necessary in 2 other patients. A fifth patient with acquired cardiomyopathy underwent orthotopic heart transplantation. CONCLUSIONS: A detailed two-dimensional echocardiographic examination, along with color flow imaging, should be done to evaluate iatrogenic aortic valve perforation in patients with a new murmur of aortic regurgitation after cardiac operations in proximity to the aortic valve. Precise preoperative diagnosis of this lesion allows optimal surgical planning and treatment.

Nonpenetrating clips for coronary anastomosis.

BACKGROUND: A nonsuture clip technique (nonpenetrating titanium clips applied to everted tissue edges at high compressive forces) was used to perform coronary anastomoses in a clinical setting. METHODS: Clipped coronary anastomoses were performed in 10 patients. The anastomoses incorporated the left internal mammary artery to the left anterior descending artery (n = 1) and the saphenous vein to the right coronary artery (n = 5), the posterior descending artery (n = 2), the diagonal artery (n = 2), and one vein-to-vein proximal anastomosis (n = 1). RESULTS: The mean duration for completion of the anastomoses was 15 minutes (range, 7 to 20 minutes). This time was reduced from 20 minutes at the beginning of the clinical experience to 7 minutes for the last 3 patients. No technical complication was related to clip application and all patients had uneventful outcomes. Three anastomoses studied by coronary angiography were patent without stenosis. CONCLUSION: The clipped anastomotic technique has a rapid learning curve, the same safety as suture methods, and the potential for facilitating endoscopic vascular reconstructions.

Uniformity of perfusion in all regions of the human heart by warm continuous retrograde cardioplegia.

BACKGROUND: Animal models have suggested that retrograde cardioplegia may be poorly distributed to septal and right ventricular regions of the heart; if true, this may have dangerous implications for warm continuous retrograde cardioplegia in humans. We have previously shown that blood gases from coronary arteries during warm continuous retrograde cardioplegia represent postcapillary "venous" gases and are reflective of myocardial perfusion. METHODS: To determine regional differences in perfusion during warm continuous retrograde cardioplegia we obtained blood gases from three regions of the heart in 141 consecutive patients undergoing coronary artery bypass grafting, aortic valve replacement, or both. Right heart perfusion was determined by blood gases from the right coronary artery orifice, acute marginal, or posterior descending coronary arteries; circumflex or lateral wall perfusion was determined by samples from obtuse marginal or intermediate coronary arteries; and anterior wall/septal perfusion was determined by left anterior descending and diagonal coronary artery blood gases. Warm continuous retrograde cardioplegia flow ranged from 150 to 300 mL/min depending on heart size. A mean of 4 +/- 1 samples/patient were obtained. RESULTS: There were no regional differences in postcapillary pH, carbon dioxide tension, or CO2 production during warm continuous retrograde cardioplegia. Oxygen tensions were lower in the right and anterior/septal regions of the heart, implying more O2 uptake. No regional acidosis, consistent with poor perfusion, could be detected. CONCLUSIONS: We conclude that, unlike experimental models, regional myocardial perfusion, including the right heart, is uniform during "high-flow" warm continuous retrograde cardioplegia in humans.

Mycoplasmas and in vitro fertilization.

Semen samples taken from 135 patients attending an in vitro fertilization clinic were shown to be colonized, 53 with Ureaplasma urealyticum (39%) and 16 with Mycoplasma hominis (12%). An unidentified mycoplasma species was isolated from the sperm of two patients. M. hominis was recovered from all the washed sperm samples taken from colonized semen, whereas washing the sperm eradicated U. urealyticum from 71% of colonized semen. The presence of mycoplasmas in semen made no significant difference to the sperm count, sperm motility, sperm abnormalities, or fertilization of eggs.

Rosamicin, a macrolide with in vitro activity against Ureaplasma urealyticum.

A new macrolide antibiotic, rosamicin, was shown to have much greater activity in vitro against ureaplasmas isolated from humans than erythromycin or the tetracyclines tested. A marked ureaplasmacidal effect was also shown.

Auxiliary transplantation of the fetal liver. I. Development of a sheep model.

Current methods of orthotopic liver transplantation are expensive, entail high morbidity and mortality, and are limited by a serious shortage of donor organs for the pediatric recipient. Auxiliary transplantation of livers from anencephalics is a potential solution to the problems of size discrepancy and organ availability for the pediatric patient. To investigate the feasibility of auxiliary fetal liver transplantation, we have developed a sheep model of auxiliary transplantation of the fetal liver into the adult neck. We report here the results of the transplantation of 32 fetal lamb livers ranging in age from 100 to 140 days gestation (term 145 days). We conclude that (1) fetal organ harvest can be effectively accomplished by surface cooling followed by umbilical cold perfusion; (2) auxiliary transplantation of the fetal lamb liver is technically feasible; (3) the fetal liver can survive on umbilical inflow alone but function is improved by hepatic arterial inflow; and (4) the fetal liver is sensitive to excessive flow or pressure and is best transplanted in a parallel vascular arrangement. Auxiliary transplantation of the fetal liver is a promising alternative to current methods of liver transplantation.

The Hayek oscillator: a new method of ventilation in microlaryngeal surgery.

The Hayek oscillator is an externally (body) mounted cuirass ventilator used in the intensive care unit. We have used it to ventilate patients undergoing microlaryngeal surgery. It was found to be a relatively safe method of ventilation in these cases, with the advantage of dispensing with any form of endolaryngeal or endotracheal intubation.

Mechanism of action of iontophoresis in the treatment of palmar hyperhidrosis.

Sweat glands from the palm of a patient with hyperhidrosis were examined by light and electron microscopy before and after treatment with tap water iontophoresis. No changes in structure were noted after treatment, disclaiming the currently accepted theory that mechanical ductal obstruction is the mechanism of action of this method. Furthermore, we believe the safety and effectiveness of this treatment are supported by our experience.

Bacterial and mycoplasma flora of a laboratory colony of the common marmoset (Callithrix jacchus).

A survey was carried out to characterise the bacterial and mycoplasma flora of a closed colony of marmosets, Callithrix jacchus. Bordetella bronchiseptica and Staphylococcus aureus were the only potential bacterial pathogens isolated from the colony; Candida albicans was also identified. S aureus and C albicans were the only organisms which were associated with macroscopic lesions or overt disease. Post mortem examination of the animals proved only reliable method of establishing the presence of some bacterial species in the colony, eg, B bronchiseptica and of obtaining a reliable estimate of the incidence of the various organisms within the colony. The marmosets were all infected with ureaplasmas in the upper respiratory tract. Mycoplasma salivarium was isolated from this site in several animals. There was no evidence to indicate that cross-infection had occurred between the animal technicians and the marmosets, except in one possible case of candidiasis.

Mycoplasmas, a review of surveys examining human genital infections and experimental infection in mice with special reference to in vitro fertilization.

Patients attending an "In Vitro Fertilization" clinic were shown to be commonly infected in the semen with Ureaplasma urealyticum (29%) and Mycoplasma hominis (12%). Other mycoplasmas were rarely recovered. M. hominis was not eradicated from sperm by washing, although washing removed 71% of the ureaplasmas from infected semen. There was a significantly higher incidence of U. urealyticum and M. hominis in patients with cervical intraepithelial neoplasia (P = less than 0.05 and P = less than 0.01 respectively) than in controls. The results showed a possible association of U. urealyticum and M. hominis with CIN type 3. Mouse experiments showed that M. pulmonis has an affinity for genital tissue, adhered to the surface of eggs and could penetrate the zona pellucida, but did not affect fertilization except where pus was present in the oviduct.

Surgical interventions for drug-resistant tuberculosis: a systematic review and meta-analysis.

BACKGROUND: With the emergence of multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB), surgery, which had been replaced by short-course chemotherapy, is again being considered a viable treatment option. OBJECTIVE: To assess the literature on the effectiveness of surgical interventions in the treatment of drug-resistant TB. METHODS: Medline, EMBASE, and PubMed were searched from 1975 to April 2012 in addition to hand searching reference lists, and the International Journal of Tuberculosis and Lung Disease. Potentially relevant studies were assessed according to pre-defined eligibility criteria: MDR- and XDR-TB patients undergoing surgical and non-surgical treatment. Treatment outcomes were extracted according to internationally accepted definitions and included in meta-analyses using random effects models. RESULTS: Summary meta-analysis of 24 comparison studies revealed a significant association between surgery and successful treatment compared to non-surgical interventions (OR 2.24, 95%CI 1.68-2.97). A meta-analysis from 23 single-arm studies demonstrated that respectively 92% (95%CI 88.1-95) and 87% (95%CI 83-91) of surgical patients achieved successful short- and long-term outcomes. Subgroup analyses showed that favorable surgical outcomes were associated with increased drug resistance in studies reporting surgical and non-surgical treatment outcomes. CONCLUSIONS: While the results suggest that surgical intervention is associated with successful treatment outcomes in patients with drug-resistant TB, there is insufficient evidence to recommend surgery plus chemotherapy over chemotherapy alone, to evaluate the potential harm from surgery and to determine the optimal conditions for surgery. Controlled studies are needed to better assess the effectiveness of surgery and to investigate other contextual issues.