Modeling the Transport of Human Rotavirus and Norovirus in Standardized and in Natural Soil Matrix-Water Systems.

We modeled Group A Rotavirus (RVA) and Norovirus genogroup II (GII NoV) transport experiments in standardized (crystal quartz sand and deionized water with adjusted pH and ionic strength) and natural soil matrix-water systems (MWS). On the one hand, in the standardized MWS, Rotavirus and Norovirus showed very similar breakthrough curves (BTCs), showing a removal rate of 2 and 1.7 log10, respectively. From the numerical modeling of the experiment, transport parameters of the same order of magnitude were obtained for both viruses. On the other hand, in the natural MWS, the two viruses show very different BTCs. The Norovirus transport model showed significant changes; BTC showed a removal rate of 4 log10, while Rotavirus showed a removal rate of 2.6 log10 similar to the 2 log10 observed on the standardized MWS. One possible explanation for this differential behavior is the difference in the isoelectric point value of these two viruses and the increase of the ionic strength on the natural MWS.

A novel patient-derived tumorgraft model with TRAF1-ALK anaplastic large-cell lymphoma translocation.

Although anaplastic large-cell lymphomas (ALCL) carrying anaplastic lymphoma kinase (ALK) have a relatively good prognosis, aggressive forms exist. We have identified a novel translocation, causing the fusion of the TRAF1 and ALK genes, in one patient who presented with a leukemic ALK+ ALCL (ALCL-11). To uncover the mechanisms leading to high-grade ALCL, we developed a human patient-derived tumorgraft (hPDT) line. Molecular characterization of primary and PDT cells demonstrated the activation of ALK and nuclear factor kB (NFkB) pathways. Genomic studies of ALCL-11 showed the TP53 loss and the in vivo subclonal expansion of lymphoma cells, lacking PRDM1/Blimp1 and carrying c-MYC gene amplification. The treatment with proteasome inhibitors of TRAF1-ALK cells led to the downregulation of p50/p52 and lymphoma growth inhibition. Moreover, a NFkB gene set classifier stratified ALCL in distinct subsets with different clinical outcome. Although a selective ALK inhibitor (CEP28122) resulted in a significant clinical response of hPDT mice, nevertheless the disease could not be eradicated. These data indicate that the activation of NFkB signaling contributes to the neoplastic phenotype of TRAF1-ALK ALCL. ALCL hPDTs are invaluable tools to validate the role of druggable molecules, predict therapeutic responses and implement patient specific therapies.

Long-term results of the bioprosthesis in elderly patients: impact on quality of life.

BACKGROUND: A wealth of data exists on acceptable mortality and morbidity for valve operations in older patients, yet information documenting quality of life is lacking. METHODS: From October 1974 to May 1998, 2,075 patients aged 65 years and older underwent valve replacement using a porcine bioprosthesis. There were 1,126 men (54.3%) and 949 women (45.7%) with a mean age of 73.9 years (range 65 to 104 years). RESULTS: The elective hospital mortality was 8.5% (158 patients), and urgent/emergent/salvage mortality was 25.8% (54 patients). Follow-up was completed for 1,863 patients (98.2%) and extended from 1 month to 23.0 years (mean 60.8 months) with a cumulative follow-up of 9,442.1 patient-years. At follow-up, surviving patients (n = 849) completed the Short Form-36 Quality of Life Survey. Results showed patients had a more favorable quality of life compared with control subjects matched for age and sex. Functional improvement was significant with 96.3% in New York Heart Association functional class I or II at follow-up. There were 74 valves that failed from all causes (33 aortic and 41 mitral valves). Actuarial freedom from valve failure at 9 years was 94.4%+/-1.1% and at 18 years was 83.7%+/-2.4%. CONCLUSIONS: Valve replacement in older patients provides excellent functional improvement, reduces late cardiac events, and enhances quality of life.

Crew support tools for Euromir 95.

The Euromir 95 long-duration mission raised many new crew-support issues for ESA. Previous mission experience indicated the need for increased emphasis on generic tools for astronaut Thomas Reiter. In addition, some possible solutions could be demonstrated to combat Mir's onboard stowage problem. Overall, the mission considerably increased ESA's operational experience, while the experimental introduction of certain items generated a vast number of 'lessons learned' in the crew-support domain. Further experience in this area would enhance Europe's role in the International Space Station's operational phase.

Bioprosthetic valve longevity in the elderly: an 18-year longitudinal study.

The issue of bioprosthetic valve durability has become of critical importance as the number of elderly patients requiring valve operation has continued to increase. Our previous study showed bioprosthetic valve durability to be in excess of 83% at 13 years for patients 70 years of age and older at the time of implantation. There is limited follow-up data in the literature beyond this time point, however. Accordingly a retrospective analysis was conducted of all patients with bioprosthetic valves who were 70 years of age and over at the time of implantation. From September 1974 to April 1994, 1007 patients 70 years of age and over underwent valve replacement using a porcine bioprosthesis. The patients ranged in age from 70 to 104 years (mean, 75.6 +/- 4.3 years). There were 549 men (54.5%) and 458 women (45.5%). Preoperatively 98.8% of the patients were in New York Heart Association functional class III or IV. Operation was performed as an emergency in 66 patients (6.6%). The hospital mortality was 10.9% (110 patients), with 897 hospital survivors. There were 961 valves at risk. Follow-up extended from 1 month to 18.8 years (mean, 56.6 months). The cumulative follow-up is 4232.3 patient-years. A total of 31 valves failed, 12 in the aortic position and 19 in the mitral position (p < 0.0024). The causes of valve failure have included structural deterioration (16 valves), prosthetic endocarditis (7 valves), nonstructural dysfunction (5 valves), prosthetic thrombosis (1 valve), and other (2 valves).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of coronary artery disease on structural deterioration of porcine bioprostheses.

The number of patients undergoing valve replacement and concomitant coronary artery bypass grafting (CABG) is increasing. To further evaluate the indications for the use of the porcine bioprosthesis, this retrospective comparative analysis of valve structural deterioration was conducted in patients with and without concomitant CABG. From September 1974 to October 1993, 1,567 patients underwent valve replacement using a porcine xenograft. The series was divided into two groups: patients with isolated valve replacement (VR; n = 876) and those with VR and CABG (VR + CABG; n = 691). Aortic valve replacement was performed in 938 patients, mitral valve in 518, tricuspid in 2, and multiple valve replacement in 109 patients. The mean age for the series was 70.7 years (range, 50 to 104 years). The hospital mortality was 8.8% (138 patients). The hospital mortality for the VR group was 7.4% (65 deaths) and the VR + CABG group, 10.6% (73 deaths) p = 0.0365. There were 1,429 patients discharged from the hospital with 1,489 valves at risk. Follow-up extended from 1 month to 17.9 years with a mean of 66.9 months and was 98.3% complete. The cumulative follow-up was 7,927.1 patient-years. Structural deterioration was found to be significantly greater in the VR group for the age category 50 to 59 years (p = 0.0121) and the 60 to 69 years (p = 0.0230). No significant difference in the rate of structural deterioration was found for the two groups for the age category 70 years and older.(ABSTRACT TRUNCATED AT 250 WORDS)

Sequential internal mammary artery grafting: a viable alternative in myocardial revascularization.

The internal mammary artery has become the conduit of choice in myocardial revascularization. The expanded use of this ideal conduit for sequential grafting has enhanced its application. Between March 1985 and June 1993, 245 consecutive patients underwent revascularization of the myocardium with internal mammary artery bypass grafts with at least one sequential anastomosis. There were 186 men and 59 women, with a mean age of 65.1 (range 40-82) years. Unstable angina was present in 141 patients (57.6%) and 36 patients (14.7%) had left main coronary artery stenosis (> 50%). Before surgery, five patients (2.0%) were in New York Heart Association (NYHA) class II, 113 (46.1%) in class III, and 127 (51.8%) in class IV. There were a total of 1041 coronary artery grafts, mean 4.2 (range 2-7) grafts per patient and 528 sequential left internal mammary artery anastomoses, mean 2.2 per patient. Hospital mortality rate was 2.4% (six patients). Almost two-thirds of the patients experienced no hospital complications. The most frequent complication included arrhythmia in 36 patients (14.7%), respiratory insufficiency in 15 (6.1)% and temporary left phrenic nerve palsy in ten (4.1%). Mean follow-up was 37.0 (range 1-94.2) months. The mean(s.e.m.) actuarial survival rate for patients discharged from hospital was 94.8(1.6)% at 36 months and 82.4(5.0)% at 72 months. At follow-up of 222 patients, 185 (83.3%) were symptom-free in NYHA class I and 27(12.2%) were in class II. Though technically demanding, multiple sequential internal mammary artery grafting is feasible and can be accomplished with low hospital mortality and morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic valve replacement: procedure of choice in elderly patients with aortic stenosis.

Aortic valve replacement is the treatment of choice for elderly patients with aortic stenosis. It can be accomplished with excellent immediate and long-term results with significant functional improvement. Unfortunately, the literature is replete with enthusiastic reports of aortic catheter balloon valvotomy. Initial findings were controversial and the long-term results have been poor due to early valve restenosis. A retrospective analysis of our surgical experience with aortic valve replacement in the elderly seems appropriate in an effort to put this issue in proper perspective. From January 1973 to June 1993, 200 consecutive patients 70 years of age and older with severe aortic stenosis underwent surgical correction. There were 105 men (52.5%) and 95 women (47.5%), with a mean age of 76.2 years (range 70 to 89). Preoperatively, 195 patients (97.5%) were in New York Heart Association (NYHA) Class III or IV. Over one half (61.0%) of the patients experienced no hospital complications. The hospital mortality was 9.0% (18 patients). This included 14 patients in NYHA Class IV. The mean follow-up was 69.3 months and ranged from 1 to 215 months. The actuarial survival for 182 patients discharged from the hospital was 70.8% +/- 4.0% (SEM) at 72 months (73 patients at risk) and 35.2% +/- 5.4% at 144 months (20 patients at risk). Considering the advanced age and preoperative functional classification in this patient group, the results of aortic valve replacement have been excellent. The survival of patients discharged from the hospital compares favorably with a normal population matched for age and sex. The results of aortic balloon valvotomy have been disappointing.(ABSTRACT TRUNCATED AT 250 WORDS)

Partial inclusion aortic root replacement with the pulmonary autograft valve.

The expanded use of autografts for aortic valve replacement has focused attention on developing an improved implantation technique with the aim of reducing the incidence of early insufficiency. While the technique for total root replacement with nonstented tissue valves is a proven and established method, it is, however, not generally accepted for use in all clinical circumstances. Through the use of a partial inclusion technique, we propose to modify the standard method of extended aortic root replacement and pedicle coronary implantation. This approach also has the advantage of leaving the recipient aortic root intact. Unlike traditional scalloped subcoronary homograft implantation, it does not enclose the transplanted valve totally within the recipient aorta. Thus, there is preservation of the patient's aorta without distortion of the transplanted valve which occurs when it is forced completely into the closed recipient aortic root. While this partial inclusion method is not as simple as total root replacement, preservation of the recipient root is generally more acceptable to implanting surgeons. Either perfection of this proposed method or the acceptance of a traditional extended aortic root replacement will result in correction of the persistent problem of early aortic insufficiency following the use of autograft valves. Decreasing valve incompetence will have the desired effect of increasing the indication for the use of autografts for aortic valve replacement in young patients.

Implantation of the unstented bioprosthetic aortic root: an improved method.

The problem of early onset aortic insufficiency as seen with the scalloped, subcoronary homograft aortic valve replacement is reduced with the use of a total root replacement. In addition, the naturally competent aortic root is more durable. From September 1985 to April 1991, 26 consecutive patients underwent aortic root replacement with 10 autografts, 14 homografts, and 2 xenografts using a modified implantation method. Twenty-five patients were discharged from the hospital. This partial inclusion root technique for implanting unstented valves in the aortic position decreases the probability of early failure secondary to technical malalignment at the time of implantation. In contrast to total root replacement, it avoids the need to destroy the recipient aortic root. A longitudinal aortotomy is performed to the aortic annulus in the mid-portion of the noncoronary sinus. The proximal suture line is interrupted with the valve oriented in the anatomical position. Circumferential running monofilament side-to-side anastomoses approximate the donor coronary ostia to the recipient. A running medial and lateral posterior suture line to the lateral superior portions of the aortotomy completes the integrity of the anterior wall of the implantation. One autograft attempt failed and one homograft patient died postoperatively. Follow-up ranges from 1 to 6 years in 24 patients. Postoperative aortic insufficiency was significant in one case due to inappropriate sizing of the proximal aortic suture line. There has been no evidence of progressive aortic insufficiency detected by the early onset of diastolic murmurs or echocardiograms as was our previous experience with the scalloped subcoronary method.

Universal method for insertion of unstented aortic autografts, homografts, and xenografts.

Since the advent of homograft aortic valve replacement surgery in the early 1960s, this procedure has been plagued by early aortic insufficiency. This problem has not been observed with total aortic root replacement. From September 1985 to April 1991, a modified method was used in 25 of 39 consecutive patients having aortic root replacement--seven having autografts, 30 having homografts, and two having xenografts. This technique is a new approach for implanting unstented valves in the aortic position. It decreases the probability of early failure resulting from technical malalignment of the valve during implantation. Further, it avoids the need to destroy the recipient aortic root. Whether the valve being used is an autograft, homograft, or xenograft, this method standardizes the insertion technique regardless of the anatomy or disease. Salient features of the method include the following: a longitudinal aortotomy to the aortic anulus in the midportion of the noncoronary sinus; a proximal interrupted suture line with the valve oriented in the anatomic position; and circumferential running monofilament side-to-side approximation of the donor coronary ostia to the recipient coronary ostia. The two anterior commissures are left untethered by nonclosure of the recipient aortotomy. Preliminary results have been impressive, with follow-up ranging from 1 to 3 years in 30 of these patients. Postoperative aortic insufficiency was significant in only two cases. There has been no progression of aortic insufficiency detectable by diastolic murmur or echocardiogram. Late complications have been minimal, and the overall clinical results have been excellent.

Bioprosthetic valve durability in the elderly: the second decade.

With an increasing number of elderly patients requiring cardiac valve surgery, the topic of bioprosthetic durability becomes critically important. Previous reports have shown expected survival of bioprosthetic valves to be in excess of 95% at 9 years. However, primary tissue failure appears to accelerate at the end of the first decade and there is limited data into the second decade. With this in mind, we proceeded to analyze all bioprosthetic valves implanted in patients 70 years of age and older. From September 1974 to December 1990, 781 patients underwent valve replacement using a bioprosthesis. Ages ranged from 70 to 88 years with a mean of 75.1. There were 423 males (54.2%) and 358 females (45.8%). Preoperatively, 99.0% of the patients were in either New York Heart Association functional Class III or IV. Fifty-nine patients (7.6%) were done as emergencies. Six hundred ninety-four patients left the hospital (30-day overall mortality 11.1%). In this cohort, there were 733 valves at risk. Follow-up extended from 1 to 186.0 months with a mean of 52.9, which resulted in 3,059.9 patient-years of cumulative follow-up. Bioprosthetic Survival: A total of 23 valves failed in the series; 15 primary tissue failures, seven from endocarditis, and one perivalvular leak. Actuarial survival at 7 years was 94.5% +/- 1.4% standard error of the mean (SEM; 168 valves at risk) and at 13 years, 83.7% +/- 4.8% SEM (11 valves at risk). This analysis provides further documentation of the long-term favorable durability of the bioprosthesis when utilized in patients 70 years of age and over.

Effect of stent mounting on tissue valves for aortic valve replacement.

Stent mounting of homograft valves was first reported by our group in 1968. Since then, there has been question as to whether or not stent mounting of bioprostheses adversely affects the incidence of structural deterioration in aortic valve replacement. Between November 1967 and July 1988, 571 consecutive patients underwent valve replacement with a stented or unstented homograft. There were 351 men (61.5%) and 220 women (38.5%). The mean age of the group was 49.2 years (range 18 to 79 years). Five hundred thirty-four patients left the hospital (30-day overall mortality 6.5%). Follow-up extends from 6 months to 22 years with a mean of 7.6 years. The cumulative follow-up for the series was 4,095.9 patient-years. Hospital mortality, early technical failure, and prosthetic valve endocarditis were considered censoring events and excluded from this study. Actuarial analysis revealed a significant difference (p less than 0.02) in the freedom from structural valve deterioration for unstented and stended isolated aortic valve replacement. Age (50 and under, and over 50) does not appear to be a factor in structural deterioration in unstented homografts but does influence the rate of failure in stented homografts (p less than 0.05). These results clearly indicate that stent mounting adversely affects tissue valve durability with aortic valve replacement. Moreover, age correlates with structural deterioration if valves are stented and does not if they are unstented. Based on these results, the use of unstented bioprostheses should be reevaluated, along with the design of porcine valve stents.

Surgical management of aortic valve disease in the elderly: a longitudinal analysis.

From November, 1972, through December, 1986, 219 consecutive patients 70 years of age and older with aortic stenosis (AS) underwent aortic valve replacement. One hundred seven of them had isolated pure AS, and 112 had AS and coronary artery disease (AS + CAD). The mean age of the AS group was 75.4 years (range, 70 to 88 years) and of the AS + CAD group, 74.8 years (range, 70 to 86 years). The mean aortic valve gradient in the AS group was 87.7 +/- 30.6 mm Hg and in the AS + CAD group, 68.0 +/- 51.3 mm Hg (p less than 0.001). Hospital mortality for the AS group was 12.1% (13 patients) and for the AS + CAD group, 8.9% (10 patients). The long-term survival at seven years was 77.2 +/- 5.5% (+/- the standard error of the mean) for the AS group and 57.0 +/- 6.9% for the AS + CAD group (p less than 0.006). Postoperative assessment reveals substantial functional improvement. These early and long-term favorable results provide a much needed reference point when valvuloplasty is being considered. Aortic valve replacement is the treatment of choice in elderly patients with symptomatic AS.

The Carpentier-Edwards bioprosthesis: a comparative study analyzing failure rates by age.

Bioprosthetic valve durability and the significance of patient age at implantation have received much attention recently. Indications and/or contraindications for implantation of the bioprosthesis in the very young and in the elderly have been reasonably well defined. Patients in the middle years (sixth and seventh decades) present a special problem in the choice of a prosthesis. To better elucidate the failure rate of the Carpentier-Edwards bioprosthesis in middle-aged patients, a comparative study of value failure rates was conducted using the Wilcoxon (Breslow) statistical technique. From September 1978 to December 1986, 502 patients underwent valve replacement with a Carpentier-Edwards bioprosthesis. All patients were operated on by a single surgical team using precisely the same method of valve implantation and myocardial preservation. The overall 30-day mortality was 8.4%. PATIENT SURVIVAL: Follow-up was obtained on all 460 hospital survivors and extends to 109.2 months with a mean of 36.8 months. The cumulative survival is 1,410.6 patient-years. VALVE SURVIVAL: The 481 patients that left the hospital were divided into two subgroups. Group I included patients aged 55 to 69 years; group II, 70 years and older. There were 8 valve failures in group I. The percent of valves free of failure plotted by the actuarial method is 95.4% at 5 years (SEM 1.7, 81 valves at risk) and 95% at 7 years (SEM 1.7, 23 valves at risk). In group II (age 70 and above), there were only two valve failures.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary artery obstruction due to giant cell arteritis.

Giant cell arteritis is often referred to in the context of polymyalgia rheumatica with temporal artery involvement. There are, however, more malignant forms of presentation of this necrotizing arteritis involving either the great vessels of the aorta or, occasionally, the pulmonary arteries. Our case relates to giant cell arteritis presenting as pulmonary artery obstruction in a patient without polymyalgia rheumatica or extensive aortic or proximal great vessel involvement.

Valve replacement in the elderly: a long term appraisal.

From July 1972 through July 1983, 360 consecutive patients 70 years of age and older (mean age 74.1; range 70-88 years) underwent 362 valve replacement procedures. There were 122 isolated aortic valve replacements (33.7%; Group I); 70 isolated mitral valve replacements (19.3%; Group II); and 170 patients had combined procedures (47.0%; Group III), which included the replacement of at least one valve. Eighteen patients (5.0%) had previous cardiac surgery. Thirty-two patients (8.8%) were operated as emergencies. Three hundred and thirty-two (86.5%) of all valves implanted were porcine heterografts. Pre-operatively, over one-half (53.6%) of the patients were in New York Heart Association Functional Class IV. The overall hospital mortality was 13.8% (50 patients). The aortic valve mortality was 11.5%, the mitral valve mortality was 15.7%, and the combined procedures 14.7%. The follow-up period for hospital survivors (312 patients) extended from 2 weeks to 127.2 months, with a mean of 38.7 months or a total of 1,006 patient-years. The long term survival computed up to six years shows a 65 +/- 3.8% (standard error of the mean) for the entire group. The aortic valve group survival was 71 +/- 5.6%; the mitral valve group 60 +/- 8.2%; and the combined procedures group was 64 +/- 5.3%. Postoperative functional improvement was significant with 71.8% of the survivors in Class I and 19.6% in Class II. Based on these results, advanced age can no longer be considered a deterrant to cardiac surgery. The porcine heterograft appears to be the valve substitute of choice for this age group.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical management of the small aortic annulus. Hemodynamic evaluation.

Replacement of the aortic valve can be accomplished with ease and safety in most instances. The presence of a small aortic root, however, remains a problem in that both mechanical and stent-mounted tissue valves produce higher resting gradients in the smaller sizes. To avoid this, a technique has been developed to enlarge the aortic annulus. In a series of 253 patients undergoing aortic valve replacement, 22 required division of the aortic annulus. Extension of the incision inferiorly to the anterior leaflet of the mitral valve and a resulting separation of the annulus facilitated implantation of a larger valve. The resulting defect is obliterated with a woven Dacron patch. Hemodynamic data obtained on 12 patients who had recatheterization one to ten months postoperatively disclosed an average resting transvalvular gradient of 13.5 mm Hg. This procedure has been used successfully in combined aortic and mitral valve replacement and heart block has not occurred. Based upon encouraging follow-up studies of the Hancock glutaraldehyde-stabilized porcine heterograft, we use this prosthesis in patients with annular diameters of less than 25 mm. Our experience suggests that enlargement of the aortic annulus is necessary in a significant number of patients undergoing aortic valve replacement.

Valve replacement in patients over 70 years.

From July, 1972, to April, 1976, 54 consecutive patients over the age of 70 years underwent valve replacement at Tampa General Hospital. Twenty-one patients had isolated aortic valve replacement (Group 1), 14 had isolated mitral valve replacement (Group 2), and 19 had combined procedures that included at least 1 valve replacement (Group 3). There was 1 operative death (in Group 1), and another patient (Group 3) died three weeks post-operatively, resulting in an early mortality of 3.7%. Follow-up of the 52 hospital survivors from one to forty-one months reveals 2 additional deaths for a late mortality of 3.8%. Cardiac status improved noticeably in the surviving 50 patients. The data suggests that with current techniques, complex intracardiac procedures can be performed safely with acceptable operative mortality and a satisfactory prognostic outlook in elderly patients.

Method of managing the small aortic annulus during valve replacement.

In a series of 130 patients undergoing aortic valve replacement, 20 had the ascending aorta enlarged with a Dacron patch. Eight of these required division of the annulus with extension of the incision inferiorly to the anterior leaflet of the mitral valve. The resulting separation of the annulus allowed a larger size valve to be inserted. Glutaraldehyde-fixed procine heterografts were used in all patients having the annulus enlarged. No deaths occurred in those patients having annular enlargement, and the post-operative studies show no evidence of mitral valve dysfunction.