A non-invasive device to objectively measure tibial rotation: verification of the device.

The purpose of this study was the correlation of the results of a new measurement device for tibial rotation (Rotameter) in comparison with the measurements of a knee navigation system as standard method. In a biomechanical laboratory study, all soft tissues were removed from 20 human cadaveric knees leaving only the intact capsule and the bone. Specific tracers were bicortically fixed in the bone in order to measure tibial rotation using a knee navigation system. The knees were fixed to a custom-made inside-boot to rule out undesirable rotation of the reconstruction inside the Rotameter measurement device. Internal and external rotation values were measured at an applied torque of 5, 10 and 15 Nm. The different methods to evaluate tibial rotation were compared using the Pearson correlation coefficient. The correlations were deemed to be reliable if a value of >or=0.80 was achieved. At 5 Nm of applied torque, high correlations for the internal rotation, external rotation and the entire rotational range were found in the Pearson correlation coefficient between the Rotameter testing device in comparison with the knee navigation system as invasive reference method. These results were also confirmed at an applied torque of 10 and 15 Nm. In conclusion, the Rotameter testing device showed high correlations compared with the knee navigation system as an invasive standard method. It might be used as a non-invasive and easy alternative to investigate tibial rotation.

A multimethod study of advanced practice nurse postdischarge care.

In the United States, increasing emphasis is being placed on understanding the roles and cost-effectiveness of advanced practice nurses (APNs). This study used both quantitative and qualitative strategies to explore the impact of APN intervention for frail rural elders being discharged from the hospital. For the quantitative component, analyses of specific postdischarge elder (n = 140) and caregiver (n = 65) outcomes were conducted using four groups receiving the following types of care: no nursing care, registered nurse (RN) care only, APN care only, and both RN and APN care. Outcomes assessed included elder cognitive functioning, self-rated health, informal services provided, and use of health care resources. Caregiver outcomes included physical, emotional, and depressive symptoms, as well as stress scores, physician visits, and missed work days. Elders in the APN-only group experienced fewer emergency room visits and hospital readmissions, although the difference was not significant. Caregivers receiving APN-only support reported significantly fewer work days missed. For the qualitative component, a focus group with four APNs who delivered the intervention was conducted to explore unique aspects of their roles and specific interventions they provided. A theme of these results was more comprehensive and autonomous delivery and management of care to both elders and their caregivers.

Laboratory process improvement through point-of-care testing.

BACKGROUND: In the 1992-1996 period Methodist Clinical Laboratory Services of the Methodist Health Group, Indianapolis, was restructuring all work processes. In one initiative, point-of-care testing (POCT) was used to optimize the decision cycle time while reducing the overall cost of providing information. DEVELOPING THE COMPARATIVE MODEL: In a typical month (May 1994) for hospital admissions and laboratory usage, events related to the traditional blood analysis process were observed. In March 1995 the same model that was applied to analyze the traditional blood analysis process was used to evaluate the newly implemented POCT blood analysis process. Comparisons of both processes, cost per test panel, nursing time spent, and overall turnaround time were made between the two methodologies. RESULTS: A restructure of delivery of blood analysis with the POCT system saved the hospital $392, 336 compared to the total annual cost of the traditional approach for delivering blood analysis. The average cost per test panel was $15.33 with the traditional model and $8.03 with the POCT system. Improvements in the overall turnaround time of test results affected the decision cycle time of the caregiver. The POCT system saved four steps on the patient care floor and ten in the laboratory. DISCUSSION: It is critical to establish a POCT committee, including the most vocal critics of POCT1-to look at how a program of this nature will affect the organization. CONCLUSIONS: POCT became more than just an isolated change-it became a core strategy of moving laboratory testing out of the traditional laboratory setting to where it could become immediately accessible to caregivers as information.

Evaluation of an implantable ventricular assist system for humans with chronic refractory heart failure. Device explant protocol.

An explant protocol was developed to investigate the effects of implantation of a left ventricular assist system (LVAS) manufactured by Novacor Division, Baxter Healthcare Corporation on the function of end organs (such as the brain, the kidney, the liver), with particular interest in examining possible complications due to LVAS support. Emphasis was placed on an analysis at the time of device removal and/or autopsy of 1) the local LVAS-host interface; 2) remote cardiovascular and end-organ effects; and 3) the impact of chronic circulatory support on the native heart. To accomplish these objectives, tissue and device samples must be obtained in an appropriate fashion to ensure photographic documentation, microscopic examination, microbiologic and biochemical assays, and compliance with regulatory and manufacturer requirements. This article describes the techniques and protocol that were proposed to ensure the quality of device explant and tissue analysis.

Increased plasma atrial natriuretic peptide levels after heart transplant: relation to ventricular expression and severity of rejection.

To determine whether elevated plasma atrial natriuretic peptide (ANP) levels observed after cardiac transplant are related to ventricular ANP expression and/or the severity of rejection, 59 ambulatory patients with cardiac transplant underwent hemodynamic evaluation, endomyocardial biopsy, and plasma ANP sampling. Forty-two of the 59 patients had right ventricular (RV) biopsy specimens immunohistochemically stained for the presence of ANP. Plasma ANP levels were elevated (p < 0.0001) in transplant patients (172 +/- 12 pg/ml) compared to normal subjects (36 +/- 4 pg/ml). Sixty-four percent of transplant patients showed stainable RV ANP on endomyocardial biopsy. There was no significant difference in plasma ANP levels between patients with or without RV ANP. The degree of RV staining did not correlate with plasma ANP levels, degree of rejection, mean atrial or systemic pressures, or specific immunosuppressive regimen. Plasma ANP levels were higher in patients with moderate or severe rejection (237 +/- 17 pg/ml) compared to patients with mild or no rejection (163 +/- 12 pg/ml; p 0.03), but there was significant overlap of values. These data suggest that ventricular ANP secretion may account for some of the increase in plasma ANP levels in cardiac transplant patients. However, increased plasma ANP levels in some transplant patients who have no RV ANP and the lack of correlation between the amount of stainable RV ANP and plasma ANP levels suggest that other mechanisms are also likely responsible for plasma ANP elevations in this setting.

Recurrence of a left ventricular thrombus after surgical excision in a young patient with normal left ventricular systolic function--a case report.

The case report of a young patient with recurrence of intraventricular thrombus represents an unusual presentation with no apparent clinical explanation despite echocardiographic, surgical, and pathologic confirmation. The other unusual feature of this case is the absence of predisposing factors for intraventricular thrombus. The patient developed the second left ventricular thrombus after he stopped taking anticoagulants. The authors' recommendation for such a patient is that he continue to receive anticoagulants for life.

Cardiac and skeletal muscle disease in systemic sclerosis (scleroderma): a high risk association.

To examine the possible relationship between cardiac and skeletal muscle disease in systemic sclerosis, we reviewed computerized records of 1095 consecutive patients with systemic sclerosis. One hundred eighty three (17%) had skeletal myopathy. Thirty-nine (21%) of the 183 fulfilled criteria for myocardial disease, compared with 90 (10%) of the 912 without myopathy (p < 0.0001.) Nineteen (10%) of the 183 had clinical CHF compared with 38 (4%) of the remainder (p < 0.002.) Fifteen (8%) of the patients with myopathy died of cardiac causes compared with 27 (3%) of the 912 without myopathy (p < 0.002.) Twenty-five patients with coexistent myopathy and myocardial disease, in the absence of other identifiable contributing causes, were identified. This group was characterized by a high incidence of cardiac conduction abnormalities (60%) and by the severity of the myocardial dysfunction and arrhythmias, both atrial and ventricular that they experienced. Eighteen of these 25 patients died; 12 (67%) died suddenly. Eight of the 18 (44%) had intractable CHF, which directly contributed to their deaths. Myocardial fibrosis was the predominant histologic abnormality at autopsy. However, autopsy of a patient who died in the context of acute "myocarditis" showed severe myocytolysis with contraction band necrosis but without inflammation or fibrosis; this is consistent with possible ischemically mediated injury. We conclude that skeletal and cardiac muscle disease in systemic sclerosis are associated. Patients with myopathy are at increased risk for CHF, sustained symptomatic arrhythmias, and cardiac death, particularly sudden death.

Development of an axial flow blood pump LVAS.

Nimbus, Inc., (Rancho Cordova, CA) and the University of Pittsburgh (Pittsburgh, PA) are collaborating to develop an implantable rotary blood pump that can be used as a left ventricular assist system (LVAS). The short-term goal of this project is to show that an LVAS based on this pump can operate safely and reliably during chronic implantations in animals. Work conducted to date includes in vitro testing of hydraulic performance, hemolysis, endurance demonstration, and flow visualization. Results indicate that the pump is capable of generating an output of up to 10 L/min at physiologic pressures. Associated electrical power to drive these pumps is in the range of 6-10 watts. One integrated pump was placed in a mock flow loop and operated continuously at a fixed speed (10,000 rpm), pressure (100 mmHg), and flow rate (6 L/min) for 90 days with no apparent difficulty. In vitro hemolysis test results have consistently ranged between 3-6 g of liberated hemoglobin/day, which is an acceptable range for chronic use. Two in vivo trials of 7 and 14 days were performed using calves, after which tests have been done using sheep as the animal model. Five short-term sheep experiments have been conducted with good results. Future studies will include implantations in sheep of 3 months duration.

Expression of mRNA for cytokines in tumor-infiltrating mononuclear cells in ovarian adenocarcinoma and invasive breast cancer.

Cytokine gene expression in tumor-infiltrating lymphocytes (TIL) in frozen-tissue sections of 2 types of human solid tumor--ovarian adenocarcinoma and invasive breast cancer--was examined by in situ hybridization with 35S-labeled cDNA probes for human cytokines. The proportion of cells containing mRNA able to hybridize to the antisense c-DNA probes for interleukin 2 (IL-2), tumor necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma) or receptors for IL-2 (either p55 or p70) was also determined in human normal peripheral lymphoid tissues and inflammatory tissues. Few cells were positive for IL2 and TNF alpha mRNA in reactive human lymph nodes and tonsils. Inflammatory lesions, such as salpingitis or chronic active hepatitis, contained 10-20 times more cells positive for cytokine mRNA than reactive lymphoid tissue. In contrast, tumor-infiltrating lymphocytes (TIL) in the stroma of ovarian carcinomas or most ductal breast tumors only rarely expressed mRNA for TNF alpha, IL2 or IFN gamma. The intensity of mononuclear cell infiltration in these tumors correlated positively with the percentage of cells which expressed mRNA for IL-2, TNF alpha and IL-2R. In those ductal breast carcinomas which contained intracellular or intraductal mucins, up to 30% of lymphoid cells in the tumor stroma were positive for IL-2, TNF alpha, IFN gamma and IL-2R. Thus, strong evidence for local activation of mononuclear cells in situ, exemplified by the expression of genes for cytokines, was obtained only in inflammatory lesions and in mucin-producing breast carcinomas. In most carcinomas studied, few TIL expressed genes for cytokines as measured by in situ hybridization. Thus, human solid tumors appear to differ in their ability to induce gene expression for cytokines in TIL.

Presence of CD4, CD8 double-negative and T-cell receptor-gamma-delta-positive T cells in lymphocyte cultures propagated from coronary arteries from heart transplant patients with graft coronary disease.

Previous studies have shown that the interleukin-2-induced propagation of lymphocytes from endomyocardial biopsy specimens, an indicator of cellular rejection, is associated with the development of graft coronary disease in heart transplant patients. To further investigate the concept of cell-mediated immune responses in graft coronary disease, we have applied the methodologies of interleukin-2-induced propagation of lymphocytes from arterial tissues. In a group of 23 patients, which included 6 heart, 6 kidney, and 11 liver transplant recipients, we observed that arterial lymphocyte growth was significantly associated with obliterative vasculopathy (p less than 0.03). T-cell phenotyping analysis of coronary artery-derived lymphocyte cultures from three heart transplant patients with graft coronary disease showed significant numbers of CD4, CD8 double-negative T cells and T-cell receptor-gamma delta cells, especially when the cultures were established with relatively high doses of 400 U/ml of interleukin-2. These data suggest that the subset of CD4-CD8-, T cell receptor-gamma delta+ T cells may play a role in the pathogenesis and progression of graft coronary disease.

Graft atherosclerosis: effects of cellular rejection and human lymphocyte antigen.

Graft atherosclerosis after heart transplantation is a problem that may limit long-term survival. The objective of this study was to establish whether an association exists between graft atherosclerosis, cellular rejection, HLA compatibility, or antilymphocyte antibodies in recipient serum. Results of cineangiograms from 306 recipients were available. Life table and logistic regression analysis identified only a significant effect of cellular rejection on development of angiogram-evident graft vessel disease. A total of 146 allografts obtained at another transplantation or autopsy were also available. Coronary vessel narrowing was measured by planimetry. Linear regression with coronary narrowing as dependent variable established a positive association with history of cellular rejection. No effect was documented for panel reactive antibody level obtained before or after transplantation. We also did not show an impact of HLA mismatch on this process. The lack of HLA antigen effect prompts us to be cautious about linking graft atherosclerosis directly to the rejection event.

Cardiac events after heart transplantation: incidence and predictive value of coronary arteriography.

Cardiac events from graft arteriopathy, including myocardial infarction, heart failure resulting from previous myocardial infarction, and sudden death, may limit long-term survival after heart transplantation. To determine the incidence of cardiac events and the use of coronary arteriography in predicting these events, the long-term results (mean follow-up, 3.5 years; standard deviation +/- 2.0) of heart transplantation in 427 patients were reviewed. Cardiac events included 19 cases of myocardial infarction, 13 cases of sudden death, and 10 cases of congestive heart failure. All these events occurred after the first year except for three cases of sudden death and one case of myocardial infarction. Cumulative incidence of cardiac events per patient year was 0.9% within the first year, increasing to 1.9% by 5 years. Cardiac events accounted for 3.8% of the deaths by the end of the first year, rising to 18% of total mortality by 7 years after heart transplantation. In patients dying after the first year of transplantation, deaths from sequelae of coronary artery disease occurred in 36% (20/55). The relative risk ("odds ratio") of any cardiac event was 3.44 (p less than 0.05) in patients with angiographic evidence of obstructive disease compared with those without evidence of disease, risk of cardiac death 4.6 (p less than 0.05) and risk of sudden death, 2.4 (not significant). Of the 13 patients who died suddenly, five seen at autopsy were found to have had a recent myocardial infarction. Of all patients who died of heart disease, recent myocardial infarction was detected in nine who were seen at autopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of panel-reactive antibody and lymphocytotoxic crossmatch on survival after heart transplantation.

Review of 463 heart transplants was undertaken to examine the relationship between level of panel-reactive antibody (PRA) and a standard donor-specific lymphocytotoxic crossmatch (LXM) on the incidence of death from hyperacute, acute, and chronic rejection. Death from chronic rejection was defined as being caused by graft atherosclerosis. Hyperacute rejection was diagnosed in 18 allografts, and only two recipients had PRA greater than 10% and another two a positive LXM. Five-year actuarial freedom from death caused by all forms of rejection correlated with PRA values as follows: PRA 0% to 10% (415 patients), 85%; PRA 11% to 25% (29 patients), 68%; PRA greater than 25% (19 patients), 57% (p less than 0.005). Additionally, there was a positive linear relationship between PRA and duration of acute rejection episodes in the first 3 months after transplantation. A positive retrospective donor-specific LXM was present in 42 of 401 patients; most of them (32 patients) were low positive (10% to 50% cell death), and none could be correlated with antibody specificity toward donor HLA antigens. Five-year actuarial freedom from death caused by rejection was 83% in those with a negative LXM, 74% in those with low-positive, and 79% in those with high-positive LXM (p = NS). Negative LXM result did not reduce the risk of death caused by rejection in any of the PRA subgroups. While PRA greater than 10% is a risk factor for rejection-related events, a negative LXM in patients with an elevated PRA does not reduce the risk of death resulting from acute or chronic rejection.

Histocompatibility and other risk factors for histological rejection of human cardiac allografts during the first three months following transplantation.

A histological analysis of 2564 endomyocardial biopsies was conducted in 349 cardiac transplant patients to determine potential risk factors for acute cellular rejection during the first three months following transplantation. This analysis dealt with the frequency, time of onset, and duration of cellular rejection. Patients on perioperative RATG experienced significantly less rejection than patients on OKT3 or without antilymphocyte antibody immunoprophylaxis. A trend was noted toward increased rejection in recipients diagnosed originally with chronic myocarditis compared with patients in other disease categories including ischemic heart disease and dilated cardiomyopathy. No significant differences were seen in histological rejection between male and female recipients. On the other hand, patients over 55 years of age were found at lower risk of histological rejection. The results of this analysis have demonstrated quite clearly, but not unexpectedly, that a greater degree of HLA mismatching correlates with increased cellular rejection. This effect was noted not only for the HLA-A,B and DR antigens, but also HLA-DQ and HLA-DRw52/53 antigens. In multivariate analysis, the highest level of statistical significance was obtained for the combined HLA-A,B,DR and DQ group. Sensitized patients with panel-reactive lymphocytotoxic antibodies of greater than 10% experienced more histological rejection than nonsensitized patients. On the other hand, a positive lymphocytotoxic crossmatch did not appear to influence cellular rejection of cardiac allografts. Also, no differences were seen in histological rejection between ABO-identical and compatible heart transplants. These findings further support the concept that donor HLA compatibility and pretransplant sensitization represent significant risk factors for cellular rejection in cardiac transplantation.