PubMed Health⌕ Search

Biomedical subjects

D M Heisey

Publications and source records attributed to D M Heisey.

At least 19 recordsLinked to original sources
PubMed1999

A probabilistic rule of mixtures for elastic moduli.

A novel approach is developed for mathematically modeling the variability observed in experimentally determined elastic moduli of longitudinally oriented fibrous tissues such as ligaments and tendons. The elastic modulus of these tissues is modeled with a rule of mixtures (ROM) where each parameter (fibril and matrix moduli and fibril volume fraction) is assumed to be an independent random variable. A joint density function formed from the independent densities results in a probabilistic ROM (pROM). This pROM is used to generate a distribution of moduli which agrees well with moduli determined from tests of rabbit medial collateral ligaments (Woo and Ohland, 1994, Unpublished experimental data as gift). Minimizing the error between the pROM and experimental distributions resulted in an integrated error of 9% for a constrained set of independent distribution parameters derived from the literature. This pROM thus incorporates microstructural observations (fibril and matrix moduli and fibril volume fraction) to partially explain the experimentally observed variability in a macroscopic property (tissue modulus).

Animals↗
PubMed1999

Association of human leucocyte antigen phenotype with vaccine efficacy in patients receiving vaginal mucosal immunization for recurrent urinary tract infection.

Immune responses to specific antigens can be influenced by an individual's genetic make-up. We examined whether the efficacy of a vaginal mucosal vaccine for urinary tract infections (UTI) was affected by a patient's human leucocyte antigen (HLA) phenotype. Urinary tract infection data and the HLA phenotypes of 47 women participating in a phase II clinical trial of immunization for recurrent UTI were statistically analysed for associations between HLA-A, -B, -DR, or -DQ phenotype and postimmunization infection course. Women who received the vaccine and had HLA-DR phenotypes other than DR2 had significantly delayed times to re-infection compared with women receiving placebo. Vaccine-treated patients with the HLA-DR2 phenotype had re-infection courses that were not different than women receiving placebo. These results indicate that the efficacy of a vaginal mucosal UTI vaccine may be influenced by an individual's HLA-DR phenotype.

Bacterial Infections↗
PubMed1998

The effect of tolerance to noninherited maternal HLA antigens on the survival of renal transplants from sibling donors.

BACKGROUND: During pregnancy and nursing, a baby's developing immune system is intimately exposed to the mother's antigens. To determine whether this exposure is of clinical benefit to patients who later receive an allograft as an adult, we analyzed the outcome of primary renal transplantations from sibling donors. METHODS: We retrospectively studied graft survival and rejection episodes in 205 patients who had received renal transplants at nine centers between 1966 and 1996 from sibling donors bearing maternal or paternal HLA antigens not inherited by the recipient. The sibling donors were categorized by analysis of family HLA-typing data. RESULTS: In the multicenter analysis, graft survival was higher at 5 years and at 10 years after transplantation in recipients of kidneys from siblings expressing maternal HLA antigens not inherited by the recipient than in recipients of kidneys from siblings expressing paternal HLA antigens not inherited by the recipient (86 percent vs. 67 percent at 5 years and 77 percent vs. 49 percent at 10 years, P=0.006 for both). Paradoxically, there was a higher incidence of early rejection in the former group, suggesting that fetal and neonatal exposure to maternal antigens results in immunologic priming. Pretransplantation transfusions of donor blood reduced the incidence of acute rejection while preserving the beneficial effect of tolerance to noninherited maternal antigens on graft survival. Since 1986, new immunosuppressive drugs have lessened the short-term, but not the long-term, survival advantage of grafts expressing maternal HLA antigens not inherited by the recipient. CONCLUSIONS: In the transplantation of a kidney from a sibling donor who is mismatched with the recipient for one HLA haplotype, graft survival is higher when the donor has maternal HLA antigens not inherited by the recipient than when the donor has paternal HLA antigens not inherited by the recipient.

Fathers↗
PubMed1998

Stable lung allograft outcome correlates with the presence of intragraft donor-derived leukocytes.

BACKGROUND: The role of bone marrow-derived "passenger" leukocytes in the outcome of solid organ transplantation remains controversial. This study tested the relationship between high levels of donor-derived leukocytes within the transplanted organ and clinical outcome after lung transplantation. METHODS: Sequential bronchoalveolar lavage samples were obtained from human lung allograft recipients. Leukocytes of donor origin in the bronchoalveolar lavage fluid were detected using two-color immunofluorescence, and the results were correlated with multiple clinical parameters. RESULTS: Mean donor leukocyte levels for the first 200 days after transplantation were higher in patients with a good transplantation outcome compared with those patients who lost their grafts due to acute rejection (AR) or developed bronchiolitis obliterans syndrome. The presence of low numbers of donor-derived leukocytes for the first 200 days after transplantation was found to be a significant risk factor for graft loss due to either acute or chronic rejection (P=0.032). Nearly all patients (85%) experienced AR episodes. However, the time to onset of severe AR episodes was significantly longer (P=0.049), and the incidence of these episodes reduced, in patients who maintained high numbers of donor-derived leukocytes for the first 200 days after transplantation. CONCLUSIONS: The presence of high numbers of donor-derived leukocytes, particularly macrophages, in the transplanted lung in the first 200 days after transplantation was associated with stable graft function. Donor-derived leukocytes were reduced or absent in patients with a poor transplantation outcome. These findings rule out a negative influence of persisting donor leukocytes and are consistent with the emerging two-way models of transplant tolerance.

Bronchoalveolar Lavage Fluid↗
PubMed1998

Donor factors affecting outcome after pancreas transplantation.

In this study, we demonstrated that Px grafts from donors older than 45 years are associated with an increased risk of developing poor glycemic control and premature loss of Px function. Previous studies corroborate our finding that age of the donor is the principal donor characteristic impacting postoperative Px survival. Whereas prior studies also implicated hyperamylasemia as a factor which contributes adversely to outcome, we were unable to demonstrate a significant influence of donor hyperamylasemia on long-term graft survival, although it did correlate with the degree of immediate postoperative pancreatitis and with the need for oral hypoglycemic agents. Similarly, elevated blood glucoses in the donor, which can be a result of many other factors unrelated to the quality of the graft, did not predict a poor outcome in the recipient. NHB donor pancreata did as well as HB pancreata with regards to all postoperative functional parameters. A marginally increased risk of developing major complications was associated with older donors. Despite the frequent use of non-ideal donors, including older and NHB donors, excellent overall Px graft survival can be achieved. Although the quality of the pancreas graft was not directly addressed in this study, we believe irrespective of hyperglycemia or hyperamylasemia, subjective assessment of organ quality by an experienced transplant surgeon is the most important determinant of suitability.

Adult↗
PubMed1998

Endourologic therapy of bladder calculi in simultaneous kidney-pancreas transplant recipients.

OBJECTIVES: To identify the incidence and the success of endourologic therapy for symptomatic bladder-related calculi in simultaneous kidney-pancreas (SPK) transplant patients with bladder drainage. METHODS: A retrospective review of 300 SPK transplant patients with bladder drainage, treated at the University of Wisconsin, Madison from December 1985 to November 1995, is presented. A 3% incidence of bladder calculi was identified. All patients underwent cystolitholapaxy using electrohydraulic lithotripsy and endoscopic suture removal. Follow-up ranged from 15 to 86 months. RESULTS: A 100% stone-free rate was achieved after cystolitholapaxy and endoscopic suture removal. Two patients (22%) developed postprocedural urinary tract infections. No pancreaticoduodenocystotomy leaks or further complications were identified. CONCLUSIONS: SPK transplant patients with nonabsorbable sutures used for the duodenocystotomy anastomosis are at an increased risk for bladder calculi. Cystolitholapaxy with electrohydraulic lithotripsy is a safe and effective treatment for these suture-related stones.

Adult↗
PubMed1998

A comparative study of major histocompatibility complex and red blood cell antigen phenotypes as risk factors for recurrent urinary tract infections in women.

Recurrent urinary tract infections (RUTI) are a significant health problem for many women, and host characteristics that increase susceptibility are not completely defined. This study evaluated data from 99 patients to examine further the question of a possible association between major histocompatibility complex (MHC) or red blood cell (RBC) antigen phenotype and predisposition to RUTIs. MHC class I and II, ABO, and Lewis RBC phenotypes were determined serologically. The MHC class II phenotypes of 55 subjects were also determined by DNA polymerase chain reaction techniques. There were no significant differences in the proportions of HLA-A or -B antigen types between patients and controls, nor in the frequencies of serologically or DNA-defined HLA-DR or -DQ phenotypes. Patient ABO and Lewis RBC phenotypes were not statistically different than those for controls. Thus, the overall risk for women to develop RUTIs does not appear to be associated with any single HLA, ABO, or Lewis phenotype.

ABO Blood-Group System↗
PubMed1998

Physiologic assessment of botulinum toxin effects in the rat larynx.

OBJECTIVE: Botulinum toxin (BT) is a currently used treatment for spasmodic dysphonia (SD) and other related focal dystonias. The goal of this study is to provide a basis for using the rat larynx to objectively assess physiological and histological effects of BT. STUDY DESIGN: Dosages and volumes of BT injection were varied and three physiological parameters were measured. These measures included: optical density of PAS-stained laryngeal muscle after electrical stimulation, which is an indirect measure of denervation, spontaneous laryngeal muscle activity, and laryngeal movement. METHODS: A new microlaryngoscopic technique was developed, which made it possible to observe and manipulate the rat larynx endoscopically. Laryngeal movement and electromyographic (EMG) measures were made prior to injection and 3 days following BT injections of various dosages and volumes. Optical density measures were made 3 days after injection. RESULTS: Significant reductions in vocal fold motion and spontaneous laryngeal muscle activity as a function of increased BT dosage were observed. In addition, the optical density of PAS-stained laryngeal muscle after electrical stimulation was increased following BT injection. Significant volume effects in optical density were observed in the lateral thyroarytenoid and lateral cricoarytenoid muscles on the contralateral side. CONCLUSIONS: The rat laryngeal model is suitable for assessing BT effects. In addition, the three physiological variables provided useful and reliable measures of laryngeal function. It is the authors' intention to use the rat laryngeal model to further examine the physiological and histological effects of BT with the goal of developing new methods for the treatment of patients with SD and other focal dystonias.

Animals↗
PubMed1998

Increased acute and chronic mitotic activity in rat laryngeal muscles after botulinum toxin injection.

OBJECTIVES: To characterize the acute and chronic cellular effects of botulinum toxin (BT) injection into rat laryngeal muscles. A complete characterization of these effects is important because patients with focal dystonias of the head and neck are commonly treated with BT injection. Further, potential muscular changes in the larynx must be carefully delineated owing to the critical phonatory and airway protective functions of these muscles. STUDY DESIGN: The acute and chronic cellular effects of BT injection were studied using 5'-bromo 2'-deoxyuridine (BrdU) following single and repeated BT injection into rat laryngeal muscles. BrdU is incorporated into mitotically active nuclei such that changes in cell proliferative behavior following BT injection can be monitored. RESULTS: Increased mitotic activity was detected in the tissue samples studied following BT injection. Differences in the times of the peak distribution of BrdU-labeled cells in each laryngeal muscle were observed. This may be related to the diffusion effects of BT. Prolonged muscle fiber changes, including splitting, were also observed as the result of repeated BT injection. CONCLUSIONS: The results of this study suggest that BT may induce a proliferative response in muscle tissue.

Animals↗
PubMed1998

Potential prognostic factors of relapse-free survival in childhood optic pathway glioma: a multivariate analysis.

There is still no consensus on the natural history and optimal management of optic pathway gliomas (OPG) in children. In order to tackle optimal management issues, we need to clearly understand the prognostic and confounding factors affecting relapse of OPG. We propose the use of the Cox proportional hazards (PH) model in a retrospective study of childhood OPG of 69 children seen from 1977 to 1994. We have developed a comprehensive model capable of multivariate analyses and handling time-dependencies. Our studies showed that relapse-free survival improves with increasing age, the presence of neurofibromatosis 1 (NF1), and chemotherapy and radiotherapy (p < 0.0005). Sex, tumor position and surgery do not significantly affect survival. Older children with NF1 have extremely good prognosis. We noted behavior that departs from the strictly proportional hazards model, but results were inconclusive.

Adolescent↗
PubMed1998

Long-term survival benefit of internal thoracic artery grafting is negligible in a patient with bad ventricle.

BACKGROUND: Although the internal thoracic artery (ITA) graft is well known for its benefit of enhancing patient longevity after coronary artery bypass grafting (CABG), whether its superior patency is associated with improved patient survival at all levels of left ventricular function is unknown. The purpose of this study was to determine whether the use of ITA grafting during CABG confers improved survival benefit to patients with impaired preoperative left ventricular function. METHODS: A retrospective chart review was performed in 966 patients who had undergone isolated primary CABG between 1984 and 1995. The study population included 320 patients with only venous conduits (no-ITA group) and 646 patients with at least one ITA conduit (ITA group). A Cox partial likelihood approach was used to model the instantaneous mortality risk ratios as functions of ITA use and preoperative ejection fraction (EF). The forward stepwise regression model specifically examined the following potential confounders in the risk analyses: year of operation, patient age, weight, body surface area, graft location, number of grafts, perfusion time, ischemia time and Veterans Administration preoperative cardiac surgical risk estimates. RESULTS: Early (30-day) mortality in the ITA group (0.5%) was lower than the no-ITA group (4.1%) (p=0.0004). While 91% of the ITA group patients were still alive, only 70% of the no-ITA group patients were long-term survivors (p=0.0001). The ITA risk ratios for the increasing proportions of EF were not the same. In patients with E<0.40, the ITA risk ratio, 2.96, was significantly different (p=0.0001). It was only for EF >0.46, a significant survival benefit due to an ITA graft could be detected. The ITA-EF relationship was not confounded by the inclusion of those potential confounding variables in the model. CONCLUSIONS: Patient survival after CABG using an ITA graft may be affected by the level of preoperative EF. The internal thoracic artery-specific patient survival benefit appears to be less in a patient with poor left ventricular function.

Aged↗
PubMed1998

Modelling time-dependent interaction in a time-varying covariate and its application to rejection episodes and kidney transplant failure.

Acute rejection episodes are thought to be prognostic of eventual kidney graft failure. The influence of rejection events on the hazard of transplant failure appears to be a complex function of how long after transplantation the rejection event occurs as well as the time elapsed since the rejection event. To examine the nature of this relationship, we propose a penalized likelihood approach to estimate the parameters of a two-dimensional rectanglewise constant hazard model. The approach appears to be fairly successful at modelling time dependency in a time-varying covariate. The approach is equally applicable for modelling fixed covariates that act in a jointly nonproportional (non-log-linear) and time-dependent manner.

Analysis of Variance↗
PubMed1997

Posttransplant diastolic hypertension: associations with intragraft transforming growth factor-beta, endothelin, and renin transcription.

BACKGROUND: Diastolic hypertension after renal transplantation leads to significant chronic morbidity and mortality. Recently, calcineurin phosphatase inhibition by cyclosporine or tacrolimus has been postulated to lead to diastolic hypertension through the induction of transforming growth factor-beta (TGF-beta) and resultant endothelin-mediated renal arteriolar vasospasm. METHODS: To investigate this hypothesis in humans, the allografts of 40 stable renal allograft recipients were biopsied 2 to 3 years after transplantation. Both cyclosporine and tacrolimus patients were included. Biopsies were divided and processed for histology and RNA extraction. RNA was then converted to cDNA and evaluated by semiquantitative polymerase chain reaction (actin-standardized, high-performance liquid chromatography-quantitated) for TGF-beta, endothelin, and renin transcription. Inflammatory cytokine gene transcription was also evaluated. Blood pressure was measured during the clinic check-in before biopsy. Variables were evaluated by Spearman rank correlation coefficient (rs) analysis. RESULTS: Diastolic hypertension was prevalent in the study population, with 40% of individuals having diastolic pressure >90 mmHg. TGF-beta and endothelin transcription were detected in 88% of biopsies studied, and renin transcription was detected in 91%. Intragraft transcription of TGF-beta (rs=0.61, P=0.0003) and endothelin (rs=0.43, P=0.0188) was strongly correlated with increasing transcription intragraft renin. In turn, renin transcription was strongly correlated with increasing diastolic blood pressure (rs=0.55, P=0.0015). Histological correlation of fibrosis score did not predict the degree of hypertension, nor did it correlate with TGF-beta transcription. Inflammatory cytokine transcription was not related to renin transcription or diastolic hypertension but was correlated with histological evidence of immune graft injury. CONCLUSIONS: These data support the hypothesis that posttransplant diastolic hypertension is a result of TGF-beta-induced, endothelin-mediated arteriolar vasoconstriction and subsequent activation of the renin-angiotensin pathway. These effects are independent of immune-mediated graft injury.

Adult↗
PubMed1997

Bladder cancer in renal transplant recipients.

OBJECTIVES: To determine if there is an increased rate of occurrence of bladder cancer in renal transplant recipients. METHODS: We reviewed the records of 3130 consecutive renal transplant recipients at the University of Wisconsin Hospital from 1980 to 1994. We then compared the rate of occurrence of bladder cancer in this population with that of the general population of Wisconsin. Using an age-specific hazard model based on the rate of bladder cancer in the general population of Wisconsin, we predicted the expected number of bladder cancer cases in this renal transplant population. RESULTS: Using this model, one would expect 1.81 cases of bladder cancer in the renal transplant data set, as opposed to the observed 6, resulting in a relative risk of 3.31 of developing bladder cancer as a result of renal transplantation. CONCLUSIONS: There is a higher incidence of bladder cancer in renal transplant recipients. Therefore, despite a higher incidence of hematuria in this population, each noninfected patient with microscopic (or gross) hematuria should undergo a careful urologic evaluation.

Adult↗
PubMed1997

Urinary symptomatology in younger men.

OBJECTIVES: We surveyed a "population" of younger men (20 to 49 years old) for lower urinary tract symptomatology and for symptomatology associated with prostatitis. METHODS: A National Guard unit was surveyed by mail with a 58-question urinary symptom questionnaire. Surveys were returned anonymously by mail. RESULTS: International Prostate Symptom Score (IPSS) of 8 or greater was seen in 5% of men in their 20s and rose to 15% of those in their 40s. Approximately 5% (0% to 7%) reported a history of prostatitis. Caffeine caused symptoms in 2% to 13%, while exercise and smoking were not associated with symptoms. Individual prostatitis symptoms were only seen occasionally across this age group. CONCLUSIONS: As measured by the IPSS, urinary symptoms increased during the 20 to 49-year age period. A history of prostatitis in much less common than most nonpopulation studies suggest.

Adult↗
PubMed1997

Soluble HLA class I in epithelial lining fluid of lung transplants: associations with graft outcome.

We hypothesized that the small amounts of donor HLA-A and HLA-B proteins detected in the serum during organ allograft rejection are indicative of higher local releases within the graft itself. We determined the concentrations of total HLA class I (HLA-I) and, in selected cases, specific donor and host HLA-A and HLA-B proteins, in the epithelial lining fluid (ELF) sampled by bronchoalveolar lavage (BAL) of lung transplant recipients (n = 37) and of normal controls (n = 25). We found that 1) HLA-I proteins were enriched in the lung ELF relative to other proteins; 2) the concentration of HLA-I in the ELF of well-functioning transplants was similar to that in normal lungs; 3) HLA-I proteins and total proteins were elevated in the ELF of patients who developed chronic rejection or refractory acute rejection; 4) the concentration of HLA-I was correlated with the percentage of neutrophils but not with the percentage of lymphocytes in the ELF of transplanted lungs; and 5) only the percentage of lymphocytes was elevated in the ELF of transplant patients with active CMV infections. Total HLA-I from the ELF was found to contain a mixture of both donor- and recipient-type HLA-A and HLA-B proteins and the donor-type HLA-A2 was found to be highly enriched in the ELF relative to serum.

Acute Disease↗