Biomedical subjects

D Heisey

Publications and source records attributed to D Heisey.

16 recordsLinked to original sources

PubMed2002

Immunization by particle-mediated transfer of the granulocyte-macrophage colony-stimulating factor gene into autologous tumor cells in melanoma or sarcoma patients: report of a phase I/IB study.

The primary objective of this phase I study was to determine the safety of an autologous tumor vaccine given by intradermal injection of lethally irradiated granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transfected autologous melanoma and sarcoma cells. Secondary objectives included validation of the gene delivery technology (particle-mediated gene transfer), determining the host immune response to the tumor after vaccination, and monitoring patients for evidence of antitumor response. Sixteen patients were treated with either of two different doses of GM-CSF-treated tumor cells. One patient received treatment with both doses of tumor cells. No treatment-related local or systemic toxicity was noted in any patient. Patients administered 100% treated cells (i.e., with a preparation of tumor cells that had all been exposed to GM-CSF DNA transfection) had a more extensive lymphocytic infiltrate at the vaccine site than did patients given 10% treated cells (a preparation of tumor cells in which 10% had been exposed to GM-CSF transfection) or nontreated tumor. The generation of a systemic immune response to autologous tumor by a delayed-type hypersensitivity response to the intradermal placement of nontransfected tumor cells was noted in one patient. One patient had a transient partial response of metastatic tumor sites. The entire procedure, from tumor removal to vaccine placement, was accomplished in less than 6 hr in all patients. Four of 17 patient tumor preparations produced greater than 3.0 ng of GM-CSF per 10(6) cells per 24 hr in vitro. The one patient with greater than 30 ng of GM-CSF per 10(6) cells per 24 hr in vitro had positive DTH, a significant histologic inflammatory response, and clinically stable disease. This technique of gene transfer was safe and feasible, but resulted in clinically relevant levels of gene expression in only a minority of patients.

Biolistics↗

PubMed2001

Induction of cross clade reactive specific antibodies in mice by conjugates of HGP-30 (peptide analog of HIV-1(SF2) p17) and peptide segments of human beta-2-microglobulin or MHC II beta chain.

HGP-30, a 30 amino acid synthetic peptide homologous to a conserved region of HIV-1(SF2) p17 (aa86-115), has previously been shown to elicit both cellular and humoral immune responses when conjugated to KLH and adsorbed to alum. However, the free HGP-30 peptide is not immunogenic in animals. In order to improve the immunogenicity of HGP-30, peptide conjugates consisting of a modified HGP-30 sequence (m-HGP-30/aa82-111) and a peptide segment, residues 38-50, of the MHC I accessory molecule, human beta-2-microglobulin (beta-2-M), referred to as Peptide J, or a peptide from the MHC II beta chain (peptide G) were evaluated in mice. The effects of carriers and adjuvants on serum antibody titers, specificities to various HIV-1 clade peptides similar to HGP-30 and isotype patterns were examined. Peptides J or especially G conjugated to modified-HGP-30 (LEAPS 102 and LEAPS 101, respectively) generated comparable or better immune responses to modified HGP-30 than KLH conjugates as judged by the induction of: (1) similar antibody titers; (2) broader HIV clade antigen binding; and (3) antibody isotype response patterns indicative of a TH1 pathway (i.e. increased amounts of IgG2a and IgG2b antibodies). The ISA 51 and MPL(R)-SE adjuvants induced higher antibody responses than alum, with the ISA 51 being more potent. Immune responses to LEAPS 102, as compared to LEAPS 101, were weaker and slower to develop as determined by antibody titers and cross clade reactivity of the antibodies induced. Compared to KLH conjugates which induced significant anti-KLH antibody titers, minimal antibody responses were observed to peptide G, the more immunogenic conjugate, and peptide J. These results suggest that modified HGP-30 L.E.A.P.S. constructs may be useful as HIV vaccine candidates for preferential induction of TH1 directed cell mediated immune responses.

AIDS Vaccines↗

PubMed2000

Determination of stone composition by noncontrast spiral computed tomography in the clinical setting.

OBJECTIVES: Several investigators have evaluated noncontrast computed tomography (NCCT) in predicting stone composition in vitro. We assessed NCCT in predicting stone composition in patients presenting to our emergency room with flank pain and stone disease. METHODS: One hundred twenty-nine patients presenting to our university hospital with flank pain underwent renal colic protocol NCCT scans at the request of the emergency room physicians. A General Electric, high-speed advantage CT scanner was used at 120 kV, 200 mA, and 1.4:1 pitch, with collimation varying between 3 and 5 mm. Ninety-nine patients with predominantly (greater than 50%) calcium oxalate or uric acid composition after either stone passage or stone removal were identified. Each scan was analyzed by one of two radiologists, who determined the predominant attenuation for each stone. Stones once passed or retrieved were analyzed by Urocor Laboratories. The attenuation and attenuation/size ratio (peak attenuation/size in millimeters) were compared with the results of the stone analysis. RESULTS: Eighty-two calculi predominantly composed of calcium oxalate and 17 calculi predominantly composed of uric acid were identified in 99 patients. The calculi ranged in size from 1 to 28 mm. A significant difference (P = 0.017, unpaired t test) was found between the Hounsfield measurement of uric acid calculi (mean 344 +/- 152 HU) and the Hounsfield measurement of calcium oxalate calculi (mean 652 +/- 490 HU). If only the Hounsfield units from stones 4 mm or larger were compared, the data were even more compelling (P = 0.002). However, using an attenuation/size ratio cutoff of greater than 80, the negative predictive value was 99% that a stone would be predominantly calcium oxalate. CONCLUSIONS: Using peak attenuation measurements and the attenuation/size ratio of urinary calculi from NCCT, we were able to differentiate between uric acid and calcium oxalate stones.

Calcium Oxalate↗

PubMed2000

Personality and voice disorders: a multitrait-multidisorder analysis.

To examine whether personality has causal, concomitant, or outcome status in common voice disorders, a vocally normal control group and 4 groups with voice disorders--functional dysphonia (FD), vocal nodules (VN), spasmodic dysphonia (SD), and unilateral vocal fold paralysis (UVFP)--were compared using the Multidimensional Personality Questionnaire (MPQ). Univariate and discriminant analyses confirmed that the FD and VN groups differed significantly from each other, the controls, and the other voice-disordered groups at both a superfactor and lower-trait level of personality description. The FD group was introverted, stress reactive, alienated, and unhappy. The VN group was described as socially dominant, stress reactive, aggressive, and impulsive. Comparisons involving the SD, UVFP, and the control subjects did not identify consistent personality differences. While group trends supported the central tenets of a trait theory outlining the dispositional bases of FD and VN, further research is needed to elucidate the specific causal mechanism(s) in individual cases. The disability hypothesis, which suggests that personality features represent the negative effects of vocal disability, was not strongly supported.

Adult↗

PubMed2000

Personality and voice disorders: a superfactor trait analysis.

To determine whether personality factors play causal, concomitant, or consequential roles in common voice disorders, a vocally normal control group and four groups with voice disorders-functional dysphonia (FD), vocal nodules (VN), spasmodic dysphonia (SD), and unilateral vocal fold paralysis (UVFP)-were compared on measures of personality and psychological adjustment. Superfactor group comparisons revealed that the majority of FD and VN subjects were classified as introverts and extraverts, respectively. Comparisons involving the SD, UVFP, and control subjects did not identify consistent personality differences. The disability hypothesis, which suggests that personality features and emotional maladjustment are solely a negative consequence of vocal disability, was not supported. Personality variables and their behavioral consequences may therefore contribute to FD and VN. Results are presented within the context of a dispositional theory offered by Roy and Bless (2000a).

Adult↗

PubMed1998

Dog model for studying detrusor instability secondary to acutely induced variable bladder outlet obstruction.

BACKGROUND: Involuntary detrusor contractions often cause irritative symptoms such as urgency and incontinence. A dog model for acutely induced variable bladder outlet resistance was developed to investigate the possible role of prostatic afferent nerve fibers in the development and maintenance of detrusor instability. METHODS: Fifty-eight mongrel dogs (weight range 19.5-36.5 kg) were divided into five groups: group I (n = 11) had surgically induced bladder outlet obstruction. Group II (n = 14) had urinary obstruction and bilateral sectioning of the lowest branches of the pelvic plexus supplying the prostate. Group III (n = 10) had prostate denervation only. Groups IV (n = 10) and V (n = 13) were sham-operated and controls, respectively. In the obstructed groups (I and II), an artificial urinary sphincter (length 4.5-6.0 cm) was placed around the bladder neck and connected to a reservoir placed subcutaneously to allow postoperative adjustments of urinary resistance. All dogs were evaluated at baseline and postoperatively at 1, 3, and 6 months with uroflowmetry, postvoid residual urine volume, cystometry as well as serum creatinine, and urinalysis. RESULTS: Occurrences of detrusor instability were not associated with prostatic denervation input. The mean peak flow rates decreased significantly in the obstructed groups at all follow-ups, but did not change significantly in the nonobstructed groups. Postoperatively, the mean maximum bladder capacity was significantly decreased for groups I and II only. However, a significant correlation between maximum bladder capacity and maximum detrusor pressure could not be detected at any time point in any of the groups. Mean postvoid residual urine volume varied considerably in all groups over time. Creation of a urinary model of infravesical obstruction was associated with considerable problems. CONCLUSIONS: In our dog model of bladder outlet obstruction, prostatic sensory nerve fibers appear not to be involved in detrusor instability. Surgical induction of a constant model of bladder outlet obstruction was difficult even in a large animal. The observations from the present study raise questions about the validity of obstructive urinary animal models.

Animals↗

PubMed1998

Position-related changes in voiding dynamics in men.

OBJECTIVES: To investigate by urodynamic study position-related changes in uroflowmetry and postvoid residual urine volume (PVR) in men because altered bladder function in the supine position may be a predisposing factor for urinary tract infections in the institutionalized elderly. METHODS: Two healthy men, 34 and 59 years of age and living at home, and 53 nursing home residents (mean age 71.8 years, range 46 to 92) were evaluated with uroflowmetry in the standing and recumbent positions (lying on the left or right side); corresponding PVRs were measured by transabdominal ultrasonic bladder scanning. The two healthy men were monitored longitudinally with multiple recordings in both voiding positions, and the nursing home residents were subjected to two observations: one measurement of the variable parameters in either position. Differences were considered to be significant at P < 0.05. RESULTS: The 34-year-old man performed 51 3 flows (368 standing and 145 recumbent). The mean of all the peak flow rates in the upright (28.2 +/- 4.2 mL/s) versus the recumbent (16.8 +/- 4.1 mL/s) position revealed a highly significant difference (P = 0.0001). Sixteen urinary flows and corresponding PVRs were completed by this subject in either voiding position. The difference between PVRs in the standing (13.1 +/- 14.7 mL) versus recumbent (15.3 +/- 17.5 mL) position was not statistically significant. The 59-year-old man completed 156 flows (128 standing and 28 recumbent). A highly significant difference was noted between the mean of all peak flows in the upright (18.9 +/- 4.1 mL/s) versus recumbent (12.6 +/- 2.0 mL/s) position (P = 0.0001). Thirty-seven urinary flows and corresponding PVRs were completed by this individual (10 PVRs were determined after voiding in the standing and 27 after voiding in the recumbent position). No significant difference was noted between PVRs in the standing (24.6 +/- 34.4 mL) versus recumbent (16.5 +/- 60.0 mL) position. In the nursing home residents, the difference between the mean peak flow rates in the standing (14.5 +/- 8.6 mL/s) versus recumbent (12.4 +/- 6.7 mL/s) position also reached statistical significance (P = 0.0084). The difference between PVRs in the standing (60.5 +/- 125.6 mL) versus recumbent (84.8 +/- 186.2 mL) position barely reached statistical significance (P = 0.0497). CONCLUSIONS: The urinary flow rate decreases in the recumbent position. Bedridden residents may be predisposed to urinary tract infections because of alterations in voiding dynamics in the supine position. This area needs further study.

Adult↗

PubMed1997

alpha-difluoromethylornithine ototoxicity. Chemoprevention clinical trial results.

OBJECTIVES: To determine the effects of low-dose oral eflornithine hydrochloride (difluoromethylornithine [DFMO]) administration on hearing and to identify factors that influence those effects. DESIGN: Combined data from 2 studies: a prospective, randomized phase 1 clinical trial of eflornithine (n = 26 subjects) and a prospective, randomized, placebo-controlled phase 2 clinical trial of eflornithine (n = 40 subjects). SETTING: Ambulatory academic tertiary care referral center. PARTICIPANTS: Sixty-six volunteer subjects who had previously treated bladder, prostate, or colon cancer with no current evidence of neoplastic disease, or who were healthy individuals at increased risk for colon cancer, all without need of hearing amplification. INTERVENTIONS: Subjects were randomized to receive oral eflornithine at daily doses between 0.5 and 3 g per square meter of body surface area (g/m2) for 6 to 12 months (phase 1 study) or randomized to receive placebo or eflornithine, 0.5 g/m2 for 12 months (phase 2 study). OUTCOME MEASURES: Auditory thresholds were measured before, during, and after eflornithine administration. Auditory thresholds and threshold shifts were evaluated with regard to eflornithine dose, serologic variables, and demographic factors. RESULTS: Predictable shifts in auditory thresholds occurred following administration of eflornithine. As the daily dose of eflornithine increased, the magnitude and incidence of threshold shift increased, and the time until onset of threshold shift decreased. Threshold changes were greater in the lower frequencies than in the higher frequencies. Subjects' sex, age, and renal function had no effect on eflornithine-associated threshold shifts. Threshold shifts were reversible after eflornithine treatment was discontinued. CONCLUSIONS: Administration of eflornithine is associated with a predictable shift in auditory thresholds. The magnitude and incidence of threshold shift correlate with the daily eflornithine dose.

Anticarcinogenic Agents↗

PubMed1997

Manual circumlaryngeal therapy for functional dysphonia: an evaluation of short- and long-term treatment outcomes.

Manual circumlaryngeal therapy (manual laryngeal musculoskeletal tension reduction) was used to treat 25 consecutive functional dysphonia patients. Pre- and post-treatment audio recordings of connected speech and sustained vowel samples were submitted to auditory-perceptual and acoustical analysis to assess the immediate and long-term effects of a single treatment session. To complement audio recordings, subjects were interviewed in follow-up regarding the stability of treatment effects. Pre- and post-treatment comparisons demonstrated significant voice improvements. No significant differences were observed between post-treatment measures, suggesting that vocal gains were maintained. Interviews revealed 68% of subjects reported occasional partial recurrences, typically less than 4 days in duration, which resolved spontaneously. These results replicate and extend previous research suggesting the utility of manual circumlaryngeal therapy for functional voice disorders.

Adult↗

PubMed1997

Psychological correlates of functional dysphonia: an investigation using the Minnesota Multiphasic Personality Inventory.

Abnormal psychological factors have been implicated in the development of functional dysphonia (FD). This investigation describes the personality and psychological characteristics of 25 female subjects who had received the diagnosis of FD. In all subjects symptoms were resolved after voice therapy. While vocally asymptomatic, these remitted subjects with FD completed the Minnesota Multiphasic Personality Inventory (MMPI), an objective personality questionnaire. When compared with a medical outpatient control group, the results showed that subjects with FD scored significantly higher on 7 of 10 clinical scales, suggesting an elevated degree of emotional maladjustment. A stepwise logistic discriminant analysis identified 2 clinical scales that provided valuable discriminatory power between the two groups. Scale 1 (Hs-hypochondriasis), which measures the number and type of reported somatic complaints, and scale 7 (Pt-psychasthenia), a measure of diffuse anxiety, discriminated the groups with 88% sensitivity and 89% specificity. The results suggested that in spite of symptom improvement after voice therapy, the subjects with FD continued to exhibit poor levels of adaptive functioning, which may represent trait-like vulnerability. The clinical implications of these results for voice practitioners are discussed.

Adolescent↗

PubMed1996

Analysis of factors affecting botulinum toxin results in spasmodic dysphonia.

This study was designed to investigate how variations in patterns of injection could improve the efficacy of botulinum toxin injections in relieving the symptoms of adductor spasmodic dysphonia. A total of 64 adductor spasmodic dysphonia patients who were injected using indirect laryngoscopic localization (for a total of 426 injections) were analyzed retrospectively using their own subjective data on duration of voice improvement, optimal voice improvement, breathiness side effects, and intervals between treatments. Injection to both the thyroarytenoid (TA) and the lateral cricoarytenoid (LCA) simultaneously gave the best voice results; the overall improvement from baseline was the longest lasting, and the period during which the voice was the best was the longest lasting. TA+LCA also gave the shortest duration of undesirable breathiness side effect. On the basis of these data, it seems reasonable to recommend that initial botulinum toxin therapy for adductor spasmodic dysphonia patients should be a single unilateral injection placed strategically at the posterior portion of the TA and directed toward the LCA so that both muscle groups are affected.

Adult↗

PubMed1996

Donor-derived human leukocyte antigen class I proteins in the serum of heart transplant recipients.

BACKGROUND: Human leukocyte antigen class I proteins are expressed on most cell types in all organ allografts but are constitutively secreted only by certain organs, for example, the liver. We hypothesized that detectable levels of donor-derived human leukocyte antigen proteins would be released from transplanted cardiac allografts only when the allograft was immunologically stimulated, that is, during rejection and perhaps during viral infection. If so, then the release of donor human leukocyte antigen might be a noninvasive monitor of these events. METHODS: We used an enzyme-linked immunosorbent assay to detect donor-derived human leukocyte antigen-A2 in the serum of 21 human leukocyte antigen-A2 negative recipients of human leukocyte antigen-A2-positive heart transplants. The level of donor human leukocyte antigen-A2 during the first 100 days after transplantation was correlated with the clinical status of the patient. RESULTS: We found little or no donor human leukocyte antigen in the serum of heart transplant recipients whose postoperative clinical course was unremarkable for infection or rejection. We did find donor-derived human leukocyte antigen in the serum of heart transplant recipients transiently in the week immediately after transplantation, continuously from patients in whom chronic rejection was developing, during cytomegalovirus infection, and during some, but not all, acute rejection episodes as determined by endomyocardial biopsy. CONCLUSIONS: These findings are consistent with the hypothesis that the donor human leukocyte antigen serum level reflects vascular diseases, rather than myocardial disease in the transplanted heart. Therefore, the serum level of donor human leukocyte antigen cannot be used as a monitor of cellular infiltration and myocyte damage as currently assessed by endomyocardial biopsy but may be an early indicator of the development of vascular disease such as chronic rejection.

Biopsy↗

PubMed1996

Foot problems in the diabetic transplant recipient.

Diabetic transplant recipients are at a high risk for foot pathology leading to amputation. This retrospective study from 1/85 to 2/95 examines the risk of foot complications in a population (n = 340) of diabetic renal and combined renal/pancreas transplant recipients. All groups suffered high lower extremity amputation and foot fracture rates. Patients with better circulation and protective sensation intact fared better. Smoking had a profoundly negative effect on the amputation rate as did an amputation prior to the transplant. Patients with pretransplant dialysis were at a higher risk for post-transplant amputation. Concomitant pancreas transplant did not in general significantly affect the risk of amputation or fracture. Females had almost twice the fracture rate of males.

Adult↗

PubMed1995

Transurethral resection versus incision of the prostate: a randomized, prospective study.

OBJECTIVES: To evaluate longer term effects of transurethral resection (TURP) and incision (TUIP) of the prostate in randomized patients. METHODS: In a randomized, prospective study, 120 patients with symptoms of bladder outlet obstruction caused by smaller benign prostates (estimated resectable weight less than 20 g) were assigned to TURP or TUIP. Patients were evaluated preoperatively and at intervals postoperatively as to urinary symptoms (Madsen's questionnaire), sexual function, and uroflowmetry. Overall evaluation of outcome of surgery was also assessed at follow-up visits. RESULTS: Fifty-six patients received a TURP and 61 a TUIP. Three patients refused to participate in the project after randomization, and 5 patients were lost to or excluded from follow-up. A group of 112 patients were obtainable for postoperative evaluation with a mean follow-up time of 34 months (1 to 82 months). Improvements in mean urinary peak flow rates were seen in both groups throughout the study period. The peak flow rates generally were higher (but not statistically so) in the TURP group. Postoperative irritative, obstructive, as well as total symptom scores decreased significantly at all follow-up visits after both TURP and TUIP (P < or = 0.034). Preoperatively and at all postoperative follow-up there was no statistically significant difference in irritative, obstructive, or total symptom scores between TURP and TUIP. The patients indicated an overall subjective improvement at all follow-ups in both groups, with no statistically significant difference between the treatment groups. Fifteen of 22 (68%) patients receiving TURP and 8 of 23 (35%) in the TUIP group who were sexually active before and after surgery developed postoperative retrograde ejaculation (P = 0.020). Postoperatively, 9 (16%) of the patients in the TURP and 14 (23%) in the TUIP group received further treatment for benign prostatic hyperplasia (BPH)-related infravesical obstruction. This difference was not statistically significant (P = 0.908). CONCLUSIONS: In small prostates TURP and TUIP were generally equally effective in relieving bladder outlet obstruction secondary to BPH. Most surgically treated BPH cases can be well managed by the incision technique, which is an underutilized procedure.

Adult↗

PubMed1995

The effect of age, ethnicity and geographical location on impotence and quality of life.

OBJECTIVE: To estimate the prevalence of impotence in men over 40 years of age and correlate impotence to age, geographical location, ethnicity and quality of life. SUBJECTS AND METHODS: While attending 'The Prostate Cancer Awareness Week' in Madison, WI, USA, New Orleans, LA, USA and New York, NY, USA, 1680 men were asked to complete a questionnaire regarding impotence, age, geographical location, ethnicity and quality of life. RESULTS: Impotence was found to be significantly associated with age, was less associated with geographical location but independent of ethnicity. Men living in Madison reported a lower potency score compared with men living in New Orleans and New York. However, potency score for men living in Madison did not appear to decline as rapidly with age when compared with men living in New Orleans and New York. Impotence and quality of life were also found to be associated even when the quality of life estimates were adjusted for age, geographical location, and age by geographical location. CONCLUSION: This study indicates that impotent men have a lower quality of life than potent men and has confirmed previous findings that age is associated with impotence. Surprisingly, answers to impotence questions were also associated with geographical location.

Adult↗

PubMed1994

Effect of age, educational status, ethnicity and geographic location on prostate symptom scores.

We evaluated the effect of patient age, educational status, ethnicity and geographic location upon the American Urological Association benign prostatic hyperplasia symptom scores. Using patients attending Prostate Cancer Awareness Week, we collected additional data on the symptom score and also on education received. A total of 2,245 records was obtained from 4 different centers. Of the population 72% were white and 13% were black. Regression analysis of patient age versus symptom score demonstrated an increase with patient age from 4.59 at age 40 years to 8.17 at age 70 years. Analysis of covariance revealed significant differences in age-adjusted scores between sites from 6.24 in New Orleans, Louisiana to 8.58 in Madison, Wisconsin. No effect was noted for education or ethnicity on symptom scores.

Adult↗