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Biomedical subjects

J E Tomaszewski

Publications and source records attributed to J E Tomaszewski.

At least 73 records · Page 4Linked to original sources
PubMed1998

Use of endorectal MR imaging to predict prostate carcinoma recurrence after radical prostatectomy.

PURPOSE: To determine the ability of endorectal magnetic resonance (MR) imaging to help predict postprostatectomy disease recurrence and, thereby, patient outcome. MATERIALS AND METHODS: The authors evaluated 116 patients referred for prostate MR imaging during 1991 and 1992 who subsequently underwent radical prostatectomy and for whom follow-up data through 1996 could be obtained. The MR reports, clinic charts, and pathology reports were reviewed. Disease recurrence was established by means of detectable levels of serum prostate-specific antigen (PSA) after surgery. RESULTS: Thirty-four patients (29%) had postoperative disease recurrence. Patients with recurrence had higher preoperative PSA values (P < .0001). These patients also more frequently had positive surgical margins (P = .0005), transcapsular tumor spread (P < .0001), seminal vesicle involvement (P = .0012), and tumors of advanced stage (P < .0001) and high grade (P = .0058). Of 13 patients whose MR examinations showed definite extracapsular disease, eight (62%) had disease recurrence. The recurrence rate when MR imaging indicated limited disease (24%) was similar to that when MR imaging showed possible microscopic extension (27%). An MR finding of definite extracapsular disease was 24% sensitive and 94% specific for the prediction of disease recurrence. CONCLUSION: MR imaging findings of definite extracapsular spread of disease helped predict prostate tumor recurrence with high specificity, although with low sensitivity.

Case-Control Studies↗
PubMed1998

Thermal preconditioning before rat arterial balloon injury: limitation of injury and sustained reduction of intimal thickening.

Heat shock proteins (HSPs) are a family of highly conserved proteins, essential to cell survival, that are induced during times of physiological stress. These proteins, when induced, can provide tolerance to subsequent injury. Several studies have documented that HSPs play an important role in the response of vascular cells to injury or stress. Whether the vasculature itself can be effectively preconditioned before arterial injury is unknown. Vascular HSP induction by whole-body hyperthermia (WBH) was evaluated with regard to its effects on the vascular response to balloon injury. WBH treatment of Sprague-Dawley rats (colonic temperatures of 41 to 42 degrees C for 15 minutes) resulted in maximal arterial HSP expression within 8 to 12 hours. Rats (male, 300 g, n=59) were randomly assigned to undergo either WBH or no treatment 8 hours before standard carotid balloon injury. At 14 (n=26) and 90 (n=21) days after balloon injury, histomorphometric analysis revealed a significant limitation of intimal accumulation in preconditioned arteries as compared to controls (intimal/medial area ratios+/-SEM: 14 days, 0.57+/-0.07 versus 0.86+/-0.08, P=0.01; 90 days, 0.78+/-0.12 versus 1.19+/-0.14, P<0.05). The medial cell proliferation index at 4 days (n=12) was significantly reduced in the treated group as well (3.6+/-0.9% versus 7.2+/-1.3%, P<0.05). Conversely, the mean total cell number in the media of heated arteries was higher (393+/-20 versus 328+/-17, P<0.05). Vascular preconditioning with brief WBH induces a heat shock response in the arterial wall that is associated with a significant and sustained reduction in intimal accumulation. This effect appears to be due in part to preservation of medial cell integrity and limitation of the proliferative response. These results suggest that thermal preconditioning of vascular tissue may be an effective strategy to improve long-term results after revascularization procedures.

Angioplasty, Balloon↗
PubMed1998

Calculated prostate cancer volume greater than 4.0 cm3 identifies patients with localized prostate cancer who have a poor prognosis following radical prostatectomy or external-beam radiation therapy.

PURPOSE: Patients with palpable extraprostatic disease (T3) have a poor prostate-specific antigen (PSA) failure-free (bNED) survival rate after radical prostatectomy (RP) or external-beam radiation therapy (RT). This study was performed to validate or refute the prognostic value of the previously defined calculated prostate cancer volume (cV(Ca)). PATIENTS AND METHODS: For patients with clinically localized disease (T1c,2), a Cox regression multivariable analysis was used to assess the ability of the cV(Ca) value to predict time to posttherapy PSA failure following RP or RT. RESULTS: The cV(Ca) value was a significant predictor (P < or = .0005) of time to posttherapy PSA failure in both an RP and RT data set independent of the one used to derive the cV(Ca)-based clinical staging system. In both RP- and RT-managed patients, estimates of 3-year bNED survival were not statistically different for patients with either T1c,2 disease and a cV(Ca) greater than 4.0 cm3 (RP, 27%; RT, 18%) or T3 disease (RP, 37%; RT, 34%). Despite pathologic T2 disease, the 3-year estimate of bNED survival was at most 51% in RP-managed patients with T1c,2 disease and cV(Ca) greater than 4.0 cm3. CONCLUSION: A cV(Ca) greater than 4.0 cm3 identified patients with T1c.2 disease whose bNED survival was poor after RT or RP despite pathologic T2 disease that suggests the presence of occult micrometastatic disease in many of these patients. Prospective randomized trials to evaluate the impact on survival of adjuvant systemic therapy in these high-risk patients are justified.

Disease-Free Survival↗
PubMed1998

Ethylene glycol poisoning: toxicokinetic and analytical factors affecting laboratory diagnosis.

Ethylene glycol poisoning is an important toxicological problem in medical practice because early diagnosis and treatment can prevent considerable morbidity and mortality. When ingested in the form of antifreeze or other automotive products, ethylene glycol results in central nervous system depression, cardiopulmonary compromise, and renal insufficiency. Metabolism of ethylene glycol to organic acids is required for metabolic derangement and organ damage. Laboratory features of ethylene glycol poisoning include increased anion gap metabolic acidosis, increased osmolal gap, calcium oxalate crystalluria, and detectable ethylene glycol in serum. This Case Conference integrates discussion of the toxicokinetic and analytical variables that affect the laboratory diagnosis of ethylene glycol intoxication.

Acidosis↗
PubMed1998

Native atherosclerosis and vein graft arterialization: association with increased urokinase receptor expression in vitro and in vivo.

Interaction of proteases with cell surface receptors may modulate cell adhesion, migration, invasion, and matrix degradation. Since the plasminogen activator system has been hypothesized to play a role in intimal thickening after various types of vascular injury, we first studied the expression of urokinase receptor (u-PAR) protein and mRNA by smooth muscle cells (SMC) grown in explant cultures from normal and diseased vessels. Using equilibrium binding studies with radiolabeled 125I-labeled single chain urokinase-type plasminogen activator (scu-PA), we determined that SMC cultured from atherosclerotic arteries expressed a higher maximal number of binding sites/cell (3.6 +/- 0.4 x 10(5) sites/cell vs. 2.1 +/- 0.3 x 10(5), +/- SEM, p < 0.05) with a similar affinity (Kd = 1.5 +/- 0.1 vs. 1.2 +/- 0.2 nM, p = ns). However, SMC subcultured from diseased saphenous vein grafts expressed the highest levels of u-PAR compared to SMC from normal saphenous vein (4.8 +/- 0.6 x 10(5) sites/cell vs. 1.6 +/- 0.9 x 10(5), +/- SEM, p < 0.05). Using binding studies and Northern analysis, we demonstrated a dose and time dependent upregulation of u-PAR protein and mRNA expression respectively in human SMC in response to serum stimulation. Using a rabbit specific u-PAR cDNA probe, we demonstrated a similar upregulation of u-PAR mRNA both in rabbit aortic SMC in culture in response to serum stimulation and up to a 20 fold increase in u-PAR mRNA in rabbit jugular veins in response to implantation as arterial grafts in vivo. Finally, to confirm that u-PAR mRNA is upregulated in human vessels after injury, we performed immunohistochemistry and in situ hybridization studies on coronary arteries, normal saphenous veins and saphenous veins from 10 weeks to 13 years after implantation as grafts. u-PAR mRNA was found mainly in the periadventitial microcirculation in normal veins, but was found to be upregulated in the neointima and media of thickened veins in both macrophages and smooth muscle cells. SMC near the internal elastic laminae in diseased coronary arteries appeared to express increased u-PAR mRNA. These data suggest that this increased expression of u-PAR may contribute to early lesion development.

Animals↗
PubMed1998

bcl-2 expression in normal adrenal glands and in adrenal neoplasms.

Archival paraffin-embedded tissue from 5 normal adrenal glands (including 1 from a fetus of 28 weeks' gestation), 6 cases of adrenal cortical hyperplasia, 9 cortical adenomas, 14 cortical carcinomas, and 11 pheochromocytomas were immunostained with monoclonal antibody against bcl-2. Ultrastructural localization of bcl-2 protein was also performed on selected cases. Positive immunostaining for bcl-2 was seen in all of the layers of the normal adrenal cortex, with different staining characteristics. bcl-2 expression was never observed in the normal adrenal medulla. Electron microscopic studies revealed bcl-2 to be localized predominantly to mitochondria, with a small number of labels along the nuclear envelope. Analysis of adrenal neoplasms showed expression of bcl-2 in cortical tumors, but only one positive case in pheochromocytomas. Restriction of bcl-2 expression to adrenal cortex-derived tissue versus adrenal medulla-derived tissue might prove to be helpful for the differential diagnosis between cortical and medullary tumors.

Adolescent↗
PubMed1997

Equivalent 5-year bNED in select prostate cancer patients managed with surgery or radiation therapy despite exclusion of the seminal vesicles from the CTV.

PURPOSE: Prostate Specific Antigen (PSA) failure free survival was determined for select prostate cancer patients managed definitively with external beam radiation therapy to the prostate only or radical retropubic prostatectomy. METHODS AND MATERIALS: A logistic regression multivariable analysis evaluating the variables of PSA, biopsy Gleason score, and clinical stage was used to evaluate the endpoint of pathologic seminal vesicle invasion (SVI) in 749 consecutive prostate cancer patients managed with a radical retropubic prostatectomy. In a subgroup of 332 surgically and 197 radiation managed patients who did not have the clinical predictors of SVI, PSA failure free survival (bNED) was determined. Comparisons were made using the log rank test between surgically and radiation managed patients in this subgroup. In this subgroup, radiation managed patients were treated to a median dose of 66 Gy (66-70 Gy) to the prostate only. RESULTS: The pretreatment PSA (> 10 ng/ml), biopsy Gleason score (> or = 7), and clinical stage (T2b, 2c, or 3) were found to be significant independent predictors (p < 0.001) of SVI. Only 2% of patients without any of these factors had SVI and 17% had extracapsular extension (15% microscopic; 2% macroscopic). In this subgroup the 5-year bNED rates were equivalent [84 vs. 89% (p = 0.67)] for surgically and radiation managed patients, respectively. CONCLUSIONS: Conventional dose external beam radiation therapy directed at the prostate alone resulted in 5-year bNED rates equivalent to surgery on retrospective comparison in patients with clinical stage T1,2a, PSA < or = 10 ng/ml, and biopsy Gleason < or = 6 prostate cancer.

Biopsy↗
PubMed1997

Development of donor-derived prostate cancer in a recipient following orthotopic heart transplantation.

OBJECTIVE: To report the development of metastatic prostate cancer in a heart transplant recipient without a primary focus in the recipient prostate gland; to present genetic evidence suggesting transplantation of the malignancy from the donor. DESIGN: Histological analysis of donor prostate and recipient prostate and rib. Molecular genetic analysis of prostate and kidney tissue from the donor and peripheral blood leukocytes and rib tissue from the transplant recipient. SETTING: University of Pennsylvania Medical Center. RESULTS: Multiple biopsies of recipient prostate were negative for malignancy but recipient rib contained prostatic adenocarcinoma with osteoblastic bone response. Molecular genetic analysis of recipient rib specimen, which contained both histologically normal and neoplastic cells, was shown to contain a combination of alleles from the donor and recipient at 4 loci. CONCLUSION: Although this is a single case report of an uncommon event, genotyping of polymorphic dinucleotide repeat elements from 4 different chromosomal regions provides strong evidence that the tumor cells arose from donor tissue and were transplanted along with the cardiac allograft.

Adenocarcinoma↗
PubMed1997

Toxicity of cordycepin in combination with the adenosine deaminase inhibitor 2'-deoxycoformycin in beagle dogs.

For 3 consecutive days, the nucleoside cordycepin (3'-deoxyadenosine) was administered as 1-hr iv infusions (0, 1, 4, 8, 10, or 20 mg/kg/day) to dogs. These doses were given 1 hr after a bolus iv injection (0.25 mg/kg/day) of 2'-deoxycoformycin (dCF), a potent inhibitor of adenosine deaminase. The hypothesis was that dCF would affect the toxicity of cordycepin. Plasma adenosine deaminase activity was strongly inhibited during the dose period and for 5 days following the final dose of dCF. Dogs given cordycepin alone showed no drug-related toxicities. In dogs given only dCF, drug-related toxicity to lymphoid tissue (lymphopenia and thymus lymphoid depletion), thrombocytopenia, and decreases in food consumption were observed. Cordycepin in combination with dCF produced symptoms associated with severe gastrointestinal toxicity (decreased body weights, emesis, diarrhea, decreased food consumption, and necrosis of the gastrointestinal tract) and bone marrow toxicity (lymphopenia, thrombocytopenia, and depletion of hematopoietic cells). The gastrointestinal tract and bone marrow were sites associated with dose-limiting toxicities. In surviving dogs, most of the effects were reversible by Day 30. The maximum tolerated dose of cordycepin administered in combination with dCF was 8 mg/kg/day (160 mg/m2/day) given daily for 3 days.

Adenosine Deaminase↗
PubMed1997

Combined modality staging of prostate carcinoma and its utility in predicting pathologic stage and postoperative prostate specific antigen failure.

OBJECTIVES: This study was performed to predict the factors that can optimize preoperative staging for clinically localized prostate cancer patients. METHODS: Logistic and Cox regression multivariable analyses were performed on 480 surgically-managed prostate cancer patients to evaluate the ability of clinical stage, prostate specific antigen (PSA), biopsy Gleason sum, percent positive biopsies, and endorectal coil magnetic resonance imaging (erMRI) results to predict for pathologic established extracapsular extension (ECE), seminal vesicle invasion (SVI), and time to postoperative PSA failure. RESULTS: The characteristics of clinically organ-confined prostate cancer patients at high risk (> 67%) for postoperative PSA failure within 3 years include: (A) PSA > 20 ng/mL; (B) Biopsy Gleason sum > or = 8; or (C) erMRI positive for extraprostatic disease and intermediate risk disease. For patients at intermediate risk (ie, either a PSA < 4 and biopsy Gleason sum of 7; PSA > 4 to 10 ng/mL and biopsy Gleason sum 5 to 7; or a PSA > 10 to 20 ng/mL and biopsy Gleason sum 2 to 7), despite 100% positive biopsies, 50% of patients had pathologic organ-confined disease. However, in the subset of intermediate-risk patients with a positive erMRI for either ECE or SVI and at least 50% positive biopsies, all had extraprostatic disease and failed biochemically by 47 months postoperatively. Intermediate-risk patients with < 50% positive biopsies had pathologic organ-confined disease in at least 77% of the cases. CONCLUSIONS: Combined modality staging using the PSA, biopsy Gleason sum, percent positive biopsies, and endorectal coil MRI findings in select patients can predict pathologic stage and postoperative PSA failure. Therefore, this combined modality staging may optimize patient selection for phase 3 trials examining the role of neoadjuvant androgen ablative therapy for patients with clinically localized disease.

Genital Neoplasms, Male↗
PubMed1997

Progressive angiomyolipoma with inferior vena cava tumor thrombus.

A 45-year-old man presented with an incidentally discovered benign renal angiomyolipoma. This lesion initially demonstrated renal vein involvement. On referral to our institution 3 years later, there was interval progression of tumor thrombus to the intrahepatic inferior vena cava. Intravascular extension of benign angiomyolipoma, though rare, has been reported. We present a new example and review the literature concerning this unusual complication of a common renal neoplasm.

Angiomyolipoma↗
PubMed1997

Immunosuppression for human saphenous vein allograft bypass surgery: a prospective randomized trial.

PURPOSE: Vein allografts are an alternative bypass conduit for patients who lack adequate autogenous vein. Animal studies have demonstrated that patency can be augmented by low-dose immunosuppression with azathioprine. METHODS: In a prospective trial, 40 patients (20 men, 20 women) were randomly assigned to receive (17) or to not receive (23) azathioprine (1 mg/kg/day) after cryopreserved vein allograft bypass grafting. Patients had pain or tissue loss that required bypass grafting to pedal or crural outflow and lacked adequate autogenous saphenous vein. Anti-HLA antibody screens were obtained before and after surgery. Biopsies of allografts were performed at implantation and at all subsequent opportunities. Postoperative physical and vascular laboratory examinations occurred every 3 months. RESULTS: During the 31-months follow-up interval (mean, 15.7 months) there were 10 deaths (none immunosuppression-related). The primary graft patency rate at 12 months was 13%, and the limb salvage rate was 42%. No significant difference (p > 0.05) was noted between immunosuppressed and control groups for mortality rate, primary graft patency rate, or limb salvage rate. As a predictor of graft failure, positive preoperative anti-HLA antibody screen (8 patients) approached significance (p = 0.09). Of 22 explanted grafts, 13 (59%) had histologic evidence of rejection (six immunosuppressed, seven control). Seven patients who had negative results of preoperative anti-HLA antibody screens converted after surgery, and six patients had positive results of preoperative screens that became more strongly positive. CONCLUSION: Vein allograft failure is in part mediated by rejection, which is not eliminated by low-dose azathioprine. Both humoral (antibody) and cellular responses to vein allografts develop. The poor patency rates of vein allograft bypass grafts may be improved by more potent immunosuppression as well as improvement in allograft procurement, preservation, and matching.

Aged↗
PubMed1997

Prostate-specific antigen failure despite pathologically organ-confined and margin-negative prostate cancer: the basis for an adjuvant therapy trial.

PURPOSE: A multivariable analysis to evaluate the potential clinical and pathologic factors that predict for early biochemical failure in patients with pathologically organ-confined and margin-negative disease was performed to define patients who may benefit from adjuvant therapy. PATIENTS AND METHODS: Three hundred forty-one prostate cancer patients treated with a radical retropubic prostatectomy between January 1989 and June 1995 and found to have pathologically organ-confined and margin-negative disease comprised the study population. A logistic regression multivariable analysis to evaluate the predictive value of the preoperative prostate-specific antigen (PSA) level, pathologic (prostatectomy) Gleason score, and pathologic stage on PSA failure occurring during the first postoperative year was performed. RESULTS: Predictors of PSA failure during the first postoperative year in patients with pathologically organ-confined disease included pathologic Gleason score > or = 7 (P = .0007) and preoperative PSA level greater than 10 (P < .0001). Corresponding 3-year freedom-from-PSA-failure rates for these pathologic organ-confined patients with both, one, or neither of these factors were 60%, 75% to 84%, and 95%, respectively (P < .0001). CONCLUSION: Prostate cancer patients with pathologically organ-confined and margin-negative disease and a preoperative PSA level greater than 10 ng/mL or a pathologic Gleason score > or = 7 have significant decrements in short-term PSA-failure-free survival. Therefore, these patients should be considered for adjuvant therapy in the setting of a phase III clinical trial.

Humans↗
PubMed1997

Expression of prolactin and its receptor in human breast carcinoma.

The growth regulatory effects of PRL on the human breast are mediated by its receptor (PRLr), a member of the cytokine receptor family. Recent reverse transcriptase-PCR studies by our laboratory and others have shown PRL expression within breast tissues at the RNA level. To confirm the role of this growth factor-receptor complex in normal and malignant breast tissues, the expression of PRL and PRLr was examined in parallel with the estrogen receptor (ER) and progesterone receptor (PR). Sixty-nine cases of primary invasive breast carcinoma were examined for PRL and PRLr expression by in situ hybridization and immunohistochemical technique, respectively. These data revealed widespread expression of PRL and its receptor in the breast cancers studied (>95%) and in the normal breast tissues (>93%), with no association between the expression of PRL-PRLr and ER or PR. These findings stand in contrast to prior RIA-based studies that detected the PRLr in only 20-60% of breast carcinomas, most commonly in ER-PR-positive cells. These results confirm prior data indicating the presence of an autocrine/paracrine loop for the PRL-PRLr complex within human breast tissues. Given the widespread expression of PRL-PRLr in breast cancer, pharmacological interventions aimed at the inhibition of function of this growth regulatory receptor complex may be of considerable utility in the therapy of this disease.

Adult↗
PubMed1997

Immunohistochemical localization of defensin in human coronary vessels.

Neutrophil defensins comprise a family of cationic peptides that possess potent antimicrobial activity. Defensins are normally sequestered in cytoplasmic granules with their primary site of action in phagolysosomes, although some peptide is released into the circulation during the course of infection or inflammation. In view of the fact that neutrophils adhere to the endothelium and that defensins have been reported to bind to human endothelial cells in vitro, we used immunohistochemistry to study the distribution of these peptides in normal and in atherosclerotic human coronary arteries. Defensin was found primarily in the intima of normal and atherosclerotic vessels, most prominently in association with intimal smooth muscle cells. Both large- and small-vessel endothelium stained focally for defensin. Defensin was also found in the media near the external elastic lamina and in some periadventitial vessels. The same distribution was seen in vessels that had been perfusion fixed immediately upon procurement, excluding diffusion of defensin from PMNs ex vivo. These data indicate that neutrophil defensin is present in the walls of human coronary arteries. The deposition of defensin in vessels may contribute to the pathophysiological consequences of inflammation in addition to their role in host defense.

Anti-Infective Agents↗
PubMed1997

Outcome based staging for clinically localized adenocarcinoma of the prostate.

PURPOSE: Some patients with clinically localized prostate cancer are not cured after radical prostatectomy because of the presence of occult systemic disease. The American Joint Commission on Cancer staging classification for prostate cancer does not reliably distinguish between clinically localized patients who are likely or unlikely to be cured after local therapy. This project was undertaken to develop a staging system capable of predicting long-term outcome after radical prostatectomy on the basis of the clinical parameters obtained routinely during the standard workup for patients with adenocarcinoma of the prostate. MATERIALS AND METHODS: A total of 688 clinically localized prostate cancer patients managed with a radical retropubic prostatectomy for adenocarcinoma of the prostate between 1989 and 1996 was evaluated for clinical features predictive of time to prostate specific antigen (PSA) failure using a Cox regression multivariate analysis. A recently defined clinical factor called the calculated prostate cancer volume and its ability to predict time to PSA failure in conjunction with PSA, biopsy Gleason score and clinical stage were evaluated. RESULTS: The calculated prostate cancer volume (p <0.0001) and the pretreatment PSA (p <0.001) provided the optimal staging system for predicting freedom from PSA failure after radical prostatectomy. CONCLUSIONS: The calculated prostate cancer volume and PSA may provide clinically useful information regarding outcome after radical prostatectomy, enabling the selection of a therapeutic approach for an individual patient with clinically localized disease. Validation of this staging system is needed.

Adenocarcinoma↗
PubMed1996

Novel p21WAF1/CIP1 mutations in superficial and invasive transitional cell carcinomas.

Alterations in the p53 gene are a predominant component in the development of transitional cell carcinoma (TCC), but the particular pathways distal to p53 alterations which contribute to urothelial transformation are not defined. Here, the p21WAF1/CIP1 gene, a p53 inducible and p53 independent gene product, was studied in TCC. p21WAF1/CIP1 expression was measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) from five cell lines and 28 tumor specimens (14 superficial, 14 muscle invasive). This was expressed as a ratio of the gene product to L7, a ribosomal housekeeping gene. In addition, exons 4 through 8 of the p53 gene as well as exon 2 of the p21WAF1/CIP1 gene were assayed for mutations by polymerase chain reaction/single stranded conformation polymorphism analysis (PCR/SSCP). Candidate mutations were verified by sequencing. p21WAF1/CIP1/L7 expression was significantly decreased in invasive lesions compared to superficial lesions (P<0.002). p53 mutations were detected by PCR/SSCP in seven tumors [25%] (one superficial, six invasive) and p21WAF1/CIP1/L7 expression was significantly decreased in all tumors that had p53 mutations (P<0.007). PCR/SSCP analysis of exon 2 in p21WAF1/CIP1 detected band shifts in four/28 tumor specimens (two superficial, two invasive), which sequencing and comparison to autologous normal matched DNA revealed as novel mutations.

Carcinoma, Transitional Cell↗