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Biomedical subjects

K O'Toole

Publications and source records attributed to K O'Toole.

At least 37 records · Page 2Linked to original sources
PubMed1995

Molecular staging of prostate cancer. II. A comparison of the application of an enhanced reverse transcriptase polymerase chain reaction assay for prostate specific antigen versus prostate specific membrane antigen.

Current imaging modalities used to stage prostate cancer clinically fail to detect extracapsular disease in a significant subset of patients. A molecular based peripheral blood assay using the reverse transcriptase polymerase chain reaction has recently been shown to be a highly sensitive staging modality for detecting extraprostatic disease preoperatively. The assay uses primers that are specific for prostate specific antigen (PSA). We compare the application of the reverse transcriptase polymerase chain reaction assay using primers specific for the human prostate specific membrane antigen with results obtained from the same specimens by reverse transcriptase polymerase chain reaction for PSA. Prostate specific membrane antigen, a recently cloned prostatic antigen, is a transmembrane glycoprotein that has been described as prostate specific. These assays were applied to ribonucleic acids extracted from the peripheral blood lymphocyte fraction of 80 patients with clinically localized prostate cancer. In addition, blood specimens from 20 female patients, 20 young male patients, 25 age-matched control men under treatment for benign prostatic hypertrophy and 20 men with established, untreated metastatic prostate cancer were tested. All 3 groups of noncancer patients had negative polymerase chain reactions for PSA as well as prostate specific membrane antigen. Of 20 metastatic prostate cancer patients 16 (80%) had positive polymerase chain reactions for PSA, while only 10 (50%) had positive results for prostate specific membrane antigen. Among the 80 patients with clinically localized disease (stages T1 to T2cN0M0), 27 and 19 had positive polymerase chain reaction for PSA and prostate specific membrane antigen, respectively, from blood specimens obtained preoperatively. Analyzing the final pathology in each patient with the reverse transcriptase polymerase chain reaction assay identified a significantly stronger correlation with tumor invasion using the results of the PSA test rather than the results of the prostate specific membrane antigen reverse transcriptase polymerase chain reaction test (67% versus 34% sensitivity for detecting capsular penetration, 87% versus 46% sensitivity for detecting disease to the surgical margin and 83% versus 16% sensitivity for detecting seminal vesicle invasion). In contrast to the reverse transcriptase polymerase chain reaction assay for PSA, a similar assay done for prostate specific membrane antigen did not correlate with pathological stage of prostate cancer.

Adenocarcinoma↗
PubMed1995

The incidence of multifocal renal cell carcinoma in patients who are candidates for partial nephrectomy.

PURPOSE: A prospective study was performed to determine the incidence of multifocal renal cell carcinoma in patients who are candidates for partial nephrectomy. MATERIALS AND METHODS: Preoperative imaging studies and surgical specimens in 44 patients suitable for partial nephrectomy but undergoing radical nephrectomy were prospectively reviewed. RESULTS: Of 44 renal cell cancers 11 (25%) demonstrated pathological multifocality, while 10 of 11 multifocal tumors (91%) occurred in the face of a primary tumor 5 cm. or smaller. Tumor multifocality was independent of the size of the primary renal tumor but occurred with a slightly higher frequency in tumors of stage T3A or greater even if the primary tumor was small. CONCLUSIONS: Partial nephrectomy in patients with unilateral renal cancer should be approached with caution and should not be performed simply because it is technically feasible.

Adult↗
PubMed1995

Thrombotic thrombocytopenic purpura associated with FK506 following bone marrow transplantation.

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) have been observed after bone marrow transplantation (BMT), typically occurring 1-6 months following BMT. We describe two patients who developed TTP very early after BMT while receiving intravenous FK506. They were treated with platelet support and plasma exchange (PE) using either fresh frozen plasma (FFP) or cryosupernatant fraction of plasma (CFP), resulting in remission of TTP activity.

Adult↗
PubMed1994

Leiomyoma of bladder: report of case and review of literature.

We recently treated a patient with leiomyoma of the bladder and reviewed the 37 most recent cases in the English language literature. Mean patient age was forty-four years. Women made up 76 percent of the patients. Patients presented most commonly with obstructive urinary symptoms (49%), irritative symptoms (38%), hematuria (11%), or flank pain (13%); 19 percent were asymptomatic. Almost all patients had cystoscopy (87%) and intravenous urograms (IVU) (81%), but fewer had masses on bimanual examination (57%), ultrasound (49%), or computed tomography (CT) scan (35%). Most patients were treated with open resection (62%), while 30 percent were treated with transurethral resection (TUR). Almost all patients were cured with a single procedure (89%). Leiomyoma of the bladder is rare and readily cured with excision.

Adult↗
PubMed1992

Arteriovenous malformation of ureter.

Congenital arteriovenous malformations of the genitourinary tract are rare. We report the first case of an arteriovenous malformation of the ureter. The patient presented with recurrent hematuria and left flank pain. Evaluation included an intravenous urogram, cystoscopy, and retrograde pyelography. A pedunculated lesion thought to be a fibroepithelial polyp was seen at the time of ureteroscopy, and the lesion treated by excisional biopsy and fulguration. Pathologic examination demonstrated an arteriovenous malformation. After thirty-month follow-up, the patient remains asymptomatic and free of recurrence.

Adult↗
PubMed1992

A pilot study of prophylactic aerosolized amphotericin B in patients at risk for prolonged neutropenia.

Invasive aspergillosis continues to be a significant cause of morbidity and mortality in patients with prolonged neutropenia. We performed a phase I trial of escalating doses of aerosolized amphotericin B given by a face mask nebulizer system with a disposable bacterial exhale filter. Five, 10, 15, and 20 mg of drug were dissolved in sterile water and inhaled over 10 to 15 minutes twice daily. Tolerance was studied in 26 patients (18 transplant recipients, and 8 leukemia patients). No side effects were observed at any dose level. Prophylactic treatment ended for 14 patients (54%) when intravenous (IV) amphotericin B was begun empirically for antifungal coverage following fevers. Eleven patients (43%) continued inhaled amphotericin B until blood counts recovered. One patient was taken off study when she developed cardiogenic pulmonary edema. No patient developed clinically suspicious or pathologically documented infection with invasive aspergillosis. Prophylactic aerosolized amphotericin B is well tolerated at 5, 10, 15, and 20 mg twice daily dosing. In addition, prophylactic aerosolized amphotericin B does not appear to sensitize patients to the subsequent use of IV amphotericin B. Although this study suggests that prophylactic inhaled amphotericin B is well tolerated and effective, a large scale controlled trial is needed.

Adult↗
PubMed1992

c-myc protein distribution. Neoplastic tissues of the human colon.

There is an extensive literature documenting the increased or deregulated expression of the c-myc oncogene in human malignancies. The authors have recently devised a sensitive immunocytochemical method for studying the tissue localization of c-myc protein in tissue sections of human colon. We have compared nuclear c-myc staining using a polyclonal rabbit anti-c-myc antibody and a mouse monoclonal myc antibody NCM II 274. Microscopic observation of the tissue specific pattern of c-myc protein distribution shows that nuclear staining intensity varies in normal and neoplastic crypt cell nuclei in parallel with morphologic criteria of neoplasia. These studies yield further information on the usefulness of c-myc protein as a prognostic indicator.

Cell Nucleus↗
PubMed1992

Bronchiolitis obliterans organizing pneumonia as a complication of allogeneic bone marrow transplantation.

We report a patient who underwent two allogeneic bone marrow transplants for chronic myelogenous leukemia, initially in 1984 and again after relapse in 1990, who developed an identical pulmonary syndrome at a similar interval following each transplant. The patient presented with a non-productive cough, bilateral inspiratory crackles, and multiple patchy infiltrates on chest X-ray. Pulmonary function testing revealed a restrictive abnormality but no obstructive defects. The appearance of this pulmonary disorder after each transplant coincided with the development of chronic graft-versus-host disease. In both instances, this pulmonary syndrome completely reversed with corticosteroid therapy. The patient's chest computed tomographic scan and lung biopsy specimens were consistent with the diagnosis of bronchiolitis obliterans with organizing pneumonia (BOOP). While bronchiolitis obliterans has been reported following allogeneic transplant, BOOP has not previously been reported in this setting.

Adult↗
PubMed1992

Phase I study of busulfan, cyclophosphamide, and timed sequential escalating doses of cytarabine followed by bone marrow transplantation.

In both animal models and human studies in leukemia, residual disease on day 8 following myelosuppressive therapy is in a proliferative phase and therefore may be sensitive to the S-phase specific drug cytarabine. Based on this concept, 17 patients with refractory or relapsed leukemia or lymphoma undergoing either autologous or allogeneic bone marrow transplantation (BMT) were treated on a Phase I protocol using high doses of busulfan (16 mg/kg, days -10, -9, -8, -7) and cyclophosphamide (120 mg/kg, days -6, -5) followed by escalating doses of a 48-h continuous infusion of cytarabine (starting dose 1000 mg/m2/48 h, days -3, -2). Ten patients received autologous transplants (two with Hodgkin's disease, seven with non-Hodgkin's lymphoma, one with chronic myelogenous leukemia (CML) in blast phase). Seven received allogeneic BMT (two with refractory acute myelocytic leukemia (AML), one with refractory acute lymphoblastic leukemia (ALL) undergoing a second BMT, one with Burkitt's-type leukemia, one with ALL in fifth relapse and two with CML in accelerated/blast phase). Two of these patients received a T cell-depleted haploidentical transplant. The maximum tolerated dose of cytarabine was 1500 mg/m2/48 h; a pulmonary syndrome including dyspnea, hypoxemia, and interstitial infiltrates which responded to aggressive diuresis was the dose limiting toxicity. Of the 10 patients who received cytarabine doses of 2000 or 2500 mg/m2/48 h, five patients developed adult respiratory distress syndrome (ARDS) with three patients requiring intubation; two recovered. Of the nine patients with lymphoma, seven responded with complete tumor clearance (CTC) with two patients tumor-free 13 and 15 months post-BMT, one remained refractory and one died too early to evaluate (TETE).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

SGP-2 expression as a genetic marker of progressive cellular pathology in experimental hydronephrosis.

The onset of hydronephrosis following unilateral ureteral obstruction is associated with the induced expression of RNA and proteins encoded by the SGP-2 gene. SGP-2 expression has been shown to demarcate mammalian cells undergoing apoptosis. Using in situ hybridization, the cellular localization of SGP-2 expression in the obstructed kidney was determined as a means to study the various phases involved in the progression of hydronephrosis. Within 30 minutes of obstruction, SGP-2 mRNA expression was localized to the adventitial layers of the hilar arteries and intrarenal arterioles. Increasing time of obstruction resulted in the notable absence or depletion of this layer. In addition, the pattern of SGP-2 expression changed with time to the collecting ducts and distal tubules. This study identifies the vascular support tissue of the kidney as the initial site of reaction and potential cell death following ureteral obstruction. We believe that this observation may be of importance in explaining the early alterations in blood flow associated with hydronephrosis.

Animals↗
PubMed1990

Flow cytometric analysis of localized adenocarcinoma of the prostate: the use of archival DNA analysis in conjunction with pathological grading to predict clinical outcome following radical retropubic prostatectomy.

Fifty-four specimens from patients undergoing radical prostatectomy for clinically confined prostate cancer between 1983 and 1987 were reviewed to determine the potential for flow cytometric (FCM) analysis of DNA ploidy and replication rate to predict disease recurrence. Each specimen was deparaffinized for FCM analysis and the pathology slides were reviewed by a single pathologist. FCM characteristics were correlated with pathological grade and stage, and both were correlated with disease status. In this series of patients, routine FCM analysis of DNA ploidy and replication rate failed to significantly enhance the ability of standard histopathological grading to predict disease recurrence in patients having clinically localized prostate cancer. Aneuploid tumors pathologically confined to the prostate did not appear to negatively affect prognosis.

Adenocarcinoma↗
PubMed1988

A report of cytomegalovirus cystitis and a review of other genitourinary manifestations of the acquired immune deficiency syndrome.

We report a case of symptomatic cytomegalovirus cystitis associated with the acquired immune deficiency syndrome related complex. The diagnosis of the acquired immune deficiency syndrome was established by bladder biopsy. The hematuria resolved after systemic acyclovir therapy. The other known urological manifestations of the acquired immune deficiency syndrome are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Contemporary cystectomy versus preoperative radiation plus cystectomy for bladder cancer.

The role of preoperative radiation therapy (RT) as an adjunct to radical cystectomy (C) was studied by reviewing 58 consecutive patients requiring bladder removal during 1980-1982 for transitional cell carcinoma (TCC). Thirty-six patients underwent RT + C; 22 had C alone. The sole reason for choosing between RT + C versus C was physician prejudice favoring one form of therapy over another. Pretreatment clinical staging was similar in both groups, slightly favoring the RT + C group with only 25 percent versus 36 percent of C patients with clinical stage exceeding B1. Pathologic stage distribution similarly favored the RT + C group slightly with only 56 percent versus 68 percent of C patients having lesions with P-stage greater than B1. Thirty-three percent of patients in the RT + C group had papillary lesions in contrast to only 27 percent in the C alone group. There was only one postoperative death in each group. Three-year minimal follow-up was available in all surviving patients. One-, two-, and three-year survival free of disease was 94 percent, 80 percent, and 70 percent, respectively, in the group treated by C alone. Similar figures for the RT + C group were 86 percent, 76 percent, and 60 percent, respectively. Projected five-year survival rates for both groups regardless of preoperative RT was over 60 percent. All but one failure in the RT + C group had 4,000 rad or more preoperative radiation. This contemporary study shows no advantage of preoperative radiation in patients requiring cystectomy for transitional cell carcinoma of the bladder.

Carcinoma, Transitional Cell↗
PubMed1988

Distribution of the c-myc oncoprotein in normal and neoplastic tissues of the rat colon.

A rat model of 5-azoxymethane induced colon cancer was studied in order to correlate histopathological changes and the differential distribution of the c-myc protein. Weanling Fisher 344 rats were injected with three, one week apart, subcutaneous injections of 5-azoxymethane (AOM) (15 mg kg-1) and the animals were divided into low and high fat diet groups. Nine colon tumors, of varying degrees of malignancy, that developed in the AOM-treated rats, and sections of normal colonic mucosa were examined. A rabbit polyclonal anti-c-myc antibody produced nuclear staining at 1:100 dilution in cryostat frozen sections of the normal rat colonic mucosa and the colon tumors when prepared with a Cryostat Frozen Sectioning Aid (CFSA). The tissue localization of the c-myc antibody staining revealed: (1) in normal mucosa, nuclei of the basal portion of the mucosa; (2) in adenomatous polyps, nuclei at all levels of the mucosa; and (3) in a carcinoma in situ, intense staining of glandular epithelial cell nuclei at all levels within the tumor. This procedure may provide a sensitive method for detecting abnormal cells in the colonic epithelium that have an altered proliferative capacity.

Animals↗
PubMed1986

The use of the implantable chemoinfusion pump in the treatment of hepatic metastases of colorectal cancer.

Fifty-five chemoinfusion devices have been implanted in patients with metastasis of colorectal cancer confined to the liver. There were no episodes of pump malfunction or of catheter clotting. Side effects included gastric ulcers in 13 patients and duodenal ulcers in four patients, including one episode of total gastric obstruction. Chemical hepatitis occurred in 13 patients, sclerosing cholangiolitis in one patient, and duodenal dismotility requiring gastroenterostomy in one patient. The response criterion was taken as reduction by at least 50% of the pretreatment carcinoembryonic antigen level; consequently, the response rate was 88%. Median survival of all patients was 19.2 months from the time of diagnosis of hepatic metastases to death, as determined by the Kaplan-Meier method. Median survival from the time of pump implantation to death was 10.1 months.

Carcinoembryonic Antigen↗
PubMed1986

Cystic duct occlusion and transcatheter sclerosis of the gallbladder in the rabbit.

We have identified a reliable sclerosant of the gallbladder in rabbits. After ligating the cystic ducts with a silk ligature in 24 rabbits and aspirating the bile from the gallbladder, we instilled a mixture of 95% ethanol and either 2 M% trifluoroacetic acid (TFA) or 5 M% TFA into the gallbladder. The animals were killed after 6 or 8 weeks. Ethanol with TFA resulted in replacement of gallbladder lumen with fibrous tissue in 22 rabbits. The two sclerosants were equally reliable and produced quantitatively similar fibrosis in the rabbits. The tendency for normal biliary mucosa to repopulate a sclerosed gallbladder can be obviated by complete occlusion of the cystic duct. The parameters for successful transcatheter sclerosis of the gallbladder have now been defined in an animal model.

Animals↗