You're the flight surgeon. Panic disorder.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
K O'Toole
Publications and source records attributed to K O'Toole.
Androgen induction of DNA synthesis in the rat penis.
OBJECTIVES: The androgen sensitivity of the mammalian penis has long been appreciated. However, the precise biochemical and structural sequelae of alterations in testosterone, and the mechanisms thereof, remain to be elucidated. Recently, the androgen dependence of rat penile erectile tissue was further clarified at our institution, where the induction of apoptosis was demonstrated in response to castration. In continuity, we report the results of a follow-up study of the regenerative capacity of the regressed, castrated rat penile erectile tissue when testosterone is replenished. METHODS: Three groups of rats were used: normal control rats, castrated without testosterone replenishment, and castrated with subsequent testosterone replenishment. In the third group, castrated rats were given testosterone and killed at 24-hour intervals over 4 days. Specimens of the penis, small bowel, and prostate were obtained from all animal groups. Immunohistochemical identification of intraperitoneally administered 5-bromo-2'-deoxyuridine, a thymidine analogue, was performed to detect new DNA synthesis. The incorporation of this molecule into high molecular weight nuclear DNA served as a measure of DNA synthesis and, hence, cellular proliferation. RESULTS: Testosterone-replenished castrated rat penile stromal cells, both cavernosal and spongiosal, showed more enhanced proliferative activity than those of both castrated unreplenished and uncastrated control rats. Trichrome staining permitted the differentiation of responsive cell subsets. Various cell types were found to respond to replenished testosterone, including myocytes, fibrocytes, endothelial cells, and Schwann cells. Pronounced DNA synthesis occurred as early as 48 hours after the replenishment of testosterone. For purposes of technique validation, sections of small bowel were examined, in which glandular crypt cells would be expected to show rapid turnover. The nuclei of these bowel sections stained in all animal groups throughout the experiment, thus validating the staining technique. The technique of castration and testosterone replenishment was validated by confirming the known response of rat ventral prostate to androgen withdrawal and replenishment. CONCLUSIONS: Our findings provide evidence that testosterone induces cellular proliferation and new DNA synthesis in the penile erectile tissue of castrated rats. This response to testosterone is not limited to one cell type, but rather is multicellular.
Animals↗
Allogeneic bone marrow transplantation with matched unrelated donors for patients with hematologic malignancies using a preparative regimen of high-dose cyclophosphamide and fractionated total body irradiation.
Allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling donor is effective therapy for patients with bone marrow failure states and those with hematologic malignancies. However, only a minority of them will have an HLA-identical sibling donor; unrelated donors, matched or partially mismatched, have been used successfully for patients lacking a related donor. Even though results with allogeneic transplants using unrelated donors are encouraging, the incidence of complications including graft-versus-host disease (GVHD) and graft rejection or late graft failure is increased compared to identical sibling transplants. The combination of cyclophosphamide and total body irradiation (TBI) has been used as an effective preparative regimen for allogeneic transplants, however, the total dosage and dosing schedule of both the cyclophosphamide and TBI has varied significantly among studies. To decrease the rate of graft rejection and late graft failure with volunteer donors, we evaluated a preparative regimen of high-dose cyclophosphamide (200 mg/kg over 4 consecutive days, days -8, -7, -6, -5) followed by fractionated TBI (1400 cGy administered in eight fractions over 4 days, days -4, -3, -2, -1). GVHD prophylaxis included FK506 and methotrexate. From July 1993 to January 1996, 43 adult patients, median age 38 years (range 18-58 years), were treated with this preparative regimen. Seventeen patients had low-risk disease and 26 had high-risk disease. Thirty-one donor/recipient pairs were matched for HLA-A, -B, and -DR by serology and molecular typing. Seven additional pairs were minor mismatched at the HLA-A or HLA-B loci. Four other donor/recipient pairs were HLA-A,-B, and -DR identical by serology but allele mismatched at either DRB1 or DQB. Forty patients were evaluable for myeloid engraftment. Engraftment occurred in all 40 patients at a median of 19 days. There were no cases of graft rejection or late graft failure. Nephrotoxicity was the primary adverse event with 26 patients (60%) experiencing a doubling of their creatinine. Hepatic veno-occlusive disease occurred in seven patients, six of whom had high-risk disease. All patients who had relapsed or refractory disease prior to BMT achieved a complete remission following BMT. Six patients transplanted for high-risk disease relapsed a median of 377 days post-BMT. None of the patients with low-risk disease have relapsed following transplant; the Kaplan-Meier survival for those patients with low-risk disease is 62% and 37% for those patients transplanted with high-risk disease (P = 0.0129). The median Karnofsky performance status is 100% (range 70-100%). Therefore, a preparative regimen of high-dose cyclophosphamide and fractionated TBI is an acceptable regimen for patients receiving an allograft from unrelated donors.
Adolescent↗
Effects of methylphenidate on attention and nonverbal learning in children with attention-deficit hyperactivity disorder.
OBJECTIVE: To examine effects of methylphenidate (MPH) doses on attention and learning tasks requiring varying levels of processing in 23 children with attention-deficit hyperactivity disorder. METHOD: Performance on a continuous performance task (CPT) and two difficulty levels of a nonverbal learning task was evaluated on two doses of MPH (0.3 mg/kg and 0.8 mg/kg) and placebo. RESULTS: CPT commission errors were significantly reduced with low-dose MPH compared with placebo while omission errors were not medication-sensitive. Performance on nonverbal learning tasks was significantly improved with MPH. On the easy level of the nonverbal learning task performance improved equally well with either dose. On the hard level, performance was significantly better at the high dose compared with placebo; no between-dose differences emerged across learning trials. However, the high dose was superior to low and placebo doses in memory recall trials. CONCLUSIONS: Impulsivity may be reduced on an attentional task with a low dose of MPH, and a high dose of MPH may optimize retention and recall of complex nonverbal information.
Analysis of Variance↗
The outcome of unrelated donor bone marrow transplantation in patients with hematologic malignancies using tacrolimus (FK506) and low dose methotrexate for graft-versus-host disease prophylaxis.
Initial studies of FK506 combined with methotrexate (MTX) in patients receiving unrelated donor BMT have demonstrated a possible-decrease in the incidence of severe GVHD but high rates of severe stomatitis and nephrotoxicity. With this background, we undertook a pilot study evaluating FK506 in combination with a lower than usual dose of MTX in an attempt to improve the tolerability of this immunoprophylaxis regimen. Between July 1993 and October 1994, 26 consecutive adults receiving unrelated donor BMT at Emory University Hospital were enrolled on this study. All patients received FK506 intravenously at an initial dose of 0.03 mg/kg/day beginning day -1 and continuing until oral FK506 was tolerated. Patients also received MTX intravenously at 5 mg/m2 on days 1, 3, 6, and 11. The preparative regimen administered to all but one patient included cyclophosphamide at 200 mg/kg over 4 days followed by total body irradiation (TBI) at 1400 cGy in twice daily fractions over 4 days. The median age of patients was 31 years (range: 19 to 52). Sixteen donor/recipient pairs were matched for HLA-A, -B, and -DR by serology and molecular typing. Ten paris were minor mismatches at either class I or class II. Twenty-two of 26 patients (85%) completed four doses of MTX on schedule. Nephrotoxicity was the most common adverse event associated with the administration of FK506: 88% of patients experienced a doubling of their serum creatinine. One patient died of central nervous system hemorrhage prior to engraftment. Twenty-four of the remaining 25 patients (96%) engrafted. Fourteen of 24 patients (50%) evaluable developed grades 2-4 acute GVHD. The rate of severe (grades 3-4) acute GVHD was 25%. Chronic GVHD developed in 11 of 20 (55%) evaluable patients. At a median follow-up of 461 days, 14 patients (54%) are alive. All are relapse-free with a median Karnofsky performance status of 90% (range: 70-100%). The cumulative probability of 2-year disease-free survival is 50% (95% confidence interval [CI]: 0.33 to 0.77); for low risk patients 67% (95% CI: 0.47 to 0.95) and for high risk patients 23% (95% CI: 0.049 to 1.00). These preliminary data indicate that FK506-based immunosuppression following unrelated donor BMT is effective in preventing severe acute GVHD and warrants comparison to CSA-based regimens.
Adult↗
Giant multilocular cystadenoma of the prostate.
Giant multilocular prostatic cystadenoma is a rare clinicopathologic entity characterized by benign histology and the ability to enlarge massively. The lesion may arise from the prostate gland either in continuity with the prostatic urethra or separate from it, or it may arise as a lesion distinct from the prostate gland. Obstructive voiding symptoms occur in all reported cases. The use of preoperative radiographic evaluation, such as magnetic resonance imaging, effectively defines the lesion's benign nature and aids in planning surgical extirpation.
Aged↗
The role of the reverse-transcriptase polymerase chain reaction assay for prostate-specific antigen in the selection of patients for radical prostatectomy.
Prostate cells present in the peripheral circulation can be detected using an enhanced reverse-transcriptase polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) assay. In one study, preoperative enhanced RT-PCR for PSA status was a significant predictor of surgical pathology and postoperative biomechanical recurrence. The use of RT-PCR may enhance the urologist's ability to stage potential candidates for radical prostatectomy, as the assay is a more sensitive and specific predictor of microscopic extracapsular extension than conventional staging modalities. This highly adaptable assay also may have roles in screening for recurrence and in staging other solid tumors.
Adenocarcinoma↗
The use of RT-PCR for prostate-specific antigen assay to predict potential surgical failures before radical prostatectomy: molecular staging of prostate cancer.
OBJECTIVE: To assess the potential role of a recently developed reverse transcriptase-polymerase chain reaction (RT-PCR) assay for prostate-specific antigen (PSA), that detects circulating prostate cells in patients with prostate cancer, in the management of clinically localized cancer. PATIENTS AND METHODS: A total of 138 men (mean age 62.5 years, range 49-70) scheduled for radical retropubic prostatectomy had an RT-PCR assay before surgery. The results were compared with the final pathological stage of disease, the results from local imaging techniques, serum PSA levels, digital rectal examination (DRE) and Gleason score. RESULTS: Enhanced RT-PCR for PSA was the best predictor of potential surgical failures; 70% of patients with positive surgical margins or invasion into the seminal vesicle were identified pre-operatively by a positive RT-PCR assay (odds ratio = 12.0, positive predictive value = 64%, negative predictive value = 87%). RT-PCR was able to identify pre-operatively patients with adverse pathology, despite low serum PSA values (< 4.0 ng/mL). In patients with high PSA level (> 10 ng/mL), RT-PCR discriminated between potentially curable candidates and those with established extraprostatic disease. CONCLUSIONS: RT-PCR for PSA adds unique prognostic information when considering patients for radical surgery. The final role for the RT-PCR assay is as yet undefined; however, the ability to detect potential surgical failures pre-operatively using a molecular approach should have a significant impact on the management of patients with prostate cancer.
Aged↗
Preoperative reverse transcriptase polymerase chain reaction for prostate specific antigen predicts treatment failure following radical prostatectomy.
PURPOSE: We previously demonstrated than an enhanced reverse transcriptase-polymerase chain reaction assay for prostate specific antigen (PSA) can predict final pathological stage in radical prostatectomy patients. The potential role of the assay in predicting serum PSA recurrence after radical prostatectomy was explored. MATERIALS AND METHODS: We evaluated 100 radical prostatectomy candidates by reverse transcriptase polymerase chain reaction preoperatively, and status was compared to serum PSA, Gleason score and final pathological results. Potential surgical failure was defined as tumor at the surgical margin or extending into the seminal vesicle. Patients were monitored postoperatively by serum PSA every 4 months. Kaplan-Meier analysis was used to evaluate the correlation between reverse transcriptase polymerase chain reaction and disease recurrence, defined as a PSA of 0.2 ng/ml. or greater. RESULTS: Enhanced reverse transcriptase polymerase chain reaction for PSA had a stronger correlation with potential surgical failure than preoperative serum PSA or Gleason score (relative risks 15.2, 5.9 and 3.2, respectively). The correlation between these modalities and PSA recurrence was evaluated during a mean followup of 13.6 months (range 5 to 26). Of 36 patients with positive reverse transcriptase polymerase chain reactions 9 had failure by PSA compared to 3 of 64 (4.7%) with negative polymerase chain reactions (p<0.0286). The relative risk for failure by reverse transcriptase polymerase chain reaction was 3.6. Gleason score and serum PSA had higher correlations with postoperative PSA elevations (relative risk 13.2 and 7.6, respectively). A Cox regression analysis model demonstrated that reverse transcriptase polymerase chain reaction for PSA can be used in conjunction with Gleason score and provides statistically significant risk information. CONCLUSIONS: Enhanced reverse transcriptase polymerase chain reaction for PSA is a statistically significant predictor of potential failure by pathological analysis and of disease recurrence by PSA. Longer followup data are required to define further the role of the assay in the management of patients with prostate cancer.
Aged↗
Telemedicine: videoconferencing in medicine.
Ten years ago the professional concern of the medical illustrator was limited to the fields of film-based image acquisition and traditional artists media. The development of affordable digital cameras and computer based illustration software is shifting the balance to computers so that currently both artists and photographers use similar tools. Telemedicine is defined by the European Foundation for the Improvement of Living and Working Conditions as: 'The use of telecommunications and informatics for medical and health purposes'. Telemedicine may incorporate medical video, still image and document transfer which may have originated in medical illustration departments. The paper attempts to explain some of the basic concepts associated with telemedicine and it's medium: videoconferencing.
Computer Communication Networks↗
Enhanced reverse transcriptase-polymerase chain reaction for prostate specific antigen as an indicator of true pathologic stage in patients with prostate cancer.
BACKGROUND: As up to 50% of all patients with prostate cancer who have undergone radical prostatectomy are found to be understaged subsequent to surgery, a more sensitive early staging modality currently is needed. A molecular assay that detects prostate specific antigen (PSA)-synthesizing cells in the peripheral circulation of patients with prostate cancer is described. METHODS: An enhanced reverse-transcriptase polymerase chain reaction (RT-PCR) assay specific for PSA mRNA was performed on RNA extracted from blood drawn from 94 patients before radical prostatectomy. Surgical specimens were examined to determine the extent of tumor spread. The assay was compared with imaging modalities, digital rectal examination, and serum PSA level as predictors of pathology. Additionally, patients were monitored postoperatively by serum PSA level to determine any potential correlation between patient RT-PCR scores and subsequent tumor recurrence. RESULTS: Postoperative pathology revealed that 36 of the 94 patients had extraprostatic disease at the time of surgery. Enhanced RT-PCR identified 26 of these patients from preoperative blood specimens (72% sensitivity). The test was negative for 51 of the 58 patients with organ-confined disease (88% specificity). An odds ratio analysis showed that no other preoperative staging modality was related more strongly to extraprostatic or organ-confined disease. Follow-up PSA determinations revealed that RT-PCR positive patients were at higher risk for a recurrence. At 6 months after surgery, the rates for an increased PSA were 19 and 2% for RT-PCR-positive and -negative patients, respectively. CONCLUSIONS: The data from this follow-up study continue to support the utility of enhanced RT-PCR as an early staging modality for radical prostatectomy candidates.
Androgen Antagonists↗
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↗
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↗
Changes in urinary cytokine mRNA profile after successful therapy for acute cellular renal allograft rejection.
Explore the source record for details and available documents.
Biomarkers↗
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↗
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↗
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↗
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↗