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Biomedical subjects

K R Loughlin

Publications and source records attributed to K R Loughlin.

At least 19 recordsLinked to original sources
PubMed2001

Psoas hitch ureteral reimplantation in adults--analysis of a modified technique and timing of repair.

OBJECTIVES: The psoas hitch ureteral reimplantation technique has been used with great success to bridge defects in ureteral length due to injury or planned resection. Several surgical principles have been historically stressed when performing this procedure, including adequate mobilization of the bladder, fixation of the bladder to the psoas tendon before reimplantation, the use of a submucosal nonrefluxing-type ureteral anastomosis, and a 6-week delay before attempting repair after a surgical injury. We retrospectively reviewed patients who underwent ureteroneocystostomy with a psoas hitch, evaluated the relevance of these principles, and describe a modification of the technique. METHODS: All patients undergoing psoas hitch ureteral reimplantation were reviewed. The indications, complications, and long-term outcomes were assessed. RESULTS: Between 1989 and 1999, 24 patients underwent psoas hitch reimplantation at our institution. The indications were operative injury in 11, planned surgical resection during nonurologic pelvic surgery in 4, cancer in 4, stricture in 4, and trauma in 1. Refluxing-type ureteral anastomoses were performed in 17 cases. One case of postoperative urosepsis occurred. A delayed repair after operative injury did not improve the operative time or overall morbidity. No cases of chronic flank pain, recurrent pyelonephritis, persistent severe hydronephrosis, or compromised renal function, as measured by a change in baseline serum creatinine level, occurred. No patient required reoperation for either early or delayed complications or failure of the repair at a follow-up of 1 to 122 months (mean 32.75). CONCLUSIONS: Psoas hitch ureteral reimplantation is an effective means of treating defects in ureteral length. Immediate repair may be safely undertaken as soon as the ureteral injury is recognized. Long-term sequelae are unusual in adults, even when using refluxing-type ureteral anastomoses.

Adult↗
PubMed2001

The use of hydrogen peroxide to enhance the efficacy of doxorubicin hydrochloride in a murine bladder tumor cell line.

PURPOSE: We determined whether the cytotoxicity of doxorubicin hydrochloride would be enhanced by adding hydrogen peroxide as a source of oxygen free radicals. MATERIALS AND METHODS: Mouse bladder tumor cells (MBT-2) were grown in RPMI 1640 medium and treated with various concentrations of doxorubicin hydrochloride for 2 hours. Protein content was assayed as a measure of cell growth. A similar set of experiments was done with cells exposed to hydrogen peroxide only and combined doxorubicin and hydrogen peroxide. Protein content was again assayed as a measure of cell growth. Cells were also assayed for glutathione peroxidase and malonyl dialdehyde, a product of lipid peroxidation, to determine the mechanism of cell damage. Furthermore, MBT-2 cells were incubated with 100 M. alpha-tocopherol, a free radical scavenger, before exposure to hydrogen peroxide to determine whether the effects of hydrogen peroxide could be reversed. RESULTS: We observed a dose dependent inhibition of MBT-2 cell growth after exposure to doxorubicin hydrochloride. Exposure to doxorubicin and hydrogen peroxide resulted in greater cell growth inhibition than exposure to either agent alone. The effects of hydrogen peroxide on cell proliferation were reversed by pre-incubation with alpha-tocopherol. CONCLUSIONS: As a source of oxygen free radicals, hydrogen peroxide enhances the antiproliferative effect of doxorubicin hydrochloride on a mouse bladder tumor cell line. Thus, hydrogen peroxide may be a relatively inexpensive, nontoxic method of augmenting the cytotoxicity of doxorubicin hydrochloride. Further studies are warranted to determine whether these observations may have clinical application.

Animals↗
PubMed2000

Smoking and alcohol use may be risk factors for poorer outcome in patients with clear cell renal carcinoma.

OBJECTIVES: To correlate the clinical outcomes of 148 patients with clear cell renal carcinoma treated at a single institution with a variety of other factors. METHODS: Cases were derived from a consecutive series of nephrectomy specimens obtained from 1980 to 1994. A retrospective review of clinical records was performed, with tobacco use, alcohol use, recurrence, and survival noted. RESULTS: The median age of the patients was 62 years. The median follow-up was 4.4 years. Of 148 patients, 82% had localized disease (MO), and 18% had suspected metastases (M1) at the time of nephrectomy. Of 121 patients without metastases at diagnosis, T classification was assessed for 117: 48 (41%) had T1 disease, 18 (15%) T2, 46 (39%) T3, and 5 (4%) T4. The Fuhrman grade was 1 or 2 in 51% of patients and 3 or 4 in 45%. Both clinical stage and grade were significantly associated with overall survival (P <0.0001 and P = 0.0028, respectively) and recurrence-free survival (P = 0.0002 and P = 0.0011, respectively). Smoking and alcohol use history was determined in 70% and 63% of patients, respectively. In patients with Stage M0, smokers had a significantly worse overall survival rate compared with nonsmokers (P = 0.039). Also, in patients with Stage M0, a trend toward a worse recurrence-free survival rate was noted in alcohol users compared with those who never used alcohol regularly (P = 0.06). CONCLUSIONS: The prognosis of clear cell renal carcinoma depends on the pathologic stage at diagnosis and the Fuhrman grade. Smoking is a known risk factor for developing renal cancer and may be associated with increased mortality from clear cell carcinoma in patients with Stage M0. Also, regular alcohol use may decrease the recurrence-free survival rate.

Adenocarcinoma, Clear Cell↗
PubMed2000

Telomerase in human bladder cancer.

Biomarkers for human bladder cancer are currently available and more are being developed. However, the ultimate goal of diagnosing bladder cancer consistently in a noninvasive fashion has not yet been achieved. Telomerase is an enzyme that may play a role in maintaining telomere sequences in the ends of chromosomes and its activity may reflect the presence of immortal or cancer cells. In this article, we reviewed the potential applications of telomerase in the diagnosis, monitoring, and treatment of human bladder cancer.

Antineoplastic Agents↗
PubMed2000

An overview of the treatment of superficial bladder cancer. Intravesical chemotherapy.

Superficial bladder cancer accounts for approximately 70% to 80% of all newly diagnosed bladder cancers. The vast majority of these cancers are transitional bladder tumors of various histologic grades (I to III). Superficial tumors include carcinoma in situ (CIS), tumors confined to the epithelium (Ta), and superficial tumors that invade the lamina propria (T1) but do not involve superficial muscle layers. The primary treatment for eradication of stage Ta and T1 bladder cancers is transurethral resection of the tumor. Many patients with superficial bladder tumors treated with endoscopic surgery alone have recurrence or tumor progression at some point in their follow-up, and, in these patients, the need for adjuvant treatment becomes a major concern.

Administration, Intravesical↗
PubMed2000

Evaluation of cyclin expression in testicular germ cell tumors: cyclin E correlates with tumor type, advanced clinical stage, and pulmonary metastasis.

The measurement of proliferative index has yielded promising yet conflicting results in the evaluation of testicular tumors. We have examined the role of Ki-67, along with the cyclins A and E in testicular tumorigenesis. We compared the immunoreactivity of 20 pure seminomas with 20 mixed germ cell tumors composed predominantly of embryonal carcinoma with a variety of proliferation markers, including Ki-67, cyclin A, and cyclin E. All 40 tumors stained for Ki-67, and 19 of 20 (95%) seminomas and 18 of 20 (90%) embryonal carcinomas stained positively for cyclin A. Cyclin E stained 14 of 19 (74%) of the embryonal carcinomas and only 4 of 20 (20%) of the seminomas (Fisher's exact two-tailed test, P = .0012). There was a trend toward larger tumor size for cyclin E-positive seminomas (median, 5.92 cm versus 3.96 cm; P = .08), although the same correlation was not significant in embryonal carcinomas. For both seminomas and embryonal carcinomas, staining with cyclin E did not correlate with the presence of lymphovascular invasion or capsular invasion. However, patients who had cyclin E-positive tumors presented with higher clinical stage (P = .0015). In addition, pulmonary spread in embryonal carcinomas (four patients) and seminomas (one patient) occurred only in patients whose tumors were cyclin E positive (P = .014). Although Ki-67 and cyclin A offer little prognostic information in testicular germ cell tumors, cyclin E immunoreactivity correlates with tumor type and is strongly predictive of distant tumor spread.

Adult↗
PubMed2000

DAZ family proteins exist throughout male germ cell development and transit from nucleus to cytoplasm at meiosis in humans and mice.

The human DAZ gene family is expressed in germ cells and consists of a cluster of nearly identical DAZ (deleted in azoospermia) genes on the Y chromosome and an autosomal homolog, DAZL (DAZ-like). Only the autosomal gene is found in mice. Y-chromosome deletions that encompass the DAZ genes are a common cause of spermatogenic failure in men, and autosomal homologs of DAZ are essential for testicular germ cell development in mice and Drosophila. Previous studies have reported that mouse DAZL protein is strictly cytoplasmic and that human DAZ protein is restricted to postmeiotic cells. By contrast, we report here that human DAZ and human and mouse DAZL proteins are present in both the nuclei and cytoplasm of fetal gonocytes and in spermatogonial nuclei. The proteins relocate to the cytoplasm during male meiosis. Further observations using human tissues indicate that, unlike DAZ, human DAZL protein persists in spermatids and even spermatozoa. These results, combined with findings in diverse species, suggest that DAZ family proteins function in multiple cellular compartments at multiple points in male germ cell development. They may act during meiosis and much earlier, when spermatogonial stem cell populations are established.

Amino Acid Sequence↗
PubMed2000

Virtual CT cystoscopy: color mapping of bladder wall thickness.

RATIONALE AND OBJECTIVES: To improve the conspicuity of bladder tumors in a virtual environment, we developed an algorithm for color mapping the thickness of the bladder wall. The purpose of this study was to demonstrate the feasibility of this algorithm as a component of virtual CT cystoscopy. METHODS: Five subjects with a history of superficial transitional-cell carcinoma of the bladder underwent helical CT scanning after insufflation of the bladder with air. Source images were transformed into three-dimensional models, and the thickness of the bladder wall was demarcated by using a new computer algorithm and a fixed color scale. Results were compared with those obtained by conventional cystoscopy. RESULTS: Three tumors, one site of benign wall thickening, and normal wall thickness were correctly identified by using axial source images and virtual cystoscopy with color mapping. CONCLUSIONS: Color mapping of bladder wall thickness is feasible and demonstrates both normal and thickened urothelium. Its value in identification of small or sessile tumors will require further trials.

Aged↗
PubMed2000

Appropriateness of prostate-specific antigen testing.

We established criteria for appropriate use of the prostate-specific antigen (PSA) assay and used them to evaluate PSA test utilization at 1 tertiary care institution. During a 6-month period, 2,330 PSA results were reported for outpatients and 95 for inpatients. We reviewed medical records for a random sample of 338 outpatient results (14.51%) and all 95 inpatient results, of which 21% (71/338) of outpatient and 17% (16/95) of inpatient results were inappropriate according to our test utilization criteria. Among outpatients, 52% of tests were done for screening and 19% for monitoring for cancer recurrence. For inpatients, workup for cancer (53/95 [56%]) was the most frequent indication for testing and screening the second (24/95 [25%]). Of tests failing the criteria, 66 (76%) of 87 resulted from excessively frequent and age-inappropriate screening. We assessed the potential effect on clinical outcome if these tests were not performed. Of the 87 tests considered inappropriate, only 1 test result influenced clinical management for patients younger than 75 years. By instituting simple limits on age and frequency, we estimate that 74% (64/87) of the inappropriate tests could have been eliminated.

Adult↗
PubMed1999

A phase II trial of methotrexate, cisplatin, 5-fluorouracil, and leucovorin in the treatment of invasive and metastatic urothelial carcinoma.

BACKGROUND: The current treatment of advanced urothelial carcinoma generates high response rates but is associated with poor overall survival. The current study evaluated the efficacy and toxicity of a new combination of active drugs in the treatment of urothelial carcinoma. METHODS: Twenty-four patients with muscle invasive or metastatic urothelial carcinoma were enrolled. Fifteen patients (63%) had metastatic disease whereas 9 patients had T2-T4 disease. Three patients were unevaluable for response because of significant toxicity. Patients were treated every 28 days with methotrexate, 60 mg/m(2), intravenously (i.v.) on Day 1; cisplatin, 25 mg/m(2)/day, by continuous i.v. infusion on Days 2-6; 5-flurouracil (5-FU) 800 mg/m(2)/day by continuous i.v. infusion on Days 3-6; and leucovorin, 500 mg/m(2)/day, by continuous i.v. infusion on Days 2-6. Dosage in subsequent cycles was adjusted according to toxicity. RESULTS: The median follow-up was 81 months (range, 53-97+ months). The overall response rate (complete response + partial response) for all 24 patients was 63% (95% confidence interval, 41-81%). The median survival was 65 months in the patients with muscle invasive disease and 17 months in the patients with metastatic disease. The duration of response in patients with metastatic disease was 6 months (range, 4-19 months). Toxicity was significant, with 82% of patients experiencing Common Toxicity Criteria Grade 3 or 4 neutropenia and 63% experiencing Grade 3 or 4 thrombocytopenia. However, only three patients developed febrile neutropenia and gastrointestinal and neurologic toxicity was moderate. CONCLUSIONS: The combination of methotrexate, cisplatin, 5-fluorouracil, and leucovorin represents an active regimen in the treatment of urothelial carcinoma with a moderate toxicity profile. As new drugs are found to treat urothelial carcinoma, further studies will be needed to evaluate the role of traditional agents such as 5-fluorouracil and methotrexate in new combination chemotherapeutic regimens.

Adult↗
PubMed1999

Squamous cell carcinoma of the penis and microscopic pathologic margins: how much margin is needed for local cure?

BACKGROUND: Total or partial penile amputation is an effective treatment for invasive squamous cell carcinoma of the penis. The authors evaluated the relation between paraffin section microscopic pathologic margins and local recurrence. METHODS: Seventeen cases of biopsy proven squamous cell carcinoma of the penis treated with partial or total penectomy were reviewed retrospectively. All resections were performed by one surgeon (K.R.L.). Permanent microscopic pathologic margins and pathologic classification were determined by one pathologist (A.A.R.) using the American Joint Committee on Cancer TNM classification of 1997. RESULTS: Seven of the 10 patients who underwent a partial penectomy were followed for a mean duration of 33.1 months (range, 3-75 months). The average microscopic pathologic margin was 14.4 mm (range, 0-40 mm) for lesions classified as T1 or greater. Three patients had a microscopic margin < or = 10 mm. There were no local or regional recurrences in this group of patients. The 7 patients who underwent a total penectomy were followed for a mean duration of 25.2 months (range, 5-76 months). There were no local recurrences and only one inguinal recurrence. The average microscopic pathologic margin was 14.8 mm (range, 0-50 mm) for all stages. There were 4 patients who had microscopic pathologic margins < or = 10 mm, and all were free of local disease at the last follow-up. CONCLUSIONS: None of the 14 patients followed developed local recurrence. Also, no recurrence occurred in 7 patients who had microscopic margins of < or =10 mm. This suggests that local control can be obtained with margins measuring less than the standard 15-25 mm.

Amputation, Surgical↗