Biomedical subjects
Publications and source records attributed to John F Ward.
Dietary factors and other naturally occurring substances may emerge as potent therapeutic or preventative agents in the battle against prostate cancer. Much of the current support for these agents is epidemiologically based, but new prospective studies are now underway which may support their use in conventional medical practice.
When claims for the long-term survival of viable organisms are made, either within terrestrial minerals or on Mars, considerations should be made of the limitations imposed by the naturally occurring radiation dose to which they have been exposed. We investigated the effect of ionizing radiation on different bacterial spores by measuring the inactivation constants for B. subtilis and S. marismortui spores in solution as well as for dry spores of B. subtilis and B. thuringiensis. S. marismortui is a halophilic spore that is genetically similar to the recently discovered 2-9-3 bacterium from a halite fluid inclusion, claimed to be 250 million years old (Vreeland et al., Nature 407, 897-900, 2000). B. thuringiensis is a soil bacterium that is genetically similar to the human pathogens B. anthracis and B. cereus (Helgason et al., Appl. Environ. Microbiol. 66, 2627-2630, 2000). To relate the inactivation constant to some realistic environments, we calculated the radiation regimen in a halite fluid inclusion and in the Martian subsurface over time. Our conclusion is that the ionizing dose of radiation in those environments limits the survival of viable bacterial spores over long periods. In the absence of an active repair mechanism in the dormant state, the long-term survival of spores is limited to less than 109 million years in halite fluid inclusions, to 100 to 160 million years in the Martian subsurface below 3 m, and to less than 600,000 years in the uppermost meter of Mars.
The ionizing radiation induced bystander effect is initiated by damage to a cellular molecule which then gives rise to a signal exported to other cells. The nature of this damage is considered with the understanding that it may not be the same as that responsible for the traditional cellular effects of radiation. Consideration is give to amounts of endogenous damage and to radiation yields of the various candidate lesions.
PURPOSE: The ideal imaging study for evaluation of the upper urinary tract in patients with microhematuria has been debated. We prospectively compared the diagnostic yield of computerized tomography (CT) to excretory urography (IVP) in the initial evaluation of asymptomatic microhematuria. MATERIALS AND METHODS: Between December 1998 and June 2001, 115 patients presenting with asymptomatic microhematuria underwent CT and IVP before cystoscopy. Helical CT images with 5 mm. adrenal and kidney slices with and without contrast material were followed by delayed 5 mm. ureteral contrast images through the bladder base. Each CT and IVP was examined by a radiologist who was blinded to the result of the other imaging study. Diagnostic yields of the imaging techniques were compared using the test of 2 proportions and chi-square analysis. RESULTS: Radiographic abnormalities were noted on CT or IVP in 38 patients. Sensitivity was 100% for CT and 60.5% for IVP, and specificity 97.4% for CT and 90.9% for IVP. CT accuracy was 98.3% compared to IVP accuracy which was 80.9% (p <0.001). A total of 40 nonurological diagnoses were made by CT, including 3 abdominal aortic aneurysms and 1 iliac artery aneurysm. No additional diagnoses were made by IVP. Fewer additional radiographic studies were recommended after CT than after IVP. CONCLUSIONS: The use of CT in the initial evaluation of asymptomatic microhematuria results in better diagnostic yield. In addition, more nonurological diagnoses can be made and less additional radiography is needed to confirm a diagnosis.
PURPOSE: Buccal mucosa has been advocated as an ideal graft material for urethral reconstruction. We report our multicenter experience with buccal mucosa ventral onlay urethroplasty for complex bulbar urethral reconstruction in adults. MATERIALS AND METHODS: A retrospective analysis of patients who had undergone buccal onlay urethroplasty at 4 military medical treatment facilities participating in the Uniformed Services Urology Research Group was performed. The database generated included demographic data, genitourinary history, preoperative symptoms (American Urological Association symptom score), preoperative urinary flow rate, stricture length and operative statistics. Postoperative followup data included symptom score, flow rate, retrograde urethrogram results, and complications. RESULTS: A total of 53 patients (average age 32 years, range 17 to 64) underwent buccal mucosa graft urethroplasty between January, 1996 and March, 1998 for refractory strictures. Sixteen patients had undergone an average of 2.2 prior endoscopic procedures (range 1 to 7). Average stricture length was 3.6 plus or minus standard deviation 1.8 cm. (range 2 to 7.5) as measured on preoperative retrograde urethrogram. Followup averaged 25 months (range 11 to 40 months). Average symptom scores decreased from 21.2 (range 14 to 33) preoperatively to 5.4 (range 3 to 8) postoperatively (p <0.001). Average peak urinary flow rates increased from 7.9 preoperatively to 30.1 ml. per second postoperatively (p <0.001). Postoperative retrograde urethrograms were available for 34 patients and were normal in 24. The overall complication rate was 5.4%. Three patients required endoscopic incisions. One patient has a recurrent narrowing and treatment is considered a failure. There were 4 sacculations (7.5%) and 6 narrowings, 3 of which required further treatment. Of the patients 50 required no additional procedures (94.3%). CONCLUSIONS: Buccal mucosa grafts used as a ventral onlay for bulbar urethral reconstruction yield reproducibly excellent results with minimal morbidity and low complication rates. Longer followup will be required to confirm the durability of our results.
PURPOSE: Lymphadenectomy, especially extended lymphadenectomy, is not commonly performed in patients undergoing a radical nephrectomy for clear cell renal cell carcinoma. Surgeons may sample suspicious regional lymph nodes, but the lymph node status of many patients with renal cell carcinoma remains unknown, termed stage pNx. Outcome models based on large institutional reviews have been criticized for grouping stages pNx and pN0 cases because of concern that the pNx category may include unrecognized stages pN1/pN2 disease. We evaluated cancer specific survival differences in patients with clear cell renal cell carcinoma and a lymph node stage of pNx, pN0 or pN1/pN2. MATERIALS AND METHODS: We searched the registry at our institution for patients who underwent radical nephrectomy for clear cell histology renal cell carcinoma between 1970 and 1998. Those with distant metastases at surgery were excluded from study. Clinical features obtained from the medical record included age at surgery, history of tobacco use, hypertension and symptomatic disease at presentation. A single urological pathologist reviewed all tumor specimens for nuclear grade, tumor necrosis, surgical margin status, 1997 tumor stage and lymph node status. These features were compared in patients with stages pNx and pN0 tumors. Cox proportional hazards models were used to compare cancer specific survival in univariate fashion, and after adjusting for tumor stage and grade. RESULTS: The study cohort consisted of 1,535 patients with sporadic, unilateral clear cell renal cell carcinoma who underwent radical nephrectomy. There were 600 patients (39%) with stage pNx, 870 (57%) with stage pN0 and 65 (4%) with stages pN1/pN2 tumors. At an average of 4.2 years after surgery 414 patients died of renal cell carcinoma. On univariate analysis patients with stage pN0 tumors were significantly more likely to die of renal cell carcinoma than those with stage pNx tumors (risk ratio 1.40, 95% confidence interval 1.12 to 1.75, p = 0.003). However, after adjusting for tumor stage and nuclear grade the difference in outcome for stages pNx and pN0 tumors was not statistically significant (risk ratio 1.07 95% confidence interval 0.85 to 1.34, p = 0.583). Patients with stage pNx disease were significantly less likely to be symptomatic at presentation (p = 0.002), have tumors that were less than 5 cm. (p <0.001) and of lower stage (p <0.001) and grade (p = 0.005), and to have tumors with necrosis (p = 0.024) than patients with stage pN0 disease. CONCLUSIONS: Combining stages pNx and pN0 cases to create outcome prediction models after radical nephrectomy for clear cell renal cell carcinoma is appropriate in a multivariate setting that includes tumor stage and grade. Clinical features available preoperatively and during surgery can help guide the decision to perform limited lymph node sampling. When the tumor is 5 cm. or greater, shows pathological necrosis or is advanced grade 3 or 4, lymph node sampling adds little prognostic information.
Cystoprostatectomy specimens removed for bladder malignancy (1988-2000) at two referral centers (Mayo Clinic, Rochester, MN, The University Hospital of Innsbruck, Innsbruck, Austria) were examined for the coincidental finding of prostate cancer (PCA). Centralized examination of the prostate by a single uropathologist was performed if at the time of surgery the patient's serum PSA was < or =2.0 ng/mL and there were no suspicious lesions by digital prostate examination. Pathologic grade, stage, morphometric volume, number of tumor foci and association with areas of high grade prostatic intraepithelial neoplasia (HGPIN) were assessed by light microscopy. DNA ploidy and cellular proliferative index were assessed through digital image analysis. Clinically significant cancers were defined as tumors with > or =0.5 cc volume, Gleason 4 or 5 architecture, pT3, positive surgical margin, multifocality >3, nondiploid DNA content or proliferation index >5%. From nearly 1600 cystoprostatectomy specimens, 129 met the enrollment criteria. Thirty-patients (23%) within this group had PCA identified. Sixty percent of these tumors met the criteria for a clinically significant cancer. Nondiploid nuclear content was present in 17%. HGPIN was present in 70% and directly abutting carcinoma in 86% of prostates. The biologic activity of PCA appears to be independent of serum PSA. Any future definition of a clinically significant PCA should not be solely based upon histologic criteria, but needs to encompass clinical parameters (age, co-morbidities) and a noninvasive assessment of tumor volume and biologic doubling time.