Laser Induced Autofluorescence Diagnosis of Bladder Cancer

Purpose

We assessed the ability of laser induced autofluorescence to differentiate malignant from nonmalignant bladder lesions.

Materials and Methods

We studied 53 patients with bladder cancer undergoing mucosal biopsies or transurethral resection of a bladder tumor. A quartz optical fiber was advanced through the working channel of a cystoscope and placed in gentle contact with the bladder. Tissue fluorescence was excited by 337 nm. light pulses (nitrogen laser). One fiber was used for transmission of the excitation and emission (fluorescence) light. An optical multichannel analyzer system was used to record fluorescence spectra of the sites of interest.

Results

We analyzed the fluorescence spectra of 114 bladder areas (1 carcinoma in situ as well as 28 malignant, 35 inflammatory, 7 dysplastic, 1 squamous metaplastic and 42 normal areas). These lesions included 44 difficult to diagnose suspicious tumors (11 malignant and 33 nonmalignant). We developed an algorithm that used the I385:I455 nm. fluorescence ratio to distinguish malignant from nonmalignant lesions, including inflammatory areas. By analyzing the data on all 114 lesions, we noted the sensitivity, specificity, and positive and negative predictive values of this method for differentiating malignant from nonmalignant bladder lesions to be 97, 98, 93 and 99 percent, respectively.

Conclusions

Under excitation with 337 nm. light a clear differentiation between malignant and nonmalignant bladder tissues can be made using the I385:I455 nm. autofluorescence ratio.     

Reduced nicotine exposure and abstinence outcome in two nicotine fading methods

Two methods of nicotine fading as a smoking cessation preparation technique were compared. A brand-switching procedure and a three-stage set of "Nicotine Faders" graduated filters were the preparation strategies. Both methods implemented a putative 30-50-80% nicotine exposure reduction schedule in three weekly phases. There were a total of 110 study participants (57 in brand switching) enrolled in eight clinic groups. Results indicated that at the 80% reduction level, meaningful reductions in nicotine (measured by its metabolite cotinine) and carbon monoxide (CO) exposure were measurable with both nicotine fading procedures. Overall pooled nicotine and CO exposure drops from baselines of 48.2% and 35.5%, respectively, were recorded. The abstinence outcome measures (pooled 1-year abstinence prevalence = 30.9%) were not significantly different between the two preparation strategies. Trends in nicotine and CO exposure drops, and abstinence outcome measures, however, were consistently in favor of the graduated filters. Potential advantages of filters in the context of a preparation-for-quitting strategy were suggested.     

Revise or preserve? A flurry of views on revision of tax-exemption standards

Many groups would be affected if Congress changes the tax laws governing not-for-profit hospitals. The community benefit standard now in place focuses on nondiscriminatory treatment of patients whose care is paid for by public programs such as Medicaid. It also fosters universal access to emergency care regardless of ability to pay. In 1990, however, a U.S. General Accounting Office (GAO) report suggested that if Congress believes tax-exempt hospitals should provide more charity care, it should consider revising the criteria for exemption. This created a flurry of responses from the groups that would be affected. In response to the GAO's report, Rep. Edward R. Roybal, D-CA, introduced H.R. 790, and Rep. Brian J. Donnelly, D-MA, introduced H.R. 1374, bills linking tax exemption to charity care. The Roybal bill requires not-for-profit hospitals to have an open-door policy for Medicare and Medicaid patients and to provide services to a reasonable number of these patients. The Donnelly bill would in essence codify the IRS's interpretation of the community benefit standard and add to it a charity care requirement. The administration reported it was opposed to a change from the current community benefit standard to an express charity care standard. Nevertheless, it would not oppose a more limited change that codifies the current position. Not-for-profit hospitals have opposed any changes, arguing that the existing community benefit standard is sufficient and that the decision of how to benefit the community should be made by an individual hospital and its community.     

Urban Indians' smoking patterns and interest in quitting.

Little is known about smoking patterns of urban American Indians and their interest in quitting. Most published research has focused upon American Indians who live on rural reservations. In this study, personal interviews were conducted with a convenience sample of patients at Urban Indian Health Clinics in four geographically diverse sites: Milwaukee, WI, Minneapolis, MN, and Seattle and Spokane, WA. A total of 419 current smokers and 173 ex-smokers completed interviews. Current smokers reported a median cigarette consumption of 11 per day. Smokers indicated both a moderate desire to quit (mean 5.97, on a scale 0-10) and moderate confidence in their ability to do so (mean 5.56, on a scale 0-10). More than 70 percent of current smokers indicated having previously tried to quit. The most common reasons cited for relapse included craving, social situations, stress, and nervousness. The most common reasons for quitting given by ex-smokers included being "sick" of smoking, health concerns, respiratory problems, and pregnancy. The estimated quit-ratio (former smokers divided by current+former smokers) was 29.7 percent. This quit-ratio, although substantial, is lower than the 45 percent quit-ratio reported for the general U.S. population. Perhaps the most striking findings are the similarities between American Indians and the overall population in both interest in quitting and reasons for doing so. Smoking cessation previously has been viewed as a low priority for this population. The current results suggest the viability of systematic efforts to encourage urban American Indians to quit smoking.     

Bicalutamide monotherapy versus leuprolide monotherapy for prostate cancer: effects on bone mineral density and body composition.

PURPOSE: Gonadotropin-releasing hormone agonists decrease bone mineral density, lean mass, and muscle size and increase fat mass in men with prostate cancer. Less is known about the effects of bicalutamide monotherapy on bone mineral density and body composition. PATIENTS AND METHODS: In a 12-month, open-label study, we randomly assigned 52 men with prostate cancer and no bone metastases to receive either leuprolide or bicalutamide (150 mg by mouth daily). Bone mineral density and body composition were measured by dual energy x-ray absorptiometry and quantitative computed tomography. RESULTS: Mean (+/- standard error) bone mineral density of the posterior-anterior lumbar spine decreased by 2.5% +/- 0.5% in the leuprolide group and increased by 2.5 +/- 0.5 in the bicalutamide group from baseline to 12 months (P <.001). Mean changes in bone mineral density of the total body, total hip, femoral neck, and trabecular bone of the lumbar spine also differed significantly between groups (P < or =.003 for each comparison). Fat mass increased by 11.1% +/- 1.3% in the leuprolide group and by 6.4% +/- 1.1% in the bicalutamide group (P =.01). Changes in lean mass, muscle size, and muscle strength were similar between the groups. Breast tenderness and enlargement were more common in the bicalutamide group than in the leuprolide group. Fatigue, loss of sexual interest, and vasomotor flushing were less common in the bicalutamide group than in the leuprolide group. CONCLUSION: In men with prostate cancer, bicalutamide monotherapy increases bone mineral density, lessens fat accumulation, and has fewer bothersome side effects than treatment with a gonadotropin-releasing hormone agonist.     

The influence of air bags and restraining devices on extremity injuries in motor vehicle collisions

The influence of air bags and other restraining devices on injury after motor vehicle collisions is not well defined. This study examined the relationship between the use of restraining devices and the incidence of extremity injuries in motor vehicle collisions. A retrospective analysis was performed on motor vehicle collision data submitted to the Pennsylvania Trauma Outcome Study database from 1990 through 1995. Criteria for submission included trauma patients who were admitted to the intensive care unit, who died during hospitalization, who were hospitalized for more than 72 hours, or who were transferred in or out of the receiving hospital. A total of 21,875 patients met these criteria. These patients were analyzed for the presence or absence of upper and lower extremity injuries and were compared based on their use of restraining devices. Restraining devices were categorized into four groups: air bag alone, air bag and seat belt, seat belt or carseat without air bag, and no restraining device. Statistical analysis was performed using the chi-squared test of association. For contingency tables with small expected frequencies, Fisher's exact test was used. Study participants included 11,688 men and 10,185 women with a mean age of 38 +/- 20 years. There were 16,033 drivers and 5,842 passengers. Air bags were deployed in 472 instances. In 297 of these cases, additional restraint was provided with a seat belt. In 6,632 cases, air bags were not deployed; however, patients were restrained with either a seat belt or a carseat. In 14,771 cases, patients were not restrained. When comparing restraining devices as a group vs. no restraint, there was a significant decrease in the incidence of upper (p = 0.018) and lower (p < 0.001) extremity injuries. Air bags, however, were associated with an increased incidence of both upper (p = 0.033) and lower (p = 0.002) extremity injuries when compared with no restraint or when compared among patients who were restrained. As a group, restraining devices decrease the incidence of upper and lower extremity trauma sustained by patients injured in motor vehicle collisions. Air bags, however, are associated with an increased incidence of upper and lower extremity injuries when compared with seat belts alone or when no restraining devices are used.     

Otoacoustic emissions as a screening test for hearing impairment in children recovering from acute bacterial meningitis

OBJECTIVES: To study the efficacy of otoacoustic emissions (OAEs) as a screening test for hearing impairment in children with acute bacterial meningitis. Hearing tests were performed before discharge from the hospital in an attempt to improve coverage and avoid delays in the diagnosis of postmeningitic hearing loss. METHODS: Children with bacterial meningitis were recruited from 21 centers. In the 48 hours before discharge from the hospital, all patients underwent a thorough audiologic assessment consisting of transient evoked OAEs, auditory brainstem responses (ABRs), otoscopy, and tympanometry. Hearing loss was defined as ABR threshold >/=30 dB. The results of OAE screening were compared with the gold standard of ABR threshold. RESULTS: Of 124 children recruited, we were able to perform both OAEs and ABRs on 110 children. Seven (6.3%) of the 110 children had ABR threshold >/=30 dB; 2 had sensorineural hearing loss and 5 had conductive hearing loss. At follow-up, hearing loss persisted in both cases of sensorineural hearing loss and no new cases were identified. All 7 children with hearing loss failed the OAE screening test. Ninety-four children with normal hearing thresholds passed the test, and 9 failed. Thus, the screening test had a sensitivity of 1.00 (95% confidence interval, 0.59 to 1.00), a specificity of 0.91 (0.85 to 0.97), a positive predictive value of 0. 44 (0.20 to 0.70), and a negative predictive value of 1.00 (0.96 to 1.00). CONCLUSIONS: OAE screening in children recovering from meningitis was found to be feasible and effective. The test was highly sensitive and reasonably specific. Inpatient OAE screening should allow early diagnosis of postmeningitic hearing loss and prompt auditory rehabilitation.     

Iron-induced oxidative DNA damage and its repair in primary rat hepatocyte culture

Iron-overload diseases frequently develop hepatocellular carcinoma. The genotoxic mechanism whereby iron is involved in hepatocarcinogenesis might involve an oxidative process via the intermediate production of reactive oxygen species. This was presently investigated by examining kinetics of formation and repair of DNA base lesions in primary rat hepatocyte cultures supplemented with the iron chelate, ferric nitrilotriacetate Fe-NTA (10 and 100 microM). Seven DNA base oxidation products have been identified in DNA extracts by gas chromatography- mass spectrometry, which showed a predominance of oxidized-purines (8- oxo-guanine, xanthine, fapy-adenine, 2-oxo-adenine) above oxidized pyrimidines (5-OHMe-uracil, 5-OH-uracil, 5-OH-cytosine) in control cultures. All these DNA oxidation products revealed a significant dose- dependent increase at 4 to 48 h after Fe-NTA supplementation, among which fapy-adenine showed the highest increase and 5-OH-cytosine was the least prominent. Involvement of iron in this oxidative process was established by a correlation between extent in DNA oxidation and intracellular level of toxic low molecular weight iron. DNA excision- repair activity was estimated by release of DNA oxidation products in culture medium. All the seven DNA oxidation products were detected in the medium of control cultures and showed basal repair activity. This DNA repair activity was increased in a time- and dose-dependent fashion with Fe-NTA. Oxidized-pyrimidines, among which was 5-OHMe-Uracil, were preferentially repaired, which explains the low levels detected in oxidized DNA. Since oxidized bases substantially differed from one another in terms of excision rates from cellular DNA, specific excision- repair enzymes might be involved. Our findings, however, demonstrate that even though DNA repair pathways were activated in iron-loaded hepatocyte cultures, these processes were not stimulated enough to prevent an accumulation of highly mutagenic DNA oxidative products in genomic DNA. The resulting genotoxic effect of Fe-NTA might be relevant in understanding the hepatocarcinogenic evolution of iron-overload diseases.      

Absence of 185delAG mutation of the BRCA1 gene and 6174delT mutation of the BRCA2 gene in Ashkenazi Jewish men with prostate cancer.

Epidemiological studies have demonstrated a clustering of breast and prostate cancers in some families. Moreover, there is an increase in the number of cases of prostate cancer in families with inherited mutations of the breast cancer susceptibility gene BRCA1. We assessed the role of BRCA1 and BRCA2 in prostate cancer. We tested for the BRCA1 185delAG frameshift mutation, found in 0.9% of Ashkenazi Jews, and the BRCA2 6174delT mutation, found in 1% of Ashkenazi Jews, in Ashkenazi Jewish men with prostate cancer. We studied 60 Ashkenazi men with prostate cancer. A family history was obtained by interview or a self-report questionnaire. Histological confirmation of diagnosis was obtained for all subjects. Ethnic background was confirmed for all subjects by self-report or interview. Mutations of BRCA1 and BRCA2 were detected by amplification of lymphocyte DNA from peripheral blood according to standard polymerase chain reaction (PCR) and dot blot procedures. Patients'' ages ranged from 55 to 80 years (mean +/- s.d. 70 +/- 5.25). There were six men with a family history of prostate cancer; three of these had a father with prostate cancer. Five of the men had a family history of breast cancer, in a mother, a sister or an aunt. None of the men had a family history of both breast and prostate cancer. None of the 60 men carried the 185delAG BRCA1 or 6174delT BRCA2 mutations. Of 268 Ashkenazi Jewish women with sporadic breast cancer, tested in an unrelated study, 16 carried either the 185delAG mutation of BRCA1 or the 6174delT mutation of BRCA2. There was a significant difference in the incidence of the BRCA1 and BRCA2 mutations in the breast and prostate cancer cases (P = 0.05, two-tailed Fisher''s exact test). The contribution of germline BRCA1 and BRCA2 mutations to prostate cancer incidence is probably small and could be limited to specific subgroups.