Jay M. Fleisher

Immunocytochemical estrogen and progestin receptor assays in breast cancer with monoclonal antibodies. Histopathologic, demographic, and biochemical correlations and relationship to endocrine response and survival

Breast cancer specimens from 600 women were assayed for estrogen receptors (ER) using an immunocytochemical assay (ICA) employing the monoclonal antiestrophilin antibody H222 Sp γ. Results showed significant correlation with biochemical ER determinations as well as with tumor grade and menopausal status. In 449 cases, results of progesterone receptor assay by ICA using the monoclonal anti‐PgR antibody KD 68, also correlated significantly with biochemical PgR measurements. The ERICA/PgRICA positivity was significantly more frequent in postmenopausal white women. Colloid carcinomas were most likely to be ERICA positive and PgRICA positive whereas medullary carcinomas were most often negative. In 47 patients with advanced mammary carcinoma, results of ERICA and PgRICA were more closely related to endocrine response than those of ER and PgR by dextran‐coated charcoal assay (DCC). In 339 women with Stage I or Stage II breast cancer, ERICA was significantly associated with disease‐free survival. Analysis by Coxs proportional hazard model, however, showed PgRICA to be the best predictor of survival and disease‐free survival in 197 women at the same stages of disease. These data indicate that ICA is more predictive of prognosis than biochemical ER and PgR. The ease of ICA performance coupled with these results indicate that the method is an acceptable substitute for DCC in analyzing breast cancers for ER/PgR.

Marine waters contaminated with domestic sewage : Nonenteric illnesses associated with bather exposure in the United Kingdom

OBJECTIVES This study identified possible dose-response relationships among bathers exposed to marine waters contaminated with domestic sewage and subsequent risk of nonenteric illness. METHODS Four intervention follow-up studies were conducted within the United Kingdom. Healthy volunteers (n = 1273) were randomized into bather and nonbather groups. Intensive water-quality monitoring was used to assign five bacteriological indices of water quality to individual bathers. Illnesses studied were acute febrile respiratory illness, and eye, ear, and skin ailments. RESULTS Fecal streptococci exposure was predictive of acute febrile respiratory illness, while fecal coliform exposure was predictive of ear ailments. Estimated thresholds of effect occurred at bather exposures above 60 fecal streptococci and 100 fecal coliform per 100 ml of water, respectively. Although no relationship was found between eye ailments and indicator organism exposure, compared with nonbathers, bathers were at higher risk for eye ailments. CONCLUSIONS Nonenteric illness can be transmitted via recreational contact with marine waters contaminated with sewage. These results argue against the use of a single indicator to establish water quality standards.

Prevalence of Salmonella serotypes in environmental waters and their relationships with indicator organisms.

The incidence of serotypes of Salmonella in three types of environmental water (sea, river and fresh reservoirs) from north-east Spain was investigated. The study was performed at specific sampling locations during the summer for a period of five years (1992–1996). A total of 823 strains were isolated and 55 different serotypes were identified, 42 were recovered from sea water, 32 from river water and 12 from freshwater reservoirs. The most frequently isolated serotypes coincided with those involved in clinical cases in the area studied. Salmonella enteritidis was the most common (111 isolates), it was found in all types of water, although most predominantly in sea water (16.1% of the isolates). This serotype, together with S. hadar, significantly increased in frequency during the five year study period. The most frequent serotypes in river water and freshwater reservoirs were S. virchow (9.5%) and S. mikawasima (23.8%) respectively. Significant differences were assessed in the indicator organism densities between the samples with serotypes of clinical significance (S. enteritidis, S. infantis, S. typhimurium, S. virchow and S. paratyphi B) and those without clinical significance. Therefore their presence in all environmental waters may be of epidemiological significance.

CURRENT TRENDS IN PROSTATE CANCER DIAGNOSIS AND STAGING AMONG UNITED STATES UROLOGISTS

PURPOSE We analyzed current practice patterns and determined whether urologists are diagnosing and staging prostate cancer in accordance with one another and with available literature. MATERIALS AND METHODS An anonymous questionnaire was mailed to 1,500 randomly selected practicing American Urological Association members throughout the United States, categorized according to practice setting and decade of residency training completion. RESULTS There were 624 respondents (41.6%). Annual routine prostate cancer detection is being aimed toward the right of the age spectrum. More than half of respondents use age specific prostate specific antigen (PSA), while fewer than half use PSA density in determining need for biopsy. The vast majority will perform radical prostatectomy on patients whose age suggests that they will not benefit from surgery. High PSA values and Gleason scores often are disregarded as independent precluding factors when deciding to perform radical prostatectomy. Computerized tomography and radionuclide bone imaging are used routinely far in excess of what the literature suggests is appropriate. Regardless of preoperative staging results, most urologists still perform lymphadenectomy with all radical prostatectomies. CONCLUSIONS Discrepancies exist in practice patterns between urologists as well as inconsistencies in logic within individuals. There is little variation between individuals in different practice settings. Our results reflect the often confusing and conflicting data published during the last decade.

Primary Care Practitioners: An Analysis of their Perceptions of Voiding Dysfunction and Prostate Cancer

PURPOSE We analyzed practice and referral patterns of primary care practitioners regarding the diagnosis of prostate cancer, and the evaluation and treatment of voiding dysfunction. MATERIALS AND METHODS An anonymous multiple-choice questionnaire was mailed to all primary care practitioners in Brooklyn, New York who were registered with the Medical Society of the State of New York. RESULTS More than 25% of primary care practitioners begin performing digital rectal examination after patient age 55 years. Compared to prostate specific antigen (PSA) 59% of practitioners believe that digital rectal examination is more sensitive or that the tests are equal, or they do not know. In regard to PSA 11% of respondents begin testing after patient age 60 years, 11% evaluate PSA only if digital rectal examination is abnormal and greater than 3% never evaluate PSA. Approximately 45% of primary care practitioners indicated that PSA of greater than 4.0 ng./ml. signifies prostate cancer regardless of patient age, prostate size or prostatis and 50% think that digital rectal examination elevates PSA in a clinically significant way. Although 93.2% of respondents refer a patient to a urologist after palpating a prostatic nodule, only 51.1% refer for an area of induration. Of the 47.2% of respondents who attempt pharmacotherapy for voiding dysfunction with finasteride, terazosin or both 15% do not know the agent mechanisms of action. Of those prescribing finasteride 68.6% are not aware of its effects on serum PSA. Overall 66.5% of primary care practitioners are not familiar with the American Urological Association Symptom Index while only 15% of those attempting pharmacotherapy use the index as a diagnostic tool. CONCLUSIONS Primary care practitioners might require further education in regard to the use of PSA, digital rectal examination and pharmacotherapy in voiding dysfunction. Consideration should be given to the establishment of guidelines for urological referral.

An investigation into parametric relationships between enterovirus and faecal indicator organisms in the coastal waters of England and Wales

Previous research has resulted in conflicting conclusions concerning possible statistical relationships between bacterial indicator and enterovirus concentrations in marine waters. Results have suggested either highly significant relationships or no significant correlation. To examine these relationships further, large compliance assessment data sets for identified bathing waters on the English and Welsh coast, between 1988 and 1992, were extended to include enterovirus and faecal streptococci counts in addition to total and faecal coliform data. The suitability of these data for parametric correlation analysis was assessed by examining the nature of the statistical distributions of raw data and residual values from regression analyses. The data were acceptable for parametric analysis when (i) zero enterovirus samples were excluded and (ii) enterovirus counts were logarithmically transformed. The analysis of over 690 data pairs produced positive Pearson correlation coefficients between coliforms, faecal coliforms, faecal streptococci and enterovirus concentrations. Though the correlations were significant (P 99.9% confidence) they were low (r < 0.5). The amount of variance in enterovirus concentration explained by bacterial concentration was only 15–16%. Relationships were similar for each bacterial determinand. Correlations above successive quartile values of bacterial concentration revealed no threshold effect in these relationships. These results suggest poor statistical relationships between concentrations of bacterial indicators of sewage pollution and enterovirus in marine waters resulting in a low predictive capability.

The enterovirus test in the assessment of recreational water-associated gastroenteritis

Abstract This study reports the results of a series of analyses designed to identify possible mathematical relationships between the numbers of fecal streptococci vs the numbers of enteroviruses present (as measured by the enterovirus assay) in marine recreational waters in order to indirectly assess the relationship between enteroviral densities and subsequent risk of gastroenteritis among bathers exposed to marine waters contaminated with domestic sewage. A database consisting of 2066 parallel fecal streptococci and enterovirus enumerations taken from 416 different marine water locations throughout the United Kingdom was used in the analyses. Polychotomous logistic regression was used to model the probabilities of zero enterovirus, a possible infectious dose and a probable infectious dose of enterovirus being present over increasing fecal streptococci densities. The results of the polychotomous logistic regression analyses showed that the probability of the absence of enterovirus (i.e., zero enteroviruses being present) remained higher than the probability of the presence of either a possible or probable infectious dose in 101 of seawater up to a fecal streptococci density of 1000/100 ml of sample (actual estimated probabilities for the three groupings of enterovirus densities described above, at a fecal streptococci density of 1000 equaled 0.44, 0.44, and 0.12, respectively). In addition, the probability of zero enteroviruses being present remained higher than the probability of one or more enteroviruses being present in 101 of seawater up to a fecal streptococci density of 450/100 ml of sample. Since previously published epidemiological studies have shown an excess risk of gastroenteritis to occur among bathers exposed to as few as 32 fecal streptococci per 100 ml of sample, these results suggest that the actual viruses enumerated by the enterovirus assay are not etiologically related to recreational water-associated gastroenteritis. Since gastroenteritis has been the most consistently reported bathing water associated illness, these findings suggest the enterovirus assay to be of limited use in assessing marine recreational water quality given the increasing tendency to formulate water quality standards based on increased risk of gastroenteritis among bathers relative to non-bathers.

Histochemical estrogen binding. An independent predictor of recurrence and survival in stage II breast cancer.

Coxs proportional hazards regression model was used to analyze the prognostic significance of multiple variables affecting recurrence and survival in patients with Stage II breast cancer. Among the variables were biochemical estrogen (ER) and progesterone receptor (PgR) values and results of a histochemical estrogen‐binding assay using a fluoresceinated bovine serum albumin—estradiol conjugate where carrier and label were bound at position 17. In 190 cases ER and PgR were not found to be significantly associated with either disease recurrence or patient survival. On the other hand, patients with tumors that were demonstrably “rich” in estradiol ligand conjugate binding by histochemistry experienced both a longer disease‐free interval (P < 0.03) and survival (P < 0.02) than did patients whose tumors were “poor” in conjugate binding or showed a heterogenous population of positively and negatively stained cells. A patient with a tumor rich in estrogen binding was five times more likely to survive than a patient with a neoplasm that was poor in estrogen binding by histochemistry. These results indicate that the histochemical technique used provides new and independent parameters for determination of prognosis in Stage II breast cancer.