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Biomedical subjects

J Frederick

Publications and source records attributed to J Frederick.

52 records · Page 3Linked to original sources

Hormone prevention of mammary carcinogenesis by norethynodrel-mestranol.

The observation that the susceptibility of the mammary gland to chemical carcinogenesis is inversely related to its level of hormonally induced differentiation led us to test whether treatment of virgin rats with an estrogenic-progestagenic hormone combination protected the gland against this carcinogenesis. Virgin Sprague-Dawley rats aged 45, 55, 65, or 75 days had implanted subcutaneously for 21 days a pellet containing norethynodrel-mestranol (NM) (98.5%-1.5%) at two doses, a physiological or low dose (LD) of 0.5 mg, equivalent to the dose used in Enovid for contraception in humans, and a pharmacological or high dose (HD) of 5.0 mg. Twenty-one days after NM pellet removal, the mammary glands of 5 animals per group were examined for the number of terminal end buds (TEBs), terminal ducts (TDs), alveolar buds (ABs) and lobules, and the DNA labeling index (DNA-LI). The remaining animals received 8 mg 7,12-dimethylbenz(a) anthracene (DMBA)/100 g body weight, and tumorigenesis was evaluated at 24 weeks. The percentage of TEBs decreased with age, and further with NM treatment at both doses. Treatment did not significantly modify the percentage of TDs, but increased that of ABs in most groups. The DNA-LI of TEBs remained constant, even during aging and after treatment, whereas both aging and treatment reduced DNA-LI in TDs and ABs. Tumor incidence declined with increasing age from 75% to 44% in the 45 and 75 day-old control groups respectively. Adenocarcinoma incidence followed the same trend. NM treatment had a dose-related protective effect against development of tumors in general and of adenocarcinomas in particular. LD treatment resulted in a marginally significant reduction in adenocarcinoma incidence, whereas HD-treated animals were 0.24 times as likely as controls to develop carcinomas. There was a statistically significant correlation between the percentage of TEBs present in the gland at the time of carcinogen administration and the incidence of adenocarcinomas. It was concluded that treatment of virgin rats with the hormone combination norethynodrel-mestranol resulted in long lasting structural changes in the mammary gland which protected this organ from a subsequent carcinogenic insult.

9,10-Dimethyl-1,2-benzanthracene↗

Milk curd syndrome in neonates.

Intestinal obstruction caused by the inspissation of formula feedings should be considered in any infant presenting with distal small bowel obstruction. There are typical radiographic changes that suggest the diagnosis. Relief of the obstruction is often possible without surgery.

Desiccation↗

Spontaneous rupture of the spleen in pregnancy with splenic conservation.

Spontaneous rupture of the spleen in pregnancy is rare. It presents with severe internal haemorrhage with a high perinatal and maternal mortality. Splenic preservation is now a well-known option in dealing with splenic damage, and is recommended where possible to avoid diminished immunological competence. This is the first reported case of splenic preservation following splenic damage in pregnancy.

Female↗

Expression of phenotypical changes by human breast epithelial cells treated with carcinogens in vitro.

In order to determine whether human breast epithelial cells undergo malignant transformation when treated with chemical carcinogens in vitro, and how host factors, such as degree of gland development, affect their response to that treatment, twenty-two reduction mammoplasty specimens from women ranging in age from 18 to 63 years and with different parity history were studied in their morphology and in their response to carcinogen treatment in vitro. Fixed tissues were processed for whole mount preparations; it was found that the lobules of the nonpregnant or resting breast tissue could be classified into three types based upon their size and number of alveolar buds composing each one of them, lobules type 1 being the least and lobules type 3 the most differentiated ones. Breast tissues were classified according to the relative proportion of lobules composing it and the reproductive and clinical history of the patient into groups A, B, or C. Fresh tissues from these three groups were digested for obtention of mammary epithelium organoids, which were plated in Dulbecco's minimal essential medium:Ham's F12 (1:1), with 5% horse serum to enhance attachment. When they reached confluence, the cells were replated in serum-free medium; 48 h postplating they were treated with 1.0 microgram/ml 7,12-dimethylbenz(a)anthracene for 24 h, or with 1.0 microgram/ml N-methyl-nitrosourea for 3 h. At every passage, the cells were monitored for colony formation efficiency, survival efficiency in agar-methocel, multinucleation assay, karyotyping, immunocytochemical detection of tumor associated antigens, lectin reactivity, and tumorigenic assay by injection into nude mice. By the fourth passage after treatment, both carcinogens induced increased survival, colony formation in agar-methocel, multinucleation, and increased reactivity with the tumor associated antigen B1:1, an epitope of carcinoembryonic antigen, and the lectins concanavalin A, Dolichos biflorus, and soybean agglutinin. This response was observed only in human breast epithelial cells obtained from less differentiated breasts (Groups A and B), whereas human breast epithelial cells from breasts exhibiting good lobular development (Group C) did not exhibit those changes. No karyotypic abnormalities were detected in treated cells, and they failed to induce tumors when injected into nude mice. It was concluded that mammary gland development is independent of age but is strongly influenced by both the reproductive and clinical history of the donor.(ABSTRACT TRUNCATED AT 400 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗

Node-negative breast cancer treated by modified radical mastectomy without adjuvant therapies: variables associated with disease recurrence and survivorship.

The present study attempts to identify poor prognosis subgroups of women with node-negative breast cancer that might benefit from systemic adjuvant therapy. The cases were collected through a cooperative effort of 57 surgeons at eight hospitals in the Detroit area and coordinated by the Michigan Cancer Foundation where data collection and analyses were completed. The primary treatment of all patients was a modified radical mastectomy. Of the 1,078 cases accessioned between October 1975 and April 1983, 537 were found to have no microscopic lymph node involvement and 462 of these cases received no adjuvant antineoplastic therapy. The period of follow-up of these cases (alive, n = 358) has been 78.75 +/- 24.6 months (mean +/- SD). Overall, the cumulative 6-year recurrence rate as calculated by life table analysis was 26%, with 16.8% dying of their disease. Tumor size was an important prognostic factor; the recurrence rate was 16.2% for those with primaries measuring less than or equal to 1 cm, with only a 6.3% mortality. Patients with tumors measuring greater than 5 cm also did well: 13.7% recurrence and 13.7% mortality rates at 6 years. The premenopausal women did slightly, but not statistically significantly, better than those who were postmenopausal. The presence or absence of quantifiable estrogen receptor protein (ER) was of little predictive value as far as rates of recurrence were concerned, but patients with an ER-positive tumor survived significantly longer. In postmenopausal women, those whose tumor lacked ER (n = 112) fared poorly: 30.4% experienced a recurrence by 6 years and 28% died of their disease. Recurrence rates and death rates were also high in a small group (n = 35) of postmenopausal women with ER+ tumors exhibiting nuclear pleomorphism (nuclear grade [NG]3) (38% and 24.3%, respectively). No poor prognosis group of premenopausal women was identified.

Actuarial Analysis↗

Influence of exercise on coronary sinus blood flow determinations.

Consecutively measured values of coronary sinus blood flow were compared to assess the reproducibility of the coronary sinus thermodilution technique. Values measured at rest and during exercise were evaluated and the influence of the respiratory cycle on reproducibility was studied. Correlation of consecutive values revealed a coefficient of 0.94 at rest and 0.93 during exercise. Differences between mean values of consecutive measurements were nonsignificant. A comparison of the coefficients of variation at rest (8.50 +/- 7.09) and exercise (8.02 +/- 4.75) revealed no significant difference. Variation about mean coronary sinus blood flow due to inspiration and expiration was similar at rest and during exercise (42% and 37%, respectively). Provided that critical variables are closely monitored, the coronary sinus thermodilution technique is a highly reproducible technique in a clinically feasible setting.

Adult↗

Predictors of recurrence and survival of patients with breast cancer.

In this study, the characteristics of 646 patient's primary breast carcinomas, including histologic grade (HG), nuclear grade (NG), mitotic grade (MG), final grade (FG), estrogen receptor (E2R) status, and patient's lymph node status (LN) at the time of surgery were correlated with recurrence-free interval and patient survival in order to determine whether any one parameter or group of parameters serve as adequate predictors of tumor behavior and, therefore, patient's prognosis. The authors' results showed that LN, tumor size, and tumor grade were themselves significant predictors of early recurrence and breast cancer death. Each unit increase in LN or MG increased the risk of death by a factor of 1.5 and 2.0, respectively. However, prediction of time to recurrence or death was considerably more accurate when those parameters were used in conjunction, rather than individually. E2R was also significant in predicting death. MG separated patients within a single LN group or E2R group into two subsets having clinically and statistically different prognoses. It was found that patients who had negative lymph nodes and whose tumors were MG1 had a better prognosis than those with MG2,3 tumors; in these latter patients recurrence and death patterns were similar to those of patients with MG1 tumors having one to three positive lymph nodes. Similarly, whereas patients with four or more positive lymph nodes had bad prognoses, those bearing MG1 tumors tended to behave more like those with MG2,3 tumors and having only one to three positive lymph nodes.

Actuarial Analysis↗

Relationship of tumor prostaglandin levels to early recurrence in women with primary breast cancer: clinical update.

We have determined the levels of prostaglandin E (PGE) and PGF in 94 and 111 primary breast carcinoma specimens, respectively. Tumor specimens were obtained at the time of surgery for primary breast cancer from women without detectable metastatic disease (other than local lymph nodes). Prostaglandins were solvent extracted from tissue homogenates, separated into class by silicic acid chromatography and PG levels determined by radioimmunoassay. These findings were compared to clinically established prognostic indicators. All samples analyzed contained measurable amounts of both PG with a high correlation between levels of PGE and PGF. No association was seen between PG levels and either degree of lymph node involvement, or estrogen receptor. With increasing tumor grade (less differentiation, more pleomorphic nuclei, numerous mitotic figures) higher levels of both PGs were seen, but this association was not statistically significant. These women have been observed for an average of 30 months postsurgery. During that period 20% of tumors have recurred. No significant association were seen between either prostaglandin and the development of recurrent disease or death due to breast cancer. In contrast to published findings, we saw lower than average levels of both E and F in tumors metastasizing to the bone.

Adult↗

Seasonal variation in tumor size at diagnosis and immunologic responses in human breast cancer.

Seasonal variations were observed in tumor size and a number of immunologic responses among patients entered in the Breast Cancer Prognostic Study. A significantly larger number of cases were diagnosed with smaller tumors, less than 2 cm, during December through February. It was also noted that elevated inflammatory reactions were seen in breast tumors removed during November, December and January. Seasonal changes were also observed in the serum IgM and IgE concentrations at the time of the patient's mastectomy. Elevated fall-winter leukocyte migration inhibition response to MCF-7 extracts correlated with the same seasonal elevations observed with serum IgM response. Implications of seasonal variation as a reflection of immune events are considered.

Analysis of Variance↗

Racial differences in breast cancer patients.

One thousand seventy-eight patients diagnosed with primary breast cancer were examined for racial differences in histopathologic and clinical parameters. There were no observed differences in tumor histopathologic type or tumor endocrine status between races. There were no differences with respect to time to breast tumor recurrence observed between black and white patients. However, differences were observed in factors that contributed to tumor stage at diagnosis and to tumor grade. Survival differences observed in univariant analysis of blacks vs. whites were explainable by the presence of more severe skin involvement, tumor grade, and tumor size at diagnosis in the black patients.

Black People↗

Presurgical serum immunoglobulin concentrations and the prognosis of operable breast cancer in women.

Serum concentrations of IgG, IgA, IgM, IgE, and allergen-specific IgE were measured in presurgical serum samples from 400 women admitted to a multidisciplinary study of primary breast cancer. The relationships between the serum immunoglobulins and patient survival were analyzed with the use of a Cox proportional hazards linear model. After adjustment for TNM stage, tumor histopathologic grade, and estrogen receptor (E2R) status, lower IgM concentrations were associated with longer survival. Lower IgE concentrations were also associated with longer survival, but only in patients whose tumors were E2R positive. IgG and IgA were not related to survival. Serum IgM and IgE concentrations, allergen-specific IgE scores, and the tumor E2R status were combined to construct a three-level risk classification that was more prognostic than any of the individual components. Cox model analysis demonstrated that this combination of immunologic and hormonal variables provided significant new information beyond that obtained from TNM staging and histopathologic grading of the tumors (P = .01). This new information may be useful to physicians in advising patients with primary, operable breast cancer about the relative risks and benefits of adjuvant therapy and in designing clinical trials of adjuvant therapy.

Breast Neoplasms↗

Self-help techniques for auditory hallucinations in schizophrenia.

Even with the best treatment available in the United States, people with schizophrenia often remain troubled by auditory hallucinations. Given the less than optimal results of traditional mental health care, the following exploratory study was conducted. A convenience sample of 33 adult outpatients with schizophrenia were interviewed to elicit what (if any) self-help strategies they used for coping with auditory hallucinations. The patients were all being treated at a community mental health clinic. The self-help strategies reported by the patients included (a) physiological changes, (b) cognitive processes, and (c) behavioral changes. The strategies were then rank-ordered by frequency of use and self-reported effectiveness. Various self-help strategies used by subgroups were examined. Men used techniques that were more isolative, and women used more interpersonal techniques to cope with their auditory hallucinations. Participants hearing hostile "voices" (both men and women) tended to use substances such as alcohol and prescribed medications. The results of this study may be used to increase understanding of socially appropriate self-help coping strategies in patients with schizophrenia who experience auditory hallucinations.

Adaptation, Psychological↗