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Biomedical subjects

C Rose

Publications and source records attributed to C Rose.

At least 253 records · Page 14Linked to original sources
PubMed1988

Repeated fine needle aspirations in the diagnosis of soft tissue metastases in breast cancer.

In 36 patients, treated for breast cancer and with a suspected metastasis in the subcutis, the diagnostic efficacy of repeated fine needle aspiration (FNA) has been evaluated in 39 tumours. By increasing FNA from one to three, the diagnostic sensitivity was increased from 0.59 (95% C.L. 0.33-0.82) to 0.83 (95% C.L. 0.52-0.98). Diagnostic specificity for one aspiration was 0.95 (0.77-1.00), and for two and three aspirates it was 0.96 (0.80-1.00) if suspicious aspirates were considered as positive, and 1.00 for one, two and three aspirations when only aspirates with tumour cells were considered positive. Statistically, three aspirates were significantly better than one in establishing the diagnosis of a soft tissue tumour in patients with breast cancer.

Biopsy, Needle↗
PubMed1988

Impact of standardization of estrogen and progesterone receptor assays of breast cancer biopsies in Denmark.

Estrogen and progesterone receptor (ER and PgR, respectively) data for the three laboratories participating in the Danish Breast Cancer Cooperative Group (DBCG) project for treatment of primary breast cancer are presented for the period 1979-1986. The frequency of ER positivity remained constant for one laboratory throughout this period, while this value changed significantly in the other two laboratories. Inter-laboratory reproducibility (evaluated as the frequency of ER positivity) was poor at the onset of the project (P = 0.0003) but, due to standardization procedures, improved after 1982. Slight but significant differences in the composition of the patient populations at the three centers (menopausal status and tumor size) may account for some of the differences observed both in frequency of PgR positivity as well as PgR concentrations determined. Greater intra- and inter-laboratory differences were observed in all three laboratories for PgR than for ER. Part of this variation is believed to have been alleviated by the addition of 10 mM sodium molybdate to the assay buffer in 1983. From having very divergent frequencies of PgR positivity in the three laboratories (31-71%) in 1981, this divergence has been reduced in 1985 (62-78%). While data regarding ER status significantly distinguish between patients with long versus short recurrence-free survival (irrespective of treatment) in one laboratory in both the 77 and the 82 generations of clinical protocols within the DBCG program, ER status from the other two laboratories makes this distinction only in the 82 protocols. We attribute this inability of ER status to distinguish among patients in the 77 protocols to the suboptimal nature of the assays performed in these two laboratories at that time. The overall improvement in comparability of data from the three laboratories during the standardization procedures as well as the fact that ER status from all three laboratories is now capable of distinguishing different patient groups attest to the fact that standardization procedures are both necessary and useful.

Aged↗
PubMed1988

Frequency dependence of synchronization of cochlear nerve fibers in the alligator lizard: evidence for a cochlear origin of timing and non-timing neural pathways.

The dependence of synchronization of spike discharges on tone frequency was measured in cochlear nerve fibers of anesthetized alligator lizards at 21 degrees C. Synchronization measures were based on the fundamental component of a Fourier analysis of the instantaneous discharge rate in response to tone bursts. Measurements were obtained from fibers innervating hair cells in both the region of the cochlea that contains a tectorial membrane (tectorial fibers) and the region where hair-cell stereocilia are free-standing in scala media (free-standing fibers). Both rate and synchronization tuning-curves were measured automatically as a function of tone frequency. For tectorial fibers, the shapes of synchronization tuning-curves are roughly similar to the shapes of rate tuning-curves: the characteristic frequencies (CF's) of both curves are approximately equal. For free-standing fibers, the shape of synchronization tuning-curves differ markedly from those of rate tuning-curves. The CF's of synchronization and rate tuning-curves differ - the ranges are 0.2-0.6 kHz and 1-4 kHz, respectively - and the two CF's are uncorrelated. Synchronization filter-functions, which are contours of synchronization index at constant average discharge rate, were measured as a function of tone frequency for both tectorial and free-standing fibers. These synchronization filter-functions have the shapes of lowpass filters. For the populations of tectorial fibers and of free-standing fibers taken separately, these functions are independent of CF. The corner frequency of these functions is 0.50 +/- 0.038 kHz for tectorial fibers and 0.37 +/- 0.037 kHz for free-standing fibers. We conclude that these populations are characterized by different synchronization filters. For free-standing fibers, synchronization filter-functions measured at average driven discharge rates of about 20 and 40 spikes/s do not differ appreciably, and the high-frequency slope is -80 to -115 dB/decade. The results show that tectorial fibers encode timing information for low-level stimuli, whereas free-standing fibers do not. It is proposed that in the alligator lizard, neural pathways that encode timing information originate in the tectorial region and those that encode non-timing information originate in the free-standing region.

Acoustic Stimulation↗
PubMed1988

Stages of degradation of timing information in the cochlea: a comparison of hair-cell and nerve-fiber responses in the alligator lizard.

Responses to clicks and tone bursts of hair cells and nerve fibers in the free-standing region of the alligator lizard cochlea were compared. The objective was to determine the extent to which the hair-cell processes that produce the receptor potential are also responsible for the attenuation of the synchronized responses of nerve fibers. The AC component of the receptor potential of these hair cells has a high-frequency attenuation of 20 dB/decade [Holton and Weiss (1983) J. Physiol. 345, 205-240], whereas the synchronized response of cochlear neurons is attenuated at a rate of least 80 dB/decade [Rose and Weiss (1988) Hear. Res. 33, 151-166]. Therefore, the processes that link the receptor potential to the nerve discharge act as a lowpass filter with a high-frequency attenuation of at least 60 dB/decade. This could be obtained from a cascade of at least three first-order lowpass filter processes.

Acoustic Stimulation↗
PubMed1988

A comparison of synchronization filters in different auditory receptor organs.

Measurements of the frequency dependence of synchronization of cochlear nerve fibers obtained in different auditory receptor organs are compared. These synchronization filter-functions are lowpass filter-functions and differ primarily in corner frequencies which we estimate to be (in kHz): 2.5 (cat), 1.1 (guinea pig), 0.48 (alligator-lizard tectorial fibers), 0.42 (tree frog), and 0.34 (alligator-lizard free-standing fibers). Some of this variation in corner frequency can be explained by temperature-dependent lowpass-filter mechanisms with a temperature factor of 2.6-3.3 for a change in temperature of 10 degrees C. However, factors in addition to temperature must be involved in producing the differences in corner frequency between cat and guinea pig fibers and between tectorial and free-standing fibers in the alligator lizard.

Acoustic Stimulation↗
PubMed1988

Adjuvant systemic treatment and the pattern of recurrences in patients with breast cancer.

The aim was to analyze the impact of adjuvant systemic treatment (AST) on the anatomical distribution, the number, and the temporal relationship of the first metastases in 635 patients (pts) with breast cancer. These patients participated in the prospective studies of AST of the Danish Breast Cancer Cooperative Group (DBCG) 77-program. All patients had primary high-risk breast cancer (i.e. node positive or local invasion or tumor size greater than 5 cm). The initial treatment was mastectomy with axillary sampling, followed by postoperative radiotherapy. The types of AST and the number of patients with recurrence were: chemotherapy (CT), 134 pts; levamisole (LEV), 96 pts; tamoxifen (TAM), 154 pts. The pattern of recurrence in these patients was compared with the pattern of recurrence in 251 pts who did not receive AST (controls). Although CT reduced the total number of metastatic sites (P = 0.04), the incidence of liver metastases was increased compared to untreated controls (P = 0.02). The median number of metastatic sites was equal in TAM- and LEV-treated pts compared to controls. The incidence of lung metastases was increased in TAM-treated pts (P = 0.03), and LEV-treated pts had a decreased incidence of lymph node (P = 0.01) and pleural recurrences (P = 0.01) compared to controls. The results may suggest that mechanisms of clonal selection during the metastatic process involve differences in sensitivity to antineoplastic treatments of metastases at various anatomical locations.

Antineoplastic Agents↗
PubMed1988

Histological grade and steroid receptor content of primary breast cancer--impact on prognosis and possible modes of action.

The clinical course of breast cancer was related to degree of anaplasia (DA) and steroid receptor (SR) content of primary tumours in 743 patients (pts) with clinical recurrence, initially enrolled in the DBCG-77 protocols. The oestrogen receptor (ER) and the progesterone receptor (PgR) content was known in 110 and 67 pts. The recurrence-free interval, survival after recurrence, and the overall survival were all prolonged in patients with well differentiated tumours or with high SR content. The tumour growth rates were estimated as clinical rates of progression (i.e., the time elapsed from a single distant metastasis until dissemination). The progression rate was prolonged in relatively well differentiated as well as in receptor rich tumours. The extent of dissemination, as indicated by the number of metastatic sites, was not associated with either DA or SR content. However, the anatomical distribution of metastases varied with both DA and SR content: signs of poor prognosis (high DA or low SR content) were associated with occurrence of visceral metastases. In contrast, SR rich tumours had a propensity for recurrence in bone. The results suggest that the impact on prognosis of the features examined here includes both variations in growth rate and metastatic pattern.

Breast Neoplasms↗
PubMed1988

A serine peptidase responsible for the inactivation of endogenous cholecystokinin in brain.

A serine endopeptidase was characterized as a major inactivating enzyme for endogenous cholecystokinin (CCK) in brain. CCK-8 released by depolarization of slices of rat cerebral cortex, as measured by its immunoreactivity (CCK-ir), undergoes extensive degradation (approximately 85% of the amount released) before reaching the incubation medium. However, recovery of CCK-ir is enhanced up to 3-fold in the presence of serine-alkylating reagents (i.e., phenylmethylsulfonyl fluoride) as well as selected active site-directed inactivators (i.e., peptide chloromethyl ketones) or transition-state inhibitors (i.e., peptide boronic acids) of serine peptidases. Among these compounds, elastase inhibitors were the most potent protecting agents, whereas trypsin or chymotrypsin inhibitors were ineffective. HPLC analysis of endogenous CCK-ir recovered in media of depolarized slices indicated that endogenous CCK-5 [CCK-(29-33)-pentapeptide] was the most abundant fragment and that its formation was strongly decreased in the presence of an elastase inhibitor. HPLC analysis of fragments formed upon incubation of exogenous CCK-8 [CCK-(26-33)-octapeptide] with brain slices showed CCK-5, Gly-Trp-Met, and Trp-Met to be major metabolites of CCK-8 whose formation was prevented or at least diminished in the presence of the elastase inhibitor. It is concluded that there is an elastase-like serine endopeptidase in brain that cleaves the two peptide bonds of CCK-8 where the carboxyl group is donated by a methionine residue and constitutes a major inactivation ectoenzyme for the neuropeptide.

Animals↗
PubMed1988

Treatment of severe cryptosporidium-related diarrhea with octreotide in a patient with AIDS.

Cryptosporidiosis commonly causes severe diarrhea in immunosuppressed patients. There currently are no antiparasitic drugs consistently effective for this infection. This case describes a 26-year-old hemophiliac patient with acquired immunodeficiency syndrome and cryptosporidiosis whose diarrhea improved with continuous intravenous administration of a long-acting somatostatin analog, octreotide. Somatostatin has a variety of inhibitory effects on gastrointestinal hormones as well as a possible nonspecific effect on gastrointestinal mucosal fluid and electrolyte secretion. The somatostatin analog should be considered for patients with secretory diarrhea refractory to other forms of therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Quality control of receptor analyses of breast cancer tissue in Denmark.

Quality control investigations of estrogen and progesterone receptor (ER and PgR respectively) analyses can be undertaken using two principally different methods. The first, and the most frequently employed, is by comparing the results of analyses of a lyophilized, standard cytosol. The second method is by comparing the frequency of receptor positivity as well as the distribution of the receptor concentrations determined on a large number of representative biopsies in different laboratories. This latter method can, however, only be used provided that the composition of the population of biopsies studied is similar in the laboratories undertaking such an investigation. Both approaches have been used by the three Danish laboratories participating in the Danish Breast Cancer Cooperative Group (DBCG) project. The international and national quality control programs that these three laboratories have participated in are reviewed in the present paper. From having a poor degree of inter-laboratory reproducibility in 1981, the inter-laboratory reproducibility has improved due to a collaborative standardization effort. Using the clinical data available through the DBCG program, we have been able to demonstrate that suboptimally performed receptor analyses can influence the conclusions of clinical studies regarding patient prognosis in relation to receptor status.

Aged↗
PubMed1988

Adjuvant therapy of premenopausal and menopausal high-risk breast cancer patients. Present status of the Danish Breast Cancer Cooperative Group Trials 77-B and 82-B.

From September 1977 to November 1987 high-risk (i.e. with positive axillary lymph nodes, or tumor size greater than 5 cm or skin/facia invasion) premenopausal and menopausal breast cancer patients have been included in 2 randomized trials. In both trials the primary surgical treatment was total mastectomy with axillary sampling. In the first trial (DBCG 77-B) 1034 patients all received postoperative radiotherapy (RT) and were further randomized to 1) no systemic treatment (0), 2) cyclophosphamide (C), or 3) cyclophosphamide + methotrexate + 5-fluorouracil (CMF). The chemotherapy was given for 1 year. With a median observation time of 7 years the actuarial survival after 9 years is 50, 60 and 65% respectively. Retrospectively, the survival benefit was observed to be most pronounced in patients with tumor size less than or equal to 5 cm and with less than or equal to 3 positive lymph nodes. In the subsequent study initiated in 1982 (82-B) all patients received CMF for 9 months. Furthermore they were randomized to 1) RT, 2) no further treatment, or 3) tamoxifen (TAM) for 1 year. As of November 1, 1987, 1308 patients have been included. At 4 years and with a median observation time of 2 years the survival is similar in the 3 groups. In conclusion, in high-risk premenopausal and menopausal patients adjuvant chemotherapy combined with RT resulted in a 20-30% relative reduction in mortality at 9 years compared with RT alone. Preliminary analysis of adjuvant CMF + RT, compared with CMF alone or with CMF + TAM, shows after a median observation time of more than 2 years no significant survival differences.

Adult↗
PubMed1988

Adjuvant treatment of postmenopausal patients with high risk primary breast cancer. Results from the Danish adjuvant trials DBCG 77 C and DBCG 82 C.

The efficacy of adjuvant treatment with tamoxifen was evaluated in protocol DBCG 77 C. Postmenopausal high risk patients (tumor greater than 5 cm, positive axillary nodes, or invasion to skin/fascia) were randomized after total mastectomy and axillary sampling to postoperative radiotherapy (control) or to radiotherapy plus treatment with tamoxifen (TAM), 30 mg daily for 1 year. A total of 1,716 patients entered the study. At 8 years of follow-up, (7 years median time of observation), we observed a significant increase of recurrence-free survival for the TAM treated group and a reduction in mortality, which is significant for patients less than 70 years of age. Retrospectively, an increased recurrence-free survival in TAM treated patients was significant in the following subgroups: tumor less than 5 cm, positive lymph nodes, anaplasia grade II and estrogen receptor level greater than 100 fmol/mg cytosol protein. In the subsequent trial (DBCG 82 C), 1,347 postmenopausal patients less than 70 years were randomized to one of the following 3 regimens: radiotherapy + tamoxifen, 30 mg daily for 1 year (TAM), TAM alone, or TAM + CMF (CMF i.v. day 1 every 4 weeks x 9). The survival is similar in the 3 groups at 4 years (2 years median time of observation).

Aged↗
PubMed1988

The pattern of metastases in human breast cancer. Influence of systemic adjuvant therapy and impact on survival.

Of the 3,802 patients enrolled in the DBCG 77 protocols, 863 developed clinical recurrence within a median follow-up time of 4.9 years (range 2.0-7.0). More than 69% of these had their first recurrence confined to a single anatomical site and 12% had more than two metastatic sites. The most common sites were bone (35%), lung (23%), skin (22%), and regional lymph nodes (16%). The observation period after first recurrence was 3.6 years (range 0.8-6.4). Survival after recurrence was significantly related both to the location and the number of metastases. Patients who were given adjuvant chemotherapy (n = 134) had significantly fewer metastatic sites and significantly more frequent liver metastases than untreated patients (n = 50). Patients who received adjuvant tamoxifen (n = 154) had the same number of metastatic sites, but more often had lung metastases than untreated patients (n = 201). These results probably reflect that metastases in different anatomical locations differ with respect to sensitivity to antineoplastic treatments.

Antineoplastic Agents↗
PubMed1988

Endocrine therapy of advanced breast cancer.

Recent research has resulted in several new options for endocrine treatment of advanced breast cancer. Since one of the most intriguing characteristics of endocrine therapy is that new remissions can be achieved when using subsequent endocrine modalities it is of importance to evaluate their optimal sequence. Tamoxifen has become the most commonly used endocrine therapy of advanced breast cancer due to its few side effects and an overall response rate of 35%, which has been obtained in randomized trials of tamoxifen compared with either ablative, additive or inhibitive treatment approaches. Crossover data from these trials indicate that the highest overall response rate is obtained when tamoxifen is used as first line endocrine therapy. Furthermore, it seems that oophorectomy in premenopausal and aminoglutethimide or progestins in postmenopausal patients are equally effective as second line endocrine therapy. Despite an obvious clinical rationale for combined endocrine therapy most trials exploring this concept have failed to show any benefit. Although data from trials combining tamoxifen with prednisolone or androgens seem exciting, the use of combined endocrine therapy still have to be considered experimental.

Adrenalectomy↗
PubMed1988

DNA ploidy and S-phase fraction in primary breast carcinomas in relation to prognostic factors and survival for premenopausal patients at high risk for recurrent disease.

Fine needle aspiration on small tumour pieces from 153 premenopausal women with primary breast cancer at high risk for developing recurrent disease has been used for flow cytometric DNA analysis; 133 of the tumours had either one or more cell populations different from diploid or a single, diploid cell population with an aspiration cytology showing presence of typical tumour cells. The distribution of tumour cell populations in this material was rather unusual with a high number of tetraploid populations. There were significant differences between various DNA ploidy classes with respect to prognostic factors such as lymph node involvement and oestrogen and progesterone receptor status. The S-phase fraction was significantly lower for diploid tumour cell populations compared to aneuploid populations. Diploid tumours with high S-phase fraction were not correlated to prognostic factors usually indicating a poor prognosis. Patients with an aneuploid tumour cell population classified as medium aneuploid had a significantly shorter recurrence-free survival than the rest of the patients. No conclusion on the effect of adjuvant treatment for patients with different tumour cell populations can be made at present.

Breast Neoplasms↗
PubMed1988

Immunohistochemical steroid receptor detection in frozen breast cancer tissue. A multicenter investigation.

Now that monoclonal antibodies against the estrogen receptor (ER) have become available, it is possible to detect the presence of ER immunohistochemically. In order to evaluate the validity of the immunohistochemical (ERICA) method in a routine detection of ER, we have tested the method in a multicenter investigation. As reference is used a conventional biochemical assay, dextran-coated-charcoal assay (DCC). The investigation analyzes the validity of the ERICA-assay, including a semiquantitative estimation of the ER-content, when the method is used in several independent departments of pathology, and the interobserver variation of the analysis. The results show that the qualitative detection of ER, obtained by the ERICA-assay and the DCC-assay has a concordance of about 90% for all the participating departments. The concordance is around 60-70%, when a semiquantitative estimation of the ER-content is used. The interobserver variation is also very low, with full agreement in 58 of 59 cases. The ERICA-assay may, therefore, be a relevant alternative to the DCC-assay. However, its clinical importance still has to be fully elucidated.

Antibodies, Monoclonal↗
PubMed1987

Prognostic value of steroid hormone receptors: multivariate analysis of systemically untreated patients with node negative primary breast cancer.

The value of estrogen and progesterone receptor (ER and PgR, respectively) determinations in predicting the recurrence-free survival (RFS) has been evaluated in a group of 807 node negative breast cancer patients. All of these patients are enrolled in the Danish Breast Cancer Cooperative Group (DBCG) 77-1a and 82-a protocols for low risk patients, and none of them have received systemic adjuvant therapy. At a median observation time of 50 months and in an evaluation of the total patient population as an entity, ER+ patients had only a marginally significant (P = 0.07) longer RFS than ER- patients while PgR+ patients experienced a significant advantage (P = 0.02). Among patients subgrouped according to menopausal status, both ER and PgR statuses were found to be significant prognostic factors for predicting RFS in the premenopausal women (less than 50 years) but not in peri- or postmenopausal women. Using Cox's multivariate analysis, nuclear pleomorphy was found to be the only significant prognostic variable, while the value of PgR status as a prognostic factor approached significance (P = 0.065). Although knowledge of ER status did not significantly improve distinction between patients with good and poor prognoses in the relatively small subgroup of premenopausal patients (n = 120) when PgR status was known, ER+PgR- patients have a lower risk of recurrence or death than ER-PgR- patients. Using a log-likelihood model, significant and distinct cut-off limits for the definition of receptor positivity were found for premenopausal patients: these were 5 fmol/mg cytosol protein for ER and 10 fmol/mg cytosol protein for PgR. These cut-off levels may reflect the ability of the ligand binding assay method used to discriminate between tissues with and without receptor proteins. Qualitative assessment of receptor status was as valuable as quantitative expression of receptor concentrations in predicting the RFS of the natural course of the disease among node negative premenopausal patients.

Adult↗