Iron Status of Cats with Chronic Kidney Disease.

BACKGROUND: Iron deficiency is a proposed mechanism for the anemia that occurs in cats with chronic kidney disease (CKD). Minimal research investigating the iron status of these cats has been performed. OBJECTIVE: To compare indicators of iron status in cats with CKD versus healthy cats and cats with nonrenal illness (NRI). To compare indicators of iron status in anemic versus nonanemic cats with CKD. ANIMALS: Thiry-nine client or employee owned healthy cats, 40 cats with CKD and 34 cats with NRI included. METHODS: Exclusion criteria included prior iron or erythropoiesis stimulating agent administration, blood transfusion, or concurrent CKD and NRI. Complete blood counts, serum chemistries, serum iron concentrations, total iron binding capacity (TIBC), and ferritin concentrations were measured and percent transferrin saturation (TSAT) calculated on all cats. Data were analyzed using nonparametric statistical testing. RESULTS: No statistically significant differences were detected among groups for iron concentration (P = .50), ferritin concentration (P = .47), or TSAT (P = .19). TIBC was significantly lower in CKD (median 262 µg/dL; IQR 233-302; range 165-488) versus healthy cats (median 316 µg/dL; IQR 272-345, range 196-464); (P = .0030). When comparing anemic (hemoglobin <9.5 g/dL) versus nonanemic cats with CKD, TSAT was significantly lower (P = .033) in anemic (median 20.2%; IQR 17.8-34.5; range 17.6-35.9) compared to nonanemic (median 29.0%; IQR 25.5-44.1; range 11.5-94.4). No statistically significant differences found for ferritin concentration (P = .94), iron concentration (P = .21) or TIBC (P = .97). CONCLUSIONS AND CLINICAL IMPORTANCE: These results indicate that an iron deficient state exists in anemic cats with CKD and is more likely functional rather than absolute.

High frequency of rare alleles of the human c-Ha-ras-1 proto-oncogene in breast cancer patients.

The c-Ha-ras-1 locus in 104 breast cancer patients and 56 unaffected individuals was examined for allelic restriction fragment-length polymorphism. Four common and 16 rare alleles were detected in the combined populations. The distribution of common and rare alleles differed significantly between the two populations. The common restriction fragments represented 91% of the allele pool in the unaffected population. In breast cancer patients, these common alleles represented only 59% of the allele pool (P less than .001). More specifically, the frequency of two of the common fragments, the 6.5- and 8.0-kilobase alleles, was significantly diminished in the breast cancer population (P less than .001 and P less than .02, respectively). The frequency of rare c-Ha-ras-1 alleles and hence genotypes composed of two rare alleles was increased in the breast cancer population (P less than .001). One of the rare alleles had a significant (P less than .05) association with these breast cancer patients. These results suggest that genotype analysis of the c-Ha-ras-1 locus, in combination with other clinical parameters, may be of prognostic value in assessing the potential for cancer.

Loss of a c-H-ras-1 allele and aggressive human primary breast carcinomas.

The human H-ras protooncogene was shown to be expressed in 16 of 22 invasive ductal carcinomas of the breast. The K- and N-ras protooncogenes were either not expressed or expressed at low levels. No amplification or rearrangement of the three ras genes was detected among the 104 breast carcinoma DNAs tested. These results indicate that the overexpression of H-ras in human breast tumors is not correlated with alteration of the protooncogene. In addition, we did not find any point mutation at the codon 12 of the H-ras or K-ras protooncogenes in 32 and 64, respectively, tumor DNAs examined. However, in tumor DNAs from 14 of 51 patients, heterozygous for H-ras-1 related BamHI restriction fragments, one allele was lost. This allele loss did not alter ras Mr 21,000 protein expression. Correlation with clinicopathological data showed, however, that the loss of one H-ras-1 allele in breast carcinoma DNAs is significantly linked to histological Grade III tumors, the lack of estrogen and/or progesterone receptors, and the subsequent occurrence of distal metastasis. Our results thus indicate that the loss of one H-ras-1 allele correlates with the most aggressive primary carcinomas of the breast.

Genetic alteration of the c-myc protooncogene (MYC) in human primary breast carcinomas.

We have studied the genomic organization of the c-myc locus (MYC) from 121 human primary breast carcinomas. Two types of alterations were observed: (i) the c-myc protooncogene appeared to be amplified 2- to 15-fold in 38 (32%) of the carcinoma DNAs and (ii) a non-germ-line c-myc-related fragment of variable size was detected in 5 primary breast carcinoma DNAs. With three exceptions, all the tumors containing a genetic alteration of the c-myc locus were invasive ductal carcinomas. A significant correlation (P less than 0.02) was observed between patients more than 50 years old and the presence of a genetically altered c-myc. Enhanced levels of c-myc RNA were observed in 10 of 14 breast carcinomas examined. The c-myc gene was genetically altered in 6 of these 10 tumors. The frequency with which the c-myc gene is altered and its correlation with age suggest that it may play a role in the development of breast carcinomas.

Breast cyst fluid proteins and breast cancer.

A specific breast cyst fluid protein was purified by the following steps: ultracentrifugation, gel filtration, DEAE and Con A chromatography, and gel filtration with guanidine, 6 M. The protein was pure, having a molecular weight of 17,800 daltons on SDS-PAGE and 68,000 daltons on gel filtration. The GCDFP 17,800 is immunologically distinct from other breast cyst fluid components and known milk and plasma proteins. A specific radioimmunoassay was developed and used to determine GCDFP 17,800 in 158 samples of breast cancer cytosol. The GCDFP 17,800 levels were significantly different between grade I tumors (mean of 813 ng protein per mg +/- 430 SEM) and grade III tumors (mean 184 ng protein per mg +/- 59 SEM) and were correlated with progesterone receptor values in postmenopausal women (Spearman's correlation, p = 0.03) but not in premenopausal women. The value of GCDFP 17,800 did not differ between the pre- and the postmenopausal women. By immunocytochemistry the intracellular localization of the GCDFP 17,800 was also found in relation to tumor grading and in correlation with PR values. GCDFP 17,800 appears as a hormone-induced protein of the breast cells. Its intracellular detection by means of radiolabeling allows a more sensitive and precise evaluation of the hormone-dependence of the breast cancer cells and emphasizes the heterogeneity of the tumor cell population.

Presence of an allelic EcoRI restriction fragment of the c-mos locus in leukocyte and tumor cell DNAs of breast cancer patients.

Structure of the human c-mos protooncogene in DNAs from breast tumors, leukemic cells, and lymphocytes from normal individuals was analyzed by restriction enzyme digestion and Southern blot. In 6 of 75 breast tumor DNAs, we found an EcoRI 5-kilobase extra band hybridizing with a human c-mos probe containing all of the sequences homologous to v-mos oncogene. This band was also found in lymphocyte DNA from 3 of these patients, indicating a restriction fragment length polymorphism. This polymorphism was not found in a series of 69 lymphocyte DNAs from the unaffected population. Moreover, 1 of 73 leukemic cell DNAs exhibited the 5-kilobase band. These results indicate that this rare polymorphism is significantly more frequently found in patients with breast cancer than in the rest of the population (P less than 0.05, by a chi 2 test with Yates correction.

Immunohistochemistry of a component protein of the breast cystic disease fluid with mol. wt 15,000.

A specific protein from the liquid of a mammary cyst with a molecular weight of 15,000 (GCDFP 15) was studied in normal and pathological mammary tissue using an immunohistochemical method (peroxidase-anti-peroxidase complex). An immunoreactivity of the GCDFP type was found in normal idrosadenoid glands having an apocrine secretion. Histologically normal mammary tissue was not immunoreactive. In benign breast tissue the GCDFP was found particularly in epithelium undergoing apocrine metaplasia (55/55) and in atypical lobular epithelial hyperplasia (8/10). Of the adenocarcinomas of the breast 136/161 (84%) were immunoreactive, especially lobular carcinoma (13/13). The proportion of tumors with a high percentage of immunoreactive cells (76-100%) was greater for Bloom's grade I (1/29: 34%) than for grade III (10/66: 15%). A significant correlation was found between the percentage of immunoreactive cells and the cytosolic concentration of progesterone receptors. The morphological intracellular identification of GCDFP (due to its greater sensitivity) and its correlation with progesterone receptors allowed a more precise evaluation of the functional state and the hormonal dependency of the breast cells by underlining the heterogeneity of the tumoral cell population.

Immunohistochemical detection of alphalactalbumin in breast lesions.

Alphalactalbumin was investigated in breast cells using the immunoperoxidase technique with a specific anti-alphalactalbumin serum. In 50 benign tumors alphalactalbumin immunoreactivity was demonstrated in the epithelium of fibroadenomas and in fibrocystic disease showing apocrine metaplasia. Alphalactalbumin immunoreactivity, investigated in 124 breast cancers, was present in all cells of lobular tumors but in only 76% of other cancers where the pattern was heterogeneous. Perineoplastic mammary tissue of normal appearance was not labeled with the anti-alphalactalbumin antiserum except where lobular hyperplasia was present. The presence of alphalactalbumin-type immunoreactivity was not correlated with the histopathological staging of Bloom and Richardson, nor with menopausal status. The incidence of positivity was 90% when estrogen and progesterone receptors were present in the tumor. The demonstration of alphalactalbumin using immunoperoxidase could be used to complement the histological classification of breast cancers.

Relationship between ultrastructure and receptor content of human primary breast cancer.

The ultrastructure of 47 primary breast cancers was studied. For each tumour, the characteristics of approximately 200 malignant cells were examined. Eleven features were scored from 1 to 3 and multivariate analysis showed that seven of these could be used to define an ultrastructural index of differentiation. Differentiation at the ultrastructural level was associated with the presence of steroid receptors. Differentiated tumoral cells contained oestrogen receptor and progesterone receptor in 81.8% and 66.7% of cases, respectively. Poorly differentiated cells contained oestrogen receptors in 50% and progesterone receptor in 14.3% of cases. Comparison of histological grading by the method described by Scarff, Bloom & Richardson with the ultrastructural index of differentiation showed a rather loose correlation which was not significant in this group of 47 patients. The authors conclude that differentiation at tissue or cellular levels yields differing information, only the latter being closely correlated with steroid receptor presence.

[General evaluation of adjuvant chemotherapy trials in breast cancer (excluding the Milan trial)]. / Bilan général des essais de chimiothérapie adjuvante dans le cancer du sein. (A l'exclusion de l'essai de Milan).

In this general review of adjuvant chemotherapy clinical trial in breast cancer (with the exception of that of Milan), we shall try to answer the following questions: Is adjuvant chemotherapy useful and if so, for what precise purpose? Is polychemotherapy superior to monochemotherapy and if so, in what cases is it to be preferred? Can we determine the best time for beginning chemotherapy in relation to surgery? Could a shorter course of chemotherapy be equivalent to a longer one? Are there breast cancer subsets which particularly need adjuvant chemotherapy? After discussion of these questions, the answers are certainly affirmative although not perfectly outlined and the need for complementary trials is paramount if we want to obtain a consensus.

Cancer treatment by methotrexate: rational use following pharmacokinetic study.

We used the test-dose method to calculate the dose of methotrexate to administer to the patients to reach the therapeutic but non-toxic blood concentration of 10(-5) mol/L. Methotrexate was tested with a radioimmunoassay technique and in 19 out of 20 patients we obtained the desired plateau during 24-h infusion.

[Place of hormone receptor determination in the therapeutic strategy of breast cancer]. / Place de la détermination des récepteurs hormonaux dans la stratégie thérapeutique des cancers du sein.

Up to the discovery of hormonal receptors it was somewhat uncertain to prescribe hormonotherapy for the treatment of a breast cancer. The presence of estrogen receptors (ER) and progesterone receptors (PR) allows the estimation of the probability of hormone-dependence. The response to endocrine therapy will be expected with a rate of: 80% of the tumors PR +; 30% of the tumors ER+ but PR-; 10% of the tumors ER - and PR -. The response to chemotherapy is no accurately correlated with the concentration of receptors. The planning of therapy will be founded on the following principles. ER -: less favourable prognosis and unlikely response to endocrine therapy, therefore chemotherapy if the other prognostic factors are bad. ER +: endocrine therapy is required, especially if PR +. The role of chemotherapy ought to be discussed with respect to the other prognostic factors. All these factors are reviewed and a decision-tree of the treatment of advanced breast cancers is put forward. In short, it is obvious that the receptors assays have to be carried out as for as possible.

[Bone metastases in cancer of the breast. Diagnostic and predictive value of quantified bone scintigraphy]. / Métastases osseuses du cancer du sein. Intérêt diagnostique et prévisionnel de la scintigraphie osseuse quantifiée.

Distant metastases from carcinoma of the breast are most commonly located in the skeleton. Although it has been clearly shown that bone radionuclide scanning is more sensitive than X-rays in detecting such metastases, diverging opinions have recently been voiced concerning its sensitivity and specificity. The authors have quantitatively analyzed 1631 focal alterations, taking the uptake index value as yardstick. They found that quantitative scanning increases the sensitivity of the method and makes it possible to differentiate between malignant and benign bone lesions.

[Prognostic histopathological features of malignant melanoma. New statistical approaches (author's transl)]. / Le pronostic des mélanomes malins cutanés primitifs. Nouvelles approches statistiques.

The records of 203 patients with cutaneous malignant melanoma treated at the Centre René Huguenin, Saint-Cloud, from october, 1959 to december, 1978 were reviewed. Histological data from 155 patients were retained after re-examination. The melanomas, which had previously been classified according to Clark's system of histological type and degree of invasiveness, were re-evaluated according to the thickness, were re-evaluated according to the thickness of the tumour as measured by Breslow's ocular micrometric method. Other histological data, as well as clinical and therapeutic data, were gathered together. One hundred and fifty cases were found to be suitable for standard single and multifactorial analysis, and 96 records contained sufficient information to be analyzed by the new "similarly aggregation" method developed by IBM. Two significant results emerged from the study: the thickness of the tumor is the single most important prognostic factor, as it correlates with the incidence of recurrences, metastases and deaths; by using a small number of clinical and histological variables, it seems possible to draw a profile of every new patient, to classify him in a well-determined prognostic category and, consequently, to institute a complementary treatment when needed.

[Results of a survey of the risk factors involved in the incidence of female breast cancer (author's transl)]. / Résultats d'une enquête sur les facteurs de risque d'incidence du cancer du sein chez la femme.

A survey of the risk factors involved in the incidence of female breast cancer was conducted in the Hauts-de-Seine and Yvelines departments, near Paris. Two hundred and fifty thousand questionnaires were sent out; 18000 women replied. The family risk factor appeared in 15% of the replies, including 6% which concerned the closest relatives (mother and/or sister). Correlations are established between the various factors, and conclusions are drawn about the possibility of cancer detection according to graded risks.

[Radical surgery and radiation in carcinoma of the uterine cervix and results (author's transl)]. / Résultats éloignés de l'association curiethérapie-chirurgie immédiate dans le traitement du carcinome du col utérin stades I et II.

A radical panhysterectomy and bilateral pelvic lymphadenectomy was performed immediately after intracavitary radiation in 240 cases of carcinoma of the uterine cervix. In some cases external radiation was performed after surgery. The 10 years survival rate was: 76 per cent in 169 stage I, 57 per cent in 71 stage II. Twenty seven patients died from recurrence or metastasis. Iatrogenic urinary tract complications were responsible of the death in 12 cases. All these cases were submitted to external radiation.