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Biomedical subjects

S Friedman

Publications and source records attributed to S Friedman.

At least 289 records · Page 16Linked to original sources

Medullary breast carcinoma. A reevaluation of 95 cases of breast cancer with inflammatory stroma.

The hallmarks of diagnosis of medullary breast cancer (MedBC) used by the authors since 1977 have been that the tumor is well circumscribed, has syncytial architecture in greater than 75% of its surface, contains diffuse inflammatory infiltrate, has atypical nuclei, and forms no glandular pattern. In order to assess the clinical utility of these criteria, we studied a series of 95 previously untreated, surgically operable patients with breast carcinoma at the Institut Gustave-Roussy (IGR) between 1960 and 1979. A diagnosis of MedBC was initially made for these patients or suspected based on abundant inflammatory stroma observed in a histologic evaluation. Using these criteria, 26 cases were identified as typical medullary carcinoma (TMC), 23 cases as atypical medullary carcinoma (AMC), and 46 cases as nonmedullary carcinoma (NMC). The 26 cases of TMC represent a very small fraction of the total infiltrating operable breast carcinomas diagnosed at IGR during the same time period. The prognosis for these 26 patients was much more favorable than for the other groups. They had a 10-year disease-free survival of 92% compared with 53% for the AMC group and 51% for the NMC group. Neither distant metastasis nor secondary primaries of the same histology were seen. Therefore, it is possible with the use of strict histologic criteria to distinguish a group of patients with a much more favorable prognosis. This histologic diagnosis alone renders a most favorable prognosis for the patient even if other factors such as large tumor size and lymph node involvement are present and, by inference, the only therapy needed is the removal of all tumor. In contrast, atypical forms have a prognosis no different from other atypical types of breast carcinomas without inflammatory stroma, and adjuvant therapy appears to be justified if other factors warrant it.

Breast Neoplasms↗

Prenatal lidocaine and the auditory evoked responses in term infants.

We examined the effects of maternal lidocaine hydrochloride anesthesia on the brain-stem auditory evoked responses (BAERs) in neonates born by cesarean delivery. Sixteen term neonates were enrolled in the study. Eight neonates were delivered by cesarean section following lidocaine anesthesia, and eight were delivered by spontaneous vaginal delivery without maternal anesthesia. A BAER was obtained on all of the neonates on the first day of life. A significant delay was noted in the central neural component of the BAER at 90 dB. The wave I through V interpeak latency for both ears was noted to be 5.3 ms for the neonates exposed to lidocaine and 4.9 ms for the controls.

Anesthesia, Epidural↗

Invasive apocrine carcinoma of the breast: a long term follow-up study of 34 cases.

We have reviewed the morpho-functional criteria for infiltrating apocrine carcinomas of the breast and analysed long term follow-up of this entity. Thirty-four cases of pure apocrine carcinomas were retrieved from the files of the Dept. of Pathology, IGR, France, for the years 1955-1982. Each case was matched with two controls of other infiltrating ductal carcinomas according to the most important prognostic parameters: nodal status, histograde, anatomic tumor size, and patient age. No significant difference between the survival curves of the two groups was seen. Apocrine carcinoma, although possessing peculiar morphological, ultrastructural, biochemical, and immunohistochemical features to merit recognition as a separate histologic variant of breast cancer, by itself has no apparent clinical significance.

Adult↗

Epidermal growth factor receptor in human breast cancers: correlation with estrogen and progesterone receptors.

Epidermal growth factor receptor (EGFR), determined by the Scatchard curve method, was found in 22 cases of a random series of 100 patients with breast carcinoma. Two groups of patients were identified, one (n = 16) with a low concentration (0-50 fm/mg protein) of EGFR but with a high affinity (Kd = 3.2 nM), and the other (n = 6) with a high concentration (90-210 fm/mg protein) of EGFR but with a lower affinity (Kd = 6.3 nM). A significant inverse relationship was found between the presence of EGFR and receptors for estrogen (p less than 0.001) and progesterone (p = 0.001). EGFR was found in no (0/8) tumors with Grade I histoprognostic grade, 17% (10/58) Grade II, and 38% (11/29) Grade III (p less than 0.05). EGFR is present therefore in poorly differentiated tumors and associated with other factors of poor prognosis. Our in vivo analyses confirm results found in tissue culture derived from human breast carcinoma cells.

Breast Neoplasms↗

Markers in breast cancer: does CEA add to the detection by CA 15.3?

211 patients with various stages of breast cancer were studied by both the CA 15.3 and CEA markers to assess whether the latter may increase the screening sensitivity of the former. While both markers were equally specific, CA 15.3 was seen to be much more sensitive than CEA (p less than 0.0001). Also, the addition of the CEA did not add appreciably (7%) to positive detection by CA 15.3. There appears to be no advantage to including CEA in a marker panel to follow the course of breast carcinoma.

Antigens, Tumor-Associated, Carbohydrate↗

A nonhuman primate model of panic disorder.

In this article we report on the reliable production of several features of panic attacks following subcutaneous administration of sodium lactate to nonhuman primates. Unrestrained monkeys were evaluated by an observer without knowledge of the subjects' treatment with either sodium lactate or a dextrose control solution. The lactate produced temporally circumscribed episodes of agitation, wariness, and motor responses, normally elicited under stressful or threatening conditions. In an initial pharmacological intervention, we found that pretreatment with imipramine blocked the response to lactate. The further development of this model offers promise for the systematic examination of etiological factors in susceptibility to lactate induction of panic attacks, the physiological basis of the response, and new modes of treatment of panic disorder.

Agoraphobia↗

Survival and mutagenic effects of 5-azacytidine in Escherichia coli.

Survival and mutagenesis caused by 5-azacytidine was studied in Escherichia coli. Survival was partially lexA- and recA-dependent and was decreased by the presence of a DNA (cytosine-5)methyltransferase. The dcm, MspI, and EcoRII methyltransferase genes all decreased survival. There was no direct relationship between amount of methylase enzyme present and cell survival, but only plasmids containing a methylase gene sensitized cells to 5-azacytidine. Survival was not affected by uvrA, uvrB or umuCD mutations. Induction of sulA::lacZ fusions by 5-azacytidine was inhibited in strains containing elevated levels of DNA methylase. Cells resistant to 5-azacytidine when they contained a plasmid specifying the EcoRII methylase were sensitive if the plasmid specified the complete EcoRII restriction-modification system. The mechanism of cell death in these situations is therefore different. Mutation of the rpoB gene by 5-azacytidine was studied. The mutation rate was decreased by the presence of recA and lexA mutations. Mutation in umuCD had little effect on the mutation rate. The recA430 mutation, which does not support SOS-dependent mutagenesis induced by UV light, does support 5-azacytidine induced mutagenesis. The presence of DNA (cytosine-5)methyltransferase had no effect on the mutation rate caused by 5-azacytidine treatment. The mutagenic and lethal lesions caused by 5-azacytidine in the absence of methylase therefore differ from the lethal lesions that occur in the presence of methylase. The former could be due to the opening of the 5-azacytosine ring in DNA. Cell death in the presence of methylase could be due to tight binding of methylase to azacytosine containing DNA as well as inhibition of induction of the SOS response.

Azacitidine↗

Lymphoblastic lymphoma in adults: a clinicopathological study of 34 cases treated at the Institut Gustave-Roussy.

We report a series of 34 adult patients with lymphoblastic lymphoma treated at our Institute between 1977 and 1986. At presentation, mediastinal involvement was seen in 76%, extranodal involvement (not including bone marrow) in 20%, stage IV in 53% and circulating blasts in 15%. In the 15 cases where immunological studies were performed, 12 proved to be of T type and the other three lacked both T and B markers. Chemotherapy with acute lymphocytic leukemia (ALL) protocols was given to 58% and lymphoma protocols to the other patients, with CNS prophylaxis given to a total of 28 patients. Although complete remission (CR) was observed overall in 74% of patients, 5 year survival was only 22% (42% in stages I-II and 8% stages III-IV) with improved results seen with recent aggressive anti-leukemic protocols. Five relapsed patients entered second CR and two were still in CR at this time. CNS relapse occurred in a total of eight patients (three without prophylaxis), and was isolated in two of six patients who achieved CR (despite CNS prophylaxis). In an analysis of prognostic factors, only the attainment of a CR was statistically significant (P less than 0.001). Thus we are unable to confirm other studies which demonstrated prognostic variations in this disease and believe that all such patients should receive aggressive chemotherapy with substantial CNS prophylaxis similar to those currently used for ALL.

Adolescent↗

Evolution of erythrocyte sedimentation rate as predictor of early relapse in posttherapy early-stage Hodgkin's disease.

A retrospective study was undertaken at the Institut Gustave Roussy (IGR) to determine the predictive ability of changes in the erythrocyte sedimentation rate (ESR) during posttherapy periods for early relapse (within 18 months from start of therapy) and long-term survival in Hodgkin's disease (HD). Three hundred one patients with clinical stages (CS) I or II HD entered in the European Organization for Research and Treatment of Cancer (EORTC) clinical trials were included in this study. All relevant data and long-term follow-up were available for these patients. A stepwise logistic regression was performed to assess the prognostic value of ESR changes independent of other prognostic parameters and treatment. The incidence of early relapse was found to be significantly increased in patients in whom ESR remained elevated (greater than 30 mm at one hour) after completion of therapy, regardless of the value before therapy. This was true whether the ESR was elevated in plateau fashion, oscillating between normal and abnormal, or was lower than at onset, but still abnormal. Moreover, early relapse predicted by elevated ESR posttherapy was associated with poor survival despite subsequent initiation of combination chemotherapy. Thus, the persistence of an abnormal ESR appears to be a reliable indicator for high probability of early relapse and subsequent poor prognosis. This might be introduced as a prognostic variable in the design of future therapy programs for HD.

Adult↗

Proton nuclear magnetic resonance spectroscopy of plasma lipoproteins in malignancy.

A recent study (N. Eng. J. Med. 315 (1986), 1369), described a method of detecting malignant tumors by water-suppressed proton nuclear magnetic resonance (1 H NMR) study of plasma. We performed a similar study of the W 1/2, a mean of the full width at half height of the resonances of the methyl and methylene groups of the lipids of plasma lipoproteins which is inversely related to the spin-spin apparent relaxation time (T 2*). W 1/2 values were measured at a fixed baseline width of 310 Hz. The study was prospective and blinded and comprised 182 subjects consisting of 40 controls, 68 patients with untreated malignancies, 45 with malignant tumors undergoing therapy and 29 benign tumor patients. No differences were seen between any groups that could serve as a basis for a useful clinical test. The major difficulty in the determination of W 1/2 was due to interference of metabolite protons (particularly lactate) within the lipoprotein resonance signal. Triglyceride level was seen to correlate inversely with W 1/2 within malignant patient groups. These discrepant results may be related to differing triglyceride-rich very low density lipoprotein (VLDL) levels in the patient populations of each study. We conclude that the water-suppressed 1H NMR of plasma lipoproteins is not a valid measurement for assessing malignancy.

Female↗

Importance of tumor cells in axillary node sinus margins ('clandestine' metastases) discovered by serial sectioning in operable breast carcinoma.

The prognostic implications of small emboli of carcinoma cells in the sinus margins of axillary lymph nodes ('clandestine' metastases) discovered by serial node sectioning at 2 mm intervals was analysed. All patients, previously untreated, were admitted between 1967 and 1978 and underwent mastectomy and axillary node dissection. Our study examined the risk of distant metastases of 1153 patients with from 0 to 3 involved axillary lymph nodes. A Cox multivariate analysis was performed, taking into account the classical prognostic factors (menopausal status, histoprognostic grade, and anatomic tumor size), and for nodal status including the notion of clandestine (CM) or parenchymal metastases (PM). Compared to patients without axillary metastases, patients with one node involved with CM had a relative risk of distant metastases of 1.7, identical to the risk for patients with one node with PM; and patients with one node containing PM and a second CM, had a relative risk of 2.2. Serial node sectioning discovers nodal metastases that would otherwise not be detected. These CM have important clinical implications and should be taken into account when considering adjuvant manipulations.

Axilla↗

A clinico-pathological and prognostic analysis of non-Hodgkin lymphoma. A study of 203 patients.

In a retrospective analysis of 203 patients with non-Hodgkin lymphoma (NHL) treated between 1975 and 1985, the relationship between pathology, clinical presentation and course, was studied, using the Kiel classification. This classification was a much better predictor of prognosis than clinical stage and within the different pathology groups there was no significant difference between the stages concerning the survival rate. In the group with low grade malignancy this latter was positively associated with nodular architecture, bone marrow involvement and complete or partial response to therapy. In the high grade group, the survival was positively correlated to complete remission, but no plateau was seen in the survival curve. All extranodal sites had poor survival. For both grades, age (greater than 60 years), systemic symptoms and biologic signs (Ann Arbor 'B' and 'b') were unfavorable prognostic factors.

Humans↗