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Purpose: To describe the ophthalmologic features observed in patients infected by the human T-cell lymphotropic virus, type 1 (HTLV-1) in Martinique (French West Indies)., Design: Prospective consecutive observational case series., Methods: A complete ophthalmic examination was performed., Patients: Of 200 patients infected by HTLV-1, 77 (38.5%) were seropositive and 123 (61.5%) had HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP)., Results: Uveitis was found in 29 cases (14.5%). Symptoms were mild and the uveitis had little effect on visual function. Ten cases of uveitis were discovered through a systematic examination and had no ocular symptoms. Most of the uveitis was anterior or intermediate. The lesions responded to corticosteroid therapy, but tended to recur. Keratoconjunctivitis sicca existed in 74 patients (37%), accompanied by lymphoplasmocytoid infiltration of the secondary salivary glands rated 3 or 4 on the Chisholm scale in nearly 50% of cases. Corneal alterations were observed in 20 cases (10%), and alterations in the retinal pigment epithelium in 3 cases., Conclusion: The three types of ocular affections seen most frequently were uveitis, keratoconjunctivitis sicca, and interstitial keratitis. In patients with HAM/TSP, uveitis was more frequent among younger patients, patients with earlier onset of HAM/TSP, and patients with severe motor disability. Because uveitis is related to a high intrathecal production of immunoglobulin, it could represent a marker for severity of HTLV-1 infection with respect to the course of HAM/TSP. The sicca syndrome related to HTLV-1 virus differs from primary or secondary Sjögren syndrome, because it does not reveal any of the immunologic anomalies generally seen in this disease. Interstitial keratitis was more frequent among patients with HAM/TSP who had high proviral DNA levels.

Background: In human arteries, angiotensin-converting enzyme (ACE) inhibitors incompletely block the production of angiotensin (Ang) II from Ang I. This ACE-independent production of Ang II appears to be caused by serine proteases, one of which presumably is chymase. However, several serine proteases may produce Ang II, and the exact role of chymase in the vascular production of Ang II has never been directly evaluated using selective chymase inhibitors., Methods and Results: Rings of human mammary arteries were subjected to either Ang I or the chymase-selective substrate [pro,(11) D-Ala(12)] Ang I in the absence or the presence of the ACE inhibitor captopril, the serine protease inhibitor chymostatin, or the selective chymase inhibitor C41. Captopril only partially inhibited (by 33%) the response to Ang I. In the absence of captopril, C41 markedly reduced (by 44%) the response to Ang I, and this effect was identical to that of chymostatin. C41 also significantly reduced the response to Ang I in the presence of captopril, although this inhibitory effect was slightly less than that of captopril in combination with chymostatin. [Pro,(11)D-Ala(12)] Ang I induced potent contractions that were not affected by captopril but were abolished by chymostatin and markedly reduced by C41. In addition, we found that prior treatment of the patients with an ACE inhibitor did not affect the in vitro response to Ang I (in the absence or the presence of captopril) or to [Pro,(11)D-Ala(12)] Ang I., Conclusions: Our results reinforce the hypothesis that chymase is a major serine protease implicated in the ACE-independent production of Ang II in human arteries.

Objective: This study aimed to describe a syndrome that the authors call human T-lymphotropic virus type I-related chronic interstitial keratitis., Methods: A consecutive series of 194 human T-lymphotropic virus type I-infected patients (divided into 119 patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis and 75 asymptomatic human T-lymphotropic virus type I carriers) was systematically examined., Results: Twenty patients (10.3%) had bilateral anterior stromal lesions made up of approximately 10 elevated, rounded or cloudy whitish opacities that were more or less confluent. The opacities were characteristically situated at the periphery of the anterior stroma, and the visual axis remained unaffected. The interstitial keratitis was chronic and unresponsive to topical administration of corticosteroids. It was mainly observed in patients affected by human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis among whom there were 18 cases (15.1%), as opposed to two cases (2.7%) in asymptomatic carriers., Conclusion: A new cause of interstitial keratitis is reported. Human T-lymphotropic virus type I infection may have a much broader spectrum of ocular manifestations than previously described. As with the other manifestations of human T-lymphotropic virus type I infection, corneal lesions could be linked to a lymphoplasmocytic infiltration of the stroma leading to corneal opacities.

In all living organisms, deoxyribonucleotides, the DNA precursors, are produced by reduction of the corresponding ribonucleotides catalyzed by ribonucleotide reductase. In mammals as in Escherichia coli, the enzyme consists of two proteins. Protein R1 is the proper reductase as it contains, in the substrate binding site, the reducing active cysteine pair. Protein R2 provides a catalytically essential organic radical. Here we report the cloning, expression, purification and characterization of protein R1 from Arabidopsis thaliana. Expression in E. coli was made possible by coexpression of tRNAArg4 which is required for the utilization of AGA and AGG as codons for arginines. Protein R1 shows extensive similarities with protein R1 from mammals: (a) it shows 69% amino-acid sequence identity to human and mouse R1 protein; (b) it is active during CDP reduction by dithiothreitol, in the presence of protein R2 [Sauge-Merle, S., Laulhère, J.-P., Coves, J., Ménage, S., Le Pape, L. & Fontecave, M. (1997) J. Biol. Inorg. Chem. 2, 586-594]; (c) activity is stimulated by thioredoxin and ATP and is inhibited by dATP, showing that as in the mammalian enzyme, the plant ribonucleotide reductase seems to be allosterically regulated by positive (ATP) and negative (dATP) effectors.

In Azotobacter vinelandii, deletion of the fdxA gene that encodes a well characterized seven-iron ferredoxin (FdI) is known to lead to overexpression of the FdI redox partner, NADPH:ferredoxin reductase (FPR). Previous studies have established that this is an oxidative stress response in which the fpr gene is transcriptionally activated to the same extent in response to either addition of the superoxide propagator paraquat to the cells or to fdxA deletion. In both cases, the activation occurs through a specific DNA sequence located upstream of the fpr gene. Here, we report the identification of the A. vinelandii protein that binds specifically to the paraquat activatable fpr promoter region as the E1 subunit of the pyruvate dehydrogenase complex (PDHE1), a central enzyme in aerobic respiration. Sequence analysis shows that PDHE1, which was not previously suspected to be a DNA-binding protein, has a helix-turn-helix motif. The data presented here further show that FdI binds specifically to the DNA-bound PDHE1.

During recent years it has become clear that the production of most cytokines could play an important role in malignancies. We previously demonstrated that a high endogenous interleukin-6 (IL-6) level is significantly correlated with a high tumour burden and resistance to biochemotherapy in metastatic malignant melanoma patients. However, little is known about the origin of IL-6 and the pattern of IL-6 receptor (IL-6R) expression. In this report, we studied the expression of IL-6R and intracellular IL-6 using flow cytometry in tumour cells provided by fine-needle aspiration of lymph nodes and palpable metastatic lesions from 14 patients refractory to biochemotherapy and six responder patients. Moreover, we established the relationship between these parameters and the serum IL-6 level. Our results demonstrated that, following treatment, the percentage of HMB45-positive (HMB45+) cells expressing functional IL-6R, intracellular IL-6 or both IL-6R and IL-6 significantly decreased in patients refractory to biochemotherapy. In contrast, in responder patients the percentage of HMB45+ cells expressing IL-6R increased and those expressing IL-6 remained stable. Regarding the serum IL-6 level, an 11-fold increase was observed in the patients refractory to biochemotherapy, but only a 1.8-fold increase in the responder patients. In conclusion, in metastatic malignant melanoma patients with a poor prognosis, the endogenous production of IL-6 is concomitant with a decrease in functional IL-6R and intracellular IL-6 expression, suggesting the involvement of an IL-6/IL-6R complex.

Ribonucleotide reductase (RNR) is a key enzyme for DNA synthesis since it provides cells with deoxyribonucleotides, the DNA precursors. Class I alpha2beta2 RNRs contain a dinuclear iron center and an essential tyrosyl radical in the beta2 component (protein R2). This is also true for the purified protein R2 of Mycobacterium tuberculosis RNR, as shown by iron analysis, light absorption and EPR spectroscopy. EPR spectroscopy at 286 GHz revealed a high g(x) value, suggesting that the radical is not hydrogen bonded, as in other prokaryotic R2s and in contrast with eukaryotic R2s (from Arabidopsis thaliana and mouse). Furthermore, it proved to be very resistant to scavenging by a variety of phenols and thiols and by hydroxyurea, similar to the Escherichia coli radical. By comparison, the plant and mouse radicals are very sensitive to drugs such as resveratrol and 2-thiophenthiol. The radical from M. tuberculosis RNR does not seem to be an appropriate target for new antituberculous agents.

One hundred and eighty-one breast cancer specimens were analyzed for nuclear p53 staining by immunochemical methods. There were 123 fine-needle cytological specimens and 58 frozen tissue sections of surgical biopsies. The microscopic evaluation of the staining fitted with a 4 group classification. Ninety-one samples (50.6%) were devoid of any staining (-), while 42 (23.3%) showed only few stained nuclei (+/-), typically around 1%. Thirty-two (17.8%) samples presented with strong nuclear staining (++) which in practically all cases concerned more than 50% of the nuclei, but a few cases showed staining heterogeneity. A further 17 cases (9.4%) presented with nuclear staining which concerned 10-20% of the cancer cells (+). This four class system was used to compare p53 expression with other prognostic parameters. A strong inverse correlation was observed with steroid hormone receptor content and p53 positivity was highly significantly associated with higher S-phase. All but one of the highly positive cases were aneuploid. Twenty-five percent (29/120) of the aneuploid tumors were strongly stained and a further 10% were considered positive (+). On the other hand, only 5 out of 59 DNA-diploid tumors were considered as + and one ++. The DNA index distribution according to p53 positivity showed peaks of positivity for hypodiploid, triploid and hypertetraploid values. Negative tumors were in all regards similar to those with only few stained nuclei, in particular mean S-phases of 2.8 and 3.3% respectively. Altogether, the typical strong p53 phenotype concerned a DNA-aneuploid tumor with above median S-phase fraction (mean of 7.1%), negative steroid hormone receptors and cytoprognostic index III. The p53 positive cases (+), were frequently steroid hormone receptor positive and had on the average intermediate S-phase fractions (4.3%). The proportion of immunochemical positivity (27% in our series), is compatible with the published frequency of p53 mutations detected in breast cancers, but the differences in the phenotype according to the level of positivity should be further investigated.

Purpose: To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma., Patients and Methods: Forty-six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25-mg/m2 short intravenous (i.v.) infusion., Results: Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose-intensity (DI) was 20 mg/m2/wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1)., Conclusion: These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted.

The present study describes the setting up of a new score which makes it possible objectively to grade ductal breast carcinomas, i.e. not-otherwise-specified (NOS) cancers, on cellular material from fine-needle aspirations (FNAs). For this purpose FNAs from 252 patients--with NOS breast cancers--were smeared onto histological slides, fixed in an ethanol-formolacetic acid mixture, Feulgen-stained and analysed by means of a cell image processor. Four parameters were taken into account in setting up the score, namely the cytological prognostic grade (CPM) of malignancies similar to the Scarff-Bloom-Richardson (SBR) grading, the nuclear area (NA), the DNA index (DI) and the DNA histogram type (DHT). Each of these four parameters was considered as a "sub-score" which may take three values, i.e. 1, 2 and 3. The final result may thus range from 4 to 12. Subscores of 4 and 5 correspond to a cytological score of I, subscores of 6, 7 and 8 to a cytological score of II, sub-scores of 9 and 10 to a cytological score of III, and sub-scores of 11 and 12 to a cytological score of IV. In the present study, the results show 17% of CPM grade 1.52% of CPM grade II and 31% of CPM grade III cancers. All the cases exhibiting a cytological score of IV (5%) fully fit in with the CPM grade III cancers. In the same way, none of the cases exhibiting a score of I fit in with CPM grade III cancers. The cancers with a CPM grade II fit in with the scores of II and III. It thus seems possible to convert a three-value malignancy grading system (CPM and/or SBR grading) into a four-value one (cytological score). The main advantage in this latter type of system is that it becomes possible to split up the over-large group of CPM grade II cancers. As things stand, we are unable to give any prognostic value for the score proposed here because our study is prospective only. A study of this type has been necessary so as to provide against problems connected with ways of preserving specimens that might be used in a retrospective study. The bank of clinical and biological data now in existence must be allowed to mature for a number of years before the prognostic worth of the cytological score can be established, always assuming that such a value exists.

Purpose: A phase I/II trial of vinorelbine (VRL) administered by continuous infusion (CIV) was conducted in advanced breast carcinoma (ABC) patients to determine the maximum-tolerated dose (MTD) and to evaluate the toxicity pattern and antitumor activity of this alternative administration schedule to the currently recommended weekly short intravenous (IV) administration., Patients and Methods: Between February 1990 and July 1991, 64 consecutive, eligible patients with ABC were treated; 33 had received one or two previous palliative chemotherapy combinations and 31 had not received chemotherapy for metastatic disease. VRL was administered, after an initial IV bolus of 8 mg/m2 on day 1, by a 4-day CIV at five different 24-hour dose levels (DLs) to be repeated every 21 or 28 days: DL1, 5.5 mg/m2; DL2, 7 mg/m2; DL3, 8 mg/m2, DL4, 9 mg/m2; and DL5, 10 mg/m2., Results: The limiting noncumulative toxicity was neutropenia, with the MTD established at 8 mg/m2 bolus plus 10 mg/m2/d for 4 days (total dose per cycle, 48 mg/m2). At DL3 and DL4, we observed mucositis (14% of patients; five percent of cycles > grade 2), alopecia, and asthenia. By contrast, neurotoxicity was minor. The toxicity was otherwise predictable and manageable. Pharmacokinetic data obtained at DL1 and DL3 showed a mean VRL plasma concentration of 967 +/- 331 ng/mL after the initial 8 mg/m2 IV bolus dose, which declined rapidly thereafter to reach mean steady-state levels of 12 ng/mL (n = 5) for the 30-mg/m2 dose and 8 ng/mL (n = 2) for the 40-mg/m2 dose. These levels were maintained over the 96-hour CIV. The mean residence time (MRT) was 29 +/- 7 hours (terminal half-life [t1/2], 23 hours), the total-body clearance (CL) was 24 +/- 11 L/hr/m2, and the volume of distribution at steady-state (Vss) was high at 1,832 +/- 359 L/m2. Two patients achieved a complete response (CR) and 21 a partial response (PR), for an objective response rate of 36% (95% confidence interval [Cl], 23 to 49). The median duration of response was 6 months. The median survival duration was 24 months (range, 3 to 37). A relationship between given dose-intensity and objective response rate was found, with an overall response (OR) rate of 13.3% (two of 15) for 8 to 10 mg/m2/wk, 35.4% (11 of 31) for 10 to 12 mg/m2/wk, and 55.5% (10 of 18) for 12 to 14.5 mg/m2/wk., Conclusion: This trial, while confirming VRL activity in ABC, shows the feasability of a CIV administration schedule. A decrease of the administrated total dose per 3- to 4-week cycle to less than the weekly schedule with the same therapeutic activity suggests a better therapeutic index. The data are also suggestive of a dose-response relationship and a dose-intensity/activity correlation.

Vinorelbine (NavelbineR) is a new antitumor agent chemically related to the Vinca alkaloid group, but differentiated by its in vivo activity relative to non-small-cell lung carcinoma (NSCLC). Studies in the NSCLC-bearing nude mouse of vinorelbine associations with drugs currently used clinically in phase III (cisplatin, 5-fluorouracil and actinomycin D) showed that such associations are ineffective or even of negative value and that it would be preferable to use vinorelbine alone in a single dose at the maximum tolerated concentration.

Peripheral blood from 77 cases of B-CLL was analyzed to evaluate the diagnostic value of SIg clonality and fluorescence intensity, mouse rosettes (MR), and CD5. Monoclonal SIg (L-chain restriction or H-chain restriction or both) was detected in 69 cases (89.61%), with weak fluorescence (mean channel number on flow cytometry <200) in 65 (94.2%); MR was positive in 66 (85.71%); CD5 positive in 64 (83.12%). The association of SIg intensity, MR, and CD5 was as follows: weak SIg/MR+/CD5+, 41 cases (53.25%); weak SIg/MR+/CD5-, 13 (16.88%); weak SIg/MR-/CD5+, 11 (14.29%); strong SIg/MR+/CD5+, 4 (5.19%); and undetected SIg/MR+/CD5+, 8 (10.39%). Thus, by performing the three markers and accepting either two or three positive results (weak SIg, MR+, CD5+) as sufficient for diagnosis, all 77 cases (100%) were diagnosed. The study demonstrated the complementary roles between L- and H- chains, and between SIg intensity, MR, and CD5 in immunophenotyping CLL.

Vinorelbine is a new 5' nor Vinca alkaloid, active by i.v. route, in various types of cancer disease such as non-small cell lung cancer and advanced breast cancer. In order to evaluate the possibility of using this drug for local treatment of cancer, Vinorelbine-loaded bioresorbable polymeric implants were prepared using a copolymer of D,L-lactic and glycolic acids (PLA 37.5 GA 25). According to the manufacturing process, the 1.2-mm-diameter cylindrical rods obtained had a drug content of 1, 5, or 20% (w/w) and released half of their content within about 6 days in vitro. In vivo release in rats was slower, half of the drug being released after about 14 days. A dose-dependent antitumoral effect was observed in mice (solid P388 leukemia model) when implants were administered into or in contact with the tumor. At highest drug loads and when administered soon after tumor implantation, Vinorelbine implants were more effective than i.v. administration (median survival time of treated animals related to untreated controls, greater than 360 versus 188). In dogs, results of toxicity experiments revealed that administration of implants in vital organs must be avoided. On the contrary, s.c. administration was well tolerated. A transient local necrosis was observed in the days following implantation, but normal skin was recovered after about 10 weeks. Thus, a clinical trial was conducted on patients with head and neck cancer; implantation of 20% loaded polymeric implants into the tumor sites succeeded in 8 of 9 patients. The sole failure was attributed to the unusual hardness of the tumor tissue. Except for a local transient inflammatory reaction (easily treated with nonsteroidal antiinflammatory agents), no other sign of toxicity was detected, and patients tolerated the device well. Fourteen days after implantation, patients underwent their planned surgery, and the implants were recovered. Residual drug content varied from 24 to 55%. In all cases, there was a clearly delimited necrotic area around the implant, ranging from 0.5 to 3.5 cm in diameter. In the smallest tumors, necrosis was also observed in the normal tissue inside this area. These results invite further studies to evaluate such drug-loaded polymeric implants.

Two enzyme-linked immunosorbent assays (ELISAs) for the detection of DNA antibodies are presented, one using lambda-phage DNA for the detection of dsDNA antibodies, the other using denatured calf thymus DNA for ssDNA antibodies. It was shown that only dsDNA antibodies of the IgG class were specific for SLE. IgM-dsDNA antibodies or ssDNA antibodies were not SLE-specific. Of 62 SLE patients 58% were positive for IgG-dsDNA antibodies. When only those patients with active disease were considered, 88% were positive. There was a positive correlation between the levels of IgG-dsDNA antibodies and the incidence of nephritis. When the ELISA for IgG-dsDNA antibodies was compared with the filter assay, the ELISA showed a considerably higher sensitivity.

Antibodies to dsDNA of the IgG-class show a strong association with disease activity in the course of systemic lupus erythematosus (SLE). Of 22 patients with low dsDNA-levels only one had an exacerbation. In 8 patients a rise of IgG-dsDNA antibodies to high levels occurred, followed by an exacerbation in 7 of them. In 6 of these 7 patients the IgG-dsDNA antibodies had a prognostic value by rising into high ranges 2-12 weeks before the exacerbation. IgG-ssDNA antibodies showed only a weak association to the clinical course. IgM antibodies to dsDNA as well as to ssDNA did not correlate with the clinical activity at all.

38 patients with locally advanced breast cancer, were treated with a program of cytotoxic chemotherapy including Adriamycin, Cyclophosphamide, 5 Fluoro-uracile and Prednisone. The concentration of hormonal receptors (Estrogen ER and Progesterone receptor PR) in the tumor were studied before starting the chemotherapy and after one to 9 courses of chemotherapy. This therapeutic response rate was not related to the initial level of ER and PR. After chemotherapy, we observed an increase of ER level in 14 cases out of 29 (59%), of PR level in 17 out of 32 cases (53%); A therapeutic response is observed in 11 cases out of 17 when the PR concentration is increased and in 3 cases out of 15 when the PR concentration was either stable or decreased. These observations let us to suppose a selective initial activity of chemotherapy on lesser differentiated tumor cells.

The effect of gastrectomy and duodenal reflux on gastric carcinogenesis was studied because gastrectomized patients may be considered at "high risk" for the development of gastric stump cancer. Wistar rats received N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (83 mg/liter) ad libitum in the drinking water for either four, eight, or twelve weeks. A control group received tap water. After MNNG administration animals were antrectomized. Antrectomy was not performed in a control group. Bowel continuity was restored either with a Billroth II (BIL) or with a ROUX en Y (ROUX) procedure. Duodenogastric reflux is possible after the BIL but not after the ROUX procedure. Eight months after the beginning of the experiment the stomachs of the animals were studied. In both operated and unoperated animals, the number of cancers observed was significantly related to the duration of MNNG administration. Animals receiving MNNG plus the BIL procedure had a significantly higher number of anastomotic cancers than the ROUX animals, indicating that duodenogastric reflux played a promotional role in gastric carcinogenesis. Three BIL gastrectomized rats not receiving the carcinogen had an adenocarcinoma on the anastomotic line further emphasizing the risk attached to the duodeno-gastric reflux.

Seventy-nine patients with an histologically proven disseminated breast cancer, never treated before with additive hormonal therapy, entered into a randomized trial between june 1981 and december 1982. In the first group 44 patients were given continually a daily dose of tamoxifen (TAM) of 20 mg/m2. In the 2nd group 35 patients were given a daily dose of TAM of 20 mg/m2 for 15 days and then an oral daily dose of medroxyprogesterone acetate of 350 mg/m2 for the next 15 days. In both groups I and II, the treatment was stopped at the first manifestation of progression of the disease. The hormonal receptor status was determined in 30 patients of the group I and 23 patients of the group II. An objective response to treatment was observed in 48 per cent of the patients of the group I and 60 per cent of the group II. This difference is not significant (X2 = 1,05). However, the mean duration of therapeutic response is significantly higher in the group II (p = 0,01).

Serum alkaline phosphatase isoenzymes were determined quantitatively by electrophoresis on cellulose acetate in 168 patients with rheumatic diseases subgrouped for disease activity. Median values of total alkaline phosphatase and bone isoenzyme activity, as well as frequency of patients showing pathological values, increased gradually and significantly corresponding to disease activity in rheumatoid arthritis and ankylosing spondylitis, from 0% in inactive to 90% in very active forms. Bone isoenzyme was much more sensitive than total alkaline phosphatase in moderate disease activity and was also correlated to the number of involved extravertebral joints and pain in ankylosing spondylitis. No correlation was found with stage or duration of disease, age, sex, and erythrocyte sedimentation rate. Additional to bone isoenzyme, liver isoenzymes were elevated in some patients, but with only a weak correlation with disease activity. The intestinal isoenzymes were always normal. We conclude that quantitative determination of serum alkaline phosphatase bone isoenzyme activity is a major indicator for the assessment of disease activity and therapeutic monitoring in rheumatoid arthritis and ankylosing spondylitis.

Enzyme immunoassay of estrogen receptors (ER-EIA) was compared to radioligand assay (ER-RLA) in fine needle aspirates of breast tumors. Fine needle aspiration is a relatively atraumatic means of harvesting malignant cells from breast tumors. Fine needle aspiration provides a homogeneous suspension (about 90% malignant cells) with a sufficient amount of cellular material (10 to 50 micrograms DNA per sample) for single point radioligand assays of extractable estrogen (ER) and/or progesterone receptor (PR) in about 85% of primary adenocarcinomas at the time of diagnosis. Sixty-one different samples of malignant mammary cells were obtained by fine needle aspiration from 43 adenocarcinomas, 11 metastatic axillary nodes or 7 cutaneous nodules. Thirteen patients were under antiestrogen therapy (tamoxifen). ER-EIA was performed with Abbott's reagents, following the manufacturer's protocol. ER-RLA was a single saturation (5 nM) dextran-charcoal assay with [3H]R2858 as the labeled estrogen. The sensitivity of ER-EIA allowed dilution of the sample up to 10 times (according to sample cellularity and ER level) with less than 20% deviation from undiluted samples. Three levels of dilution of the samples (1/1, 1/2, and 1/10) allowed them to fall at least once into the range of the ER-EIA standard curve. Quantitative correlation between ER-EIA and ER-RLA was high (r = 0.86), and highest (r = 0.97) when samples from patients undergoing tamoxifen treatment were excluded. Major discrepancies between ER-EIA and ER-RLA appeared in those patients undergoing tamoxifen therapy; much higher values were obtained by ER-EIA. Eight of 13 of these patients were ER negative by ER-RLA but ER positive by ER-EIA. This preliminary observation indicates that in vivo ER modulation by hormones and antihormones should be reevaluated.

Prolactin is determined by means of radioimmunoassay in the postovulatory phase of a group of women with mammary dysplasia. A specially increased concentration of prolactin is found in the proliferative dysplasias (multiple intraductal papillomatosis and invasive sclerosing adenosis), that may be considered as preneoplastic processes.

Evidence of blood in discharge from one breast and from one duct in an indication to operate on for most surgeons. We have used hemoccult to demonstrate the presence of blood in certain discharges. Discharge cytology was systematic and when it was possible a correlation was done with the operative specimen. 55 patients were studied. In 23 cases hemoccult was positive and there was blood on the cytological smear. In 28 cases hemoccult was negative and the cytological smear showed no blood. In the remaining 4 cases the hemoccult was positive but the cytological smear failed to show any blood. There was no false negative test. There were three breast cancers. Among this series of 55 patients and the test was positive in each case. Using slides of hemoccult to detect blood in a nipple discharge is rapid and simple can be done in the doctor's office. However, the results of the test have to be strictly correlated with other elements of the work up in particular with mammography and galatography.