Effect of alpha-interferon, 17 beta-estradiol, and tamoxifen on estrogen receptor concentration and cell cycle kinetics of MCF 7 cells.

The interaction of alpha-interferon, 17 beta-estradiol, and tamoxifen on estrogen receptor content, growth fraction, proliferative rate, and total protein synthesis of MCF 7 cells was investigated under culture conditions (minus phenol red and at low concentrations of "stripped" fetal calf serum) allowing for direct stimulation of proliferation by estrogens. Exposure to estradiol alone resulted in a decrease of estrogen receptor content as measured by immunoassay, an increase of the proportion of cells in S phase, and increases in cell proliferation as well as total protein synthesis. alpha-Interferon treatment resulted in cell cycle arrest with reduced proliferation, an increase of estrogen receptor content, but a decrease in the rate of total protein synthesis. Pretreatment with alpha-interferon inhibited the estrogen induced stimulation of cell growth as well as the associated decrease of estrogen receptor content. Tamoxifen treatment resulted in decreased cell proliferation and decrease of estrogen receptor content and of total protein synthesis. These results suggest that the estrogen receptor concentration of MCF 7 cells is growth fraction related. Pretreatment with alpha-interferon enhanced the inhibitory effect of tamoxifen on cell proliferation while preventing the tamoxifen induced reduction of estrogen receptor content. The synergistic effect of alpha-interferon and tamoxifen are most marked following 72 h pretreatment with interferon, when the maximum interferon induced increase of estrogen receptor concentration is evident. The mechanism is thus due probably to an increase of cellular receptor as a ligand for tamoxifen binding and suggests a possible role for the clinical use of interferons combined with tamoxifen.

High-dose chemotherapy with hematopoietic rescue as primary treatment for metastatic breast cancer: a randomized trial.

PURPOSE: The aims of this study were to compare in a randomized trial the results of high-dose versus conventional-dose chemotherapy as first-line treatment for metastatic breast cancer. The comparison included complete response (CR) rate, duration of response, and duration of survival. PATIENTS AND METHODS: Ninety patients were entered onto a study to compare two cycles of high-dose cyclophosphamide 2.4 g/m2, mitoxantrone 35 to 45 mg/m2, and etoposide (VP16) 2.5 g/m2 (HD-CNV) versus six to eight cycles of conventional-dose cyclophosphamide 600 mg/m2, mitoxantrone 12 mg/m2, and vincristine 1.4 mg/m2 (CNV) as first-line treatment for metastatic breast cancer. The high-dose regimen included either autologous bone marrow or peripheral-blood stem-cell rescue. All 90 patients are assessable. RESULTS: The response rates were significantly different. The overall response rate for HD-CNV was 43 of 45 (95%), with 23 of 45 patients (51%) achieving CR. Twenty-four of 45 patients (53%) who received conventional CNV have responded, with only two patients achieving CR. Both duration of response and duration of survival were significantly longer for patients, who received HD-CNV. Toxicity of the high-dose therapy was moderate in most patients. Grade 2 to 3 mucositis and hematologic suppression that required supportive treatment was universal, but hematologic recovery to a neutrophil count more than 500/microL and platelet count more than 40,000/microL occurred at day 18 (median) after therapy. CONCLUSION: HD-CNV appears to be a promising schedule that results in a significant proportion of CRs and increased survival in patients with metastatic breast cancer.

Weekly gemcitabine with monthly cisplatin: effective chemotherapy for advanced non-small-cell lung cancer.

PURPOSE: The aim of this study was to examine the efficacy of a regimen of initial gemcitabine followed by cisplatin in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-three patients (36 men and 17 women; age range, 35 to 74 years) were enrolled. Patients had bidimensionally measurable disease. Gemcitabine (phase-specific agent) was administered on days 1, 8, and 15 at a dose of 1,000 mg/m2. Cisplatin (cycle-specific agent) was administered on day 15 (100 mg/m2). Chemotherapy was administered in 28-day cycles. RESULTS: Of 53 patients enrolled, 50 were assessable for response. The overall response rate was 52%. There were two complete responses (4%) and 24 partial responses (48%). The median survival duration was 13 months and the 1-year survival rate was 61%. The regimen was generally well tolerated. World Health Organization (WHO) grade 3 and 4 neutropenia occurred in 38.8% and 19.2% of patients, respectively. Grade 3 and 4 thrombocytopenia occurred in 13.3% and 7.7% of patients, respectively. Most patients experienced mild nausea and vomiting. Few patients had hair loss and oral toxicity was mild. Relatively few patients required dose modifications for any of the three weekly doses of chemotherapy. For the first two cycles of chemotherapy, the dose-intensity per infusion was 947 mg/m2 for gemcitabine and 85 mg/m2 for cisplatin. CONCLUSION: This regimen of gemcitabine and cisplatin was effective, with high response and survival rates and few dosage modifications during its administration. Prospective randomized studies with other cisplatin-based combination chemotherapy regimens are indicated.

Efficacy and safety profile of gemcitabine in non-small-cell lung cancer: a phase II study.

PURPOSE: The aim of this study was to evaluate the efficacy and toxicity of gemcitabine at higher doses than had been used previously in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Eighty-four patients (65 men, 19 women; age range, 35 to 75 years; mean age, 59 years) with locally advanced or metastatic pathologically documented NSCLC were enrolled. Patients had bidimensionally measurable disease, as defined by computed tomographic (CT) scan or chest x-ray. A total of 28.6% had previously been surgically treated, while 9.5% had received radiotherapy. Fifty-three patients commenced at a dose of 1,000 mg/m2, and 31 at a dose of 1,250 mg/m2. Patients were to receive two dose escalations of 25%, provided that overall toxicity was no worse than World Health Organization (WHO) grade 1 or WHO grade 0 for platelets. Responding patients were reviewed and validated by a blinded oncology review board (ORB) of experts not involved with the study. Of the original 84 patients enrolled, 76 were assessable. RESULTS: The overall response rate was 20% (95% confidence interval [CI], 11.6% to 30.8%). There were two complete responses (3%) and 13 partial responses (17%). Hematologic toxicity was negligible. WHO grade 3 WBC toxicity occurred in 0.9% of doses and WHO grade 4 in 0.1%. WHO grade 3 and 4 thrombocytopenia occurred in 0.1% and 0.1% of all doses, respectively. Nonhematologic toxicity was minor and easily controlled. Common side effects included peripheral edema, asthenia, and transient malaise. CONCLUSION: The single-agent efficacy of gemcitabine is equivalent to other agents commonly used to treat NSCLC. Gemcitabine has an unusually mild side effect profile for such an active agent. The nausea and vomiting experienced with gemcitabine are mild and generally well controlled with standard antiemetics; 5-HT3 receptor antagonists are typically not required. The use of gemcitabine does not cause significant alopecia, and hematologic toxicity is modest and unlikely to require hospitalization. Gemcitabine may have a role as monotherapy in patients with inoperable NSCLC.

Prospective randomized placebo-controlled study of granulocyte-macrophage colony-stimulating factor without stem-cell transplantation after high-dose melphalan in patients with multiple myeloma.

PURPOSE: To evaluate the impact of granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo on the durations of intravenous (IV) antibiotic use, hospitalization, neutropenia, and fever, as well as remission rates, after high-dose melphalan (HDM) without stem-cell transplantation (SCT) in patients with multiple myeloma (MM). PATIENTS AND METHODS: One hundred two patients with high-risk MM were randomized 2:1 in a prospective multicenter trial to receive 5 microg/kg/d GM-CSF (69 patients) or placebo (33 patients) starting the day after 140 mg/m2 IV melphalan for up to 21 days. RESULTS: GM-CSF significantly reduced neutropenia after HDM (median, 23.5 v 29 days; P = .0468), with a trend to reduce the duration of hospitalization (median, 32 v 38 days; P = .0841). Nevertheless, GM-CSF did not significantly reduce infectious toxicity as regards the number of days with fever (median, 5 v 3; P = .359), the number of days with IV antibiotics (median, 22 v 27; P = .14), or early deaths, with an 11.5% treatment-related mortality rate in the GM-CSF group (eight of 69 v two of 32 patients in the placebo group; P = .686). There was no difference in response rates between the two groups of patients. CONCLUSION: GM-CSF after HDM without SCT is feasible and significantly shortens neutropenia with a trend toward reduction of hospitalization duration, but does not significantly reduce the morbidity and mortality of such therapy. Thus, when intensive therapy is indicated, given that the mortality of HDM followed by SCT reported in the literature is less than 5% and patients are discharged at approximately day 15, despite the risk of contamination by clonogenic malignant cells, SCT appears to be preferable to GM-CSF after HDM.

Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer.

PURPOSE: To perform a randomized three-arm comparison of tamoxifen (TAM; 20 mg/d) and two separate doses of toremifene (TOR; 60 mg/d [TOR60] and 200 mg/d [TOR200]) in postmenopausal patients with hormone receptor-positive or -unknown metastatic breast cancer. MATERIALS AND METHODS: Six hundred forty-eight patients with hormone receptor-positive or -unknown metastatic breast cancer were randomly assigned to receive TAM (n = 215), TOR60 (n = 221), or TOR200 (n = 212). RESULTS: The combined response rates (by intent to treat) were as follows;: TAM, 44%; TOR60, 50%; and TOR200, 48%. Complete and partial response rates were as follows: TAM, 19%; TOR60, 21%, and TOR200, 23% (not statistically different). Median times to progression and overall survival were not significantly different. Adverse events (lethal, serious but nonlethal, and important but non-life-threatening) were similar in all three arms, except that patients in the TOR200 arm had a statistically significantly increased rate of nausea (37% v 26% and 26% for TOR200, TAM, and TOR60, respectively; P = .027). Quality-of-life assessments were not different among the three arms. CONCLUSION: The activity, toxicity, and side effects of TOR in postmenopausal women with hormone receptor-positive or -unknown metastatic breast cancer are similar if not equivalent to those of TAM. We detected no clear evidence of a dose-response effect for TOR. TOR60 is an effective and safe agent for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer and can be considered an alternative to TAM as first-line treatment for such patients.

Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group.

PURPOSE: This phase III study compared docetaxel with mitomycin plus vinblastine (MV) in patients with metastatic breast cancer (MBC) progressing despite previous anthracycline-containing chemotherapy. PATIENTS AND METHODS: Patients (n=392) were randomized to receive either docetaxel 100 mg/m2 intravenously (i.v.) every 3 weeks (n=203) or mitomycin 12 mg/m2 i.v. every 6 weeks plus vinblastine 6 mg/m2 i.v. every 3 weeks (n=189), for a maximum of 10 3-week cycles. RESULTS: In an intention-to-treat analysis, docetaxel produced significantly higher response rates than MV overall (30.0% v 11.6%; P < .0001), as well as in patients with visceral involvement (30% v 11%), liver metastases (33% v 7%), or resistance to previous anthracycline agents (30% v 7%). Median time to progression (TTP) and overall survival were significantly longer with docetaxel than MV (19 v 1 weeks, P=.001, and 1 1.4 v 8.7 months, P=.0097, respectively). Neutropenia grade 3/4 was more frequent with docetaxel (93.1 % v62.5%; P < .05); thrombocytopenia grade 3/4 was more frequent with MV (12.0% v 4.1%; P < .05). Severe acute or chronic nonhematologic adverse events were infrequent in both groups. Withdrawal rates because of adverse events (MV, 10.1%; docetaxel, 13.8%) or toxic death (MV, 1.6%; docetaxel, 2.0%) were similar in both groups. Quality-of-life analysis was limited by a number of factors, but results were similar in both groups. CONCLUSION: Docetaxel is significantly superior to MV in terms of response, TTP, and survival. The safety profiles of both therapies are manageable and tolerable. Docetaxel represents a clear treatment option for patients with MBC progressing despite previous anthracycline-containing chemotherapy.

In vitro maintenance of a new ovarian cancer cell line in protein-free media: a potential model for autonomous growth and tumor progression.

A new cell line UWOV2 (pf) capable of long-term growth in the absence of any added serum protein, exogenous growth factor, insulin or transferrin, is described. The original cell line (UWOV2 and UWOV2 (sf), adapted to grow in serum-free conditions) was derived from the ascitic tumor of a patient with ovarian carcinoma. Under continuous culture conditions further adaptations have occurred enabling UWOV2 (pf) to maintain anchorage-dependent growth without requiring exogenous anchorage or growth factors. These cells produce a structured extracellular matrix which acts as an adhesive substrate for the UWOV2 (pf) cells themselves as well as for a number of other long-term cell lines including NRK and 3T3 cells. Furthermore, while UWOV2 (pf) cells produce a transforming growth factor beta (TGF beta)-like growth factor, they appear to be only partially dependent on autocrine growth stimulation, and other mechanisms for autonomous growth stimulation appear to exist. This cell line may be a useful model for the study of progressive growth autonomy in human tumors.

The treatment of disseminated malignant melanoma with special reference to the role of interferons, vinca alkaloids and tamoxifen.

Malignant melanoma continues to increase in incidence. While early melanoma is highly curable by surgical means, the prognosis of patients with more advanced lesions and/or metastatic disease remains poor. Conventional chemotherapy with dacarbazine has a low frequency and short duration of response. Alternative drugs with single-agent activity include vinca alkaloids, nitrosoureas, procarbazine and platinum compounds. The addition of tamoxifen to chemotherapy, particularly cisplatin-based chemotherapy, appears to be beneficial. Recent studies suggest that combination chemotherapy may give better outcomes than single-agent treatment. Significant clinical activity has also been demonstrated with the use of interferons, particularly interferon alpha, and also with IL-2. Two recent studies suggest that the addition of interferon to chemotherapy may be beneficial. In addition, specific active immunotherapy with tumour vaccines has shown promise. The optimal methods of combining these treatment methods, such as chemotherapy and biological response modifiers/immunotherapy, however, remain to be defined.

Inhibitory effect of nuts on iron absorption.

The effects on iron absorption of nuts, an important source of dietary protein in many developing countries, were measured in 137 Indian women. When the absorption from bread and nut meals (walnuts, almonds, peanuts, and hazelnuts) was compared with that from bread meals, the overall geometric mean absorption from the nut meals (1.8%) was significantly less than from the bread meals alone (6.6%, t = 9.8, p less than 0.0005). In contrast, coconut did not reduce absorption significantly. All the nuts tested contained significant amounts of two known inhibitors of Fe absorption (phytates and polyphenols) but the amounts in coconut were significantly less than in the other nuts. Fifty milligrams ascorbic acid overcame the inhibitory effects of two nuts that were tested (Brazil nuts and peanuts). This is different from that found previously for soy protein, another potent inhibitor of Fe absorption.

A randomised trial of vindesine plus interferon-alpha 2b compared with interferon-alpha 2b or vindesine alone in the treatment of advanced malignant melanoma.

60 patients were entered into a randomised study comparing vindesine (3 mg/m2/week) plus interferon-alpha 2b (6 U/m2 3 times per week) to vindesine alone or to interferon alone for the treatment of metastatic malignant melanoma. Patients receiving the combination therapy arm (schedule A; vindesine plus interferon-alpha 2b) showed a complete and partial response rate of 8/20 (40%) which was significantly higher (P < 0.05) than that achieved with either single-agent treatment schedule. In addition, patients receiving the combined treatment schedule had a significantly prolonged survival (median 19 months) when compared to a median of 10 months for interferon alone and 5 months for vindesine alone. The combination was generally well tolerated with only additive toxicity. It is concluded that combination treatment regimens utilising interferons together with chemotherapeutic agents deserve further study in the treatment of metastatic malignant melanoma.

Treatment of malignant ascites due to recurrent/refractory ovarian cancer: the use of interferon-alpha or interferon-alpha plus chemotherapy in vivo and in vitro.

Intraperitoneal treatment with interferon (IFN) for malignant ascites due to advanced ovarian carcinoma refractory to chemotherapy gave an objective response rate of 36% (7/19 patients treated). In vitro studies demonstrated that cytotoxicity of peripheral blood monocytes/macrophages was stimulated by IFN. However, peritoneal exudate cells obtained after intraperitoneal treatment with interferon were not stimulated to kill autologous tumour cells. Clinical response was therefore most probably due to a direct inhibitory effect of IFN on growth of malignant cells rather than due to an immune modulatory effect. Using a newly established ovarian cancer cell line (UWOV1), synergy between the growth inhibitory/antitumour effects of IFN and cisplatin was demonstrated at clinically achievable concentrations of each agent. IFN plus cisplatin proved to be more effective than intraperitoneal cisplatin alone in control of peritoneal carcinomatosis. The response rate was 5/7 (77%) for combined modality therapy vs. 2/9 (22%) for intraperitoneal chemotherapy alone. Both in vitro and in vivo studies suggest a role for interperitoneal therapy for control of refractory ascites in ovarian cancer.

Weekly gemcitabine and monthly cisplatin for advanced non-small cell lung carcinoma.

Most chemotherapy for non-small cell lung cancer (NSCLC) currently includes combination chemotherapy based on cisplatin. Gemcitabine is a nucleoside analog with demonstrated activity against NSCLC, yet it has low toxicity. This phase II study was designed to examine the efficacy of a combination chemotherapy regimen consisting of gemcitabine followed by cisplatin. The patient population comprised 53 patients with pathologically confirmed locally advanced or metastatic NSCLC. Gemcitabine 1,000 mg/m2 was administered on days 1, 8, and 15 and cisplatin 100 mg/m2 was given on day 15. Chemotherapy was administered every 28 days. Of the 50 patients evaluable for response, there were two complete responses (4%) and 24 partial responses (48%). The median duration of response was 8.5 months, median survival was 13 months, and the 1-year survival rate was 61%. The regimen was generally well tolerated. World Health Organization grade 3 leukopenia occurred in 28.8% of patients, while grade 3 and 4 neutropenia occurred in 38.8% and 19.2% of patients, respectively. Grade 3 and 4 thrombocytopenia was seen in 13.3% and 7.7% of patients, and grade 3 and 4 anemia occurred in 11.5% and 1.9% of patients, respectively. Alopecia and oral toxicity was mild, although most patients experienced mild nausea and vomiting. Relatively few patients required dose modifications for any of the three weekly doses of chemotherapy. We conclude that the combination of gemcitabine and cisplatin is an effective regimen for NSCLC, resulting in high response and survival rates. Additional prospective randomized studies with other cisplatin-based combination chemotherapy regimens are warranted.

Radiation therapy in endemic (African) Kaposi's sarcoma.

PURPOSE: Evaluating the role of radiation therapy in the treatment of the endemic, African variant of Kaposi's sarcoma. A retrospective analysis. METHODS AND MATERIALS: Between 1978 and 1990, 28 symptomatic African patients with the African Human Immunodeficiency Virus negative type of Kaposi's sarcoma were referred to the Johannesburg General Hospital. Following staging, all patients were treated with radiation therapy. Doses ranged between 8-10 Gy (single fraction) or 14-24 Gy fractionated over 1-3 weeks. RESULTS: Complete and partial regression of cutaneous lesions was achieved in 9 (32%) and 15 (54%) patients, retrospectively. A complete/near-complete alleviation of symptoms was achieved in all patients. Response rate and duration of response was not influenced by age, radiation modality or schedule. Side effects were minimal. CONCLUSION: Our study emphasizes the high radiosensitivity of the endemic, African type of Kaposi's sarcoma, indicating its usefulness as the treatment of choice for this disease.

Radiation therapy for non-AIDS associated (classic and endemic African) and epidemic Kaposi's sarcoma.

PURPOSE: A retrospective analysis of patients with non-AIDS and AIDS-related Kaposi's sarcoma, who were treated with radiation therapy. METHODS AND MATERIALS: Between 1978 and 1992, 56 patients with one of the three major types (classical, endemic, epidemic) of Kaposi's sarcoma received radiation therapy as their sole treatment modality. Extent of fields, daily fractionation, and total dose were applied on a clinical basis. These lesions received superficial x-ray therapy, Co-60 teletherapy, or 6-8 MeV electron beams. Field sizes depended on extent of the lesion. Total dose administration ranged from 8-12 Gy in one exposure, or a total of 24-30 Gy fractionated over 2-3 weeks. RESULTS: The majority of patients responded to radiation therapy. Symptomatic relief was achieved in 80-100% of patients irrespective of the type of Kaposi's sarcoma, treatment modality, or schedule. Side effects were tolerable in all but three patients with epidemic type Kaposi's sarcoma, who developed severe mucositis. CONCLUSION: Radiotherapy is the most useful mode of palliative treatment for all forms of Kaposi's sarcoma in southern African patients.

Adjuvant chemotherapy (CMF) for stage III breast cancer: a randomized trial.

A randomized trial of the effect of adjuvant CMF chemotherapy in patients with Stage III breast cancer receiving primary local radiation or local radiation plus surgery, failed to reveal a survival benefit from early systemic treatment. The subset of premenopausal patients receiving chemotherapy did, however, show a significant prolongation of disease-free survival from 23 to 55 months. Overall survival of this subgroup was not increased. The study included the use of two dose levels of CMF to assess whether higher chemotherapy doses would be more effective. No dose effect was observed. Initial local control with radiation therapy or radiation plus surgery was achieved in the majority (90.9%). Distal recurrence and death from metastatic disease were the major causes of treatment failure. Treatment benefit among premenopausal patients was mainly delayed onset of distal metastatic disease. Among premenopausal patients, salvage therapy for metastatic disease appeared more effective in those not previously exposed to systemic treatment.

Neutrophil lactoferrin content in viral infections.

In an attempt to elucidate the previously observed decrease in plasma lactoferrin-neutrophil ratio in subjects with acute viral infections, a study of the neutrophil lactoferrin content in such infections was undertaken. With the use of an immunoperoxidase stain for lactoferrin, neutrophils in viral illness were shown to have reduced lactoferrin content (mean score 97.9 +/- SD [38.0] per 100 neutrophils) as compared with normal subjects (mean score 196.4 +/- SD [3.6] per 100 neutrophils) (t = 7.69; P less than 0.0005). This suggests an acquired defect of neutrophil lactoferrin synthesis in viral infection. This finding is of importance when seen against the well-recognized increased risk of bacterial superinfection in subjects who have recently had a viral infection.

The routine diagnostic utility of immunoglobulin and T-cell receptor gene rearrangements in lymphoproliferative disorders.

Immunophenotypic studies have a well-documented role in the assignment of lineage in the lymphoproliferative disorders. With the exception of mature B-cell disorders, it is difficult to demonstrate clonality by immunophenotypic studies. The advent of specific DNA probes for immunoglobulin and T-cell receptor genes has greatly facilitated the detection of clonality and, to a lesser degree, lineage, in these cases. The authors have evaluated the diagnostic utility of these probes and compared them with standard immunophenotyping in 65 patients with a variety of lymphoproliferative disorders. Their results show a significant correlation (P less than 0.01) between lineage assignment as determined by phenotyping and gene rearrangement studies, with the latter far superior in determining clonality. Furthermore, analysis of gene rearrangements facilitated the documentation of lineage and/or clonality in six cases in which standard techniques had failed. Although the scientific basis of the study of gene rearrangements has been well established, the authors wish to emphasize the role that these techniques have in evaluating problem cases in the routine diagnostic laboratory.

Hematologic and iron-related measurements in rheumatoid arthritis.

The hematologic status of 265 patients with rheumatoid arthritis was assessed. In the group as a whole, a mild depression in the hemoglobin concentration and mean cell volume (MCV) was associated with an increase in the red blood cell distribution width (RDW), erythrocyte sedimentation rate (ESR), and platelet count. Bone marrow trephine biopsies and further measurements of iron status and disease activity were done in [a further] 38 more anemic patients, and the findings in those with absent marrow iron (iron deficiency) were compared with those having stainable stores (anemia of chronic disorders). The RDW was raised in both, and there was no significant difference between the two groups. The concentrations of nonheme iron in the marrow and of serum ferritin were significantly lower in the iron-deficient group, but the geometric mean serum ferritin of 34 micrograms/L was still a good deal higher than that associated with uncomplicated iron deficiency. This was presumably because of the fact that the serum ferritin, which was significantly correlated with the ESR (r 0.55; P less than 0.0004) and C-reactive protein (CRP) r 0.41; P less than 0.01), was also functioning as an acute phase protein. While there was a weak correlation (r 0.37; P less than 0.04) between the marrow nonheme iron and the serum ferritin concentrations, it disappeared when nonactive patients with normal CRP concentrations were excluded. The absence of a correlation is unlike the findings that have previously been noted in other chronic inflammatory conditions and in neoplasia. This raises the possibility that serum ferritin concentrations in rheumatoid arthritis may reflect, in part at least, another store of iron located in affected joints.

Red blood cell distribution width in the anemia secondary to tuberculosis.

A study was done to explore the claim that anisocytosis as measured by the red blood cell volume distribution width (RDW) is raised in iron-deficiency anemia, but is normal in the anemia of chronic disorders. Measurements were done on 283 normal patients, 22 iron-deficient patients, and 102 tuberculotic patients, using a model S plus Coulter Electronic Counter with standard calibration. Mean (+/- SD) values for RDW were as follows: normals, 7.36 (+/- 0.57); untreated iron deficiency, 10.39 (+/- 1.37); and 15 untreated anemic patients with tuberculosis, 10.44 (+/- 0.63). Mean values remained above 10.4 in 69 patients with tuberculosis during treatment, irrespective of whether or not the patients were anemic, but had fallen towards the normal mean (8.49 +/- 0.8) in the 18 subjects in whom it was measured at the end of therapy. By this time the mean corpuscular volume (MCV) and hemoglobin concentrations had risen to normal. It is concluded that RDW values in the chronic inflammatory disorder tuberculosis are not significantly different from those occurring in iron-deficiency anemia.