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Dietary cells and the vitamins B12 and folate are necessary for the production of the red blood cells (erythrocytes), which carry oxygen from the lungs to the tissues and carbon dioxide from tissues to lungs. Deficiency of either one results in anaemia, which is characterised by low haemoglobin concentration. Symptoms result from reduced tissue oxygenation and include weakness, lethargy, palpitation, headache and shortness of breath. The first-time laboratory test of all patients suspected of being anaemic is the full blood count. Results of a full blood count may suggest the anaemia is caused by a nutritional deficiency of B12 folate or iron. Laboratory measurement of the concentration in blood of iron and vitamin B12 and folate, along with several other tests described here, are useful in the differential diagnosis of the anaemic patients.
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PMID:Deficiency testing for iron, vitamin B12 and folate. 760 52

Twenty-two cases of rickettsiosis imported to Germany (13 men, nine women, average age 42 years) in a 5-year period were analyzed retrospectively regarding the travel histories, symptoms and clinical findings, laboratory features and course of the disease. The two primary rickettsial diseases were boutonneuse fever (18 patients) and scrub typhus (three patients). One patient had murine typhus. The main symptom was fever in 91% followed by headache (64%), myalgia (40%), arthralgia (50%) and diarrhea (36%). The most frequent clinical finding was lymphadenopathy in 65%. Eschar was detectable in 55% of patients with Rickettsia conori infection and in one patient with Rickettsia tsutsugamushi infection. All patients with R. tsutsugamushi infection as well as 33% of the patients with R. conori infection had a macular exanthema. One patient with scrub typhus had pleural and pericardial effusions. Seventy-three percent had an increased ESR. Three patients had leucocytosis, three increased transaminases and two normochromic anemia. The incubation period for R. conori infection was 5 to 28 days (average 14 days), for R. tsutsugamushi infection 7 to 21 days (average 16 days). Twenty-one patients were treated with tetracycline or doxycycline, one with erythromycin. All patients were cured. One patient had a relapse. Due to the fact that the symptoms are often not characteristic and that the routine laboratory findings are of only marginal help, the diagnosis of rickettsial diseases is often not easy. A detailed travel history sometimes gives an important hint for diagnosis.
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PMID:Imported rickettsioses in German travelers. 762 71

We describe two siblings affected by chronic relapsing thrombotic thrombocytopenic purpura from infancy. The elder brother, a 12-year-old boy had 50 such episodes characterized by acute onset of fever, headache, drowsiness, vomiting, dark urine, thrombocytopenia and anemia. The younger sister, a 6-year-old girl, had 8 episodes with the same clinical manifestations. Petechiae and ecchymoses on the extremities were present throughout their lives. Furthermore, anemia with evidence of red blood cell fragmentation and thrombocytopenia were present chronically. Periodical transfusion of frozen fresh plasma prevented recurrent episodes. These cases suggest that there is a congenital variant of thrombotic thrombocytopenic purpura.
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PMID:A congenital variant of thrombotic thrombocytopenic purpura in two siblings. 771 55

In a phase I/II study, 11 patients with marrow failure (10 with acquired aplastic anaemia and one with pancytopenic Fanconi anaemia) were treated with recombinant human interleukin-6 (rhIL-6) to assess the safety and tolerability of rhIL-6 and its effects on peripheral blood counts, bleeding complications and transfusion requirements. All patients with acquired aplastic anaemia were refractory to immunosuppressive treatment or had relapsed after immunosuppressive therapy and were not bone marrow transplantation candidates. Recombinant hIL-6 was to be given as a once-daily subcutaneous injection for 28 d at doses ranging from 0.5 to 5.0 micrograms/kg. After an observation period of 2 weeks, five patients received a second treatment course of 28 d. Only one patient had a sustained increase in platelet count from 18,000 to 72,000/microliters. Bleeding occurred in four patients and caused premature discontinuation of rhIL-6 therapy in three patients. A deterioration of pre-existing anaemia was observed in nine patients. No significant changes of leucocyte counts were observed during the first cycle. During the second cycle the peripheral blood monocyte counts decreased significantly. No significant changes in bone marrow cellularity were observed. Recombinant hIL-6 induced a dose-dependent increase in acute-phase reactants in all patients. Other adverse events included fever, headache, arthralgia, tachycardia and hypertension. In conclusion, rhIL-6 given alone at low doses does not increase platelet counts in the majority of patients with aplastic anaemia and can precipitate a sudden worsening of pre-existing anaemia and thrombocytopenia. This study was discontinued prematurely on account of the toxicity of rhIL-6 seen in patients with aplastic anaemia.
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PMID:A phase I/II trial of recombinant human interleukin-6 in patients with aplastic anaemia. 779 47

Packed red cells (RBC) are customarily infused slowly to allow time for re-equilibration of intravascular volume, but they may be given rapidly for convenience during hemodialysis or partial RBC exchange when blood volume can be adjusted extracorporeally. We describe an apheresis procedure for rapid transfusion of RBC to patients with chronic anemia in which an equivalent volume of recipient plasma is withdrawn as donor RBC are infused. Fifteen such procedures, transfusing 3 to 5 RBC units each, have been performed on nine patients (4 of them outpatients) with either COBE Spectra or COBE 2997. Mean +/- SD procedure duration was 1.79 +/- .44 hr; patient hemoglobin rose from 7.3 +/- 1.5 to 12.0 +/- 1.5 g/dl. Comparison to conventional transfusion was possible for nine procedures on six patients in which rapid transfusion required .52 +/- .12 vs. 2.70 +/- .37 hr per unit (P < .001) and raised hemoglobin by 1.22 +/- .30 vs .88 +/- .34 g/dl per unit (P < .02). Pink plasma noted during one procedure was attributable to infusion of an older AS-1 unit with extensive storage hemolysis. Rapid transfusion was subjectively well tolerated. Immediate post-procedure systolic blood pressures did not differ significantly from baseline, although one hypertensive patient had headache followed by increased blood pressure 4 hours after a procedure. We conclude that rapid transfusion of RBC is a technically feasible and more time efficient means for RBC transfusion. It is particularly attractive in the outpatient setting, and could also prevent fluid overload associated with RBC transfusion in some volume-sensitive patients.
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PMID:Rapid red cell transfusion by apheresis. 779 64

Retinoids have anti-tumor activity in several malignant and premalignant conditions. Since Kaposi's sarcoma is regulated by steroid hormones both in vivo and in vitro, we hypothesized that retinoids may have anti-tumor effects in AIDS-related Kaposi's sarcoma. Thus, 27 patients with mucocutaneous, non-visceral AIDS-related Kaposi's sarcoma were treated with all-trans retinoic acid (tRA). Poor tolerance was observed at the initial starting dose of 150 mg/m2, and thus subsequent patients were treated using a weekly dose escalation, starting with 45 mg/m2 (given daily, in subdivided doses), to the target dose of 150 mg/m2 (given daily in three subdivided doses). Nearly half (46%) of the patients had extensive mucocutaneous disease with over 25 lesions. No patient had received prior cytotoxic chemotherapy. Ten patients had CD4 lymphocytes of 200/mm3 or greater (strata I); and 17 had under 200/mm3 CD4 lymphocytes (strata II). The median of the average daily tRA dose administered was 150 mg (90 mg/m2; there was no significant difference in the dose tolerance between the two strata). Adverse effects consisted of transient mild to moderate headaches in 65% of patients, mild to moderate skin dryness and cheilitis in 61%, and nausea and vomiting in 31%. Hematologic toxicities included hypertriglyceridemia in 62%, anemia in 23%, and neutropenia in 23%. Partial response to therapy was observed in 4/24 (17%) evaluable patients, occurring after 12, 20, 24, and 28 weeks of therapy, and lasting 4-24 weeks. Three responders had baseline CD4 lymphocyte counts < 200/mm3. Three additional patients experienced reduction in measured indicator lesions of greater than 25% but less than 50%, and seven patients experienced disease stabilization of 16 weeks or greater. In evaluable patients, the median time to disease progression was 22 weeks and the overall median survival in all patients was 27.3 months. No significant changes in CD4 lymphocyte counts, p24 antigen, and beta 2 microglobulin were observed over time. However, a statistically significant increase was observed in soluble IL-2 receptor levels while on tRA (p = 0.037). We conclude that tRA has activity in patients with mucocutaneous AIDS-related Kaposi's sarcoma with acceptable toxicity. tRA has immunological effects without upregulation of HIV parameters. Additional studies in combinations or with more active retinoids are warranted.
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PMID:All-trans retinoic acid for the treatment of AIDS-related Kaposi's sarcoma: results of a pilot phase II study. 780 21

Combination chemotherapy with anti-proliferative agents is the usual treatment for patients with advanced non-small cell lung cancer (NSCLC), good performance status and no major clinical contraindications. Lonidamine (LND), a new drug with an innovative mechanism of action, might potentiate anti-cancer activity of conventional cytotoxic drugs, with no increase of specific toxicity. Following a pilot study of feasibility, we now report the results of a randomised trial evaluating MACC chemotherapy, as originally described, versus the same regimen+LND. 151 patients with advanced NSCLC were assigned at random to the two treatment arms. LND 150 mg was given orally three times daily. Treatment was continued until progression of disease, unacceptable toxicity or refusal by the patient (median number of cycles of MACC, three for both arms; median duration of LND administration, 8 weeks in the arm concerned). Actual dose intensities (DI) of MACC and LND were, respectively, 100 and 83% of those intended (median values). There was a negative correlation between duration of chemotherapy and the DI of MACC reached in each patient, but no correlation between the duration of treatment with LND and its DI. DIs of LND and MACC were not correlated with each other. In all, 15 objective responses (one complete and four partial responses in the MACC group, 10 partial responses in patients on MACC+LND) were observed. Median progression-free survivals were 20 weeks (confidence interval, CI 14-22) for the group on LND and 17 weeks (CI 12-17) for the control group (non-significant difference). Median overall survivals were, respectively, 30 weeks (CI 23-40) and 27 weeks (CI 22-34), P = non-significant. Toxicity was as expected by the use of MACC, and similar in both arms, except for more severe anaemia and gastric toxicity in the group on MACC+LND. Other uncommon side-effects, seen only in this latter group, were mild to moderate and reversible and included myalgia, asthenia, testicle pain, headache, visual troubles, incubi and dizziness. Subjective tolerance to the treatment, and perception of physical and psychological well-being were rated similarly by patients of both groups. MACC plus LND is a moderately active regimen in advanced NSCLC, with a foreseeable and reversible toxicity of low-medium grade. Potential enhancements of anti-tumour efficacy of chemotherapy, and possible host survival benefits derived from the use of LND are not substantiated by the results of this trial.
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PMID:A randomised trial of MACC chemotherapy with or without lonidamine in advanced non-small cell lung cancer. Cuneo Lung Cancer Study Group (CuLCaSG) 783 93

To define the toxicity profile of recombinant human interleukin-6 (rhIL-6) and to study its effect on hematopoiesis, biochemical parameters and other cytokines, rhIL-6 was administered in a phase I-II study to 20 patients with breast carcinoma or nonsmall cell lung cancer. RhIL-6 doses were 0.5, 1.0, 2.5, 5.0, 10, and 20 micrograms/kg/d, with at least three patients per dose level. RhIL-6 was administered 24 hours by continuous intravenous infusion followed by subcutaneous (SC) administration for 6 days, partly on an outpatient basis. RhIL-6-related side effects were fever, headache, myalgia, and local erythema. Starting at 2.5 micrograms/kg/d, these side effects were compounded by nausea, reversible increase in liver enzymes, and anemia. Flu-like symptoms were controllable up to and including 10 micrograms rhIL-6/kg/d with acetaminophen. RhIL-6 increased platelet counts with a decrease in mean platelet volume and increased leukocytes caused by neutrophil, monocyte, and lymphocyte increase, with an increase in T cells and natural killer cells at 1.0 and 2.5 micrograms rhIL-6/kg/d. The reversible anemia was characterized by a decrease in serum iron, and an increase in ferritin and erythropoietin without reticulocytosis. RhIL-6 reduced total cholesterol levels and a dose-related increase of C-reactive protein and serum amyloid A plasma levels was observed. Serum IL-6 levels were increased, especially at 10 and 20 micrograms/kg/d, whereas no change in IL-1 beta and tumor necrosis factor alpha levels was observed. RhIL-6 can be administered with controllable side effects in this setting, up to and including a SC dose of 10 micrograms/kg/d on an outpatient basis, and has a promising stimulating effect on leukopoiesis and thrombopoiesis.
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PMID:Effects of recombinant human interleukin-6 in cancer patients: a phase I-II study. 806 39

A total of 4676 patients and 1759 patients were treated with lisinopril and nifedipine respectively in a post-marketing surveillance study conducted in general practice in the UK. Patients were followed up for 12 months. Most of the lisinopril patients had hypertension, but a small number (180) had heart failure. Most of the nifedipine patients had uncomplicated hypertension, but some (22.57%) had other cardiovascular disease with or without hypertension. Lisinopril and nifedipine were equally effective in reducing blood pressure. During the study, 1.5% of hypertensive patients assigned to lisinopril died compared with 1.8% of patients assigned to nifedipine, and 15.1% of lisinopril patients compared with 19.7% of patients in the nifedipine group withdrew because of adverse events. Cough, malaise and fatigue, nausea and vomiting were more frequent causes of withdrawal from lisinopril than nifedipine. Conversely, headaches, pallor and flushing, oedema and palpitations caused more frequent withdrawals from nifedipine. Anaemia was more often encountered on nifedipine treatment than on lisinopril. In hypertensive patients, the frequency of first-dose hypotension was similar on both treatments. Serious events occurred in 0.8% and 0.5% of patients given lisinopril and nifedipine respectively. Lisinopril was well tolerated by heart failure patients: 16 patients (8.88%) died and an incidence of 4.44% of serious adverse events was reported, a pattern to be anticipated in such patients; dizziness, giddiness, dyspnoea, cough, nausea and vomiting were the most frequent causes of withdrawal; the incidence of first-dose hypotension was low (2.22%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Post-marketing surveillance of lisinopril in general practice in the UK. 811 50

The introduction of carboplatin as a replacement for cisplatin into treatment strategies against ovarian cancer has ameliorated major toxicities related to cisplatin, but carboplatin-evoked myelosuppression requires further study, especially since the addition of growth factors for bone marrow and hematologic support has been introduced into clinical practice. Since higher doses of platinating agents seem to be related to higher response rates, the protective effect of interleukin-3 on 800 mg carboplatin, a twofold increment over the usual dose, was studied. A modest myeloprotective potency was documented in the second treatment cycle of this aggressive chemotherapy program, but this effect tapered away in subsequent treatment courses, which occasionally included severe side effects (eg, headache, kidney function impairments). Another study addressed the anemia frequently observed with both cisplatin- and carboplatin-based treatment regimens in ovarian cancer, which is probably related to low erythropoietin levels. Very preliminary analysis of an ongoing phase III trial studying two erythropoietin doses given continuously subcutaneously versus a retrospective analysis of a "control group" (drawn from historical data on the occurrence of anemia in cisplatin- and/or carboplatin-treated patients) has shown beneficial effects of erythropoietin during treatment with these platinating agents.
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PMID:Further studies to ameliorate toxicity of carboplatin. 820 18


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