Renal pathology and retinol status in multiple myeloma patients.

Renal dysfunction is a common and serious complication in multiple myeloma (MM) patients. Renal proximal tubule injury is characteristic in MM, and may result in disturbed renal handling of various vitamins. The abnormal excretion of vitamins in urine may result in their low serum levels. The goal of this study was to investigate the urinary excretion of retinol in MM and its relationship with serum retinol concentration. For this purpose, 24 MM patients and 10 healthy individuals were studied. Serum and urinary retinol and retinol-binding protein (RBP) were measured by the high-performance liquid chromatography method and enzyme-linked immunosorbent assay, respectively. The study showed that 58% of MM patients excreted retinol in urine, while only 29% had elevated serum creatinine (P<0.05). There was a strong and highly significant correlation between urinary retinol and RBP (r=0.973, P<0.006). Patients with normal and mildly elevated serum creatinine who excreted retinol in urine had a marked decrease in serum retinol (P<0.007). On the other hand, serum retinol was not decreased in patients with moderate or severe renal failure, despite its urinary loss. Our data indicate that (i) urinary retinol is a more frequent marker of renal dysfunction than elevated serum creatinine in MM patients, (ii) serum retinol is decreased in MM with normal or mildly elevated serum creatinine, but not in patients with moderate/severe renal failure, and (iii) urinary retinol may serve as a diagnostic marker of renal proximal tubule dysfunction in MM patients.

The need for routine pre-operative coagulation screening tests (prothrombin time PT/partial thromboplastin time PTT) for healthy children undergoing elective tonsillectomy and/or adenoidectomy.

In some medical centers, the routine pre-operative evaluation of healthy children undergoing elective tonsillectomy and/or adenoidectomy (T and A) includes coagulation screening tests (PT, prothrombin Time; PTT, partial thromboplastin time; and INR, international normalized ratio). In this retrospective study, we determined whether there is a positive correlation between prolonged PT/PTT/INR tests in healthy children, with no prior medical history of coagulation problems, and bleeding during surgery and/or bleeding in the month following surgery. We reviewed the records of 416 elective T and A surgeries performed at the Soroka University Medical Center in Beer-Sheva, Israel, over the course of 1999. One hundred and twenty-one (29.1%) patients had preoperative prolonged PT values but only four (3.3%) of these patients experienced light bleeding during surgery. Seven (5.8%) of the 121 patients with prolonged PT tests experienced bleeding episodes during the 1st month subsequent to the surgery. Of the 65 (15.6%) patients who had prolonged pre-operative INR values, only three (4.6%) experienced light bleeding during surgery. Two (3.1%) patients with prolonged INR values experienced light bleeding during the 1st month subsequent to surgery. Sixty-one (14.7%) patients had prolonged first preoperative PTT values, only five of whom (8.2%) experienced light bleeding during surgery. Two (3.3%) of the 61 with prolonged PTT values experienced light bleeding during the 1st month subsequent to surgery. We therefore concluded that pre-operative coagulation screening tests provide low sensitivity and low bleeding predictive value. As such, routine coagulation tests before T &A are not indicated unless a medical history of bleeding tendency is suspected.

Quality assessment of oral anticoagulant treatment in the Beer-Sheba district.

OBJECTIVE: To evaluate the adequacy of oral anticoagulation therapy in patients with either prosthetic heart valves or atrial fibrillation. DESIGN: Adequacy of anticoagulation therapy of patients treated with warfarin was determined before and after implementation of an improvement programme. SETTING: The central haematology laboratory of the Soroka Medical Center, Beer-Sheba Israel. STUDY PARTICIPANTS: One hundred and ten patients treated with chronic anticoagulation therapy were evaluated by measuring the international normalized ratio of the prothrombin time before and after implementation of an improvement plan aimed at improving anticoagulation control. INTERVENTION: A programme that included physician and patient education and procedural changes covering all aspects of anticoagulation therapy was implemented. MAIN OUTCOME MEASURE: The percent of international normalized ratio tests below, within and above the therapeutic range was determined. RESULTS: Prior to implementation of an improvement plan, only 32% of the measured international normalized ratio values were within the therapeutic range. 16% were above and 52% were below therapeutic range. Improvement intervention led to an increase in the proportion of international normalized ratio tests that fell within the therapeutic range from 32% to 43.2%. CONCLUSIONS: Improvement in the control of anticoagulation therapy of patients receiving long-term warfarin treatment is possible. A combined effort involving the community, physician and patient is required.

Acute blast crisis with EBV-infected blasts, in a patient with chronic myeloid leukemia, and vasculitis.

Unless they undergo transplantation, all patients with chronic myeloid leukemia (CML) will eventually develop a late phase of acute blast crisis (ABC). Although additional chromosomal abnormalities to the Philadelphia (Ph) chromosome may herald ABC in many CML cases, the mechanisms leading to this fatal event are obscure. Viral etiology, including the Epstein-Barr virus (EBV) has never been implicated in the pathogenesis of ABC in CML. Iloprost is an analogue of epoprostenol (prostacyclin; PGI2) commonly used for the treatment of peripheral vascular diseases and acts via inhibition of platelet activation, and by vasodilation. A case of ABC with blasts of undetermined lineage showing EBV infection in a male patient with Ph positive CML is described here. This unusual event developed during a course of treatment with the prostacyclin analogue, iloprost administered for vasculopathic leg ulcers. The proliferating blasts stained positively by immunohistochemistry only for the leukocyte common antigen (LCA/CD-45), and the EBV-latent membrane protein 1 (LMP-1). The only chromosomal abnormality detected by cytogenetic analysis was the conventional Ph-chromosome. It is suggested that ABC in this case of CML, was associated with EBV-activated blasts of undetermined lineage.

Quantitative determinations of microcytic-hypochromic red blood cell population and glycerol permeability in iron-deficiency anemia and beta thalassemia minor.

The Hl/H2 Technicon automated cell analyzer measures, in addition to the usual red blood cell (RBC) parameters, subpopulations of microcytic (M) and hypochromic (H) red blood cells. The M/H ratio may be useful in the differential diagnosis of iron-deficiency anemia (IDA) and beta thalassemia minor (Thal). Thirty-three iron-deficient patients and 26 thalassemia patients were studied. The M/H ratio was found to be higher in thalassemia patients than in IDA patients. Using a cut-off point of 1.9 M/H ratio, the calculated discriminant efficiency was 88%. When glycerol lysis values were determined at 70 s as a cut-off point, the discriminant efficiency was slightly higher, at 91%. Thus, the combination of the M/H ratio and the glycerol lysis time (GLT) improves the discriminant efficiency and provides a good diagnostic tool to differentiate between the two microcytic-hypochromic anemias. The study suggests that the M/H ratio together with the GLT could serve as a useful screening tool, prior to the application of other more sophisticated methods.

Lycopene and 1,25-dihydroxyvitamin D3 cooperate in the inhibition of cell cycle progression and induction of differentiation in HL-60 leukemic cells.

Lycopene, the major tomato carotenoid, has been found to inhibit proliferation of several types of cancer cells, including those of breast, lung, and endometrium. By extending the work to the HL-60 promyelocytic leukemia cell line, we aimed to evaluate some mechanistic aspects of this effect. Particularly, the possibility was examined that the antiproliferative action of the carotenoid is associated with induction of cell differentiation. Lycopene treatment resulted in a concentration-dependent reduction in HL-60 cell growth as measured by [3H]thymidine incorporation and cell counting. This effect was accompanied by inhibition of cell cycle progression in the G0/G1 phase as measured by flow cytometry. Lycopene alone induced cell differentiation as measured by phorbol ester-dependent reduction of nitro blue tetrazolium and expression of the cell surface antigen CD14. Results of several recent intervention studies with beta-carotene, which have revealed no beneficial effects of this carotenoid, suggest that a single dietary component cannot explain the anticancer effect of diets rich in vegetables and fruits. Thus another goal of our study was to examine whether lycopene has the ability to synergize with other natural anticancer compounds, such as 1,25-dihydroxyvitamin D3, which when used alone are therapeutically active only at high and toxic concentrations. The combination of low concentrations of lycopene with 1,25-dihydroxyvitamin D3 exhibited a synergistic effect on cell proliferation and differentiation and an additive effect on cell cycle progression. Such synergistic antiproliferative and differentiating effects of lycopene and other compounds found in the diet and in plasma may suggest the inclusion of the carotenoid in the diet as a cancer-preventive measure.

The effect of EDTA as an anticoagulant on the osmotic fragility of erythrocytes.

The osmotic fragility test is used to determine the extent of red blood cell haemolysis produced by osmotic stress. Since the quality of this test may easily be influenced by environmental and technical factors we have determined osmotic fragility reference values in our own conditions. The results show significantly increased osmotic resistance of erythrocytes in our conditions vs the published values for blood samples anticoagulated with heparin. Furthermore, the use of EDTA as an anticoagulant increased the osmotic fragility of red blood cells as compared with heparin. We conclude that EDTA can be used as an anticoagulant for the osmotic fragility test in order to simplify routine procedures. However, every laboratory should determine its own reference values which would reflect the local environmental and technical factors.

Protein C and protein S in pediatric nephrotic patients.

Nephrotic syndrome (NS) is associated with an increased incidence of various thromboembolic complications in adult patients. It was found to be due to elevated factor IX (FIX) F.VII, F.VIII, F.V, fibrinogen, thrombocytosis and increased platelet reactivity. Acquired AT-III deficiency, reduced functional levels of protein S and reduced activity of protein C were also reported. We evaluated 15 children aged 1 to 13 years. Thirteen of these children suffered from nephrotic syndrome and two others had non-nephrotic proteinuria. All patients but one were normotensive. Two patients were not steroid responsive. Serum creatinine was normal for age in 14 patients. Kidney biopsy was carried out only in three children. Haemostatic parameters included protein C and S antigenicity in plasma and urine. Plasma levels of protein C and protein S were within the normal range. Protein C antigenicity in urine was increased in five children out of 14 examined. Protein S in urine was increased in seven out of 12 children examined. No thromboembolic phenomena were documented even though protein C and protein S antigenicity were identified in the urine.

Interleukin-1 and tumor necrosis factor-alpha in the Reed-Sternberg cells of Hodgkin's disease. Correlation with clinical and morphological "inflammatory" features.

We examined paraffin sections for the expression of interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor-alpha, in 40 cases of Hodgkin's disease. Our purpose was to study the role of these cytokines in the "inflammatory" histological features and "B" symptoms in this disease. Immunohistochemistry with the avidin-biotin-peroxidase complex method was used. The findings were compared with those of 20 cases of non-Hodgkin's lymphomas and of 20 non-neoplastic lymphadenopathies. Evidence for EBV infection and myc and ras oncoproteins expression was also studied in these patients, but no correlation between any of these features and cytokine expression was found. We found a significant correlation between the expression of interleukin-1 beta and several "inflammatory" histological features, as well as between the expression of tumor necrosis factor-alpha and B symptoms and tumor bulk. The differential correlations between these major pro-inflammatory cytokines expression and the "inflammatory" manifestations in Hodgkin's disease are remarkable, considering the complexity of the cytokines composing the cytokine network involved in this disease.

Expression of c-myc and c-ras oncogenes in the neoplastic and non-neoplastic cells of Hodgkin's disease.

The oncogenes c-myc and c-ras are known to elicit a cooperative tumorigenicity. In this study we investigated their role in the pathogenesis of Hodgkin's disease. The expression of these oncogenes was determined in Hodgkin's disease patients by avidin-biotin peroxidase complex immunohistochemical staining and was compared to their expression in patients with non-Hodgkin's lymphomas and inflammatory reactive lymph nodes. Of 29 examined patients with different histological types of Hodgkin's disease, 21 (72.4%) showed an elevated expression of c-myc and 28 (96.5%) of c-ras. Although this expression was marked especially in the neoplastic Reed-Sternberg cells, it was also noted in the numerous reactive cells present in the involved lymph nodes. By contrast, a much lower frequency of increased expression of these oncogenes was recorded in 19 patients with different grades of non-Hodgkin's lymphoma and in 29 patients with inflammatory reactive lymph nodes. The elevated expression of c-myc and c-ras in the neoplastic Reed-Sternberg cells may reflect an oncogenic event that directly activates these genes. However, their increased expression in the surrounding non-neoplastic cells probably results from signal transduction induced by certain growth-promoting factors possibly released by the Reed-Sternberg cells and that act paracrinally to stimulate the proliferation of the neighboring cells. Furthermore, the continuous c-ras elevation may impair the normal cell cycle control and thereby promote mutagenesis and overt malignancy.

[Coomb's-positive hemolytic anemia and tuberculosis in Kaposi's sarcoma treated with interferon].

Immune hemolytic anemia and reactivated tuberculosis developed in a patient treated with alpha-interferon for Kaposi's sarcoma and splenic non-Hodgkin's lymphoma. The hemolytic process stopped on cessation of interferon and initiation of corticosteroid therapy, and the Coomb's test became negative. The possibility of reactivation of tuberculosis by interferon is discussed.

Radiation damage to the erythrocyte membrane: the effects of medium and cell concentrations.

Human erythrocytes suspended in plasma, or in phosphate buffered saline (PBS), were exposed to ionizing radiation. Potassium leakage from irradiated erythrocytes is significantly higher in PBS than in plasma. The potassium leakage decreases when PBS is gradually replaced by plasma. These findings suggest that some of the plasma constituents have radioprotective properties. The potassium leakage per cell is independent of the hematocrit, Hct. The potassium leakage is attributed to the formation of radiation defects in the membrane. Analysis of the effect of radiation dose, plasma and cell concentrations on the product of the number and surface area of the radiation defects indicates that the radiation damage is mainly due to the direct formation of free radicals in the cell membrane. The radioprotective effect of plasma is attributed to surface reactions of these free radicals with plasma constituents adsorbed on the membrane.

Familial thrombotic thrombocytopenic purpura in a Bedouin family.

A 24-year-old Beduin pregnant woman in her 22nd week of gestation was treated successfully by plasmaphereses and steroids as soon as the diagnosis of TTP was confirmed by the clinical and laboratory criteria needed. Her sister died due to complications of TTP in pregnancy five years earlier while her other sister recuperated from TTP during pregnancy. However, fetal loss ensued. Thus, family history in pregnant women presenting with toxemia of pregnancy--like--syndrome may be the first clue to familial TTP.

Acquired auto-anti D in a patient with myelodysplastic syndrome.

Modification of blood group in the course of malignant haemopathy in an aged patients is described. To our knowledge, this is the first published case describing the appearance of autoantibody due to anti-D in a patient with Rh typing DCcee who has myelodysplastic syndrome in transition to acute leukaemia. We present a patient who developed acquired autoantibody to Rh locus as co-phenomenon of myelodysplastic syndrome in transition to acute leukaemia.

[Toxicity to rodenticides and its treatment].

A case is presented of exposure to a rodenticide which caused a severe disorder of hemostasis, including macroscopic hematuria, several months after the patient was exposed to it. Response to treatment with vitamin K and barbiturates came only after 70 days. The cause-and-effect relationship between exposure to the rodenticide and the disorder in hemostasis is based on the clinical course and on the late response to treatment.

Aggressive behavior of carcinoma of the colon associated with nonsecreting plasma cell myeloma. A case report.

A patient was diagnosed for nonsecreting myeloma stage IIIA (Salmon-Durie) 6 months after colectomy for adenocarcinoma of the colon, Duke's stage A. The patient had not received chemotherapy for the colonic carcinoma and its clinical course was much more aggressive than expected. Although it might be coincidental, to our knowledge this is the first reported case of an association between a nonsecreting myeloma and adenocarcinoma of the colon.

Traumatic total hyphema in a patient with severe hemophilia.

A 12-year-old hemophilic boy suffered from secondary glaucoma in his right eye due to total hyphema following trauma. An emergency operation was performed to evacuate the hyphema under a tight anti-hemophilic treatment. A careful postoperative treatment with factor VIII concentrate, antiglaucomatous drugs and aminocaproic acid was administered. Intraocular pressure returned to normal and remained so during the four months follow-up period. Visual acuity returned to 6/9 and there was no rebleeding into the anterior chamber. To the best of our knowledge, this is the first reported case of traumatic hyphema and of an operation to wash this hyphema in a hemophiliac. The dilemma of management of such a case is discussed.