Gurhan Kadikoylu

Oral Versus Intramuscular Cobalamin Treatment in Megaloblastic Anemia: A Single-Center, Prospective, Randomized, Open-Label Study

BACKGROUND Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administration and lower cost. OBJECTIVE This study assessed the effects and cost of p.o. versus i.m. cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency. METHODS This was a 90-day, prospective, randomized, open-label study conducted at the Division of Hematology, Department of Internal Medicine, Adnan Menderes University Research and Practice Hospital (Aydin, Turkey). Patients aged > or =16 years with megaloblastic anemia due to cobalamin deficiency were randomized to receive 1000-microg cobalamin p.o. once daily for 10 days (p.o. group) or 1000-microg cobalamin i.m. once daily for 10 days (i.m. group). After 10 days, both treatments were administered once a week for 4 weeks, and after that, once a month for life. Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected. Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0, 10, 30, and 90 and serum vitamin B12 concentration on days 0 and 90. The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing. Neurologic sensory assessment, including soft-touch and pinprick examinations, was used to identify neuropathy at baseline and study end. Tolerability was assessed using laboratory tests and patient interview. Cost was assessed using the cost of the study drug and of the injection. RESULTS Sixty patients completed the study 26 in the p.o. group (16 men, 10 women; mean [SD] age, 60 [15] years) and 34 in the i.m. group (17 men, 17 women; mean [SD] age, 64 [10] years). Reticulocytosis was observed in all patients. In the p.o. group, at days 30 and 90, all hematologic parameters changed significantly versus day 0 (mean hemoglobin levels increased [both P<0.001]; mean corpuscular volume decreased [both P<0.001]; mean white blood cell count increased [day 30, P<0.01; day 90, P<0.001]; and mean platelet count increased [both P<0.001]). The mean serum vitamin B12 concentration increased significantly from day 0 to 90 (P<0.001). These hematologic parameters and the recovery patterns were similar between the 2 groups. Neurologic findings included sensitive peripheral neuropathy in 9 patients (15.0%), alteration of cognitive function (loss of memory, impaired concentration) in 7 patients (11.7%), and loss of sense of vibration in 5 patients (8.3%). Neurologic improvement was detected in 7 of 9 patients (77.8%) in the p.o. group and 9 of 12 patients (75.0%) in the i.m. group at day 30. CONCLUSIONS In this study of patients with megaloblastic anemia due to cobalamin deficiency, p.o. cobalamin treatment was as effective as i.m. cobalamin treatment. P.o. treatment also was better tolerated and less expensive compared with IM treatment. However, because of the small sample size and the short term of this study, further long-term studies are needed to determine the efficacy of p.o. cobalamin treatment.

Iron deficiency anemia and restless legs syndrome: is there an electrophysiological abnormality?

OBJECTIVE The pathogenesis of restless legs syndrome (RLS) is unknown. Although iron deficiency anemia (IDA) is related with RLS, the mechanism of this relationship is still unknown. Therefore, we decided to examine some neurophysiological parameters that reflect the function of brainstem, spinal cord and peripheral nervous system. MATERIALS AND METHODS 34 patients diagnosed with IDA at the hematology department were questioned with a structured battery for RLS and additional symptoms. Of those, 14 patients had symptoms of RLS, while remaining 20 had no signs of this disorder. In both groups, electrophysiological examination including motor and sensory nerve conduction, F-responses, H-reflex, blink-reflex, and mixed nerve silent periods was performed. RESULTS Neurological examination of all patients was normal. The two groups were identical for age and sex, and the difference between both groups concerning motor and sensory nerve conduction, F-wave, H-reflex, blink-reflex, and mixed nerve silent periods was insignificant. CONCLUSION Results suggest that IDA does not cause electrophysiological changes in the peripheral nerves, spinal cord and brainstem, and therefore, measurement of these parameters in IDA patients does not seem effective for the confirmation of RLS.

Brucellar orchitis in Innerwest Anatolia Region of Turkey. A report of 12 cases.

Brucellosis, which affects the genitourinary system in rate of 2–20%, is a multiorgan infectious disease. Twelve patients were diagnosed as having brucellar orchitis serologically, clinically and ultrasonographically. In 2 patients, Brucella melitensis was isolated in blood cultures. All the patients were working in cattle dealing. They were treated with 600 mg/day rifampicin plus 200 mg/day doxycycline for 6 weeks and followed up during 1 year. They recovered clinically within 3 weeks. Although they did not have any symptoms or findings, in 4 patients, serological titers did not return to normal after 6 weeks. In 2 of these patients, relapse was seen in the 6th and 8th months, respectively. These 2 patients recovered with 1 g/day ciprofloxacin plus 2 g/day tetracycline for 6 weeks. Relapse did not occur again. Conclusively, brucellosis must be considered as a cause of orchitis in especially endemic regions where cattle dealing is widespread. The patients must be followed for relapse during at least 1 year.

The importance of CD7 and CD56 antigens in acute leukaemias

The prognostic significance of immunophenotypical properties of leukaemic cells is well known. However, the biological and clinical significance of CD7 and CD56 antigen expression in acute leukaemias are not clearly established. In patients with acute leukaemias, we identified CD7 and CD56 expression and analysed their associations with markers expressed early in haemopoietic ontogeny and clinical parameters. Among 22 patients with acute leukaemia [12 acute myeloblastic leukaemia (AML), 10 acute lymphoblastic leukaemia (ALL)], we found CD7 positivity in 15 of 22 patients (68%) and CD56 positivity in four patients (18%). CD7 positivity was observed in seven patients (58%) with AML and in eight patients (80%) with ALL. CD56 positivity was observed in three patients (25%) with AML and one patient (10%) with ALL. Lymphadenopathy was present in five patients and associated with hepatosplenomegaly in three patients with ALL. Splenomegaly and hepatomegaly were present in three patients with AML. Central nervous system involvement was seen in one patient with ALL. Complete remission was achieved in nine patients (41%) (five ALL and four AML). Our data showed that CD7 and CD56 positivity at diagnosis associated with low remission rate and biological aggressiveness in a significant proportion of patients. We suggest the evaluation of CD7 and CD56 in all patients with acute leukaemias at the time of diagnosis in view of poor clinical outcome.

Emergent therapy with therapeutic plasma exchange in acute recurrent pancreatitis due to severe hypertriglyceridemia.

Hypertriglyceridemia causes acute pancreatitis in 1.3-3.8% of patients. We report here on two cases with severe (triglyceride level >1000 mg/dL) hypertriglyceridemia-induced acute recurrent pancreatitis. Both patients had uncontrolled hypertriglyceridemia and suffered from acute pancreatitis. No cause of secondary hypertriglyceridemia was detected. While stage E pancreatitis (Ransons score: 2) was diagnosed in the first case, stage D pancreatitis with a null Ransons score was detected in the second case. Both patients were treated with classical treatment with fluid replacement, analgesic, antibiotics and discontinuation of oral intake. Therapeutic plasma exchange (TPE) with fresh frozen plasma was performed consecutively and with two procedures on the 2nd and 3rd day in the first case. After TPE, while the triglyceride levels decreased from 4408 to 302 mg/dL, the amylase levels dropped from 4234 to 171 IU/L. In the second case, TPE was performed once daily. After TPE, the levels of triglyceride and amylase decreased from 2210 mg/dL and 1618 IU/L to 154 mg/dL and 110 IU/L, respectively. Local and systemic complications due to acute pancreatitis were not observed. Clinical signs and laboratory values improved. At the two-year follow-up of both patients, acute pancreatitis had not recurred with regular fenofibrate treatment. Hypertriglyceridemia should be considered in patients with acute recurrent pancreatitis. Although there is no definitive evidence for early application of TPE in severe hypertriglyceridemia-induced acute pancreatitis yet, therapy with TPE may be of benefit, improving the clinical course.

A new perspective on cardiotoxicity of 5-fluorouracil. A novel research tool 'cardiac ultrasonic integrated backscatter analysis' indicates transient, subclinical myocardial dysfunction due to high-dose leucovorin and infusional 5-fluorouracil regimen.

Background: The pathophysiology of 5-fluorouracil (5-FU) cardiotoxicity is still controversial. The objective of this study was to assess the influence of high-dose leucovorin and infusional 5-FU regimen (HDLV5FU) on cardiac tissues. Methods: We monitored 28 patients (median age 68 years) under HDLV5FU chemotherapy with complete blood counts, cardiac enzymes, C-reactive protein, coagulation tests, Holter electrocardiogram, and conventional echocardiography. Cardiac ultrasonic tissue characterization with integrated backscatter (IBS) analysis was performed in the 16 last enrolled patients. Results: The magnitude of both anterior and posterior cardiac IBS values significantly decreased at the 48th hour of treatment compared to both 0th hour and day 15 (p < 0.003). Cardiac IBS values on the 15th day were not different from the 0th hour. Clinical cardiotoxicity was not observed and other monitored parameters did not change significantly in any patient (p > 0.5 for all). Conclusion: Cardiac IBS analysis suggests that 5-FU might cause reversible subclinical myocardial dysfunction.

Is Blastocystis hominis a new etiologic factor or a coincidence in iron deficiency anemia

Iron deficiency anemia (IDA) is a frequent health problem. Gut parasites such as N. americanus and A. duodenale are known to cause blood loss, but the role of Blastocystis hominis is uncertain. In this study, 212 patients (193 female, 19 male, mean age 41 SD 15 yrs) with IDA were enrolled and 90 persons without IDA (78 female, 12 male, mean age 45 SD 17 yrs). Microscopic examination of stools for B. hominis using the native lugol method was done three times on each subject. If any specimen contained five or more cysts per ×400 field, the person was considered positive. B. hominis was found in 48 out of 212 subjects with IDA (22.6%) and in five of 90 (5.6%) subjects without IDA. This difference is highly statistically significant (P < 0.001). Few subjects had other gut parasites and there was no statistical difference in the ir frequencies between IDA and non‐IDA subjects. Blastocystis hominis may play a role in the development of IDA either on its own or in conjunction with some other agent.

Hemostatic Effects of Atorvastatin versus Simvastatin

OBJECTIVE: To compare the effects of simvastatin and atorvastatin on hemostatic parameters. METHODS: Sixty-one patients with primary hypercholesterolemia without coronary heart disease were treated with atorvastatin 10–20 mg/d or simvastatin 10–20 mg/d. At baseline, 4, 12, and 24 weeks, lipid levels such as low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), triglycerides (TGs), and hemostatic parameters such as platelet counts, partial thromboplastin time (PTT) prothrombin time (PT), and fibrinogen levels were measured. RESULTS: At 12 weeks, the doses of the statins were increased to 20 mg/d in 10 of 35 (28.5%) patients treated with atorvastatin and 18 of 26 (69.2%) patients treated with simvastatin when the target level of LDL-C (130 mg/dL) was not reached. Mean doses were atorvastatin 12.8 mg/d and simvastatin 16.9 mg/d. After 24 weeks, 5 patients (14.3%) in the atorvastatin group and 4 patients (15.3%) in the simvastatin group had not reached the goal. In patients with diabetes, target level (LDL-C <100 mg/dL) was not reached in 35.7% of patients in the atorvastatin group and 44.4% of patients in the simvastatin group. Both simvastatin and atorvastatin were effective in lowering TC and LDL-C levels (p < 0.001). Atorvastatin lowered TGs significantly (p < 0.01). Neither atorvastatin nor simvastatin significantly reduced VLDL-C levels. HDL-C levels increased with atorvastatin, but there was no significant difference between the 2 groups. Platelet counts decreased with both statins nonsignificantly. Moreover, fibrinogen levels decreased with simvastatin and atorvastatin, but these reductions were significant only for simvastatin (p < 0.05). We detected prolongation of the PT with both drugs (p < 0.05); however, prolongation of the PTT was significant only with simvastatin (p < 0.001). Effectiveness of both statins on lipid and hemostatic parameters was dose related. Adverse effects were seen in 5 patients (14.2%) treated with atorvastatin and 3 patients (11.5%) treated with simvastatin. Elevations in serum transaminase levels >3 times the upper limit of normal and in creatine phosphokinase >5 times the upper limit of normal were not observed in any group. CONCLUSIONS: Atorvastatin was more effective than simvastatin on lipid parameters, although statistically insignificantly, while simvastatin produced more significant changes than atorvastatin on hemostatic parameters. The mean dose of simvastatin was greater than that of atorvastatin. Both statins had increased effects on lipid and hemostatic parameters when doses were increased. Atorvastatin and simvastatin were well tolerated. Different effects of statins on lipid levels and on coagulation parameters should be considered in patients with hypercholesterolemia and tendency to coagulation, especially in preventing thrombotic events. Further studies in larger trials are needed to confirm these observations.

Extravasation of paclitaxel into breast tissue from central catheter port.

Abstract. A 53-year-old woman with advanced-stage ovarian cancer experienced extravasation of paclitaxel into the breast tissue as a result of inappropriate needle insertion and/or dislodgement; it came from a central catheter port (CCP) that was found to be intact under radiological examination with contrast material. The breast became tender and oedematous with erythema, and local warming was observed within a few hours. The patient improved in the next few days during nonsteroidal anti-inflammatory medication and close observation, and the breast healed with thickened and darkened skin and central scarring in the 6th month of follow-up. To the best of our knowledge, extravasation into breast tissue is rare in the literature. Extravasation of vesicant drugs from CCP can cause tissue necrosis; it is therefore essential that ports be carefully assessed and used by experienced staff to lessen the likelihood of such an unpleasant complication.

The Leser–Trelat sign is a associated with acute myeloid leukemia

Dear Editor, A 69-year-old male was admitted with fatigue. His physical examination was normal except that he was pallor. Dermatologic examination revealed multiple eruptive seborrheic keratoses, which he reported had developed over the previous 2 to 3 years (Fig. 1a–b). WBC was 1.9×10/L, hemoglobin 6.4 g/dl, hematocrit 19.3%, and platelet count 18×10/L. There were blastic cells on peripheral smear and bone barrow aspiration. Bone marrow aspiration revealed hypercellular particles with erythropoiesis and megakaryopoiesis being depressed. The differential counts revealed blasts at 76%, promyelocytes 2%, myelocytes 12%, metamyelocytes 4%, and neutrophils 6%. Dysgranulopoiesis and hypolobation was seen in the granulocytic series. Acute myeloid leukemia with multilineage dysplasia according to WHO classification (AML-M1 according to FAB) was diagnosed after bone marrow biopsy and flow cytometry. The Leser– Trelat sign is an eruptive appearance or increase in itchy multiple seborrheic keratoses. This process occurs in a short period of time, and is sign of internal malignancy. The cutaneous findings were consistent with the diagnosis of the Leser–Trelat sign, which is usually associated with gastrointestinal adenocarcinoma. This sign is a controversial physical finding, however, since seborrheic keratoses are common with aging (except sudden appearance, rapid increase in size and number). Induction chemotherapy with mitoxantrone 10 mg/m IV over 30 min on days 1–3 and cytosine arabinoside 100 mg/m IV over 30 min every 12 h on days 1–7 was initiated. Now, he is alive and in remission for 3 months. But these lesions remained unchanged. To our knowledge, this is the first report of an association of the Leser–Trelat sign with acute myeloid leukemia. Fig. 1 Multiple eruptive seborrheic keratoses