Irfan Yavasoglu

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.

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 Novel Association Between Polycystic Ovary Syndrome and Helicobacter pylori

Background:Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies. Chronic infections may increase the risk of infertility. Helicobacter pylori infection has been found to be associated with infertility, and PCOS is also one of the most common causes of infertility. To the best of our knowledge, the possible association between H. pylori seropositivity and PCOS has never been investigated. Methods:We performed a prospective study between a group of PCOS subjects and an age-matched group of controls. This prospective study included 35 women (mean age, 25 ± 5 years) with PCOS, selected by using revised diagnostic criteria of European Society for Human Reproduction and Embryology and the American Society for Reproductive Medicine 2003, who were compared with their age-matched control group (50 women; mean age, 26 ± 5 years). The 1-step H. pylori test device was used to detect IgG-type antibodies to H. pylori in serum, to aid in the diagnosis of H. pylori infection. Results:H. pylori seropositivity was found to be significantly higher in the PCOS group (PCOS 40%; control 22%; P = 0.007). Conclusion:We suggest a possible association between H. pylori seropositivity and PCOS. It is early to state that H. pylori is a new etiological factor for PCOS or the association of PCOS and H. pylori infection is coincidental with these data. Further studies evaluating more subjects are required.

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.

Diastolic dysfunction in rheumatoid arthritis and duration of disease

Dear Editor, The article entitled “Diastolic heart function in RA patients” written by Wislowska et al. and published in one of the recent issues of your journal was quite interesting [1]. There is no good deWnition for early Rheumatoid arthritis (RA). Early disease has been taken as a symptom with duration of less than 2 year (more conventionally, a time point of 5 year) [2, 3]. Our study included 82 patients (67 females and 15 males) diagnosed as RA according to criteria of ARA and 47 healthy control subjects (31 females and 16 males). In our study, duration of disease was ranging from 1 to 30 years in the patients with RA and mean duration of the disease was 4.8 § 5.2 years. All the patients and control subjects were evaluated prior to the initiation of the study for previous cardiac disease as exclusion criteria. Thus, our study used tissue Doppler and Vp (velocity of Xow propagation) methods in addition to conventional pulse wave Doppler method in order to detect diastolic dysfunction. We categorized the patients into two groups as those with disease duration of less and more than 5 years (early and late RA), there were a signiWcant diVerence between two groups in mitral E/A ratio, tissue Doppler mitral annulus E /A ratio and Vp values (Table 1) [4]. The other study conWrms a high frequency of left ventricular diastolic dysfunction characterised by impaired E/A ratio, prolonged Isovolemic relaxation time (IVRT) and increased late diastole Xow velocity in patients with RA without evident cardiovascular disease. The correlation between transmitral Xow alteration and disease duration suggests a subclinical myocardial involvement with disease progression [5].

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

Thrombotic thrombocytopenic purpura as the first manifestation of metastatic adenocarcinoma in a young woman

Thrombotic microangiopathy occurs in 5-10% of patients with mucin-producing disseminated adenocarcinoma. A 28-year-old woman complained of fatigue, bone pain, and weight loss. There were pallor, icterus, and tenderness in the bones on physical examination. Microangiopathic hemolytic anemia, leukoerythroblastic picture, thrombocytopenia, and normal coagulation tests were detected. Thrombotic thrombocytopenic purpura (TTP) was diagnosed and therapeutic plasma exchange was performed on the patient. On day 5 a laparotomy had to be performed because of acute abdomen due to the rupture of a corpus hemorrhagicum follicle of an ovary. Signet ring cell adenocarcinoma stained with cytokeratin 7 and mucicarmine was seen on ovaries and bone marrow, after the pathological examination. The primary site of tumor could not be investigated, because of the patients refusal. Although chemotherapy including cis-platinum, infusional 5-fluorouracil, and calcium leucovorin were administered in two courses, she died from respiratory failure. In conclusion, malignancy and bone marrow involvement should be considered when associated with leukoerythroblastic picture and TTP.

Knowledge, attitudes, and practices of hematologists regarding fertility preservation in Turkey.

Objective: Fertility preservation stands before us as an issue of quality of life for cancer patients and their partners and families. Therefore, the object of the present study was to determine the extent of the knowledge that hematologists have about fertility preservation and to understand their attitudes and practices regarding this matter.
 Materials and Methods: A total of 25 hematologists participated in a survey. The questionnaire included questions on sociodemographic characteristics and awareness concerning the subject of fertility preservation, as well as questions designed to determine the extent of the knowledge that hematologists had on the subject and to understand their attitudes and practices in this context. Results: Of the participants in the study, all expressed their awareness of the adverse effects that the various treatments they were prescribing could have on fertility; 2 (8%) revealed that they had never heard of the concept of fertility preservation. Of the participants, 19 (76%) indicated that they did not have adequate knowledge about fertility preservation, but 22 (88%) fortunately expressed a need for acquiring more knowledge about the subject. Of the respondents, 23 (92%) said that they did not have any brochures or published resources on this subject and stated their belief that if hematologists did have such documents, they would have more opportunity to discuss the various fertility preservation options with patients. All of the participants in the survey supported the idea of the Turkish Society of Hematology publishing a guidebook on this subject and organizing a session on fertility preservation in their regular congress. Conclusion: Meeting the needs of hematologists for training and knowledge in the subject of fertility preservation and ensuring the development of appropriate attitudes and practices in this area is an important issue. The Turkish Society of Hematology may play a significant key role. Conflict of interest:None declared.