Mehmet Sencan

Efficacy of oral ribavirin treatment in Crimean-Congo haemorrhagic fever: a quasi-experimental study from Turkey.

OBJECTIVE The aim of this study was to evaluate the efficacy of oral ribavirin treatment in patients with Crimean-Congo haemorrhagic fever (CCHF). METHODS In 2004, all patients diagnosed with CCHF were treated with oral ribavirin, however in 2003 none of the CCHF patients had been given treatment due to lack of confirmatory diagnostic information at that time in Turkey. In this study, patients treated with ribavirin in 2004 (n=126) were compared with ribavirin-untreated CCHF patients (n=92) in 2003. Patients only with a definitive diagnosis of CCHF (clinical symptoms plus the presence of specific IgM antibodies against CCHF virus and presence of viral antigen) were included in this study. RESULTS There was no difference in the case-fatality rate between treated and untreated patients (7.1% vs. 11.9%; P>0.05). A Cox Proportional Hazards regression analysis revealed that altered sensorium and prolonged international normalized ratio were independent predictors of mortality. CONCLUSION Our results showed that oral ribavirin treatment did not improve the survival rate in CCHF patients. Ribavirin and supportive care are the only available choices for treatment of CCHF patients, but to ascertain the efficacy of ribavirin, more laboratory and observational studies are necessary and ultimately, to elucidate these conflicting results and evaluate the efficacy undoubtedly, a multicenter randomised controlled trial will be needed.

Is Neutrophil/Lymphocyte Ratio Associated with Subclinical Inflammation and Amyloidosis in Patients with Familial Mediterranean Fever?

Background. The purpose of the present study is to determine the association between neutrophil/lymphocyte ratio and both subclinical inflammation and amyloidosis in familial Mediterranean fever. Methods. Ninety-four patients with familial Mediterranean fever and 60 healthy volunteers were included in the study. Of the patients, 12 had familial Mediterranean fever related amyloidosis. The neutrophil/lymphocyte ratio of the patients was obtained from the hematology laboratory archive. Results. The neutrophil/lymphocyte ratio was significantly higher among persons with familial Mediterranean fever compared to healthy individuals (P < 0.0001). Also, neutrophil/lymphocyte ratio was significantly higher in patients with amyloidosis than in amyloidosis-free patients (P < 0.0001). Since NLR was evaluated in nonamyloid and amyloid stages of the same patient population (type 1 phenotype), we obtained significant statistical differences (1.95 ± 0.30 versus 2.64 ± 0.48, P < 0.05, resp.). With the cutoff value of neutrophil/lymphocyte ratio >2.21 and AUC = 0.734 (P = 0.009), it was a reliable marker in predicting the development of amyloidosis. Conclusion. The neutrophil/lymphocyte ratio, an emerging marker of inflammation, is higher in patients with familial Mediterranean fever in attack-free periods. The neutrophil/lymphocyte ratio may be a useful marker in predicting the development of amyloidosis.

The relation between serum leptin levels and body fat mass in patients with active lung tuberculosis.

The relationship of leptin to diminished appetite and weight loss has been investigated in many diseases. Diminished appetite and weight loss are the most apparent characteristics of patients with active lung tuberculosis and in this study the relation of leptin to such diminished appetite and weight loss has been investigated in patients with active lung tuberculosis before and after treatment. Twenty‐five patients (7 female, 18 male) with active tuberculosis having an age range of 18–70 years (mean 47.48 ± 15.36 y) and 25 normal individuals (9 female, 16 male) having an age range of 25–71 years (mean 44.60 ± 13.80 y) were included in this study. Leptin levels, body mass index (BMI), body fat ratio (BFR), and waist hip ratio (WHR) were measured before and after 6 months of antituberculosis treatment. The same measurements were also made in the control group and the results were compared. While the pretreatment BMI (22.02 ± 4.31 kg/m2) and BFR (16.60% ± 9.30%) values in the patient group were significantly lower than in the control group, we found no difference in their pretreatment WHR values. Pretreatment leptin levels (3.49 ± 3.34 µg/L) were significantly higher in patients with tuberculosis than in the control group (2.33 ± 1.10 µg/L). Leptin levels were found to be significantly increased at the 6th month of antituberculosis treatment (5.65 ± 5.41 µg/L) than the pretreatment values (p < 0.05). We observed an evident increase in BMI (24.10 ± 4.87 kg/m2) and BFR (17.51% ± 9.25%) due to antituberculosis treatment (p < 0.05). This study suggests that leptin has a role in the diminished appetite and weight loss symptoms in patients with active lung tuberculosis.

Sequential determination of serum viral titers, virus-specific IgG antibodies, and TNF-α, IL-6, IL-10, and IFN-γ levels in patients with Crimean-Congo hemorrhagic fever

BackgroundAlthough there have been a number of studies on the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) recently, knowledge on this topic is still insufficient. This study aims to reveal the kinetics of serum CCHF virus (CCHFV) titers, serum levels of anti-CCHFV immunoglobulin (Ig)G, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and interferon (IFN)-γ in CCHF patients.MethodsIn total, 31 CCHF cases (11 fatal) were studied. Serum samples were obtained daily from all patients from the time of admission and continued for a 7-day hospitalization period for serologic (ELISA), virologic (real-time PCR), and cytokine (ELISA) analysis.ResultsThe mean serum CCHFV titer at admission was 5.5E + 09 copies/mL in fatal cases and 5.7E + 08 copies/mL in survivors (p < 0.001). Compared to survivors, both the mean serum levels of IL-6 and TNF-α at admission were found to be significantly increased in fatal cases. The serum levels of IL-6, TNF-α and serum CCHFV titer at admission were significantly and positively correlated with disseminated intravascular coagulation (DIC) scores (r = 0.626, p = 0.0002; r = 0.461, p = 0.009; and r = 0.625, p = 0.003, respectively). When the data obtained from the sequential determination of CCHFV titer and levels of anti-CCHFV IgG, IL-6, TNF-α, IL-10 and IFN-γ were grouped according to the days of illness, the initial serum CCHFV titer of a fatal patient was 5.5E + 09 (copies/mL) and it was 6.1E + 09 (copies/mL) in a survivor on the 2 day of illness. While significant alterations were observed in all cytokines during the monitoring period, IL-6 levels remained consistently higher in fatal cases and TNF-α levels increased in both in fatal and non-fatal CCHF cases.ConclusionsThe increased CCHFV load and higher concentrations of IL-6 and TNF-α, the presence of DIC, and the absence of CCHFV specific immunity are strongly associated with death in CCHF.

Therapeutic plasma exchange in patients with thrombotic thrombocytopenic purpura: A retrospective multicenter study

UNLABELLED Thrombotic thrombocytopenic purpura (TTP) is a particular form of thrombotic microangiopathy typically characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological abnormalities, and renal dysfunction. TTP requires a rapid diagnosis and an adapted management in emergency. Daily sessions of therapeutic plasma exchange (TPE) remain the basis of management of TTP. Also, TTP is a rare disease that is fatal if it is not treated. TPE has resulted in excellent remission and survival rates in TTP patients. AIM We aimed to present our experience in 163 patients with TTP treated with TPE during the past 5years from 10 centers of Turkey. PATIENTS AND METHODS One hundered and sixty-three patients with TTP treated with TPE during the past 5years from 10 centers of Turkey were retrospectively evaluated. TPE was carried out 1-1.5times plasma volume. Fresh frozen plasma (FFP) was used as the replacement fluid. TPE was performed daily until normalization of serum lactate dehydrogenase (LDH) and recovery of the platelet count to >150×10(9)/dL. TPE was then slowly tapered. Clinical data, the number of TPE, other given therapy modalities, treatment outcomes, and TPE complications were recorded. RESULTS Fifty-eight percent (95/163) of the patients were females. The median age of the patients was 42years (range; 16-82). The median age of male patients was significantly higher than female (53 vs. 34years; p<0.001). All patients had thrombocytopenia and microangiopathic hemolytic anemia. At the same time, 82.8% (135/163) of patients had neurological abnormalities, 78.5% (128/163) of patients had renal dysfunction, and 89% (145/163) of patients had fever. Also, 10.4% (17/163) of patients had three of the five criteria, 10.4% (17/163) of patients had four of the five criteria, and 6.1% (10/163) of patients had all of the five criteria. Primary TTP comprised of 85.9% (140/163) of the patients and secondary TTP comprised of 14.1% (23/163) of the patients. Malignancy was the most common cause in secondary TTP. The median number of TPE was 13 (range; 1-80). The number of TPE was significantly higher in complete response (CR) patients (median 15.0 vs. 3.5; p<0.001). CR was achieved in 85.3% (139/163) of the patients. Similar results were achieved with TPE in both primary and secondary TTP (85% vs. 87%, respectively; p=0.806). There was no advantage of TPE+prednisolone compared to TPE alone in terms of CR rates (82.1% vs. 76.7%; p=0.746). CR was not achieved in 14.7% (24/163) of the patients and these patients died of TTP related causes. There were no statistical differences in terms of mortality rate between patients with secondary and primary TTP [15% (21/140) vs. 13% (3/23); p=0.806]. But, we obtained significant statistical differences in terms of mortality rate between patients on TPE alone and TPE+prednisolone [14% (12/86) vs. 3% (2/67), p<0.001]. CONCLUSIONS TPE is an effective treatment for TTP and is associated with high CR rate in both primary and secondary TTP. Thrombocytopenia together with microangiopathic hemolytic anemia is mandatory for the diagnosis of TTP and if these two criteria met in a patient, TPE should be performed immediately.

Do neutrophil gelatinase-associated lipocalin and interleukin-18 predict renal dysfunction in patients with familial Mediterranean fever and amyloidosis?

Abstract Background: The aim of this study was to evaluate whether neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) predict renal disfunction in patients with familial Mediterranean fever (FMF). Methods: This prospective study consisted of 102 patients with FMF in attack-free period, and 40 matched healthy controls. Of the patients, nine were diagnosed as amyloidosis. The patients were divided into two groups according to eGFR as below 120 mL per minute and above 120 mL per minute. Also, patients were divided into three groups according to the degree of urinary albumin excretion as normoalbuminuric, microalbuminuric, and macroalbuminuric. The serum levels of IL-18 (sIL-18) and NGAL (sNGAL), and urinary levels of IL-18 (uIL-18) and NGAL (uNGAL) were measured by using ELISA kits. Results: The levels of sIL-18, sNGAL, uIL-18, and uNGAL were detected significantly higher in FMF patients, particularly in patients with amyloidosis, when compared to controls. sNGAL, uIL-18, and uNGAL were significantly higher in patients with eGFR < 120 mL per minute than in patients with eGFR ≥ 120 mL per minute. sNGAL, uIL-18, and uNGAL were correlated significantly with urinary albumin excretion, additionally, were inverse correlated with eGFR. The most remarkable findings of this study are of the higher values of sIL-18, sNGAL, uIL-18, and uNGAL in both normoalbuminuric FMF patients and patients with eGFR ≥ 120 mL per minute. Conclusions: The results of this study suggest that sIL-18, uIL-18, sNGAL, and uNGAL are reliable markers of early renal disfunction in FMF patients, and may let us take measures from the early stage of renal involvement.

Is there a link between mean platelet volume and thrombotic events in antiphospholipid syndrome

Abstract The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the production of antiphospholipid antibodies (aPL) that promote vascular thrombosis and pregnancy loss. APS can occur in the absence of underlying or associated disease (primary APS) or in combination with other diseases (secondary APS). Mean platelet volume (MPV) is largely regarded as a useful surrogate marker of platelet activation. We aimed to investigate if there is a relationship between MPV and thrombotic events in APS. The study consisted of 22 patients and 22 healthy controls. Group 1 is defined as all the patients in the first day of thrombotic event. Group 2 is defined as the same patient population three months after the thrombotic event. The erythrocyte sedimentation rate, C-reactive protein, white blood cell count, platelet count, and MPV levels were retrospectively recorded from patient files. Statistical analyses showed that MPV was significantly higher in group 1 than group 2 (p < 0.0001) and healthy controls (p < 0.05). However, there was no difference between group 2 and healthy controls (p = 0.888). WBC, hemoglobin and other platelet indices such as platelet distribution width and platecrit did not differ in groups. In conclusion, MPV was increased at initial thrombotic event of APS, and then it was normalized three months later by therapeutic interventions. To our knowledge, this is the first study demonstrating a correlation between MPV and thrombotic events in APS.

Unusual manifestations of acute Q fever: autoimmune hemolytic anemia and tubulointerstitial nephritis

Q fever is a worldwide zoonotic infection that caused by Coxiella burnetii, a strict intracellular bacterium. It may be manifested by some of the autoimmune events and is classified into acute and chronic forms. The most frequent clinical manifestation of acute form is a self-limited febrile illness which is associated with severe headache, muscle ache, arthralgia and cough. Meningoencephalitis, thyroiditis, pericarditis, myocarditis, mesenteric lymphadenopathy, hemolytic anemia, and nephritis are rare manifestations. Here we present a case of acute Q fever together with Coombs’ positive autoimmune hemolytic anemia (AIHA) and tubulointerstitial nephritis treated with chlarithromycin, steroids and hemodialysis. Clinicians should be aware of such rare manifestations of the disease.

Effects of rhG-CSF on Neutrophil Functions and Bone Marrow Parameters in Diabetic Rats

Neutrophils have an important role in the host defense. The elevated serum glucose levels of diabetics affect traditional host defenses such as neutrophil counts and functions. The causes of these impairments are not clear. We aimed to investigate changes of peripheral neutrophil counts and functions and their relation with bone marrow cells in diabetic rats. Thirty-two rats were divided into four equal groups. Group 1 were controls and Groups 2 and 4 were made diabetic by a single intraperitoneal injection of streptozotocin. Granulocyte colony stimulating factor (G-CSF) was injected subcutaneously into Groups 3 and 4. White blood cell count, neutrophil counts and function and bone marrow cell count were determined. Peripheral blood cell counts, neutrophil phagocytosis index were decreased but neutrophil adhesivity index was not different in the diabetes-induced group. There was a difference in circulating white blood cell counts and neutrophil counts between the rhG-CSF treated and non-treated groups. The phagocytosis index of neutrophil in diabetic rats was significantly diminished by rhG-CSF treatment. A hyperplasia of early cells of the myeloid series in G-CSF treated groups was observed when compared with those of nontreated groups (p<0.001). A significant decrease was noted in the number of mature marrow segmented cells diabetic groups (p<0.001). Finally, G-CSF has been shown to cause neutrophilia by acting as a releasing factor for mature marrow neutrophils in diabetic rats. These results suggest that G-CSF may be used to improve nonspecific immunity in diabetic patients.

A Case of Acute Renal Failure Caused by Hodgkin's Lymphoma: Concurrent Membranous Glomerulonephritis and Interstitial HL-CD 20 Lymphoid Infiltration

Although acute renal failure developing due to malignancies is a frequent condition, malignant renal infiltration is rarely observed among these causes. Among all malignant diseases, the hematolymphoid malignancies are the most prone to renal infiltration. Other types involved in cases with lymphoma are glomerulopathies, including immune-complex glomerular diseases such as minimal change disease, membranous glomerulonephritis, membranoproliferative glomerulonephritis, and focal segmental glomerulosclerosis. We present herein the rare case of a 22-year-old male with both membranous glomerulonephritis and CD20 (+) lymphoid infiltration related to Hodgkins lymphoma in the renal interstitial tissue, as detected on biopsy. The patient was treated with adriamycin, bleomycin, vinblastine, and dacarbazine protocol after pulse corticosteroid treatment, and a dramatic improvement in renal function was observed after 2 days of treatment. In this article, an exceptional renal involvement of Hodgkins lymphoma is discussed in light of the related literature.