Ahmet Faik Öner

Combinatorial antibody libraries from survivors of the Turkish H5N1 avian influenza outbreak reveal virus neutralization strategies

The widespread incidence of H5N1 influenza viruses in bird populations poses risks to human health. Although the virus has not yet adapted for facile transmission between humans, it can cause severe disease and often death. Here we report the generation of combinatorial antibody libraries from the bone marrow of five survivors of the recent H5N1 avian influenza outbreak in Turkey. To date, these libraries have yielded >300 unique antibodies against H5N1 viral antigens. Among these antibodies, we have identified several broadly reactive neutralizing antibodies that could be used for passive immunization against H5N1 virus or as guides for vaccine design. The large number of antibodies obtained from these survivors provide a detailed immunochemical analysis of individual human solutions to virus neutralization in the setting of an actual virulent influenza outbreak. Remarkably, three of these antibodies neutralized both H1 and H5 subtype influenza viruses.

Effectiveness of Antiviral Treatment in Human Influenza A(H5N1) Infections: Analysis of a Global Patient Registry

BACKGROUND Influenza A(H5N1) continues to cause infections and possesses pandemic potential. METHODS Data sources were primarily clinical records, published case series, and governmental agency reports. Cox proportional hazards regression was used to estimate the effect of treatment on survival, with adjustment using propensity scores (a composite measure of baseline variables predicting use of treatment). RESULTS In total, 308 cases were identified from 12 countries: 41 from Azerbaijan, Hong Kong SAR, Nigeria, Pakistan, and Turkey (from clinical records); 175 from Egypt and Indonesia (from various sources); and 92 from Bangladesh, Cambodia, China, Thailand, and Vietnam (from various publications). Overall crude survival was 43.5%; 60% of patients who received ≥1 dose of oseltamivir alone (OS(+)) survived versus 24% of patients who had no evidence of anti-influenza antiviral treatment (OS(-)) (P <.001). Survival rates of OS(+) groups were significantly higher than those of OS(-) groups; benefit persisted with oseltamivir treatment initiation <or=6-8 days after symptom onset. Multivariate modeling showed 49% mortality reduction from oseltamivir treatment. CONCLUSIONS H5N1 causes high mortality, especially when untreated. Oseltamivir significantly reduces mortality when started up to 6-8 days after symptom onset and appears to benefit all age groups. Prompt diagnosis and early therapeutic intervention should be considered for H5N1 disease.

Deadly nightshade (Atropa belladonna) intoxication: an analysis of 49 children.

Deadly nightshade (Atropa belladonna) intoxication has been infrequently reported in both children and adults in the literature. In this article, the clinical and laboratory findings of 49 children with acute deadly nightshade intoxication are reviewed. Our purpose was to enlighten the findings of deadly nightshade intoxication in childhood. The most common observed symptoms and signs were meaningless speech, tachycardia, mydriasis, and flushing. None of the children required mechanical ventilation or died in our series. The patients were categorized into two groups, mild/moderate and severe intoxication. Children with and without encephalopathy were accepted as severe and mild/moderate intoxication, respectively. While 43 children were placed in the group of mild/moderate intoxication, six were in severe intoxication group. We found that meaningless speech, lethargy, and coma were more common, but tachycardia was less common in the severe intoxication group (children with encephalopathy) (P B-0.05). In the treatment, neostigmine was used in all children because of no available physostigmine in our country. In conclusion, our findings showed that the initial signs and symptoms of acute deadly nightshade intoxication might be severe in some children, but no permanent sequel and death were seen in children. We also showed that meaningless speech, lethargy, coma, and absence of tachycardia were ominous signs in deadly nightshade intoxication in childhood. Lastly, we suggest that neostigmine may be used in cases of deadly nightshade intoxication if physostigmine cannot be available.

Myelopathy due to intrathecal chemotherapy: report of six cases.

Intrathecal chemotherapy and systemic chemotherapy are used for both prophylaxis and treatment of central nervous system disease in hematologic malignancies. However, intrathecal treatment has some adverse effects, such as arachnoiditis, progressive myelopathy, and leukoencephalopathy. The authors describe six children in whom myelopathy and adhesive arachnoiditis developed after administration of intrathecal chemotherapy including methotrexate, cytosine arabinoside, and prednisolone. Urinary retention and incontinence, the main presenting complaints in all patients, developed within 12 hours after intrathecal therapy and spontaneously resolved within 7 days. Two patients were unable to walk. In these two, weakness in the lower extremities gradually recovered by 1 month but urinary incontinence did not improve. None of the children had sensory loss. On follow-up periodic recurrent urinary tract infection was noted in four patients. MRI findings corresponded to arachnoiditis. No response was recorded on tibial nerve somatosensory evoked potentials in all patients. Intrathecal chemotherapy, especially methotrexate, can cause spinal cord dysfunction in children with acute lymphoblastic leukemia and non-Hodgkins lymphoma. Arachnoiditis should be kept in mind as a causative factor in recurrent urinary tract infection in patients receiving intrathecal chemotherapy.

Report of Eight Infants with Acute Infantile Hemorrhagic Edema and Review of the Literature

Acute infantile hemorrhagic edema (AIHE) is a cutaneous leukocytoclastic vasculitis, clinically characterized by the symptom triad of fever, large purpuric skin lesions, and edema. The clinical picture has a violent onset, a short benign course, and spontaneous complete recovery. In this article, we present eight patients who were admitted with rashes on the skin and edema on the eyelids and extremities, and were diagnosed with AIHE according to their clinical and histopathological features (immunohistological study was also performed in three of them). Our purpose was to emphasize that, aside from Henoch‐Schönlein purpura, meningococcemia, septicemia, and purpura fulminans, AIHE benign disorder should also be considered in the differential diagnosis to determine the clinical course and treatment protocol in patients with purpuric rashes.

Vincristine induced cranial polyneuropathy.

We describe a 5-year-old girl showed recovery of vincristine induced cranial polyneuropathy with pyridoxine and pyridostigmine treatment. A 5-year-old girl was diagnosed preB cell Acute Lymphoblastic Leukemia (ALL). She received chemotherapy according to the previously described modified St. Jude total therapy studies XIII. Five days after the fourth dose of vincristine, she presented with bilateral ptosis. Neurological examination revealed bilateral ptosis, and complete external opthalmoplegia with normal pupillary and corneal reflexes. She received 3.8 mg cumulative dose of vincristin before development of ptosis. A neuroprotective and neuroregenerative treatment attempt with pyridoxine and pyridostigmine was initiated. The bilateral ptosis markedly improved after 7 days of pyridoxine and pyridostigmine treatment and completely resolved after two weeks. The both agents were given for 3 weeks and were well tolerated without any side effects. During the follow up period we did not observe residue or recurrence of the ptosis.

Clinical and molecular aspects of Turkish familial hemophagocytic lymphohistiocytosis patients with perforin mutations

The aim of this study was to elucidate the pathologic sequence changes and associated clinical phenotypes in 9 new patients showing homozygosity for perforin gene among a total of 37 (24%) Turkish FHL families studied by linkage analysis. These 9 unrelated patients (5M/4F) were coming from consanguineous families and their presentation ages of systemic symptoms were ranged from birth to 15 years. Direct sequencing of coding exons of the perforin gene led to the identification of five different homozygous alterations. The nonsense W374X mutation was identified in three patients while four different missense mutations namely G149S, V50M, A91V and novel A523D were detected in the rest six patients.

Childhood brucellosis is still a severe problem in the eastern region of Turkey.

Of the 103 patients, 52 (50.4%) were girls, 51 (49.6%) were boys, and ages ranged from 20 months to 16 years (8.31± 3.58 years). The mean period between onset of symptoms and admission to hospital ranged from 2 days to 3 years (68.0± 192.8 days). A positive family history for brucellosis was noted in 14 (13.5%) patients. The most frequently observed symptoms and signs are summarized in Table 1. The most commonly observed symptoms and signs were fever, arthralgia, malaise, hepatosplenomegaly, hepatomegaly and arthritis. Neurobrucellosis was diagnosed in one (0.9%) patient. Anaemia was observed in 18 (17.4%) patients; leukocytosis in 15 (14.5%); and leukopenia in eight (7.7%) patients. Erythrocyte sedimentation rate was studied in 84 (81.5%) patients; it was found to be high in 61.9%. Brucella agglutination test was 1/160 or higher in all patients; it was 1/160 in 17 (16.5%) patients, 1/320 in 28 (27.0%) patients, 1/640 in 41 (39.8%) patients, and 1/1280 in 17 (16.5%) patients. Brucella was cultured in only three patients. It was isolated from both blood and bone marrow in two patients and from blood in one patient and also from cerebrospinal fluid in one of two patients who had positive blood and bone marrow cultures for Brucella.

Auditory brainstem response in children with iron deficiency anemia.

To investigate the neurosensorial influences with auditory brainstem response (ABR) in iron deficiency anemia. We recorded ABR in 33 children with iron deficiency anemia followed and in 31 healthy children (control group 1, 0-12 months, control group 2, 13-36 months, control group 3, 37-60 months) as a control group. The patients and controls were divided into three group: group I, at 12 months of age, group II, 13-36 months, and group III, 37-60 months. In all groups, composed latency time, inter-peak latency, amplitude of peaks, I-V wave amplitude ratio and waveform were evaluated and compared with control groups. In group I, I-V interpeak latency was increased compared with control group I (4.58 vs. 4.20 ms, p < 0.05). In group II, Wave V latency time and III-V interpeak latency were increased compared with control group 2 (6.21 ms vs. 5.63 ms. p < 0.005 and 0, 48 vs. 0.22 p < 0.005, respectively). In group III, wave I latency time was increased compared with control group 3 (1.56 ms vs. 1.46 ms) (p < 0.05). We considered that increases in ABR latencies might be explained by delayed maturation of myelinisation, which requires iron, and/or by dysfunction of iron containing enzymes.

An Analysis of Children with Brucellosis Associated with Pancytopenia

Brucellosis produces a variety of nonspecific hematologic abnormalities. Hematologic complications of mild anemia and leukopenia have been frequently associated with acute brucellosis, but pancytopenia is less frequently seen. In this study, records of children with brucellosis aged under or equal to 16 years, admitted to Yuzuncu Yil University Hospital between 2004 and 2010, were analyzed retrospectively. Over this time period, 187 patients with brucellosis were diagnosed. Twenty-five (13.3%) of 187 patients had pancytopenia during admission to hospital. The diagnosis of brucellosis was confirmed by standard tube agglutination test in all patients; titers were 1:320 in 1 patient and 1:1280 in 24 patients. Blood culture was positive for Brucella melitensis in 3 patients (12%). Fever was the most common manifestation, followed by malaise, anorexia, sweating, and weight loss. Fever and splenomegaly were the common signs in most patients. In addition, arthritis was observed in 5 patients, and epistaxis, headache, and abdominal pain were observed in 3 patients. The common bone marrow aspiration findings consisted of increased megakaryocytes and hyperplasia of erythroid series, with a shift to the left of the granulocytic series. Histiocytic hyperplasia was observed in the bone marrow smear of 2 patients. Mild hemophagocytosis was observed in the bone marrow of 3 patients. All patients recovered completely, and their peripheral blood counts returned to normal by 2 to 6 weeks after antibiotic treatment of brucellosis. In conclusion, the authors would like to emphasize that brucellosis should be considered in the differential diagnosis of children with pancytopenia.