Hüseyin Çaksen

CLP1 founder mutation links tRNA splicing and maturation to cerebellar development and neurodegeneration.

Neurodegenerative diseases can occur so early as to affect neurodevelopment. From a cohort of more than 2,000 consanguineous families with childhood neurological disease, we identified a founder mutation in four independent pedigrees in cleavage and polyadenylation factor I subunit 1 (CLP1). CLP1 is a multifunctional kinase implicated in tRNA, mRNA, and siRNA maturation. Kinase activity of the CLP1 mutant protein was defective, and the tRNA endonuclease complex (TSEN) was destabilized, resulting in impaired pre-tRNA cleavage. Germline clp1 null zebrafish showed cerebellar neurodegeneration that was rescued by wild-type, but not mutant, human CLP1 expression. Patient-derived induced neurons displayed both depletion of mature tRNAs and accumulation of unspliced pre-tRNAs. Transfection of partially processed tRNA fragments into patient cells exacerbated an oxidative stress-induced reduction in cell survival. Our data link tRNA maturation to neuronal development and neurodegeneration through defective CLP1 function in humans.

Septic arthritis in childhood

Abstract Background: The purpose of the present study was to determine whether there was a difference between septic arthritis (SA) combined with osteomyelitis and SA alone with regard to clinical and laboratory findings, such as symptoms on admission, age, sex, joint involvement and isolated micro‐organisms, and a relationship between age and joint involvement in SA. In addition, we also aimed to determine the prognostic factors in SA.

Comparison of low and high dose of vitamin D treatment in nutritional vitamin D deficiency rickets.

In this study, we compared three different therapy modes (150,000 IU, 300,000 IU, and 600,000 IU vitamin D p.o.) in infants with nutritional vitamin D deficiency rickets (VDR). Our purpose was to determine the most effective dosage of vitamin D with least side effects for treating VDR. The study included 56 patients, 3-36 months of age, with nutritional VDR and 20 age-matched control infants. In all infants, serum calcium, phosphorus, alkaline phosphatase, magnesium, serum 25-hydroxycholecalciferol, plasma intact parathormone levels and urinary Ca/creatine ratio were determined. Of 56 patients, 52 were able to be followed long-term. These patients were reexamined on the 3rd day, 7-10th day, and 25-30th day after treatment. On the 30th day post-treatment, we did not find any difference between the doses in the improvement of rickets. However, hypercalcemia was present in eight infants who had been administered 300,000 IU (two infants) and 600,000 IU (six infants) of vitamin D. In conclusion, our findings showed that 150,000 IU or 300,000 IU of vitamin D was adequate in the treatment of VDR, but 600,000 IU of vitamin D may carry the risk of hypercalcemia.

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.

Surgical Treatment Outcome of Subdural Empyema: A Clinical Study

A retrospective study of 28 patients identified with subdural empyema (SE) at the Department of Neurosurgery between the years 1995 and 2005 was carried out. SE occurred in all patients following bacterial meningitis. The six most frequently encountered clinical features included: (1) fever in 22 (79%) patients; (2) disturbed consciousness in 16 (57%) patients; (3) papilledema in 11 (39%) patients; (4) hemiparesis in 4 (14%) patients; (5) meningismus or meningeal signs in 4 (14%) patients, and (6) seizures in 3 (11%) patients. In the majority of cases, the most frequent causative pathogen of SE was Staphylococcus aureus. Surgery was performed on all patients, which included craniotomy in a group of 20 patients and burr hole drainage in a group of 8 patients. In conclusion, we believe that infants and young children should be carefully monitored following meningitis, in case of SE development, and that surgical intervention in patients presenting with meningitis may facilitate the development of SE. Furthermore, from a surgical point of view, our experience has led us to believe that craniotomy in comparison with burr hole surgery is the best surgical modality for management of SE as the recurrence rate of SE associated with burr hole surgery is high.

Acute amitriptyline intoxication: an analysis of 44 children.

The tricyclic antidepressant agents, particularly amitriptyline and dothiepin, are recognized for their potentially lethal cardiovascular and neurological effects in poisoned patients. In this article, the clinical and laboratory findings of 44 children with amitriptyline intoxication are reviewed. Our purpose was to investigate amitriptyline intoxication in childhood. Of 44 patients, 21 (47.7%) were boys, 23 (52.3%) were girls, and the ages ranged from 12 months to 14 years (mean9 / SD; 4.099 / 2.9 years). All children except one who took an overdose of amitriptyline to decrease his pain accidentally ingested an overdose of amitriptyline. The amount of amitriptyline ingested was between 2 mg/kg and 97.5 mg/kg (mean9 / SD; 13.69 / 17.7 mg/kg per dose) (the drug dosage was not known in 13 children). The most commonly observed clinical and laboratory findings were lethargy, tachycardia, convulsion, hyperglycemia and leukocytosis. In all patients except for two children who died the abnormal clinical and laboratory findings returned to normal within a few days after admission and they were discharged from the hospital in good health within the fourth day of admission. One of the children ingested 97.5 mg/kg amitriptyline and probably died due to status epilepticus and another child who died ingested 36 mg/ kg amitriptyline and died due to cardiopulmonary arrest. In conclusion, our findings showed that initial symptoms and signs of acute amitriptyline intoxication appeared severe, but they disappeared with only supportive care required in most children except for cases that ingested high doses of drug within a few days. In contrast to adults, we infrequently noted respiratory insufficiency, arrhythmia and hypotension in children with acute amitriptyline intoxication.

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.

Pott's disease.

A 15-year-old boy was hospitalized with a 1-month history lumbago and fever. His family history was noncontributory for tuberculosis, and the findings of the physical examination were normal. The sedimentation rate and C-reactive protein level were 55 mm/hour and 48 mg/l, respectively. The result of a purified protein derivative test was 11 x 10 mm. Results of other tests, including rheumatologic studies, serum agglutination for brucellosis, chest radiography, abdominal ultrasonography, and myelography, were normal. The bone biopsy revealed chronic active inflammation. Mycobacterium tuberculosis was not cultured from clinical specimens. However, the patients symptoms improved after antituberculosis drugs were begun.