Sultan Durmus Aydogdu

Ceftriaxone-associated biliary sludge and pseudocholelithiasis during childhood: a prospective study.

Abstract Background : Cholelithiasis is a rare condition seen during childhood. The aim of this study was to determine frequency of biliary sludge and cholelithiasis with ceftriaxone therapy.

Breastmilk ghrelin, leptin, and fat levels changing foremilk to hindmilk: is that important for self-control of feeding?

The aim of this study was to evaluate the changes in the ghrelin, leptin, and fat levels in the foremilk and hindmilk and the possible relationship between these levels with the age and growth of term healthy infants. Sixty-two babies were subdivided (according to their nutrition) into breastfed (BF), formula-fed (FF), and BF plus FF (BF + FF) groups. The total and active ghrelin and tryglyceride levels and the total cholesterol levels in the foremilk and hindmilk were studied at the first and second visits (mean of the second and fifth months, respectively). At both visits, the total and active ghrelin and the total cholesterol levels were lower in the hindmilk than in the foremilk. However, the triglyceride levels were higher in the hindmilk than in the foremilk (p < 0.001). The leptin levels were also higher in the hindmilk, but this difference was not statistically significant. At the second visit, the mean total foremilk ghrelin (p < 0.01), leptin (p < 0.05), tryglyceride (p < 0.001), and cholesterol (p < 0.01) levels in the BF group were decreased compared with the levels at the first visit, whereas the active ghrelin levels increased (p < 0.001). At the second visit, we observed a 3.5% increase in the body mass index in BF infants, a 14.6% increase in FF infants, and an 11.8% increase in BF + FF infants (p < 0.01). The foremilk leptin levels were lower in the BF + FF group than in the BF group at both visits. In conclusion, at the first and second visits, the decreased ghrelin and increased tryglyceride and leptin levels in the hindmilk might be associated with the important role of self-control when feeding BF infants. The stable content of formulas might be associated with a lack of self-control during feeding and increased nutrition. Changing the breast milk ghrelin, leptin, and fat levels between the foremilk and hindmilk and between the first and second visits might explain the differences in the weight gain patterns of BF and FF infants.

The effect of smoking on bone metabolism: maternal and cord blood bone marker levels

BACKGROUND To clarify the effect of smoking on bone metabolism in the fetus, we measured osteocalcin (OC), bone isoenzyme of alkaline phosphatase (BALP), procollagen type 1 C-terminal propeptide (PICP) in maternal serum and umbilical cord blood. METHODS 15 active smoker, 14 passive smoker, 15 nonsmoker women and their newborn were included in this study. OC, BALP, PICP were determined by enzyme immunoassay. RESULTS Of the bone markers tested only OC was different in the serum of the three groups of women. Infants of smoker women have significantly lower umbilical cord blood OC levels than those of infants from both passive smoker and nonsmoker women.(25.6 +/- 6.6, 35.8 +/- 10.4, 37.2 +/- 16.1 ng/mL respectively, p < 0.05). Infants of smoker women have significantly lower umbilical cord blood BALP levels than those of infants from nonsmoker women. (46 +/- 12, 57 +/- 15 U/L p < 0.05). All bone markers except total ALP were significantly higher in umbilical cord blood as compared to maternal blood levels (p < 0.001 for all). CONCLUSION High umbilical cord blood bone marker levels may reflect the altered bone metabolism of fetus. Moreover, chronic hypoxia due to smoking may cause the suppression of bone matrix synthesis or placental synthesis as reflected by low OC and BALP levels in umbilical cord blood of infants from smoker women.

Diagnostic values of lipid and lipoprotein levels in late onset neonatal sepsis.

Serum lipids/lipoproteins were assayed to evaluate the diagnostic values of serum lipids/ lipoproteins in neonatal late onset sepsis (NLS) in 36 episodes of NLS (15 of the 36 in preterm newborns and 21 of the 36 in term newborns) while 36 healthy newborns were used as controls. On d 0, levels of total cholesterol (TC), triglyceride (TG), lipoprotein-a (Lp-a), high-density lipoprotein (HDL) and apolipoprotein-A (Apo-A) and B (Apo-B) were found to be significantly lower in the NLS group than in the control group (p=0.001). The sensitivity and specificity values were 61.5% and 69.4% for TC, 96.2% and 44.4% for HDL, 73% and 50% for Lp-a, 69.2% and 83.3% for triglyceride, 73% and 97.2% for Apo-A and 77% and 69.4% for Apo-B, respectively, at diagnosis. In conclusion, Apo-A appeared to be a useful marker for detection of NLS. Low TG levels may be due to impaired triglyceride-related neutralization of lipopolysaccharides in NLS.

Infant with chromhidrosis

Apocrine chromhidrosis is the secretion of colored sweat by the apocrine glands. The color of the sweat varies. Apocrine chromhidrosis may develop at any age but it is observed more often after puberty. We report an infant with chromhidrosis. A 9-month-old girl presented with a history of staining of her undershirt, especially the axillary region. This coloration was present for 3 months after complementary feeding was started. She was born after a normal pregnancy from non-consanguineous parents. She had no history of drug use or illness. She was fed with human milk for 6 months then complementary feeding was started. On physical examination it was noticed that her undershirt was bluish colored (Fig. 1). The rest of the physical examination was normal. Routine laboratory investigations were normal. Urinary homogentisic acid level was within normal limits. No heavy metal or toxin was found in analysis of the tap water. Microbiological examination of her skin revealed normal skin flora. Apocrine chromhidrosis refers to the secretion of colored sweat. Apocrine sweat glands are located in the axillae, anogenital skin, areolae and over the skin of the trunk, face and scalp. The color of chromhidrosis may be yellow, green, blue, brown or black, depending on the level of oxidation of lipofuscin secreted in sweat. Darker colors are due to higher states of oxidation. The chromhidrotic apocrine glands have elevated levels of lipofuscins that cannot be explained by dietary or metabolic alterations. However it was seen that the chromhidrosis of our case was recognized after the addition of complementary food to her diet. This condition might be a coincidence. Sex, occupation, season and climate have no influence on chromhidrosis. Pseudochromhidrosis may be accidental or occupational and occur from surface compounds or molecules mixed with sweat, giving the sweat a specific color. Toxins or heavy metals were not found in the tap water. The chromhidrosis of our patient was detected after complementary food was started. The modification of her diet does not cause any change in the color of her sweat. The differential diagnosis includes hyperbilirubinemia, pseudomonas infection, bleeding diathesis, alkaptonuria and poisoning. Chromhidrosis persists throughout life, but slow regression of the disease is noted, as apocrine glands regress with time. Apocrine chromhidrosis has no satisfactory treatment. Temporary, successful treatments of apocrine chromhidrosis with capsaicin cream and botulinum toxin were reported. We did not apply any treatment modality. In conclusion, although apocrine chromhidrosis may develop at any age, it is more often after puberty. Our patient was chromhidrotic for 3 months. To the best of our knowledge, our 9-monthold patient might be the youngest case in the literature.

Glutaric aciduria type 1 presenting as subdural haematoma.

Glutaric aciduria type 1 (GA1) is an autosomal recessive disorder caused by deficiency of glutaryl CoA-dehydrogenase. The metabolism of lysine, hydroxylysine and tryptophan is blocked, leading to accumulation of glutaric acid (GA) and increased urinary concentrations of GA and 3-hydroxy GA. Onset usually involves an acute encephalopathic episode in a macrocephalic infant, associated with fever. Unlike other organic acidemias, metabolic and lactic acidosis, hyperammonemia and hypoglycaemia are rarely present. Subsequently, there is gross motor delay with marked dystonia-dyskinesia. Subdural haematoma is a rare presenting feature of GA1. We report a case who presented with subdural haematoma and diagnosed as GA1. A 17-month-old girl presented to emergency department with minor head trauma. She had fallen down a chair. Her initial neurological examination was completely normal in the emergency unit. She had a generalised seizure. Computerised brain tomography revealed subdural haematoma and she was operated on. During follow-up, her muscle tone increased gradually and previosuly achieved developmental milestones lost. At the age of 24 months, she was unable to sit and walk. Brain magnetic resonance imaging showed bilateral temporal atrophy (Fig. 1). In tandem mass spectrometry, low free carnitine [(5.6 mmol/L) (N:10–60)] and high C5 DC glutarile carnitine [(0.71 mmol/L) (N:0.0–0.40)] levels were detected. Urine organic acid analysis revealed a 20-fold increase in the GA level. With the help of these findings, GA1 was diagnosed. The child was commenced on a reduced lysine/tryptophan diet with carnitine supplementation. GA1 is a relatively rare disease and the ‘typical’ presentation is within the first 12 months of life of an acute metabolic encephalopathic crisis followed by loss of motor skills and development of a dystonic-dyskinetic movement disorder. The presence of acute and chronic subdural collections has been reported in 20% to 30% of patients with GA1 and might be the presenting feature. The pathogenesis of subdural haematomas in GA1 is unclear. It was hypothesised as caused by expanded extra-axial cerebrospinal fluid spaces that result in stretching of the bridging cortical veins. Consequently, patients are prone to developing subdural haemorrhages after minor trauma. In the absence of a history of adequate trauma, the presence of subdural collections of may lead clinicians to suspect nonaccidental trauma in a child with undiagnosed GA1. In our case with minor trauma, subdural haematoma was detected by brain tomography and magnetic resonance imaging showed temporal atrophy, which is the most frequent radiological feature of GA1. The diagnosis of GA1 explained the subdural haematoma. The case is being presented to emphasise that subdural haematoma might be an initial feature of GA1 in children.

Prevalence of cystinuria among elementary schoolchildren in Eskisehir, Turkey.

Objective. Cystinuria is an inherited transport disorder due to defects in intestinal and renal transport of cystine and dibasic amino acids. Early diagnosis is required for some general and specific treatments because cystinuric patients have an increased risk of recurrent urinary stone formation. The prevalence of cystinuria varies widely in different countries. The aim of this study is to determine the prevalence of cystinuria among schoolchildren in Eskisehir, a central Anatolian city in Turkey. Material and methods. The sodium cyanide–nitroprusside spot test was applied to the first morning urine samples from 8260 schoolchildren (4087 female, 4173 male, aged between 6 and 12 years). Urine and blood amino acids were determined with paper chromatography and special cystine–homocystine chromatography were performed if a child had a positive spot-test result. Urinary cystine levels of two children were measured quantitatively. Results. Spot-test results were positive in four students. Increased levels of cystine and dibasic amino acids in the urine were determined with paper chromatography and cystine spots were also detected with special cystine–homocystine chromatography for these four students. Urinary cystine levels were elevated in two children whose urine could be studied. The prevalence of cystinuria in this study was 1:2065. There was no history or symptoms related to urolithiasis in these students. Conclusion. The prevalence of cystinuria in this study is higher than many other countries. Patients in Turkey with urinary stones or with symptoms related to urolithiasis must also be investigated for cystinuria.

Thromboelastogram as a Tool to Predict Hypercoagulability in Children With Cystic Fibrosis.

Increased thrombophilic tendency in patients with cystic fibrosis (CF) has recently been reported. The determinants of thrombosis in children with CF remain largely unknown. Our aim in this study was to evaluate the thromboelastography (TEG) profile of children with CF through ROTEM (whole blood rotation thromboelastometry). Nineteen patients with CF and 20 controls were included in the study. Whole blood count, prothrombin time, activated prothrombin time, fibrinogen, d-dimer levels, and ROTEM assays (INTEM, EXTEM) were performed. Clotting time, clot formation time (CFT), and maximum clot firmness (MCF) were determined by INTEM and EXTEM analysis. In INTEM assay, MCF (P = .001) value was significantly increased and CFT (P = .031) value was decreased in patients with CF compared with those of the control group. In the EXTEM assay, there was a similar significant increase in MCF (P = .023) value in patients with CF compared with that of the control group. There was a significant positive correlation between fibrinogen levels and MCF in EXTEM (r = .72) and INTEM (r = .76) assays, whereas there was a negative correlation with CFT in EXTEM (r = −.61) and INTEM (r = −.67). The results of our study indicated that TEG profiles in patients with CF were more hypercoagulable compared with those of the control group.

Ceftriaxone-associated cholelithiasis: 30 min drip infusion versus bolus injection

Ceftriaxone, a third-generation cephalosporin, is still the preferred antimicrobial for treating infection during childhood in both ambulatory and hospital settings. Previously we published a prospective, open-label study on ceftriaxone in 2004. We prospectively evaluated 38 children aged between 1 month and 17 years who were evaluated on ultrasound at the initiation of ceftriaxone therapy and on the 10th day of therapy, consecutively. Abnormal gallbladder sonograms were demonstrated in 36.8% of patients on the 10th day of therapy and cholelithiasis was detected in 28.9% of patients and biliary sludge was detected in 7.9%. Two children still had cholelithiasis on the 30th day after therapy, and cholelithiasis disappeared at 90th day. Schaad et al. reported that i.v. drip infusion of ceftriaxone is better than bolus injection. In the present study we conducted a prospective, open label investigation of sonographic evaluation of 30 min drip infusion of ceftriaxone therapy in children, with the intention of comparing the results with those of the previous study. Thirty-two consecutive hospitalized children (18 boys, 14 girls, aged 6 months–16 years) in the Pediatric Unit in the Faculty of Medicine, Eskisehir Osmangazi University, Turkey, were included. The study was approved by the institutional ethics comities and parents gave written consent. They received ceftriaxone therapy for bacterial meningitis (n = 14), urinary tract infections (n = 11) and community-acquired pneumonia (n = 7). All the patients received 100 mg/kg ceftriaxone daily and two equal doses of drip infusion during 30 min. Children who had a history of total parenteral nutrition or drugs that caused stone formation were excluded. Abdominal sonography was performed before the first day of therapy and on the 10th day of therapy. If abnormal, scans were repeated every month until abnormalities disappeared. All ultrasound examinations were performed after 8 h of fasting, except during infancy when fasting was 4-6 h. Sonography was performed using a Toshiba 270 SSA (Toshiba, Japan) with 3.75 mHz convex-air transducer, on an empty stomach, in the morning. Statistical analysis was performed using SPSS for Windows 17.0 (SPSS, Chicago, IL, USA). At initiation of therapy all sonograms were normal. Abnormal gallbladder sonograms were demonstrated in 28.1% (n = 9) of patients on the 10th day of therapy. Cholelithiasis was detected in 9.3% (n = 3) of patients and biliary sludge was detected in 18.7% (n = 6). Cholelithiasis still persisted on ultrasound in one 7-year-old boy with bacterial meningitis (3.1%) and disappeared on the 60th day of therapy. When we compare the present study results with those of the previous study, demographic and clinical findings were similar between the study groups; the presence of abnormal gallbladder sonograms including biliary sludge and cholelithiasis were lower in the 30 min infusion group (28.1%) than the previous bolus injection group (36.8%), without statistical difference (P > 0.05). When we compared the incidence of cholelithiasis between the drip infusion group and bolus injection group, the incidence of cholelithiasis was lower in the drip infusion group (9.3%) than in the bolus injection group (28.9%; 3/32 children in drip infusion group vs 11/38 children in the bolus injection group; Fisher’s exact test, P = 0.07; two-sided test). Ceftriaxone-associated pseudocholelithiasis is a very well known, benign and recovering condition and clinical signs are usually absent. The present study was a prospective cohort study on the comparison of bolus versus drip infusion of ceftriaxone in children, and there are few previous reports evaluating the incidence between these two groups. Schaad et al. reported that cholelithiasis was confirmed in 55% of patients who received 3-5 min injections and in 29% who received 30 min injections. The present results on the occurrence of abnormal biliary sonograms with 30 min infusion of ceftriaxone are similar to those of the Schaad et al. study, while the present results also indicate that occurrence of cholelithiasis was low in the 30 min infusion group (9.3% vs 28.9%, P = 0.07), without statistical difference. According to the results, bolus drip infusion of ceftriaxone therapy is safer than bolus injection. The present sample size was small, so further randomized controlled trials are needed on pharmacodynamic profile, efficacy and other adverse events associated with infusion therapy of ceftriaxone in large cohorts.

Acrodermatitis enteropathica: A novel mutation of the SLC39A4 gene in a Turkish boy.

pustules on the trunk with a wedge-shaped symmetrical distribution (Fig. 1a–d). Punch biopsy from the lesion showed subcorneal spongiotic pustules composed of neutrophils with a negative result on Gram staining. The basal layer presented vacuolar degeneration, and superficial perivascular inflammatory infiltrations composed of lymphocytes and eosinophils were evident in the dermis (Fig. 1e,f). Laboratory examinations showed normal results. She had been given systemic and topical steroid over 3 weeks with poor response. Doxycycline 200 mg/day was started and the lesions resolved in 2 weeks leaving a brown reticulated hyperpigmentation. Based on the clinical findings, the skin biopsy result and dramatic response to doxycycline, the patient was diagnosed with pustular prurigo pigmentosa (PP). Prurigo pigmentosa is characterized by the sudden onset of pruritic erythematous papules, involving the trunk and neck that coalesce to reticulated and mottled patches. In severe cases, they may form edematous infiltrative plaques, and the vesicles are rarely found. Lesions resolve within several weeks leaving postinflammatory hyperpigmentations, and recurrences are usual. Because the pustular type of PP has not been reported, we considered various pustular diseases first, including subcorneal pustular dermatosis, acute generalized exanthematous pustulosis and pustular psoriasis. The treatment and prognosis of PP differ with these diseases, therefore, early diagnosis with proper treatment would be important. The exact cause and pathogenesis of PP are unclear. Even the histology of PP is non-specific. B€ oer et al. emphasized the presence of neutrophils in the histopathological findings. From the histological finding of this case, which showed nonfollicular subcorneal sterile spongiotic neutrophilic pustulosis, we could support the importance of neutrophilic finding of PP, and hypothesize that the pustules had formed as a result of severe spongiosis and liquefaction of the basal cell layer. A variety of agents are used in the treatment of PP, the most effective of which are oral antibiotics such as minocycline, doxycycline and sulfonamides. Medications that have been reported to be useful in PP are due to their ability to inhibit the migration or function of neutrophils. This case showed a dramatic response to doxycycline with the inhibition of new pustule formation in 2 weeks. Finally, the patient was diagnosed with pustular PP, because of clinical characteristics showing sudden onset of symmetrical pruritic skin lesions, histopathological findings, and clinical course resolving with doxycycline and leaving postinflammatory reticulated hyperpigmentations. In summary, PP can present with pustular lesions and thus should be considered in the differential diagnosis of pruritic pustular diseases. Clinical features which include the distribution of lesions, coexistence of reticulate pigmentation, and good response to minocycline or doxycycline therapy distinguish PP from other dermatoses.