Drugs and juvenile crime: evidence from a panel of siblings and twins.

Using data from the U.S. National Longitudinal Study of Adolescent Health, this chapter investigates the impact of individual drug use on robbery, burglary, theft, and damaging property for juveniles. Using a variety of fixed-effects models that exploit variations over time and between siblings and twins, the results indicate that drug use has a significant impact on the propensity to commit crime. We find that the median impact of cocaine use on the propensity to commit various types of crimes is 11 percentage points. The impact of using inhalants or other drugs is an increase in the propensity to commit crime by 7 percentage points, respectively.

A phenocopy of CAII deficiency: a novel genetic explanation for inherited infantile osteopetrosis with distal renal tubular acidosis.

The rare bone thickening disease osteopetrosis occurs in various forms, one of which is accompanied by renal tubular acidosis (RTA), and is known as Guibaud-Vainsel syndrome or marble brain disease. Clinical manifestations of this autosomal recessive syndrome comprise increased bone density, growth failure, intracerebral calcification, facial dysmorphism, mental retardation, and conductive hearing impairment. The most common cause is carbonic anhydrase II (CAII) deficiency. Several different loss of function mutations in CA2, the gene encoding CAII, have been described. To date, there have been no exceptions to the finding of CAII deficiency in patients with coexistent osteopetrosis and RTA. Most often, the RTA is of mixed proximal and distal type, but kindreds are reported in which either distal or proximal RTA predominates. We report the molecular genetic investigation of two consanguineous kindreds where osteopetrosis and distal RTA (dRTA) were both manifest. One kindred harbours a novel homozygous frameshift alteration in CA2. In the other, CAII levels were normal despite a similar clinical picture, and we excluded defects in CA2. In this kindred, two separate recessive disorders are penetrant, each affecting a different, tissue specific subunit of the vacuolar proton pump (H(+)-ATPase), providing a highly unusual, novel genetic explanation for the coexistence of osteopetrosis and dRTA. The osteopetrosis is the result of a homozygous deletion in TCIRG1, which encodes an osteoclast specific isoform of subunit a of the H(+)-ATPase, while the dRTA is associated with a homozygous mutation in ATP6V1B1, encoding the kidney specific B1 subunit of H(+)-ATPase. This kindred is exceptional firstly because the coinheritance of two rare recessive disorders has created a phenocopy of CAII deficiency, and secondly because these disorders affect two different subunits of the H(+)-ATPase that have opposite effects on bone density, but which have only recently been determined to possess tissue specific isoforms.

Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss.

Autosomal recessive distal renal tubular acidosis (rdRTA) is characterised by severe hyperchloraemic metabolic acidosis in childhood, hypokalaemia, decreased urinary calcium solubility, and impaired bone physiology and growth. Two types of rdRTA have been differentiated by the presence or absence of sensorineural hearing loss, but appear otherwise clinically similar. Recently, we identified mutations in genes encoding two different subunits of the renal alpha-intercalated cell's apical H(+)-ATPase that cause rdRTA. Defects in the B1 subunit gene ATP6V1B1, and the a4 subunit gene ATP6V0A4, cause rdRTA with deafness and with preserved hearing, respectively. We have investigated 26 new rdRTA kindreds, of which 23 are consanguineous. Linkage analysis of seven novel SNPs and five polymorphic markers in, and tightly linked to, ATP6V1B1 and ATP6V0A4 suggested that four families do not link to either locus, providing strong evidence for additional genetic heterogeneity. In ATP6V1B1, one novel and five previously reported mutations were found in 10 kindreds. In 12 ATP6V0A4 kindreds, seven of 10 mutations were novel. A further nine novel ATP6V0A4 mutations were found in "sporadic" cases. The previously reported association between ATP6V1B1 defects and severe hearing loss in childhood was maintained. However, several patients with ATP6V0A4 mutations have developed hearing loss, usually in young adulthood. We show here that ATP6V0A4 is expressed within the human inner ear. These findings provide further evidence for genetic heterogeneity in rdRTA, extend the spectrum of disease causing mutations in ATP6V1B1 and ATP6V0A4, and show ATP6V0A4 expression within the cochlea for the first time.

Infantile-onset megalencephalic leucoencephalopathy in two siblings.

Infantile-onset megalencephalic leucoencephalopathy (IML) is a recently recognized autosomal recessive white matter disorder. Unlike other megalencephalic leucoencephalopathies, in patients with IML a mild clinical course, a slowly progressive delay in motor development and mild mental deterioration are typical. We report on two affected siblings who have typical clinical and radiological findings of IML. Cranial magnetic resonance imaging showed involvement of the capsula externa, extrema and interna, nucleus dentatus, crus cerebri, periventricular and subcortical white matter. In addition, bilateral cystic changes were determined predominantly in the temporal lobes. There were no clear biochemical or metabolic disturbances. In the present paper, we discuss the clinical and neuroimaging findings of IML.

Microscopic nephrocalcinosis and hypercalciuria in nephrotic syndrome.

Focal calcification is an occasional tubular abnormality seen in minimal-change nephrotic syndrome. Nephrocalcinosis was also reported in premature infants as a consequence of hypercalciuria resulting from long-term furosemide therapy. We describe 4 nephrotic children (3 minimal change, 1 diffuse proliferative glomerulonephritis) with transient hypercalciuria and intraluminal calcifications in renal histopathological specimens without radiologic evidence of renal calcification. These children were resistant to corticosteroid therapy and were receiving furosemide therapy along with albumin for management of oedema. Two of the children also had urinary infection. We were concerned that children with nephrotic syndrome are at risk for nephrocalcinosis, and urinary calcium and pH should be monitored carefully during prolonged furosemide use, especially in children with nephrotic syndrome with reduced initial responsiveness to corticosteroid therapy. HUM PATHOL 31:1363:1367.

Breath holding spells in 91 children and response to treatment with iron.

To evaluate the prognosis of breath holding spells (BHS) after iron treatment, 91 children (56 boys, 35 girls) aged between 6 months and 40 months (median, 17) were followed prospectively for a median of 45 months (range, 6-89). In 49 of the children, the frequency of BHS was less than 10 each month, in 22 it was 10-30 each month, and in 20 more than 30 each month. The spells were cyanotic in 60 children. All patients were evaluated initially and during follow up for haematological indices. Electroencephalographic and electrocardiographic abnormalities were also recorded. Sixty three patients were found to have iron deficiency anaemia and were treated with iron (6 mg/kg/day) for three months. Other patients were not given any treatment. After three months, there was a significant difference for correction of cyanotic spells between children who had been treated with iron and those who had not (84.1% v 21.4%). During further follow up, febrile convulsions occurred in 10 children (six were on iron treatment initially). It appears that treating iron deficiency anaemia is effective in reducing the frequency of BHS.

Oxidative damage of erythrocyte membrane in nephrotic syndrome.

Erythrocytes are target cells for peroxidative damage. Abnormal susceptibility of erythrocyte lipids to peroxidation is believed to reflect a similar abnormality in other organs and tissues. The changes in erythrocyte lipid peroxidation [measured by malonyldialdehyde (MDA) concentration] and erythrocyte membrane cholesterol (EMC) and their correlation with plasma lipid changes were studied in 36 children with steroid-responsive minimal change nephrotic syndrome (MCNS) (16 in relapse, 20 in remission) and 30 matched healthy controls. Erythrocyte MDA levels were significantly higher in relapse [126.3+/-40.6 nmol/g hemoglobin (Hb)] compared with remission (101.2+/-21.3 nmol/g Hb, P<0.02) and in controls (95.4+/-20.4 nmol/g Hb, P<0.001). Plasma MDA levels in relapse were also higher than in remission (4.26+/-1.19 nmol/ml vs. 3.16+/-1.18 nmol/ml, P<0.01), and in controls (2.49+/-0.86 nmol/ml, P<0.001). The EMC content changed significantly during remission (1.22+/-0.15 mg/10(10) cells in relapse, 1.09+/-0.19 mg/10(10) cells in remission, P<0.04). These results show an increased sensitivity of red cells to lipid peroxidation in patients with steroid-sensitive nephrotic syndrome without the development of renal failure and anemia. Lipid peroxidation of plasma lipids and erythrocyte membrane may be a primary phenomenon, but this should be confirmed by investigation of peroxidation of renal lipids.

Roberts SC phocomelia with isolated cleft palate, thrombocytopenia, and eosinophilia.

The Roberts-SC (Pseudothalidomide) syndrome is a rare autosomal recessive disorder. We present a Roberts-SC Syndrome in a 20-day-old girl with phocomelia of the upper limbs, isolated cleft palate, micrognathia, prominent eyes, pectus excavatum, and pes equinovarus. Peripheral blood smear revealed thrombocytopenia and hypereosinophilia. Premature centromere separation in the child and also in her normal mother was noted.

The effect of ATP-MgCl2 on lipid peroxidation in ischemic and reperfused rabbit kidney.

Oxygen metabolites formed during reperfusion of ischemic kidneys prevent recovery of renal function after short periods of renal ischemia. The administration of ATP-MgCl2 is beneficial to the survival of animals after hemorrhagic shock, severe burns, septicemia-peritonitis, post-ischemic hepatic failure, bowel ischemia, and endotoxic shock. In this study, the effect of ATP-MgCl2 on lipid peroxidation and its curative effect were evaluated by measuring the decomposition products of lipid peroxidation, detected as thiobarbituric-acid reactive substances in homogenized kidney tissues in ischemic and reperfused rabbit kidneys. Ischemia was performed by clamping the right renal artery for 60 minutes followed by 30 minutes of reperfusion. Thirty-six rabbits were classified into 6 groups containing 6 rabbits in each. In the first group, no renal ischemia-reperfusion (I-R) was designed (Sham group), the right kidney was removed 90 minutes later. In the second group, I-R was established but nothing given. Saline 0.25 cc/kg was given into the right renal artery in group 3 two minutes before ischemia, and in group 4 two minutes before reperfusion. ATP-MgCl2 17.5 mumol/kg (0.25 cc/kg) was given two minutes before ischemia in group 5, and before reperfusion in group 6. The right kidneys of the rabbits were removed and thiobarbituric-acid reactive substances in the homogenates were measured. In addition, histopathological evaluation was performed. High lipid peroxidation products were recorded in groups 2-5, whereas in group 6, these levels were low similar to those obtained in Sham group (76.72 +/- 1.01 nmol/g tissue). On histopathological evaluation, a considerable cell damage resulting from I-R trauma especially in proximal tubules was observed. In groups which were under saline effect, no histopathological damage was found. Histophatological preservation was better in group 6 rather than in group 5. The results of this study indicate that ATP-MgCl2 is remarkably effective for preventing the lipid peroxidation if given before reperfusion but not before ischemia in experimental I-R injury in rabbit kidneys.

Fatal polyarteritis nodosa with massive mesenteric necrosis in a child.

Polyarteritis nodosa (PAN) is a rare vasculitic syndrome in childhood. There are few reported cases of ischaemic necrosis of the intestine and even fewer survivors in adults. We report the case of a 10-year-old boy with PAN and an acute abdomen that required operative intervention. Evidence was found of mesenteric arteritis with large ischaemic segments resulting in infarction and perforation.

Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness.

H+-ATPases are ubiquitous in nature; V-ATPases pump protons against an electrochemical gradient, whereas F-ATPases reverse the process, synthesizing ATP. We demonstrate here that mutations in ATP6B1, encoding the B-subunit of the apical proton pump mediating distal nephron acid secretion, cause distal renal tubular acidosis, a condition characterized by impaired renal acid secretion resulting in metabolic acidosis. Patients with ATP6B1 mutations also have sensorineural hearing loss; consistent with this finding, we demonstrate expression of ATP6B1 in cochlea and endolymphatic sac. Our data, together with the known requirement for active proton secretion to maintain proper endolymph pH, implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function. ATP6B1 is the first member of the H+-ATPase gene family in which mutations are shown to cause human disease.

High dose methylprednisolone therapy in nephrotic syndrome.

This study was done to determine the efficacy of oral high dose methylprednisolone (HDMP) therapy in the treatment of childhood nephrotic syndrome (NS). Fifteen patients were enrolled in the study. Patients were arbitrarily divided into two groups. Group I received prednisolone (daily 60 mg/m2 for 4 weeks, 45, 30, 20, 10, 5 mg/m2 on alternate days for 4 weeks) and group II received HDMP (30 mg/kg/d for 3 days, 20 mg/kg/d for 4 days, 10 mg/kg/ for a week, before 9 am, orally). The patients were followed-up for a duration of 38.0 +/- 5.5 months (range 24-68 months) in group I and 42.1 +/- 5.5 months (range 16-72 months) in group II. No significant difference was obtained in the duration of remission between both groups (p > 0.05), while HDMP induced early remission than prednisolone (p < 0.05). The mean relapse rate was 0.8/year in group I and 0.8/year in group II (p > 0.05). Although, the number of the patients were limited in the study it can be recommended that patients with NS can be treated with oral HDMP therapy as an alternative to standard oral prednisolone therapy.

Kasabach-Merrit syndrome in infants.

METHODS: Four infants with Kasabach-Merrit syndrome syndrome have been treated at the University Hospital, Trabzon. They had large varied-site cutaneous hemangiomas. Diagnosis was performed with clinical and laboratory studies. All patients has severe thrombocytopenia and anemia. Fibrinogen and fibrin split products were examined in two patients and lower fibrinogen and over fibrin split products levels were detected in them. All patients were admitted to the intensive care unit and they were treated with antibiotics, fresh blood transfusion and thrombocyte suspension. Two out of four patients were previously treated with steroids unsuccessfully and one patient died due to disseminated intravascular coagulopathy. Three patients were treated with interferon alfa-2a and compression. RESULTS: In two patients the lesions regressed 60-80% following the five months therapy and in the other patient the lesion was completely excised after one month therapy. CONCLUSIONS: Interferon alfa-2a and compression were found to be remarkably effective in the treatment of Kasabach-Merrit syndrome.

Noonan syndrome associated with central giant cell granuloma.

We report a case of Noonan syndrome associated with central giant cell granuloma. The patient was a 10 1/2-year-old boy with the chief complaint of proptosis of the right eye. He also had various malformations such as short stature, webbed neck, pectus excavatum, cubitus valgus, pulmonary valve stenosis and patent foramen ovale, a characteristic face appearance and cryptorchidism and so on. Chromosome analysis showed a 46,XY karyotype. A computed tomographic scan and magnetic resonance imaging showed a mass originated from the lateral wall of the right maxillary sinus. The patient underwent Caldwell-Luc operation. Histological examination of the mass showed the characteristics of central giant cell granuloma. This case report describes a patient with the features of the recently described Noonan-like/multiple giant cell lesion syndrome.

Postpartum hemolytic uremic syndrome with a more severe liver involvement.

A 22-year-old woman presented with postpartum hemolytic uremic syndrome with a more severe hepatic involvement. The patient was dialysed and successfully treated with plasma infusion and intravenous immunoglobulin. Two months following discharge her creatinine clearance was 105 ml/min/1.73 m2, 99mTc DTPA scan and brain CT were normal. Here child is also alive and healthy.

Cutaneous polyarteritis nodosa in a child and a review of the literature.

The cutaneous form of polyarteritis nodosa in children is extremely rare. Findings are usually limited to the skin, muscles and joints. It has a benign but often chronic course. We describe an 8-y-old girl with cutaneous PAN, with extensive livedo reticularis on lower and upper extremities, tender subcutaneous nodules, arthralgia and right ankle swelling. Skin biopsy revealed vasculitis of small and medium-sized blood vessels characterized by fibrinoid necrosis. The use of prednisolone resulted in clinical improvement initially, but recurrence occurred during tapering. She showed marked improvement with additional high dose methyl prednisolone monthly.

Plasma soluble interleukin-2 receptor levels in patients with idiopathic thrombocytopenic purpura.

Soluble interleukin-2 receptor (slL-2R) was measured in the plasma of 31 patients with idiopathic thrombocytopenic purpura (ITP) and 22 normal controls. When thrombocytopenia persisted longer than 6 months, the diagnosis of chronic ITP was made. Twenty patients had acute ITP, 11 patients had chronic ITP, and all patients received high-dose methylprednisolone (HDMP) (30 mg/kg/d for 3 days, 20 mg/kg/d for 4 days). The sIL-2R levels of the patients were determined before being giving HDMP and 14 days after the end of HDMP therapy. Platelet counts were determined before administration of HDMP, one day after the end of HDMP therapy, and once every 28 days for 7 months thereafter. There was not a significant difference between the mean pre-treatment plasma sIL-2R levels of both acute and chronic ITP groups (P > 0.05), and these were higher than that of the control group (P < 0.001). The mean post-treatment sIL-2R level of the chronic ITP group was significantly higher than those of both the control and post-treatment acute ITP groups (P < 0.001). There were negative correlations between the plasma sIL-2R levels and platelet counts of both group patients in the pre-treatment period and between post-treatment sIL-2R levels and platelet counts in chronic ITP group (P < 0.05). We think that there was a good correlation between prognosis of ITP and sIL-2R levels after HDMP therapy, and platelet counts in patients with ITP are linked to sIL-2R levels.

Multiple intracranial hemorrhages at the time of a transiently prolonged activated partial thromboplastin time in an infant with congenital factor VII deficiency.

Factor VII (FVII) deficiency is a rare autosomal recessive hereditary disorder characterized by a normal partial thromboplastin time and a prolonged prothrombin time. For definitive diagnosis, the specific FVII level should be investigated. We report on a 7-month-old boy with congenital FVII deficiency suffering from convulsions and intracerebral hemorrhage. Hematologic tests revealed prolonged prothrombin time associated with a decreased FVII level of 1.7%. Computerized tomography of the brain revealed multifocal hemorrhagic lesions. To our knowledge, multifocal intracranial hemorrhages at the time of a transiently prolonged partial thromboplastin time of unknown origin in a child with congenital FVII deficiency of about 2% has not been reported so far.