The renal lesion of congenital hepatic fibrosis: pathologic and morphometric analysis, with comparison to the renal lesion of infantile polycystic disease

The renal lesion of congenital hepatic fibrosis (CHF = Blyth and Ockenden's juvenile polycystic disease of liver and kidneys) was analyzed from 6 specimens from patients aged 3 3/12 to 19 3/12 years and compared with that of 5 patients with infantile polycystic disease (IPCD) aged 6 months to 14 4/12 years. Pathologic, microdissection, injection, and morphometric studies show that the predominantly medullary cystic lesion of CHF shows different distribution in medullary, cortico-medullary, and cortical zones of kidney from the lesion of IPCD, and shows a different time course, from early life to renal insufficiency, from that of IPCD. The renal cysts in CHF affect deep or central collecting tubules, in contrast to the involvement of more peripheral orders of collecting tubules in IPCD. Papillary pore counts, performed for 1 patient, gave significantly low values, in contrast to normal values reported for IPCD. The findings support the previously published conclusion, based on differences in the hepatic lesions of the two conditions, that CHF and IPCD are difference diseases, rather than different permissible manifestations of a single disease.     

The Renal Lesion of Congenital Hepatic Fibrosis: Pathologic and Morphometry Analysis, with Comparison to the Renal Lesion of Infantile Polycystic Disease

The renal lesion of congenital hepatic fibrosis (CHF = Blyth and Ockenden's juvenile polycystic disease of liver and kidneys) was analyzed from 6 specimens from patients aged 3 3/12 to 19 3/12 years and compared with that of 5 patients with infantile polycystic disease (IPCD) aged 6 months to 14 4/12 years. Pathologic, microdissection, injection, and morphometric studies show that the predominantly medullary cystic lesion of CHF shows different distribution in medullary, cortico-medullary, and cortical zones of kidney from the lesion of IPCD, and shows a different time course, from early life to renal insufficiency, from that of IPCD. The renal cysts in CHF affect deep or central collecting tubules, in contrast to the involvement of more peripheral orders of collecting tubules in IPCD. Papillary pore counts, performed for 1 patient, gave significantly low values, in contrast to normal values reported for IPCD. The findings support the previously published conclusion, based on differences in the hepatic lesions of the two conditions, that CHF and IPCD are difference diseases, rather than different permissible manifestations of a single disease.     

Net acid excretion during first week of life

Metabolic acidosis occurs frequently in newborns. Net acid excretion (NAE) in 34 preterm and 12 term infants was measured during the first week of life. Twenty preterm infants received breast milk or formula; the remaining infants received total parenteral nutrition (TPN) -- synthetic amino acids or casein hydrolysate solution. NAE for breast milk vs formula fed infants was 5.4 +/- 0.4 and 7.8 +/- 0.6 muEq/min/m2 (mean +/- SEM). The corresponding values for the two TPN solutions in preterm infants were significantly higher at 12.5 +/- 1.4 and 19.4 +/- 3.5 muEq/min/m2. Term infants produced even greater amount of net acid, 20.6 +/- 2.9 and 35 +/- 3.7 muEq/min/m2 respectively for the two TPN solutions. Milk fed infants are less prone to acidosis because of base generated from milk consumption. Due to its inherent acidogenic effect, TPN solutions induce acidosis more readily. Infants receiving TPN are therefore required to generate a higher NAE rate to maintain acid-base homeostasis compared to milk fed infants.     

Metabolic acidosis, nitrogen balance and weight gain in preterm infants.

Nitrogen balance, urinary NAE and the acid base parameters in the blood of 15 male preterm infants with birth weights of 1000--2370 g (mean 1715 g) and gestational age of 29--37 weeks (mean 33.3 weeks) were determined weekly, in the first six weeks of life. The sum of NAE plus acid retention, as "total acid", was used to investigate the relationship between nitrogen balance, weight gain and acid-base homeostasis. During the first three postnatal weeks, nitrogen intake, urinary and faecal loss of nitrogen as well as the nitrogen retention were rapidly increasing. Later, urinary excretion continued to rise, the intake remained unchanged and as a result, the amount of retained nitrogen decreased slightly. Urinary NAE was steadily increasing to reach the maximum of 2.8 mEq/kg by the fourth week. Acid retention was the most pronounced in the second and third week, thereafter it fell until the end of the study. The importance of NAE relative to acid retention was continuously increasing throughout the observation period. The "total acid" increased gradually and reached its peak value in the third week of life. Subsequently a continuous fall was seen. During the first three weeks of life there was a significant positive correlation between "total acid" and nitrogen intake and urinary nitrogen extraction. Since the increase in "total acid" went parallel with the increasing nitrogen retention, the latter may be assumed to be an additional factor in producing acidosis. Calculated per 100 mg nitrogen ingested, retained or excreted with urine, "total acid" was decreasing with the increasing rate of weight gain. This indicates that the growth process -- irrespective of the postnatal development of renal H+ handling -- is also involved in the elimination of acids.     

Abnormalities of carbamyl phosphate synthetase and ornithine transcarbamylase in liver of patients with Reye's syndrome.

Urea cycle function was evaluated in liver obtained from six patients with Reye's syndrome and from five control subjects. Reye's syndrome patients demonstrated normal activities for the extramitochondrial portion of the urea cycle, but showed marked abnormalities of the mitochondrial enzymes, i.e., carbamyl phosphate synthetase (CPS) and ornithine transcarbamylase (OTC) (Tables 2,3). CPS activity was reduced to less than 15% of control values in all four patients from whom tissues was obtained during the first 72 hr after the onset of encephalopathy. Two patents from whom tissue was not obtained until after 9 days of symptoms showed no reduction in CPS activity. The OTC activity was also reduced (3-67% of control values) in the four patients from whom tissue was obtained early in the illness. In addition, greater than 60% reduction in Vmax and Km for carbamyl phosphate was noted in all four patients in whom sample size permitted kinetic analysis, including both patients in whom CPS and OTC activity were not markedly reduced. The same kinetic abnormality as well as decreased CPS activity were experimentally produced in normal rate liver incubated in the presence of 1.0 mM 4-pentenoic acid, a short chain fatty acid and known hepatic mitochondrial toxin (Table 4).     

Congenital hepatic fibrosis in Saudi Arabia.

Congenital hepatic fibrosis (CHF) is a recognized cause of portal hypertension with oesophageal varices, gastro-intestinal haemorrhage and cholangitis in children without significant impairment of hepatic or renal function. This report describes the varied clinical presentation of CHF as seen at King Faisal Specialist Hospital and Research Centre (KFSH & RC) and emphasizes the clinical patterns that should enable a pediatrician to consider the diagnosis. Fourteen children with CHF were diagnosed between 1981 and 1988. The age at presentation ranged from 1.8-14 years (mean: 7.5 years); clinical manifestations at diagnosis were splenomegaly (12), hepatomegaly (11), failure to thrive (10), marked abdominal distention (4), and fever (4). Liver function tests were normal except for high alkaline phosphatase. Eight patients had polycystic kidneys confirmed on ultrasound examination. Upper gastro-intestinal endoscopy showed oesophageal varices of variable severity in all eight patients examined. Splenoportography revealed splenic vein occlusion in one patient. One patient died within days of admission with convulsions, coma, and aspiration pneumonia. One patient was lost to follow-up. The remaining 12 patients are all alive and receive regular follow-up. Two patients required splenorenal shunt. In view of the prevalence of consanguinity in Saudi Arabia, the diagnosis of CHF should be considered in children with hepatomegaly despite normal liver function tests, and particularly in those with renal abnormalities and/or evidence of portal hypertension.     

Reduction of serum carnitine concentrations during anticonvulsant therapy with phenobarbital, valproic acid, phenytoin, and carbamazepine in children

We determined four carnitine constituents (total and free carnitine and short- and long-chain fatty acid carnitine esters) in serum from 471 patients treated for convulsions with phenobarbital, valproic acid, phenytoin, and/or carbamazepine. The 471 patients were in eight treatment groups; four were treated with monotherapy and four with polytherapy. The means of all four carnitine constituents were significantly reduced in all treatment groups (except for free carnitine in four groups). Total carnitine was reduced by 23% to 48%, free carnitine by 9% to 45%, short-chain fatty acid carnitine by 46% to 64%, and long-chain fatty acid carnitine by 6% to 29%. Patient frequency of reduction for total carnitine was 20% of all patients (10% for free carnitine), 23% of patients receiving valproate (9% for free carnitine), 36% of those receiving phenobarbital (21% for free carnitine), 12% of those receiving phenytoin (8% for free carnitine), and 8% of those receiving carbamazepine (1% for free carnitine). Only for phenobarbital was there an inverse correlation between the serum concentration of the drug and that of carnitine concentration. One patient receiving carbamazepine had a 59% reduction in the total and a 65% reduction in the free carnitine concentration and a fivefold increase in long-chain fatty acid carnitine, values similar to those seen in neonatal lethal carnitine palmitoyl transferase II deficiency. It remains to be determined whether a reduction in serum carnitine values in patients receiving anticonvulsant therapy is of clinical consequence, whether the reduction is present in some patients before the start of therapy, when and by what mechanism carnitine levels may become reduced during therapy, and whether the reduction exists in the solid tissues of these patients.     

Low R-wave amplitude in the right precordial leads in children with symptomatic doxorubicin cardiomyopathy

Summary Electrocardiographic (ECG) findings were studied in four patients with doxorubicin cardiomyopathy. In all patients with congestive heart failure (CHF), the ECGs had a low R-wave and low R/S ratio in lead V₁. Our study suggests that increased injury to myocardial cells in the regions of the anterior septum and anterior left ventricular wall may be important in the pathogenesis of doxorubicin cardiomyopathy. Eight years later, cardiac recovery from CHF occurred with a normal ECG and left ventricular ejection fraction in one patient, indicating that CHF may be reversible in certain cases.     

充血性心力衰竭与重症肺炎患儿血清脑钠素浓度变化的研究

目的：B型利钠肽即脑钠素(B-typeorbrainnatriureticpeptide,BNP)在成人充血性心力衰竭(con-gestiveheartfailure,CHF)时血浆浓度显著升高,对成人CHF有重要诊断价值,对成人急性呼吸困难有重要的鉴别诊断价值。在小儿有关BNP的研究不多,该实验旨在研究小儿CHF及肺炎时血清BNP浓度变化,探讨BNP对小儿急性呼吸困难的鉴别诊断价值;进一步探讨小儿重症肺炎是否会合并心衰,为肺炎合并心衰的诊断寻找客观指标。方法：将65例有呼吸困难症状的患儿分为3组CHF组(即心源性呼吸困难组)24例;肺炎组(即肺源性呼吸困难组)23例;临床诊断肺炎心衰组18例。对10例肺炎合并心衰患儿在病情平稳2~3d后再次收集血清。正常对照组15例。用ELISA法测血清BNP浓度。结果：CHF组血清BNP浓度显著高于临床诊断肺炎心衰组、肺炎组及正常组(P<0.01);临床诊断肺炎心衰组显著高于肺炎组(P<0.01)及正常组(P<0.01),肺炎组与正常组比较差异无显著性。BNP对心源性呼吸困难鉴别诊断的受试者作业特征曲线(receiveoperatorcharacteristic,ROCcurve)下面积是0.978(P<0.01);BNP以49pg/mL为诊断界值,对呼吸困难由CHF引起的诊断敏感度是87.5%,特异度是95.8%;临床诊断肺炎心衰的18例患儿中,BNP浓度>49pg/mL的11例,其BNP浓度为172.08±56.47pg/mL,显著高于肺炎组(P<0.01),与CHF组相比无差异;这11例中有10例治疗后复查血清BNP,其浓度为26.12±15.71pg/mL,低于治疗前(P<0.01)。另7例血清BNP浓度为20.46±11.78pg/mL,与肺炎组及正常组相比差异无显著性(均P>0.05)。结论：BNP浓度检测对小儿呼吸困难是否由CHF引起有鉴别诊断价值;小儿重症肺炎时可以合并心力衰竭;BNP检测可鉴别小儿重症肺炎是否合并心力衰竭。     

Does digoxin still have a role in congestive heart failure?

The role of digoxin in the treatment of congestive heart failure is (CHF) being questioned. Digoxin continues to be the drug of choice for patients with atrial fibrillation in CHF. Large randomised trials have shown that digoxin (in addition to ACE inhibitors and diruetiec) is beneficial in CHF due to systolic dysfunction, although it does not reduce mortality. Limited data suggest that digoxin benefit some, but not all patients with CHF due to left to right shunts. Digoxin does not benefit CHF due to diastolic dysfunction and it is not routinely recommended for prematures with patent ductus and CHF. The treatment with digoxin should be individualised.     

Complications and outcome in left-sided endocarditis in children

We retrospectively assessed the clinical course and outcome of left-sided endocarditis in pediatric patients to find out the prognostic significance of the presence and size of echocardiographically detected vegetations. Among the children admitted to our institution with endocarditis between January 1987 and October 1999, 16 patients (mean age 9.03 +/- 4.95 years) who met the Duke criteria for the diagnosis of infective endocarditis (IE) were included in this study. Rheumatic valvular disease was the most frequent underlying heart disease (10 patients: 62.5%). Five patients were operated at a mean of 13.9 months before endocarditis, and all had residual defects. Vegetation was detected in 11 cases (69%). Ten patients had major complications (within 2 weeks in 6 patients). Three patients developed congestive heart failure (CHF), six had intracranial and one had lower extremity emboli. Among them four were operated because of complications (CHF: 3 cases, intracranial emboli: 1 case). All the operated cases are doing well. The association between intracranial embolic events and echocardiographically detected vegetations was determined by calculating specificity (40%), sensitivity (100%), positive predictive value (50%), and negative predictive value (100%). No intracranial embolism occurred in patients without vegetations. All vegetations were < or = 6 mm in patients with systemic embolism. There were four deaths, three of which were because of intracranial embolism. This study suggests that intracranial emboli have a major risk of mortality in left-sided endocarditis. The larger size of the vegetation is not a predictor of complications; furthermore, the absence of vegetations predicts that the patient is safe from embolic events. Therefore all patients with left-sided IE should be considered for earlier surgical intervention.     

Myocardial dysfunction in birth asphyxia

Evidence of myocardial dysfunction was present in all the 50 newborns who had suffered from moderate and severe birth asphyxia. Myocardial status were dependent on the degree of asphyxia. In 10 newborns who suffered from moderate asphyxia, myocardial status was as follows: respiratory distress in eight (80%) cardiac murmur in two (20%), cardiomegaly on X-ray was present in three (30%) and ischemic changes in form of ST, T changes in ECG in all. Shock and CHF were absent. Of 40 cases of severe birth asphyxia features observed were shock in four (100%) CHF in nine (22.5%) respiratory distress in 40 (100%) cardiac murmur in 30 (100%) ischemic changes inform of ST depression, abnormal Q and T waves in 40 (100%) cardiomegaly in 28 (70%). Early diagnosis and treatment of these cases reduced mortality in moderate asphyxia to zero and in severe asphyxia to 40% in the present study.     

不同病因急性心力衰竭患儿血清氨基末端脑钠素原水平变化及其与肺动脉高压的关系

目的探讨先天性心脏病、肺炎并心力衰竭患儿血清氨基末端脑钠素原(NT-proBNP)水平变化及其与肺动脉高压(PH)的关系。方法采用竞争性酶免疫法检测66例住院心力衰竭患儿(肺炎并心力衰竭25例,先天性心脏病并肺炎心力衰竭22例,先天性心脏病并中重度PH心力衰竭19例)及60例对照组患儿(肺炎、先天性心脏病、健康儿童各20例)外周血NT-proBNP水平。多普勒超声心动图检测心力衰竭患儿心室射血分数(LVEF)、缩短分数(FS),对先天性心脏病患儿估测肺动脉压力。结果1.肺炎心力衰竭组及先天性心脏病心力衰竭组NT-proBNP水平无显著差异(P>0.05),但二组均较相应对照组(肺炎对照组、先天性心脏病对照组)显著增高(Pa<0.001);先天性心脏病并中重度PH心力衰竭组较先天性心脏病无PH或轻度PH心力衰竭组水平亦明显增高(Pa<0.05)。2.三组心力衰竭患儿间LVEF、FS水平比较差异无显著性(Pa>0.05)。3.肺炎对照组、先天性心脏病对照组较正常对照组NT-proBNP水平略高,但无统计学意义(Pa>0.05)。结论血清NT-proBNP对肺炎心力衰竭、先天性心脏病并心力衰竭均有较敏感而特异的诊断价值,且随肺动脉压力增高而呈增高趋势。     

Neurologic adverse events following influenza A (H1N1) vaccinations in children

Background: Since the monovalent pandemic influenza A (H1N1) vaccine was recommended worldwide in October 2009, there has been a shortage of pediatric clinical data for post‐vaccine neurologic adverse events (NAE), including Guillain–Barré syndrome. We reviewed pediatric NAE data following H1N1 vaccinations and for patients with peripheral neuropathy, we followed their progress. Methods: In our single‐center study, we retrospectively reviewed 14 cases of children who visited the Division of Pediatric Neurology in the Department of Pediatrics of Chonnam National University Hospital due to NAE following monovalent influenza A (H1N1) vaccination between November 2009 and March 2010. Results: Clinical diagnoses for major NAE included: polyneuropathy in the extremities (11/14, 78.6%), sensory mononeuropathy with numbness in the left fibula area (1/14, 7.1%), Bell's palsy (1/14, 7.1%) and recent‐onset acute headache only (1/14, 7.1%). Therefore, most patients were diagnosed as having peripheral neuropathy (13/14, 92.9%), and two met the Brighton Collaboration Guillain–Barré syndrome definition criteria for level 3 (the lowest level of diagnostic certainty). Conclusions: Post‐vaccine NAE were mainly motor weakness due to polyneuropathy, which had a good prognosis of complete improvement within a few months without sequelae.     

Anorexia nervosa in male adolescents. II. Psychoneuroendocrinologic findings

Female patients with anorexia nervosa (a.n.) are characterized by distinct endocrine features probably due to hypothalamic pituitary dysfunctions. There is only a limited number of case reports available on patients with a.n.; mostly with few data on hormones. In six male patients with a.n. we examined basal and stimulation values of several hormones performing three pituitary function tests. Basal and stimulated values of luteinizing hormone (LH) and of follicle stimulating hormone (FSH) after LHRH were low comparable to results in prepuberal boys. Similarly, testosterone levels in serum were also markedly reduced. By exploring the pituitary-thyroidal axis total T4 was diminished in one patient and at the lower limit in two patients; concentration of free T4 was in the normal range, while five of six subjects had reduced total T3 concentration and two of six patients showed increased reversed T3 levels; TBG concentration was always in the normal range. Basal TSH was normal, while in two patients the TSH stimulation levels after TRH were diminished; in all patients the TSH stimulation levels were found to be delayed. The basal levels of growth hormone were normal, but the growth hormone response after insulin was diminished in four patients. In all six patients basal prolactin (PRL) and PRL concentration after TRH stimulation was in the normal range. The neuroendocrine results in the six patients with a.n. confirm in males a similar hypothalamic-pituitary dysfunction as it is already known for female patients.     

氨基末端脑利钠肽前体在室间隔缺损合并心力衰竭诊断中的价值

目的　探讨血浆氨基末端脑利钠肽前体(NT-proBNP)水平在室间隔缺损合并心力衰竭(简称心衰)诊断及心功能评估中的价值。方法　51例室间隔缺损患儿,按照小儿心衰改良Ross标准分为 0~2分 (无心衰 )、3 ~6分 (轻度心衰 )、7 ~12分 (中 重度心衰 )三组;对照组 15例。应用ELASA方法测定血浆NT proBNP浓度。同时测定左室舒张末期容量指数(leftventricularenddiastolicvolumeindex,LVEDVI)、左室收缩末期室壁应力(leftventricularendsystolicwallstress,LVESWS)、心率校正的平均周径缩短速率(heartratecorrectedmeanvelocityofcircumferentialfibershortening,mVcFc)、左室射血分数 (leftventricularejectionfraction,LVEF)、左室缩短分数 (leftventricularfractionalshortening,LVFS)、心肌收缩力 (contractilityindex,Con)等超声心动图指标。结果　 ( 1 )血浆NT proBNP水平与临床评分之间呈明显正相关 (r=0. 75,P<0. 01 ),中 重度心衰组 [ ( 2061±908 )fmol/ml]高于轻度心衰组[ (810±335)fmol/ml];轻度心衰组高于无心衰组[ (309±68)fmol/ml];但是无心衰组与正常对照组间[ (275±62)fmol/ml]差异无统计学意义。(2)血浆NT proBNP水平与LVESWS、LVEDVI呈正相关;与LVEF、LVFS、Con、mVcFc等无明显相关性。 ( 3     

Spontaneous closure of ventricular septal defects followed up from <3 months of age

BACKGROUND: This study evaluates the incidence and timing of spontaneous closure (SC) of ventricular septal defect (VSD) using Doppler color flow mapping. METHODS: A total of 225 infants (mean age 30 days) were diagnosed with uncomplicated VSD: 31 (14%) subpulmonary VSD, 159 (70%) perimembranous, and 35 (16%) muscular. The patients were divided into two groups according to the presence or absence of congestive heart failure (CHF). SC was confirmed with color Doppler. RESULTS: Surgical closure was performed in 59 patients (26%). SC occurred in 107 patients (48%); three (10%) of 31 with subpulmonary VSD, 75 (47%) of 159 with perimembranous VSD, and 29 (83%) of 35 with a muscular VSD. Average age at SC was 19 months. In three SC patients with a subpulmonary VSD, there was no aortic valve prolapse and no aortic regurgitation. SC occurred in 96% of SC patients with a perimembranous VSD by the age of 6 years, and in 93% of those with a muscular VSD by the age of 3 years. In patients without CHF, the rate of SC was 72%; 23% in subpulmonary VSD, 74% in perimembranous, and 85% in muscular. SC occurred in only 23% of patients with a perimembranous VSD with CHF. Mean age at the final examination was 6.9 years in 59 patients with a VSD remaining open, and 63% of patients with a perimembranous VSD remaining open had an aneurysm of the ventricular membranous septum. CONCLUSIONS: The SC rate of VSD by mean age of 6.9 years was 48%, but it was 72% in patients without CHF. In patients with CHF, SC was seen only in patients with a perimembranous VSD. The rate of SC was 10% in subpulmonary VSD. The authors contend that SC probably occurred by growth of muscular septum surrounding VSD. Muscular VSD spontaneously closed earlier than perimembranous VSD.     

Anthracycline—Induced Congestive Heart Failure in two Pediatric Leukemia Cases and Long Term Follow—Up

Endomyocardial biopsy was performed on two leukemia patients who had recovered from severe congestive heart failure (CHF) due to anthracycline cardiomyopathy at 41 months and 47 months after CHF. Microscopic myocardial findings in both patients revealed that myocytes were hypertrophic, but interstitial fibrosis was not observed, suggesting a compensatory mechanism for the damaged heart muscle during the acute episode of CHF. The improvement of clinical symptoms and the normalization of cardiac function, including fractional shortening and ECG changes, is thought to have been associated with this myocardial repairing process.     

Impaired skin fibroblast carnitine uptake in primary systemic carnitine deficiency manifested by childhood carnitine-responsive cardiomyopathy

Evidence is emerging that primary systemic carnitine deficiency, a potentially lethal but eminently treatable inborn error of fatty acid oxidation, involves a cellular defect in the uptake of carnitine. We present four unrelated children with primary carnitine-responsive cardiomyopathy, weakness (with or without hypoketotic hypoglycemic encephalopathy), low serum and/or tissue carnitine concentrations, and severe renal carnitine leak. Dicarboxylic acids were absent in the urine of three children who were tested, and all four had a rapid and dramatic improvement in cardiac function, strength, and somatic growth after carnitine therapy. We studied carnitine uptake in cultured skin fibroblasts from all four children and seven of the eight healthy nonconsanguinous parents. [3H]L-carnitine uptake was evaluated in vitro under linear time kinetics. Substrate concentrations were varied from 0.1 to 1000 microM. Physiologic uptake was determined at carnitine concentrations between 0.1 and 50 microM. Nonspecific uptake was determined at a concentration of 10 mM. The four patients had negligible uptake throughout the physiologic range, implying a marked deficiency in the specific high-affinity, low-concentration, carrier-mediated uptake mechanism. At a concentration of 5 mumol/L, the mean velocity of uptake in the four patients was 2% of control values. Their parents showed intermediate maximal rates of carnitine uptake ranging from 13 to 44% of control Vmax values, but normal Km values, suggesting that the heterozygotes had a reduced number of normal functioning carnitine transporters. The observed reduction in Vmax values for the parents supports an autosomal recessive inheritance pattern and may be a more sensitive indicator of heterozygosity than serum carnitine concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)