Acute gastric perforation after acid ingestion

Gastric outlet obstruction is a common late result after acid ingestion; early complications, such as gastric necrosis or perforations are unusual. This is a report of a patient with the history of strong acid ingestion who underwent total gastrectomy due to perforation and extensive necrosis of the stomach.     

Survival rate in children with fulminant hepatitis improved by a combination of twice daily plasmapheresis and intensive conservative therapy

Six of seven children with fulminant hepatitis (FH) were treated with a combination of twice daily plasmapheresis and intensive conservative therapy including special amino acid solution, glucagon-insulin therapy, dexamethasone, and so on. The remaining child was treated with intensive conservative therapy only because his condition was not so severe, in spite of being diagnosed as having fulminant hepatitis. Although five patients with biopsy-documented bridging hepatic necrosis or confluent hepatic necrosis in the acute phase made recoveries, the remaining two with massive hepatic necrosis died (the overall survival rate was 71%). The prognostic factors were considered to be the degree and pattern of liver cell necrosis, the degree of coma, and the etiology. The combination of twice daily plasmapheresis and intensive conservative therapy was effective for these pediatric patients with fulminant hepatitis, except those with massive hepatic necrosis.     

Low dose,oral epsilon aminocaproic acid for renal papillary necrosis and massive hemorrhage in hemoglobin SC disease

Renal papillary necrosis in sickling hemoglobinopathies can lead to significant complications, including hemorrhage, obstruction, and infection. Despite its frequency, there are limited therapies for protracted hemorrhage. In the past, massive hemorrhage was managed with nephrectomy. Here, we report a patient with hemoglobin SC disease and prolonged, life‐threatening hemorrhage from papillary necrosis successfully treated with oral, low‐dose epsilon aminocaproic acid (EACA). Although further study is warranted, this case illustrates the need to consider EACA in the conservative management of renal papillary necrosis and significant hemorrhage in sickle cell hemoglobinopathies. Pediatr Blood Cancer 2010; 54:148–150. © 2009 Wiley‐Liss, Inc.     

Recurrent exercise-induced acute renal failure in renal hypouricemia

We describe a male patient with four episodes of acute renal failure after strenuous exercise occurring between the age of 14 and 25 years. He was found to have low serum uric acid (0.4mgdl⁻¹ after recovery) and high fractional excretion of uric acid. A benzbromarone, pyrazinamide test suggested that renal hypouricemia was due to defective proximal tubular reabsorption of uric acid at a pre-secretory site. A renal biopsy revealed acute tubular necrosis, a renal computer tomography scan showed patchy contrast enhancement and a treadmill exercise test induced an immediate fall in creatinine clearance. These findings suggest that the cause of acute renal failure was renal vasoconstriction rather than obstruction by uric acid crystals.     

Role of oxidant stress in the permeability transition induced in rat hepatic mitochondria by hydrophobic bile acids

Hydrophobic bile acids may cause hepatocellular necrosis and apoptosis during cholestatic liver diseases. The mechanism for this injury may involve mitochondrial dysfunction and the generation of oxidant stress. The purpose of this study was to determine the relationship of oxidant stress and the mitochondrial membrane permeability transition (MMPT) in hepatocyte necrosis induced by bile acids. The MMPT was measured spectrophotometrically and morphologically in rat liver mitochondria exposed to glycochenodeoxycholic acid (GCDC). Freshly isolated rat hepatocytes were exposed to GCDC and hepatocellular necrosis was assessed by lactate dehydrogenase release, hydroperoxide generation by dichlorofluorescein fluorescence, and the MMPT in cells by JC1 and tetramethylrhodamine methylester fluorescence on flow cytometry. GCDC induced the MMPT in a dose- and Ca(2+)-dependent manner. Antioxidants significantly inhibited the GCDC-induced MMPT and the generation of hydroperoxides in isolated mitochondria. Other detergents failed to induce the MMPT and a calpain-like protease inhibitor had no effect on the GCDC-induced MMPT. In isolated rat hepatocytes, GCDC induced the MMPT, which was inhibited by antioxidants. Blocking the MMPT in hepatocytes reduced hepatocyte necrosis and oxidant stress caused by GCDC. Oxidant stress, and not detergent effects or the stimulation of calpain-like proteases, mediates the GCDC-induced MMPT in hepatocytes. We propose that reducing mitochondrial generation of reactive oxygen species or preventing increases in mitochondrial Ca(2+) may protect the hepatocyte against bile acid-induced necrosis.     

亚细亚酸对兔未成熟肺缺血再灌注损伤的保护作用

目的 观察亚细亚酸对兔未成熟肺缺血再灌注损伤的保护作用。方法 选用15~21日龄新西兰白兔60只,分为5组：假手术组,对照组,亚细亚酸低、中和高剂量组,每组各12只。建立单肺缺血再灌注模型,肺门阻断1 h后,开放再灌注4 h。亚细亚酸低、中和高剂量组分别于术前3 d给予亚细亚酸7.5、15和30 mg·kg-1,假手术组仅开胸不阻断肺门,对照组不予干预。术毕收集肺组织,光镜和电镜观察肺组织病理和超微结构改变。测定肺组织丙二醛（MDA）,细胞毒性活性氧（ROS）-HR、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）水平。Western Blot检测髓样生化因子（MyD）88和核转录因子（NF-κB）水平。ELISA法检测IL-1β、TNF-α水平。结果 ①亚细亚酸中和高剂量组肺缺血再灌注损伤明显减轻,光镜下肺泡与肺泡间隔肿胀程度明显轻于对照组,肺泡腔渗液减少,出血少见。电镜下可见肺泡上皮与血管内皮细胞脱落明显减少。②亚细亚酸中和高剂量组较对照组肺组织MDA,ROS-HR水平明显降低,SOD及GSH-PX水平明显升高;各时点的IL-1β、TNF-α水平也有不同程度下降,特别是再灌注后的2 h和4 h(P<0.05);肺组织中MyD88和NF-κB表达显著下降。③亚细亚酸中和高剂量的保护效果较好。结论 亚细亚酸对未成熟肺缺血再灌注损伤有一定的保护作用,其机制与清除氧自由基和减轻全身炎性反应有关。     

Myocardial necrosis following general anesthesia in hemoglobin SC disease.

A 4-year-old girl with hemoglobin SC disease died following general anesthesia. Autopsy showed widespread intravascular sickling; staining with hematoxylin-basic fuchsin-picric acid demonstrated newly developed massive myocardial necrosis, a rarely documented finding. Anesthesia may produce conditions that provoke "crises" in patients with sickle hemoglobinopathies. Preoperative identification of sickle states and careful attention to hydration and oxygenation may minimize anesthetic risks in these patients.     

A rare complication due to sulfuric acid ingestion.

The authors present a case of pyloric and duodenal obstruction in an 8-year-old child, resulting from accidental ingestion of sulfuric acid. A marked pyloric and duodenal cicatrizing stenosis resulting from ingestion of sulfuric acid is seen infrequently, especially in pediatric age. Sulfuric acid produces a coagulation necrosis of the gastric mucosa and submucosa, and the process may involve the entire thickness of the gastric wall, with subsequent ulceration and fibrosis. This dynamic pathophysiologic event imposes postponement of surgical intervention because of various time length between ingestion of acid and onset of gastric outlet obstruction (17 days to 5 years). Clinical features included postprandial epigastric distress, repeated non-bilious vomiting, and marked weight loss. The authors also discuss the various surgical procedures that were employed to relieve the obstruction. Notwithstanding a potential risk of malignant evolution, a gastro-jejunostomy is the treatment of choice because of the age of the patient, and good postoperative results are confirmed by barium studies.     

Beta-carotene prevents bile acid-induced cytotoxicity in the rat hepatocyte: Evidence for an antioxidant and anti-apoptotic role of beta-carotene in vitro

Hydrophobic bile acids are implicated in the pathogenesis of cholestatic liver disorders through mechanisms involving oxidative stress and mitochondrial dysfunction. Antioxidants ameliorate bile acid-induced cytotoxicity in rat hepatocyte suspensions. The purpose of the current study was to evaluate the potential protective role of beta-carotene (betaC), a putative fat-soluble antioxidant that is reduced in patients with cholestasis, against bile acid-induced hepatotoxicity. In freshly isolated rat hepatocyte suspensions that were exposed to the toxic hydrophobic bile acid glycochenodeoxycholic acid (100 or 500 microM), betaC (100 microM) decreased generation of reactive oxygen species by >50%, similar to the inhibition afforded by alpha-tocopherol. Commensurate with this antioxidant effect, 100 microM betaC also protected hepatocytes against both glycochenodeoxycholic acid-induced cellular necrosis and apoptosis, which was associated with reduction in caspase 3 activation, inhibition of mitochondrial cytochrome c release in rat hepatocytes, and prevention of the mitochondrial permeability transition in both liver mitochondria and rat hepatocytes. A lower concentration of betaC (50 microM) produced similar antioxidant and anti-apoptotic protection but with less inhibition against cell necrosis, suggesting that the higher concentration of betaC may have conferred additional cytoprotection not directly related to its antioxidant function. These results demonstrate that the antioxidant effects of betaC may provide hepatoprotection against cholestatic liver injury by preventing bile acid-induced oxidative stress and mitochondrial perturbations.     

Aspiration cytology for diagnosis of tuberculosis--perspectives in India

Tuberculosis (TB) a common cause of mortality can readily be diagnosed by fine needle aspiration. The technique is a simple, cost effective, out patient procedure with a high diagnostic accuracy both in adults and children. The diagnostic morphologic findings comprise of epithelioid cell granulomas and giant cells with or without necrosis. Often an acute inflammatory exudate is obtained. Stain for acid fast bacilli immensely augments diagnosis especially in cases where necrosis or an inflammatory exudate is obtained. Culture studies on aspirated material are time consuming though diagnosis is enhanced. PCR can be applied to detect mycobacterial DNA and has been applied on aspirated material and found to be more sensitive in the detection of tuberculosis. In children TB of lymph nodes is readily identified and so also from other sites such as bone and soft tissues. In children FNAC also plays a role in detection of BCG adenitis, infection with atypical mycobacteria and co-existing infections such as HIV and AIDS.     

Amino acid transport systems beta and A in fetal T lymphocytes in intrauterine growth restriction and with tumor necrosis factor-alpha treatment

Intrauterine growth restriction (IUGR) is associated with reduced activity of placental amino acid transport systems beta and A. Whether this phenotype is maintained in fetal cells outside the placenta is unknown. In IUGR, cord blood tumor necrosis factor (TNF)-alpha concentrations are raised, potentially influencing amino acid transport in fetal cells. We used fetal T lymphocytes as a model to study systems beta and A amino acid transporters in IUGR compared with normal pregnancy. We also studied the effect of TNF-alpha on amino acid transporter activity. In fetal lymphocytes from IUGR pregnancies, taurine transporter mRNA expression encoding system beta transporter was reduced, but there was no change in system beta activity. No significant differences were observed in system A mRNA expression (encoding SNAT1 and SNAT2) or system A activity between the two groups. After 24 or 48 h TNF-alpha treatment, fetal T lymphocytes from normal pregnancies showed no significant change in system A or system beta activity, although cell viability was compromised. This study represents the first characterization of amino acid transport in a fetal cell outside the placenta in IUGR. We conclude that the reduced amino acid transporter activity found in placenta in IUGR is not a feature of all fetal cells.     

Minimal tissue concentrations of glutamate required to produce necrosis of hypothalamic neurons in newborn mice.

Groups of 4-day-old Cox Swiss albino mice were injected once subcutaneously with monosodium glutamate at several doses between 0.2 and 0.5 mg/g body weight. Glutamate, at a dose of 0.35 mg/g, produced neuronal necrosis of a very limited nature in only 60% of the animals and was defined as the minimal effective neurotoxic dose in the 4-day-old mouse. Neuronal loss was not detected in any animals treated with less than 0.35% mg/g of the amino acid whereas lesions became more extensive as the dose was increased to 0.5 mg/g. Glutamate was measured in the arcuate nucleus and plasma 0, 15, 30, 60 and 90 min after injection. These data indicated that duration of glutamate accumulation in the arcuate nucleus may be as important a variable in producing neuronal degeneration in the hypothalamus as concentration of the amino acid in that nucleus.     

Hypercalcämie und Adiponecrosis subcutanea mit Kalkablagerungen im frühen Säuglingsalter

Zusammenfassung Es wird über ausgedehnte Fettgewebsnekrosen mit Kalkablagerung und Hypercalcämie bei einem Säugling in den ersten Lebensmonaten berichtet. Wahrscheinlich handelt es sich um eine besonders schwere Verlaufsform der Adiponecrosis subcutanea neonatorum. Das Kind wurde erfolgreich mit calciumarmer Nahrung und Natriumsulfat behandelt. Als Ursache wird eine noch ungeklärte, generalisierte Stoffwechselentgleisung angenommen, die schon vor der Geburt einsetzt. Zur Diskussion gestellt wird eine Reaktion im Sinne der Calciphylaxie, wobei möglicherweise die Citronensäure eine Rolle spielt. Dem Vitamin D dürfte nur ein begünstigender Einfluß zukommen. Dennoch ist es ratsam, bei Säuglingen mit Adiponecrosis subcutanea mit der Gabe von Vitamin D zur Rachitisprophylaxe zurückhaltend zu sein.

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Summary An infant with extensive fat necrosis, subcutaneous calcification, and hypercalcemia is described. Massive subcutaneous calcifications were demonstrated by x-ray. Vitamin D activity in the serum, however, was found to be low, whereas citric acid was elevated in the serum and urine. The child was successfully treated with low-calcium diet and sodium sulfate.It is suggested that this case represents a severe course of subcutaneous fat necrosis of the newborn (Adiponecrosis subcutanea neonatorum). The possible pathogenesis of this disease (metabolic deficiency, calciphylaxis) is discussed.It is advised to be very cautious in the administration of Vitamin D to infants with subcutaneous fat necrosis.

     

White matter necrosis in very low birth weight infants: neuropathologic and ultrasonographic findings in infants surviving six days or longer

We describe the neuropathologic and ultrasonographic findings in 22 very low birth weight infants (mean weight 948 gm) who survived at least 6 days and for whom cranial ultrasonography had been performed three or more times in life. White matter necrosis was found in 15 of the 22 subjects and was judged chronic (5 days' duration or longer) in seven subjects. The most common pattern was diffuse necrosis of hemispheric white matter, found in 10 of 15 infants; restriction of necrosis to the periventricular region was found in only three infants. The classic histologic features of periventricular leukomalacia were absent from 7 of the 15 infants with necrosis. Seventeen infants had intraventricular hemorrhage, but extension of ventricular blood into white matter unaffected by infarction was not found. Two ultrasonographic features were associated with white matter necrosis: increased parenchymal echogenicity and ventricular enlargement. One or both of these findings were present in 67% of infants with white matter necrosis, in 90% of infants with diffuse necrosis, but in no infant without necrosis. Increased parenchymal echogenicity was seen in all four infants with hemorrhagic necrosis, in 60% of infants with diffuse necrosis, but in none of the five infants with localized necrosis. We conclude that the very small infants now dying in nurseries have a form of white matter damage that is more extensive than, and in some cases histologically different from, periventricular leukomalacia as originally described. Ultrasonography as used in this study identified most but not all infants with pathologically verified white matter necrosis.     

Hepatic Cell Necrosis with Congenital Heart Disease in the Newborn

Hepatic cell necrosis is a recognized complication of circulatory failure. Histological examination of the adult liver in such cases reveals centrilobular necrosis and hepatic congestion. Two cases of hepatic cell necrosis in infancy are reported: a four-day-old girl with the hypoplastic left heart syndrome, and a nine-day-old girl with interruption of the aortic arch. In the former, midzonal hepatic necrosis (and not centrilobular necrosis) was demonstrated at autopsy. Both patients exhibited severe hepatic insufficiency, but hepatic function improved rapidly with treatment of the coexistent heart failure. It is suggested that there is milder form of hepatic cell necrosis than that previously reported in autopsies.     

Endotoxin and hypoxia-induced intestinal necrosis in rats: the role of platelet activating factor.

We have previously shown that intravascular platelet activating factor (PAF) causes ischemic bowel necrosis in rats morphologically similar to neonatal necrotizing enterocolitis (NEC). Because endotoxin (LPS) and hypoxia are risk factors for NEC, we studied their effect on PAF metabolism and the development of intestinal injury. Young male Sprague-Dawley rats were anesthetized with pentobarbital and divided into six experimental groups: 1) control, 2) LPS alone (2 mg/kg), 3) hypoxia alone (5% O2), 4) LPS+hypoxia, 5) WEB 2086 (PAF antagonist)+LPS+hypoxia, and 6) SRI 63-441 (PAF antagonist)+LPS+hypoxia. Evaluations included blood pressure recording, superior mesenteric artery blood flow, arterial blood gas, white blood cell count, hematocrit, plasma PAF, plasma acetylhydrolase, plasma tumor necrosis factor, intestinal perfusion, and intestinal injury at 3 h. We found that LPS+hypoxia synergistically contributed to hypotension (mean blood pressure 27 +/- 5.6% baseline versus 101 +/- 3.9% control), metabolic acidosis (pH 7.05, base deficit 24 mEq/L), hemoconcentration, decreased superior mesenteric artery blood flow (2.2 +/- 0.3 mL/min versus 5.8 +/- 0.2 mL/min control), and intestinal injury. The morbidities resulting from LPS+hypoxia were partially or completely prevented by PAF antagonists. In addition, animals treated with LPS+hypoxia had neutropenia, elevated plasma acetylhydrolase, and elevated plasma TNF. These results suggest that endogenous PAF may contribute to LPS+hypoxia-induced intestinal hypoperfusion and necrosis.     

Percentage tumor necrosis following chemotherapy in neuroblastoma correlates with MYCN status but not survival

The percentage of chemotherapy-induced necrosis in primary tumors corresponds with outcome in several childhood malignancies, including high-risk metastatic diseases. In this retrospective pilot study, the authors assessed the importance of postchemotherapy necrosis in high-risk neuroblastoma with a histological and case notes review of surgically resected specimens. The authors reviewed all available histology of 31 high-risk neuroblastoma cases treated with COJEC (dose intensive etoposide and vincristine with either cyclophosphamide, cisplatin or carboplatin) or OPEC/OJEC (etoposide, vincristine and cyclophosphamide with alternating cisplatin [OPEC] or carboplatin [OJEC]) induction chemotherapy in 2 Children's Cancer & Leukaemia Group (CCLG) pediatric oncology centers. The percentage of postchemotherapy necrosis was assessed and compared with MYCN amplification status and overall survival. The median percentage of postchemotherapy tumor necrosis was 60%. MYCN status was available for 28 cases, of which 12 were amplified (43%). Survival in cases with ≥ 60% necrosis or ≥ 90% necrosis was not better than those with less necrosis, nor was percentage necrosis associated with survival using Cox regression. However, MYCN-amplified tumors showed a higher percentage of necrosis than non-MYCN-amplified tumors, 71.3% versus 37.2% (P = .006). This effect was not related to prechemotherapy necrosis and did not confer improved overall survival. Postchemotherapy tumor necrosis is higher in patients with MYCN amplification. In this study, postchemotherapy necrosis did not correlate with overall survival and should not lead to modification of postoperative treatment. However, these findings need to be confirmed in a larger prospective study of children with high-risk neuroblastoma.     

Percentage Tumor Necrosis Following Chemotherapy in Neuroblastoma Correlates with MYCN Status but not Survival

The percentage of chemotherapy-induced necrosis in primary tumors corresponds with outcome in several childhood malignancies, including high-risk metastatic diseases. In this retrospective pilot study, the authors assessed the importance of postchemotherapy necrosis in high-risk neuroblastoma with a histological and case notes review of surgically resected specimens. The authors reviewed all available histology of 31 high-risk neuroblastoma cases treated with COJEC (dose intensive etoposide and vincristine with either cyclophosphamide, cisplatin or carboplatin) or OPEC/OJEC (etoposide, vincristine and cyclosphosphamide with alternating cisplatin [OPEC] or carboplatin [OJEC]) induction chemotherapy in 2 Children's Cancer & Leukaemia Group (CCLG) pediatric oncology centers. The percentage of postchemotherapy necrosis was assessed and compared with MYCN amplification status and overall survival. The median percentage of postchemotherapy tumor necrosis was 60%. MYCN status was available for 28 cases, of which 12 were amplified (43%). Survival in cases with ≥60% necrosis or ≥90% necrosis was not better than those with less necrosis, nor was percentage necrosis associated with survival using Cox regression. However, MYCN-amplified tumors showed a higher percentage of necrosis than non–MYCN-amplified tumors, 71.3% versus 37.2% (P = .006). This effect was not related to prechemotherapy necrosis and did not confer improved overall survival. Postchemotherapy tumor necrosis is higher in patients with MYCN amplification. In this study, postchemotherapy necrosis did not correlate with overall survival and should not lead to modification of postoperative treatment. However, these findings need to be confirmed in a larger prospective study of children with high-risk neuroblastoma.     

Bone Marrow Necrosis Associated with Medulloblastoma

A 9-year-old Japanese boy with bone marrow necrosis associated with metastatic medulloblastoma is reported. The diagnosis of bone marrow necrosis was obtained nine months after operative removal of the medulloblastoma. Bone marrow necrosis was treated with a combination chemotherapy, but unfortunately he died of disseminated metastasis of medulloblastoma. This case suggests that the prognosis of bone marrow necrosis would be attributable to the behavior of the original tumor.     

Subcutaneous fat necrosis in newborn—an unusual case and review of literature

Subcutaneous fat necrosis (SCFN) of the newborn is an uncommon, self-limiting panniculitis mostly occurring within the first few weeks after birth. SCFN has been described mostly in term or post-term newborn infants in literature. We report a preterm infant developing extensive subcutaneous fat necrosis within the first week of life after significant perinatal hypoxic injury. The infant was conservatively managed for subcutaneous fat necrosis but developed hypercalcaemia and required prolonged medical treatment. Hypercalcaemia is a rare but serious complication of subcutaneous fat necrosis and needs prolonged follow-up. The etiopathogenesis of both subcutaneous fat necrosis in newborn and the resultant hypercalcaemia are poorly understood. Conclusion: Significant subcutaneous fat necrosis can develop in both preterm and term infants, and preterm infants also develop significant complications including hypercalcaemia.