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Biomedical subjects

S L Werlin

Publications and source records attributed to S L Werlin.

At least 37 records · Page 2Linked to original sources

Hepatocellular injury in Streptococcus pneumoniae-associated hemolytic uremic syndrome in children.

Streptococcus pneumoniae is an uncommon etiological organism in hemolytic uremic syndrome (HUS). Production of neuraminidase by S. pneumoniae results in exposure of red blood cell T-antigen, resulting in hemolysis, thrombocytopenia, and acute renal failure. Hepatic involvement in this form of HUS has not been described in the literature. We report in three children with S. pneumoniae-associated HUS the presence of severely elevated transaminases and conjugated hyperbilirubinemia. Increases in asparagine transaminase ranged from 11 to 46 times normal values and an increase in alanine transaminase ranged from 1.6 to 8 times normal. In all patients the rise in total bilirubin was 7-15 times normal. Biliary tree obstruction and viral causes for liver dysfunction were absent. Hepatocellular injury in S. pneumoniae-associated HUS likely results from mechanisms involved in sepsis and pneumonia-induced jaundice, combined with severely increased bilirubin production following massive hemolysis. The hepatic injury in all three patients resolved within 9, 5, and 10 days. Our experience suggests that an extensive evaluation including liver biopsy is not indicated.

Alanine Transaminase↗

The induction of hepatic cytochrome P450 3A in rats: effects of age.

Liver microsomal cytochrome P450 3A (CYP3A) concentrations were evaluated by Western blots using specific antisera. Low levels of CYP3A protein were found in untreated animals. Dexamethasone (DX) treatment resulted in a significant induction of CYP3A. The induction was dose and time dependent. Addition of U486 (a specific type II glucocorticoid receptor antagonist), but not spironolactone (a specific type I receptor antagonist) blocked the induction of CYP3A proteins by dexamethasone, suggesting a receptor-mediated mechanism. Concomitant administration of either actinomycin D or cyclohexamide, together with dexamethasone completely abolished the induction of CYP3A protein by dexamethasone, suggesting the requirement of both protein and RNA synthesis. A comparison of the inducibility of CYP3A protein by dexamethasone in rats from different age groups showed that the degree of increase was higher in the younger than in the older groups (e.g., 5 days versus adult). Thus, there is an attenuation in the responsiveness to dexamethasone induction of CYP3A proteins with age. Evaluation of the steady-state levels of CYP3A mRNA by Northern blots showed increases in mRNA following DX treatment in both young and old rats. The final level of CYP3A mRNA reached after DX treatment was higher in the pups than that found in similarly treated older rats. This decrease in responsiveness in older animals appeared to manifest at least in part of the pretranslational level.

Aging↗

Hypernatremic dehydration in breast-fed infants.

Three cases highlight the association between elevated breast milk sodium and hypernatremic dehydration in the infant. All three mothers, breast-feeding exclusively, had sodium levels in breast milk elevated significantly above normal. Severe hypernatremic dehydration in otherwise normal infants who are exclusively breast fed can be due to elevated sodium levels in breast milk.

Bottle Feeding↗

Proximal pH-metry for diagnosis of upper airway complications of gastroesophageal reflux.

Otolaryngologic complications of gastroesophageal reflux (GER) are well described in adults, but this relationship has not been as carefully studied in children. We reviewed 26 dual pH-probe studies performed on 22 children with upper airway symptoms. The proximal probe was placed in the nasopharynx or hypopharynx. The distal probe was placed in the mid-proximal oesophagus. The proximal recording was considered normal if no episodes of pH < 4 were recorded. Indications for the studies were upper airway obstruction (UAO) and congenital choanal atresia (CCA). The age range was from 2 weeks to 47 months. The distal pH probe study was normal in 13 of 22 patients overall. Seventeen UAO patients had abnormal proximal pH probe studies. After treatment, 16 of 17 had improved airways. Twelve with UAO (67%) were premature and/or had developmental delay. Three CCA patients had abnormal proximal pH-probe studies and all improved after treatment. Four follow-up pH studies were normal or improved. GER-induced UAO is more frequent in infants or children with a history of prematurity or developmental delay. Proximal pH-metry is a useful technique to document the relationship between upper airway symptoms and GER. Patients with GER-induced UAO should undergo endoscopy to rule out simultaneous airway lesions.

Airway Obstruction↗

Pancreatitis associated with remote traumatic brain injury in children.

Vomiting, abdominal distension, and feeding intolerance are common findings following brain injury in children, and are usually attributed to the brain injury or to delayed gastric emptying: a specific cause is usually not sought. We report six children who developed mild to moderate pancreatitis at least 7 days following apparently isolated brain injury, a previously unreported association. Five of the six patients received drugs that are known or suspected pancreatotoxins; all recovered without changes in the medications. When children develop feeding intolerance or upper gastrointestinal symptoms following traumatic brain injury pancreatitis should be suspected.

Acute Disease↗

Effect of abrupt discontinuation of high glucose infusion rates during parenteral nutrition.

We measured serum glucose and insulin levels in 15 children older than 2 years of age for 30 minutes after abrupt discontinuation of total parenteral nutrition. Initially high insulin levels rapidly became normal, and glucose levels were stable after 15 minutes. No patient had biochemical or symptomatic hypoglycemia. Glucose infusion rate, age, or use of steroid therapy had no apparent influence. Abrupt discontinuation of total parenteral nutrition is safe in most children older than 2 years of age.

Adolescent↗

Serious bacterial illnesses in recently hospitalized young infants.

We undertook a retrospective chart review of 27 patients less than 60 days of age, hospitalized for possible serious bacterial illness (SBI), but who were culture negative, and then readmitted within seven days for the same reason. Upon repeat evaluation for sepsis, five of these infants had significant illnesses; two (7.4%) had SBIs (one had pneumococcal bacteremia and the other a urinary tract infection), and three (11.1%) had aseptic meningitis. Our results suggest that young infants, despite recent hospitalization for possible SBI, may be at risk for a serious infectious process and need reevaluation if symptoms recur.

Bacterial Infections↗

Age and gender effect on the inducibility of steroid metabolizing cytochrome P450 in rat liver.

Liver microsomal steroid hydroxylases and 5 alpha reductase activities were evaluated by quantitation of specific metabolites from 4-C14 progesterone after TLC separation. Each enzyme showed a different developmental profile depending on the gender of the rat. Dexamethasone induced both 6 beta and 16 alpha progesterone hydroxylase, being more potent for 6 beta (3 to 4 folds) than 16 alpha (1.2 to 1.6 folds). A comparison of the inducibility of 6 beta and 16 alpha hydroxylase by dexamethasone in rats from different age groups showed that for both enzymes, the degree of increase was higher in the younger than older groups. Thus there is a blunting in the responsiveness to dexamethasone induction of both 6 beta and 16 alpha hydroxylase with age particularly in female animals. This decrease in responsiveness in older females could potentially affect their capacity to metabolize endogenous and exogenous agents.

Aging↗

Pancreatitis associated with brain tumor therapy.

PURPOSE: Four children with prolonged emesis during brain tumor therapy were diagnosed with pancreatitis. PATIENTS AND METHODS: All were exposed to medications or radiotherapy that potentially contributed to pancreatitis. CONCLUSIONS: Because recognition of pancreatitis may necessitate changes in supportive care, pancreatitis should be included in the differential diagnosis of vomiting in this population.

Adolescent↗

Endoscopic retrograde cholangiopancreatography in children.

Endoscopic retrograde cholangiopancreatography (ERCP) is playing an increasingly important role in the evaluation and treatment of children with disorders of the pancreas and biliary tree. In this article the technique, indications, and complications of diagnostic and therapeutic ERCP in children are reviewed. ERCP, when used properly, improves the ability of the clinician to diagnose and treat. Therapeutic ERCP reduces the need for surgery, and preoperative ERCP provides surgeons with a "road map" when surgery is required.

Abdominal Pain↗

Control and variability of gastric pH in critically ill children.

OBJECTIVES: To determine the effect of illness severity and acute central nervous system injury on the control and variability of gastric pH in pediatric intensive care unit (ICU) patients receiving ranitidine. DESIGN: Prospective, descriptive study. SETTING: Pediatric ICU of a children's hospital. PATIENTS: Fourteen pediatric ICU patients. INTERVENTIONS: Ranitidine (4 mg/kg/day) was administered to all patients. MEASUREMENTS AND MAIN RESULTS: Patients enrolled in the study were divided into two groups based on illness type and severity. Illness severity was measured by the Pediatric Risk of Mortality (PRISM) score, with a PRISM score of > or = 20 defining severe illness. Illness type was designated as central nervous system or noncentral nervous system. Gastric pH was continuously monitored in all patients using an intragastric, pH-sensitive electrode. Poor control of gastric pH was defined as a pH of < 4.0 for > 20% of the time monitored. The statistical significance of the differences between groups was measured using the Wilcoxon two-sample test or Fisher's exact test. Patients with severe illness or acute central nervous system injury had a lower mean gastric pH than all other patients (4.6 vs. 6.4; p = .008) and spent more time with a gastric pH of < 4.0 than other patients (47.5% of time monitored vs. 12.5% of time monitored; p = .003). Poor control of gastric pH occurred in 100% of patients with severe illness or acute central nervous system injury, while only 20% of the remaining patients had poor control of gastric pH (p = .01). Using power-spectrum analysis to evaluate gastric pH variability, gastric pH in patients receiving bolus ranitidine was more variable than gastric pH in patients receiving ranitidine continuously (p = .045). Illness severity or type had no effect on gastric pH variability (p = .78). CONCLUSIONS: a) Continuous infusion of ranitidine decreases variability of gastric pH in pediatric ICU patients; b) gastric pH variability may make intermittent monitoring of gastric pH inaccurate; c) children with acute central nervous system injury or PRISM scores of > or = 20 have poor control of gastric pH; d) type of injury and PRISM scores predict response to ranitidine therapy.

Central Nervous System Diseases↗

The diagnostic and therapeutic role of endoscopic retrograde cholangiopancreatography in children.

We performed 121 endoscopic retrograde cholangiopancreatographies (ERCPs) in 92 patients (60 girls and 32 boys), aged 4 months to 19 years, as part of diagnostic evaluation for suspected pancreatic or biliary tract disease or as therapeutic intervention. ERCP was successful in 116 attempts. The most common indications were recurrent pancreatitis (35 children), nonresolving acute pancreatitis (20), unexplained elevated amylase or lipase (19), postcholecystectomy syndrome (14), and elevated biliary tract enzymes (12). One hundred and one ERCPs were performed for more than one indication. The most common findings included chronic pancreatitis (26 cases), pancreas divisum (14), dilated pancreatic duct (10), gallstones or sludge (8), and abnormal common bile duct (8). Complications were uncommon and usually minor. ERCP is a safe and helpful procedure in the evaluation of suspected pancreatic and biliary tract disease in children and frequently allows for nonoperative treatment of these disorders.

Abdominal Pain↗

Development of lipolytic activity in gastric aspirates from premature infants.

Neonates, having little or no pancreatic lipase, would have a compromised ability to digest lipids if not for lingual and gastric lipases. To document the postnatal developmental profile of preduodenal lipase activity, 350 premature infants who were at various gestational ages and who had an orogastric tube had their gastric aspirates collected. Two hundred one infants had their gastric aspirates collected within 12 h after delivery. Serial collections were performed in 25 infants at various postnatal ages. Gastric aspirates collected from premature infants had a pH activity profile similar to that of lingual and gastric lipase but different from that of pancreatic lipase, indicating that their origin was from the tongue and/or stomach. Lipolytic activity and pH of these aspirates were quite variable, but no correlation was found between pH and enzyme activity. At birth, lipase activity was lower in the younger infants (< or = 26 weeks, n = 13). It increased to a peak at 30-32 weeks of gestational age and then declined to a lower level at term (> or = 40 weeks, n = 40). Postnatally, a composite plot of the serially collected aspirates also showed a predominant peak at 28-33 weeks of age. Comparison among siblings in twins (n = 12 pairs) and triplets (n = 3) showed great variations in their lipolytic activities, suggesting that the hereditary factor is not a major determinant. Various combinations of antibiotic medications (ampicillin, cefotaxime, gentamicin, and vancomycin) and drugs (dexamethasone, heparin, furosemide, phenobarbital, albumin, and vitamin K) apparently had no effect on the level and development of gastric lipolytic activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Thyroidal regulation of lingual lipase development in suckling rats.

Rat lingual lipase undergoes maturational increases during postnatal development. The role of thyroxine (T4) in the control of lingual lipase during development was evaluated. T4 given at an early suckling stage (starting day 4 or 5) moderately increased lingual lipase (20-30%) compared to age-matched controls. A similar dose of T4 given later (age > 2 weeks) was ineffective. The T4-sensitive period coincides with a time of low circulating T4, suggesting a role of T4 in modulating the development of lingual lipase in rat pups. Since simultaneous treatment with U486, a type II glucocorticoid receptor antagonist only partially blocked the T4 induction of lingual lipase, T4 appeared to have a direct action on the lingual gland. Pups of propylthiouracil (PTU)-treated dams (previously found to be hypothyroid) showed a delay in the maturation of lingual lipase compared to age-matched pups whose dam was not given PTU. Pups were most sensitive to PTU in the early suckling stage. PTU-induced delayed maturation of lingual lipase was a result of hypothyroidism, since T4 replacement when given early (at the age of 5 days) abolished most of the effect of PTU. When T4 was given later (at the age of 10 days), recovery was much less. This suggests the presence of an early period that is critically dependent on T4 for the full expression of lingual lipase in the rat tongue serous glands.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Crohn's disease presenting as unilateral labial hypertrophy.

We describe a child who had unilateral hypertrophy of the vulva, a rare extraintestinal manifestation of Crohn's disease. A biopsy specimen revealed a noncaseating granuloma. Flexible sigmoidoscopic examination revealed punctate 1 mm lesions with surrounding erythema in the rectum and sigmoid colon. Response to treatment with sulfasalazine was excellent. Gastrointestinal symptoms developed 1 year later when sulfasalazine was discontinued.

Child↗

Developmental delay of lingual lipase expression after guanethidine-induced sympathectomy.

Rat lingual lipase increases during postnatal development. To evaluate the role of the sympathetic nervous system in the control of lingual lipase during development, suckling rats were chemically sympathectomized by chronic treatment with guanethidine. This treatment was found to be effective in suppressing the developmental increase of lingual lipase. The effect was age dependent and also related to the dose of guanethidine given (i.e., the higher the dose, the more effective the suppression is, up to 40 micrograms/g body wt). The effect of guanethidine on lingual lipase suppression was not a result of induced stress, since simultaneous treatment with RU-38486, a known glucocorticoid receptor antagonist, did not prevent the decrease in lingual lipase activity. Ephedrine, a known sympathomimetic agent, restored the lingual lipase to a near normal level in guanethidine-treated animals, confirming that guanethidine acts through the sympathetic nerves. Furthermore, histochemical studies showed that guanethidine-treatment resulted in the reduction or elimination of catecholaminergic fibers in the von Ebner's glands. The effect of guanethidine was found to be transient, in that the lingual lipase activity showed complete recovery upon withdrawal of the treatment for 1 week. Together, the results indicated that sympathetic nerves have an important regulatory role in lingual lipase in rat pups during development.

Age Factors↗

Herpetic esophagitis in an immunocompetent boy.

An immunocompetent 12-year-old boy had epigastric pain, odynophagia, fever, and hematemesis. Esophagoscopy demonstrated ulceration of his proximal and distal esophagus. Although histopathologic analysis of biopsies obtained from the lesions was nondiagnostic, herpes simplex virus type 1 was isolated from these samples. The patient responded rapidly to acyclovir therapy. Only a handful of cases of herpes esophagitis have been reported previously in immunocompetent children. This infection must be considered in children having odynophagia and fever, even if they are not immune compromised.

Acyclovir↗