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Biomedical subjects

R Shamir

Publications and source records attributed to R Shamir.

70 records · Page 4Linked to original sources

Total parenteral nutrition-associated cholestasis after selective damage to acinar zone 3 hepatocytes by bromobenzene in the rat.

Total parenteral nutrition is known to cause cholestasis, but the hepatic site of this effect has not been determined. The purpose of our study was to observe the effect of TPN on bile flow and bile salt secretion rate in rats after selective damage to acinar zone 3. Bromobenzene, 3.8 mmol/kg, was injected i.p., and the animals were studied 48 hours later. Experimental groups received either parenteral nutrition or saline for 2 hours. Bromobenzene caused selective damage to acinar zone 3 hepatocytes, and reduced baseline bile flow (23.99 +/- 1.09 vs 37.2 +/- 1.66, mean +/- SEM, microliter/min/kg, p < 0.001). Bromobenzene had no effect on bile salt secretion rate. Total parenteral nutrition decreased bile flow in the bromobenzene treated groups, despite the selective hepatic damage to acinar zone 3 (20.54 +/- 1.07 vs 23.28 +/- 1.63, mean +/- SEM, p < 0.001). Total parenteral nutrition reduced bile salt secretion rate in healthy animals, but this reduction was not seen in bromobenzene treated rats. Our results suggest that bile flow reduction in response to total parenteral nutrition is mediated through an effect on acinar zones 1 and 2, as this reduction is still observed after zone 3 destruction by bromobenzene. Zone 3 hepatocytes may be involved in the effect of parenteral nutrition on bile salt secretion, as the reduction in secretion rate seen in healthy animals was not observed in bromobenzene treated rats.

Analysis of Variance↗

Risk of infection during adrenocorticotropic hormone treatment in infants with infantile spasms.

We reviewed the clinical features and laboratory findings of 27 infants with infantile spasms treated with adrenocorticotropic hormone or prednisone during febrile episodes in order to evaluate the incidence of bacteremia, the risk of serious infection, determination of whether serious infections can be identified at presentation and the outcome of febrile episodes. There were 75 febrile episodes including 4 episodes of identified bacteremia (5.3%). Three children who were treated with adrenocorticotropic hormone dosage larger than recommended died. Leukocytosis and a differential count with many immature granulocytes predicted bacteremia in this population. Chest radiography was useful in identifying the cause of fever. The pathogens isolated were similar to those found in this age range. We conclude that the frequency of bacteremia in our patient population is similar to that observed in infants of the same age; however, the outcome is frequently fatal. In addition this increased mortality may be associated with the use of a larger dosage of adrenocorticotropic hormone than recommended.

Adrenocorticotropic Hormone↗

Bromobenzene accelerates hepatocyte streaming in rats.

Sixty male adult rats weighing between 250 and 300 g were divided in two equal experimental groups. The first experiment was designed to evaluate hepatocyte streaming. Animals were injected with 0.5 microCi [3H]thymidine and 1 hour later received one intraperitoneal injection of bromobenzene (3.8 mmol/kg, dissolved in corn oil). The animals were then killed in groups of five at 1 hour and 2, 4, 7, 14, and 30 days. The aim of the second experiment was to evaluate labeling index changes with time. Animals received one intraperitoneal injection of bromobenzene and were killed in groups of five at 1, 2, 3, 4, 7, and 14 days. They received [3H]thymidine 1 hour before killing. Bromobenzene induced a necrosis in the third acinus zone that disappeared within a week. On day 0 the labeling index of hepatocytes and littoral cells was 0.3% +/- 0.04% and 0.4% +/- 0.05%, respectively. On the second day, it reached 14.6% +/- 2.6% and 10.1% +/- 3.1% and returned to its initial value after 1 week. Dead cells in the third zone were replaced by inflowing cells from the intact zones. Hepatocytes and littoral cells streamed at the same velocity of 6 +/- 0.5 micron/day, faster than in untreated animals with velocity of 3.2 microns/day. Parenchyma and stroma responded to injury in a coordinated fashion. From the functional point of view, hepatocytes and littoral cells operate as a unit that is called proliferon. The maximal proliferon life span was 57 days after bromobenzene treatment and 108 days in controls.

Animals↗

Nevus flammeus. Discordance in monozygotic twins.

Nevus flammeus has been described as an inherited vascular anomaly. We report two cases of nevus flammeus, each appearing in one of two monozygotic twins. This finding supports the idea that nevus flammeus results from embryologic mishap rather than genetic transmission.

Adolescent↗

Butterfly-shaped mark: a variant form of nevus flammeus simplex.

A red-violet, rhomboid-shaped mark on the sacrum of 25 children is described. It is recognized, for the first time, as a part of the nevus flammeus simplex distribution; it is less common than the erythema nuchae or the facial salmon patch. It has the tendency to disappear more slowly than other forms of nevus flammeus simplex. No further investigations seem indicated.

Child↗

Alagille syndrome associated with moyamoya disease.

A 22-month-old girl with the typical manifestations of Alagille syndrome presented with acute right hemiparesis. Cerebral angiographic studies demonstrated the presence of complete occlusion of both internal carotid arteries with the formation of a collateral network of vessels compatible with the diagnosis of Moyamoya disease. This rare association has not been reported previously.

Arterial Occlusive Diseases↗

Sacral nevus flammeus simplex: the role of imaging.

Neonates with midline lumbar, thoracic, or occipital cutaneous lesions should be suspected of having spinal dysraphism and should undergo an imaging study. The aim of the present study was to evaluate whether sacral nevus flammeus simplex (SNFS) in neonates is associated with spinal dysraphism. During a period of 6 months, we prospectively examined all neonates in our center for the presence of SNFS. Those affected were evaluated for associated anomalies by physical and neurologic examination and ultrasound imaging of the lumbosacral area. Twenty-eight of 3623 neonates (0.77%) were diagnosed as having SNFS. In 64% of the SNFS patients, nevus flammeus simplex (NFS) was noted as well. Physical and neurologic examinations were unremarkable. Ultrasound imaging of the lumbosacral area was performed in 25 patients (89%) and revealed diastematomyelia in one. The results show that SNFS may constitute the only cutaneous sign of spinal dysraphism. In conclusion, we recommend that neonates with SNFS be investigated for occult spinal dysraphism.

Female↗

Algorithms for optical mapping.

Optical mapping is a novel technique for determining the restriction sites on a DNA molecule by directly observing a number of partially digested copies of the molecule under a light microscope. The problem is complicated by uncertainty as to the orientation of the molecules and by erroneous detection of cuts. In this paper we study the problem of constructing a restriction map based on optical mapping data. We give several variants of a polynomial reconstruction algorithm, as well as an algorithm that is exponential in the number of cut sites, and hence is appropriate only for small number of cut sites. We give a simple probabilistic model for data generation and for the errors and prove probabilistic upper and lower bounds on the number of molecules needed by each algorithm in order to obtain a correct map, expressed as a function of the number of cut sites and the error parameters. To the best of our knowledge, this is the first probabilistic analysis of algorithms for the problem. We also provide experimental results confirming that our algorithms are highly effective on simulated data.

Algorithms↗

Clustering gene expression patterns.

Recent advances in biotechnology allow researchers to measure expression levels for thousands of genes simultaneously, across different conditions and over time. Analysis of data produced by such experiments offers potential insight into gene function and regulatory mechanisms. A key step in the analysis of gene expression data is the detection of groups of genes that manifest similar expression patterns. The corresponding algorithmic problem is to cluster multicondition gene expression patterns. In this paper we describe a novel clustering algorithm that was developed for analysis of gene expression data. We define an appropriate stochastic error model on the input, and prove that under the conditions of the model, the algorithm recovers the cluster structure with high probability. The running time of the algorithm on an n-gene dataset is O[n2[log(n)]c]. We also present a practical heuristic based on the same algorithmic ideas. The heuristic was implemented and its performance is demonstrated on simulated data and on real gene expression data, with very promising results.

Algorithms↗

Thiamine deficiency in children with congenital heart disease before and after corrective surgery.

BACKGROUND: Malnutrition is common in children with congenital heart disease, while thiamine deficiency (TD) is common in malnutrition, in critically ill children, and in adults with congestive heart failure treated with loop diuretics. Our goal was to determine whether children with congenital heart disease had TD and whether treatment with loop diuretics is related to TD in these patients. METHODS: Twelve children with ventricular septal defect (VSD) treated with furosemide, and 10 children with tetralogy of Fallot (TOF) referred for corrective surgery were consecutively enrolled into a prospective study. Data were collected 24 hours before surgery and 5 days after surgery for nutrition evaluation, medications used, anthropometric measurements, and laboratory markers of malnutrition. Thiamine and pyridoxine deficiencies were evaluated using activated enzyme assays. RESULTS: Seven children (32% of patients) did not meet the recommended daily allowance (RDA) for calories and 18% of patients did not meet the RDA for thiamine intake. Anthropometric measurements were low in both groups, more so in those with VSD, although the difference did not reach statistical significance. Overall, 18% (1/12 with VSD and 3/10 with TOF) of children with congenital heart disease had thiamine deficiency before surgery. Three of the four children with TD had adequate intake of thiamine. Six children (27%) had TD 5 days postsurgery (3 children with VSD and 3 children with TOF). CONCLUSIONS: TD is common in children with congenital heart disease (CHD) referred for corrective surgery both before and after surgery. Our results suggest that neither diuretic treatment nor malnutrition can fully explain the development of TD in these children.

Anthropometry↗

Parenteral nutrition-associated cholestasis in preterm neonates: evaluation of ursodeoxycholic acid treatment.

BACKGROUND/OBJECTIVE: Parenteral nutrition is an integral part of the care of premature infants. Cholestatic liver disease is a frequent complication of prolonged parenteral nutrition, especially in premature infants. It has been suggested that ursodeoxycholic acid may alter the course of parenteral nutrition-associated cholestasis in children and adults. We attempted to determine the efficacy of ursodeoxycholic acid in premature infants with parenteral nutrition-associated cholestasis. METHODS: Retrospective chart review of all infants receiving ursodeoxycholic acid for parenteral nutrition-associated cholestasis in a 40 bed neonatal intensive care unit. Efficacy of ursodeoxycholic acid was evaluated by response of bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase over a treatment period of at least 1 month. RESULTS: Six infants with parenteral nutrition-associated cholestasis who had received ursodeoxycholic acid for one month were identified. Doses of ursodeoxycholic acid ranged from 15-30 mg/kg/day. Cholestasis appeared at a mean age of 47 +/- 17 (mean +/- SD) days after a mean of 42 +/- 15 days of parenteral nutrition. Transaminase levels decreased in three, and either increased or did not change in the other three infants. Bilirubin levels decreased in all infants. Alkaline phosphatase showed a non significant trend to decreased levels. Consistent improvement in all infants was noted only after 10 days of full enteral nutrition. No toxicity was found during ursodeoxycholic acid treatment. CONCLUSIONS: Ursodeoxycholic acid treatment in premature infants appears to be safe, and leads to an early sustained decrease in bilirubin levels by two weeks of therapy. The response of transaminase levels was not sustained in our small cohort.

Alanine Transaminase↗