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Biomedical subjects

Y Kluger

Publications and source records attributed to Y Kluger.

At least 19 recordsLinked to original sources
PubMed2006

Endoscopic sphincterotomy and temporary internal stenting for bile leaks following complex hepatic trauma.

BACKGROUND: Biliary leak secondary to blunt or penetrating hepatic trauma and damage to the intrahepatic biliary tree remains a challenging problem. The role and safety of endoscopic retrograde cholangiopancreatography (ERCP) and stenting in this setting were studied. METHODS: All trauma victims who developed a bile leak secondary to hepatic trauma were included. Bile leak was defined as the appearance of bile in a surgical wound or intra-abdominal drain after surgery, following percutaneous drainage of a perihepatic bile collection, or evidence of a leak on hepatobiliary scintigraphy. ERCP was performed within 24 h of diagnosis and included biliary sphincterotomy and internal stenting. Recovery was defined as cessation of leakage. RESULTS: Between 1996 and 2004, six patients with penetrating injuries and five with blunt abdominal injuries were treated according to the study protocol. Eight underwent surgery to control bleeding or for additional intra-abdominal injuries. All bile leaks resolved completely within 10 days of ERCP. One patient died from pulmonary sepsis; ten recovered without hepatobiliary sequelae. CONCLUSION: ERCP, biliary sphincterotomy and temporary internal stenting, together with percutaneous drainage of intra-abdominal or intrahepatic bile collections, represent a safe and effective strategy for the management of bile leaks following both blunt and penetrating hepatic trauma.

Adolescent↗
PubMed2004

Recombinant activated factor VII (NovoSeven): addition to replacement therapy in acute, uncontrolled and life-threatening bleeding.

BACKGROUND AND OBJECTIVES: Recombinant activated factor VII (rFVIIa, NovoSeven) has been used off-label for various conditions. A protocol for its use in acute, uncontrolled life-threatening bleeding, was devised and employed. A haematologist/transfusion specialist was assigned as a member of the team. MATERIALS AND METHODS: The clinical data were reviewed and summarized. A scoring system for the assessment and monitoring of coagulopathy was employed. Each parameter of prothrombin time (PT), activated partial thromboplastin time (aPTT), platelet number and fibrinogen level was allocated points according to the degree of abnormality. Three scoring levels emerged. RESULTS: Between April 2001 and April 2003, 13 patients received rFVIIa for acute, uncontrolled life-threatening bleeding. Nine of 13 patients remained alive for 15 days or longer after rFVIIa infusion. All patients who experienced a reduction or cessation of bleeding after rFVIIa infusion, also had a lower coagulopathy score after replacement therapy, prior to rFVIIa infusion, compared with their score at rFVIIa request. There was a reduction in the average use of blood products after rFVIIa infusion. The coagulopathy score was statistically predictive of response to rFVIIa and survival. CONCLUSIONS: In an area where very little data exists, we report the usefulness of rFVIIa. We propose that transfusion replacement should aim to correct coagulopathy before infusion of rFVIIa and that a haematologist/transfusion specialist should be involved in the management of these patients. A prognostically significant coagulopathy scoring system is offered.

Acute Disease↗
PubMed2004

Terror bombing-mechanisms, consequences and implications.

Our objective in this review is to describe the unique features of bombing injury and to outline some special elements of their management. This is to allow the timely improvement and adjustment of existing mass casualty protocols. Forensic studies, detonation and explosion, mechanisms of injury in explosion and their bodily effects, chemical effects of the explosive, site of the explosion and the wounding potential, the Multidimensional Injury Pattern, diagnostic evaluation of Multidimensional Injury Pattern, and surgical and treatment dilemmas associated with it are described and discussed.

Blast Injuries↗
PubMed2002

Portal vein air embolization after blunt abdominal trauma: a case report and review of the literature.

Gas in the portal vein is a rare and often fatal condition in surgical patients. However, the presence of gas in the mesenteric and portal veins in association with abdominal trauma is a transient incidental finding that resolves spontaneously. We describe a young patient with Crohn's disease who suffered air embolism of the portal veins secondary to blunt abdominal trauma. The condition was clinically benign and resolved spontaneously. The pathogenesis is discussed and a review of the literature is provided.

Abdominal Injuries↗
PubMed2001

Genomic and proteomic analysis of the myeloid differentiation program.

Although the mature neutrophil is one of the better characterized mammalian cell types, the mechanisms of myeloid differentiation are incompletely understood at the molecular level. A mouse promyelocytic cell line (MPRO), derived from murine bone marrow cells and arrested developmentally by a dominant-negative retinoic acid receptor, morphologically differentiates to mature neutrophils in the presence of 10 microM retinoic acid. An extensive catalog was prepared of the gene expression changes that occur during morphologic maturation. To do this, 3'-end differential display, oligonucleotide chip array hybridization, and 2-dimensional protein electrophoresis were used. A large number of genes whose mRNA levels are modulated during differentiation of MPRO cells were identified. The results suggest the involvement of several transcription regulatory factors not previously implicated in this process, but they also emphasize the importance of events other than the production of new transcription factors. Furthermore, gene expression patterns were compared at the level of mRNA and protein, and the correlation between 2 parameters was studied. (Blood. 2001;98:513-524)

Animals↗
PubMed2001

SPINE: an integrated tracking database and data mining approach for identifying feasible targets in high-throughput structural proteomics.

High-throughput structural proteomics is expected to generate considerable amounts of data on the progress of structure determination for many proteins. For each protein this includes information about cloning, expression, purification, biophysical characterization and structure determination via NMR spectroscopy or X-ray crystallography. It will be essential to develop specifications and ontologies for standardizing this information to make it amenable to retrospective analysis. To this end we created the SPINE database and analysis system for the Northeast Structural Genomics Consortium. SPINE, which is available at bioinfo.mbb.yale.edu/nesg or nesg.org, is specifically designed to enable distributed scientific collaboration via the Internet. It was designed not just as an information repository but as an active vehicle to standardize proteomics data in a form that would enable systematic data mining. The system features an intuitive user interface for interactive retrieval and modification of expression construct data, query forms designed to track global project progress and external links to many other resources. Currently the database contains experimental data on 985 constructs, of which 740 are drawn from Methanobacterium thermoautotrophicum, 123 from Saccharomyces cerevisiae, 93 from Caenorhabditis elegans and the remainder from other organisms. We developed a comprehensive set of data mining features for each protein, including several related to experimental progress (e.g. expression level, solubility and crystallization) and 42 based on the underlying protein sequence (e.g. amino acid composition, secondary structure and occurrence of low complexity regions). We demonstrate in detail the application of a particular machine learning approach, decision trees, to the tasks of predicting a protein's solubility and propensity to crystallize based on sequence features. We are able to extract a number of key rules from our trees, in particular that soluble proteins tend to have significantly more acidic residues and fewer hydrophobic stretches than insoluble ones. One of the characteristics of proteomics data sets, currently and in the foreseeable future, is their intermediate size ( approximately 500-5000 data points). This creates a number of issues in relation to error estimation. Initially we estimate the overall error in our trees based on standard cross-validation. However, this leaves out a significant fraction of the data in model construction and does not give error estimates on individual rules. Therefore, we present alternative methods to estimate the error in particular rules.

Animals↗
PubMed2001

RNA expression patterns change dramatically in human neutrophils exposed to bacteria.

A comprehensive study of changes in messenger RNA (mRNA) levels in human neutrophils following exposure to bacteria is described. Within 2 hours there are dramatic changes in the levels of several hundred mRNAs including those for a variety of cytokines, receptors, apoptosis-regulating products, and membrane trafficking regulators. In addition, there are a large number of up-regulated mRNAs that appear to represent a common core of activation response genes that have been identified as early-response products to a variety of stimuli in a number of other cell types. The activation response of neutrophils to nonpathogenic bacteria is greatly altered by exposure to Yersinia pestis, which may be a major factor contributing to the virulence and rapid progression of plague. Several gene clusters were created based on the patterns of gene induction caused by different bacteria. These clusters were consistent with those found by a principal components analysis. A number of the changes could be interpreted in terms of neutrophil physiology and the known functions of the genes. These findings indicate that active regulation of gene expression plays a major role in the neutrophil contribution to the cellular inflammatory response. Interruption of these changes by pathogens, such as Y pestis, could be responsible, at least in part, for the failure to contain infections by highly virulent organisms.

Cells, Cultured↗
PubMed2001

Lung preconditioning with N-acetyl-L-cysteine prevents reperfusion injury after liver no flow-reflow: a dose-response study.

BACKGROUND: Circulating xanthine oxidase activity and the generated oxidants have been linked to lung reperfusion injury from no flow-reflow conditions in other organs after organ transplantation or surgery. N-acetyl-1-cysteine (NAC), an oxidant scavenger, promotes glutathione in its reduced form (GSH) that is depleted during ischemia. We have recently demonstrated its efficacy in protecting lungs from reperfusion injury if administered during reperfusion of postischemic liver. We now investigated whether preconditioning of lungs with NAC could attenuate lung respiratory or vascular derangement after no flow-reflow (ischemia-reperfusion, IR) and if this depends on lung GSH levels. METHODS: Rat isolated livers were stabilized and perfused with modified Krebs-Henseleit solution (KH) (control, n=12) or made ischemic (no flow, IR-0, n=12) for 2 hr. Meanwhile, lungs were isolated, ventilated, and stabilized (KH+bovine albumin 5%). Serial perfusion (15 min) of liver+lung pairs took place followed by lung only recirculation (45 min) with the accumulated solution. Another three controls and three ischemic groups included lungs treated during stabilization with NAC at 100 mg x kg(-1), 150 or 225 mg x kg(-1) (in 2.5, 3.7 or 5.5 mmol solutions, respectively). Results. Ischemic liver damage, expressed by circulating hepatocellular constituents, was associated with pulmonary artery and ventilatory pressure increases by 70-100% of baseline, abnormal wet-to-dry weight ratio, and abnormal bronchoalveolar lavage volume and content in the IR-0 (nontreated) and the IR-100 and IR-225 pretreated lungs. NAC-150 pretreatment afforded preservation for most parameters. GSH content in the IR-150 lung tissue was only 11% higher than that of IR-225, but 2-fold that in IR-0 and IR-100 GSH lungs. CONCLUSION: Lung preconditioning with NAC prevents reperfusion injury but not in a dose-related manner. Although enhanced GSH tissue content explains lung protection, GSH-independent NAC activity is another possibility.

Acetylcysteine↗
PubMed2001

Effect of methylene blue on resuscitation after haemorrhagic shock.

OBJECTIVE: To compare prehospital hypotensive resuscitation with volume resuscitation, and find out whether reagents that inhibit free-oxygen radical formation, such as methylene blue, can improve resuscitation and survival. DESIGN: Randomised controlled trial. SETTING: Animal laboratory, Israel. ANIMALS: 48 adult male Wistar rats. INTERVENTIONS: After 30 minutes of controlled haemorrhage, rats were subjected to 60 minutes of uncontrolled haemorrhage with simultaneous resuscitation. Hartmann's solution alone, or with blood or with a bolus of methylene blue were infused to maintain the mean arterial pressure (MAP) at 80 or 40 mm Hg. Then haemorrhage was stopped and Hartmann's solution plus whole blood were infused to obtain a MAP that was within normal limits. MAIN OUTCOME MEASURES: Volumes of shed blood and resuscitation fluids, MAP, packed cell volume, blood pH and base deficit, and survival. RESULTS: During uncontrolled haemorrhage. a MAP of 80 mm Hg could not be reached in animals resuscitated with Hartmann's solution alone, and all died. All the rats given Hartmann's solution with a bolus of methylene blue or with whole blood achieved a higher MAP. MAP of 40 mm Hg was attained in all animals regardless of the resuscitation fluid. Only 15 of 24 animals resuscitated to a MAP of 80 mm Hg survived, compared with 22 survivors of the 24 rats resuscitated to a MAP of 40 mm Hg (p <0.04). Methylene blue or whole blood drastically reduced the volumes of shed blood and of fluids required, and moderated the reduction in packed cell volume, particularly during hypotensive resuscitation. CONCLUSION: Hypotensive protocols should be used to improve survival. Methylene blue given with the electrolyte solutions could negate their detrimental effects during resuscitation.

Analysis of Variance↗
PubMed2001

Peritoneal cultures and antibiotic treatment in patients with perforated appendicitis.

OBJECTIVE: To question the common practice of sending material for microbiological examination during appendicectomy for perforated appendixes. DESIGN: Uncontrolled retrospective study. SETTING: Teaching hospital, Israel. SUBJECTS: 89 patients who had their perforated appendixes removed. INTERVENTIONS: Appendicectomy and antibiotic treatment. MAIN OUTCOME MEASURE: Whether a change in antibiotic regimen was required after bacteriological identification of bacteria isolated during the operation. RESULTS: In only 43 of the cultures (48%) taken during the operation were bacteria grown, and these were mainly Escherichia coli. In 65 patients (73%) there was no need to change the previously initiated antibiotic regimen, and in 23 (26%) it was changed purely on clinical grounds. In only one patient (1%) was the change the consequence of microbiological testing, as the organisms identified in 42 of the 43 cultures (98%) were sensitive to at least one of the antibiotics that had already been given. CONCLUSION: The practice of culturing samples taken from a ruptured appendix is redundant, because the antibiotic that has already been initiated is effective in most of the patients and the decision to modify the therapeutic regimen is dominated by clinical considerations.

Adolescent↗
PubMed2001

Stab wounds to the gluteal region: a management strategy.

OBJECTIVE: To examine the utility of a protocol for treating stab wounds to the gluteal region. These are uncommon and potentially lethal, and the location of injury influences the rate and severity of associated injuries. This was a retrospective, uncontrolled study. METHODS: Patients who sustained gluteal stab wounds and were treated according to our predetermined protocol that classifies injuries as upper or lower zone were reviewed, and associated injuries and outcome were measured. RESULTS: Of 27 gluteal stab wounds in 17 patients, 53% were classified as upper zone and 47% as lower zone injuries. Sixty-six percent of the upper zone injuries had associated neurologic, vascular, or visceral injuries that required invasive procedures or surgery, compared with 12.5% for lower zone injuries (p < 0.05). CONCLUSION: Upper zone gluteal stab wounds require prompt multisystem evaluation with mandatory angiography and aggressive management. Lower zone wounds need observation and repeated evaluations.

Adolescent↗
PubMed2001

Methylene blue abolishes aortal tone impairment induced by liver ischemia-reperfusion in a dose response manner: an isolated-perfused double-organ rat model study.

Liver ischemia-reperfusion (IR) generates remote organ reperfusion injury attributable to oxidative mediators. We tested the protective properties of methylene blue (MB) on aortal dysfunction. An ex vivo rat liver-aortal ring model was used to study the results of aortal exposure to post-ischemia (IR) hepatic effluent and its response to phenylephrine and isosorbide dinitrate in the absence or presence of increasing concentrations of MB in the effluent. Aortal incubation with IR effluents resulted in abnormal contraction. Ring's response to the vasoactive drugs was abnormally weak both during and following this exposure. Return to stabilization tone was irregular. MB (1.28 mM) best avoided overall dysfunction; 0.86 mM was partially effective, and 0.42 mM was ineffective. Nitrite/nitrate levels were similar to controls in the only IR 1.28 mM perfusate. Liver IR interferes with aortal tone and its response to vasoactive drugs, probably via oxidative interaction with nitric oxide. MB reverses these effects in a dose-dependent fashion.

Acetylcholine↗
PubMed2001

The management of stab wounds to the heart with laceration of the left anterior descending coronary artery.

Penetrating cardiac injuries are an increasing cause of traumatic deaths in urban areas. The management of these injuries has undergone a transition from simple pericardiocentesis to cardiac ultrasound evaluation in the stable patient, and emergency thoracotomy and repair of myocardial wounds in the unstable patient in extremes. The incidence of traumatic coronary artery injury is not accurately known because not all victims are examined. With the improvement in emergency medical services, including speed of transportation of these patients, better resuscitation, and knowledgeable use of cardiac ultrasound or emergency room thoracotomy, more patients with coronary artery injuries will survive and reach the operating room. The operative management of the injured coronary artery is dependant on the location of the injury and whether there is myocardial dysfunction. Distal injuries with small myocardial infarction should be treated by ligation alone. Proximal injury and those injuries associate with larger area of ischaemia or infarction are best treated with coronary artery bypass. The role of cardiopulmonary bypass pump in these patients should be evaluated depending on the homodynamic stability of the patient. We present two cases of cardiac stab wounds with transection of the left anterior descending (LAD), which were successfully managed. A literature review regarding the management of combined cardiac and coronary artery injuries is also provided.

Adult↗
PubMed2001

[Selective embolization of hepatic arteries--an additional precaution to control hemorrhage in the management of severe liver trauma].

Two cases of severe hepatic injury in which selective hepatic artery embolization was used to control hemorrhage are presented. The first case is that of a 35 year old patient who sustained a severe liver injury after a car accident. A CAT scan of the abdomen revealed an AAST grade 5 liver injury, pooling of contrast material within the liver parenchyma, and blood within the peritoneal cavity. The patient was given fluid resuscitation and taken to angiography where bleeding from branches of the right hepatic artery was demonstrated. While angiography was being undertaken the hemodynamic status of the patient deteriorated, blood transfusion was started, and a selective embolization of the right hepatic artery was performed. The bleeding stopped promptly and hemodynamic stability was regained. The second case is that of a 40 year old pedestrian run over by a car. Abdominal ultrasound revealed free fluid in the peritoneal cavity and the patient was rushed to the O.R. Crushed right lobe of the liver, and inferior vena cava and bowel tears were found. After perihepatic packing and resection of the right and sigmoid colons retrohepatic vena cava tear was repaired and perihepatic packing restored. The abdominal cavity was closed and the patient was taken to the ICU for the correction of hypothermia, metabolic acidosis, and coagulopathy that had developed during the surgery. After 8 hours in the ICU the patient was transferred for angiography and a selective embolization of branches of the right hepatic artery was performed. The clinical course of the patients after angiographic embolization of the hepatic arteries is described and the literature that discusses the use of angiography and embolization of hepatic arteries after traumatic hepatic bleeding is reviewed.

Accidents, Traffic↗