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Biomedical subjects

G Zamir

Publications and source records attributed to G Zamir.

At least 19 recordsLinked to original sources

A novel system to study adenovirus tropism to normal and malignant colon tissues.

We describe here a new organ culture system for the evaluation of viral tropism to colon carcinomas and normal colon tissues. Organ cultures of mouse and human colon retained viability for several days and thus facilitated studies of viral tropism. Two adenoviral vectors (AD) were compared in the study: AD5, that utilizes the CAR receptor, demonstrated poor infectivity to both normal and carcinoma tissues, while a capsid-modified-AD, recognizing haparan-sulfate receptor, demonstrated efficient infectivity of both tissues. Immunohistochemistry analysis demonstrated different viral tropism; while AD5 infected only the colon epithelia, the capsid-modified-adeno infected both the epithelia and mesothelial layers. To investigate other determinants in the tissue that influence viral tropism, human cancer tissues were pretreated with collagenase and infected with the AD viruses. Increased infectivity and altered tropism were noted in the treated tumor tissue. Taken together, this ex vivo system indicated that receptor utilization and extracellular-matrix components influence AD viral tropism in solid tissues.

Adenoviridae↗

Urinary tract infection: is there a need for routine renal ultrasonography?

AIMS: To assess the yield of routine renal ultrasound (RUS) in the management of young children hospitalised with first uncomplicated febrile urinary tract infection (UTI). METHODS: All children aged 0-5 years who had been hospitalised over a two year period with first uncomplicated febrile UTI in a medium size institutional regional medical centre were included. Children with known urinary abnormalities and/or who had been treated with antibacterial agents within seven days before admission were excluded. All included children underwent renal ultrasonography during hospitalisation and voiding cystouretrography (VCUG) within 2-6 months. The yield of RUS was measured by its ability to detect renal abnormalities, its sensitivity, specificity, and positive and negative predictive values for detecting vesicoureteral reflux (VUR), and by its impact on UTI management. RESULTS: Of 255 children that were included in the study, 33 children had mild to moderate renal pelvis dilatation on RUS suggesting VUR, of whom only nine had VUR on VCUG. On the other hand, in 36 children with VUR on VCUG the RUS was normal. The sensitivity, specificity, positive predictive value, and negative predictive value of abnormal RUS for detecting VUR were 17.7%, 87.6%, 23.5%, and 83.2% respectively. In none of the patients with abnormal RUS was a change in the management at or following hospitalisation needed. CONCLUSION: Results show that the yield of RUS to the management of children with first uncomplicated UTI is questionable.

Bacterial Infections↗

Modified AdCTLA-4 vector blocks alloimmune response in vitro.

BACKGROUND: Gene transfer of the costimulatory blockade molecule CTLA-4Ig into cold-preserved rat liver allografts results in indefinite allograft survival. Despite local delivery, this mode of immunomodulation is associated with systemic immunosuppression. In an effort to restrict immunosuppression to the graft, we have constructed a novel adenoviral vector, AdCTLA-4ex-TAG, in which the Ig sequence of CTLA-4Ig DNA has been deleted to destabilize the gene product to promote rapid extrahepatic degradation while maintaining its immunosuppressive activity within the graft milieu. METHODS: (1) Vector construction. CTLA-4 extracellular binding domain (CTLA-4ex) was prepared by PCR-based cloning methods and fused in frame to a genetic element encoding an epitope TAG allowing identification of the transgene product CTLA-4exTAG. CTLA-4exTAG was subcloned into a shuttle vector enabling isolation of AdCTLA-4exTAG. (2) In vitro transfection: AdCTLA-4exTAG was transfected into MH(1)C(1) cells and then supernatant was recovered for Western blot analysis. (3) In vitro alloimmune response was characterized by CFSE proliferation assay. (4) Extrahepatic effect of AdCTLA-4exTAG was characterized by the ability to control tumor growth after implantation of a regressive, immune sensitive cancer cell line (REGb) in the skin of BDIX rats after liver transduction with AdCTLA-4exTAG. RESULTS: Expression and secretion of the recombinant protein were documented by Western blot after infection of the MH(1)C(1) cell line() with AdCTLA-4exTAG. Addition of infected MH(1)C(1) cell supernatant resulted in abrogation of alloimmune response as shown by markedly diminished division of CD4(+) T cells in a CFSE proliferation assay. Extrahepatic tumor regressed normally after liver transduction with AdCTLA-4exTAG. CONCLUSIONS: These results show efficient in vitro expression of CTLA-4exTAG after transfection with AdCTLA-4exTAG. The modified protein retains its ability to abrogate in vitro alloimmune response. Efficient control of extrahepatic tumor growth after liver-directed delivery of AdCTLA-4exTAG suggests that the immunosuppressive effect of this vector is restricted to the liver. These results set the ground for the utilization of this novel adenoviral vector in the transplant setting.

Abatacept↗

Combined colon and hepatic resection for synchronous colorectal liver metastases.

BACKGROUND AND OBJECTIVES: The surgical strategy for the treatment of resectable synchronous hepatic metastases of colorectal cancer remains controversial. This study was performed to assess the outcome of combined resection of colorectal cancer and liver metastases. METHODS: The perioperative data, morbidity, and survival of the patients who underwent combined colon and liver resections for synchronous colorectal liver metastases from 1988 to 1999 were compared to the parameters of the patients who underwent colon resection followed by resection of liver metastases in a staged setting. RESULTS: 198 hepatic resections were performed, of which 112 procedures in 103 patients were done for metastatic colorectal carcinoma. Twenty six patients (25%) had combined hepatic and colon resection and were compared to 86 patients with metachronous metastases who underwent colon and hepatic resection in the staging setting. Postoperative morbidity was 27 and 35%, respectively. There was no hospital mortality in the combined group vs. 2.3% in the staged group. Blood loss, intensive care unit (ICU) stay and length of postoperative stay (LOS) were similar in both groups. The 5 years cumulative survival of the group after combined surgery was 28% vs. 27% of the group after isolated hepatic resections (P = 0.21). CONCLUSION: Combined colon and hepatic resection is a safe and efficient procedure for the treatment of synchronous colorectal liver metastases. It can be performed with acceptable morbidity and no perioperative mortality. The survival after combined procedure is comparable to the one achieved after staged procedure of colon resection followed by liver resection.

Adult↗

Role of plasmapheresis in the management of acute hepatic failure in children.

OBJECTIVE: To assess the efficacy of plasmapheresis in the treatment of children with acute hepatic failure. SUMMARY BACKGROUND DATA: Acute liver failure is expressed with severe encephalopathy, coagulopathy, and subsequent multisystem organ failure, resulting in a high death rate. Liver transplantation is considered the best option, with long-term 1-year survival rates exceeding 88%. It has been suggested that plasmapheresis may improve coagulopathy and prevent bleeding complications while maintaining adequate fluid, electrolyte, and acid-base balance. METHODS: Forty-nine patients with acute liver failure underwent a total of 243 therapeutic plasma exchanges (TPE). Indications for treatment included candidacy for liver transplant and prolonged prothrombin time. Pheresis was performed daily until the patient recovered, died, or was transplanted. Four patients were anhepatic during pheresis. RESULTS: Coagulation profiles after TPE significantly improved compared with mean preexchange values while maintaining euvolemia. No bleeding episodes were observed during the course of treatment. There was no sustained improvement in neurologic function. Spontaneous recovery was observed in three patients; the remaining either underwent transplantation (32/49) or were not considered transplant candidates because of irreversible neurologic insults (11/49) or sepsis (3/49). CONCLUSION: For children with acute liver failure, TPE is extremely effective in preventing life-threatening bleeding while maintaining appropriate volume status in small children. This method of treatment has no effect on the neurologic complications of liver failure and has no impact on the ability of the liver to regenerate.

Acute Disease↗

[Laparoscopic adrenalectomy].

Constant advances and increasing experience in laparoscopic surgery renders it applicable for adrenal surgery. The wide exposure required for open adrenal surgery makes this minimally invasive procedure an attractive and advantageous alternative. Between 1996-1999, we performed 35 laparoscopic adrenalectomies in 30 patients 20-72-years old. Indications included: Conn's syndrome--14, pheochromocytoma--11, Cushing's syndrome--6, nonfunctioning adenoma--3, and metastatic sarcoma--1. 5 underwent bilateral laparoscopic adrenalectomy. In 3 (8.5%) the procedures were converted to open operations. Overall morbidity was 13% and there was no mortality. Mean operative time was 188 minutes, but only 130 in our last 10 cases. Mean hospital stay was 4 days and they returned to normal activity an average of 2 weeks later. According to our study and previous reports, laparoscopic adrenalectomy is feasible and safe and it may soon become the procedure of choice for adrenal tumors.

Adenoma↗

Mallory-Weiss syndrome: possible link to water immersion and subsequent air flight.

Mallory-Weiss Syndrome (MWS) lesions account for up to 15 per cent of upper gastrointestinal bleeding episodes. Typically these lesions present as a consequence of vomiting that is often associated with alcoholism. Recently other conditions such as pregnancy, migraine, hiatal hernia, gastric ulcer, biliary disease, and various medications have been associated with MWS. We report on a 32-year-old male who developed a MSW lesion after a prolonged period of swimming followed by an extended commercial airplane flight. The hemodynamic changes associated with swimming (increased central distribution of blood volume) and the pressure changes in commercial aircraft (a reduction of 0.3 atmospheres of pressure) are discussed. We conclude that the combination of these factors contributed to the development of a MWS lesion and gastrointestinal bleeding in this patient. We recommend that both air travel and athletic activities be considered as possible contributing factors in the evaluation of the cause of new-onset gastrointestinal bleeding.

Adult↗

The fate of the dropped gallstones during laparoscopic cholecystectomy.

Stones can be spilled from the gallbladder during laparoscopic cholecystectomy. These stones can be left in the peritoneal cavity or trapped at the trocar site. The potential late sequel and associated morbidity are not well documented. We reviewed the records of four patients who underwent laparoscopic cholecystectomy at Mount Sinai Medical Center in New York City who suffered from late complications attributed to gallstones left in the peritoneal cavity or abdominal wall. Four patients presented 1-14 months after laparoscopic cholecystectomy with intraabdominal and abdominal wall abscesses. The spillage of gallstones was noticed during the initial operation only in one of the patients. Three patients required laparotomy and open drainage of intraabdominal abscesses with drainage of pus and gallstones after failed attempts at percutaneous drainage. Two patients underwent local exploration of an abdominal wall abscess containing stones. Stones left in the abdominal cavity or trapped in trocar sites after laparoscopic cholecystectomy can cause serious late complications requiring repeated surgical interventions. Every effort should be made in order to avoid spillage of stones during dissection of the gallbladder and cystic duct and during retrieval of the gallbladder through the abdominal wall.

Abdominal Abscess↗

Duodenal duplication cyst manifested by duodeno-jejunal intussusception and hyperbilirubinemia.

A rare case of duodenal duplication cyst containing stones in a 17-year-old patient is presented. The cyst, acting as a leading point for duodeno-jejunal intussusception caused proximal small bowel obstruction and hyperbilirubinemia. Preoperative diagnosis was based on abdominal computerized tomography. At operation, the cyst wall was unroofed creating free drainage into the duodenal lumen without damaging the biliary and pancreatic ducts with resolution of symptoms.

Adolescent↗

Primary presacral adenocarcinoma. Report of a case.

A rare of a patient who presented with a presacral tumor is described. The tumor, after complete resection, was shown to be a primary adenocarcinoma. After potential sources such as gastrointestinal, pancreas, or prostate were eliminated, the diagnosis of primary presacral adenocarcinoma was made. Possible origins of this unusual tumor are discussed.

Adenocarcinoma↗

Prevention of intestinal adhesions after laparotomy in a rat model--a randomized prospective study.

We prospectively studied the effect of a foam composite containing glycerin, propylene glycol, polyol, stearine, stearate and silicone oil, which is known to form a temporary barrier layer when applied to epithelial surface, on adhesion prevention in rats. The small intestine abrasion model was used for creation of adhesions. Sixty male Sabra rats of a mean weight of 295 +/- 23 g were randomly assigned into four groups: group 1 (n = 20) underwent laparotomy and abrasion; group 2 (n = 20) underwent laparotomy, abrasion and intraperitoneal instillation of the foam composite; group 3 (n = 10) underwent laparotomy with abrasion and a second laparotomy with adhesiolysis 2 weeks later; and group 4 (n = 10), was treated in the same way as group 3 but during the second laparotomy the foam composite was instilled intraperitoneally. All animals were relaparotomized 2 weeks (groups 1 and 2) and 4 weeks (groups 3 and 4) after the initial laparotomy for adhesion scoring performed by a blinded independent investigator using the standard 0-3 adhesion grading score. Representative specimens of small intestine and liver from animals in groups 2 and 4 were analyzed. A significantly lower mean adhesion score was noted in group 2 (1.15 +/- 0.3) compared with that of group 1 (2.65 +/- 0.1) or group 3 (2.60 +/- 0.1) (P < 0.01). Group 4 had a significantly lower score (1.4 +/- 0.3) than group 3 or group 1 (P < 0.05). There was no significant difference in the mean adhesion score between groups 1 and 3. Histological examination revealed no evidence of residual foam composite or adverse reaction to its use in the intestine and liver. The foam composite tested may reduce the severity of intestinal adhesions after laparotomy and may also reduce the severity of recurrent adhesions after adhesiolysis. Intraperitoneal use of this composite is safe in rats. The exact mechanism of action is unclear but may be related to the formation of a temporary microlayer that coats the injured surface of the intestine and facilitates healing without adhesion formation. Further investigation is needed to evaluate its full potential.

Animals↗

Results of reconstruction in major pelvic and extremity venous injuries.

PURPOSE: Outcome and venous patency after reconstruction in major pelvic and extremity venous injuries was studied. METHODS: We retrospectively reviewed 46 patients with 47 venous injuries. RESULTS: Injuries were caused by penetrating trauma in 37 extremities, blunt trauma in 6 patients, and were iatrogenic in 4 patients. Pelvic veins were injured in 4 patients, lower-extremity veins were injured in 39 limbs in 38 patients, and upper-extremity veins were injured in 4 patients. Concomitant arterial injuries occurred in 37 patients. Venous repairs were mostly of the complex type and included spiral or panel grafts in 15 (32%) reconstructions, interposition grafts or patch venoplasty in 19 (40%) reconstructions, end-to-end and lateral repair in 11 patients, and ligation in 2 patients. Two patients underwent early amputation. Early transient limb edema occurred in 2 patients, and postoperative venous occlusions were documented in 4 patients. Full function was regained in 39 (81%) extremities. No variable, including 4 retrospectively applied extremity injury scores (mangled extremity severity score [MESS], limb salvage index [LSI], mangled extremity syndrome index [MESI], predictive salvage index [PSI]), correlated with outcome. High values on all 4 scores were significantly associated with reexplorations (P <.02), which were done in 8 patients for debridement (5), arrest of bleeding (2), and repair of a missed arterial injury (1). Follow-up of 28 +/- 6 months on 27 patients (57%; duplex scan in 18, continuous-wave Doppler and plethysmography in 9, and venography in 3) showed 1 occlusion 6 weeks after the injury and patency of all other venous reconstructions. CONCLUSION: Reconstructions of major venous injuries with a high rate of complex repairs result in a large proportion of fully functional limbs and a high patency rate. A high extremity injury score predicts the need for reexploration of the extremity. Mostocclusions occur within weeks of injury, and the subsequent delayed occlusion rate is very low.

Adolescent↗