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Biomedical subjects

E Shiloni

Publications and source records attributed to E Shiloni.

At least 37 records · Page 2Linked to original sources
PubMed1997

Salivary gland transplantation: a canine model.

Impaired salivary function with resultant severe dryness of the mouth, or xerostomia, may occur in association with a variety of systemic disorders or therapies. No adequate treatment exists for this debilitating condition, which impedes normal oral function, in particular alimentation and phonation. This study explores the feasibility of salivary gland autotransplantation, using a canine model. A salivary gland with its duct and surrounding blood vessels still attached was excised and reimplanted in the dog's thigh by anastomosing the graft's blood vessels to the femoral artery and vein. The duct was sutured to an artificial orifice cut in the thigh's skin, from which the saliva was collected. Salivary secretion was induced by a single intravenous bolus of pilocarpine (5 mg). Preoperative (normal) salivation was measured by collecting saliva from the gland in situ. Periodic functional studies showed normal saliva production during the first month after grafting, after which the salivary flow was reduced by 35% over the next 2 months. This reduction was interpreted as a sign of disuse atrophy resulting from the lack of autonomic innervation. To overcome this impediment, oral pilocarpine (5 mg/day) was administered to the recipient dog, after which normal levels of saliva were excreted through the graft during the 3-month follow-up period. The quality of the graft saliva was assessed by its protein and electrolyte levels, which showed close to normal values.

Animals↗
PubMed1997

Pancreaticogastrostomy after pancreatoduodenectomy. A retrospective study of 28 patients.

OBJECTIVE: To attempt to reduce the frequency and severity of postoperative anastomotic leakage from pancreaticojejunostomy in patients undergoing pancreatoduodenectomy. DESIGN: Retrospective case series. SETTING: Tertiary referral center, department of general surgery, in the 31-month period between April 1, 1993, and November 30, 1995. PATIENTS AND INTERVENTION: Twenty-eight patients underwent pancreatoduodenectomy with pancreaticogastrostomy. Indications for surgery included carcinoma of the pancreas (n = 14), carcinoma of the ampulla of Vater (n = 8), distal cholangiocarcinoma (n = 3), duodenal carcinoma (n = 1), an islet cell tumor (n = 1), and cystadenoma of the pancreas (n = 1). The median patient age was 62 years (range, 34-76 years). The median duration of surgery was 6.75 hours (range, 4-12 hours). MAIN OUTCOME MEASURES: An anastomotic leak was defined as a recovery of more than 50 mL/d of amylase-rich fluid from the drains (> 3 times the normal plasma levels) on or after the seventh postoperative day. RESULTS: An anastomotic leak that lasted between 7 and 14 days developed in 4 patients (14.3%). A pancreatic leak led to no major morbidity. In all cases, leakage was treated by temporary restriction of oral intake and nasogastric drainage. An intra-abdominal collection did not develop in any of these 4 patients. No patient required another surgical procedure for a pancreatic fistula or abdominal collection. One patient (3.6%) died postoperatively. The median duration of the postoperative hospital stay was 20 days (range, 12-43 days), and all patients were discharged from the hospital after restoration of normal oral feeding. CONCLUSIONS: Pancreaticogastrostomy is a safe method for reconstruction of the pancreatic remnant after pancreatoduodenectomy for periampullary tumors. It results in an acceptable incidence of anastomotic leakage that is easily controlled by conservative measures.

Adult↗
PubMed1997

Tumor necrosis factor inhibits the transcriptional rate of glucose-6-phosphatase in vivo and in vitro.

Recombinant human tumor necrosis factor-alpha (TNF) injection in mice was associated with a reduced blood glucose level, already manifest 6 hours following cytokine administration. Insulin levels were not affected. Glycogen content was decreased in a dose-dependent and time-response manner. The activity of glucose-6-phosphatase (G6Pase) was already reduced 6 hours after TNF injection and was sustained 12 hours afterward. Phosphoenolpyruvate carboxykinase (PEPCK) activity was not affected initially (6 hours after injection), but a 50% reduction was observed 12 hours following cytokine administration compared with levels in fasting controls. Both liver G6Pase and PEPCK mRNAs were markedly reduced due to an inhibition of the transcriptional rate. A direct inhibitory effect of TNF on G6Pase promoter activity was demonstrated using HuH-7 cells transiently transfected with G6Pase promoter, fused to a reporter gene.

Animals↗
PubMed1997

Interleukin-6 secretion in mice is associated with reduced glucose-6-phosphatase and liver glycogen levels.

Mice bearing interleukin-6 (IL-6)-secreting tumor were used to study the chronic effect of IL-6 on carbohydrate metabolism. Mice were injected with allogeneic tumor cells transduced with the murine IL-6 gene. Serum IL-6 levels were correlated exponentially with tumor weight. Secretion of IL-6 from the developed tumors was associated with decreased food consumption, reduced body weight, and reduced blood glucose levels. Insulin levels did not change, and 2-deoxyglucose uptake was not affected in most tissues examined. A significant increase of 2-deoxyglucose uptake was measured in the liver. Glycogen content in the liver determined 0, 6, 12, and 18 days after tumor inoculation was 42, 23, 12, and 3 mg/g, respectively. The activity of phosphoenolpyruvate carboxykinase was not affected. The activity of glucose-6-phosphatase (G-6-Phase) determined 6, 12, and 18 days after tumor injection was 84, 70, and 50% of G-6-Pase activity in pair-fed mice bearing nonsecreting tumors, respectively. G-6-Pase mRNA levels were markedly reduced due to inhibition of G-6-Pase gene transcriptional rate.

Animals↗
PubMed1996

A late retroperitoneal hematoma mimicking acute appendicitis--an unusual complication of coronary angioplasty.

Peripheral vascular complications following coronary angiography and angioplasty are well established. They consist of arterial bleeding, occlusion, false aneurysm, and a-v fistula. Bleeding and thrombosis are usually evident within the twelve hours after the procedure. A case of acute right lower quadrant abdominal pain five days following thrombolytic therapy and percutaneous transluminal coronary angioplasty is presented. A computerized tomography was compatible with a periappendiceal inflammation, and the patient underwent laparotomy. A large retroperitoneal hematoma was the only positive finding on operation. A late complication of coronary angioplasty, such as retroperitoneal hematoma, presenting as an acute abdomen, should be a part of the differential diagnosis in such cases.

Angioplasty, Balloon, Coronary↗
PubMed1996

Metastatic adenocarcinoma in a thyroid colloid nodule: a rare presentation of colon cancer.

Colorectal cancer can remain asymptomatic for years. Frequently symptoms develop insidiously and may often remain unnoticed for long periods, even in the presence of disseminated disease. We herein report an unusual case of a patient with carcinoma of the sigmoid colon and multiple liver metastases. The diagnosis was established only after the patient was operated on for a large colloid nodule, a single microscopic metastatic focus being noticed in the histologic sections. The differential diagnosis compared with the columnar type of papillary carcinoma is discussed.

Adenocarcinoma↗
PubMed1996

Conservative treatment of a traumatic tear of the left hepatic duct: case report.

Injury to the extra-hepatic biliary system in blunt abdominal trauma is rare and difficult to diagnose. In adults, all reported cases were treated surgically. We report a case of a traumatic tear of the left hepatic duct that was treated successfully by endoscopic retrograde cholangiopancreatography and stenting.

Abdominal Injuries↗
PubMed1995

[Kidney transplantation from living, related donors].

Kidney transplantation is the best treatment for selected end-stage renal patients. The shortage of cadaveric organs for transplantation has led to the development of a protocol for kidney transplantation from living, related donors. In the past 20 years, 58 living, related kidney transplantations were done in our department. Mean patient age was 30 +/- 10 (SD) years and mean donor age was 36 +/- 10. There were 34 transplantations between brothers or sisters, 15 from parent to child, 4 between cousins, 4 between spouses and 1 from son to father. Mean follow-up time was 4 years. 1 and 5 years after transplantation, patient survival rates were 85% and 80%, respectively, graft survival rates were 85% and 75%. The introduction of cyclosporin-A as an immunosuppressive agent in 1985 led to improvement in graft survival rates: from 77% and 51% after 1 and 5 years, respectively, to 88% and 84%. No correlation between HLA match or patient's age and graft survival rates was found. We conclude that living, related donor transplantation is effective for suitable cases of end-stage renal disease. It should be recommended to patients who have a healthy, interested family member.

Adult↗
PubMed1995

Pancreaticojejunostomy versus controlled pancreaticocutaneous fistula in pancreaticoduodenectomy for periampullary carcinoma.

BACKGROUND: Anastomotic leak of the pancreaticojejunostomy is a major cause of morbidity and mortality following pancreaticoduodenectomy. Reports have described a large variety of techniques for performing this anastomosis and managing the pancreatic stump. In an attempt to obviate the pancreaticojejunostomy, we prospectively studied the technique of ligating the pancreatic duct and using external drains to create a temporary controlled pancreaticocutaneous fistula. PATIENTS AND METHODS: Thirty-five consecutive patients who were to undergo pancreaticoduodenectomy for periampullary carcinoma were prospectively randomized to one of two groups: pancreaticojejunostomy (PJ) (n = 18) or controlled pancreaticocutaneous fistula (CPF) (n = 17). The groups were well matched for age, sex, coexisting medical illnesses, type of tumor, and preoperative condition. Except for the management of the pancreatic remnant, all patients in both groups underwent an identical procedure. Major morbidity, length of hospitalization, duration of the controlled pancreatic fistula, and mortality were analyzed over a mean follow-up interval of 26 months (range 5 months to 7.5 years). RESULTS: The CPF group experienced lower overall operative morbidity rates than the PJ group (24% versus 56%, P < 0.01). Two patients (11%) in the PJ group and none in the CPF group died (P = NS). Half the morbidity in the PJ group and both mortalities were related to anastomotic leak. The CPF and PJ groups left the hospital after mean stays of 26.4 and 42.2 days respectively (< 0.01). CONCLUSIONS: Compared to pancreaticojejunal anastomosis, creation of a temporary controlled pancreaticocutaneous fistula in patients who undergo pancreaticoduodenectomy for periampullary malignancy has no appreciable risk. It is associated with reduced morbidity and shorter length of hospitalization.

Adult↗
PubMed1994

Metabolic effects of nicotine on human adipose tissue in organ culture.

Fragments of human adipose tissue were maintained in culture for 1 week in a medium containing 1 mU/ml insulin and 100 ng/ml dexamethasone. Under these conditions lipoprotein lipase activity was present in human adipose tissue fragments which converted [14C]glucose to 14CO2 and [14C]triglyceride. Both metabolic parameters studied were affected by human tumor necrosis factor and brefeldin A. When fragments of human adipose tissue after 1 week in culture were incubated with nicotine tartrate for 20 h, a slight but significant increase in lipoprotein lipase activity was observed, and an increased conversion of [14C]glucose to 14CO2 and [14C]triglyceride occurred. Nicotine was taken up by human adipose tissue, but no conversion to cotinine was observed. Our data demonstrate a direct effect of nicotine on human adipose tissue metabolism. Furthermore, it is suggested that weight loss in smokers is a multifactorial phenomenon, and one of the important factors to be considered is the direct effect of nicotine within the tissue.

Adipose Tissue↗
PubMed1994

Increased thromboxane mediates the adverse renal effects of interleukin-2 in rats.

The capillary leak syndrome with decreased GFR and renal water and sodium retention after recombinant interleukin-2 (IL-2) administration may arise from endothelial activation via an increase in prostaglandin synthesis. This study was undertaken to better define the role of the prostaglandin system in the renal and metabolic effects of IL-2 administration in rats. The chronic administration of IL-2 (100,000 U/kg, thrice daily, ip) resulted in a significant increase in body weight, a decrease in GFR and in the urinary excretion of sodium and potassium, and an increase in the urinary excretion of thromboxane (TXB2). After combined IL-2 and low-dose indomethacin (1.7 mg/kg per day po), a significant decrease in body weight with normalization of GFR, of the urinary excretion of Na, and of urinary TXB2 was noted in animals receiving combined therapy as compared with those receiving IL-2 alone. In contrast, high-dose indomethacin administration (33.3 mg/kg po for the last 3 days of the study) was associated with a further decrease in GFR, enhancement of the sodium and potassium retention, and suppression of prostaglandin E2 excretion. The administration of the thromboxane receptor antagonist SQ 29548 in IL-2-treated rats led to a reversal of the fall in GFR induced by the lymphokine without significant changes in urinary sodium excretion. These results support the hypothesis that thromboxane is an important mediator of the renal and systemic effects of IL-2. These effects are reversed at least partly by low-dose indomethacin, which selectively suppresses thromboxane A2 (TXA2) synthesis, or by TXA2 receptor antagonism.

Animals↗
PubMed1994

Effect of interleukin-2 on salivary gland morphology and function in mice.

C57BL mice were injected intraperitoneally with 300,000 Cetus units/day of human recombinant interleukin-2 (rIL-2) for 2, 4, and 5 days to study its effect on salivary gland function and morphology. The pilocarpine-stimulated parotid salivary flow was collected via cannulation of the glandular duct. Total salivary protein was assayed spectrophotometrically, salivary electrolytes were determined by atomic absorption, and glandular lymphoid cell infiltration was evaluated histologically. After 5 days of rIL-2 administration salivary output and total salivary protein concentrations were reduced significantly. Similar changes, albeit to a lesser extent, were observed following 2 and 4 days of rIL-2 treatment. Increased lymphoid infiltration of the salivary glands was observed, and was directly related to the duration of rIL-2 administration. The effect of the lymphokine on the parotid gland gradually dwindled after cessation of treatment: 4 days posttreatment this salivary gland showed signs of recovery, which at 10 days proved to be complete. The possible use of this animal model in the study of lymphocyte-induced salivary gland diseases is discussed.

Animals↗
PubMed1993

Cytokine secretion by genetically modified nonimmunogenic murine fibrosarcoma. Tumor inhibition by IL-2 but not tumor necrosis factor.

Recent investigations have demonstrated that the in vivo growth of weakly immunogenic murine tumors can be inhibited by genetic manipulations that enable them to secrete a variety of cytokines. Inasmuch as most human tumors fail to elicit a detectable host immune response we questioned whether the growth of a nonimmunogenic murine tumor could be inhibited by the secretion of cytokines. We have thus inserted the cDNA encoding for human IL-2 or TNF into the nonimmunogenic murine fibrosarcoma MCA 102. Tumor cells secreting IL-2 failed to grow in vivo despite normal in vitro growth. This growth inhibition required an intact immune system as tumors grew progressively in mice sublethally irradiated before tumor injection. Tumor inhibition was abrogated by the in vivo depletion, by specific mAb before tumor injection, of either CD8+ T cells or NK cells, but not CD4+ T cells. IL-2 secretion by tumor afforded a significant survival benefit to the animal, and IL-2-secreting tumor limited the growth of admixed nonsecreting parental tumor. Histologic evidence and FACS analyses revealed a dense lymphocytic infiltration of IL-2-secreting tumors composed of both CD4+ and CD8+ T cells. In contrast, secretion of TNF failed to inhibit the growth of MCA 102, and similar lymphocyte subset depletions, or administration of specific anti-TNF mAb had no effect on the growth of TNF secreting MCA 102. In summary, these investigations demonstrated that the host response to this nonimmunogenic tumor can be markedly enhanced by the genetic manipulation of the tumor cells to secrete IL-2, but not TNF. This strategy has potential application for the development of immunotherapies for nonimmunogenic tumors.

Animals↗
PubMed1993

High-grade retroperitoneal sarcomas: role of an aggressive palliative approach.

Between 1968 and 1988 we treated 41 patients with high-grade soft tissue retroperitoneal sarcomas. Clinical, pathological, and treatment variables were analyzed retrospectively with regard to their influence on recurrence rate and mortality. The actuarial 5-year median survival for the whole group was 48 months, with 33% of the patients surviving 10 years. Gender, clinical presentation, tumor size, and histological types did not predict outcome by multivariate analysis. Complete tumor resection was performed in 56% of the patients, but at 10 years after surgery only 10% of those patients remained disease free. Patients were classified into four groups according to the most aggressive surgical procedure employed: (1) total gross tumor resection; (2) subtotal resection, in which the major tumor bulk was excised (often with adjacent organs), but in which obvious residual disease remained; (3) palliative resection, in which minimal tumor resection was performed in order to alleviate symptoms; and (4) exploration only. Patients who were either explored and had no tumor removed or who underwent a palliative resection had a similarly poor prognosis, with a median survival of 12 and 20 months, respectively. To our surprise, patients after total resection had no survival benefit over patients who had undergone subtotal resection. However, both groups together had a significantly longer median survival of 241 months compared to the median survival of the patients with either no resection or only palliative resection (P < 0.02). The addition of chemotherapy or radiation therapy failed to show any advantage in this series. We claim from our experience that the impossibility of performing a complete resection should not prevent attempts at aggressive subtotal tumor excision, including the removal of adjacent organs, since this aggressive surgical approach may prolong survival significantly.

Combined Modality Therapy↗
PubMed1993

Retroviral transduction of interferon-gamma cDNA into a nonimmunogenic murine fibrosarcoma: generation of T cells in draining lymph nodes capable of treating established parental metastatic tumor.

Gene modification of tumor cells with the cDNA for interferon gamma (IFN gamma) has been shown to increase the immunogenicity of some tumor cells. In order to explore further the possible therapeutic relevance of these previous findings, two clones of the nonimmunogenic MCA-102 fibrosarcoma of C57BL/6 origin were retrovirally transduced with the cDNA encoding murine IFN gamma: 102.4JK (4JK), a clone with relatively high major histocompatibility complex (MHC) class I expression, and 102.24JK (24JK), a clone with low expression of surface MHC class I molecules. Retroviral transduction of tumor cells with the cDNA encoding for IFN gamma resulted in a substantial up-regulation of MHC class I surface expression in the 24JK clone but little change of class I in the 4JK clone. In an attempt to generate antitumor lymphocytes, these gene-modified cells were inoculated into mouse footpads and draining lymph nodes (DLN) were removed, dispersed, and cultured in vitro for 10 days with irradiated tumor cells and interleukin-2. DLN from mice bearing either unmodified tumor or tumor transduced with cDNA encoding neomycin resistance (NeoR) or IFN gamma, were used to treat recipients harboring 3-day pulmonary metastases induced by the parental, unmodified tumor. Treatment with DLN cells obtained following the injection of 24JK tumor cells modified with the gene for IFN gamma significantly reduced the number of pulmonary metastases in four separate experiments, compared to groups treated by DLN cells generated from inoculation of either the unmodified, parental 24JK clone or the same clone transduced with the NeoR gene only. In contrast, DLN cells induced either by IFN gamma-transduced 4JK (high expression of MHC class I) or an unmodified 4JK tumor (moderate expression of MHC class I) had significant but equal therapeutic efficacy. Although the in vitro growth rate of tumor cell lines was unaffected by the insertion of the mouse IFN gamma cDNA, their in vivo (s.c.) growth rates were significantly slower than those of the nontransduced tumors. Thus, after retroviral transduction of the murine IFN gamma cDNA into a nonimmunogenic tumor with a very low level of surface expression of MHC class I, modified tumor cells could elicit therapeutic T cells from DLN capable of successfully treating established pulmonary metastases upon adoptive transfer. This strategy significantly confirms previous observations on the potential therapeutic effects of gene modification of tumor cells with IFN gamma and extends the realm of therapeutic possibilities to include the use of DLN cells for the development of T-cell based immunotherapies against nonimmunogenic human tumors.

Animals↗