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Biomedical subjects

O Kaplan

Publications and source records attributed to O Kaplan.

At least 73 records · Page 4Linked to original sources

Concerning antisense inhibition of the multiple drug resistance gene.

Recently, Vasanthakumar and Ahmed reported (Vasanthakumar, G.; Ahmed, N.K., Cancer Communications 1:225-232; 1989) a complete inhibition of the multiple drug resistance gene (MDR1) in the K562/III erythroleukemia cells, using a 15 bases-long methylphosphonate oligodeoxynucleotide analog. The sequence used, however, contained three mismatches relative to the corresponding fragment of the human MDR1 gene and, hence, the results reported cannot at present be regarded as a classical antisense effect. We have made attempts to inhibit the expression of the MDR1 gene in MCF-7 human breast cancer cells selected for resistance to Adriamycin using phosphorothioate analogs of oligodeoxynucleotides. Studies with model 35S-labeled-phosphorothioates indicated poor uptake of the compounds into the cells; the radioactivity was located mainly in the soluble fraction (cytoplasm), but membranes and the nuclear fraction were also labeled. Unmodified oligodeoxynucleotides were toxic to the cells, whereas the phosphorothioates were not. The MDR1 inhibition with phosphorothioates was studied by measuring their effects on adriamycin toxicity and by immunocytochemical titration of P170. Elevation of adriamycin cytotoxicity consistent with a decreased drug resistance was observed with one antisense sequence, but the immunocytochemical assay indicated only slight inhibition of the synthesis of P170. In the wild type (drug sensitive) MCF-7 cells phosphorothioates decreased adriamycin toxicity in a sequence-independent manner. The results indicate that the effects of antisense oligodeoxynucleotides on cells are complex. Computer simulation of the secondary structure of MDR1 mRNA indicated not only extensive folding but, also, the presence of many regions not involved in intramolecular hybridization, which are of potential interest as targets for antisense oligodeoxynucleotides.

Base Sequence↗

Surgical palliation combined with synchronous therapy in pancreatic carcinoma.

Palliative surgery has a role in nonresectable pancreatic carcinoma. We attempted to evaluate the efficacy of palliative surgery followed by synchronous therapy in such cases. A group of 92 patients was studied. Sixty-six patients (Group 1) with biliary obstruction underwent surgical biliary bypass. Twenty-six patients (Group 2) underwent explorative laparotomy only. Thirty patients (45.5%) in Group 1 and 10 patients (38.5%) in Group 2 received synchronous therapy consisting of 10 intravenous administrations of 5-fluorouracil (750 mg/m2) over 8 h, followed 8 h later by radiation with 400 rads repeated every 4 days. The mean survival for the entire group was 8.9 months. Those in Group 1 who received synchronous therapy had a mean survival of 13.5 months; those who did not 8.9 months (P less than 0.01). Patients in Group 2 who received synchronous therapy survived with a mean of 5.4 months, those who did not 2.7 months (P less than 0.01). Toxicity due to synchronous therapy was minimal. Of the 40 patients receiving synchronous therapy, 37 suffered from abdominal pains prior to initiation of therapy, 29 of which (78.4%) were free of pain upon completion of therapy. In nonresectable carcinoma of the pancreas, surgical palliation provides an acceptable survival. When combined with synchronous therapy, it results in prolonged survival and an ameliorated quality of life.

Adult↗

Metabolism of peripheral lymphocytes, interleukin-2-activated lymphocytes and tumor-infiltrating lymphocytes from 31P NMR studies.

31P NMR spectra of tumor-infiltrating lymphocytes (TILs) were found to be significantly different from those of normal peripheral lymphocytes. The greatest difference was in the phosphodiester (PDE) region, mainly in the glycerophosphocholine (GPC) signal. Short-term activation of peripheral lymphocytes with interleukin-2 induced a small increase in ATP levels. In all lymphocytes the phosphomonoester (PME) region is dominated by phosphoethanolamine (PE), while there is an unusual absence of phosphocholine (PC). Perfusion of these cells with high concentrations of choline caused only a minimal increase in PC, indicating that choline kinase is not the rate limiting step of lecithin synthesis in lymphocytes.

Adenosine Triphosphate↗

[Retroperitoneal ganglioneuroma].

Ganglioneuroma is an infrequent tumor composed of sympathetic ganglion cells and sheathed neurites. It arises mainly from the large sympathetic chains, most frequently in the posterior mediastinum and retroperitoneum, but rarely may develop from the peripheral sympathetic chains. It is usually benign, and may grow asymptomatically to relatively large size. However, it can cause symptoms due to local expansion and pressure on adjacent structures. It does not seem to have hormonal activity. Some ganglioneuromas contain immature cells or elements of neuroblastoma or pheochromacytoma and can metastasize. The preoperative diagnosis of retroperitoneal tumors has now become more frequent due to the extensive use of imaging modalities, mainly computed axial tomography. Whenever the imaging correlates with the clinical presentation, or there is a reasonable suspicion of a malignancy, operation is indicated. Many retroperitoneal space-occupying lesions are found in asymptomatic patients during attempts to diagnose other diseases. In these cases opinions differ as to therapeutic approach. Many adrenal tumors may be benign adenomas, and several therapeutic protocols have been proposed. The clinician can decide on the basis of clinical presentation and radiographic features whether a conservative approach rather than operation is indicated. Since the majority of retroperitoneal tumors are malignant, histologic diagnosis is essential and in such cases surgical intervention is warranted. A young patient with a retroperitoneal ganglioneuroma is presented.

Adult↗

[Dieulafoy's lesion].

Massive upper gastrointestinal tract bleeding from a ruptured abnormal gastric artery was reported by Gallard in 1884. The lesion is rare and its characteristics were only described 24 years later by the French surgeon Dieulafoy. It is characterized by an abnormal, tortuous, submucosal artery protruding from a small lesion in otherwise normal gastric mucosa, and is usually located in the posterior wall of the lesser curvature near the cardia. Preoperative diagnosis is very difficult and it is easily overlooked, even during operation. Hence, rebleeding and second laparatomy are common. Treatment is mainly surgical: by wedge resection or oversewing the lesion. A 30-year-old patient with this condition who was operated on for upper gastrointestinal bleeding is presented.

Adult↗

Role of cholecystostomy in the management of critically ill patients suffering from acute cholecystitis.

Between the years 1976 and 1985, 60 patients underwent cholecystostomy for acute cholecystitis in the surgical department of the Rokach hospital in Tel Aviv. The patients' average age was 73 years; 78 per cent were 70 years or older at the time of operation. The decision to perform cholecystostomy was taken before the operation which was performed as an emergency procedure for patients considered to be at high risk for cholecystectomy. Forty-six patients (77 per cent) had severe concomitant diseases, and 42 per cent of them had two or more associated diseases simultaneously. The cardiac risk index was high in most patients (90 per cent). Fifty-two patients recovered promptly after surgery. Five patients (8 per cent) developed significant postoperative complications. Three other patients (5 per cent) died of cardiovascular complications. Forty-two patients (70 per cent) underwent an elective cholecystectomy 6-8 weeks later with no further morbidity or mortality. Eleven patients who were at high risk had no further surgery. No residual stones were found in these patients and no relapse of the disease was recorded in the long term follow-up. Four patients were lost to follow-up. We conclude that cholecystostomy may still be used as an initial life saving procedure for critically ill patients with acute cholecystitis, and serves as a definitive procedure for patients considered to be at very high operative risk and who have no residual stones.

Acute Disease↗

Proximal colostomy: still an effective emergency measure in obstructing carcinoma of the large bowel.

Large bowel obstruction constitutes an emergency abdominal condition and necessitates prompt surgical treatment. The optimal approach is still controversial as to whether to perform a diverting colostomy only or a tumor resection with or without primary anastomosis. Seventy-one elderly and high-risk patients were treated by proximal diverting colostomy through a right upper abdominal incision. The operative mortality was 8.5%, with an additional morbidity of 20.5%. Stomal complications appeared in 6.1% of the survivors. Seventy-five percent of surviving patients underwent successful resection and closure of colostomy within 3 months without additional mortality. Others were not operated because of metastatic disease or severe concomitant disease. We conclude that although primary resection should be attempted in good risk patients, for those patients who are elderly and at high risk, a simple life-saving procedure, such as fecal diversion, could alleviate obstructions with relatively low morbidity and mortality and improve the patient's prospects for subsequent definitive surgery.

Aged↗

Identification of a characteristic 31P NMR signal in acute experimental pancreatitis with the aid of 1H-31P correlated 2D measurements of intact pancreas.

Two-dimensional 1H-31P correlation spectroscopy and relaxation time measurements of intact diseased pancreas were performed in order to identify an unknown peak appearing at -0.18 +/- 0.04 ppm in a 31P NMR spectrum of taurocholate-induced experimental acute pancreatitis in rats. The signal was identified as a solubilized lecithin taurocholate complex.

Animals↗

Penetration of prophylactic antibiotics into peritoneal fluid.

This study evaluates the penetration of cephalosporins into the peritoneal fluid. Forty-six patients scheduled for abdominal surgery were randomized into three groups. On call to the operating room each patient was given a single 1 g dose of cefazolin, cefuroxime, or ceftazidime. Samples of the peritoneal fluid and blood were simultaneously obtained immediately after opening the peritoneal cavity. The mean serum cefazolin concentration was the highest. High peritoneal fluid levels of all three antibiotics were found; however, the antibacterial activity against common intestinal pathogens varied significantly. Cefazolin is the only study drug that possesses marginal in vitro activity against Streptococcus faecalis, a species generally considered resistent to cephalosporins. This study suggests that prophylactic second and third generation cephalosporins are not superior to cefazolin.

Abdomen↗

Gangrene of the lower limbs in diabetic patients: a malignant complication.

Diabetic foot lesions are a common medical problem with major socioeconomic impact. Gangrene is usually a late and sometimes fatal complication. A series of 118 diabetic patients who underwent amputation of the lower limb at our institution over a 10 year period has been presented. Forty-two patients underwent amputation of the toes or part of the foot, 48 underwent below-knee amputation, and 18 underwent above-knee amputation. In 24 (20.3 percent), the necrotic process advanced postoperatively and necessitated additional amputation. The average hospital stay was 33.6 days. Twenty-eight patients (23.7 percent) died during the postoperative period, and the main cause of death was sepsis. Patients who presented with extensive gangrene had a higher mortality rate. There was no correlation between mortality and the duration of conservative treatment, number of repeated operations, the treatment of diabetes before hospitalization, onset of symptoms, or status of the peripheral pulses. The solution to the problem is early and vigorous preventive treatment. This could be accomplished through highly specialized clinics within the community.

Aged↗

Acute pancreatitis in rats: a 31P nuclear magnetic resonance study.

High resolution 31P nuclear magnetic resonance (NMR) was used to evaluate the severity of acute pancreatitis in rats. Experimental pancreatitis was induced by intraparenchymal injection of 10% sodium taurocholate. pancreases were removed at various time periods and the NMR spectrum of the whole organ was recorded. Metabolic changes taking place during the progression of the disease were measured and correlated with the pathologic changes. Gradual depletion of the high energy compounds, adenosine triphosphate and phosphocreatine, was observed. The NMR spectral changes paralleled the extension of the pathologic lesions and were found to constitute a reliable indicator of the severity of acute pancreatitis. It is suggested that high resolution NMR may be used to evaluate the pathogenesis and therapy of various forms of experimental pancreatitis.

Adenosine Triphosphate↗

Gastrointestinal anastomotic healing during treatment with perioperative 5-fluorouracil.

This clinical study examines the influence of perioperative administration of 5-fluorouracil (5-FU) on gastrointestinal anastomotic healing. Intravenous 5-FU, 10 mg/kg body weight, was started during surgery and continued for 9 days only when advanced cancer was detected. A total of 32 gastric and enteric anastomoses were performed. All 32 patients with anastomoses recovered without any clinical evidence of leakage. Side effects attributed to 5-FU appeared in five patients, usually in a mild form of diarrhea and vomiting. On the whole, the course of recovery of this group was no different than expected from patients with advanced malignancy undergoing extensive surgery. Based on this, it appears that 5-FU administration during and immediately after surgery has no deleterious effect on the gastrointestinal tract.

Aged↗

Acid ingestion: another cause of disseminated intravascular coagulopathy.

This report presents a case of disseminated intravascular coagulopathy developing within 2 h after ingestion of 96% (glacial) acetic acid in an attempted suicide. Although bleeding from the GI tract is found commonly in acid injury, this case illustrates that it may also be an early manifestation of disseminated intravascular coagulopathy.

Acetates↗