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O Kaplan

Publications and source records attributed to O Kaplan.

At least 19 recordsLinked to original sources
PubMed1998

Octreotide ameliorates glucose intolerance following acute experimental pancreatitis.

The long-term effects of octreotide, the synthetic analog of the hormone somatostatin, on acute experimental pancreatitis were studied. Acute pancreatitis was induced in rats by intraparenchymal injections of 0.5 ml 5% or 10% sodium taurocholate. Octreotide (10 mg/kg/day, subcutaneously), or saline injections as controls, were started four hours later, and their effects were assessed 30, 60, and 90 days after the induction of pancreatitis. Neither intrapancreatic saline injections nor octreotide administration without the induction of pancreatitis caused any biochemical or histological abnormalities. Taurocholate-induced pancreatitis was followed by remarkable hyperglycemia, which was ameliorated by octreotide. Thirty days after induction of pancreatitis, glucose levels were 269+/-21 mg/100 ml and 153+/-17 mg/100 ml in the control and octreotide treated animals, respectively (P < 0.02). Octreotide administration was associated with increased pH values after 60 and 90 days (P < 0.05 for the 90 days group). The levels of hematocrit, calcium, and amylase were already within the normal ranges after 30 days and were unaffected by octreotide. There were no signs of chronic exocrine insufficiency and all the surviving rats gained weight during the follow-up. However, the relative weights of the pancreases of the octreotide-treated animals were higher than those of the controls 30 days after IOP. Histopathological evaluation demonstrated regeneration of the pancreatic tissue, and increased number and hypertrophy of the islets of Langherhans. There were no significant differences whether the octreotide treatment was given for only 48 or 96 hr. Survival was significantly improved by octreotide; only one octreotide-treated rat (2.5%) with 10% taurocholate-induced pancreatitis died, while six (15%) of the control animals succumbed (P < 0.05). These studies provided data on the sequelae of acute pancreatitis and showed that octreotide may have long-term beneficial effects in this disease.

Acute Disease↗
PubMed1998

Management of breast fibroadenomas.

OBJECTIVE: To identify from the literature and clinical experience a rational approach to management of fibroadenomas of the breast. METHOD: Recent literature on detection, diagnosis, and natural history of fibroadenomas was reviewed. Experience with over 4,000 women evaluated in the breast clinic at the Tel-Aviv Medical Center contributed to the management strategies suggested by review of the literature. RESULTS: Fibroadenomas of the breast are common, accounting for 50% of all breast biopsies performed. Physical examination, sonography, and fine needle aspiration are effective in distinguishing fibroadenomas from breast cancer. Transformation from fibroadenoma to cancer is rare; regression or resolution is frequent, supporting conservative approaches to follow-up and management. CONCLUSION: Age-based algorithms that allow for conservative management and that limit excision to patients whose fibroadenomas fail to regress are presented.

Adult↗
PubMed1997

Tumor necrosis factor-alpha increases ATP content in metabolically inhibited L929 cells preceding cell death.

The effects of tumor necrosis factor-alpha (TNF) on ATP levels were studied in metabolically inhibited L929 cells. Treatment of these cells with TNF in the presence of actinomycin D or cycloheximide induces cyclic changes in the intracellular ATP content preceding cell death. After 3 h of incubation, the intracellular ATP content increased by 48 +/- 6% (p < 0.001), but at 4 h, it decreased to the control level. Two hours later, it increased again by 23 +/- 5% over the control level (p < 0.001). Coinciding with cell death, ATP content decreased progressively until almost complete depletion. These changes in ATP content were associated with parallel alterations in the respiratory coupling and with increased generation of reactive oxygen species. The mechanism by which TNF/actinomycin D or TNF/cycloheximide increased cellular ATP seemed to be dependent on the mitochondrial ATP synthesis and related to the cytotoxic effect of TNF, since blockade of mitochondrial electron transport prevented the increase in cellular ATP, the formation of reactive oxygen species, and the apoptotic cell death caused by TNF. We suggest that the TNF/actinomycin D- or TNF/cycloheximide-induced changes in intracellular ATP levels may be involved in the cytotoxic effect of TNF in metabolically inhibited L929 cells.

Adenosine Diphosphate↗
PubMed1997

Role of nuclear magnetic resonance spectroscopy (MRS) in cancer diagnosis and treatment: 31P, 23Na, and 1H MRS studies of three models of pancreatic cancer.

The role of nuclear magnetic resonance spectroscopy (MRS) in pancreatic cancer diagnosis and its treatment were assessed in three models of pancreatic neoplasms. Perfused MIA PaCa-2 human pancreatic cancer cells, s.c. implanted pancreatic tumors in hamsters, and pancreatic tumors induced in situ in rats by direct application of the carcinogen 7,12-dimethyl benzanthracene, were studied by phosphorous ((31)P), sodium ((23)Na), and proton ((1)H) MRS. (31)P spectra of pancreatic cancer were qualitatively similar to those of intact organs. There were, however, variations in peak intensities and ratios. Phosphomonoester signals were prominent in both normal pancreases and tumors, but their levels depended on the proliferation rate and on environmental conditions. Thus, the phosphomonoester:beta-nucleoside triphosphate ratio was 1.15 +/- 0.32 in 90% confluency and 1.31 +/- 0.43 in 70% confluency, and this ratio increased upon lowering the perfusion rate. Total (intra- and extracellular) sodium concentrations, measured in the solid tumors, were 39-40 micromol/g wet weight in normal pancreases. Contrary to a previous hypothesis that malignant transformation is associated with increased sodium content, our (23)Na MRS data showed that there were no significant differences between pancreatic tumors and intact organs. Proton spectra of perchloric acid extracts revealed several differences between tumors and control pancreases. The principal findings were elevated levels of the amino acid taurine, from 1.17 +/- 0.39 micromol/g wet weight in healthy pancreases, to 2.79 +/- 0.71 micromol/g wet weight in pancreatic carcinoma in rats, and lactate levels that increased from 0.92 +/- 0.2 to 6.19 +/- 1.93 micromol/g wet weight, respectively. On the other hand, creatine and glutamate were higher in the normal pancreases. Pancreatic cancer is usually resistant to chemotherapy, and we evaluated the effects of the metabolic inhibitors 2-deoxyglucose and lonidamine on the human pancreatic cancer cells by MRS and cytotoxicity studies. The IC50 of Adriamycin and 2-deoxyglucose were 1.49 +/- 0.18 x 10(6) and 136 +/- 17 microg/ml, respectively. These results were similar to data obtained previously in multidrug-resistant human breast cancer cells, which were highly resistant (33-fold) to Adriamycin but were more susceptible (9-fold) to 2-deoxyglucose than their parental cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

In vitro cytotoxic effects of tumor necrosis factor-alpha in human breast cancer cells may be associated with increased glucose consumption.

Tumor necrosis factor-alpha inhibited growth of cultured MCF-7 human breast cancer cells in a dose dependent manner. Tumor necrosis factor-alpha also markedly increased glucose consumption, and its cytotoxicity was modified by glucose concentrations in the growth medium; higher glucose levels were associated with increased cell survival. However, when the cells were perfused in physiological conditions, very high levels of tumor necrosis factor-alpha (200 ng/ml) in the perfusion solution had no inhibitory effects. Moreover, tumor necrosis factor-alpha had no effects on 31P nuclear magnetic resonance spectra of the perfused cells. In the traditional growth inhibition assays, cells are incubated for several days with a drug, a situation where their metabolism is altered due to the depletion of nutrients, the accumulation of toxic waste materials and pH changes. Perfusion experiments are more relevant to in vivo conditions, and may be used for studying metabolic processes and the mechanisms of action of therapeutic agents.

Breast Neoplasms↗
PubMed1997

Comparison of action of the anti-neoplastic drug lonidamine on drug-sensitive and drug-resistant human breast cancer cells: 31P and 13C nuclear magnetic resonance studies.

Lonidamine (LND) is a relatively new anti-cancer drug, and several clinical trials have indicated that it may be effective in combinations with other therapeutic modalities. LND is classified within the metabolic inhibitor agents. Multidrug resistance (MDR) phenomenon is often associated with increased energy requirements, and enhanced glycolysis rate. These studies were performed to delineate the mechanism of action of LND on MDR human breast cancer cells, and to investigate whether LND as a single agent, or in combination with another anti-metabolism drug, 2-deoxyglucose (2-DG), may be useful against MDR tumors. The effects of LND on intact perfused drug-sensitive (WT) and 33-fold resistant to Adriamycin (Adr) MCF-7 cells, embedded in alginate micro capsules, were continuously monitored by 31P and 13C nuclear magnetic resonance (NMR) spectroscopy. 31P NMR studies showed that LND induced intracellular acidification and depletion of NTP in both WT and Adr cells. However, pH and NTP levels decreased less in the Adr cells than in the WT cells (p < 0.05 for both parameters). 13C NMR demonstrated that LND inhibited lactate transport, and lactate signals were elevated in both cell lines. However, the intracellular lactate levels increased to a greater extent in the WT than in the Adr cells (p < 0.05). There were major differences in the effects of LND on metabolism between sensitive and resistant cells. While LND enhanced glucose uptake in the WT cells, and its administration was followed by continuous increase of lactate signal, both processes were not affected by LND in the Adr cells. 2-DG is a glucose analogue that inhibits both cellular uptake and utilization of glucose, leading to cell starvation. Combined treatment with LND and 2-DG yielded at best additive, but not synergistic, cellular toxicity, and the metabolic effects of LND were attenuated by 2-DG. These results showed that the principal mechanism of action of LND is inhibition of lactate transport leading to intracellular lactate accumulation and acidification in both WT and Adr cells. The Adr cells were only 2-fold resistant to LND (compared to the WT cells), and since cellular uptake of alkaloid chemotherapy is improved in acidic environment, LND may have a role in the treatment protocols of MDR tumors, especially when given as the initial means for induction of intracellular acidification.

Antineoplastic Agents↗
PubMed1997

Visual search as a function of type of prior experience with target and distractor.

In a visual search task, participants identified the presence of a unique shape against a background of homogeneous distractors. Types of prior experience with the target, the distractor, or both were examined. In 2 experiments, a preexposure (PE) phase was followed by a test phase. The test display consisted of a target that was either target or distractor in PE or novel. Distractors were either targets or distractors in PE or novel. Reaction time was fastest for novel targets with familiar distractors, irrespective of the source of familiarity, and slowest for novel targets with novel distractors. Results are discussed in terms of attentional explanations of latent inhibition (LI) and perceptual learning and of visual search phenomena, such as novel popout. LI, previously attributed only to a deficit in the stimulus preexposed group, may also be due to enhanced performance in the nonpreexposed group.

Association↗
PubMed1996

Effects of delayed administration of octreotide in acute experimental pancreatitis.

Multiple therapeutic modalities studied for acute pancreatitis often show a poor correlation between results obtained in experimental studies and results of clinical trials. One of the main reasons for this discrepancy is that in most experimental studies the drugs were administered immediately after induction of pancreatitis, whereas in the clinical setting there is almost always a delay between the onset of the disease and initiation of the treatment. We studied the effects of a delayed treatment with octreotide, the synthetic analogue of the hormone somatostatin, on acute experimental pancreatitis in rats. The disease was induced by intraparenchymal injections of 0.5 ml 5% sodium taurocholate, and octreotide (10 mg/kg/day s.c.) was started either 4 or 12 hr later. Subcutaneous saline injections were used in controls. One-half of the animals of each study group was sacrificed after 36 hr, and the following parameters were examined: pancreatic weight, plasma pH, serum calcium and amylase, and histopathological damage. The same parameters, as well as survival, were assessed after 20 days in the remaining rats. Neither intrapancreatic saline injections, nor octreotide administration without the induction of pancreatitis, caused any biochemical or histological alterations. Hypocalcemia and acidosis in pancreatitis-induced rats were improved by octreotide, but, as expected, it had no effect on amylase levels. Octreotide ameliorated pancreatic edema, intestinal dilatation, and the histopathological injury score 36 hr after induction of pancreatitis. Mortality was 40% in control animals, and only 20% in rats treated with octreotide. Overall, octreotide had beneficial effects in acute experimental pancreatitis, and was more effective when started earlier. These results indicate that octreotide may have a role in the management of acute pancreatitis.

Acute Disease↗
PubMed1996

Effect of the somatostatin analogue octreotide on experimental pancreatitis in rats.

Somatostatin and its analogue octreotide have a profound inhibitory effect on the endocrine and exocrine secretions of the pancreas, stomach, and small intestine. Previous studies have been inconclusive about the possible therapeutic effect of somatostatin and its analogues in the treatment of pancreatitis. This study assessed the effect of the long acting somatostatin analogue, octreotide, in two models of experimental pancreatitis in rats. Necrotizing pancreatitis was induced by pancreatic injection of 5 ml taurocholate, 5% in male Wistar rats. In a second model mild edematous pancreatitis was induced by intravenous injection of caerulein at a supramaximal dose, 6 micrograms/kg/hr, for 5 hr. Compared to untreated rats, treatment with octreotide either prior to or following the induction of necrotizing pancreatitis resulted in less hypocalcemia (P < 0.05) and acidosis (P < 0.05), and prevented the increase in pancreatic weight (P < 0.05). Amylase levels remained high. After 20 days, there was less pancreatic damage, lower mortality rates (P < 0.05), and increase in body weight (P < 0.05). In the model of milder pancreatitis, octreotide treatment attenuated the increase in pancreatic weight (P < 0.05) and pathological damage (P < 0.05). We concluded that the somatostatin analogue octreotide has a beneficial effect in the treatment of experimental acute pancreatitis.

Acute Disease↗
PubMed1996

Endometriosis in abdominal scars: a diagnostic pitfall.

Endometriosis is ectopic endometrial tissue that responds to hormonal stimulation and is found in 8 to 15 per cent of all menstruating women. Endometrioma in a surgical scar is rare and appears in 0.1 per cent of women who have undergone cesarean section; 25 per cent of these women have concomitant pelvic endometriosis. Endometrioma in a scar can present as a painful swelling on the scar that worsens during cough and effort, with the patient's complaints resembling those of a postoperative hernia occurring in a scar. It can also mimic other lesions of the abdominal wall, such as hematomas, granulomas, abscesses, and tumors. Four cases of endometriomas in a cesarean section scar are described. Two were diagnosed preoperatively as postoperative ventral hernias, and the other two presented with an abdominal wall mass causing pain and discomfort. All patients underwent surgery, and the error of their preoperative diagnosis was revealed by histology, which confirmed endometrioma. We contend that endometrioma in scarring is a diagnostic pitfall that should be considered in the differential diagnosis of postoperative ventral hernias and various abdominal wall masses.

Abdominal Muscles↗
PubMed1995

Mechanism of action of the antineoplastic drug lonidamine: 31P and 13C nuclear magnetic resonance studies.

The mechanism of action of the antineoplastic drug lonidamine (LND) on MCF-7 human breast cancer cells was studied with the use of 31P and 13C nuclear magnetic resonance (NMR) spectroscopy. The cells were embedded in alginate microcapsules, perfused with growth media and LND at physiological conditions in the NMR tube, and continuously monitored in vivo for the effects of LND. 31P NMR demonstrated intracellular acidification after LND perfusion concomitant with ATP depletion and changes in phospholipid metabolites. 13C NMR showed marked LND-induced accumulation of lactate, and spectra of the perfusate disclosed that LND inhibited lactate transport. Kinetic 13C NMR also furnished information on LND effects on glucose metabolism; LND decreased initial glucose uptake and lactate formation, although the final intracellular glucose levels were higher compared with those in controls. Combined administration of LND and the metabolic inhibitor 2-deoxyglucose yielded additive but not synergistic cytotoxicity and enabled assessment of hexokinase activity. Overall, the results indicate that the major metabolic changes induced by LND are inhibition of lactate transport and its accumulation, which lead to intracellular acidification.

Antineoplastic Agents↗
PubMed1995

Hormone dependence of breast cancer cells and the effects of tamoxifen and estrogen: 31P NMR studies.

Many breast tumors appear to progress from estrogen-dependent growth to a more malignant phenotype characterized by estrogen-independent growth, antiestrogen resistance, and a high metastatic potential. Utilizing 31P NMR spectroscopy on human breast cancer cells growing in vitro, we have investigated the effects of 17 beta-estradiol and tamoxifen on the metabolic/bioenergetic spectra of a series of human breast cancer cells that vary in their estrogen and antiestrogen responsiveness. A comparison of baseline spectra associates higher levels of phosphodiesters and UDP-glucosides (e.g. UDP-glucose, UDP-N-acetylglucosamine), and lower phosphocholine/glycerylphosphocholine and phosphocholine/phosphoethanolamine ratios, with the acquisition of estrogen-independent growth in estrogen receptor expressing cells. No metabolic changes are clearly associated with the metastatic phenotype. Whilst estrogen treatment produces no consistently significant spectral changes in any of the cell lines, the estrogen-independent and estrogen-responsive MCF7/MIII cell line responds to tamoxifen treatment by significantly increasing all spectral resonances 30%-40% above baseline values. This may reflect a tamoxifen-induced change to a more differentiated or apoptotic phenotype, or an attempt by the cells to reverse the inhibitory effects of the drug. The ability to detect metabolic changes in response to tamoxifen by NMR spectroscopy may provide a novel means to identify those tumors that are responsive to antiestrogen therapy.

Adenocarcinoma↗
PubMed1995

Preliminary report of a prospective randomized study of octreotide in the treatment of severe acute pancreatitis.

BACKGROUND: Experimental and clinical studies on the effect of octreotide in the treatment of patients with acute pancreatitis have presented controversial results. Since January 1992, we have been conducting a prospective randomized study on the clinical effect of octreotide in severe acute pancreatitis, at three hospitals in Israel. STUDY DESIGN: The entering criteria included three or more of the Ranson's prognostic signs and computed tomographic findings of severe pancreatitis. Patients were randomly assigned to conservative treatment either with or without octreotide (0.1 mg injected subcutaneously three times a day). The end points of the study included: complication rate (adult respiratory distress syndrome [ARDS], sepsis, renal failure, pseudocyst, fistula, and abscess), length of hospital stay, and mortality. RESULTS: During the first two years (from January 1992 to December 1993), 51 patients entered the study. After evaluation, 13 patients were excluded due to failure to meet the entering criteria, incomplete data, or incorrect diagnosis. Of the remaining 38 patients, 19 were assigned to octreotide (treatment group) and 19 to conservative treatment alone (control group). The two groups were matched with regard to age, sex, etiology, and severity of disease. The complication rate was lower in the treatment group compared with the control group with regard to sepsis (26 compared with 74 percent, p = 0.004) and ARDS (37 compared with 63 percent, p = 0.1). The hospital stay was shorter in the treatment group compared with the control group (17.9 compared with 34.1 days, p = 0.02). Death occurred in two patients in the treatment group and six patients in the control group. CONCLUSIONS: Although some of the parameters did not reach statistical significance, these preliminary results suggest that octreotide may have a beneficial effect in the treatment of patients with severe acute pancreatitis. This study is scheduled to continue for two more years.

Abscess↗
PubMed1995

[Abdominal wall endometriosis imitating incisional hernia].

Pain and swelling in abdominal wall scars that become more severe on coughing and straining, are typical symptoms of postoperative ventral hernias. Other abdominal wall lesions, such as hematomas, granulomas and neoplasms, can evoke similar symptoms. Usually the diagnosis can be made by physical examination, but occasionally only at operation. Endometriosis in a postoperative scar is rare, and the symptoms are usually associated with the menstrual cycle. We describe a 40-year-old woman who suffered from pain and swelling in a cesarean section scar of 8 years duration. The symptoms worsened on coughing and during exercise. At operation, a 3 x 5 cm nodule was excised from the depths of the scar; endometriosis was found on histopathological examination. Endometriosis should be included in the differential diagnosis of abdominal scar lesions following gynecological operations.

Abdominal Muscles↗
PubMed1994

[Sclerotherapy of postoperative lymphocele].

Postoperative lymphocele is a well-documented complication of gynecological operations involving pelvic and retroperitoneal lymph node dissection. It is not uncommon following renal transplantation. We report a 77-year-old woman with a lymphocele which developed 4 months after panhysterectomy. Diagnosis was by CT scan, confirmed by aspiration and cytology. Percutaneous drainage and sclerotherapy with tetracycline was curative. This appears to be the treatment of choice for lymphocele and is superior to repeated aspirations and surgical intervention, the current usual treatment.

Aged↗
PubMed1994

Lymphocyte activation-31P magnetic resonance studies of energy metabolism and phospholipid pathways.

31P NMR spectra of perfused lymphocytes embedded in alginate capsules and activated by interleukin-2 (IL-2) are remarkably different from those of control lymphocytes. The main differences are the appearance and gradual increase of phosphodiester signals, glycerophosphocholine and glycerophosphoethanolamine. These metabolic changes also occur following perfusion with phorbol ester and after incubation with phytohemagglutinin (PHA) and are not dependent on a special growth medium. Nifedipine, a calcium channel blocking drug, inhibits the effects of PHA, but not of IL-2. There are no NMR spectral differences between peripheral lymphocytes, stimulated for 3 weeks, and tumor-infiltrating lymphocytes. Thus, sustained accelerated turnover of phosphatidylcholine (PC) and phosphatidylethanolamine is an inherent feature of the activation process. 31P NMR spectra of lymphocytes are characterized by a low phosphocholine signal. Perfusion studies with high concentrations of choline and the use of dapsone, an inhibitor of phosphocholine cytidyltransferase, indicate that choline kinase plays a key role in regulating PC synthesis in human lymphocytes.

Choline Kinase↗
PubMed1994

Metabolism of breast cancer cells as revealed by non-invasive magnetic resonance spectroscopy studies.

The basis for the use of nuclear magnetic resonance (NMR) spectroscopy as a tool to study the metabolism of breast cancer cells is described. The differences between proton (1H), carbon (13C), and phosphorus (31P) NMR methods is explained, and the techniques of cell extracts, cell suspensions and perfusion methods for cells are detailed. In order to perfuse cells they are preferably trapped in a gel matrix, either in the form of a thread or a bead. The gel must have appropriate properties that enables efficient oxygenation and availability of nutrients and drugs. The metabolic effects of perfusion of breast cancer cells with nutrients, drugs, and hormones are reported, and the clinical relevance of these results and methods are outlined.

Adenocarcinoma↗