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Biomedical subjects

R Catane

Publications and source records attributed to R Catane.

At least 55 records · Page 3Linked to original sources
PubMed1990

[Somatostatin analogue in the treatment of neuroendocrine gut tumors].

Somatostatin is a short-acting natural peptide secreted by specialized cells in the GI tract, the central and peripheral nervous systems, and a variety of other tissues. Its many actions include suppression of the secretion of GH, TSH, GI hormones, and inhibition of GI exocrine secretion. A long-acting analogue developed by Sandoz (Sandostatin, SMS 201-995) has been used to treat acromegaly and neuroendocrine tumors. We report our experience with it in carcinoid tumors (4 cases), glucagonomas (2), gastrinoma (1), VIPoma (1) and nonfunctioning islet cell tumor (1). It was given by continuous subcutaneous infusion, using a small portable pump, in doses ranging from 300 to 1500 mcg/day, without significant side-effects. 7 of the 9 patients had complete relief of symptoms, and tumoral hormone secretion decreased in 4 of the 5 in whom it was measurable, but there was no evidence of tumor regression. SMS 201-995 is useful for the symptomatic treatment of patients with neuroendocrine gut tumors.

Adenoma, Islet Cell↗
PubMed1990

Monoclonal antibodies against carcinoembryonic antigen (CEA) discriminate between CEA produced by gastrointestinal tumors and CEA produced by other tumors.

Carcinoembryonic antigen (CEA) is a common tumor marker. It is not specific since many tumor types express it. We report here the use of a series of monoclonal anti-CEA antibodies with apparent restricted activity. These antibodies reacted histochemically with CEA produced by tumors originating in the gastrointestinal tract, but they did not react with CEA-secreting tumors of nongastrointestinal origin. We have used this phenomenon to accurately diagnose the tumor of origin in 20 patients who had a CEA-producing metastatic tumor, but in whom the primary origin was clinically not yet discovered. The use of such antibodies for diagnostic purposes may be an adjunct to other methods in evaluating tumors of unknown origin.

Aged↗
PubMed1990

Immunologic effects of AS101 in the treatment of cancer patients.

AS101 [ammonium trichloro(O,O'-dioxyethylene)tellurate] is a new immunomodulator previously shown to stimulate the production of different cytokines in vitro and in vivo. We report here our results of a phase I clinical trial conducted on 47 cancer patients with advanced malignancies. AS101 was administered intravenously at escalating doses from 1 to 10 mg/m2, twice or thrice a week. The maximal tolerated dose has not yet been determined. However, significant immunologic responses were noted at dose levels of 1-3 mg/m2 administered three times a week. At these doses statistically significant rises in gamma-interferon, natural killer cell activity, tumor necrosis factor and interleukin-2 (IL-2) levels as well as the expression of IL-2 receptors were noted. In most of the immunologic parameters the maximal response was seen at 3 mg/m2. Throughout the study toxicity was minimal. In view of these results phase II studies are currently being initiated.

Adjuvants, Immunologic↗
PubMed1989

Systemic administration of doxorubicin-containing liposomes in cancer patients: a phase I study.

A clinical study was designed to evaluate the tolerance of cancer patients to liposome-associated doxorubicin (L-DXR). The liposomes used contain phosphatidylglycerol, phosphatidylcholine, cholesterol, and DXR intercalated in the lipid bilayer, and have a mean size in the range of 0.3-0.5 microns. Thirty-two patients, most of them with primary or metastatic liver cancer refractory to conventional therapy, were entered into the study. A total of 69 courses of therapy was administered by intravenous infusion of a suspension of L-DXR (0.5-2.0 mg DXR/ml) in physiologic saline at an approximate rate of 2 ml/min given on a 3-week intermittent schedule. The L-DXR and phospholipid doses were escalated from 20 mg/m2 and 0.3 g/m2 to 120 mg/m2 and 3.2 g/m2 respectively. Treatment was generally well tolerated and acute toxic effects such as nausea and vomiting were mild and infrequent. Chills and fever (greater than 38.0 degrees C) were observed in three patients during infusion of L-DXR and in seven patients 6-12 h after the end of infusion. Median WBC nadir counts were 2700, 2300 and 700/microliters at 85, 100 and 120 mg/m2 respectively. All three patients receiving 120 mg/m2 developed grade 4 leukopenia and fever requiring intravenous antibiotics, and, in two of them, severe stomatitis (grades 3 and 4) was observed. Significant hair loss was apparent in all patients receiving doses higher than 50 mg/m2. The maximal tolerated dose of L-DXR appears to be 120 mg/m2, with leukopenia and stomatitis being the dose-limiting factors. While the subacute toxicity of L-DXR appears to be qualitatively similar to that of free DXR, its tolerance exceeds the recommended dose of free DXR (75 mg/m2) in the standard 3-weekly schedule.

Adult↗
PubMed1989

Chlorpromazine and dexamethasone versus high-dose metoclopramide and dexamethasone in patients receiving cancer chemotherapy, particularly cis-platinum: a prospective randomized crossover study.

Sixty-nine patients with malignant tumors receiving cancer chemotherapy, 90% including cis-platinum, were evaluated in a randomized crossover study for the antiemetic efficacy and the side effects of two antiemetic regimens: chlorpromazine (CPM) 2.5 mg/kg in 5 doses plus dexamethasone (DXM) 0.2 mg/kg in 2 doses, and high-dose metoclopramide (HD-MCP) 10 mg/kg in 5 doses plus the same dose of DXM. In 69% of 173 courses of chemotherapy, antiemetic response was achieved, and in 26% emesis was completely prevented. There was no statistical difference in the response to the antiemetic regimens, but 65% of the patients who completed 3 courses of chemotherapy preferred HD-MCP plus DXM. The main side effects of the treatment were drowsiness, nervousness, diarrhea and extrapyramidal reactions. HD-MCP plus DXM is recommended as a first line antiemetic treatment in patients receiving cancer chemotherapy. Patients resistant to this treatment should receive CPM plus DXM treatment.

Adolescent↗
PubMed1988

Early and delayed neurotoxicity of mitoxantrone and doxorubicin following subarachnoid injection.

Doxorubicin (DXR) and Mitoxantrone (MXN) were administered into the subarachnoid space of mice or the ventricular system of rats. The maximal non-toxic systemic single dose (zero mortality = LDo) of DXR or MXN was used as reference for planning drug doses for CSF administration. LDo in mice were: 8 mg/kg DXR and 6 mg/kg MXN; in rats: 6 mg/kg DXR and 4.5 mg/kg MXN. Signs of neurotoxicity were remarkably similar in DXR or MXN treatment animals and included: head tremor, atactic-dystonic posture and circling behavior. The toxicity was dose dependent. Doses of greater than or equal to 10% the LDo caused early appearance of clinical signs: a dose of 10% LDo caused neurotoxicity in 90% of DXR treated mice and in only 15% of MXN-treated animals. Treatment with 25% LDo MXN caused neurotoxicity in 30% of treated animals. Doses of less than or equal to 5% the LDo caused a delayed onset of DXR neurotoxicity in one third of treated mice (after 60-90 days). In rats, neurotoxicity was of an early onset and augmented severity following doses of greater than or equal to 5% LDo. Abnormal histopathological findings were detected only in symptomatic animals with early toxicity and were usually restricted to superficial cortical layers in mice or the basal surface of the brainstem in rats. Brains of mice with delayed toxicity were unremarkable. The levels of monoamine neurotransmitters and their metabolites (DA, DOPAC, HVA, NE, 5HT) in the striatum, cortex and cerebellum of mice with early and delayed DXR neurotoxicity did not differ from normal brains.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Indomethacin and dexamethasone treatment in experimental neoplastic spinal cord compression: Part 1. Effect on water content and specific gravity.

Water content and specific gravity were measured in the cervical, high thoracic, thoracic, and lumbar segments in an experimental model of neoplastic epidural spinal cord compression in rats harboring a thoracolumbar tumor. Increased content of water was observed only in the compressed lumbar cord segments of paralyzed rats (P less than 0.04). A progressive increase in specific gravity values of the compressed segments accompanied the increasing severity of neurological dysfunction (P less than 0.003 in paraplegic rats). Electron microscopy of the compressed cord revealed enlarged interstitial spaces, myelin breakdown, and extravasated blood cellular elements. Treatment with dexamethasone (10 mg/kg q 12 hr x 3) failed to reduce the increased content of water, but corrected specific gravity changes. Treatment with indomethacin (10 mg/kg q 12 hr x 3) reduced both elevated water content and specific gravity values back to normal levels. In untreated animals, the interval between the first neurological sign (limp tail) and paraplegia was 2.8 +/- 0.34 days (mean +/- SE). Treatment with dexamethasone lengthened this period by 28.6% (P less than 0.05); treatment with indomethacin lengthened it by 66.4% (P less than 0.005). We conclude that, because the specific gravity measurements in this model reflect complex pathophysiological processes, their translation into water content values is not advisable. Pharmacological intervention with indomethacin compares favorably with dexamethasone in reduction of spinal cord edema and in delaying the onset of paraplegia.

Animals↗
PubMed1987

Alteration of blood-brain-CSF barrier in experimental meningeal carcinomatosis. A morphologic and adriamycin-penetration study.

An experimental model of meningeal carcinomatosis has been produced by subarachnoid inoculation of B16 melanoma cells into C57BL mice. Injection of 10(3) viable cells was sufficient to cause 100% tumor incidence and death within a median survival time of 17 days. The tumor infiltrated diffusely the meninges of the brain and spinal cord and filled the ventricular system. Electron microscopic study of the leptomeningeal tumor revealed newly formed microvessels with fenestrated endothelium. The integrity of the blood-brain barrier was studied by the extravasation of the Evans blue and the Horseradish peroxidase tracers. Barrier disruption became evident from the seventh day on, using Evans blue. Electron microscopy study showed peroxidase activity in the luminal and abluminal sides of the meningeal microvessels, and within the tight junctions. Similar findings were noted in cortical capillaries adjacent to the meningeal tumor. Brain concentrations of Adriamycin (ADR) following administration of an intravenous dose of either 10 mg/kg or 50 mg/kg were measured on days 0 to 14 after tumor inoculation. A significant increase in mean +/- SEM content of whole brain ADR was observed only with the 50 mg/kg dose in days 7 to 14 (0.69 +/- 0.02 micrograms/g wet tissue weight) as compared to tumor-free controls (0.43 +/- 0.01, p less than 0.05). Our study suggests that barrier alteration in meningeal carcinomatosis allows extravasation of tracer solutes. Still, in order to achieve a significant increase in a water soluble drug penetration through the disrupted barrier, a high-dose drug regimen is required.

Animals↗
PubMed1987

Experimental neoplastic spinal cord compression: evoked potentials, edema, prostaglandins, and light and electron microscopy.

Spinal cord compression was induced in Fischer rats by percutaneous inoculation of 10(6) cells of malignant fibrous histiocytoma anterior to the T13 vertebral body. Paraplegia and incontinence occurred in all animals after 14-27 days (median, 23 +/- 3.0 days). Autonomic dysfunction and a measurable increase in tumor volume were documented with the use of computer tomography. The tumor penetrated the vertebral bone, invaded the epidural space, and gradually compressed the lumbar spinal segments. Electron-microscopic examination revealed dilated intermyelin spaces containing exuded homogenous material and extravasated leukocytes and erythrocytes. Myelin breakdown was accompanied by the presence of lipid-laden macrophages. Sequential recording of somatosensory evoked potentials (SEP) revealed a progressive increase in the latency of the cervical responses, which preceded the onset of clinical signs. In the presence of paraplegia, spinal cord conductivity was abolished. The levels of the prostaglandins TXB2, 6-keto-PGF1 alpha, and PGE2 were measured in the compressed and remote spinal cord segments during the presymptomatic and symptomatic periods. Only PGE2 was significantly elevated (P less than 0.001) in the paraplegic rats, all along the spinal cord segments. A significant increase in water content was measured in the compressed lumbar segments in the presymptomatic period, and when paralysis set in it was increased in the adjacent low thoracic area as well. Tissue specific gravity was significantly increased only in paraplegic rats in the compressed (P less than 0.01) and the adjacent low thoracic areas (P less than 0.05) but no significant change occurred during the presymptomatic period. Multiple mechanisms play a role in the pathogenesis of neurologic symptoms in neoplastic spinal cord compression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Adriamycin, vinblastine and mitomycin C as second-line chemotherapy in advanced breast cancer.

Thirty-six evaluable patients with metastatic measurable breast carcinoma previously treated with CMF or CMFVP were given second-line chemotherapy with Adriamycin, vinblastine, and mitomycin C (AVM), as follows: Adriamycin 20 mg/m2 and vinblastine 6 mg/m2 by i. v. push on days 1, 8, and 15, and mitomycin C 10 mg/m2 i. v. on day 1, every 6 weeks. Ten patients (28%) achieved partial remission (PR) lasting a median of 10 months, and eight patients (22%) experienced improvement of a lesser level than PR. An additional nine patients (25%) had disease stabilization; in the remaining nine patients (25%), persistent disease progression was observed. The median survival from the onset of AVM was 7 months for all patients; patients with PR survived a median of 13 months. Myelotoxicity was substantial and frequently interfered with the optimal administration of AVM, especially in patients with skeletal metastases; four patients were hospitalized with leukopenia and fever; all recovered promptly; one death was probably related to thrombocytopenia and CNS bleeding. Our results with AVM are similar to the average response rate published in the literature with the use of Adriamycin as a single agent in previously treated patients with advanced breast cancer.

Adult↗
PubMed1986

Selective route of doxorubicin administration improves outcome in experimental malignant epidural cord compression.

Epidural spinal cord compression was produced in adult Fischer rats by injection of 10(6) viable cells of malignant fibrous histiocytoma anterior to the T-13 vertebral body. Using a tracer dye, it was demonstrated that a portion of the inoculum was always present in the anterior epidural space at the time of inoculation. Paraplegia and incontinence occurred consistently on Days 14 to 27 (median, 23 +/- 3.0). By sequential computed tomographic scans, the growth of the paravertebral tumor was documented and its volume was calculated. A single dose of cisplatin (i.p., 6 mg/kg) or doxorubicin (DXR, i.v. jugular, 6 mg/kg) was administered on Day 1. On Day 18, tumor volume was significantly reduced by DXR (P less than 0.001) and cisplatin (P less than 0.01), but paraplegia continued to occur as in the untreated rats. Comparison of treatment outcome with DXR administered via the jugular vs. the tail vein revealed that both were equally effective in retarding the growth of the paravertebral tumor, and both caused a similar transient leukopenia. However, only the tail DXR brought about a significant delay in the onset of paraplegia (P less than 0.004) and significantly increased the survival (P less than 0.001). It is suggested that the lack of efficacy of systemic chemotherapy for tumors located in the epidural space is probably related to inadequate drug exposure. The improved outcome with tail DXR infusion may be explained by the regional spinal venous perfusion, which allows an increase in the local drug concentration during its first passage through the epidural venous plexus.

Animals↗
PubMed1985

Continuous epidural narcotic analgesia for intractable pain due to malignancy.

Eighty consecutive cancer patients with severe pain, uncontrolled by conventional narcotic analgesics, received a 2-mg test dose of morphine epidurally. Thirty-four of them had significant pain relief and were thus selected to receive continuous treatment. This consisted of 2-6 mg of morphine administered every 8-24 hours through an indwelling epidural catheter. The duration of treatment was from 1 to 28 weeks with a median of 4 weeks. Twenty-five (76%) of the patients experienced complete relief of pain, while nine had only a partial analgesic response. Complications were minimal. No sepsis, hypotension, or respiratory depression occurred. It is recommended that cancer patients with intractable pain will be selected for continuous epidural analgesia by evaluating their response to a test dose of epidural morphine.

Adult↗