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Biomedical subjects

M Inbar

Publications and source records attributed to M Inbar.

At least 37 records · Page 2Linked to original sources

Interferon-related mental deterioration and behavioral changes in patients with renal cell carcinoma.

Five out of 38 patients (13%) with metastatic renal cell carcinoma had mental deterioration 3 weeks to 13 months after the start of treatment with recombinant interferon alpha-C. Metastatic spread to the brain, paraneoplastic effect of the tumor on the central nervous system and other causes of dementia were excluded. Computed tomography of the brain in these patients was normal and the width of the cerebral sulci and ventricles did not correlate with the severity of dementia. Specific patterns of atrophy were not seen. General deterioration, assessed by the change in Karnofsky performance status, was associated with dementia. The dementia may have been caused by a neurotoxic effect of interferon.

Aged

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

Phase II study of recombinant interferon alpha-C in patients with metastatic renal cell carcinoma.

Recombinant interferon alpha-C is a new strain of the alpha interferon family. It was given to 33 patients with measurable metastatic renal cell carcinoma of whom 31 were evaluable. Protocol consisted of 3 million U/d for 2 weeks, then 3 million U/m2 every other day until progression. No complete response was observed. Three patients (9.7%) had partial response for a mean duration of 5.6 months and eight patients (25.8%) were stabilized for a mean of 4.3 months. Responsive sites were mainly lung, bone, and kidney, while side effects were generally mild. better results were observed in previously nephrectomized patients who had not received chemotherapy or hormonotherapy for recurrent or metastatic disease (p less than 0.05), and also in patients with a brief disease-free interval and short delay from presenting symptoms of the primary tumor until interferon treatment (p less than 0.05). Median survival was significantly longer in responders than in progressors (p less than 0.05). We suggest that the efficacy of recombinant interferon alpha-C in a low-dose regime versus other types of interferon as first-line therapy for inoperable, metastatic, or locally recurrent renal cell carcinoma should be investigated in a prospective, controlled, randomized study.

Adult

Sequential treatment of melanoma patients who progressed on interleukin-2 and dacarbazine by alpha-interferon and dacarbazine--a preliminary report.

alpha-Interferon, 3 x 10(6) U/m2 every other day, and dacarbazine, up to 800 mg/m2 every 3 weeks, were given to nine patients with metastatic malignant melanoma who had progressed on a combination of interleukin-2 and dacarbazine. Partial response was documented in two patients for 9 and 4 months. Responsive sites were the lungs, lymph nodes, liver, and skin. Failure to respond to one biologic response modifier does not predict the response to another modifier.

Adult

Late recurrence of stage I malignant melanoma.

Although the introduction of well-established risk factors has made the clinical course and prognosis of malignant melanoma disease much more predictable, in a considerable number of patients the disease's course is still not as expected. One group to which this applies are stage I melanoma patients who develop metastatic disease after 10 years or more of a disease-free interval. In our series of 94 such patients, 6 developed late relapse of their disease. The subsequent survival of these patients did not relate to any of the primary tumors' characteristics, but to the pattern of the late recurrence. Four patients with visceral metastases were dead within 1 to 5 years following relapse, one patient with lymph node involvement is alive with metastases, and another patient with skin metastases has no signs of disease following surgery and immunotherapy. Our conclusion is that malignant melanoma patients should be placed under close follow-up for the rest of their lives.

Abdominal Neoplasms

Prolonged fever as a presenting symptom in adrenal tumors.

Four patients with adrenal tumors in whom prolonged fever was the foremost symptom are presented. Two of the patients had nonfunctional adrenocortical carcinoma, one had a pheochromocytoma without adrenergic hyperactivity, and in the fourth, an aldosteronoma was found. Only in 1 case was the tumor (pheochromocytoma) resectable and this patient became afebrile post surgery. A review of the literature revealed that fever is encountered in 6-10% of cases with adrenal tumors, sometimes as the first manifestation of disease. However, a survey of the large series of fever of unknown origin revealed no mention of adrenal tumors in that group of solid tumors which many cause prolonged fever.

Adrenal Gland Neoplasms

Relationship of nuclear appearance to stromal invasion in human breast cancer.

Two biopsies of intraductal and invasive lobular carcinoma of the breast and 11 biopsies of intraductal and invasive carcinoma of the breast were examined by automated micromensurative techniques for mean nuclear area of carcinoma cells in intraductal and in invasive compartments. The nuclei of invasive carcinoma cells tended to be smaller when they invaded stroma as single cells or as "thin strands" than when they invaded as part of large sheets of cells. Cells in direct apposition with the stroma usually had smaller nuclei than cells which were found centrally in large confluent sheets of cells. Intraduct carcinoma cells approached, in size, invasive cells which formed confluent sheets, rather than cancer cells which invaded as single cells. The nuclei of cells which invaded in small groups were usually darker than those of cells in confluent sheets, which were usually more vesicular.

Adult

Conventional fractionation radiotherapy combined with 5-fluorouracil for metastatic malignant melanoma.

Clinical and experimental data suggest a synergistic antitumoral effect with the combined treatment of radiotherapy and 5-fluorouracil (5-FU) serving as a radiosensitizer. This combined modality was studied in 30 malignant melanoma patients with advanced locoregional or isolated, bulky, soft-tissue or visceral metastases. All patients were symptomatic, pain being the chief complaint, followed by symptoms related to large tumors. Treatment was given on an ambulatory basis, twice weekly, and consisted of 5-FU, 500 mg/m2 administered in 8-h i.v. drip infusion, followed by radiotherapy 8 h after completion of the 5-FU administration. 60Co teleunit, delivering 400 rad per dose per fraction, was given over 6 1/2 weeks to a total of 5,200 rad. The overall response rate was 70% (21 of 30 patients). Three patients (10%) achieved a complete response lasting from 3 to 11 months, and 18 (60%) achieved a partial response lasting from 3 to 13 months. The response rate was 82% for skin, 75% for lymph node, and 43% for visceral metastases. Symptomatic relief was obtained in 83% (25 of 30) of the patients. This palliative therapy was well-tolerated, and patients were able to maintain their routine lifestyles throughout. Only in one patient was 5-FU abandoned after 3 weeks, due to cardiac ischemia. Similar response rates have only been achieved with radiotherapy alone employing individual fractions of 600 rad or higher. Since the 5-FU we added is known to have a very limited effect on malignant melanoma, this study suggests its potential as a radiosensitizer in malignant melanoma.

Abdominal Neoplasms

Stereospecific antibodies to propranolol.

The beta-adrenergic antagonist propranolol was activated through its side chain, coupled to bovine serum albumin, and injected into BALB/c mice. After fusion of the splenocytes from these immunized mice with the NS-1 myeloma cell line, two hybridomas, producing monoclonal anti-propranolol antibodies, were isolated. Clone P-49 was monospecific for propranolol, with a significant preference for the 1-stereoisomer, as compared to the d form. On the other hand, clone P-28 cross-reacted with alprenolol as well as some other beta-antagonists. Both classes of antibodies competed with A431 epidermoid carcinoma beta 2-adrenoceptors for the binding of [3H]propranolol. When ascites cells from clone P-28 were fixed with glutaraldehyde, the anti-propranolol monoclonal antibody became cell bound. These cell-bound P-28 antibodies bind propranolol and other beta-adrenergic ligands with a similar ranking order to the soluble monoclonal antibody. The cell-bound antibody displayed a 5-fold higher affinity towards 1-propranolol than the soluble monoclonal antibody. The practical implications of these findings are discussed.

Antibodies, Monoclonal

Monoclonal antibodies embedded in their hybridoma cells: an immunodiagnostic concept.

Aldehyde fixation of hybridoma cells during active production of monoclonal antibodies (MAbs) resulted in the formation of an insoluble phase because a large number of immunologically active antibody molecules were immobilized on the fixed hybridoma cells. Such MAb preparations specific to large protein molecules and small haptens were used for the development of a homogeneous immunoassay concept.

Antibodies, Monoclonal

Dynamics and composition of serum lipids in hyperlipoproteinemias.

The microviscosity of serum lipids in patients with hyperlipoproteinemia and normal donors was determined by monitoring the degree of fluorescence polarization of the fluorescent probe 1,6-diphenyl-1,3,5-hexatrine (DPH). Determination of serum lipids--serum total cholesterol, serum triglycerides, and serum phospholipids--revealed that an increase in the ratio of cholesterol/triglyceride + phospholipid is accompanied by an increase in the degree of fluorescence polarization and an increase in the microviscosity values. Similar results were obtained with sonicated liposomes prepared from serum lipids extracts. This correlation between dynamics and composition of serum lipids was further supported by results obtained with an artificial model system of sonicated lipids dispersions. The results have shown that high microviscosity values are characteristic in patients with high levels of serum cholesterol, and that low microviscosity values are characteristic in patients with high levels of serum triglycerides. It is suggested therefore that this technique may serve as a basis for a rapid screening test for hyperlipoproteinemias.

Adult

Fluorescence polarization of DPH-labeled cells adsorbing viruses and its diagnostic potential.

Mammalian or avian cells were labeled with a fluorescent probe DPH (1,6-diphenyl-1,3,5-hexatriene). Within a few minutes after adsorption of various naked and enveloped viruses, the degree of fluorescence polarization (P) of the DPH embedded in the adsorbing cells as measured at 37 degrees C, was reduced, a finding indicating a decrease in the microviscosity of the lipids in the cell membrane. This change of fluidity was proportional to the concentration of the adsorbing virus and could be abolished or inhibited by homologous specific antiviral sera, but not by heterologous sera. Potential use of fluorescence polarization tests is described for titration of virus concentration, as well as for serological identification of a virus.

Adsorption