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Biomedical subjects

I D Kurzman

Publications and source records attributed to I D Kurzman.

35 records · Page 2Linked to original sources
PubMed1993

In vitro and in vivo canine mononuclear cell production of tumor necrosis factor induced by muramyl peptides and lipopolysaccharide.

Tumor necrosis factor (TNF) is a potent mediator of tumor cell killing by activated monocytes and macrophages. We measured TNF activity induced by muramyl peptides and lipopolysaccharide (LPS) in normal dogs. Canine adherent mononuclear cells were isolated and cultured in either medium alone or medium containing muramyl dipeptide (MDP) or MDP plus LPS. After 18 h, culture supernatants were collected and assayed for TNF activity. Sera from dogs injected with liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) were also evaluated for TNF activity. TNF activity both in supernatants and in sera was detected in a 18 h WEHI-164 cell cytotoxicity assay and was confirmed by a monoclonal antibody directed against recombinant human TNF-alpha. Results showed a significant increase in TNF activity from mononuclear cells exposed to MDP or MDP plus LPS of 20% and 88%, respectively; P < 0.0005. Serum TNF activity rapidly increased within 2-3 h post L-MTP-PE injection and subsequently declined to pretreatment level at 4 h post administration. This study demonstrates that MDP +/- LPS can stimulate canine adherent mononuclear cells to release TNF and intravenous injection of L-MTP-PE is capable of rendering the in vivo release of TNF in normal dogs.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1993

Muramyl peptides augment the in vitro and in vivo cytostatic activity of canine plastic-adherent mononuclear cells against canine osteosarcoma cells.

A tumor cytostasis assay was developed that measured the effect of the immunomodulator muramyl dipeptide (MDP) on the in vitro cytostatic activity of canine plastic-adherent mononuclear cells. Mononuclear cells were isolated from the peripheral blood of healthy Beagle donors and allowed to adhere to a 96-well microtiter plate. The adherent cell population was characterized by cell morphology, non-specific esterase staining, and flow microfluorometry to be approximately 42% monocytes, 49% lymphocytes, and 8% eosinophils. Canine plastic-adherent mononuclear cells spontaneously caused cytostasis of D-17 canine osteosarcoma target cell proliferation. The spontaneous cytostatic activity of adherent mononuclear cells was significantly augmented by exposure to MDP or to lipopolysaccharide (LPS), with maximal cytostatic activity being observed after combined exposure to MDP and LPS. Mononuclear cell cytostasis toward D-17 canine osteosarcoma and A375 human melanoma cells was enhanced (P < 0.05) when normal dogs were administered liposome-encapsulated muramyl tripeptide phosphatidylethanolamine, a lipophilic derivative of MDP, by intravenous injection.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1992

Risk factors, clinical signs, and survival in cats with a clinical diagnosis of idiopathic hypertrophic cardiomyopathy: 74 cases (1985-1989).

Population characteristics, risk factors, and survival characteristics were evaluated in 74 cats with hypertrophic cardiomyopathy (HC) seen at North Carolina State University veterinary teaching hospital from 1985 to 1989, and compared with 82 clinically normal cats. The mean (+/- SD) age of cats with HC was 6.5 (4.0) years. Neutered males were at significantly greater risk (odds ratio 3.1) than neutered females. Breed, body weight, or coat color were not determined to be risk factors for HC. Tricolor cats were significantly underrepresented, probably reflecting the male predisposition for HC and not a true risk reduction associated with coat color. Forty-one cats were without clinical signs of heart disease (murmur and/or gallop sound only), 24 were in congestive heart failure, and 9 had systemic arterial embolism, 3 of which had concomitant congestive heart failure. The median survival time for 61 cats with HC, for which survival information could be obtained and that were not euthanatized on day 1, was 732 days. Survival was not affected by age at diagnosis, breed, body weight, or sex. However, clinical signs were important in determining prognosis; cats with heart rates greater than 200 beats/min survived significantly longer (median survival greater than 1,830 days) than those with heart rates greater than or equal to 200 beats/min (median survival = 152 days). Cats without clinical signs (median survival greater than 1,830 days) survived longer than those with clinical signs, and cats in heart failure survived a median of 92 days, compared with 61 days for those with systemic arterial embolism. Analysis of survival revealed no significant difference between the 2 groups of cats with clinical signs; however, all cats with embolism and only 60% of cats with heart failure were dead 6 months after diagnosis.

Animals↗
PubMed1992

Effect of colony-stimulating factors on number and function of circulating monocytes in normal dogs.

Recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) and recombinant canine granulocyte colony-stimulating factor (rcG-CSF) were administered to normal dogs, and effect on monocyte number and function was evaluated. rhuGM-CSF, administered for 14 days, induced a 2.5-fold increase in monocyte counts on day 3. Leukocytes increased two-fold after 1 day. Counts peaked on day 11, then declined, approaching pretreatment counts by day 15. On day 7, in vivo monocyte cytostasis activity was significantly enhanced, and declined on day 14. rcG-CSF induced a 4.5-fold increase in monocyte counts on day 3. Leukocyte counts increased three-fold after 1 day. Increased counts were maintained for 69 days, at which time treatment was discontinued. There was no effect of rcG-CSF on in vivo monocyte cytostasis activity on days 7 and 14.

Animals↗
PubMed1991

Obesity in the dog: role of the adrenal steroid dehydroepiandrosterone (DHEA).

It is estimated that 25-50% of pet dogs are overweight. In rodents and humans the adrenal steroid dehydroepiandrosterone (DHEA) has been associated with loss of body weight and reduction in total body fat content. We have shown that administration of DHEA results in weight loss in spontaneously obese dogs. DHEA also lowered serum cholesterol, in particular, the low density lipoprotein component of the plasma cholesterol. We hypothesize that treatment of obese dogs with DHEA in combination with a low energy, high fiber diet will result in greater weight loss when compared with dogs on the same diet, without DHEA. In the current study, spontaneously obese dogs were fed a uniform low energy, high fiber diet and then randomized to receive DHEA or placebo. Preliminary results show that the mean total body weight lost for dogs receiving DHEA was 3.59 kg compared with 2.38 kg for dogs receiving placebo (P greater than 0.05). The percent excess body weight (above ideal body weight) lost for the DHEA group was 65.7 versus 31.4 for the placebo group (P less than 0.02). The percent excess body weight lost per month on the study for the DHEA group was 15 versus 8.2 for the placebo group (P = 0.069). Although these results are preliminary, they indicate that DHEA combined with a low energy, high fiber diet enhances the loss of excess body weight compared with diet modification alone.

Animals↗
PubMed1991

Evaluation of two applanation tonometers in cats.

Comparisons of the MacKay-Marg and Tono-Pen applanation tonometers in open and closed in vitro systems were made for the eyes of cats. Both instruments significantly underestimated intraocular pressure (IOP) vs direct manometry (P less than 0.001), but in readily predictable manner, with high coefficients of determination (r2 = 0.99). For tonometer 1 (MacKay-Marg), calculated actual IOP = 1.36 x (MacKay-Marg measurement) - 1.67 mm of Hg; and for tonometer 2 (Tono-Pen), calculated actual IOP = 1.37 x (Tono-Pen measurement) + 0.8 mm of HG, using measurements from 11 enucleated eyes. In vivo comparisons were initially made in 81 clinically normal eyes (n = 41 cats) by applying the Tono-Pen first followed by the MacKay-Marg. Compared with the MacKay-Marg, the Tono-Pen significantly (P less than 0.001) underestimated IOP in these cats. When the order of tonometer applanation was subsequently reversed in 73 clinically normal eyes (n = 37 cats) the Tono-Pen again significantly (P less than 0.001) underestimated IOP, compared with the MacKay-Marg. Alterations in tonometer order did not result in significant differences in measured IOP for the MacKay-Marg when compared with itself, but Tono-Pen measurements were significantly (P less than 0.05) less when its use followed, rather than preceded, that of the MacKay-Marg. Mean (+/- SD) IOP in clinically normal cats when each tonometer was used first was 22.6 +/- 4.0 mm of Hg (range, 14 to 32 mm of Hg) for the MacKay-Marg and 19.7 +/- 5.6 mm of Hg (9 to 31 mm of Hg) for the Tono-Pen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Reduction in body weight and cholesterol in spontaneously obese dogs by dehydroepiandrosterone.

We studied the effect(s) of exogenous dehydroepiandrosterone (DHEA) in spontaneously obese dogs. Nineteen euthyroid obese and six non-obese normal dogs were evaluated. Dogs received DHEA for three months at an escalating dose of 30-75 mg/kg p.o. daily. We found a 3 percent reduction in total body weight/month in 68 percent of the obese dogs, without reduction in food intake. The normal dogs did not lose weight or reduce food intake. Serum cholesterol in obese dogs went from 226 to 173 mg/dl post-treatment and in normal dogs from 128 to 89 mg/dl. Analysis of lipoproteins in four normal dogs revealed that the marked reduction in cholesterol most significantly affected the LDL-HDL1 fraction.

Animals↗
PubMed1989

Therapy for osteosarcoma in dogs with intravenous injection of liposome-encapsulated muramyl tripeptide.

Canine osteosarcoma is a spontaneous malignancy in dogs, characterized by micrometastasis to pulmonary and extrapulmonary tissues at the time of diagnosis. Standard treatment involves amputation of the affected leg, but median survival time is 3-4 months with death due to metastasis. A randomized double-blind trial was conducted to evaluate liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (liposome/MTP-PE) as a treatment for metastasis in dogs undergoing amputation for osteosarcoma. Fourteen dogs were treated with liposome/MTP-PE, and 13 were treated with empty liposomes. Median survival time was 222 days for dogs treated with liposome/MTP-PE, compared to 77 days for dogs treated with empty liposomes (P less than .002). In the liposome/MTP-PE-treated group there were still four dogs alive and free of metastasis at greater than 1 year post surgery. Treatment was well tolerated; no significant toxic effects were noted except for mild elevations in body temperature (1-2 degrees C) for 2-6 hours post injection.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Radiotherapy of malignant nasal tumors in 67 dogs.

The nasal cavity of 67 dogs with malignant nasal neoplasia was treated with radiation. Preirradiation surgical cytoreduction of the tumor was done in 41 dogs. Fifty dogs were irradiated by use of 10 fractions over 22 days, and 17 dogs were given a similar total dose in 5 fractions over 35 days. The range of survival times (0.5 to 42 months), median survival time (8.5 months), and 1- and 2-year survival rates (38% and 30%, respectively) were better than those expected for other methods of treatment. Serious complications were few (4%). Survival times for dogs were determined on the basis of histologic tumor type and on the basis of megavoltage (cobalt or linear accelerator) vs softer deep radiation (cesium or orthovoltage) treatment, with or without cytoreductive surgery. Survival times of 10 dogs given softer radiation without surgery were shorter than those of 14 dogs that were given softer radiation and had cytoreductive surgery. Survival times of dogs that were given softer radiation and had surgery were similar to those of dogs that were given megavoltage radiation only. Cytoreductive surgery did not improve survival times for dogs that were given megavoltage radiation. Median survival time for 38 dogs with adenocarcinoma was 12 months, compared with 6 months for 14 dogs with squamous cell or undifferentiated carcinoma. Median survival time for 16 dogs with a variety of sarcomas was 11.2 months. Survival times of dogs with adenocarcinoma or sarcoma were significantly better (P less than 0.02 or 0.03) than for dogs with squamous cell or undifferentiated carcinoma. Necropsies were performed on 27 of 58 dogs that died or were euthanatized.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1983

Canine mammary epithelial neoplasms: biologic implications of morphologic characteristics assessed in 232 dogs.

We studied 232 dogs that underwent mastectomy for mammary epithelial neoplasms. The mastectomy specimens were evaluated according to structural parameters found to be prognostically significant in human mammary neoplasms, such as grade of atypia in non-invasive proliferations of duct epithelium, extent of malignant disease, and nuclear differentiation in malignant neoplasms. In this study, the biologic behavior of mammary lesions was assessed according to the frequency of development of de novo or recurrent invasive carcinoma within two years. Our data indicate that we can recognize structural variables which permit classification of mammary neoplasms into categories with distinct patterns of biologic behavior. In addition to normotypic proliferative lesions and invasive malignant neoplasms, we were able to identify precancerous atypic and non-invasive malignant neoplasms that are considered precursor lesions in women. Also, as in women, nuclear differentiation was found to be a prognostically significant variable. Lymphoid cellular reactions, considered to be structural correlates of host-tumor immune responses in women, were noted in 35% of dogs with precancerous or malignant neoplasms. Application of the described parameters should facilitate comparative studies of canine and human mammary carcinogenesis and use of the dog as a model for the development of new therapeutic modalities and immunoprophylaxis of human mammary cancer.

Animals↗
PubMed1983

Alveolar lavage in dogs.

Alveolar lavage was performed in 10 healthy dogs. After tracheal intubation was done, a sterile fiberoptic bronchoscope was wedged in a distant bronchus and the lungs were lavaged with sterile saline solution. An average of 140 ml of saline solution was flushed into the lungs of each dog, and an average of 79% of the solution was recovered. Examination of the recovered fluid revealed average total cell counts of 6.4 X 10(6) cells/dog. Average differential cell counts were as follows: macrophages, 50.5%; lymphocytes, 46.0%; and neutrophils, 3.5%. Results of bacterial culture of the recovered fluid were negative in 8 dogs and positive in 2; Bordetella bronchiseptica was isolated in 1 dog and Klebsiella pneumoniae was isolated in the other.

Animals↗
PubMedDate not supplied

Evaluation of L-asparaginase: polyethylene glycol conjugate versus native L-asparaginase combined with chemotherapy. A randomized double-blind study in canine lymphoma.

L-asparaginase is an enzyme that inhibits protein synthesis by the depletion of sources of L-asparagine, which is necessary for transformed lymphoid cells to proliferate. L-asparaginase is used in the treatment of childhood acute lymphoblastic leukemia. A problem with L-asparaginase therapy is the immunogenicity of the enzyme and the development of anaphylactic reactions. Canine lymphoma is a predominantly B-cell tumor with widespread disease; without treatment, dogs with lymphoma usually survive 1-2 months. Canine lymphoma will respond to L-asparaginase therapy. A randomized double-blind study evaluated a polyethylene glycol (PEG) conjugate L-asparaginase combined with chemotherapy (vincristine, cyclophosphamide, doxorubicin, and prednisone). Thirty-five dogs were randomized to the PEG L-asparaginase group, and 34 dogs were randomized to the native L-asparaginase group. Thirty dogs (85.7%) achieved a complete remission (CR) with a median time to relapse of 217 days, and 32 (94.1%) dogs in the native L-asparaginase group achieved a CR with a median time to relapse of 214 days (P greater than 0.05). The asparaginase was well tolerated in both groups. Two dogs in the native L-asparaginase group had severe allergic reactions, and one dog in the PEG asparaginase group had a generalized urticarial reaction after repeated injections. This study indicates that PEG L-asparaginase has equal therapeutic efficacy to native L-asparaginase.

Animals↗
PubMedDate not supplied

Amputation and carboplatin for treatment of dogs with osteosarcoma: 48 cases (1991 to 1993).

Forty-eight dogs with histologically confirmed appendicular osteosarcoma (OSA) entered a prospective clinical trial evaluating treatment with amputation and up to 4 doses of carboplatin given every 21 days. The median disease-free interval (DFI) was 257 days, with 31.2% of the dogs disease-free at 1 year. The median survival time was 321 days, with 35.4% of the dogs alive at 1 year. Dogs with proximal humeral OSA had shorter DFI (P = .016) and survival (P = .037) times than dogs with OSA at other locations. Dogs with lower body weights ( < 40 kg) had longer DFI (P = .0056) and survival (P = .007) times than larger dogs. Survival times for dogs that received carboplatin were statistically longer than those previously reported for amputation alone (P < .001). DFI and survival times are similar to those previously reported for 2 to 4 doses of cisplatin. Carboplatin appears to be a well-tolerated chemotherapeutic drug that can be given safely every 21 days at a dose of 300 mg/m2. Neutropenia was the dose-limiting toxicity in this study.

Amputation, Surgical↗
PubMedDate not supplied

Cisplatin and doxorubicin combination chemotherapy for the treatment of canine osteosarcoma: a pilot study.

Sixteen dogs with histologically confirmed appendicular osteosarcoma were treated by amputation followed by cisplatin and doxorubicin chemotherapy. All dogs began chemotherapy within 24 hours of surgery. Cisplatin was administered at 50 mg/m2 intravenously (IV) concurrent with saline-induced diuresis. Doxorubicin was administered 24 hours later at 15 mg/m2 as a slow IV bolus. This protocol was given on a 21-day cycle for 4 cycles. No dose delays were required, but dose reduction of doxorubicin was required in 2 dogs because of neutropenia. Thoracic radiography was performed every 2 months after completion of therapy to monitor for metastatic disease. Two dogs were still alive and free from disease at the time of last contact (24 and 75 months, respectively). Postmortem examinations were performed on 13 of the 14 dogs that died. Eight of these dogs were euthanized because of metastatic osteosarcoma. Of the remaining 5 dogs, euthanasia was performed because of complications of idiopathic megaesophagus (n = 1), arthritis (n = 2), and hemangiosarcoma (n = 2). The median disease-free interval and survival times were 15.7 and 18 months, respectively. When compared to a historical group of 36 dogs with appendicular osteosarcoma treated with surgery and 4 doses of cisplatin. both disease-free interval and overall survival were significantly longer in the study population (P < .015 and P < .007, respectively).

Amputation, Surgical↗
PubMedDate not supplied

Hypocholesterolemic effect of exogenous dehydroepiandrosterone administration in the rhesus monkey.

The effect(s) of exogenous dehydroepiandrosterone (DHEA) was studied in healthy non-obese rhesus monkeys. Six monkeys were given 60 mg/kg/day DHEA for 4 weeks. The dose was then increased to 75 mg/kg/day for an additional 4 weeks. Another six monkeys were given placebo, daily for 8 weeks. Body weight, activity level, average daily food intake, and plasma T4, insulin, total androgen and cortisol concentrations remained unchanged for all 12 monkeys throughout the 8 weeks. Both groups had a significant (p < 0.05) decrease in total plasma cholesterol, however the DHEA treated monkeys were significantly lower than the placebo monkeys. The change in cholesterol in the DHEA treated group primarily affected the fraction containing the low density lipoprotein cholesterol which remained overall unchanged for the placebo monkeys. Both groups had a decrease in high density lipoprotein cholesterol, however there was no difference between the treatment groups. We conclude that in the rhesus monkey, exogenous administration of DHEA acutely reduces cholesterol concentration, particularly the lipoprotein fraction containing low density lipoprotein, without changing food intake, activity level, or body weight.

Animals↗
PubMedDate not supplied

The effect of high fat diet and dehydroepiandrosterone (DHEA) administration in the rhesus monkey.

Dehydroepiandrosterone (DHEA) lowers serum cholesterol, particularly the low density lipoprotein (LDL) fraction, in rhesus monkeys on a commercial diet (12% calories from fat, 0.0083% cholesterol). We fed rhesus monkeys a diet of 30% calories from fat and 0.1% cholesterol for 12 weeks, then commercial chow for 7 weeks. Six monkeys each received DHEA or placebo, orally for 17 weeks. Food intake increased the first 6 weeks, but decreased thereafter. Monkeys had a 22% mean weight gain while on high fat diet. DHEA monkeys had higher T4 levels than placebo monkeys at weeks 8 and 16. After 12 weeks on high fat diet, all monkeys had elevated serum cholesterol concentrations, an increase in amount and percentage of intermediate density lipoprotein and LDL cholesterol, and an increase in amount, but a decrease in percentage of high density lipoprotein cholesterol. There were no significant differences in serum cholesterol or plasma lipoprotein concentrations between DHEA and placebo monkeys while on high fat diet (a trend toward lower levels was noted in the DHEA group). On commercial chow, plasma lipoprotein concentrations decreased for all monkeys, and DHEA monkeys had significantly lower total and LDL cholesterol than placebo monkeys. We conclude that a high fat diet (30% fat) masks any cholesterol-lowering effects of DHEA.

Administration, Oral↗