Search PubMed⌕ Search

Biomedical subjects

B Ng

Publications and source records attributed to B Ng.

At least 55 records · Page 3Linked to original sources
PubMed1994

Isolated single lung perfusion with doxorubicin is effective in eradicating soft tissue sarcoma lung metastases in a rat model.

The only effective therapy for patients with metastatic soft tissue sarcoma in the lung is surgical resection, with a 5-year survival of approximately 25%. Because systemic chemotherapy has not significantly affected survival in these patients, we began to investigate locoregional chemotherapy. We have previously shown that isolated single lung perfusion with doxorubicin in the rat results in higher lung tissue levels and lower systemic toxicity than does high-dose intravenous therapy. In the present study, we examined the safety of isolated lung perfusion with doxorubicin and its efficacy in the treatment of experimental pulmonary metastases from soft tissue sarcoma. In experiment 1, 15 F344 rats were randomized into three groups (n = 5): group I had isolated left lung perfusion with doxorubicin 320 micrograms/ml in saline solution; group II had left isolated lung perfusion with doxorubicin 480 micrograms/ml and group III with doxorubicin 640 micrograms/ml. All perfusions with doxorubicin were at 0.5 ml/min for 10 minutes followed by perfusion of saline solution for 5 minutes. On day 21, all animals underwent right (contralateral) pneumonectomy and were observed for over 10 days. In experiment 2, two groups of F344 rats were injected intravenously with 10(7) viable methylcholanthrene-induced sarcoma cells on day 0. On day 7, group I (n = 12) had left isolated lung perfusion with saline solution only and group II (n = 15) had isolated lung perfusion with doxorubicin 320 micrograms/ml. On day 21, all animals were killed, and their lungs were stained for metastases. Routine histologic sections from three animals from group II were examined. In experiment 1, 80% of the animals in group I survived contralateral pneumonectomy. There were no survivors in groups II and III. In experiment 2, three animals died after isolated lung perfusion (one from group I and two from group II), and one animal (group I) was excluded because of mediastinal tumor. All animals in both groups had massive tumor replacement of the right (untreated) lung. Group I animals had massive tumor replacement of the left (treated) lung, whereas animals in group II had eradication of metastases in nine of ten cases; no microscopic evidence of tumor was detected in all three animals evaluated for microscopic disease. Isolated lung perfusion with doxorubicin 320 micrograms/ml is safe and effective in eradicating experimental pulmonary sarcoma metastases in this model.

Animals↗
PubMed1993

Growth hormone administration preserves lean body mass in sarcoma-bearing rats treated with doxorubicin.

Cachexia and malnutrition play a significant role in the morbidity associated with antineoplastic chemotherapy regimens. Conventional nutritional support during cancer therapy has shown little benefit in terms of reducing morbidity and mortality. We examined the anabolic properties of growth hormone (GH) that preserve normal body composition in sarcoma-bearing animals treated with doxorubicin. On day 0, 40 male Fischer 344 rats were inoculated with 10(6) methylcholanthrene-induced sarcoma cells s.c. in the left flank. On day 9, animals were randomized into 3 groups: control (CTL, n = 13); doxorubicin (DOX, n = 13); and doxorubicin plus GH (DOX-GH, n = 14). Two CTL animals were excluded due to tumor invasion into the peritoneal cavity. From day 9 to day 23, the DOX-GH group received daily s.c. recombinant rat GH injection (1 mg/kg). On day 13, DOX and DOX-GH groups received 7 mg/kg of DOX i.v. while the CTL group received sham i.v. sterile saline injection. Body weight and tumor dimensions were measured daily. On day 23, all animals were weighed and sacrificed. Tumors were resected and weighed. Body composition analysis was performed. Plasma GH levels were measured by radioimmunoassay and insulin growth factor 1 levels were measured by chondrocyte proliferation bioassay. The DOX-GH group had a significantly higher mean body weight, carcass weight, total fat free body mass, insulin growth factor 1, and GH plasma levels as compared to the DOX group. No difference in total food intake was observed between the DOX and DOX-GH groups. There was no difference in final tumor weight and tumor growth rate between DOX and DOX-GH groups. Exogenous growth hormone can attenuate weight loss and preserve host body composition in tumor-bearing rats treated with doxorubicin without stimulating tumor growth.

Animals↗
PubMed1993

Isolated single-lung perfusion with doxorubicin is pharmacokinetically superior to intravenous injection.

To investigate new modalities in the treatment of pulmonary metastases we developed a model of isolated single-lung perfusion in the rat. In this study we compare the pharmacokinetics of isolated lung perfusion and intravenous doxorubicin. In the first experiment, designed to evaluate lung tissue levels of doxorubicin, 35 rats were randomized into seven groups (n = 5). The first five groups underwent isolated lung perfusion with 72.1 +/- 6.9, 118.4 +/- 12.1, 255.2 +/- 12.8, 384.1 +/- 46.2, and 457.6 +/- 32.5 micrograms/mL of doxorubicin, respectively, for 10 minutes. Groups 6 and 7 received 5 mg/kg and 7 mg/kg of intravenous doxorubicin, respectively. A second study was designed to measure heart tissue level of doxorubicin in 3 groups of 5 rats each. Two groups received 5 or 7 mg/kg of intravenous doxorubicin and a third group underwent isolated lung perfusion with 255.2 +/- 12.8 micrograms/mL of doxorubicin for 10 minutes. A third study, designed to evaluate toxicity in vivo, had a similar design, and the animals were followed up for 21 days after treatment. Lung doxorubicin concentration after isolated lung perfusion was significantly higher than after intravenous doxorubicin (p < 0.01). Tissue doxorubicin concentration was 25 and 20 times higher after isolated lung perfusion with 255.2 +/- 12.8 micrograms/mL than after 5 or 7 mg/kg of intravenous doxorubicin, respectively. Heart concentration of doxorubicin was significantly lower after isolated lung perfusion with 255.2 +/- 12.8 micrograms/mL of doxorubicin as compared with 5 or 7 mg/kg of intravenous doxorubicin (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Isolated single lung perfusion in the rat: an experimental model.

To evaluate isolated single lung perfusion with chemotherapy in a rat lung metastasis model, we developed a model of in vivo isolated single lung perfusion. Twenty male rats were anesthetized with pentobarbital sodium (50 mg/kg) and intubated endotracheally. A left thoracotomy was performed with an operating microscope (x16 magnification), the left pulmonary artery was cannulated, and a left pulmonary venotomy was performed. Isolated left lung perfusion was performed for 10 min at 0.5 ml/min with heparinized whole blood (n = 10) or 0.9% normal saline (n = 10). Pulmonary vein effluent was collected by suction. Nineteen of the 20 (95%) animals survived isolated left single lung perfusion. Twenty-one days after isolated left lung perfusion right pneumonectomy was performed. Fifteen of the 19 animals (78%) survived right pneumonectomy. Postoperatively, animals that survived surgery recovered preoperative body weight. In vivo isolated single lung perfusion in rats is feasible with low mortality and morbidity and may be useful in the study of isolated perfusion with chemotherapy and in diverse physiological and pharmacological experiments.

Anesthesia↗
PubMed1993

Dextropropoxyphene addiction--a drug of primary abuse.

In order to establish a profile of the abuser of dextropropoxyphene (DPX) in our community, we reviewed all the records from the Detoxification Unit in the Mental Health Institute in Mexicali, Baja California, Mexico. A total of 209 records were reviewed, and 73 were included in our study. Those included had a diagnosis of DPX dependence according to DSM-III-R and no associated psychiatric pathology. Most of them were single, unemployed males, with a history of at least 4 years of continuous DPX abuse. They were consuming an average dose per day 3.5 times higher than the maximum therapeutic dose recommended. The onset of generalized seizures associated with the DPX abuse was confirmed in 53% of the cases. The drug most frequently abused along with DPX was a benzodiazepine (p < .01), followed by marijuana, heroin, alcohol, stimulants (cocaine and amphetamines), and inhalants; 17% of the cases were pure DPX abusers. DPX was the first opiate ever abused in 67% of the cases, 19% had abused heroin before DPX, and 14% started the use of both at the same time. The difference among these groups (p < .01) suggests DPX as an opiate of primary abuse and not as secondary to heroin dependence.

Adult↗
PubMed1992

Vascular permeability during the early and late phases of ocular anaphylaxis.

The role of enhanced vascular permeability in a model of ocular anaphylaxis was investigated during both early- and late-phase reactions (EPR and LPR). Vascular permeability was assessed by measuring the extravascular retention of 125I-bovine serum albumin (125I-BSA) in ocular tissues. Ten groups of guinea pigs (n = 5-12 per group) were injected with dinitrophenylated (DNP) bovine gamma globulin emulsified in Freund's adjuvants and challenged after a 4-week interval by topical application of di-DNP-lysine to one eye and phosphate-buffered saline to the other eye. Thereafter, the eyes were examined and the animals were killed at different intervals after topical challenge. They were injected intravenously with 125I-BSA 0.5 hr before death. Retained radioactivity was measured separately in four tissues. The EPR (period between 0.5-1.5 hr after challenge) was characterized by enhanced retention of radioactivity in lids, conjunctiva, and orbital content. There was no significant retention of extravascular radioactivity in the globe and lacrimal gland. Thereafter (period between 2-3.5 hr after challenge), retained radioactivity was significantly diminished. The subsequent period, between 4.5-6.5 hr (LPR), was characterized by a smaller, although significant, increment of radioactivity retained in lids and conjunctiva but not in the other tissues examined. These findings indicate that enhanced microvascular permeability occurs during two phases in actively immunized guinea pigs challenged topically with di-DNP-lysine and that these phases correspond to the clinical signs that constitute the EPR and LPR of ocular anaphylaxis.

Anaphylaxis↗
PubMed1981

Cellular and extracellular siderophores of Aspergillus nidulans and Penicillium chrysogenum.

Aspergillus nidulans and Penicillium chrysogenum produce specific cellular siderophores in addition to the well-known siderophores of the culture medium. Since this was found previously in Neurospora crassa, it is probably generally true for filamentous ascomycetes. The cellular siderophore of A. nidulans is ferricrocin; that of P. chrysogenum is ferrichrome. A. nidulans also contains triacetylfusigen, a siderophore without apparent biological activity. Conidia of both species lose siderophores at high salt concentrations and become siderophore dependent. This has also been found in N. crassa, where lowering of the water activity has been shown to be the causal factor. We used an assay procedure based on this dependency to reexamine the extracellular siderophores of these species. During rapid mycelial growth, both A. nidulans and P. chrysogenum produced two highly active, unidentified siderophores which were later replaced by a less active or inactive product--coprogen in the case of P. chrysogenum and triacetylfusigen in the case of A. nidulans. N. crassa secreted coprogen only. Fungal siderophore metabolism is varied and complex.

Aspergillus nidulans↗
PubMed1979

The effect of cortisol on the adenosine 3',5'-monophosphate response to parathyroid hormone of bone in vitro.

Newborn rat calvariae, cultured for 24 h in the presence of cortisol (10(-6) M) have a cAMP response to parathyroid hormone (PTH) about twice as high as calvariae cultured in a control medium. This effect of cortisol is dose related; a maximal effect is evident at 10(-6) M, while none is detectable at 10(-9) M or less. With 10(-6) M estradiol, progesterone, or cholesterol, no effect on cAMP responsiveness is observed. This indicates that the effect observed with cortisol is specific. The effect of cortisol is more pronounced when isobutyl-methylxanthine (10(-4) M) is present during the subsequent incubation with PTH. Preincubation of the tissue with cortisol for 30 min before the addition of PTH has no effect. Similarly, when cortisol is added in conjunction with PTH, no effect is found. In no case did cortisol (10(-6) M) alter the time course of the PTH-induced cAMP effect when compared to the response of fresh calvariae. The results indicate that corticosteroids have an important function in maintaining cAMP responsiveness of bone to PTH in vitro.

1-Methyl-3-isobutylxanthine↗
PubMed1977

Parathyroid hormone- and prostaglandin E1-response in a selected population of bone cells after repeated subculture and storage at -80C.

Five different cell populations, designated I to V, were isolated from minced newborn rat calveria by 5-sequential 20 min incubations with an enzyme mixture containing collagenase, elastase and DNAse. In primary culture, all five populations responded to parathyroid hormone (PTH) to a different degree, population IV giving the highest increase in cyclic-3'5'-adenosine monophosphate (cAMP) level. None of the five populations gave any response to calcitonin. Upon subsequent subcultures, all populations, except population IV, either lost or considerably decreased their response to PTH. Population IV gave a two to three-fold increase in cAMP concentration in response to PTH up to the third subculture. No morphological differences could be observed among the five populations. The third subculture of population IV cells that had been stored in 10% glycerol at -80C for four months was subsequently thawed and subcultured to the sixth subculture. These cells still responded to PTH with an increase in cAMP level. In a second experiment, 5 different cell populations designated I to V were isolated in a similar way by incubation with collagenase and DNAse. The maximum response to PTH was found in population 3. The preservation of the PTH-responsiveness of this population, after subculturing, freezing, storing in 10% glycerol at -80 C and subsequent subculturing, was likewise demonstrated. The hormone-responsiveness of cells from the sixth subculture of previously frozen and thawed population IV cells was further analyzed. These cells responded to PTH at a concentration of 0.1 U/ml to 5U/ml and to prostaglandin E1 (PGE1) at a concentration of 0.1 microng/ml to 10 microng/ml. The time course of action on population IV of PTH was found to be different from that of PGE1, suggesting a possible difference in the regulation of intracellular cAMP levels by these hormones.

Bone and Bones↗
PubMedDate not supplied

Modulation of prostacyclin and thromboxane secretion by cytotrophoblasts from normal and pre-eclamptic human pregnancies.

We and others have previously observed an imbalance in cytotrophoblast secretion of the vasoactive prostanoids prostacyclin and thromboxane A(2) in pre-eclampsia. To examine the effects of potential modulators of this imbalance, cytotrophoblasts isolated from normal and pre-eclamptic pregnancies were incubated in the presence of lipopolysaccharide, the calcium ionophore A23187, tumour necrosis factor alpha, or interleukin 1beta, with or without the cyclo-oxygenase inhibitor, indomethacin. Further incubations included the drugs tranylcypromine, a prostacyclin synthetase inhibitor (0.1, 10 microM ), or the thromboxane synthetase inhibitor, pirmagrel (0.001, 1 microM ). Results showed that cytotrophoblasts from pre-eclamptic pregnancies had increased thromboxane production and significant stimulation of prostacyclin production by lipopolysaccharide and calcium ionophore. Lipopolysaccharide stimulated thromboxane production in normal cytotrophoblasts, while indomethacin almost completely inhibited production of both prostanoids. Tranylcypromine mildly inhibited prostacyclin production in normal cytotrophoblasts only, whereas pirmagrel strongly inhibited thromboxane production in a dose-related manner, with reciprocal increase in prostacyclin production occurring in cytotrophoblasts from pre-eclamptic pregnancies. This study confirmed that cytotrophoblasts from pre-eclamptic women had increased thromboxane production and showed that pirmagrel, at the relatively low dose of 0.001 microM, was able to normalize the imbalance of thromboxane and prostacylin production and may therefore warrant further investigation as a treatment for pre-eclampsia.

Adult↗
PubMedDate not supplied

Ethnic differences in analgesic consumption for postoperative pain.

OBJECTIVE: To examine the influence of patient ethnicity on receipt of postoperative analgesia. METHOD: Chart review of 250 consecutive patients hospitalized for open reduction and internal fixation of a limb fracture. Analgesics consumption in the postoperative period was measured in terms of morphine equivalents. RESULTS: There were significant differences (p < .005) in analgesics administered to black, Hispanic, and white patients. Whites received 22 mg/day, blacks 16 mg/day, and Hispanics 13 mg/day. These ethnic differences persisted after controlling for possible confounding variables. CONCLUSION: Ethnicity exerts a powerful impact on medical care. We cannot determine from our data whether these differences stem from differences in pain behavior of the patients or differences in medical staff's perception and treatment of such patients.

Adult↗
PubMedDate not supplied

Hypoglycemia with glycerol salvage: a role in anti-neoplastic therapy?

UNLABELLED: Most tumors are obligate glucose consumers and severe glucose depletion has anti-neoplastic effects. However, an alternate energy source is necessary to support the host. Since glycerol is utilized by all hypoglycemic sensitive normal tissues but not tumors, glycerol may be an ideal alternate energy source. The effects of glycerol on tumor growth, animal survival during systemic hypoglycemia induced by 3-mercaptopicolinic acid (3-MP, a gluconeogenesis inhibitor), and effects of 3-MP on gluconeogenesis from glycerol were studied. Experiment 1-glycerol effect on tumor cell growth; and glycerokinase activity assay. Methylcholanthrene-induced (MCA) sarcoma cells were plated in either glucose free, glucose or glycerol containing medium. Cell counts and viabilities were recorded daily. Cells in glucose group had normal growth pattern and cell viability, while cell counts and viabilities in control and glycerol groups decreased markedly. F344 rats were injected with MCA-sarcoma cells in the flank. Glycerokinase activities in tumor and host liver were assayed on day 20. Activities were 12.3 +/- 2.8, 148.2 + 17.5 assayed on day 20. Activities were 12.3 +/- 2.8, 148.2 +/- 17.5 mumol/g protein/min in tumor and liver, respectively. Experiment 2-glycerol effect on animal survival during hypoglycemia induced by 3-MP. Following a 48 hour fast, 12 Fischer 344 rats were injected (ip) with 3-MP (200mg/kg) and randomized to saline or glycerol perfusion (100mg/kg/hr) groups. Four of 6 rats in the saline group died of hypoglycemia. All rats in the glycerol group survived, but blood glucose levels were increased as compared to the saline group. Experiment 3-3-MP effect on gluconeogenesis from glycerol as compared to lactate. 5 x 10(6) hepatocytes were incubated in glucose-free HBSS containing glycerol (20mM) or lactate (20mM) in the presence (0.5mM) or absence of 3-MP. Glucose production was assayed every 30 minutes for 2 hrs. Glucose production from glycerol was not significantly inhibited in the presence of 3-MP as compared to lactate. CONCLUSION: Glycerol does not support MCA-sarcoma growth and promotes animal survival during severe systemic hypoglycemia induced by 3-MP. However, glycerol also led to increased gluconeogenesis in this model. The use of hypoglycemic agents with glycerol protection of host tissues warrants further study.

Animals↗
PubMedDate not supplied

Regional chemotherapy via pulmonary artery with blood flow occlusion in a solitary tumor nodule model.

This study is to evaluate low dose doxorubicin pulmonary artery perfusion with blood flow occlusion compared to systemic administration in a model of solitary intrapulmonary sarcoma nodule in the rat. Tumor nodule was developed via injection of methylcholanthrene-induced sarcoma into the left lung. Doxorubicin was perfused into the left pulmonary artery at a rate of 50 microliters/min for 2 min with 20 min blood flow blockage in all experiments. Pharmacokinetics, toxicity, treatment efficacy were compared between lung perfusion groups and intravenous groups. Doxorubicin levels in tumor, left lung, right lung, heart and serum were measured. Animal daily weights were recorded and a right pneumonectomy was performed following treatment to assess toxicity and tolerated perfusion dose. Tumors were weighed following treatment to evaluate treatment efficacy. Doxorubicin delivered via pulmonary artery caused a significant higher drug level in tumor tissue and perfused lung with a low drug level in heart, right lung and serum as compared to intravenous administration. Animals in perfusion groups had normal growth pattern and survived after pneumonectomy when a dose of 0.5 mg/kg doxorubicin was perfused. Tumor weight was significantly decreased after treated with 0.5 mg/kg of doxorubicin lung perfusion as compared to same dose of doxorubicin intravenous treatment. Pulmonary artery perfusion with blood flow occlusion may offer an effective lung chemotherapeutic model. 0.5 mg/kg doxorubicin for lung perfusion has acceptable local lung toxicity and no significant systemic toxicity and is pharmacokinetically and therapeutically superior to systemic administration in this solitary intrapulmonary tumor nodule model in the rat.

Animals↗