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Biomedical subjects

H Chang

Publications and source records attributed to H Chang.

At least 235 records · Page 13Linked to original sources

Effects of hyperthermia and photodynamic therapy on BALB/c mice bearing subcutaneous tumors.

The therapeutic effects of photodynamic therapy and hyperthermia on mice bearing subcutaneous tumors were investigated. Ehrlich ascites tumor cells (1 x 10(7)) were implanted subcutaneously into the femoral area of BALB/c mice. A total of 134 tumor-bearing mice were treated with photodynamic therapy, i.e., administration of laser irradiation (514.5 nm, 112.5 mW/cm2 for 11.12 min with a total energy 75 J/cm2) after injection (i.p.) of hematoporphyrin derivative (HPD, 7.5 and 10.0 mg/kg body weight) and/or hyperthermia (by electric heating needles to 44 and 45 degrees C for 30 min) once a day for three successive days. The results revealed that the therapeutic effects of the combination of photodynamic therapy and hyperthermia were improved when compared with photodynamic therapy or hyperthermia alone. A combination of photodynamic therapy (10.0 mg HPD/kg body weight and 75 J/cm2 of total laser irradiation energy) and hyperthermia (44 degrees C for 30 min) had the best therapeutic effect, indicating that the mortality rate within 120 days (MR120) was 12.5% and the mean survival time (MST120) was 113.8 days.

Animals↗

Traumatic aorto-right atrial fistula after blunt chest injury.

A extremely rare case of traumatic fistula between the aortic root and the right atrium is reported. The patient was involved in a traffic accident 18 months before admission. Aortogram demonstrated a fistulous tract from the noncoronary sinus into the right atrium. Operation revealed a traumatic dissection of the aortic root with rupture into the right atrium. The aortic dissection was repaired and the patient was discharged from the hospital in good condition.

Adult↗

Impaired insulin-mediated inhibition of lipolysis and glucose transport with aging.

Regulation of hormone action with aging has been extensively studied; adipocytes provide an interesting model for some of these questions. We have compared the ability of insulin to stimulate glucose uptake and suppress lipolysis in adipocytes isolated from two month and twelve month-old rats. The ability of insulin to stimulate maximal glucose transport was decreased in adipocytes from the older rats (P less than 0.001); as well, insulin's EC50 was also higher (P less than 0.01) in these cells. Furthermore, these defects were present when insulin-stimulated glucose transport was measured in the presence or absence of adenosine deaminase which metabolizes endogenously released adenosine. Endogenously released adenosine is a stimulator of glucose transport and an inhibitor of lipolysis. Maximal suppression of isoproterenol-induced lipolysis by insulin was similar when adipocytes isolated from the two age groups were incubated in the absence of adenosine deaminase. However, maximal insulin-mediated suppression of lipolysis was found to be significantly decreased (P less than 0.001) in adipocytes isolated from older rats when the experiments were done in the presence of adenosine deaminase; also, insulin's EC50 was increased in these cells under these conditions (P less than 0.001). These results emphasize the importance of the adenosine receptor in modulating the response of isolated adipocytes to insulin, particularly for lipolysis, and document the presence of age-associated defects in insulin regulation of both glucose transport and lipolysis.

Adipose Tissue↗

Cellular tolerance to adenosine receptor-mediated inhibition of lipolysis: altered adenosine 3',5'-monophosphate metabolism and protein kinase activation.

Prolonged exposure of many types of cells to drugs or hormones that inhibit the activity of the enzyme adenylate cyclase, such as narcotics and alpha 2-adrenergic agonists, leads to enhanced accumulation of cAMP upon removal of the inhibitory drug. We have found previously that chronic infusion of the adenosine A1 receptor agonist phenylisopropyladenosine (PIA), an inhibitor of adenylate cyclase, into rats leads to enhanced isoproterenol-stimulated cAMP accumulation in adipocytes isolated from these animals. The enhanced cAMP accumulation was associated with an impaired ability of PIA to inhibit lipolysis in these cells. In the present study we have investigated the mechanism of the enhanced cAMP accumulation in adipocytes from PIA-infused rats and the relationship of these changes to the impaired antilipolytic action of the drug. The enhanced isoproterenol-stimulated cAMP accumulation in adipocytes prepared from PIA-infused rats was due to both an increased rate of cAMP synthesis and a decreased rate of cAMP metabolism at high concentrations of cAMP without a change in phosphodiesterase activity. There was heterologous desensitization of the ability of PIA, prostaglandin E1, and nicotinic acid to inhibit cAMP accumulation in the adipocytes from PIA-infused rats; there was an increase in the EC50 of each of these agonists, although maximal inhibition of cAMP accumulation was similar. The relationship between the activation of cAMP-dependent kinase and extent of lipolysis was similar in the two groups of cells. We demonstrated that the explanation for the impaired ability of PIA to decrease the rate of isoproterenol (10(-7) M)-stimulated lipolysis in the cells from the PIA-infused rats was due to the markedly increased concentrations of cAMP in these cells, which led to sufficient activation of the kinase to maintain a high rate of lipolysis even in the presence of PIA. In addition, we found that the changes induced by the PIA infusion were largely reversible over a 2-day period after discontinuing the PIA infusion. These results demonstrate that adipocytes from PIA-infused rats provide an interesting model to investigate the mechanisms of tolerance to inhibitory drugs.

3',5'-Cyclic-AMP Phosphodiesterases↗

Interstitial iridium-192 implantation for malignant brain tumours. Part II: Clinical experience.

The treatment results of 37 patients with malignant brain neoplasms treated with a computed-tomography-guided stereotactic iridium-192 implant are reviewed. Of these, 29 patients with high-grade gliomas (20 with glioblastoma multiforme (GBM), nine with anaplastic astrocytoma (AA] received an implant as part of their initial management. The median survival was 14.5 and 15.5 months in the patients with previously untreated GBM and AA, respectively. In those patients with recurrent tumour after external-beam irradiation, durable local control over a year was achieved with implantation. Increasing the total tumour dose from 120 to 160 Gy did not improve survival or local control. Karnofsky Performance Status (KPS) was used as an indicator of quality of life and was seen to decrease with a median interval of 8.5 months following treatment. No severe complications were noted in the entire group of patients treated with this implant procedure.

Adult↗

Resistance to insulin-stimulated glucose uptake in adipocytes isolated from spontaneously hypertensive rats.

The ability of insulin to stimulate glucose uptake and inhibit catecholamine-induced lipolysis was measured in adipocytes of similar size isolated from SHR and WKY rats. The results indicate that glucose transport was decreased in adipocytes from SHR rats; both basal (19 +/- 2 vs. 32 +/- 2 fmol.cell-1.s-1, P less than .001) and maximal (207 +/- 30 vs. 373 +/- 20 fmol.cell-1.s-1, P less than .01) insulin-stimulated glucose transport were lower in SHR than in WKY rats. In addition, the EC50 of insulin-stimulated glucose uptake was higher (921 +/- 82 vs. 557 +/- 69 pM insulin, P less than .05) in adipocytes from SHR rats than from WKY rats. The ability of phenylisopropyladenosine (PIA) to modulate basal and maximal insulin-stimulated glucose uptake was compared in adipocytes from SHR and WKY rats. These results also demonstrated that glucose uptake was decreased in adipocytes from SHR rats and that PIA similarly enhanced both basal and maximal insulin-stimulated glucose uptake in adipocytes from both groups. Although maximal isoproterenol-stimulated lipolysis was decreased in adipocytes from SHR rats, the ability of insulin to inhibit catecholamine-stimulated lipolysis was at least as great in adipocytes from SHR as from WKY rats. Despite the decrease in insulin-stimulated glucose transport in isolated adipocytes from SHR rats, total number of insulin receptors, their affinity for insulin, and the ability of insulin to stimulate receptor-associated tyrosine kinase activity were similar in adipocytes from SHR and WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Surgical treatment of prosthetic valve endocarditis.

From January 1980 to June 1987, a total of 16 consecutive patients underwent surgical therapy in addition to an antimicrobial regimen for prosthetic valve endocarditis at the National Taiwan University Hospital. The ages ranged from 26 to 55 years, with a mean of 40. Nine of these 16 patients (56%) were men and 7 (44%) women. The infected valve prostheses were located at the aortic position in 5 patients, at the mitral position in 6 patients and at both mitral and aortic position in 5 patients. Among the total of 21 infected valve prostheses, 19 were bioprosthetic tissue valves and only 2 were mechanical valve prostheses. Hospital death occurred in 5 patients with an early mortality rate of 31%. Among them, 1 had fungal infection, 2 had streptococcal infection, and 2 had enterococcal infection. Four patients died of low cardiac output due to extensive myocardial involvement and one patient died of uncontrollable upper gastrointestinal bleeding. Late mortality occurred in 1 patient with fungal endocarditis and the cause of death was clinical deterioration due to multiple organ failure. The follow-up period ranged from 7 to 93 months. Except for one who was lost to follow-up, all of the patients survived in good condition without any complication.

Adult↗

Death due to disruption of sternal fixation wire--a rare complication after open heart surgery through sternotomy: report of a case.

Following sternotomy for open heart surgery, a 57-year-old man had the sternum closed in the usual manner with six No.22 gauge stainless steel wire sutures. Twenty-four days later, sternum disruption occurred with only one wire suture in place, 3 wire sutures cutting through the bone, and 2 wire sutures fractured. A lacerating injury over the anterior surface of the right ventricle was rendered by these 2 fractured wires followed by fatal outcome. To our knowledge, death induced by fractured wires has not been reported. We report in this communication what we believe to be the first case in the literature.

Bone Wires↗

Comparison of lorazepam and flurazepam as hypnotic agents in chronic insomniacs.

Hypnotic efficacy and safety of 3 weeks of daily doses of 2 mg lorazepam or 30 mg flurazepam were compared in a double-blind cross-over study in eight chronic insomniacs between the ages of 29 and 60 years. Subjects were monitored in the sleep laboratory twice weekly for a total of 25 nights. Also, subjective estimates of sleep, vigilance tests, and adverse effects were recorded throughout the study. Findings indicated lorazepam performed better than flurazepam in most sleep parameters. With lorazepam there was improvement from baseline in percentage of sleep time (P less than .05); in total wake time after sleep onset (P less than .01) and in last third of night (P less than .05); in percentage of stage 2 (P less than .05) (weeks 1, 2, 3) and in percentage of night in stage 4 (weeks 2 and 3). Only total wake time from baseline improved (P less than .05) with flurazepam (week 2). Objective and subjective sleep parameters did not correlate well for either drug. Neither drug impaired REM sleep or vigilance test performance. Side effects (grogginess, lethargy; flurazepam only) were few and none was unexpected; neither rebound insomnia nor early morning insomnia occurred with either drug. In summary, both lorazepam 2 mg at bedtime and flurazepam 30 mg at bedtime were found to be effective and safe for treating chronic insomnia, as measured by parameters of sleep and daytime functioning. Lorazepam had more favorable effects on sleep than did flurazepam.

Adult↗

Ca2+-activated K+ conductance causes membrane hyperpolarizations in a monkey kidney cell line (JTC-12).

We have previously reported hyperpolarizing membrane potential changes in a monkey kidney cell line (JTC-12) which has characteristics resembling proximal tubular cells. These hyperpolarizations could be observed spontaneously or evoked by mechanically touching adjacent cells. In this report, we have shown further evidence that these hyperpolarizations are elicited by an increase in membrane conductance to K+ which is caused by an increase in cytosolic Ca2+ concentration. In addition, we have found another type of hyperpolarization which is evoked by applying flow of extracellular fluid to the cell. Intracellular injection of Ca2+ and Sr2+ evoked hyperpolarizations, while intracellular injection of Mn2+ and Ba2+ did not. Intracellular injection of EGTA suppressed both spontaneous and mechanically evoked hyperpolarizations. In Ca2+-free medium, both spontaneous and flow-evoked hyperpolarizations were not observed, while mechanical stimuli consistently evoked hyperpolarization. In Na+-free medium, the incidence of cells showing the spontaneous or flow-evoked hyperpolarization increased, and the amplitude and the duration of the mechanically evoked hyperpolarization became greater. Quinidine inhibited all types of hyperpolarization. These data suggest that hyperpolarizations in JTC-12 cells are due to an increase in Ca2+-activated K+ conductance.

Animals↗

Serotonin uptake in panic disorder and agoraphobia.

Because of reports of reduced serotonin uptake in depression and the frequent association between panic disorder and depression, this study was designed to assess the neurobiologic relationship between panic disorder and depression. Platelet serotonin uptake studies were done on 47 patients with panic disorder, 17 patients with primary major depression, and 15 healthy volunteers. The authors found that the rate of uptake of serotonin to platelets (Bmax) was significantly lower in both the depressed and panic disorder groups than the healthy control group. The panic disorder patients with a present or past history of major depression had slightly higher values than the panic disorder patients without such a history.

Adult↗

Advanced head and neck cancer: response to and toxicity of multimodality therapy.

This pilot study for resectable stage III and stage IV squamous cell carcinoma of the head and neck used a cytoreduction phase of preoperative radiation with cisplatin, followed by an eradicative treatment phase with radical surgery (group 1) or radical dose radiation and cisplatin (group 2), followed by adjuvant chemotherapy with 5-fluorouracil infusion and cisplatin delivered at 4-week intervals for six cycles following initial radiation therapy to the primary site. A total of 43 patients were treated between January 1984 and January 1987; 14 were classified with stage III carcinoma, 28 with stage IV, and one patient was not staged. Out of 43 patients, two did not complete therapy. Forty-one patients completed the eradicative phase of treatment. Complete tumor clearance at the end of the eradicative treatment phase was 88% (36 of 41 patients), 95% (18 of 19) in group 1 and 82% (18 of 22) in group 2. Actuarial recurrence-free survival was 61% at 3 years. Among 36 patients with complete tumor clearance after the eradicative treatment phase, there was no statistically significant difference for overall and recurrence-free survival between group 1 and group 2. In general, toxicity was not excessive, although mucositis, weight loss, and hematologic and neurologic toxicity were observed in varying degrees in these patients.

Adult↗

Lowering of plasma glucose in diabetic rats by antilipolytic agents.

Both nicotinic acid (NA) and the adenosine receptor agonist phenylisopropyladenosine (PIA) are potent antilipolytic agents. We have evaluated the ability of these compounds to lower plasma glucose concentration in 450-g male diabetic rats. Diabetes was induced by intravenous streptozotocin, and the rats were studied 7-10 days later. Mean (+/- SE) fasting glucose decreased 4 h after subcutaneous injections of PIA at 0 and 2 h. A similar change in plasma glucose level was also seen in rats injected with NA. The decrease in the concentration of plasma glucose in both instances was preceded by marked sustained reductions in plasma free fatty acid (FFA) concentrations; FFA decreased in PIA-injected rats and in response to NA. With injection of normal saline, neither plasma glucose nor FFA concentrations decreased in diabetic rats. There was no change in the plasma insulin concentration of rats that had hypoglycemic responses to PIA or NA. In vitro glucose uptake was determined in isolated adipocytes, and both PIA and NA were shown to increase basal and maximal insulin-stimulated glucose uptake. The stimulating effect of the two compounds was similar, and the magnitude of the effect was comparable in adipocytes from either normal or diabetic rats. As a result, neither NA nor PIA could restore the defects in glucose transport to normal in adipocytes from diabetic rats. Insulin-stimulated glucose uptake was assessed in vivo by determining the steady-state glucose response of diabetic rats to a continuous infusion of insulin and glucose and was found to be significantly enhanced in response to NA compared with NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Additive hypoglycemic effects of drugs that modify free-fatty acid metabolism by different mechanisms in rats with streptozocin-induced diabetes.

In this study the effect of two drugs [etomoxir and nicotinic acid (NA)] on plasma glucose, free-fatty acid (FFA), and triglyceride (TG) concentrations was determined in rats with streptozocin (STZ)-induced diabetes. The two compounds modify FFA metabolism by different mechanisms, etomoxir (ethyl-2-[6-(4-cholorophenoxyl)-hexyl]oxirane-2-carboxylate) by inhibiting hepatic fatty acid oxidation, and NA by inhibiting lipolysis in adipose tissue. Diabetes was induced in male Sprague-Dawley rats, weighing approximately 400 g, by STZ injection (30 mg/kg i.v.), and the metabolic effects of the two drugs were studied 7-10 days later. The acute administration of either etomoxir or NA lowered plasma glucose concentrations in diabetic rats by approximately 150 mg/dl (P less than .001) in 4 h. However, the two drugs differed dramatically in their effects on plasma FFA and TG concentrations. Specifically, etomoxir produced striking increases in plasma FFA and TG concentrations, whereas NA administration caused a marked decrease. However, when NA was given in conjunction with etomoxir, NA prevented the increase in plasma FFA and TG concentration seen with etomoxir; the combination of NA and etomoxir approximately doubled the decrease in plasma glucose concentration produced by NA or etomoxir when given alone. Because plasma insulin concentrations did not change in response to either drug, whether administered singly or in combination, these metabolic effects do not result from a change in insulin secretion. These results suggest that modulation of FFA metabolism at the level of the adipocyte or the liver can have dramatic effects on carbohydrate and lipid metabolism.

Adipose Tissue↗