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Biomedical subjects

H C Shih

Publications and source records attributed to H C Shih.

At least 37 records · Page 2Linked to original sources

Alternations of surface antigens on leukocytes after severe injury: correlation with infectious complications.

OBJECTIVE: To investigate the alternations of surface antigens of leukocytes after severe injury and the correlation with clinical outcome. SETTING: Emergency Department and Intensive Care Unit of a university hospital. PATIENTS: Patients with severe trauma (injury severity score > 16) were enrolled. Those who were transferred or had critical injuries were excluded. MEASUREMENTS AND RESULTS: Polymorphonuclear cells (PMN) and mononuclear cells (MN) were isolated from patients on the 1st, 3rd and 7th day following injury. The mean fluorescent expressions of CD11b and CD16 of PMN, and CD25 of MN were measured and compared with those obtained from paralleled controls. Sixteen injured patients were included. The CD11b expressions of PMN increased on the 1st day and were still high on the 7th day. The CD16 expressions decreased on the 1st day and CD25 decreased on the 3rd day; both were still low on the 7th day. Six patients developed infectious complications. CD11b expression remained high and CD16 expression remained low on three measurements of the infectious patients, whereas both expressions recovered on the last measurement of non-infectious patients. CD25 expression remained low in both groups. Three infectious patients with pneumonia died from multiple organ failure. CONCLUSIONS: Phenotypic alternations of leukocytes develop early after severe injury. The alternations may represent a state of activation of PMN and subsequent suppression of IL-2 related immunity. Persistent activation of PMN with enhanced CD11b and attenuated CD16 expression indicates the development of infectious complications and a poor prognosis can be anticipated if the infectious sites can not be controlled early.

Adolescent↗

Effects of ovarian steroid hormones and thyroxine on calcitonin secretion in pregnant rats.

In the present study, the roles of ovarian steroid hormones and thyroxine (T4) in regulating the secretion of calcitonin (CT) in pregnant rats were examined. The levels of plasma progesterone, pre- and post-CaCl2 plasma CT, and recovery time of plasma CT and calcium after calcium challenge were greatest in midterm pregnant rats. The levels of basal plasma progesterone, CT, calcium, and recovery time of plasma CT after calcium challenge were less in late pregnant rats, but basal plasma estradiol was highest in late pregnancy. The concentrations of plasma T4 were gradually decreased in rats during pregnancy. Regardless of the presence of estradiol, administration of progesterone in ovariectomized (Ovx) rats resulted in an increase of plasma T4 as well as the basal and calcium-induced secretion of CT. Administration of estradiol alone did not alter the CaCl2-induced levels but decreased the post-CaCl2 levels of plasma calcium in Ovx rats. The basal levels of plasma CT were decreased in Ovx rats treated with T4. These results suggest that the hypercalcitoninemia in midterm pregnant rats is due to an increased secretion of progesterone. Hypocalcitoninemia in late pregnant rats, however, is due in part to lower plasma calcium.

Animals↗

Lactate and the effects of exercise on testosterone secretion: evidence for the involvement of a cAMP-mediated mechanism.

The effects of swimming and lactate on the release of testosterone were examined in male rats. During in vivo experiments, male rats were catheterized via the right jugular vein and blood was collected at 0, 10, 15, 30, and 60 min following the exercise, or they were catheterized via the right jugular vein and the left femoral vein and blood was collected at 0, 2, 5, 10, 15, 30, 60, and 120 min after a 10-min infusion at lactate (13 mg.kg-1.min-1). Trunk blood and blood from the testicular vein were also collected after 10 min of swimming or water immersion. In an in vitro experiment, testicular fragments were challenged with lactate (0.01-10 mM) and/or human chorionic gonadotropin (hCG; 0.5 IU.mL-1), and the mediobasal hypothalamus (MBH) was challenged with lactate (8 mM). The post-exercise levels of plasma lactate and testosterone at 10, 15, and 30 min were higher than resting levels. Plasma luteinizing hormone (LH) was increased following 30 min of swimming. Administration of lactate or hCG increased in a dose dependent manner testicular cyclic adenosine 3':5' monophosphate (cAMP) and testosterone release. Plasma testosterone increased after swimming and lactate infusion. Incubation of MBH with lactate increased the gonadotropin-releasing hormone (GnRH) level in the medium. These results suggest that the increased plasma testosterone levels in male rats during exercise is at least partially a result of a direct and LH-independent stimulatory effect of lactate on the secretion of testosterone by increasing testicular cAMP production. Swim-elevated plasma LH may be a result of a rise of GnRH caused by lactate.

Animals↗

Gastric emptying and gastrointestinal transit during lactation in rats.

Female sex hormones can influence gastrointestinal function. To understand whether postpartum changes in female sex hormones may affect such function, gastric emptying and gastrointestinal transit were measured in rats on days 1-2, 10, 15, and 21 of lactation, on day 7 postweaning, and at the nonpregnant diestrous stage. Gastric emptying and gastrointestinal transit were assessed in conscious rats 15 min after intragastric instillation of a test meal containing charcoal and (51)Cr. The results showed that gastric emptying was increased throughout the first 2 wk of lactation, with a gradual decrease as lactation proceeded toward weaning, and returned to the level of the virgin rats by 1 wk postweaning. Gastrointestinal transit was greater in the early stage of lactation and was related to gastric emptying (P < 0.001). Increases in gastric emptying and intestinal length were correlated with lactation (P < 0.001) and plasma prolactin levels (P < 0.05) but not with plasma progesterone or estradiol levels. We concluded that the sex steroid hormones associated with lactation do not mediate a change in gastric emptying and gastrointestinal transit during lactation.

Animals↗

Inhibition of bufalin on pituitary and testicular function in rats.

The effects of bufalin on the secretion of testosterone and luteinizing hormone (LH) and the accumulation of testicular adenosine 3':5'-cyclic monophosphate (cAMP) were studied. Male rats were injected with bufalin, human chorionic gonadotropin (hCG), gonadotropin releasing hormone (GnRH), hCG plus bufalin or GnRH plus bufalin via a jugular catheter. Blood samples were collected at several intervals subsequent to the challenge. In the in vitro study, rat testis blocks were incubated with bufalin, hCG or both for 1 h. The anterior pituitary gland was incubated with bufalin, GnRH or both for 30 min. The media were analyzed for testosterone or LH. For studying cAMP accumulation, testicular blocks were incubated for 1 h with the medium containing isobutyl-1-methylxanthine. After incubation, tissues were extracted by ethanol before measuring cAMP concentration. A single intravenous injection of bufalin decreased the basal and hCG-stimulated levels of plasma testosterone. Administration of bufalin in vitro resulted in an inhibition of both basal and hCG-stimulated release of testosterone. Bufalin diminished cAMP accumulation in rat testes. However, the basal levels of plasma and medium LH were not altered by bufalin administration. Likewise, the LH response to GnRH was diminished by bufalin administration, both in vivo and in vitro. These results suggest that the inhibition of testosterone production by bufalin is partly caused by a decrease of testicular cAMP accumulation and LH response to GnRH in rats.

1-Methyl-3-isobutylxanthine↗

Response of resuscitation in multiple trauma with pelvic fracture.

BACKGROUND: The early management of patients with pelvic injury remains a great challenge for emergency physicians and trauma surgeons. A retrospective study was performed in this hospital to identify the clinical significance of different responses in the resuscitation of pelvic injury. METHODS: From March 1989 to May 1995, 75 patients with pelvic ring injury who had initially had unstable hemodynamic status were studied. They were divided into four groups as "good response" (GR), "delayed response" (DR), "poor response" (PR) and "no response" (NR) according to the time when hemodynamics became stable after immediate resuscitation. RESULTS: Motor vehicle accidents (MVA) had a higher incidence than other causes in the trauma mechanism. The fracture types of pelvis had no correlation with the response to resuscitation. The injury severity score (ISS) was higher in the PR group (41.7 +/- 18.3) than in the GR (17.5 +/- 8.6) or DR (19.5 +/- 17.0). The incidence of extrapelvic hemorrhage (EPH) and of mortality rates was higher in the PR group (38% and 75%, respectively), and the DR group (25% and 13%, respectively), than in the GR group (6% and 2%, respectively). CONCLUSIONS: The responses of resuscitation is a valuable parameter in the management of multiple trauma with pelvic injury. Nonoperative treatment may be tried in patients of good response to resuscitation with EPH. In those patients with poor or delayed response, delayed extrapelvic bleeding (especially from abdominal injury) must be ruled out besides aggressive management for pelvic injury. Poor prognosis can also be expected in those patients with poor response.

Accidents, Traffic↗

Unilateral pulmonary edema during general anesthesia--report of two cases.

Unilateral presentation of pulmonary edema, though well known to occur, is an uncommon entity. Previous reviews of this subject have discussed the different etiologies, which include rapid reexpansion of collapsed lung, down lung syndrome (gravitational edema), systemic-to-pulmonary arterial shunts, heart failure, compression or occlusion of pulmonary vasculatures, obstruction of a bronchus and an acute manifestation of neuropulmonary reaction (neurogenic pulmonary edema). Occurrence of this complication during surgery, however, is even rarer. We report 2 cases of unilateral pulmonary edema occurring during general anesthesia for elective surgery.

Adult↗

Effect of aging on erythropoietin secretion in male rats.

The secretion of erythropoietin (EPO) and testosterone in response to hypoxia in old (22-25 months), middle (mid)-aged (15-17 months), adult (6-7 months), and young (3 months) male rats was studied. Rats of different ages were bled by cardiac puncture before and subsequent to 8 h exposure to 12% O2. The metabolic clearance rate of EPO was determined by a single-injection method. The effects of orchidectomy and replacement of testosterone propionate on plasma EPO concentrations were also investigated. Analysis of the direct effects of testosterone on EPO release from kidney tissue was carried out in an in vitro study. Both basal and hypoxia-induced EPO levels were lower in old rats than in mid-aged, adult, and young rats (p < .01). Plasma testosterone levels decreased in response to hypoxia in all rats (p < .01 for young, adult, and mid-aged rats, and p < .05 for old rats). The old rats also had lower plasma testosterone levels following hypoxia when compared with other rats (p < .05). The metabolic clearance rate of EPO was not affected by age. Orchidectomy decreased rat plasma EPO concentration (p < .05). This decrease could be restored to intact levels after testosterone propionate replacement. Both 10(-10) M (p < .05) and 10(-9) M (p < .01) testosterone stimulate EPO release from kidney tissue in vitro. Our findings indicate that the basal levels of plasma EPO and testosterone are decreased, and the hypoxia-induced EPO is also diminished with aging in male rats. These data suggest that the mechanism of tolerance to hypoxia and the endocrine function of the kidneys in male rats during the aging process are testosterone-dependent.

Aging↗

Inhibition by amphetamine of testosterone secretion through a mechanism involving an increase of cyclic AMP production in rat testes.

1. The effect of amphetamine on the secretion of testosterone and the production of testicular adenosine 3':5'-cyclic monophosphate (cyclic AMP) in rats was studied. 2. A single intravenous injection of amphetamine decreased the basal and human chorionic gonadotropin (hCG)-stimulated levels of plasma testosterone. Plasma LH levels were not altered by the injection of amphetamine. 3. Administration of amphetamine in vitro resulted in a dose-dependent inhibition of both basal and hCG-stimulated release of testosterone. 4. Amphetamine enhanced the basal and hCG-increased levels of cyclic AMP accumulation in vitro in rat testes. 5. These results suggest that amphetamine inhibits the spontaneous and hCG-stimulated secretion of testosterone from the testes through a mechanism involving an increase in cyclic AMP production.

Amphetamine↗

Lactate stimulates progesterone secretion via an increase in cAMP production in exercised female rats.

The effect of exercise on the production of ovarian progesterone was examined in female rats. During in vivo experiments, diestrous rats were catheterized via the right jugular vein (RJV), and blood samples were collected before and after 10, 15, 30, and 60 min of swimming. In addition, blood samples were collected from the RJV before and 2, 5, 10, 15, 30, 60, and 120 min after 10 min of infusion of lactate (13 mg.kg-1.min-1) through the left femoral vein. To explore if lactate modulates progesterone secretion by acting directly on rat ovary or on anterior pituitary gland (AP), an in vitro experiment that mimicked the in vivo condition was performed. The ovarian tissue was challenged with lactate (0.01-10 mM) or porcine follicle-stimulating hormone (1 microgram/ml) and 3-isobutyl-1-methylxanthine (1 mM) for 60 min, and the AP was challenged with lactate ranging from 0.1 to 10 mM or 10 nM gonadotropin-releasing hormone for 30 min. The postexercise levels of plasma glucose, lactate, and progesterone at 10, 15, and 30 min were significantly higher than the corresponding basal levels. Plasma luteinizing hormone (LH) did not change after exercise. An elevation of plasma lactate and progesterone was found at 15 and 30 min subsequent to 10 min of infusion of lactate. Lactate ranging from 0.01 to 10 mM significantly increased ovarian adenosine 3',5'-cyclic monophosphate (cAMP) and progesterone production in a dose-dependent manner. LH concentration in plasma was not changed subsequent to lactate infusion. LH level in media samples was not altered after incubation of AP with lactate. These results suggest that the increase of plasma progesterone level in rats during exercise is independent of LH secretion and at least in part is due directly to a stimulatory effect of lactate on the production of ovarian cAMP.

1-Methyl-3-isobutylxanthine↗

Progesterone stimulates in vitro release of prolactin and thyrotropin involving cAMP production in rat pituitary.

Effects of progesterone administration in vivo or in vitro on the release of pituitary prolactin (PRL) and thyroid stimulating hormone (TSH) in vitro, as well as the generation of pituitary cyclic adenosine 3', 5'-monophosphate (cAMP) were studied in ovariectomized (Ovx) rats. Ovx rats were either decapitated or injected subcutaneously with progesterone, or oil for 3 days before decapitation. The anterior pituitary glands (APs) of progesterone treated Ovx rats were incubated with Locke's medium containing thyrotropin-releasing hormone (TRH, 10 nM) and/or 3-isobutyl-1-methylxanthine (IBMX, 1 mM) at 37 degrees C for 30 min. The APs of untreated Ovx rats were incubated in vitro with IBMX and progesterone (0, 0.1, 1, 10 nM). Progesterone increased spontaneous and TRH-induced release of PRL and TSH in vitro. Administration of progesterone, either in vivo or in vitro, increased the production of pituitary cAMP following incubation of IBMX. These results suggest that progesterone increases the release of PRL and TSH through a mechanism associated with an increase of cAMP production in rat APs.

Animals↗

Role of chloride groups in the nephrotoxic potential of N-(3,5-dichlorophenyl)-2-hydroxysuccinimide, an oxidative metabolite of N-(3,5-dichlorophenyl)succinimide.

Although the addition of chloride groups to the phenyl ring of N-phenylsuccinimide (NPS) is known to enhance the nephrotoxic potential of NPS, the mechanism of this enhancement is unknown. One chlorinated NPS derivative, N-(3,5-dichlorophenyl)succinimide (NDPS), is a potent nephrotoxicant which induces marked proximal tubular necrosis at i.p. doses of 0.4 mmol/kg or greater. The purpose of this study was to compare the nephrotoxic potential of 2-hydroxy-N-phenylsuccinimide (HNPS) and N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS), an oxidative and nephrotoxicant metabolite of NDPS, to determine the importance of the chloride groups for the nephrotoxic potential of NDHS. Male Fischer 344 rats (4/group) were administered a single i.p. injection of HNPS (1.0 or 1.5 mmol/kg), NDHS (0.1 mmol/kg) or vehicle (25% dimethyl sulfoxide in sesame oil), and renal function measured at 24 and 48 h. HNPS was a nonnephrotoxicant at both doses tested, while NDHS induced marked nephrotoxicity characterized by diuresis, increased proteinuria, glucosuria, elevated blood urea nitrogen (BUN) concentration and kidney weight, decreased organic ion accumulation by renal cortical slices and proximal tubular necrosis. In vitro, HNPS reduced p-aminohippurate (PAH) and tetraethylammonium (TEA) accumulation beginning at HNPS bath concentrations of 0.05 and 0.5 mM, respectively. The results of this study indicate that although HNPS has direct effects on renal function in vitro, HNPS is not a nephrotoxicant in vivo at doses up to 15 times the minimal nephrotoxicant dose of NDHS. Therefore, the chloro groups present on NDHS play an essential role in the nephrotoxic potential of NDHS and contribute to aspects of the nephrotoxic mechanism of NDPS beyond NDPS oxidation to form NDHS.

Analysis of Variance↗

Blunt gastrointestinal injury in trauma patients.

The evaluation, management, and final outcome of 34 patients with blunt gastrointestinal injury (BGI) were reviewed. Initial absence of symptoms and signs led to two delayed diagnoses. Sonography provided 80% (12/15) positive-predictive value, and three false-negative patients were subsequently detected by diagnostic peritoneal lavage (DPL). Besides repeated clinical surveillance, screening by sonography complemented with DPL provided early detection of blunt bowel injury in trauma patients. In the outcome analysis, BGI patients with high injury-severity scores, intraoperative hypotension, or accompanying major medical diseases were associated significantly with increased risk of infectious complications (P < .05).

Adolescent↗

Urgent laparotomy versus emergency craniotomy for multiple trauma with head injury patients.

In blunt multiple trauma (MT) with head injury (HI) patients, it is difficult to decide whether to proceed with immediate laparotomy or craniotomy. In August 1989, abdominal ultrasonography (US) using a simple US scoring system was introduced for MT and HI patients as an initial rapid screening procedure. In MT and HI patients with a US score > or = 3 (n = 14), urgent laparotomy was the procedure of first choice. However, immediate head CT scan, then emergency craniotomy, may be justified in hemodynamically stable MT and HI patients with a US score < 3 (n = 98). Appropriate decision making can be applied to decide which procedure is most exigent.

Abdomen↗

Sequential cytogenetic alterations in hamster oral keratinocytes during DMBA-induced oral carcinogenesis.

Using the hamster cheek pouch oral cancer model, we have performed a comprehensive analysis of the cytogenetic changes in hamster oral keratinocytes during 7,12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis. Tumour induction in the hamster cheek pouch required repeated application of the carcinogen for 14 weeks. We have found that this hamster oral cancer model to be suitable for cytogenetic studies. Unlike human oral cancers where chromosome breaks have been shown, this is only infrequently observed in DMBA-treated hamster oral keratinocytes. Of importance is the finding that at the beginning of the second week of DMBA treatment, there is a significant increase of karyotypes demonstrating tetraploid or near-tetraploidy. We propose that the significant increase in hamster oral keratinocytes exhibiting tetraploidy be further evaluated as a marker of premalignancy/malignancy.

9,10-Dimethyl-1,2-benzanthracene↗

Ultrasonography for the evaluation of hemoperitoneum during resuscitation: a simple scoring system.

To assess the need for therapeutic laparotomy in patients with blunt abdominal trauma (BAT), ultrasonography (US) and a simple US scoring system were used to estimate the amount of hemoperitoneum during resuscitation. In group I (BAT with a US score > or = 3), 24 of 25 patients (96%) required therapeutic laparotomy. In group II (BAT with a US score < 3), therapeutic laparotomy was required in only 9 of 24 patients (38%); nonsurgical treatment may be justified in hemodynamically stable patients. Appropriate decisions can be made to perform urgent laparotomy when intra-abdominal bleeding is the culprit in BAT patients. Unnecessary laparotomy can be avoided when the major site of blood loss is not in the abdomen. Ultrasonography, an initial rapid screening procedure in BAT patients, is useful for trauma surgeons in decision making during resuscitation.

Abdominal Injuries↗

New adenosine kinase inhibitors with oral antiinflammatory activity: synthesis and biological evaluation.

Several 5-iodotubercidin analogues in the pyrazolo[3,4-d]pyrimidine ring system were synthesized as potential inhibitors of adenosine kinase by a direct Lewis acid-catalyzed glycosylation procedure using both the preformed carbohydrate and the heterocyclic base as starting materials. The 5'-hydroxyl, -chloro, -azido, -deoxy, -amino, and -fluoro derivatives were prepared and evaluated in three systems for biological activity relative to adenosine, the true substrate, and 5-iodotubercidin, a known inhibitor. First, each compound was studied kinetically for inhibition of purified human placental adenosine kinase activity. The order of potency was: iodotubercidin > hydroxyl > amino > or = deoxy > fluoro > chloro >> azido. The Ki values for the 5'-hydroxyl and 5'-amino compounds, the two most potent inhibitors, were 80 and 150 nM, respectively. The inhibition appeared to be essentially competitive in nature, although a noncompetitive component of significance for the more potent inhibitors cannot be ruled out. Second, a bioassay was conducted in which the toxicity of 6-methylmercaptopurine riboside toward human CEM lymphoblasts was reversed by varying concentrations of the compounds. The order of effectiveness of the compounds in this system, representing a functional inhibition of adenosine kinase in cultured cells, was about the same as that with the purified enzyme, except that the 5'-chloro and 5'-fluoro compounds were ineffective. Third, the 5'-hydroxyl derivative was evaluated in vivo in a rat pleurisy inflammation model and displayed biological activity at a dose of 30 mg/kg given orally. Finally, the in vitro toxicity of each compound was assessed in CEM lymphoblasts. Results indicated that the two most potent inhibitors in the pyrazolo[3,4-d]pyrimidine ring system, the 5'-hydroxyl (7) and the 5'-amino (20), were 15-fold and 75-fold, respectively, less growth inhibitory than 5-iodotubercidin.

Adenosine Kinase↗

Role of para-hydroxylation in phensuximide-induced urotoxicity in the Fischer 344 rat.

Phensuximide (PSX) is an antiepileptic agent which has been shown to induce hemorrhagic cystitis and mild nephrotoxicity following repeated administration in man or rats or when acutely administered to phenobarbital-pretreated rats. The purpose of this study was to explore the role of para-hydroxylation of the phenyl group of PSX in PSX-induced urotoxicity. Two PSX derivatives, 2-(4-fluorophenyl)-N-methylsuccinimide (FMPS) and N-methyl-2-(4-methylphenyl)succinimide (MMPS), were synthesized and evaluated for urotoxic potential. Male Fischer 344 rats (four rats/group) were administered intraperitoneally (i.p.) a succinimide (0.4 or 1.0 mmol/kg) or vehicle and renal function monitored for 48 h. In a separate experiment, rats were pretreated with phenobarbital (75 mg/kg/day; 3 days, i.p.) prior to succinimide or succinimide vehicle. In non-phenobarbital pretreated rats, acute FMPS or MMPS treatment had little effect on renal function or morphology at the doses tested. Hematuria (+) was noted in the FMPS (1.0 mmol/kg) group on post-treatment day 2. However, in the phenobarbital-pretreated rats, FMPS (0.4 or 1.0 mmol/kg) induced marked hematuria (++) and increased proteinuria while having little or no effect on other renal functional parameters or renal morphology. At killing, bladders of treated rats were distended with bloody urine and exhibited hemorrhagic areas within the bladder wall. In phenobarbital-pretreated rats, MMPS administration had little effect on any renal functional parameter measured or urological morphology. These results suggest that para-hydroxylation does not contribute to the hemorrhagic cystitis induced by PSX.

Animals↗