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Biomedical subjects

H C Lin

Publications and source records attributed to H C Lin.

At least 109 records · Page 6Linked to original sources

Lipopolysaccharide enhances substance P-mediated neutrophil adherence to epithelial cells and cytokine release.

Lipopolysaccharide (LPS) is implicated in many respiratory tract inflammatory diseases. Tachykinins, especially substance P (SP) through the NK-1 receptor, mediate leukocyte adhesion to the endothelial or airway epithelial cells. Here we assessed the enhancement by LPS of tachykinin-mediated neutrophil adherence to alveolar epithelial cells, and associated interleukin-1 beta (IL-1beta) and tumor necrosis factor (TNF-alpha) release. Neutrophil adherence to A549 epithelial cell was not increased by LPS (100 ng/ml), or SP (10(-)(12)-10(-)(8) M) alone, but was significantly enhanced by their combination (LPS + SP). Neutrophil adherence to epithelial cells induced IL-1beta and TNF-alpha release from A549 cells either spontaneously or stimulated by SP or LPS. LPS + SP significantly enhanced IL-1beta and TNF-alpha release. The NK-1 receptor antagonist L-732,138 inhibited this enhancement response. Prevention of neutrophil adherence by CD11b/CD18 blocking antibody or by placing a filter on the epithelial monolayer diminished spontaneous or LPS + SP-enhanced IL-1beta and TNF-alpha release. Pretreatment with the serine protease inhibitor cocktail also inhibited LPS + SP-enhanced neutrophil adherence-dependent IL-1beta and TNF-alpha release as well as their mRNA expression. In conclusion, we have demonstrated LPS enhanced SP-mediated neutrophil adherence and associated IL-1beta and TNF-alpha release from the A549 epithelial monolayer, partly through NK-1 receptors. Neutrophil adherence to epithelial cells may release serine protease to induce IL-1beta and TNF-alpha release and their synthesis.

CD18 Antigens↗

Symptomatic esophageal stricture after endoscopic variceal ligation--success of endoscopic balloon dilation.

Endoscopic variceal ligation is a preferred endoscopic method to treat esophageal variceal bleeding. Esophageal stricture complicated by endoscopic ligation is very unusual. We report a case of symptomatic esophageal stricture after variceal ligation. Endoscopic balloon dilatation was used to treat the stricture successfully. The possible mechanism of stricture formation is discussed.

Aged↗

Sequential changes in plasma cytokine and endotoxin levels in cirrhotic patients with bacterial infection.

To delineate the clinical roles of plasma cytokine or endotoxin levels in the natural course of infection in patients with decompensated cirrhosis, 66 cirrhotic patients were studied within a 1.5-year period. Plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8 and endotoxin were determined on days 1, 4 and 7 after admission when hospital infection was suspected and 4 months later. A total of 24 patients (36.4%) were proven to be infected during hospitalization (group A), while 42 others were not infected (group B). Fever occurred in a very high proportion (22/24) of group A patients. Baseline levels of TNF-alpha (37.7+/-15.2 compared with 8.7+/-1.2 pg/ml; P<0.01) and IL-6 (180.5+/-20.5 compared with 24.6+/-7.5 pg/ml; P<0.0001) were higher in group A patients, while IL-1beta, IL-8 and endotoxin levels were not significantly different between the two groups. For patients with hospital infection, IL-6 levels determined during the episode were significantly higher than baseline levels. Using IL-6 >80 pg/ml as a baseline cut-off level to diagnose bacterial infection, the sensitivity, specificity and accuracy were 87.5, 100 and 95.5% respectively. The one-year cumulative probability of mortality (61.1% compared with 23.7%; P<0.001) and of bacterial re-infection (72.2% compared with 18.4%; P<0.0001) was higher in group A than in group B. Plasma TNF-alpha and IL-6 levels determined at 4 months were not different between the two groups. In conclusion, fever or elevated plasma IL-6 levels in patients with decompensated cirrhosis calls for early antibiotic treatment to prevent life-threatening bacterial infection. Bacterial infection is likely to recur in those patients with increased IL-6 levels, while severe episodes of infection occur in patients with increased TNF-alpha levels.

Aged↗

Endotoxemia augments neurogenic plasma exudation in guinea pig lungs.

BACKGROUND: Lipopolysaccharide (LPS) is closely associated with the development of infection-induced deleterious pulmonary reactions. In this study, we investigated the enhancement effects of LPS on tachykinin-mediated plasma exudation in the lungs of guinea pigs. The role of oxidants was also explored. METHODS: Intravenous LPS (100 mu kg-1) or its vehicle was administered 0 to 3 hours prior to bilateral electrical or sham stimulation of the cervical vagus nerves in animals anesthetized with urethane and artificially ventilated. Plasma exudation into the lungs was assessed by measurement of extravasated 125I-albumin which had been intravenously administered before stimulation. RESULTS: The plasma exudation in the lungs increased after bilateral cervical vagal stimulation. LPS alone did not induce significant plasma exudation. The vagally-mediated plasma exudation was enhanced by LPS with the peak effect 1 hour after LPS administration. LPS also enhanced exogenous substance P (10(-8) mol kg-1, i.v.)-induced plasma exudation. The vagally-induced plasma exudation was abolished by a specific neurokinin-1 (NK-1) receptor antagonist, L-732,138. The LPS-induced enhancement response was also attenuated by L-732,138. The vagally-induced plasma exudation was not affected by superoxide dismutase (SOD, 5000 U kg-1, i.p.) pretreatment. However, SOD significantly inhibited the LPS-enhanced neurogenic plasma leakage. The LPS-induced enhancement was not completely abolished by either L-732,138 or SOD pretreatment alone, but by a combination of both. CONCLUSION: LPS augments neurogenic plasma exudation partly through NK-1 receptors to increase vascular permeability and partly via the generation of oxidative metabolites. Tachykinins released from nerve endings may contribute to endotoxin-related pulmonary inflammatory responses.

Animals↗

Splanchnic endotoxin levels in cirrhotic rats induced by carbon tetrachloride.

BACKGROUND: Bacterial translocation (passage of intestinal bacteria to mesenteric lymph nodes) observed in cirrhosis may be a source of endotoxin that can stimulate nitric oxide production and participate in the pathogenesis of hyperdynamic circulation. Currently, there are no published data concerning splanchnic endotoxin levels in cirrhotic rats. This study was designed to determine systemic and portal hemodynamics and to detect endotoxins in the portal and systemic circulation. METHODS: Liver cirrhosis was induced by carbon tetrachloride intragastric gavage. Systemic and splanchnic endotoxin levels in control rats and cirrhotic rats with or without ascites were measured using a chromogenic Limulus assay. In addition, systemic and portal hemodynamic data were obtained using a thermodilution technique and catheterization. RESULTS: Cirrhotic rats with ascites had the lowest systemic vascular resistance (2.6 +/- 0.1 mmHg.ml-1.min.100 g body weight, BW) compared with control rats (6.3 +/- 0.3 mmHg.ml-1.min.100 g BW; p < 0.05) and cirrhotic rats without ascites (3.7 +/- 0.3 mmHg.ml-1.min.100 g BW; p < 0.05). Cirrhotic rats with ascites displayed the highest splanchnic levels of endotoxin (10.6 +/- 3.1 pg/ml) compared with cirrhotic rats without ascites (2.0 +/- 0.7 pg/ml; p < 0.05) and control rats (2.0 +/- 0.4 pg/ml; p < 0.05). There was no difference in the splanchnic endotoxin levels between control rats and cirrhotic rats without ascites (p > 0.05). Similar results were observed with systemic endotoxin values (cirrhotic rats with ascites, 10.8 +/- 2.8 pg/ml; cirrhotic rats without ascites, 2.7 +/- 0.6 pg/ml; control rats, 2.5 +/- 0.4 pg/ml; p < 0.05). A significant correlation existed between portal and systemic endotoxin values in cirrhotic rats with or without ascites (r = 0.96, p < 0.001 and r = 0.9, p < 0.05, respectively), whereas this correlation did not exist in control rats (r = 0.5, p > 0.05). CONCLUSIONS: Cirrhotic rats with ascites had the lowest systemic vascular resistance and the highest splanchnic endotoxin levels when compared with cirrhotic rats without ascites and control rats. These results suggest that splanchnic endotoxemia may be involved in the development and/or maintenance of hyperdynamic circulation.

Animals↗

Establishment of an animal model of hepatic encephalopathy.

BACKGROUND: Hepatic encephalopathy is a neuropsychiatric syndrome associated with acute liver failure, chronic parenchymal liver disease or portal systemic anastomosis. The spectrum of symptoms may vary from subtle mental changes to a disrupted circadian rhythm to hepatic coma. In order to investigate the possible pathogenetic mediators and the use of potential new therapies, the aim of our study was to create a reliable animal model for research on hepatic encephalopathy. METHODS: Forty male Sprague-Dawley rats were used. Fulminant hepatic failure was induced by intraperitoneal injection of thioacetamide (TAA, 350 mg/kg) for three consecutive days (n = 30). Rats treated with normal saline served as controls (n = 10). The clinical stage of hepatic encephalopathy in TAA-treated rats was graded according to neurobehavioral testing. Spontaneous motor activities of rats were calculated using the Opto-Varimex animal activity meter. We also investigated the relationships between the neurobehavioral score and the motor activity count. RESULTS: Compared with normal, saline-treated rats, those receiving consecutive injections of TAA had apparently lower neurobehavioral scores (p < 0.001) accompanied by significantly blunted motor activities (p < 0.001). A significant correlation was demonstrated between the neurobehavioral score and total movements in rats with encephalopathy (r = 0.71, p < 0.001). In addition, the neurobehavioral score also correlated well with ambulatory movements (r = 0.73, p < 0.001) and vertical movements (r = 0.45, p < 0.05). CONCLUSIONS: The rat model is acceptable for the study of hepatic encephalopathy, as established in this study. This experimental model can be used to explore the pathogenesis and management of hepatic encephalopathy.

Animals↗

Pertussis seroepidemiology in Taipei.

PURPOSE: We evaluated the seroprevalence of pertussis among apparently healthy Taipei residents. METHODS: From January 1992 through December 1994, we recruited subjects from a well baby clinic (children < 3 years), kindergartens, primary, and secondary schools and colleges (3-20 years), a health exam clinic (> 20 years), and obstetric clinics (pregnant women). Subjects were stratified into 12 groups according to age and pregnant women were considered separately. The serum antibody titers against filamentous hemagglutinin (FHA) and pertussis toxin (PT) were measured by enzyme-linked immunosorbent assay. RESULTS: The anti-PT and anti-FHA titers were elevated in the 4 to 6-month and 19 to 20-month age groups, coinciding with regular pertussis vaccinations. The anti-PT titers rose again in the 3 to 4-year age group, reflecting a higher prevalence of natural pertussis infection. The anti-PT titers gradually decreased among older age groups, although a peak occurred in the 11 to 15-year age group. The sequential changes in anti-FHA titers followed those of anti-Pt titers in the younger age groups, but the anti-FHA titers were persistently elevated beyond 15 years of age. The antibody levels were similar in the two sexes, except that anti-PT titers were higher in males of 19 to 20 months and 21 to 30 years of age. Anti-PT titers were equivalent between neonates (0-2 months) and pregnant women, but anti-FHA titers were much lower in neonates. CONCLUSIONS: The seroprevalence patterns in this study indicate that young children, adolescents, and even adults remain at risk of pertussis, despite the current immunization program. Booster vaccinations after completion of the current four-dose immunization schedule, possibly continuing into adolescence, should be considered to block the transmission of infection.

Adhesins, Bacterial↗

The effect of incentive spirometry on chest expansion and breathing work in patients with chronic obstructive airway diseases: comparison of two methods.

BACKGROUND: Chronic obstructive airway diseases (COAD), characterized by mucus hypersecretion, lead to exercise intolerance. Incentive spirometry has been used to prevent postoperative pulmonary atelectasis. METHODS: To compare the efficacy of two incentive spirometers, Coach (volume-oriented) and Triflo (flow-oriented), in the work of breathing in COAD patients, 22 patients were randomized in this study: 12 patients (Triflo-II group) initially used Triflo-II for 10 minutes and then Coach for the same period. In contrast, the Coach group, including 10 patients, started with Coach followed by Triflo-II. After receiving incentive spirometry, lung expansion and work of breathing were assessed. RESULTS: Patients in the Coach group significantly increased chest wall expansion (p = 0.041), as compared with patients using Triflo-II. Similarly, there was also a significantly increased abdominal wall expansion in the Coach group (p = 0.0056), compared with that in the Triflo-II group. The need of accessory muscle assistance for breathing in the Coach group was significantly less than in the Triflo-II group (p = 0.047). It was easier for patients in the Coach group to start a breath (p = 0.0058) than for those in the Triflo-II group. For the entire group, 17 patients (77.3%) preferred Coach to assist their breathing, and only 4 patients (18.2%) favored Triflo-II. CONCLUSION: COAD patients achieved a larger expansion of the chest and abdomen with a Coach device. Our data provide a good rationale for an outcome study on the use of incentive spirometer in COAD patients.

Adult↗

Enteric adenovirus infection in children in Taipei.

Enteric adenoviruses (EAds), including type 40 (Ad40) and 41 (Ad41), can cause acute and severe diarrhea in young children. To delineate the epidemiological features of pediatric EAds infection in Taiwan, we conducted a retrospective study of all cases of EAds gastroenteritis in children treated at National Taiwan University Hospital for the period from July 1993 to December 1997. Stool samples were tested for the presence of Ad40 or Ad41 by enzyme immunoassay (EIA). A total of 64 cases of EAds infection in 63 children aged from 8 days to 81 months old with a median age of 9.5 months treated during the study period were identified. The male-to-female ratio was 1.63 (39/24). No obvious seasonal clustering of EAds cases was noted. Most patients (76.6%) were infected before the age of 2 years. Clinical features included diarrhea (96.9%), fever (54.7%), vomiting (45.3%), mild dehydration (43.8%), symptoms of upper respiratory tract infection (21.9%), and abdominal pain (12.5%). Analysis of fecal samples in patients with diarrhea showed watery diarrhea in 72.2%, diarrhea with mucus in 20%, diarrhea with blood in 3.1% and diarrhea with mucus and blood in 1.6 % of all patients. Nearly one-half (43.5%) of the patients had diarrhea for more than 7 days. Thirty-seven patients (57.8%) were hospitalized due to gastroenteritis or other unrelated diseases, and 11 patients (17.2%) acquired enteric adenovirus infection during hospitalization for other underlying disease. Twelve patients (18.8%) had mixed infections, which included rotavirus, respiratory syncytial virus (RSV) and Salmonella species. There were no deaths in this series. The findings of this study suggest that EAds are important etiologic microbes of pediatric gastroenteritis.

Adenoviridae Infections↗

Rotavirus gastroenteritis in children: 5-year experience in a medical center.

Rotavirus infection is the leading cause of childhood gastroenteritis. We retrospectively reviewed cases of rotavirus gastroenteritis at National Taiwan University Hospital from January 1993 to December 1997. During the study period there were 429 patients with rotavirus infection with ages ranging from 1 day to 16 years with a median of 13 months. The male-to-female ratio was 1.2:1. Infection occurred before the age of 2 years old in 76% of patients. The seasonal peak occurred in the late winter and early spring during 1993 to 1996, but the case number increased in late spring and summer in 1997. The G serotype of the rotavirus was identified in 302 patients (70%). Vomiting and dehydration developed more frequently following infection with G1 rotaviruses, while an increased frequency of seizures was noted following G2 infection; the differences were not statistically significant. One patient had two episodes of infection; the first one was caused by G1 rotavirus, and the strain causing the second infection could not be typed. In conclusion, the results suggest that there is a strong seasonal variation in the incidence and characteristics of rotavirus infection in Taipei area. The infections caused by G1 and G2 rotaviruses were clinically indistinguishable.

Adolescent↗

Penicillamine induced lupus-like syndrome: a case report.

Several drugs have been suggested to cause lupus-like syndrome. However, penicillamine-induced lupus-like syndrome has only rarely been reported in patients with Wilson's disease. We describe a 6- year-old Taiwanese girl, with a diagnosis of Wilson's disease in November, 1997, who developed lupus-like syndrome 17 months after penicillamine treatment. After treatment with prednisolone and decrease in the dose of penicillamine, her symptoms subsided gradually. This is the first such case reported in a Taiwanese patient. Because the symptoms of drug-induced lupus (DIL) are nonspecific, subjective and variable, the diagnosis of DIL requires awareness of DIL-inducing potential of chronic medication.

Child↗

Splanchnic hyposensitivity to glypressin in a haemorrhage/transfused rat model of portal hypertension: role of nitric oxide and bradykinin.

Hyposensitivity to vasopressin is a well documented phenomenon in animals with portal hypertension and patients with cirrhosis subject to haemorrhage. Haemorrhage is associated with the endogenous release of bradykinin, which may subsequently stimulate the formation of nitric oxide (NO). The present study investigated the relative contribution of NO synthase (NOS) isoforms and the role of bradykinin in the pathogenesis of splanchnic hyposensitivity to a long-acting vasopressin analogue, glypressin, in rats with portal hypertension induced by partial portal vein ligation (PVL). At 14 days after the operation, systemic and portal haemodynamics were measured in stable or bleeding PVL rats receiving an intravenous infusion of glypressin (0.07 mg/kg). In the treatment groups, N(G)-nitro-L-arginine methyl ester (L-NAME; a non-selective NOS inhibitor), L-canavanine (a specific inhibitor of inducible NOS) or HOE 140 (a bradykinin B(2) receptor antagonist) was administered 45 min before the infusion of glypressin. In rats with a hypotensive haemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was re-infused before the administration of glypressin or various inhibitors. Splanchnic hyposensitivity to glypressin was demonstrated in the haemorrhage/transfused PVL rats. The infusion of L-NAME elevated the mean arterial pressure in the bleeding PVL rats without the modulation of portal pressure. The addition of L-NAME or HOE 140, but not L-canavanine, significantly and similarly potentiated the portal-hypotensive effects of glypressin. It is concluded that constitutive NOS and bradykinin are responsible, at least partly, for the splanchnic hyposensitivity to glypressin observed in the early stages of the haemorrhage/transfused rat model of portal hypertension.

Animals↗

The value of transbronchial lung biopsy in the diagnosis of peripheral lung tumors according to cell type.

BACKGROUND: Transbronchial lung biopsy (TBLB) is a useful diagnostic tool for peripheral lung tumors. However, the success rate is variable. Our study was designed to investigate the value of TBLB without fluoroscopic guidance in the diagnosis of variable cell types of peripheral lung cancers. METHODS: A retrospective study was conducted to investigate a total of 597 patients who had undergone fiberoptic bronchoscopy for lung mass on chest X-ray in Chang Gung Memorial Hospital from January 1996 to December 1998. The lung masses were proven to be malignant by cytology and histology. RESULTS: Of 358 patients (60.0%) proven with malignancy, 107 patients presented with peripheral lung cancer (17.9%), including 59 with adenocarcinoma, 26 with squamous cell carcinoma, 11 with poorly differentiated carcinoma, 3 with small cell carcinoma, and 8 with metastatic cancers. The diagnostic rate of peripheral lung cancer by TBLB reached 54.2%. The sensitivity rates of detection of non-small cell type by TBLB were adenocarcinoma, 50.9%; squamous cell carcinoma, 61.5%; and poorly differentiated carcinoma, 72.7%, while that of small cell carcinoma was 100%. In contrast, the sensitivity rate of TBLB for metastatic cancers was lower (12.5%) than for primary lung cancers. Repeated TBLB of peripheral lung cancers increased the diagnostic rate from 49.5% to 54.2%. CONCLUSION: TBLB is an effective bronchoscopic sampling technique in the diagnosis of peripheral lung tumors without additional risk. The use of TBLB in the clinical routine should be encouraged.

Biopsy, Needle↗

Value of bronchoalveolar lavage combined with transbronchial lung biopsy in the diagnosis of peripheral lung cancer.

BACKGROUND: Bronchoalveolar lavage (BAL) is a safe and established procedure to evaluate interstitial lung diseases and pulmonary tuberculosis. The diagnostic rate of peripheral lung cancer invisible through bronchoscopy applied by transbronchial lung biopsy (TBLB) is still low. The study was designed to evaluate whether BAL combined with TBLB might improve the positive value in the diagnosis of peripheral lung cancer. METHODS: Thirty-seven of 72 patients who presented with peripheral lung lesions in chest radiography were proven to have a malignancy according to the final reports of cytology, histology, and clinical evidence. Each patient received BAL with or without TBLB. The patterns of chest radiography of the malignancies included 33 of infiltrative type and 4 of massive or nodular type. RESULTS: BAL alone revealed positive malignant cells in 18 of 37 cases (sensitivity 48.6%), and the diagnostic value significantly increased to 73.0% (p < 0.05) with BAL + TBLB. In the infiltrative type of lung cancer, the diagnostic rate of BAL + TBLB (78.8%) was significantly improved compared to that of BAL alone (51.5%, p < 0.05). There was no difference of diagnostic value in those with nodular type. BAL + TBLB can achieve a very high diagnostic rate (100%) in cases of metastatic malignancy (n = 4). Only 2 patients developed bleeding post BAL + TBLB, and it was easily controlled by epinephrine spraying. One patient developed self-limited hemoptysis. CONCLUSION: BAL + TBLB is a safe and valuable procedure to achieve a high sensitivity rate in the diagnosis of peripheral lung cancer, especially of the infiltrative type.

Adult↗

Systemic administration of D-amphetamine induced a delayed production of nitric oxide in the striatum of rats.

Nitric oxide (NO) is a free-radical gas with a role in various signal transduction processes. In the CNS, NO acts as an important central nervous messenger, but in excess it may be neurotoxic. Chronic or high dose administration of D-amphetamine (AMPH) has been shown to induce striatal neurotoxicity in rodents and primates. In this study, we studied whether AMPH given systemically elicits NO formation in the striatum of rats and determined the relationship between NO formation and striatal DAergic terminal damage. Our results demonstrated that a single large dose administration of AMPH with desipramine elicited a delayed production of NO and concomitant long-term DA loss in the striatum. These phenomena were blocked by treatment with either the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) or the glutamate N-methyl-D-aspartate antagonist MK-801. It appears that AMPH-induced NO formation is critical for development of long-lasting DAergic terminal toxicity in the striatum of rats.

Animals↗

Nitric oxide signaling pathway mediates the L-arginine-induced cardiovascular effects in the nucleus tractus solitarii of rats.

We have previously demonstrated that L-arginine produces profound cardiovascular effects when microinjected into the nucleus tractus solitarii (NTS) of the rat. The present study extended our earlier work and examined further the underlying mechanisms of action of L-arginine in the NTS. Our results showed that intra-NTS microinjection of L-arginine (0.1-10 nmol) elicited dose-dependent depressor and bradycardic effects that were not significantly evoked by equivalent doses of D-arginine. The effects of L-arginine were blocked by pre-injection of 7-nitroindazole (0.02-1 nmol), a neuronal nitric oxide synthase inhibitor. Additionally, application of the calmodulin inhibitor W-7 (0.01-0.33 nmol) reduced cardiovascular responses to L-arginine (10 nmol) in a dose-dependent manner. Pre-injections of soluble guanylyl cyclase inhibitors, LY83583 (0.01-0.33 nmol) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 0.03-1 pmol) both suppressed the L-arginine-induced depressor and bradycardic effects. Finally, the cardiovascular effects of L-arginine in the NTS were attenuated by HA1004 (0.1-1 nmol), a cGMP-dependent protein kinase inhibitor, but not by the protein kinase C inhibitor H-7 (1 nmol). Taken together, the results indicate that the cardiovascular effects produced by L-arginine in the NTS are inhibited by pharmacological interventions that block nitric oxide production and cGMP-PKG signaling pathway within the nucleus.

Aminoquinolines↗

Chemistry and biological activities of constituents from Morus australis.

A novel constituent named australone B (1) was further isolated from the cortex of Morus australis (Moraceae). The structure of 1 has been elucidated by one- and two-dimension spectra. In human citrated platelet-rich plasma, 1 showed strong inhibition of aggregation induced by adrenaline in a concentration-dependent manner with an IC(50) value of about 33.3 microM. Compound 1 (30 microM) also showed inhibitory effects on superoxide anion formation from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB). Morusin (2) inhibited superoxide anion formation from rat neutrophils stimulated with phorbol myristate acetate (PMA) in a concentration-dependent manner with an IC(50) value of 66.9+/-2.5 microM.

Animals↗

Prevention of chronic lung disease in preterm infants by early postnatal dexamethasone therapy.

Recent studies suggest that early dexamethasone therapy may lessen the pulmonary inflammation in preterm infants with respiratory distress syndrome (RDS). To investigate whether early (<12 hr) postnatal dexamethasone therapy would reduce the incidence of chronic lung disease (CLD), a randomized, double-blind, controlled trial was conducted in 40 infants (birth weights from 500 to 1,999 gm) who had severe RDS and required mechanical ventilation within 6 hr of birth. All infants received one dose of Survanta before they were randomly assigned to control (saline placebo) or dexamethasone-treated groups (0.5 mg/kg/d for 1 week, then tapered over 3 weeks). Sequential analysis was performed with the end point of assessment being the presence or absence of CLD on postnatal Day 28. Statistical significance favoring dexamethasone was reached when 12 consecutive pairs in which one infant had CLD and the other did not have CLD showed that ten pairs favored dexamethasone and two pairs favored control treatment. Among the survivors, 12/15 were extubated in the dexamethasone group and 9/16 in the control group at the end of study. Infants in the treated group had transient hyperglycemia and hypertension. There was no difference between the groups in mortality and in incidence of sepsis or intraventricular hemorrhage. We conclude that early postnatal dexamethasone therapy is potentially effective in the lessening of CLD in preterm infants. To substantiate our result, large randomized controlled trials are needed and warranted.

Anti-Inflammatory Agents↗