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Biomedical subjects

J C Lam

Publications and source records attributed to J C Lam.

10 recordsLinked to original sources

Resuscitation with lactated ringer's does not increase inflammatory response in a Swine model of uncontrolled hemorrhagic shock.

Lactated Ringer's (LR) and normal saline (NS) are widely and interchangeably used for resuscitation of trauma victims. Studies show LR to be superior to NS in the physiologic response to resuscitation. Recent in vitro studies demonstrate equivalent effects of LR and NS on leukocytes. We aimed to determine whether LR resuscitation would produce an equivalent inflammatory response compared with normal saline (NS) resuscitation in a clinically relevant swine model of uncontrolled hemorrhagic shock. Thirty-two swine were randomized. Control animals (n = 6) were sacrificed following induction of anesthesia for baseline data. Sham animals (n = 6) underwent laparotomy and 2 h of anesthesia. Uncontrolled hemorrhagic shock animals (n = 10/group) underwent laparotomy, grade V liver injury, and blinded resuscitation with LR or NS to maintain baseline blood pressure for 1.5 h before sacrifice. Lung was harvested, and tissue mRNA levels of interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and tumor necrosis factor-alpha (TNF-alpha) were determined using quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR). Sections of lung were processed and examined for neutrophils sequestered within the alveolar walls. Cytokine analysis showed no difference in IL-6 gene transcription in any group (P = 0.99). Resuscitated swine had elevated G-CSF and TNF-alpha gene transcription, but LR and NS groups were not different from each other (P= 0.96 and 0.10, respectively). Both resuscitation groups had significantly more alveolar neutrophils present than controls (P < 0.01) and shams (P < 0.05) but were not different from one another (P= 0.83). LR and NS resuscitation have equivalent effects on indices of inflammation in the lungs in our model of uncontrolled hemorrhagic shock.

Animals↗

Interleukin-6 infusion blunts proinflammatory cytokine production without causing systematic toxicity in a swine model of uncontrolled hemorrhagic shock.

BACKGROUND: Serum elevations of interleukin-6 (IL-6) correlate with multiple organ dysfunction syndrome and mortality in critically injured trauma patients. Data from rodent models of controlled hemorrhage suggest that recombinant IL-6 (rIL-6) infusion protects tissue at risk for ischemia-reperfusion injury. Exogenous rIL-6 administered during shock appears to abrogate inflammation, providing a protective rather than a deleterious influence. In an examination of this paradox, the current study aimed to determine whether rIL-6 decreases inflammation in a clinically relevant large animal model of uncontrolled hemorrhagic shock, (UHS), and to investigate the mechanism of protection. METHODS: Swine were randomized to four groups (8 animals in each): (1) sacrifice, (2) sham (splenectomy followed by hemodilution and cooling to 33 degrees C), (3) rIL-6 infusion (sham plus UHS using grade 5 liver injury with packing and resuscitation plus blinded infusion of rIL-6 [10 mcg/kg]), and (4) placebo (UHS plus blinded vehicle). After 4 hours, blood was sampled, estimated blood loss determined, animals sacrificed, and lung harvested for RNA isolation. Quantitative reverse transcriptase-polymerase chain reaction was used to assess granulocyte colony-stimulating factor (G-CSF), IL-6, and tumor necrosis factor-alpha (TNFalpha) messenger ribonucleic acid (mRNA) levels. Serum levels of IL-6 and TNFalpha were measured by enzyme-linked immunoassay (ELISA). RESULTS: As compared with placebo, IL-6 infusion in UHS did not increase estimated blood loss or white blood cell counts, nor decrease hematocrit or platelet levels. As compared with the sham condition, lung G-CSF mRNA production in UHS plus placebo increased eightfold (*p < 0.05). In contrast, rIL-6 infusion plus UHS blunted G-CSF mRNA levels, which were not significantly higher than sham levels (p = 0.1). Infusion of rIL-6 did not significantly affect endogenous production of either lung IL-6 or mRNA. As determined by ELISA, rIL-6 infusion did not increase final serum levels of IL-6 or TNFalpha over those of sham and placebo conditions. CONCLUSIONS: Exogenous rIL-6 blunts lung mRNA levels of the proinflammatory cytokine G-CSF. The administration of rIL-6 does not increase the local expression of IL-6 nor TNFalpha mRNA in the lung. Additionally, rIL-6 infusion does not appear to cause systemic toxicity.

Animals↗

Lymphoepithelioma-like carcinoma of the lung in a patient with silicosis.

Silicosis is an important form of pneumoconiosis, which is caused by significant exposure to crystalline silica. The carcinogenicity of silica, despite traditional beliefs, in relation to lung cancer has been controversial. Lymphoepithelioma-like carcinoma of the lung, an Epstein-Barr virus-associated undifferentiated carcinoma, is a rare entity of pulmonary malignancy, which tends to affect young nonsmoking Asians. The first case of silicosis, initially complicated by pulmonary tuberculosis, which later developed into advanced lymphoepithelioma-like carcinoma of the lung is reported. A combination of 5-fluorouracil, cisplatin and calcium folinate resulted in partial tumour response.

Aged↗

Follow-up survey of children and adolescents with chest pain.

BACKGROUND: The purposes of this study were to identify the outcome of chest pain in children and to identify the incidence of recurrent chest pain and the need for further medical services. METHODS: A telephone survey was conducted of pediatric patients evaluated in the cardiology clinic for chest pain. RESULTS: In the majority of patients (53 of 55), chest pain was thought to be noncardiac in origin. Fifteen patients were offered therapy, and all followed the therapy. Most (10 of 15) thought the therapy was helpful. Forty-one (75%) were satisfied with the explanation given to them. Twenty-six had recurrent chest pain, 12 had pain that was severe, 13 thought the pain interfered with daily activities, and 10 sought further medical care. With the secondary evaluation of chest pain, the diagnosis changed in 9 of 10 cases. CONCLUSION: Chest pain in children is generally benign. However, chest pain can be recurrent and severe, interfering with activities of daily life.

Adolescent↗

Haplotype fine mapping by evolutionary trees.

To refine the location of a disease gene within the bounds provided by linkage analysis, many scientists use the pattern of linkage disequilibrium between the disease allele and alleles at nearby markers. We describe a method that seeks to refine location by analysis of "disease" and "normal" haplotypes, thereby using multivariate information about linkage disequilibrium. Under the assumption that the disease mutation occurs in a specific gap between adjacent markers, the method first combines parsimony and likelihood to build an evolutionary tree of disease haplotypes, with each node (haplotype) separated, by a single mutational or recombinational step, from its parent. If required, latent nodes (unobserved haplotypes) are incorporated to complete the tree. Once the tree is built, its likelihood is computed from probabilities of mutation and recombination. When each gap between adjacent markers is evaluated in this fashion and these results are combined with prior information, they yield a posterior probability distribution to guide the search for the disease mutation. We show, by evolutionary simulations, that an implementation of these methods, called "FineMap," yields substantial refinement and excellent coverage for the true location of the disease mutation. Moreover, by analysis of hereditary hemochromatosis haplotypes, we show that FineMap can be robust to genetic heterogeneity.

Algorithms↗

Domestic violence.

Domestic violence is alarmingly prevalent, yet medical students, residents, and experienced physicians are often handicapped by insufficient knowledge and expertise in the diagnosis and care of these patients. This article reviews the epidemiology of domestic violence, highlights risk factors, discusses current obstacles in the diagnosis and treatment of domestic violence, identifies history taking and physical examination skills to increase diagnosis of this condition, and outlines treatment plans for victims.

Adolescent↗

Activation of the Ah receptor signal transduction pathway by bilirubin and biliverdin.

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates many of the biological and toxicological actions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related chemicals. Although no endogenous physiological ligand for the AhR has yet been described, persistent expression of hepatic CYP1A1 gene expression (an AhR-dependent response) in congenitally jaundiced Gunn rats indirectly supports the existence of such a ligand(s) in these animals. High plasma levels of the heme degradation product bilirubin (BR) in these animals prompted us to evaluate whether BR is an endogenous AhR agonist. Expression of dioxin responsive element (DRE)-driven luciferase gene expression in stably transfected mouse, guinea pig, rat, and human cells was induced by treatment with physiological concentrations of BR. Biliverdin (BV), the metabolic precursor of bilirubin, also induced luciferase activity in all species. BR and BV not only stimulated AhR transformation and DRE binding in vitro andin cells in culture, but competitive inhibition of [3H]TCDD-specific binding to the cytosolic AhR revealed that these chemicals are AhR ligands. The significantly greater inducing potency of these chemicals in intact cells, compared to their ligand binding and AhR transformation potency in vitro, suggests that BR and BV may also be converted within the cell to a more potent activator(s). Our results demonstrate that the heme degradation products BR and BV are AhR ligands which can regulate the AhR-dependent gene expression pathway.

Animals↗

Measurement of irradiated small bowel volume in pelvic irradiation and the effect of a bellyboard.

From June 1992 to January 1993, 51 consecutive patients with pelvic cancers treated with radiotherapy alone, or surgery plus post-operative radiotherapy, were included in a study of the effectiveness of a false table-top (bellyboard) in displacing small bowel loops out of anteriorposterior (AP) and posterioranterior (PA) opposing pelvic fields. The small bowel was opacified with barium. The volume of small bowel within the radiotherapy fields in the prone position with a bellyboard was reduced by 134-300 ml (29%-61%) when compared with that in supine position, and by 136-216 ml (28%-50%) when compared with that in prone position without a bellyboard, depending on the type of previous surgical procedures. The differences were highly statistically significant and likely to be clinically significant. The bellyboard we used is simple, economical, convenient and well tolerated. Its use is recommended, especially when AP and PA pelvic fields are used.

Adult↗

Comparative diagnostic value of exercise polarcardiography and 14-lead electrocardiography in the detection of coronary artery disease.

Early postexercise polarcardiographic (PCG) changes in the ST segment vector, as reflected in the variable MS X theta, are reported to clearly distinguish normal subjects from those with myocardial ischemia. We prospectively assessed the value of this test in detecting coronary artery disease (CAD) during treadmill exercise in 178 patients within 1 week of diagnostic coronary angiography. The average postexercise MS X theta was 16.9 +/- 9.7 mV degrees in patients with CAD, whereas it was 16.2 +/- 10.2 mV degrees in patients with CAD (p = NS). The optimal ratio of sensitivity to specificity, using different normal-abnormal cutoff values, was 57% and 56%, respectively, for a delineating MS X theta value of 12. The sensitivity and specificity of a simultaneously recorded 14-lead ECG using the criterion of exercise-induced horizontal downsloping ST segment depression greater than or equal to 0.1 mV, was 71% and 78%, respectively. The PCG results were not improved by analyzing MS X theta during exercise, or by analyzing the difference in MS X theta between rest and exercise or rest and postexercise. The sensitivity of the PCG for multivessel or left anterior descending CAD was higher than for less severe forms of CAD, but was significantly less sensitive than the 14-lead exercise ECG (70% versus 84%; p = 0.02; and 62% versus 75%; p = 0.05, respectively). Thus, exercise polarcardiography, as employed in the present study, does not improve the diagnostic content of the 14-lead exercise ECG. Contrary to previous reports, there is no clear separation of normal from abnormal MS X theta values when a prospective series of patients is tested.

Coronary Disease↗

Initial experience with octreotide in the pediatric population.

Octreotide is a somatostatin analogue that has been suggested as a therapeutic agent in various diverse disease processes including gastrointestinal bleeding, pancreatitis, hypoglycemia related to hyperinsulin states, and chylous peritoneum/thorax. Despite successful use in the adult population, there is limited information concerning its use in pediatric patients. The authors retrospectively review their experience with octreotide in 10 infants and children ranging in age from 14 days to 17 years. Octreotide, administered by continuous intravenous infusion or intermittent bolus dosing, was used in the treatment of gastrointestinal bleeding in four patients, pancreatitis in three patients, chylous leaks in two patients, and hypoglycemia related to nesidioblastosis in one patient. The clinical course of these patients and the potential therapeutic impact of octreotide are evaluated. Additionally, previous experiences with octreotide in pediatric patients, dosing regimens, and the potential role of the drug in other disease processes are discussed.

Adolescent↗