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Biomedical subjects

P Latham

Publications and source records attributed to P Latham.

At least 19 recordsLinked to original sources

Pulmonary tuberculosis and extreme prematurity.

A mother, newly found to be positive for HIV, delivered her first baby at 25 weeks gestation. The infant initially did well in spite of a symptomatic patent duct and a severe intraventricular haemorrhage, but became severely unwell needing further respiratory support on day 18. Acid fast bacilli were found in endotracheal secretions. After the baby's death, the bacilli were confirmed to be Mycobacterium tuberculosis, and the same organism was grown from the mother's urine. The case raised challenging issues in relatively uncharted territory in terms of treatment of the infant, public health issues, ethical decision making, and media management.

Confidentiality↗

Response of old-growth conifers to reduction in stand density in western Oregon forests.

The positive growth response of healthy young trees to density reduction is well known. In contrast, large old trees are usually thought to be intrinsically limited in their ability to respond to increased growing space; therefore, density reduction is seldom used in stands of old-growth trees. We tested the null hypothesis that old-growth trees are incapable of responding with increased growth following density reduction. The diameter growth response of 271 Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco), ponderosa pine (Pinus ponderosa Dougl. ex Laws) and sugar pine (Pinus lambertiana Dougl.) trees ranging in age from 158 to 650 years was examined 20 to 50 years after density reduction. Density reduction involved either light thinning with removal of less vigorous trees, or shelterwood treatments in which overstory trees were not removed. Ratios of basal area growth after treatment to basal area growth before treatment, and several other measures of growth, all indicated that the old trees sometimes benefited and were not harmed by density reduction. Growth increased by 10% or more for 68% of the trees in treated stands, and nearly 30% of trees increased growth by over 50%. This growth response persisted for at least 20 years. During this 20-year period, only three trees in treated stands (1.5%) exhibited a rapid decrease in growth, whereas growth decreased in 64% of trees in untreated stands. The length of time before a growth response to density reduction occurred varied from 5 to 25 years, with the greatest growth response often occurring 20 to 25 years after treatment. These results have important implications both for the basic biology of aging in woody plants as well as for silvicultural practices in forests with old-growth trees.

Forestry↗

Aprotinin but not epsilon-aminocaproic acid decreases interleukin-10 after cardiac surgery with extracorporeal circulation: randomized, double-blind, placebo-controlled study in patients receiving aprotinin and epsilon-aminocaproic acid.

BACKGROUND: Extracorporeal circulation induces a systemic inflammatory response, which may adversely affect organ function. One manifestation of this response is increased fibrinolysis. Antifibrinolytic drugs such as aprotinin and epsilon-aminocaproic acid have been effective in reducing fibrinolysis and blood loss after extracorporeal circulation; however, the effects of antifibrinolytic drugs on proinflammatory and anti-inflammatory mediators are not known. This study examined the effects of aprotinin and epsilon-aminocaproic acid on plasma levels of proinflammatory [interleukin-6 (IL-6)] and anti-inflammatory [interleukin-10 (IL-10)] cytokines during and after extracorporeal circulation. METHODS AND RESULTS: Seventy-two patients undergoing coronary artery bypass grafting with extracorporeal circulation were randomly assigned in a double-blind study to receive high-dose aprotinin, epsilon-aminocaproic acid, or saline placebo. Plasma levels of IL-6 and IL-10 were measured at 5 time points before, during, and after extracorporeal circulation. In all 3 groups, both IL-6 and IL-10 rose significantly after institution of extracorporeal circulation and remained elevated through the first postoperative day. Compared with saline, aprotinin significantly reduced IL-10 (P=0.02) and peak IL-6 (P=0.02) after extracorporeal circulation. In contrast, none of the reductions in IL-6 and IL-10 by epsilon-aminocaproic acid achieved statistical significance. Both aprotinin and epsilon-aminocaproic acid decreased blood loss compared with saline, but there was no significant difference in the number of patients receiving blood products among the treatment groups. CONCLUSIONS: These data suggest that aprotinin and epsilon-aminocaproic acid differ in their effects on the inflammatory response to extracorporeal circulation. Aprotinin but not epsilon-aminocaproic acid appears to attenuate the rise in the proinflammatory and anti-inflammatory cytokines IL-6 and IL-10. Further studies will be required to determine if these cytokine alterations translate to changes in clinical outcomes.

Aminocaproic Acid↗

Transcriptional repression and developmental functions of the atypical vertebrate GATA protein TRPS1.

Known vertebrate GATA proteins contain two zinc fingers and are required in development, whereas invertebrates express a class of essential proteins containing one GATA-type zinc finger. We isolated the gene encoding TRPS1, a vertebrate protein with a single GATA-type zinc finger. TRPS1 is highly conserved between Xenopus and mammals, and the human gene is implicated in dominantly inherited tricho-rhino-phalangeal (TRP) syndromes. TRPS1 is a nuclear protein that binds GATA sequences but fails to transactivate a GATA-dependent reporter. Instead, TRPS1 potently and specifically represses transcriptional activation mediated by other GATA factors. Repression does not occur from competition for DNA binding and depends on a C-terminal region related to repressive domains found in Ikaros proteins. During mouse development, TRPS1 expression is prominent in sites showing pathology in TRP syndromes, which are thought to result from TRPS1 haploinsufficiency. We show instead that truncating mutations identified in patients encode dominant inhibitors of wild-type TRPS1 function, suggesting an alternative mechanism for the disease. TRPS1 is the first example of a GATA protein with intrinsic transcriptional repression activity and possibly a negative regulator of GATA-dependent processes in vertebrate development.

Algal Proteins↗

Complications of thoracoscopy.

Thoracoscopy is a minimally invasive thoracic surgical technique that is gaining widespread use for several surgical procedures. Although the complication rate is relatively low, there are definable risks associated with the technique. Careful attention to patient selection and an understanding of the complications associated with one-lung ventilation and video-assisted surgical techniques can help one to anticipate and prevent complications.

Contraindications↗

Effects of cellular redox balance on induction of apoptosis by eicosapentaenoic acid in HT29 colorectal adenocarcinoma cells and rat colon in vivo.

BACKGROUND AND AIMS: Epidemiological evidence suggests n-3 polyunsaturated lipids may protect against colorectal neoplasia. Consumption of fish oil modulates crypt cytokinetics in humans, and crypt apoptosis in animal models. To explore these effects, we investigated involvement of caspase enzymes and cellular redox balance in the induction of apoptosis by eicosapentaenoic acid (EPA) in HT29 cells, and in rat colon in vivo. METHODS: Survival of HT29 cells grown with EPA in the presence of caspase inhibitors, antioxidants, or buthionine sulphoximine, an inhibitor of glutathione neosynthesis, was determined. The effects of EPA enriched fish oil and glutathione depletion on apoptosis in rat colon were assessed using microdissected crypts. RESULTS: Treatment of HT29 cells with EPA reduced viable cell number and activated caspase 3, prior to cell detachment. Antioxidants and caspase inhibitors blocked HT29 cell death whereas glutathione depletion increased it. Rats fed fish oil had higher crypt cell apoptosis than those fed corn oil, and glutathione depletion enhanced this effect. CONCLUSIONS: Incorporation of EPA into colonic epithelial cell lipids increases apoptosis. The results of this study, using both an animal and cell line model, support the hypothesis that this effect is mediated via cellular redox tone, and is sensitive to glutathione metabolism. The data suggest a mechanism whereby polyunsaturated fatty acids may influence the susceptibility of colorectal crypt cells to induction or progression of neoplasia.

Animals↗

Esophageal Doppler monitor determinations of cardiac output and preload during cardiac operations.

BACKGROUND: Perioperative management of cardiac surgical patients frequently mandates measurements of cardiac output and left ventricular filling. This study compared cardiac output and left ventricular filling measured by pulmonary artery (PA) catheter and esophageal Doppler monitor (EDM). METHODS: Thirty-four patients undergoing coronary artery bypass grafting were prepared by implanting a PA catheter, an EDM, and a transit-time ultrasonic flow probe around the ascending aorta. In 20 patients, left ventricular end-diastolic short-axis area (EDA) was measured by transesophageal echocardiography. At five time points, cardiac output was measured from the flow probe, the EDM, and the PA catheter (by thermodilution), and left ventricular filling was assessed from the PA catheter (as PA diastolic pressure), the EDM (corrected flow time), and the EDA. For cardiac output, concordance correlations relating EDM to flow probe and PA catheter to flow probe were calculated, transformed (Fisher's z transformation), and compared by Student's t test. For left ventricular filling, regression coefficients were created between corrected flow time and EDA and between PA diastolic pressure and EDA. Spearman correlations were compared by Wilcoxon rank sum test. RESULTS: The EDM and the PA catheter exhibited similar relationships to the flow probe (concordance correlations, 0.55 +/- 0.35 [mean +/- standard deviation] and 0.49 +/- 0.34, respectively; p = 0.088). The correlation between corrected flow time and EDA was better than the correlation between PA diastolic pressure and EDA (concordance correlations, 0.49 +/- 0.55 versus 0.10 +/- 0.43, respectively; p < 0.01). CONCLUSIONS: These data suggest that the EDM may offer a less invasive technique for evaluating cardiac output and a more accurate estimate for preload compared with the PA catheter.

Aged↗

Fast-track cardiac anesthesia: a comparison of remifentanil plus intrathecal morphine with sufentanil in a desflurane-based anesthetic.

OBJECTIVE: To compare the effects of an intravenous remifentanil infusion plus intrathecal morphine with intravenous sufentanil infusion with respect to intraoperative hemodynamic variables, extubation times, and recovery profiles when administered as part of a desflurane-based fast-track anesthetic regimen for cardiac surgery. DESIGN: A prospective, randomized, nonblinded study. SETTING: University hospital. PARTICIPANTS: Forty patients undergoing elective primary coronary artery bypass graft, aortic valve replacement, or mitral valve replacement surgery. INTERVENTIONS: After a standardized anesthetic induction, anesthesia was maintained with a remifentanil infusion, 0.1 microg/kg/min, and desflurane, 3% to 10%, inspired (group I, n = 20) or a sufentanil infusion, 0.3 microg/kg/h, and desflurane, 3% to 10%, inspired (group II, n = 20). Patients receiving remifentanil were administered intrathecal morphine, 8 microg/ kg, for postoperative analgesia. MEASUREMENTS AND MAIN RESULTS: Both anesthetic regimens provided comparable intraoperative hemodynamic stability and similar recovery profiles, with extubation times of 5.1 +/- 4.3 hours (group I) and 5.8 +/- 6.7 hours (group II). CONCLUSIONS: Use of remifentanil in combination with intrathecal morphine did not facilitate earlier tracheal extubation or improve intraoperative hemodynamic stability compared with sufentanil alone for fast-track cardiac anesthesia.

Adjuvants, Anesthesia↗

Fast-track cardiac anesthesia: use of remifentanil combined with intrathecal morphine as an alternative to sufentanil during desflurane anesthesia.

UNLABELLED: The purpose of this cardiac fast-track study was to evaluate the use of remifentanil (R) combined with intrathecal (IT) morphine as an alternative to sufentanil (S) during desflurane anesthesia with respect to postoperative pain control. Prior to entering the operating room, patients in the R group (n = 20) received morphine, 8 microg/kg IT. Anesthesia was induced using a standardized anesthetic technique in all patients. In the R group, anesthesia was maintained with R, 0.1 microg. kg(-1). min(-1) in combination with desflurane 3-10%. In the S group (n = 20), patients received S 0.3 microg. kg(-1). h(-1) and desflurane 3-10%. There were no differences between the two groups with respect to time from arrival in the intensive care unit to tracheal extubation (5.1 +/- 4.3 h vs 5.8 +/- 6.7 h for R and S groups, respectively). After extubation, patients in the R group had significantly lower visual analog pain scores, reduced patient-controlled analgesic requirements, and greater satisfaction with their perioperative pain management, compared with patients in the S group. We conclude that R combined with IT morphine provided superior pain control after cardiac surgery compared with a S-based general anesthetic technique. IMPLICATIONS: As part of a cardiac fast-tracking program involving desflurane anesthesia, the use of intrathecal morphine in combination with a remifentanil infusion provided improved postoperative pain control, compared with IV sufentanil alone.

Analgesics, Opioid↗

Effect of eicosapentaenoic acid on the proliferation and incidence of apoptosis in the colorectal cell line HT29.

Fish oil has been shown to reduce the induction of colorectal cancer in animal models by a mechanism which may involve suppression of mitosis, increased apoptosis, or both. We used the human colonic adenocarcinoma cell line HT29 to explore the effects of the long-chain n-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on cell proliferation and death in vitro. Cells were cultured in media containing EPA at 5, 10, and 15 microg/mL. Cell number and thymidine incorporation were used to quantify proliferation, and cell cycle effects were studied using flow cytometry. Gel electrophoresis, annexin-V binding, and morphological criteria were used to characterize apoptosis. Adherent cells and freely floating detached cells were treated as two distinct populations. In the presence of EPA at 10 and 15 microg/mL there was a marked reduction in the growth rate of adherent HT29 colonies, owing to an increased detachment of adherent cells. After treatment with 10 or 15 microg/mL EPA the proportion of adherent cells in S-phase increased, indicating either a block in late S-phase or early G2. Floating cells showed evidence of extensive DNA cleavage, but the proportion of floating cells with sub GO DNA content declined on treatment with 10 or 15 microg/mL EPA even though the number of floating cells increased. We conclude that EPA does not inhibit mitosis of adherent cells, but increases the rate at which they become detached from the substrate, probably at an early stage in the initiation of apoptosis. This mechanism may be analogous to "anoikis," or induction of apoptosis in response to loss of cell contact, and may contribute to the anticarcinogenic effects of fish oil in vivo.

Acridine Orange↗

Dietary n-3 PUFA increases the apoptotic response to 1,2-dimethylhydrazine, reduces mitosis and suppresses the induction of carcinogenesis in the rat colon.

The effect of dietary fish oil on colonic crypt cell apoptosis and proliferation was examined in male Wistar rats, 24 and 48 h after administration of 1,2-dimethylhydrazine (DMH), and its influence on the induction of aberrant crypt foci (ACF) in the distal colon was assessed. Rats (125-150 g) fed a high-fat semi-synthetic diet containing corn oil (CO) were given DMH (30 mg/kg body wt) or a sham injection of EDTA/NaCl. Animals were then fed either the CO diet or a diet in which fish oil (EPA 18.7%; DHA 8%) was substituted for corn oil. Subgroups of rats (n = 5) were killed after 24 and 48 h, and crypt cell apoptosis and proliferation were quantified by morphological criteria in isolated intact crypts from the mid and distal colon. Consumption of the fish oil diet (FO) was associated with increased apoptotic cell death (P < 0.001) and suppression of proliferation (P < 0.05) in colonic crypts both 24 and 48 h after DMH. In a second experiment, animals were given three injections of DMH or sham injections of carrier at weekly intervals. For 48 h after each injection animals were fed either the CO or FO diet, but otherwise maintained on the CO throughout. The number and crypt multiplicity of ACF in the distal colon were determined after 18 weeks, and animals given the FO diet for the 48 h period following carcinogen administration were found to have significantly fewer ACF than rats fed the CO diet (P < 0.05). The data demonstrate that the fatty acid composition of the diet is an important determinant in the induction of carcinogenesis by DMH. The proliferative and apoptotic response of the colonic crypt to carcinogen and fish oil, coupled with the reduced incidence of ACF, suggest n-3 PUFA can protect against the carcinogenic effects of DMH by mediating changes in the balance proliferation and cell death.

1,2-Dimethylhydrazine↗

Carbohydrate-deficient transferrin as an indicator of drinking status during a treatment outcome study.

Biological markers of alcohol consumption have been used in both clinical and research settings to aid in the identification of relapse drinking. Although carbohydrate-deficient transferrin (CDT) has been shown to be a sensitive and specific marker for the identification of heavy drinkers, little data are available as to its utility as a marker for relapse drinking during treatment, particularly in comparison with the more widely used serum gamma-glutamyltransferase (GGT). CDT and GGT were measured in 35 male alcoholics before entering, and every 4 weeks during, a 12-week outpatient treatment trial combining pharmacotherapy and cognitive behavioral therapy. CDT and GGT were again measured 14 weeks after completion of treatment. During the 12-week treatment period, CDT showed a significant difference in those individuals who abstained from drinking (30% decrease), compared with those who relapsed (10% increase). GGT decreased on average in all individuals, and the change from treatment entry did not differ significantly across the drinking outcome groups. The change in CDT, but not GGT, from study entry to termination, significantly correlated with total alcohol consumption during the trial. At the 14-week posttreatment, follow-up evaluation CDT showed about a 60% elevation and GGT showed a 30% elevation, on average, from study entry values in those individuals who had relapse drinking by self and/or collateral report. The change in both markers differed between those individuals who remained abstinent or relapsed during the poststudy period. In general, the change in CDT from pretreatment levels seemed more sensitive to drinking status during treatment and follow-up than GGT. This indicates that CDT may be more sensitive marker for evaluating drinking status during both clinical and research treatment trials.

Adult↗

The Obsessive Compulsive Drinking Scale: a self-rated instrument for the quantification of thoughts about alcohol and drinking behavior.

It has been suggested that a crucial dimension of alcohol "craving" includes the concept of both obsessive thoughts about alcohol use and compulsive behaviors toward drinking. An interview-based rating scale, the Yale-Brown Obsessive Compulsive Scale-heavy drinkers (YBOCS-hd), has been found useful in quantifying this concept in alcohol-dependent individuals. A self-rating scale, the Obsessive Compulsive Drinking Scale (OCDS) has been developed by us as a modification of the YBOCS-hd. The YBOCS-hd showed excellent interrater reliability in our hands. The correlation between the YBOCS-hd and the OCDS total scores obtained on 60 alcohol-dependent individuals was 0.83. The test-retest correlation for the OCDS total score was 0.96, and the obsessive and compulsive subscales test-retest correlations were 0.94 and 0.86, respectively. The internal consistency of the items in the OCDS was high (0.86) and did not improve significantly with removal of individual items. The shared variance between the OCDS scores and alcohol consumption during the period of evaluation was only approximately 20%, indicating that the dimension measured by the scale was somewhat independent of actual drinking. As such, it might act as an independent measure of the "state of illness" for alcohol-dependent individuals. When used during a prospective 12-week treatment research study, initial results indicate that the OCDS seems to validly measure a dimension of alcohol dependence, because it decreased from baseline during alcohol reduction and increased in relationship to relapse drinking.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗