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Biomedical subjects

L Davis

Publications and source records attributed to L Davis.

At least 19 recordsLinked to original sources
PubMed2006

Characteristics of work related asthma: results from a population based survey.

OBJECTIVES: Many risk factors for asthma have been investigated, one of which is the workplace. Work related asthma is a frequently reported occupational respiratory disease yet the characteristics which distinguish it from non-work related asthma are not well understood. The purpose of this study was to examine differences between work related and non-work related asthma with respect to healthcare use and asthma control characteristics. METHODS: Data from the Massachusetts Behavioral Risk Factor Surveillance System for 2001 and 2002 were used for this analysis. Work related status of asthma was determined by self-report of ever having been told by a physician that asthma was work related. Healthcare measures evaluated were emergency room visits and physician visits for worsening asthma and for routine care. Characteristics of asthma control evaluated were frequency of asthma symptoms, asthma attacks, difficulty sleeping, and asthma medication usage in the last 30 days and limited activity in the past 12 months. RESULTS: The prevalence of lifetime and current asthma in Massachusetts were 13.0% and 9.2%, respectively. Approximately 6.0% (95% CI 4.8 to 7.3) of lifetime and 6.2% (95% CI 4.7 to 7.8) of current asthma cases were work related. In the past 12 months, individuals with work related current asthma were 4.8 times (95% CI 2.0 to 11.6) as likely to report having an asthma attack, 4.8 times (95% CI 1.8 to 13.1) as likely to visit the emergency room at least once, and 2.5 times (95% CI 1.1 to 6.0) as likely to visit the doctor at least once for worsening asthma compared to individuals with non-work related asthma. CONCLUSIONS: Work related asthma is associated with increased frequency of asthma attacks and use of healthcare services. A better understanding of factors that contribute to differences in healthcare use and asthma control is needed to improve prevention and control strategies for individuals suffering from the disease.

Activities of Daily Living↗
PubMed2006

Transportation of prion protein across the intestinal mucosa of scrapie-susceptible and scrapie-resistant sheep.

To determine the mechanisms of intestinal transport of infection, and early pathogenesis, of sheep scrapie, isolated gut-loops were inoculated to ensure that significant concentrations of scrapie agent would come into direct contact with the relevant ileal structures (epithelial, lymphoreticular, and nervous). Gut loops were inoculated with a scrapie brain pool homogenate or normal brain or sucrose solution. After surgery, animals were necropsied at time points ranging from 15 min to 1 month and at clinical end point. Inoculum-associated prion protein (PrP) was detected by immunohistochemistry in villous lacteals and in sub-mucosal lymphatics from 15 min to 3.5 h post-challenge. It was also detected in association with dendritic-like cells in the draining lymph nodes at up to 24 h post-challenge. Replication of infection, as demonstrated by the accumulation of disease-associated forms of PrP in Peyer's patches, was detected at 30 days and sheep developed clinical signs of scrapie at 18-22 months post-challenge. These results indicate discrepancies between the routes of transportation of PrP from the inoculum and sites of de novo-generated disease-associated PrP subsequent to scrapie agent replication. When samples of homogenized inoculum were incubated with alimentary tract fluids in vitro, only trace amounts of protease-resistant PrP could be detected by western blotting, suggesting that the majority of both normal and abnormal PrP within the inoculum is readily digested by alimentary fluids.

Animals↗
PubMed2006

PPARalpha agonist fenofibrate improves diabetic nephropathy in db/db mice.

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the ligand-activated nuclear receptor superfamily, and plays an important role in lipid metabolism and glucose homeostasis. The purpose of this study is to determine whether the activation of PPARalpha by fenofbrate would improve diabetes and its renal complications in type II diabetes mellitus. Male C57 BLKS db/db mice and db/m controls at 8 weeks of age were divided to receive either a regular diet chow (db/db, n=8; db/m, n=6) or a diet containing fenofibrate (db/db, n=8; db/m, n=7). Mice were followed for 8 weeks. Fenofibrate treatment dramatically reduced fasting blood glucose (P<0.001) and HbA1c levels (P<0.001), and was associated with decreased food intake (P<0.01) and slightly reduced body weight. Fenofibrate also ameliorated insulin resistance (P<0.001) and reduced plasma insulin levels (P<0.05) in db/db mice. Hypertrophy of pancreatic islets was decreased and insulin content markedly increased (P<0.05) in fenofibrate-treated diabetic animals. In addition, fenofibrate treatment significantly reduced urinary albumin excretion (P<0.001). This was accompanied by dramatically reduced glomerular hypertrophy and mesangial matrix expansion. Furthermore, the addition of fenofibrate to cultured mesangial cells, which possess functional active PPARalpha, decreased type I collagen production. Taken together, the PPARalpha agonist fenofibrate dramatically improves hyperglycemia, insulin resistance, albuminuria, and glomerular lesions in db/db mice. The activation of PPARalpha by fenofibrate in mesangial cells may partially contribute to its renal protection. Thus, fenofibrate may serve as a therapeutic agent for type II diabetes and diabetic nephropathy.

Albuminuria↗
PubMed2005

A phase II trial of gefitinib with 5-fluorouracil, leucovorin, and irinotecan in patients with colorectal cancer.

Inhibition of epidermal growth factor receptor (EGFR) signalling contributes to the therapy of colorectal cancer. Gefitinib, an oral EGFR tyrosine kinase inhibitor, shows supra-additive growth inhibition with irinotecan and fluoropyrimidines in xenograft models. We designed a study to determine the tolerability and efficacy of gefitinib in combination with irinotecan, infusional 5-fluorouracil (5-FU) and leucovorin (LV), on a 2-week schedule. Among 13 patients with advanced colorectal cancer, 10 required dose reductions of irinotecan and 5-FU because of dehydration, diarrhoea, and neutropenia, seven of whom required hospitalisation, three with neutropenic fever. One patient achieved partial response and seven had disease stabilisation. The combination of this standard chemotherapy regimen with gefitinib is associated with excessive toxicity, suggesting an interaction at a pharmacokinetic or pharmacodynamic level.

Adenocarcinoma↗
PubMed2005

The effects of anaemia as a programming agent in the fetal heart.

The intrauterine environment plays a powerful role in determining the life-long risk of cardiovascular disease. A number of stressors are well known to affect the development of the cardiovascular system in utero including over/under maternal nutrition, excess glucocorticoid and chronic hypoxia. Chronic fetal anaemia in sheep is a complex stressor that alters cardiac loading conditions, causes hypoxic stress and stimulates large changes in flow to specific tissues, including large increases in resting coronary blood flow and conductance. Decreased viscosity can account for approximately half of the increased flow. It appears that immature hearts are 'plastic' in that increases in coronary conductance with fetal anaemia persist into adulthood even if the anaemia is corrected before birth. These large changes in conductance are possible only through extensive remodelling of the coronary tree. Adult hearts that were once anaemic in utero are more resistant to hypoxic stress as adults but it is not known whether such an adaptation would be deleterious in later life. These studies indicate the need for investigation into the basic mechanisms of coronary tree remodelling in the immature myocardium. New information on these mechanisms is likely to lead to better prevention of and therapies for adult-onset coronary disease.

Anemia, Neonatal↗
PubMed2005

Intramembranous absorption rate is unaffected by changes in amniotic fluid composition.

Experiments were performed to determine the effect of amniotic fluid dilution on the rate of intramembranous absorption. Seven fetal sheep at 118 days gestation were instrumented with a shunt between the trachea and esophagus and arterial and venous vascular catheters. In addition, the urachus of the fetal bladder was ligated, and a catheter was placed in the bladder. Ligation of the urachus does not interfere with urine flow into the amnion. After 5 days of recovery, fetuses were randomly assigned to one of two protocols; all fetuses completed both protocols. In the fetuses in the control period, continuous urine flow measurement was begun. In the fetuses assigned to the isovolumic dilution protocol, continuous urine flow measurement was also begun and, in addition, amniotic fluid was continually exchanged with lactated Ringer solution on an isovolumic basis. After 3-4 days, fetal blood pressures and amniotic fluid volumes were determined. Amniotic fluid volumes were determined by drainage. Each fetus was then assigned to the remaining protocol. The presence of the tracheal-esophageal shunt and the ligation of the urachus allowed the rate of intramembranous absorption to be calculated. Isovolumic exchange showed no effect on fetal vascular pressures, blood-gas values, or urine production. We could demonstrate no effect of isovolumic dilution of amniotic fluid on its volume. However, we were able to demonstrate an inverse relationship between amniotic fluid volume and intramembranous absorption (P < 0.02).

Absorption↗
PubMed2004

Regulatory response to washout of amniotic fluid in sheep.

To test the hypothesis that a substance present in the amniotic fluid could serve as a regulator of amniotic fluid volume, we drained and discarded amniotic fluid while replacing it with lactated Ringer solution that was isotonic to amniotic fluid. Seven ewes with singleton fetuses at 119 +/- 1 days of gestation (mean +/- SE) were instrumented with multiple indwelling catheters in the pedal artery, pedal vein, and amniotic cavity. During the exchange periods, an average of 3,019 +/- 171 ml/day of lactated Ringer solution was infused into the amniotic cavity while an equal amount of amniotic fluid was pumped out and discarded. During the control period, amniotic fluid composition and volume were not altered. Exchange and control periods started with the same amniotic fluid volume, lasted 3 or 4 days, and were randomized with regard to order. Amniotic fluid volume measured by vacuum drainage was 556 +/- 98 ml at the end of the control period and 986 +/- 209 ml (P = 0.03) at the end of the exchange period. Fetal arterial blood gases, hemodynamic parameters and the osmolality gradient between fetal plasma and amniotic fluid were not altered by the exchange process. A linear relationship between the control amniotic fluid volume and the volume at the end of the exchange period (P = 0.003) suggests that the animals with larger control volumes responded to isovolumic dilution with a larger volume increase. We conclude that amniotic fluid may contain a substance that regulates amniotic volume.

Absorption↗
PubMed2004

Predictors of attrition in HIV-positive subjects with peripheral neuropathic pain.

The objective of this paper was to identify predictors of attrition in a study designed to assess whether cognitive behavioural therapy (CBT) was more helpful than supportive therapy (SP) in reducing pain associated with peripheral neuropathy in HIV-positive patients. Sixty-one subjects were randomized into either CBT or SP for six weekly one-hour sessions. Twenty-eight subjects dropped out before week six. Demographic variables such as age, gender, ethnicity, socioeconomic status and level of education were not predictive of attrition. However, higher scores on the Hamilton Depression Inventory (HAM-D, 17-item) (t (59) = - 0.09, p<0.05) were predictive. These findings suggest that while dropouts were not more physically ill (e.g. CD4 counts, viral loads and opportunistic infections were not statistically higher), they reported greater psychological distress.

Cognitive Behavioral Therapy↗
PubMed2003

Duct-to-duct biliary anastomosis for patients with sclerosing cholangitis undergoing liver transplantation.

BACKGROUND: Due to the association of strictures within the biliary ductal system, Roux-en-Y choledochojejunostomy has been the preferred method of anastomosis for liver transplant recipients with primary sclerosing cholangitis (PSC). The aim of this study was to evaluate duct-to-duct anastomosis in patients with PSC who undergo liver transplantation. METHODS: Data were collected and evaluated based on demographics, type of anastomosis preformed, malignancies, outcomes comparisons, and survival. RESULTS: Of the 60 patients transplanted for PSC, 58 were diagnosed PSC prior to transplantation and 2 were diagnosed on explant. The Roux-en-Y group (n = 38) were similar in age, gender, and race when compared to the duct-to-duct (d-d) group (n = 22). There were similar rates of anastomotic revisions when comparing d-d anastomosis with Roux-en-Y (2 [9.1%] versus 2 [5.3%], P = NS) owing to bile leaks. Based on radiologic interventions of the bile ducts, seven (18.4%) in the Roux-en-Y group had interventions compared to two (9.1%) in the duct-to-duct group (P = NS). There was also no difference in recurrence of PSC: three (7.9%) in the Roux-en-Y group compared to two (5.3%) in the duct-to-duct group (P = NS). Survival at 4 years were similar between each group (76.5% [+/- 0.07] Roux-en-Y versus 84.9% [+/- 0.08] duct-to-duct, P = NS). CONCLUSION: Duct-to-duct anastomosis at the time of liver transplantation is both safe and efficacious when used in patients with PSC. Outcomes as described by surgical interventions, radiologic interventions, retransplantation, and survival were similar between groups.

Anastomosis, Roux-en-Y↗
PubMed2003

Nonresponders of interferon/ribavirin treatment for recurrent hepatitis C following liver transplantation.

BACKGROUND: Treatment of recurrent hepatitis C (HCV) following liver transplant currently includes alpha-interferon with ribavirin. OBJECTIVE: The aim of this study is to evaluate nonresponder protocols for patients failing current treatment for recurrent hepatitis C following liver transplantation. METHODS: From February 1998 through November 2002, 67 patients, all serum RNA-positive for hepatitis C with histological evidence of recurrent hepatitis C, underwent treatment with alpha-interferon and ribavirin. For patients who failed initial treatment, patients were begun on either amantadine along with interferon/ribavirin or peginterferon with ribavirin. RESULTS: Of the initial 67 patients, there was a complete viral clearance in only 14.9% (10/67). Of the 57 remaining patients not clearing the virus, 30 (52.6%) were taken off treatment due to adverse events associated with bone marrow or hemoglobin suppression. In the amantadine group (n = 12), three (25%) had to discontinue due to CNS side effects of slurred speech, dizziness, and increased depression. In the amantadine group, no patients cleared the virus but there was a one log drop in viral load (1.6 x 10(6) vs 0.9 x 10(6); P =.4). In the peginterferon group, there were three (20%) patients with complete viral clearance during treatment with similar drops to amantadine. There was also seen a biochemical response by month 3 with peginterferon, which was not seen with amantadine. CONCLUSIONS: Peginterferon with ribavirin appears to be superior to amantadine with interferon/ribavirin when used in nonresponders for hepatitis C viral clearance.

Antiviral Agents↗
PubMed2002

Augmentation of coronary conductance in adult sheep made anaemic during fetal life.

Maximal coronary conductance with adenosine in anaemic fetal sheep is twice that of non-anaemic fetuses. To investigate whether this increase in conductance persists into adulthood we studied twin sheep as fetuses and again as adults. Nine anaemic fetuses (118 days gestation) underwent isovolaemic haemorrhage for 18.0 +/- 4.6 days (means +/- S.D.) during which time the haematocrit was reduced from 39.9 +/- 5.2 % to 16.3 +/- 3.4 % and oxygen content from 8.6 +/- 1.3 to 2.3 +/- 0.2 ml dl-1. At 138 days the anaemic fetuses were transfused; at delivery the haematocrit was 29.3 +/- 6.8 % compared to nine control fetuses in which the haematocrit was 38.5 +/- 4.3 %. The weight at delivery was 3.5 +/- 0.36 kg in the anaemic fetuses vs. 4.2 +/- 0.83 kg in controls. Twenty-eight weeks later, we placed an occluder on the descending thoracic aorta and inferior vena cava, a flow probe around the proximal left circumflex coronary artery, and catheters in the left atrial appendage, jugular and carotid vessels. Maximal coronary conductance was determined in the adults by recording coronary blood flow as driving pressure was altered by inflating the occluders while adenosine was infused into the left atrium. Right atrial, left atrial, systolic and mean arterial pressures, systemic vascular resistance and haematocrit were not different between 'in utero anaemic' and control adults. The adults that were anaemic in utero weighed less than the controls 39.4 +/- 4.6 kg vs. 45.0 +/- 5.6 kg. Maximal conductance was greater in the adults that were anaemic in utero: 11.2 +/- 4.0 ml min(-1) (100 g)(-1) mmHg-1 as compared to 6.1 +/- 1.8 ml min(-1) (100 g)(-1) mmHg(-1) in the controls. Vascular reactivity of the mesenteric arteries was not different. These data suggest that coronary conductance can be modified in utero by anaemia (high flow and hypoxaemia) and that the remodelled coronary tree persists to adulthood.

Adenosine↗
PubMed2002

Increased coronary blood flow signals growth of coronary resistance vessels in near-term ovine fetuses.

We measured maximal coronary artery conductance in near-term fetal sheep before and after chronic infusion with adenosine to determine whether an increase in coronary flow without hypoxemia results in increased coronary vascular growth. Adenosine was infused into the circumflex coronary artery for 12 h each day for 4 days. Coronary flow was maintained at double the resting level by regulating the infusion of adenosine via a computerized servocontrol device signaled by a Doppler flow-velocity sensor. Total arterial hemoglobin, oxygen content, and hemodynamics were unchanged. Resting circumflex coronary blood flow increased from control of 250 +/- 111 to 530 +/- 216 ml x min(-1) x 100 g left ventricle(-1) with adenosine on day 1 and from 194 +/- 74 to 878 +/- 210 ml x min(-1) x 100 g left ventricle(-1) with adenosine on the last day (P < 0.01). Coronary conductance, determined during maximal vasodilation, increased from 14.0 +/- 5.0 to 26.9 +/- 3.9 ml x min(-1) x 100 g(-1) x mmHg(-1) over the 4 days (P < 0.001). Coronary flow reserve, the difference between resting and maximal myocardial blood flow interpolated at 40 mmHg, increased from 299 +/- 196 to 672 +/- 266 ml x min(-1) x 100 g(-1) (P < 0.001). Maximal coronary conductance was unchanged in control saline-infused fetuses (18.5 +/- 5.1 vs. 18.5 +/- 8.7 ml x min(-1) x 100 g(-1) x mmHg(-1)). We conclude that chronic intracoronary adenosine administration to the fetal myocardium modulates coronary vascular growth, even in the absence of tissue hypoxia.

Adenosine↗