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Biomedical subjects

L Murray

Publications and source records attributed to L Murray.

At least 19 recordsLinked to original sources

In ovo vaccination technology.

More than 80% of the U.S. broiler industry has converted to the in ovo vaccination process for control of Marek's disease. Providing certain criteria are met, including timing and site of vaccine placement, vaccine mixing, machine sanitization, and hatchery management specifications, this has proven to be an efficacious and convenient method of vaccination. Efforts to extend the technology for other viral vaccines including Newcastle, bronchitis and bursal disease, and bacterial and parasitic vaccines are in progress. Collectively, these studies demonstrate that in ovo vaccination technology using approved vaccine is a safe, efficacious, and convenient method for vaccination of poultry.

Animals

Symptomatic benefit from eradicating Helicobacter pylori infection in patients with nonulcer dyspepsia.

BACKGROUND: The eradication of Helicobacter pylori infection is beneficial in patients with gastric or duodenal ulcers. The value of eradicating the infection in patients with dyspepsia and no evidence of ulcer disease is not known. METHODS: We performed a randomized, placebo-controlled trial comparing the efficacy of treatment for two weeks with 20 mg of omeprazole orally twice daily, 500 mg of amoxicillin three times daily (with 500 mg of tetracycline three times daily substituted for amoxicillin in patients allergic to penicillin), and 400 mg of metronidazole three times daily (160 patients) with that of omeprazole alone (158 patients) for resolving symptoms of dyspepsia in patients with H. pylori infection but no evidence of ulcer disease on upper gastrointestinal endoscopy. Symptoms were assessed with the Glasgow Dyspepsia Severity Score, with resolution of symptoms defined as a score of 0 or 1 in the preceding six months (maximal score, 20). One year later the patients were assessed to determine the frequency of the resolution of symptoms. RESULTS: One month after the completion of treatment, 132 of 150 patients (88 percent) in the group assigned to received omeprazole and antibiotics had a negative test for H. pylori, as compared with 7 of 152 (5 percent) in the group assigned to receive omeprazole alone. One year later, dyspepsia had resolved in 33 of 154 patients (21 percent) in the group given omeprazole and antibiotics, as compared with 11 of 154 (7 percent) in the group given omeprazole alone (95 percent confidence interval for the difference, 7 to 22 percent; P<0.001). Among the patients in the group given omeprazole and antibiotics, the symptoms resolved in 26 of the 98 patients (27 percent) who had had symptoms for five years or less, as compared with 7 of the 56 patients (12 percent) who had had symptoms for more than five years (P=0.03). CONCLUSIONS: In patients with H. pylori infection and nonulcer, or functional, dyspepsia, treatment with omeprazole and antibiotics to eradicate the infection is more likely to resolve symptoms than treatment with omeprazole alone.

Adolescent

Interleukin-2 and -6 induce behavioral-activating effects in mice.

Interleukin (IL)-1, IL-2 and IL-6 influence central monoamine activity in a cytokine-specific manner. We demonstrated that whereas IL-2 increased hypothalamic and hippocampal norepinephrine (NE) utilization, and DA turnover in the prefrontal cortex, IL-6 induced profound elevations of serotonin (5-HT) and mesocortical dopamine (DA) activity in the hippocampus and prefrontal cortex [S. Zalcman, J.M. Green-Johnson, L. Murray, D.M. Nance, D.G. Dyck, H. Anisman, A. H. Greenberg, Cytokine-specific central monoamine alterations following IL-1, -2 and -6 administration, Brain Res. 643 (1994) 40-49]. IL-1, in contrast, induced a wide range of central monoamine alterations. We presently report that these cytokines also differentially influence behavior. Profound reductions in non-ambulatory and ambulatory exploration were induced in BALB/c mice following IL-1 administration. In contrast, IL-2-treated mice displayed significant increases in the time spent engaged in non-ambulatory exploration, digging, rearing (particularly the number of free rears), and in the investigation of a novel stimulus (i.e., increased number and duration of stimulus contacts). IL-6-treated mice, moreover, exhibited significant increases in the time spent engaged in ambulatory exploration, digging and rearing (particularly the number of free rears, which tended to be of short duration). Modest increases in locomotion and grooming were also observed in IL-6-treated animals. Plasma corticosterone levels did not vary significantly as a function of IL-6 treatment. Hence, cytokine-specific behavioral-activating effects were induced following administration of IL-2 and IL-6. We suggest that these effects have adaptive significance and relevance to sickness behavior; however, pathological outcomes (e.g., schizophrenia, anxious-like states, anxious depression, motor abnormalities) could develop should these cytokines be overproduced or dysregulated.

Adaptation, Physiological

Diorthosubstituted polychlorinated biphenyls in caudate nucleus in Parkinson's disease.

As it had previously been demonstrated that there were reduced brain dopamine concentrations in monkeys who had been given polychlorinated biphenyls (PCBs) chronically, we hypothesized that organochlorine compounds in general, and PCBs in particular, might be important in the pathogenesis of Parkinson's disease (PD). In a study of caudate nucleus obtained post mortem from patients with Parkinson's disease and from controls, there were significantly higher concentrations of the organochlorine insecticide dieldrin and the PCB congener 153 in the PD tissue. DDE, PCB congener 180, and total PCBs (matched with a commercial preparation) also tended to be higher in Parkinson's disease tissue. We think that this is important preliminary evidence that diorthosubstituted PCBs may contribute to the pathogenesis of Parkinson's disease, and a greater presence of organochlorine insecticides in the PD tissue suggests that this may be in part the explanation for the association between PD and rural living.

Animals

Determinants of the blood pressure response to the first dose of ACE inhibitor in mild to moderate congestive heart failure.

AIMS: To investigate the relationship in patients with heart failure between BP response to the first dose of ACE inhibitor and (1) plasma drug concentration and (2) baseline clinical and laboratory variables. METHODS: We studied individual placebo-corrected BP responses to initiation of treatment with one of a number ACE inhibitor preparations in 132 patients with mild to moderate CHF. Various pharmacokinetic/pharmacodynamic models were compared. We assessed the strength of association between baseline physiological and laboratory variables and the BP response as assessed directly from the AUC(0,10 h) and indirectly from the slope of the PK/PD relationship. Predictive models for response variables were developing using regression analysis. RESULTS: BP response was primarily related to plasma drug concentration. The association between the fall in BP and baseline variables was weak. The strongest single predictor of BP response was baseline mean arterial pressure (r2 = 5.8%, P = 0.02). The best combinations of predictor variables contained mean arterial pressure, plasma renin activity, creatinine concentration and age (r2 = 14.4%, P = 0.37). When the choice of ACE inhibitor was added, the predictive power of the model increased (r = 23.6%, P < 0.01) but left the majority of the variability in response unexplained. CONCLUSIONS: The first-dose blood pressure response to ACE inhibition cannot be accurately predicted from baseline pathophysiological variables in patients with mild to moderate CHF. The choice of ACE inhibitor accounts for a small proportion of the variability in response but wide inter-individual variability exists in the response to each treatment.

Aged

Comparison of helisal rapid blood test and 14C-urea breath test in determining Helicobacter pylori status and predicting ulcer disease in dyspeptic patients.

OBJECTIVE: Noninvasive tests for Helicobacter pylori are used increasingly. Our aim was to compare the Helisal Rapid Blood (HRB) test and 14C-urea breath test (UBT) for determining H. pylori status and predicting ulcer disease. METHODS: Three hundred fifty-one consecutive patients with dyspepsia (mean age 40 yr; range 16-77 yr) had an HRB test and UBT followed by endoscopy with biopsies of the antrum and body for histology and antral urease slide test (CLO test). Patients were excluded if they had previously confirmed ulcer disease, gastric surgery, or anti-H. pylori therapy or were taking nonsteroidal anti-inflammatory drugs. RESULTS: Sixty-three percent of the patients were "gold standard" H. pylori positive (positive CLO test, positive staining), 34% were gold standard negative (negative CLO test, negative staining), and 3% had conflicting CLO test and histology. The UBT was superior to HRB for determining H. pylori status (sensitivity 98% vs 92%, p = 0.04; specificity 100% vs 69%, p < 0.001). The specificity of the HRB decreased with increasing patient age (74% for age <46 yr; 57% for age > or =46 yr). A negative UBT was superior to a negative HRB test for predicting the absence of ulcer disease (47% vs 36 %; p < 0.01). A positive UBT was similar to a positive HRB in predicting the presence of ulcer disease (92% vs 84%; p = 0.23). CONCLUSIONS: The HRB test is inferior to the UBT for determining H. pylori status. The tests have a similar ability to predict the presence of ulcer disease when positive, but a negative UBT is a better predictor of the absence of ulcer disease.

Adolescent

Subgingival temperature and microbiota in initial periodontitis.

The association between subgingival temperature, other clinical characteristics, and the subgingival microbiota was examined in adult subjects with initial periodontitis and differing levels of gingival inflammation. 43 subjects were measured at 6 sites per tooth for pocket depth, attachment level, presence of plaque, gingival redness, bleeding on probing and subgingival temperature at 3-month intervals for 1 year. Subgingival plaque was sampled from 15 initial active periodontitis sites (10 subjects), 121 gingivitis, sites (20 subjects) and 202 healthy sites (13 subjects), and included the 5 hottest and 5 coldest sites in each subject. Plaque samples were analyzed for 13 subgingival species using whole-genomic DNA probes. The major influences on the subgingival microbiota were the clinical status of sites, pocket depth, and the presence of supragingival plaque. No significant association between species and site temperature was observed. Initial active sites were associated with Bacteroides forsythus and Campylobacter rectus, and had a higher mean subgingival temperature and deeper mean pocket depth than inactive sites. A weak association between pocket depth and site temperature was noted. The major influence on subgingival temperature of sites was the anterior to posterior anatomical temperature gradient in the mandible and maxilla.

Adult

Testing for Helicobacter pylori in primary care: trouble in store?

STUDY OBJECTIVE: To assess the role of testing for Helicobacter pylori in the management of dyspeptic patients in primary care. DESIGN: Selective review of literature frequently quoted to support use of H pylori testing. MAIN RESULTS: Testing for H pylori and referral of only positive cases for endoscopy aims to reduce the number of "unnecessary" endoscopies. Patients with negative results may receive short-term reassurance and subsequently place fewer demands on health services. However, studies to date have only assessed this practice in secondary care settings. Given the relatively high prevalence of both dyspepsia and H pylori infection, the transfer of this practice to primary care may lead to a paradoxical increase in endoscopy referrals. Identification of H pylori and prescribing of eradication treatment also aims to reduce endoscopy referrals. No primary care trials have yet assessed this approach. Given that fewer than one in four of dyspeptic patients have peptic ulceration, a high proportion may fail to respond to eradication treatment and subsequently require referral for endoscopy. The longer term clinical and psychosocial sequelae of treating or labelling patients with an infection associated with gastric cancer remain unknown. CONCLUSIONS: Given uncertainty concerning the possible adverse effects of H pylori testing in primary care, we suggest a moratorium on its use in this setting until results from relevant clinical trials become available.

Aged

Effects of postnatal depression on children's adjustment to school. Teacher's reports.

BACKGROUND: Little is known of the behavioural adjustment of children of postnatally depressed mothers. Previous studies have relied on maternal reports, and have produced inconsistent findings. METHOD: In a prospective, longitudinal study of the five-year-old children of a community sample of postnatally depressed and well women, evidence was collected concerning the children's adjustment in the context of school, teachers being asked to complete questionnaires after the children had finished their first term. RESULTS: Family social class and the child's gender had the most pervasive influences on adjustment. However, both postnatal and recent maternal depression were associated with significantly raised levels of child disturbance, particularly among boys and those from lower social class families. CONCLUSIONS: The findings indicate a persistent effect of postnatal depression on child adjustment. They highlight the need for resources devoted to supporting mothers of young children and particularly routine screening and treatment for postnatal mood disorder.

Adaptation, Psychological

Recombinant soluble interleukin-11 (IL-11) receptor alpha-chain can act as an IL-11 antagonist.

We have expressed a soluble N-glycosylated form of the murine interleukin-11 (IL-11) receptor alpha-chain (sIL-11R) and examined signaling in cells expressing the gp130 molecule. In the presence of gp130 but not the transmembrane IL-11R, the sIL-11R mediated IL-11-dependent differentiation of M1 leukemic cells and proliferation in Ba/F3 cells. Early intracellular events stimulated by the sIL-11R including phosphorylation of gp130, STAT 3, and SHP-2 were similar to signaling through the transmembrane IL-11R. IL-11 bound to sIL-11R with low affinity (kd 10 to 50 nmol/L). Binding of sIL-11R to gp130 was IL-11 dependent with intermediate affinity (kd 1.5 to 3.0 nmol/L). However, the concentration of IL-11 required for signaling through the sIL-11R was 10- to 20-fold greater than that required for cells expressing the transmembrane IL-11R and gp130 in the absence of sIL-11R. Furthermore, the sIL-11R was capable of antagonizing the activity of IL-11 when tested on cells expressing the transmembrane IL-11R and gp130. We propose that the observed IL-11 antagonism by the sIL-11R may depend on limiting numbers of gp130 molecules on cells already expressing the transmembrane IL-11R.

Amino Acid Sequence

Clinical presentation and outcome of brown recluse spider bite.

STUDY OBJECTIVE: To examine the clinical presentation and outcome of patients treated in the ED or toxicology clinic for suspected brown recluse spider bites. METHODS: We assembled a retrospective case of patients at a southeastern US university hospital. Our study group comprised 111 patients with suspected brown recluse spider bites treated during a 30-month period. Our main outcome measures were the need for skin grafting and the development of other complications. RESULTS: The mean age of our subjects was 34 +/- 17 years. Thirteen patients (12%) brought the spider to the hospital, 22 (20%) saw a spider at the time of the bite, and an exclusively clinical diagnosis was made in the remaining 76 (68%). Most wounds (59%) involved the leg. At the time of presentation, 81% had central discoloration and 37% necrosis. Sixteen patients (14%) were systemically ill, and 6 (5%) were admitted to the hospital. Most (86%) were treated with antibiotics. Dapsone was infrequently used (9%) and had usually been prescribed before the patient's presentation to our ED. Only three patients (3%; 95% confidence interval, 1% to 8%) required grafting. Mild hemolytic anemia developed in one patient, and another had mild hemolysis and a mild coagulopathy; neither patient was taking dapsone. No deaths or serious complications occurred in our study group. CONCLUSION: In our series, long-term outcome after brown recluse spider bite was good. Serious complications were rare, as was the need for skin grafting. Because the vast majority of bites heal with supportive care alone, aggressive medical therapy does not appear warranted.

Adolescent

DHA feeding provides host protection and prevents fibrosarcoma-induced hyperlipidemia while maintaining the tumor response to araC in Fischer 344 rats.

Fischer 344 rats were inoculated with fibrosarcoma tumor cells and fed diets containing 5% or 10% (wt/wt) safflower oil or 10% oil containing docosahexaenoic acid (DHA). Animals were then treated with arabinosylcytosine (araC) or saline for six days. Tumor weights were highest in animals fed 10% safflower oil and treated with saline, intermediate in animals fed oil containing DHA and 5% safflower oil and treated with saline, and lowest in araC-treated animals from all diets. Plasma cholesterol and triglyceride levels correlated highly with final tumor size, regardless of diet or treatment group. Animals fed safflower oil had lower intestinal weights than those fed DHA, which histology demonstrated to be a result of differences in villus height and crypt depth. Substantial loss of bone marrow cells occurred in all dietary groups treated with araC; however, the proportion of granulocyte-macrophage precursors remaining in the DHA animals was higher than in saline-treated animals and twofold higher than in the animals fed 10% safflower oil and treated with araC. These data suggest that, even in the face of rapid tumor growth and chemotherapeutic challenge, consumption of a diet rich in DHA can slow tumor growth, prevent hyperlipidemia, enhance bone marrow cellularity, and promote intestinal growth compared with a moderate-fat n--6-rich diet.

Animals

The Helicobacter pylori breath test: a surrogate marker for peptic ulcer disease in dyspeptic patients.

BACKGROUND: There is interest in noninvasive H pylori testing as a means of predicting diagnosis and determining management in dyspeptic patients. AIMS: To assess the value of the 14C urea breath test as a predictor of peptic ulcer disease in patients presenting with dyspepsia. PATIENTS AND METHODS: 327 consecutive patients referred for investigation of dyspepsia had a 14C urea breath test performed before endoscopy. Patients were not included if they had previously confirmed ulcer disease, previous gastric surgery, or were taking non-steroidal anti-inflammatory drugs. RESULTS: Of the 182 patients with a positive 14C urea breath test, duodenal and/or gastric ulcers were present in 45% and erosive duodenitis in a further 2%. Oesophagitis was present in 12% of the breath test positive patients with two thirds of the oesophagitis patients having co-existent ulcer disease. The prevalence of ulcer disease in the H pylori positive dyspeptic patients was independently related to smoking and previous investigation status. If previously uninvestigated, the prevalence of ulcers was 67% in smokers and 46% in non-smokers. If previous upper gastrointestinal investigations were negative, the prevalence of ulcers was 53% in smokers and 28% in non-smokers. Of the 136 patients with a negative breath test, only 5% had peptic ulcers. The most frequent endoscopic finding in these H pylori negative subjects was oesophagitis, being present in 17%. CONCLUSIONS: This study demonstrates that a positive H pylori test is a powerful predictor of the presence of underlying ulcer disease in dyspeptic patients, especially if smokers, and that a negative H pylori test is a powerful predictor of the absence of ulcer disease. It also indicates that a negative upper gastrointestinal investigation does not preclude subsequent presentation with ulcer disease.

Adolescent