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Biomedical subjects

J Barnett

Publications and source records attributed to J Barnett.

At least 37 records · Page 2Linked to original sources

A double-blind multicenter comparison of domperidone and metoclopramide in the treatment of diabetic patients with symptoms of gastroparesis.

OBJECTIVE: A double-blind, multicenter, randomized trial was conducted to compare the side effects and efficacy of domperidone and metoclopramide in symptomatic diabetic gastroparesis. METHODS: Ninety-three insulin-dependent diabetes patients with a > or = 3-month history of gastroparesis symptoms were recruited; 48 received domperidone 2 x 10-mg tablets 4 times daily, and 45 received metoclopramide 1 x 10-mg tablet + 1 placebo tablet 4 times daily. Nausea, vomiting, bloating/distension, and early satiety were evaluated for severity after 2 and 4 wk. Adverse central nervous system (CNS) effects of somnolence, akathisia, asthenia, anxiety, depression, and reduced mental acuity were elicited and graded for severity at 2 and 4 wk. RESULTS: Domperidone and metoclopramide were equally effective in alleviating symptoms of diabetic gastroparesis. Elicited adverse CNS effects were more severe and more common with metoclopramide. Somnolence was acknowledged by 49% of patients (mean severity score, 1.03) after 4 wk of metoclopramide compared with 29% of patients (mean severity score, 0.49) after 4 wk of domperidone (incidence, p = 0.02; severity; p = 0.03). A reduction in mental acuity was acknowledged by 33% of patients (mean severity score, 0.62) after 4 wk of metoclopramide, compared with 20% of patients (mean severity score, 0.27) after 4 wk of domperidone (incidence, p = 0.04; severity, p = 0.04). Akathisia, asthenia, anxiety, and depression were also acknowledged less often, and at a lower severity, after 4 wk of domperidone, although these differences were not statistically significant. CONCLUSIONS: Domperidone and metoclopramide effectively reduce the symptoms of diabetic gastroparesis; CNS side effects are more pronounced with metoclopramide.

Adult↗

The validity of dietary assessment in general practice.

OBJECTIVE: To validate a range of dietary assessment instruments in general practice. METHODS: Using a randomised block design, brief assessment instruments and more complex conventional dietary assessment tools were compared with an accepted "relative" standard--a seven day weighed dietary record. The standard was checked using biomarkers, and by performing test-retest reliability in additional subjects (n = 29). OUTCOMES: Agreement with weighed record. Percentage agreement with weighed record, rank correlation from scatter plot, rank correlation from Bland-Altman plot. Reliability of the weighed record. SETTING: Practice nurse treatment room in a single suburban general practice. SUBJECTS: Patients with risk factors for cardiovascular disease (n = 61) or age/sex stratified general population group (n = 50). RESULTS: Brief self completion dietary assessment tools based on food groups caten during a week show reasonable agreement with the relative standard. For % energy from fat and saturated fat, non-starch polysaccharide, grams of fruit and vegetables and starchy foods consumed the range of agreement with the standard was: median % difference -6% to 12%, rank correlation 0.5 to 0.6. This agreement is of a similar order to the reliability of the weighed record, as good as or better than test standard agreement for more time consuming instruments, and compares favourably with research instruments validated in other settings. Under-reporting of energy intake was common (40%) and more likely if subjects were obese (body mass idex (BMI) > or = 30 60% under-reported; BMI < 30 29%, p < 0.001). CONCLUSION: Under-reporting of absolute energy intake is common, particularly among obese patients. Simple self assessment tools based on food groups, designed for practice nurse dietary assessment, show acceptable agreement with a standard, and suggest such tools are sufficiently accurate for clinical work, research, and possibly population dietary monitoring.

Adolescent↗

Effects of feeding Lunaria oil rich in nervonic and erucic acids on the fatty acid compositions of sphingomyelins from erythrocytes, liver, and brain of the quaking mouse mutant.

Feeding an oil from Lunaria biennis rich in 22:1n-9 and 24:1n-9 to homozygous quaking (qk.qk) mice caused a large increase in the percentage of 24:1n-9 and corresponding decreases in the percentage of 24:0 and 22:0 in sphingomyelins from liver, erythrocytes, and milk. Brain sphingomyelin from 2-wk-old qk.qk pups born to qk.qk mothers maintained on the Lunaria oil had essentially normal percentage of 24:1n-9 and 18:0, in contrast to pups born to mothers maintained on a control oil rich in 18:1n-9 whose brain sphingomyelin had a markedly reduced percentage of 24:1n-9 and an increased percentage of 18:0. After 2 wk and up to and beyond weaning, the qk.qk pups from Lunaria-fed mothers weaned on to the Lunaria diet had a markedly decreased percentage of 24:1n-9 in their brain sphingomyelin, accompanied by an increased percentage of 18:0, as compared to heterozygous quaking mice. However, the percentage of 24:1n-9 in brain sphingomyelin in qk.qk pups weaned on to the Lunaria diet continued throughout this period (2-8 wk postbirth) to be significantly higher than in qk.qk pups weaned on to the control diet. We conclude that dietary 24:1n-9 influences the fatty acid composition of brain sphingomyelin in qk.qk mice, but only via the mother in pre- or early postnatal animals. We further consider that the dietary effects may be elicited mainly in the sphingomyelin of nonmyelinated brain cells, and that the nervonic acid in myelin sphingomyelin may be formed mainly by chain elongation in oligodendrocytes from shorter chain fatty acid precursors.

Animal Nutritional Physiological Phenomena↗

Low- versus high-dose azithromycin triple therapy for Helicobacter pylori infection.

BACKGROUND: We report a clinical trial which evaluated the effectiveness of triple therapy containing low- and high-dose azithromycin to treat Helicobacter pylori infection. METHODS: From March 1997 to March 1998, patients infected with H. pylori were assigned to receive either: Treatment 1: ranitidine bismuth citrate (RBC) (400 mg b.d.) and amoxycillin (1 g b.d.) for 10 days with azithromycin 500 mg o.m. for 3 days: or Treatment 2: RBC and amoxycillin for 10 days with azithromycin 1 g o.m. for 3 days. H. pylori eradication was established by a urea breath test at least 4 weeks after therapy. Side-effects and compliance were assessed using a diary. RESULTS: Sixty-eight patients were enrolled. Fifty-seven per cent of patients were treated for active peptic ulcer disease or a history of peptic ulcer disease. Treatment 1 cured H. pylori in 44% and 44% by per protocol and intention-to-treat analysis, respectively. The corresponding eradication rates for Treatment 2 were 79% and 75%. Two patients taking Treatment 2 dropped out of the study because of side-effects. CONCLUSIONS: With RBC and amoxycillin for 10 days, azithromycin at a dose of 1 g/day for 3 days was significantly better at curing H. pylori infection than azithromycin 500 mg/day for 3 days.

Adult↗

Liposomes enriched in oleic acid are less susceptible to oxidation and have less proinflammatory activity when exposed to oxidizing conditions.

As there is frequently a reciprocal relationship between oleic acid and linoleic acid content in LDL after dietary supplementation, it is difficult to determine the independent effects of oleic and linoleic acid on LDL oxidation. It is also unknown whether monounsaturated fatty acid enrichment might reduce the generation of proinflammatory products that occur when the polyunsaturated fatty acid-rich phospholipids within lipoproteins undergo mild oxidation. To address these issues, we exposed liposomes containing variable amounts of oleic, linoleic, and arachidonic acid to oxidizing conditions. Liposomes enriched in oleic acid but with constant amounts of linoleic acid were less susceptible to oxidation and had significantly greater lag times and time to half maximum conjugated diene formation. When mildly oxidized, liposomes containing either linoleic acid or arachadonic acid increased monocyte chemotaxis and monocyte adhesion to endothelial cells nearly 5-fold, demonstrating that oxidation products of both these polyunsaturated fatty acids are bioactive. The addition of a platelet activating factor receptor antagonist to endothelial cells inhibited stimulation of monocyte adhesion by oxidized liposomes, suggesting that some bioactive oxidation products of polyunsaturated fatty acids may resemble platelet activating factor in structure. In contrast, when liposomes were enriched in oleic acid, monocyte chemotaxis and monocyte adhesion were nearly completely inhibited. These results suggest that enriching lipoproteins with oleic acid may reduce oxidation both by a direct "antioxidant"-like effect and by reducing the amount of linoleic acid available for oxidation as well as reduce the generation of bioactive particles that occur during mild oxidation.

Animals↗

Antibodies to Brucella in marine mammals around the coast of England and Wales.

Following the isolation of previously unrecognised species of Brucella from stranded seals and cetaceans in Scotland and northern England, a serological survey was carried out to investigate the range of marine mammal species which may have been exposed to Brucella species around the coasts of England and Wales, the prevalence of infection and the temporal and geographical distribution of seropositive animals. Serum collected from 153 stranded marine mammals from the coasts of England and Wales between 1989 and 1995 were tested by competitive and indirect ELISA. Positive titres were recorded for six of 62 (10 per cent) grey seals (Halichoerus grypus), one of 12 (8 per cent) common seals (Phoca vitulina), 11 of 35 (31 per cent) harbour porpoises (Phocoena phocoena) and nine of 29 (31 per cent) common dolphins (Delphinus delphis) tested. Positive titres were also found in a striped dolphin (Stenella coeruleoalba), a bottlenose dolphin (Tursiops truncatus), a killer whale (Orcinus orca) and a pilot whale (Globicephala melas). The seropositive animals were from all around the coasts of England and Wales and the first seropositive sample was from a common dolphin in 1990.

Animals↗

Differential allosteric regulation of prostaglandin H synthase 1 and 2 by arachidonic acid.

Prostaglandins are synthesized by prostaglandin H synthase (PGHS) 1 and 2. PGHS2 is regulated through inducible expression. We report here the regulation of PGHS1 activity by substrate-dependent cooperative activation. The cooperativity is characterized by a Hill coefficient of 1.29 +/- 0.06, a curved Eadie-Scatchard plot, and activation by low concentrations of competitive inhibitors. The activation also appears to induce a conformational change in the cyclooxygenase site. The cooperativity produces a 2-4-fold greater rate of PGHS2-dependent prostaglandin formation compared with PGHS1-dependent prostaglandin formation at arachidonic acid concentrations below 0.5 microM. A consequence of the PGHS1 cooperativity is that the affinity of many cyclooxygenase inhibitors for PGHS1 decreases in parallel to the activation by arachidonic acid. In contrast, the affinity of these inhibitors for PGHS2 is unaffected by the changes in arachidonic acid concentration. This results in a dramatic difference in PGHS2/PGHS1 selectivity at different arachidonic acid concentrations.

Arachidonic Acid↗

Control of varicella-zoster infection on renal and other specialist units.

The introduction of chickenpox onto our renal unit recently raised several issues surrounding the management of patient and staff contracts. This paper describes the action taken and makes various recommendations for future management of similar cases. Guidelines are proposed for the management of patients and staff as well as the role of the infection control team in handling a chickenpox problem. Future developments, including the use of VZ vaccine for patient and staff, are also discussed.

Chickenpox↗

Expression of human dopamine beta-hydroxylase in Drosophila Schneider 2 cells.

Human dopamine beta-hydroxylase (DBH) has been expressed in transformed Drosophila Schneider 2 (S2) cells with yields of > 16 mg/l. Most of the activity was found in the culture fluid. Similarly, human neuroblastoma cells also secrete native DBH into the medium, but at a much lower level than recombinant Drosophila cells. We have purified native and recombinant human DBH by a modified purification procedure using SP-Sepharose, lentil lectin-Sepharose and gel-filtration chromatography and carried out studies to compare the two enzymes. Two variants of human DBH that differ by a single amino acid (either serine or alanine) at position 304 were expressed in Drosophila cells, purified, and found to have no significant difference in enzyme activity. The molecular mass of human DBH monomer has been determined from SDS/PAGE to be 73 kDa, but the recombinant DBH from Drosophila is smaller at 66 kDa. The difference may be due to glycosylation as deglycosylated enzymes from both sources are identical in size (61 kDa). The Km of tyramine for native and recombinant human enzymes are virtually the same but higher than bovine DBH by about 3-fold. Likewise, the inhibition of native and recombinant human DBH by fusaric acid and SKF102698 is not significantly different but IC50 values are 2-3-fold higher than that for the bovine enzyme. These results strongly support the conclusion that recombinant human DBH from Drosophila S2 cells can be used in place of human neuroblastoma-derived DBH for drug screening, characterization of the enzyme's physicochemical properties, and determination of structure-function relationships. The Drosophila expression system has thus provided a convenient source for large quantities of human DBH enzyme.

Amino Acid Sequence↗

Flexibility of the NSAID binding site in the structure of human cyclooxygenase-2.

The first crystal structure of human cyclooxygenase-2, in the presence of a selective inhibitor, is similar to that of cyclooxygenase-1. The structure of the NSAID binding site is also well conserved, although there are differences in its overall size and shape which may be exploited for the further development of selective COX-2 inhibitors. A second COX-2 structure with a different bound inhibitor displays a new, open conformation at the bottom of the NSAID binding site, without significant changes in other regions of the COX-2 structure. These two COX-2 structures provide evidence for the flexible nature of cyclooxygenase, revealing details about how substrate and inhibitor may gain access to the cyclooxygenase active site from within the membrane.

Anti-Inflammatory Agents, Non-Steroidal↗

Nitric oxide metabolite levels in acute vaso-occlusive sickle-cell crisis.

OBJECTIVES: 1) To measure nitric oxide (NO) metabolite levels in patients presenting to the ED in acute vaso-occlusive sickle-cell crisis (SCC), and 2) to determine whether a relationship exists between NO metabolite levels and pain. METHODS: A prospective, observational study of patients with documented sickle-cell anemia (SCA), aged > or = 18 years, presenting in typical, acute SCC was conducted in an urban, university teaching hospital. Excluded were those with atypical pain or acute, coexistent disease (as evidenced by fever, tachycardia, tachypnea, or hypotension). Pain scores were measured by a 10-cm visual analog scale (VAS). Blood NO metabolite levels for SCC patients and control subjects (healthy volunteers, n = 9; SCA control subjects not in SCC, n = 10) were determined using an NO-specific chemiluminescence technique that measured plasma nitrite and nitrate, the stable end-products of NO. The acute SCC patients were divided into 3 groups, with the range for the SCC-normal (n = 5) group defined as within 2 SD of the healthy volunteer control patients. The SCC-low patients (n = 21) had NO metabolite levels below this range and the SCC-high (n = 21) patients had levels above this range. RESULTS: The SCA and healthy volunteer control groups had similar NO metabolite levels (25.3 vs 22.6 mumol; p = 0.10). The 3 acute SCC groups had the following mean NO levels: 1) SCC-normal = 21.3 +/- 1.6 mumol; 2) SCC-low = 7.2 +/- 1.1 mumol; and 3) SCC-high = 43.7 +/- 3.5 mumol. The SCC-high NO-level group had significantly lower VAS pain scores when compared with the SCC-low and SCC-normal NO-level groups (6.52 +/- 1.85 cm vs 8.76 +/- 0.83 cm, and 8.62 +/- 1.29 cm, p = 0.02). CONCLUSION: NO metabolite levels vary in SCC patients. Elevated levels are associated with lower pain scores, while lower levels are associated with higher pain scores, indicating that NO metabolites may potentially represent a marker for compensatory mechanisms in SCC tissue ischemia. Further work is needed to delineate the usefulness of NO metabolites in assessing the severity of SCC.

Acute Disease↗

Effect of antioxidants alone and in combination with monounsaturated fatty acid-enriched diets on lipoprotein oxidation.

Previous studies have demonstrated that compared with more buoyant LDL, dense LDL (D-LDL) is more susceptible to oxidation and less readily protected from oxidation by antioxidant enrichment. However, diets enriched in monounsaturated fatty acids (MUFAs) appear particularly effective in protecting D-LDL from oxidation. We therefore evaluated in 12 non-insulin-dependent diabetes mellitus subjects the effects of supplementation with alpha-tocopherol (1600 IU/d) and probucol (1 g/d) alone and in combination with an MUFA-enriched diet on LDL and LDL subfraction susceptibility to oxidation and monocyte release of superoxide anion. Subjects received either alpha-tocopherol or probucol for 4 months, and during the fourth month both groups also received an MUFA-enriched diet. alpha-Tocopherol levels were significantly increased in LDL and LDL subfractions (P < .05) after 3 months of supplementation. MUFA-enriched diets led to further increases in alpha-tocopherol in LDL fractions in the alpha-tocopherol group as well as in those receiving probucol. In the alpha-tocopherol-supplemented group, lag times were increased significantly (1.6- to 2.0-fold) for all LDL fractions, although the absolute increase was least for D-LDL. Although probucol supplementation increased lag times of LDL and LDL subfractions three- to fourfold, D-LDL was still more readily oxidized. In both the alpha-tocopherol- and probucol-supplemented groups the benefit of adding MUFA-enriched diets was greatest for D-LDL, with further increases in lag time of 26% and 18%, respectively. Neither antioxidant supplementation nor the addition of an MUFA-enriched diet reduced unstimulated or phorbol ester-stimulated monocyte superoxide anion production. These data demonstrate the markedly different effects that antioxidants and diet may have on different LDL subfractions, which may be particularly important in individuals with non-insulin-dependent diabetes mellitus, who frequently have increased amounts of D-LDL.

Adult↗

Size, detail, and line heaviness in children's drawings as correlates of emotional distress: (more) negative evidence.

This study examined the reliability and validity of three commonly used indicators of emotional distress in children's projective drawings--size, detail, and line heaviness--and assessed their relation to established objective and projective measures of childhood depression and anxiety. Participants were 80 child and adolescent psychiatric inpatients (53 boys, 27 girls; ages 6 to 16; M = 10.69, SD = 2.94). Although the present results indicated that these drawing indices can be assessed with very high reliability, they were not significantly associated with self-report or thematic projective measures of depression and anxiety. Age and defensiveness did not moderate the relation between the drawing indices and the non-drawing measures of emotional distress. The patterning of the intercorrelations among and within the drawing indices, projective stories, and self-report measures indicated greater support for the self-report measures, in terms of convergent and discriminant validity. This study did not support the continued use of these three projective drawing indices of emotional distress.

Adolescent↗