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Biomedical subjects

D Rutherford

Publications and source records attributed to D Rutherford.

At least 19 recordsLinked to original sources
PubMed2006

Tissue disposition, excretion and metabolism of 2,2',4,4',6-pentabromodiphenyl ether (BDE-100) in male Sprague-Dawley rats.

The absorption, disposition, metabolism and excretion study of orally administered 2,2',4,4',6-pentabromodiphenyl ether (BDE-100) was studied in conventional and bile-duct cannulated male rats. In conventional rats, >70% of the radiolabelled oral dose was retained at 72 h, and lipophilic tissues were the preferred sites for disposition, i.e. adipose tissue, gastrointestinal tract, skin, liver and lungs. Urinary excretion of BDE-100 was very low (0.1% of the dose). Biliary excretion of BDE-100 was slightly greater than that observed in urine, i.e. 1.7% at 72 h, and glucuronidation of phenolic metabolites was suggested. Thiol metabolites were not observed in the bile as had been reported in other PBDE metabolism studies. Almost 20% of the dose in conventional male rats and over 26% in bile-duct cannulated rats was excreted in the faeces, mainly as the unmetabolized parent, although large amounts of non-extractable radiolabel were also observed. Extractable metabolites in faeces were characterized by mass spectrometry. Monohydroxylated pentabromodiphenyl ether metabolites were detected; mono- and di-hydroxylated metabolites with accompanying oxidative debromination were also observed as faecal metabolites. Tissue residues of [(14)C]BDE-100 in liver, gastrointestinal tract and adipose tissue contained only parent material. The majority of the 0-72-h biliary radioactivity was associated with an unidentified 79-kDa protein or to albumin.

Animals↗
PubMed2001

Provision of laboratory services for heart and lung transplantation in Australia.

BACKGROUND: Laboratory services for the support of heart and lung transplantation in Australia have adapted to the special needs of the clinicians looking after the heart and lung transplantation patients. METHODS: Pre-transplantation standardized tests encompassing a wide variety of different parameters are carried out both to establish the suitability of patients for a transplant and to maximize the chance of success following this procedure. Potential solid organ recipients routinely have blood samples sent to a number of centers Australia-wide so that human leukocyte antigen (HLA) presensitization can be checked for at the time a donor becomes available in any state in Australia. Although prospective HLA matching is not performed for thoracic organ transplant recipients, pre-existing antibodies to donor HLA antigens are a contra-indication to transplantation. Following transplantation, the predominant roles of the laboratory are in the monitoring of immunosuppressive drug levels, in the detection of allograft rejection, and in the detection of bacterial infection or viral reactivation. While a number of markers have been proposed in the detection of rejection, we currently rely on interpretation of the histological analysis of biopsies. The treatment with immune suppressive agents, in particular cyclosporin A, has made organ transplantation from non-HLA identical donors possible. As cyclosporin A and other immune suppressive drugs have significant side effects, their concentrations need to be carefully followed to guarantee sufficient immune suppression while avoiding renal failure and other complications including excessive immunosuppression and infectious disease risk. Recently, the role of viral reactivation with the human cytomegalovirus (HCMV) has attained more prominence. HCMV is a potential pathogen in up to 90% of thoracic organ transplant recipients and in the pre-gancyclovir era, it was a major cause of morbidity and mortality in at-risk lung transplant recipients. New PCR-based assays that measure the viral load levels of HCMV allow earlier intervention and more appropriate treatment strategies to prevent the HCMV disease syndromes and optimize the HCMV prophylaxis strategy. CONCLUSIONS: Diagnostic pathology testing to support heart and lung transplantation is a combination of routine testing and specialized testing. Depending on the time-critical nature of the tests, this testing has to be done on site or in more centralized testing facilities. Further developments in the laboratory support of heart and lung transplantation will hopefully continue to improve both the short- and long-term outcomes of thoracic organ transplant recipients.

Australia↗
PubMed1995

Selective antinociceptive effect of excitatory amino acid antagonists in intact and acute spinal rats.

Results of neurophysiologic and behavioral studies suggest that excitatory amino acid (EAA) antagonists may provide a new class of analgesic agents, which might be selective for neuropathic pain states that are resistant to opiate treatment. Most of these paradigms involve animal models of peripheral injury. The present study evaluated the antinociceptive effect of spinally [intrathecally (IT)] administered EAA antagonists after central injury, produced by spinal transection. Intrathecal injection of the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione produced dose-dependent antinociception on the thermal tail withdrawal [tail-flick (TF)] reflex test in Intact rats, which was significantly potentiated after spinal transection. In contrast, IT injection of the NMDA antagonist, 2-amino-5-phosphonopentanoic acid (AP5) did not affect the TF in intact rats, but significantly blocked this response in spinal rats. However, some of the spinal rats did not recover the reflex, suggesting a possible toxic action of AP5.

2-Amino-5-phosphonovalerate↗
PubMed1994

Effects of plant diterpenes on the neuronal GABAA receptor-operated chloride current.

The effects of plant diterpenes, horminone (HMN) and taxodione (TXN), on the GABAA receptor-operated Cl-current (IGABA) were investigated in voltage-clamped and internally perfused neurones dissociated from frog dorsal root ganglia. Both diterpenes depressed IGABA in a concentration-dependent manner similar to that of picrotoxin. Concentrations required to elicit 50% depression of the IGABA were 10(-6) M for picrotoxin, 10(-5) M for HMN and 10(-4) M for TXN. Blocking and restoration kinetics of the IGABA with HMN were also similar to those of picrotoxin. Time constants for both the blockade and restoration of the IGABA with TXN were more than five times greater than those with HMN.

Abietanes↗
PubMed1994

Construct validation study of the Fear of Powerlessness Scale.

To establish construct validity with 129 subjects for the Fear of Powerlessness Scale parallels were drawn among Levenson's Locus of Control Scales, the Fear of Powerlessness, and the Desire for Control Scale. Analysis yielded significant correlations between scores on the Fear of Powerlessness Scale, the Desire for Control Scale (negative), and 2 of Levenson's Locus of Control Scales, the Chance Scale and the Powerful Others Scale (positive).

Adolescent↗
PubMed1994

Repeat consultations after antibiotic prescribing for respiratory infection: a study in one general practice.

BACKGROUND: Several new antibacterial drugs have been introduced in the last 10 years with the aim of improved treatment of respiratory tract infection. AIM: The study set out to use repeat consultations as a measure of the outcome of antibiotic treatment for respiratory tract infection, and to develop a simple model for discussion of the cost effectiveness of alternative antibiotic treatments. METHOD: All consultations to one practice during a single winter were reviewed by one general practitioner. RESULTS: A total of 1140 patients had acute symptoms suggestive of respiratory infection. Of these, 899 patients (79%) were prescribed antibiotics at the first consultation and 160 of the 899 patients (18%) returned for one or more repeat consultations; only nine repeat consultations were due to adverse effects of the antibiotics prescribed. Only two patients were admitted to hospital for respiratory symptoms following initial antibiotic therapy and both patients had additional reasons for their admission. Using the highest estimates, the cost of a repeat consultation was found to be 28.54 pounds. These data were used to calculate how much more might be spent on more effective antibiotics at the first consultation. It would be difficult to justify increasing the cost of antibiotic treatment by more than 5 pounds per patient, even if the new treatment were 100% effective and all repeat consultations were due to treatment failure (5 pounds is equal to 28.54 pounds x 0.18, which is the maximum cost of a repeat consultation multiplied by the proportion of patients prescribed antibiotics who make repeat consultations). CONCLUSION: From these results and a review of the literature it can be concluded that new antibacterial drugs will have to be carefully targeted if they are to prove cost effective in practice. Other methods for reducing repeat consultation merit investigation.

Adolescent↗
PubMed1990

A double-blind, randomized, prospective trial of a topical antiseptic versus a topical antibiotic in the treatment of otorrhoea.

The clinical efficacy was assessed of a topical antiseptic (aluminium acetate) and a topical antibiotic (gentamicin sulphate) for the initial treatment of otorrhoea. Evidence of resistant organisms developing to either treatments after 9 and 21 days was also examined. 139 affected ears were entered into the trial and of these, 102 (74%) completed the study. Improvement in the otorrhoea occurred in 68% of ears treated with gentamicin and 67% of ears treated with aluminium acetate, with no significant difference between the two treatments. No resistant organisms to aluminium acetate were encountered. Twelve gentamicin-treated ears had gentamicin-resistant organisms at presentation and one patient developed a gentamicin-resistant Pseudomonas during treatment. We therefore recommend a topical antiseptic such as aluminium acetate rather than a topical antibiotic in the initial treatment of otorrhoea on the grounds of cost, avoidance of resistance and toxicity.

Acetates↗
PubMed1989

Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease.

We have determined the sequences of isoforms of human tau protein, which differ from previously reported forms by insertions of 29 or 58 amino acids in the amino-terminal region. Complementary DNA cloning shows that the insertions occur in combination with both three and four tandem repeats. RNAase protection assays indicate that transcripts encoding isoforms with the insertions are expressed in an adult-specific manner. Transcripts encoding four tandem repeats are also expressed in an adult-specific manner, whereas mRNAs encoding three tandem repeats are expressed throughout life, including in fetal brain. The levels of transcripts encoding the 29 or 58 amino acid inserts were not significantly changed in cerebral cortex from patients with Alzheimer's disease. Antisera raised against synthetic peptides corresponding to these different human tau isoforms demonstrate that multiple tau protein isoforms are incorporated into the neurofibrillary tangles of Alzheimer's disease.

Alzheimer Disease↗
PubMed1986

Small bowel permeability in patients with nasal polyposis.

Small bowel absorption defects have been noted in a proportion of patients with atopic eczema. Eighteen patients with recurrent nasal polyps had the cellobiose/mannitol ratio test performed in order to assess their small bowel function. Evidence for atopy was found in 11 of 18 patients. Histologically the polyps were described as allergic but the cellobiose/mannitol ratio was normal in all cases. No evidence for a small bowel absorption defect was obtained.

Adult↗
PubMed1981

Benzodiazepine withdrawal symptoms and propranolol.

40 patients seen in general practice and psychiatric outpatient clinics who had taken lorazepam or diazepam alone in regular dosage for a mean period of 3.6 years had their benzodiazepine replaced by propranolol (60--120 mg/day) or placebo for two weeks under double-blind conditions. Depending on the criteria for the definition of an abstinence syndrome, 27--45% of the patients had withdrawal symptoms during the study. Propranolol did not affect the drop-out rate or the incidence of withdrawal symptoms but significantly reduced their severity in patients completing the study. The percentage fall in serum levels of desmethyldiazepam in patients who experienced withdrawal symptoms after stopping diazepam was significantly greater in patients with no withdrawal symptoms.

Anti-Anxiety Agents↗