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Biomedical subjects

D Clifford

Publications and source records attributed to D Clifford.

At least 19 recordsLinked to original sources
PubMed2006

Influence of colostrum deprivation and concurrent Cryptosporidium parvum infection on the colonization and persistence of Escherichia coli O157 : H7 in young lambs.

Escherichia coli O157 : H7 and Cryptosporidium parvum infections of man have been associated with direct contact with small ruminants. Colostrum protects neonates against gastrointestinal pathogens, and orphan lambs, which are common on petting farms, may be deprived of this protection. In a recent study, it was demonstrated that high shedding of E. coli O157 : H7 by an 8-week-old goat kid was associated with coincidental C. parvum infection. Furthermore, both pathogens were co-located in the distal gastrointestinal tract. It was hypothesized that colostrum deprivation and pre-infection with C. parvum predisposed young ruminants to colonization and increased shedding of E. coli O157 : H7. To test this, 21 lambs 5 weeks of age were divided into four groups as follows: (A) colostrum-deprived and inoculated with E. coli O157 : H7, (B) colostrum-deprived and inoculated with C. parvum and then E. coli O157 : H7, (C) conventionally reared and inoculated with E. coli O157 : H7, (D) conventionally reared and inoculated with C. parvum and then E. coli O157 : H7. C. parvum was detected between 8 and 12 days post-inoculation in most of the infected lambs. At 24 h post-inoculation with E. coli O157 : H7, all lambs were shedding between 5 x 10(4) and 5 x 10(7) c.f.u. E. coli O157 : H7 per gram of faeces. E. coli O157 : H7 was shed in higher numbers in the groups pre-inoculated with C. parvum, whether conventionally reared or colostrum-deprived. Interestingly, for the colostrum-deprived lambs on day 3, a significant difference in shedding of E. coli O157 : H7 was observed (P = 0.038), with the lambs inoculated with E. coli alone yielding higher counts than those pre-inoculated with C. parvum. From day 15 onwards, shedding of E. coli O157 : H7 was highest from the colostrum-deprived C. parvum-infected lambs, then (in descending order of shedding) the colostrum-deprived lambs, the conventionally reared lambs infected with C. parvum, and the conventionally reared animals. In total, four animals were euthanized, two at 24 h and two at 96 h post inoculation with E. coli O157 : H7 (two conventionally reared and two colostrum-deprived). All animals euthanized were from groups pre-inoculated with C. parvum prior to challenge with E. coli O157 : H7. On examination of tissues, in three of the four animals examined, multifocal attaching and effacing lesions were observed in the caecum, colon, rectum and at the recto-anal junction, and were confirmed by immunohistochemistry to be associated with E. coli O157 : H7.

Animals↗
PubMed2005

Anti-sulfatide antibodies in HIV-infected individuals with sensory neuropathy.

We used ELISA to estimate the prevalence of anti-sulfatide antibodies in HIV-infected individuals with distal sensory neuropathy (DSP) and compared the results with the prevalence in HIV-infected individuals without DSP and in individuals with neuropathy who are not infected with HIV. We found that 36% of HIV+/DSP+ individuals had immunoglobulin (Ig) G anti-sulfatide antibody titers greater than 1,500, whereas IgG anti-sulfatide antibodies were rarely found in HIV+/DSP- or HIV-/DSP+ patients.

Autoantibodies↗
PubMed2005

Colonization of 8-week-old conventionally reared goats by Escherichia coli O157 : H7 after oral inoculation.

Enterohaemorrhagic Escherichia coli O157 : H7 infections of man have been associated with consumption of unpasteurized goat's milk and direct contact with kid goats on petting farms, yet little is known about colonization of goats with this organism. To assess the contribution of flagella and intimin of E. coli O157 : H7 in colonization of the goat, 8-week-old conventionally reared goats were inoculated orally in separate experiments with 1x10(10) c.f.u. of a non-verotoxigenic strain of E. coli O157 : H7 (strain NCTC 12900 Nal(r)), an aflagellate derivative (DMB1) and an intimin-deficient derivative (DMB2). At 24 h after inoculation, the three E. coli O157 : H7 strains were shed at approximately 5x10(4) c.f.u. (g faeces)(-1) from all animals. Significantly fewer intimin-deficient bacteria were shed only on days 2 (P = 0.003) and 4 (P = 0.014), whereas from day 7 to 29 there were no differences. Tissues from three animals inoculated with wild-type E. coli O157 : H7 strain NCTC 12900 Nal(r) were sampled at 24, 48 and 96 h after inoculation and the organism was cultured from the large intestine of all three animals and from the duodenum and ileum of the animal examined at 96 h. Tissues were examined histologically but attaching-effacing (AE) lesions were not observed at any intestinal site of the animals examined at 24 or 48 h. However, the animal examined at 96 h, which had uniquely shed approximately 1x10(7) E. coli O157 : H7 (g faeces)(-1) for the preceding 3 days, showed a heavy, diffuse infection with cryptosporidia and abundant, multifocal AE lesions in the distal colon, rectum and at the recto-anal junction. These AE lesions were confirmed by immunohistochemistry to be associated with E. coli O157 : H7.

Adhesins, Bacterial↗
PubMed2003

Lamotrigine for HIV-associated painful sensory neuropathies: a placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and tolerability of lamotrigine (LTG) for the treatment of pain in HIV-associated sensory neuropathies. METHODS: In a randomized, double-blind study, patients with HIV-associated distal sensory polyneuropathy (DSP) received LTG or placebo during a 7-week dose escalation phase followed by a 4-week maintenance phase. Randomization was stratified according to whether or not patients were currently using neurotoxic antiretroviral therapy (ART). RESULTS: The number of patients randomized was 92 (62 LTG, 30 placebo) in the stratum receiving neurotoxic ART and 135 (88 LTG, 47 placebo) in the stratum not receiving neurotoxic ART. Mean change from baseline in Gracely Pain Scale score for average pain was not different between LTG and placebo at the end of the maintenance phase in either stratum, but the slope of the change in Gracely Pain Scale score for average pain reflected greater improvement with LTG than with placebo in the stratum receiving neurotoxic ART (p = 0.004), as did the mean change from baseline scores on the Visual Analogue Scale for Pain Intensity and the McGill Pain Assessment Scale and patient and clinician ratings of global impression of change in pain (p </= 0.02). The incidence of adverse events, including rash, was similar between LTG and placebo. CONCLUSIONS: Lamotrigine was well-tolerated and effective for HIV-associated neuropathic pain in patients receiving neurotoxic antiretroviral therapy. Additional research is warranted to understand the differing response among patients receiving neurotoxic antiretroviral therapy compared with those not receiving neurotoxic antiretroviral therapy.

Adult↗
PubMed2003

DNA injection in combination with electroporation: a novel method for vaccination of farmed ruminants.

Injection of plasmid DNA encoding antigens into rodents followed by electroporation improved the immune response when compared with injection without electroporation (Widera et al. J Immunol 2000;164:4635-40; Zucchelli et al. J Virol 2000;74:11598-607; Kadowaki et al. Vaccine 2000;18:2779-88). The present study describes the extension of this technology to farm animals, by injecting plasmid DNA encoding mycobacterial antigens (MPB70, Ag85B and Hsp65) into the muscles of goats and cattle using two different types of electrodes, both allowing DNA delivery at the site of electroporation. The animals were vaccinated under local anaesthesia without any observed immediate or long-term distress or discomfort, or any behavioural signs of muscle damage or pathological changes after the electroporation. DNA-injected and electroporated goats showed increased humoral response after the primary vaccination when compared with nonelectroporated animals. Improved T-cell responses following electroporation were observed in hsp65 DNA-vaccinated cattle. DNA injection with or without electroporation did not compromise the specificity of the tuberculin skin test. In conclusion, a protocol applying in vivo electroporation free of side effects to farmed ruminants was established. In addition, we show that DNA vaccination in combination with electroporation can improve the primary immune responses to the encoded antigens.

Animals↗
PubMed2003

Modulation of the bovine delayed-type hypersensitivity responses to defined mycobacterial antigens by a synthetic bacterial lipopeptide.

The use of defined protein and peptide antigens can overcome specificity limitations of purified protein derivatives in the detection of bovine tuberculosis when the antigens are used in blood-based tests. Since the use of these specific antigens as skin test reagents could have practical advantages, we investigated the potential of Mycobacterium bovis-specific antigens to stimulate delayed-type hypersensitivity (DTH) responses in cattle experimentally infected with M. bovis. A cocktail of the recombinant antigens ESAT-6, MPB83, and MPB64 failed to stimulate in vivo DTH in cattle that had been experimentally infected with M. bovis despite the fact that the antigens were recognized in vitro by the same animals. However, it was possible to stimulate antigen-specific bovine DTH responses by using ESAT-6 in combination with a synthetic bacterial lipopeptide. This lipopeptide stimulated the release of the proinflammatory cytokine tumor necrosis factor alpha from monocyte-derived bovine dendritic cells in vitro, thereby providing a possible mechanism for its DTH-enhancing properties.

Animals↗
PubMed2001

HIV-1 reverse transcriptase sequence in plasma and cerebrospinal fluid of patients with AIDS dementia complex treated with Abacavir.

OBJECTIVE: To assess HIV-1 RNA levels and the relationship between HIV-1 reverse transcriptase (RT) genotype from plasma and cerebrospinal fluid (CSF) during treatment with abacavir (Ziagen, ABC) or placebo in combination with stable background therapy (SBG) in subjects with AIDS dementia complex (ADC) (study CNA3001). DESIGN: One-hundred and five HIV-1 infected adults with ADC were randomized to receive either ABC (600 mg twice daily) or ABC-matched placebo (twice daily) in addition to SBG for 12 weeks. METHODS: Plasma and CSF were collected for population sequencing at baseline and week 12 (CSF optional). Sequences were analyzed for mutations associated with resistance to nucleoside reverse transcriptase inhibitors (NRTI). RESULTS: Sixty out of sixty-seven subjects with baseline plasma HIV-RT sequence data harbored virus with > or = 1 NRTI-associated mutations; 50 out of 67 had the M184V mutation. At week 12, more subjects in the ABC group had plasma HIV-1 RNA < or = 400 copies/ml than the SBG group (46% versus 13%, P = 0.002). Non-response to ABC was associated with multiple baseline zidovudine (ZDV)/stavudine (d4T)-associated mutations. Baseline RT mutation patterns differed in 14 out of 21 (67%) paired samples from plasma and CSF. Four subjects experienced > 1 log10 copies/ml reductions in CSF HIV-1 RNA, two in the absence of reductions in plasma HIV-1 RNA and two with undetectable plasma HIV-1 RNA at baseline. CONCLUSIONS: Substantial decreases in plasma and CSF HIV-1 RNA following addition of ABC were not precluded by baseline HIV-1 NRTI-associated mutations, including the M184V mutation, but non-responders commonly harbored multiple ZDV/d4T-associated mutations. HIV-1 RNA responses and RT genotype appear to be discordant between CSF and plasma in some subjects.

AIDS Dementia Complex↗
PubMed2000

Effective DNA vaccination of cattle with the mycobacterial antigens MPB83 and MPB70 does not compromise the specificity of the comparative intradermal tuberculin skin test.

The current tuberculin test and slaughter strategy for the control of bovine tuberculosis in cattle has failed to prevent a sharp rise in cases over recent years, especially in the south-west of England. A recent scientific review has concluded that the development of a cattle vaccine holds the best prospect for tuberculosis control in British herds. In order to continue with test and slaughter-based control strategies, the development of TB vaccines that do not compromise the specificity of the tuberculin skin test are required. This report describes results of cattle vaccination experiments with TB DNA vaccines expressing the mycobacterial antigens MPB70, MPB83, and Ag85A and constitutes the first published vaccination study with DNA vaccines undertaken in a target host species. All calves vaccinated with the MPB83 expressing plasmid demonstrated potent cellular immune responses, characterised by CD4(+) T cells producing interferon-gamma as well as humoral immunity characterised by IgG1 biased specific antibodies. Vaccination with MPB70 was less effective with immune responses only observed in half of the vaccinated animals, while vaccination with Ag85A did not result in vaccine-induced immune responses. Intramuscular vaccination was found to stimulate stronger cellular responses than intradermal immunisation. Significantly, the specificity of tuberculin skin testing was not compromised by DNA vaccination since none of the vaccinated calves showed positive skin test reactivity.

Administration, Cutaneous↗
PubMed1998

Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. AIDS Clinical Trials Group 243 Team.

BACKGROUND: Progressive multifocal leukoencephalopathy affects about 4 percent of patients with the acquired immunodeficiency syndrome (AIDS), and survival after the diagnosis of leukoencephalopathy averages only about three months. There have been anecdotal reports of improvement but no controlled trials of therapy with antiretroviral treatment plus intravenous or intrathecal cytarabine. METHODS: In this multicenter trial, 57 patients with human immunodeficiency virus (HIV) infection and biopsy-confirmed progressive multifocal leukoencephalopathy were randomly assigned to receive one of three treatments: antiretroviral therapy alone, antiretroviral therapy plus intravenous cytarabine, or antiretroviral therapy plus intrathecal cytarabine. After a lead-in period of 1 to 2 weeks, active treatment was given for 24 weeks. For most patients, antiretroviral therapy consisted of zidovudine plus either didanosine or stavudine. RESULTS: At the time of the last analysis, 14 patients in each treatment group had died, and there were no significant differences in survival among the three groups (P=0.85 by the log-rank test). The median survival times (11, 8, and 15 weeks, respectively) were similar to those in previous studies. Only seven patients completed the 24 weeks of treatment. Anemia and thrombocytopenia were more frequent in patients who received antiretroviral therapy in combination with intravenous cytarabine than in the other groups. CONCLUSIONS: Cytarabine administered either intravenously or intrathecally does not improve the prognosis of HIV-infected patients with progressive multifocal leukoencephalopathy who are treated with the antiretroviral agents we used, nor does high-dose antiretroviral therapy alone appear to improve survival over that reported in untreated patients.

AIDS-Related Opportunistic Infections↗
PubMed1998

Cerebellar degeneration associated with human immunodeficiency virus infection.

Cerebellar disorders associated with HIV infection are typically the result of discrete cerebellar lesions resulting from opportunistic infections such as toxoplasmosis and progressive multifocal leukoencephalopathy or primary CNS lymphoma. Clinical symptoms and pathologic abnormalities related to the cerebellum may also be observed with HIV dementia. A primary cerebellar degeneration with HIV has not previously been reported. Ten patients were identified over an 8-year period at five medical centers. All patients had clinical, laboratory, and radiologic evaluations, and three had neuropathologic examinations. Patients presented with progressively unsteady gait, slurred speech, and limb clumsiness. Examination revealed gait ataxia, impaired limb coordination, dysarthria, and abnormal eye movements. Cognition, strength, and sensory function remained normal. CD4 lymphocyte counts varied between 10 and 437 cells/mm3. Neuroimaging studies showed prominent cerebellar atrophy. Neuropathology showed focal degeneration of the cerebellar granular cell layer and unusual focal axonal swellings in the brainstem and spinal cord. Cultures, histopathology, and immunochemical studies showed no conclusive evidence of infection. We report a syndrome of unexplained degeneration of the cerebellum occurring in association with HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Erythropoietin response in anaemic patients with multiple myeloma and other lymphoid malignancies infiltrating the bone marrow.

Immunoreactive erythropoietin levels were measured in 42 patients with lymphoid malignancies with anaemia and bone marrow involvement. Results were compared to a control group of 16 patients suffering from anaemia due to other causes. Significant inverse correlations between serum erythropoietin level and haemoglobin concentration were shown for the patients with lymphoid malignancies and also for the control subjects. Overall, the erythropoietin levels of patients with lymphoid malignancies with bone marrow infiltration and with normal renal function did not differ significantly from erythropoietin levels of the anaemic controls. We conclude that anaemia in patients with lymphoproliferative disorders with bone marrow infiltration and normal renal function is caused primarily by a diminished/inadequate response to erythropoietin at the level of the target cell.

Anemia↗
PubMed1986

Plasma vitamin E levels in a chronically hemolyzing group of dialysis patients.

Plasma vitamin E levels and the ascorbate cyanide test were assessed in 15 chronic hemodialysis (HD) patients (group A) exposed to persistently elevated chloramine levels in the dialysis water. The vitamin E levels in these patients, who had evidence of oxidant induced hemolytic anemia, were compared to 15 chronic HD patients exposed to low chloramine levels (group B) and 17 controls (group C). Vitamin E levels were found to be significantly lower in group A than in either groups B or C (p less than 0.001). Within group A, levels were lower in those patients who had a positive ascorbate cyanide test (p less than 0.05). Upon removal of chloramines from the dialysis water, vitamin E levels in group A were no longer significantly different from those found in groups B or C.

Ascorbic Acid↗
PubMed1978

A one-year report on rights violations under Michigan's new protection system.

A total of 1034 complaints were received in the first 11 months after the implementation of Michigan's new system to safeguard the rights of recipients of services from state institutions. Twenty-eight per cent of the complaints resolved during that period were substantiated as violations of statutorily protected rights. Both the volume of complaints and the number of substantiated violations were far higher in hospitals for the mentally ill than in facilities for the mentally retarded; however, facilities for the retarded had twice the percentage of substantiated complaints. There were significant differences in the numbers and categories of complaints and substantiated violations both between the two types of institutions and between large and small institutions. The findings sugtest directions for further action by the institutions and by the state office of recipient rights, which was established to oversee the system.

Consumer Behavior↗
PubMedDate not supplied

Group interventions for anger in people with intellectual disabilities.

This paper describes an evaluation of a group intervention for reducing inappropriately expressed anger (as aggression) in people with intellectual disabilities. Group intervention was compared to a treatment as usual group consisting of people referred to the group but who had to wait to participate. The intervention used was based on the work of Novaco (1976; 1978) and Benson (1994). However, further modifications to the group that emphasized the contextual perspective of anger, such as the participants being accompanied by a support worker and more collaborative recording procedures, were devised. A reduction in expressed anger and measured levels of depression occurred after group treatment. Reductions in expressed anger were maintained at 6 and 12 months follow up. However, scores on the depression scale tended to increase on follow up. While caution must be expressed when considering these results, this type of intervention shows promise for reducing inappropriately expressed anger in people with intellectual disabilities Suggestions are made for future research and clinical practice.

Adult↗