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Biomedical subjects

D Wray

Publications and source records attributed to D Wray.

At least 55 records · Page 3Linked to original sources
PubMed1994

Recent non-sterile inoculation injuries to dental professionals in the Lothian region of Scotland.

A retrospective study of inoculation injuries in dental practice was conducted by means of a questionnaire distributed to 310 dental practitioners in the Lothian region of Scotland. Recent injuries were independently classified by a hospital dentist, general dental practitioner and immunologist as constituting high, moderate or low risk of transmission to the dentist. A consultant physician in infectious diseases assessed the follow-up actions. The results indicate that non-sterile inoculation injuries are a common hazard of dental practice with 56% of respondents reporting at least one such injury within the last year. A total of 30% of reported injuries constituted a moderate or high risk of transmission to the dental practitioner. Action taken following such injuries was often considered to be inadequate. While many injuries could possibly be avoided by changes in surgery design, avoidance of other injuries would probably require fundamental changes in routine dental practice. While the incidence of such injuries is high, dental practice within the UK appears to be associated with a low risk of acquiring HIV infection by occupational exposure. The increasing awareness of the importance of other blood-borne viral infections makes this a continuing issue.

Blood-Borne Pathogens↗
PubMed1994

Passive transfer of seronegative myasthenia gravis to mice.

Muscle weakness in myasthenia gravis is due to autoantibody-induced loss of functional acetylcholine receptors (AChR). About 15% of myasthenia gravis patients, however, do not have detectable anti-AChR antibodies. To investigate the effect of their plasma immunoglobulins on neuromuscular transmission, mice were injected with plasma (and in some cases purified immunoglobulin G (IgG)) from 7 "seronegative" myasthenia gravis (SMG) patients, and neuromuscular transmission parameters were examined. When injected for 15 days, all patients' plasma caused reductions in miniature endplate potential amplitudes, while endplate potential quantal content was significantly reduced by plasma from 4 of the 7 patients. There were no changes in ACh-induced depolarization or single channel properties, and 125I-alpha-bungarotoxin binding studies showed no effect on AChR number, except in 1 case. Purified IgG injected for 3 days had similar effects to plasma injected for 15 days. Our findings confirm that SMG is autoantibody mediated and that there are pathogenic IgG antibodies. SMG appears to be a heterogeneous disorder and the target(s) for the antibodies may be diverse.

Acetylcholine↗
PubMed1994

Modulation by protein kinase A of a cloned rat brain potassium channel expressed in Xenopus oocytes.

A potassium channel from rat brain was expressed in Xenopus oocytes in order to study modulation of channel function by phosphorylation via protein kinase A. Application of 8-Br-cAMP to oocytes expressing the drk1 channel (with the first 139 amino acids of the N terminus deleted, delta Ndrk1) caused a voltage-independent elevation of current amplitude, which was not seen for endogenous currents or for wild-type full-length drk1 channel. This effect on delta Ndrk1 was blocked by pre-injection of oocytes with Walsh-peptide protein kinase A inhibitor, suggesting mediation via protein kinase A. The protein kinase inhibitor also reduced both delta Ndrk1 and full-length drk1 currents. Substitution of the serine residues by alanine at one or both of the two consensus protein kinase A phosphorylation sites on the C terminus (residues 440 and 492) of delta Ndrk1 resulted in a loss of function of the expressed channels. These results indicate that phosphorylation via protein kinase A modulates drk1 channel function and that both consensus phosphorylation sites seems to be essential for channels to function.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Appropriate and inappropriate prescribing of narcotics for ambulatory HIV-positive patients.

OBJECTIVE: To assess the appropriateness of narcotic-prescribing practices in an ambulatory clinic for patients infected with HIV. DESIGN, SETTING, AND PATIENTS: The medical records of 220 (190 HIV-positive) patients, seen in a clinic primarily designed for the long-term follow-up of ambulatory HIV-infected patients and located in an inner-city, public teaching hospital, were retrospectively reviewed to determine the prevalence and appropriateness of prescribing Drug Enforcement Administration schedule 2 narcotics. Appropriateness was based on published guidelines for the use of narcotics in the treatment of cancer patients. MEASUREMENTS AND MAIN RESULTS: The prevalence of narcotic use among the HIV-positive patients was 15%. Narcotics were prescribed for 38% of the patients who died, 33% of those with AIDS [Centers for Disease Control and Prevention (CDC) clinical class C], 4% of those with AIDS-related complex (ARC) (CDC clinical class B), and 5% of asymptomatic HIV-positive patients (CDC clinical class A). None of the HIV-negative patients seen in the clinic received narcotics. Narcotics were more likely to be prescribed for patients with AIDS than for patients with ARC (p < 0.001) or for HIV-positive patients (p < 0.001). For the three CDC clinical classes, there was no significant difference among the proportions of patients receiving narcotics inappropriately (p = 0.108). Among the risk groups, intravenous drug abusers were more likely to be prescribed narcotics inappropriately than were men who were homosexual (p < 0.001) or individuals who were heterosexual (p = 0.013); transfusion recipients were also more likely to be prescribed narcotics inappropriately than were homosexual men (p = 0.026) or heterosexual men or women (p = 0.032). Narcotics were more likely to be prescribed for patients with disseminated histoplasmosis (p = 0.022), Pneumocystis carinii pneumonia (p = 0.001), candidal esophagitis (p = 0.020), Kaposi's sarcoma (p < 0.001), or wasted appearance (p = 0.043). Inappropriate prescriptions were more likely to be given to patients with dementia (p = 0.005) or wasted appearance (p = 0.019). CONCLUSIONS: Physicians tend to prescribe narcotics inappropriately to patients known to have previously abused drugs and to those who appear wasted or have dementia. Physicians have a duty to prescribe narcotics appropriately as guided by recognized medical indications and the patients' views concerning their current medical needs.

AIDS-Related Complex↗
PubMed1994

Occupational risk and precautions related to HIV infection among dentists in the Lothian region of Scotland.

This retrospective study used a postal questionnaire to measure occupational risks and to assess infection control procedures among 310 dental practitioners. The study comprised general dental practices in the Lothian region of Scotland, Lothian Health Board Community Dental Service and Edinburgh Dental Hospital. Altogether, 217 dental practitioners responded by the due date giving recall of inoculation injuries within the previous 5 years and infection control measures employed. The study revealed that 191 practitioners (88%) had completed a course of hepatitis B vaccination but one-third of them had not been tested for post-vaccination antibody. In 1991, two thirds of dentists (66%: 137 of 207 respondents) wore the same pair of gloves, and 80% of dentists (142 of 177 respondents) wore the same mask, for dealing with more than one patient. The usual practice was to change gloves during sessions (44%: out of 71 dentists) and to change masks for each session or less often (75%: 73 out of 97 dentists). The proportion of dentists who never used gloves fell from 56% in 1981 to 1% in 1991. An autoclave was used for sterilisation by 85% of practitioners in 1991. Reported non-sterile inoculation injuries averaged 1.7 (S.D. = 3.2) injuries per dentist in the previous year with 56% of practitioners having had an injury. The average was 6.8 (S.D. = 15.9) injuries per dentist in the previous 5 years with 76% of practitioners having had an injury. Of recent non-sterile inoculation injuries described by dental practitioners, 30% constituted a moderate or high risk of transmission of infection to the practitioner (43 of 141 described injuries). Combined with HIV seroprevalance rates, probabilities of transmission and numbers of practising dentists, the mean reported number of non-sterile inoculation injuries in the previous 5 years may be used to provide estimates of expected numbers of dental practitioners occupationally infected with HIV in the previous 5 years. U.K. estimates were 0.004 dentists in Lothian region and 0.05 dentists in the Thames region occupationally infected with HIV in the previous five years. Non-sterile inoculation injuries appear to be a common hazard of dental practice. In any year, most dentists are exposed to the risk of blood-borne viral infection. Despite a high reported incidence of such injuries, dental practice within the U.K. appears to carry a low risk of acquiring HIV infection from occupational exposure.

Dentists↗
PubMed1994

Characterization of somatostatin receptors on human neuroblastoma tumors.

Neuroblastoma is the most common extracranial solid tumor of children. Neuroblastoma tumors derive from the neural crest and synthesize neurotransmitters including the neuropeptide somatostatin. This study was designed to characterize somatostatin receptors both in primary neuroblastoma tumors and in two neuroblastoma cell lines, SKNSH and IMR32. Somatostatin receptors were identified in 6 of 7 Stage I and II compared to 7 of 19 Stage III and IV tumors. Down-regulation of somatostatin receptor binding was observed in five tumors during disease progression. A lack of high affinity binding of somatostatin was identified as a poor prognostic indicator; negative binding correlated with advanced disease and death. Somatostatin receptor binding was observed in the IMR32 cell line, but not in the SKNSH cell line. IMR32 cells demonstrated a single class of high affinity binding sites for both somatostatin and a synthetic analogue, octreotide (Kd 0.16 +/- 0.05 nM and 0.89 +/- 0.23 nM, respectively). Somatostatin and octreotide inhibited both vasoactive intestinal peptide-mediated and forskolin-mediated cyclic AMP accumulation in IMR32 cells. Somatostatin and octreotide inhibition of signal transduction was attenuated by pretreatment of the cells with pertussis toxin. Octreotide inhibited proliferation of IMR32 cells by 70% in a 6-day culture. In contrast, octreotide did not exhibit high affinity binding in SKNSH cells and had no effect on cyclic AMP accumulation or on proliferation in SKNSH cells. Together, these data indicate that octreotide interacts with high affinity somatostatin receptors to modulate signal transduction and regulate proliferation in neuroblastoma cell lines. These data also suggest that somatostatin receptor expression may be an independent prognostic factor in primary neuroblastoma tumors.

Binding, Competitive↗
PubMed1993

Non-competitive antagonism of calcium by magnesium ions at the K(+)-depolarised mouse neuromuscular junction.

The effect of raising the external Ca2+ concentration on miniature end-plate potential (m.e.p.p.) frequency was measured in the K(+)-depolarised mouse phrenic nerve/hemidiaphragm preparation in the presence of a range of Mg2+ concentrations. With increasing external Mg2+, a plot of external Ca2+ concentration vs. m.e.p.p. frequency was shifted to the right and the maximum frequency attained was reduced. A Schild plot of the data gave a slope factor close to two. These data suggest a non-competitive antagonism of Ca2+ by Mg2+ under these conditions.

Animals↗
PubMed1993

Cross-linking of presynaptic calcium channels: a mechanism of action for Lambert-Eaton myasthenic syndrome antibodies at the mouse neuromuscular junction.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of neuromuscular transmission. Immunoglobulin G (IgG) autoantibodies act presynaptically to cause functional loss of Ca2+ channels by down-regulation. This in turn causes reduced release of acetylcholine in response to nerve stimulation (i.e. reduced quantal content). We show here that in vitro application of LEMS IgG for 24 h was as effective in causing reduced quantal content in mice as injecting animals with the antibody for 2 days. Furthermore, incubation with divalent (F(ab')2) fragments also significantly reduced quantal content. However, monovalent (Fab) fragments were without significant effect. No antibody or antibody fragment preparation affected spontaneous release. Whole LEMS IgG and F(ab')2 (but not Fab) fragments also inhibited K(+)-evoked 45Ca2+ flux in a small cell carcinoma cell line. These findings present functional evidence that LEMS IgG-induced down-regulation of nerve terminal Ca2+ channels arises due to antibody cross-linking of these channels.

Acetylcholine↗
PubMed1993

Current classifications of HIV-associated periodontal diseases.

The occurrence of unusual and severe forms of periodontal disease in HIV-infected individuals is well recognised. Several classification schemes have been proposed in an effort to associate periodontal deterioration with progressive stages of HIV infection and to determine aetiological factors in tissue destruction. No classification to date has proved entirely satisfactory. This paper reviews current classification schemes and suggests an alternative based upon the periodontal status of a cohort of HIV seropositive patients in Edinburgh. The proposed classification includes 'conventional', non-specific gingivitis and adult periodontitis such as occur in HIV seronegative individuals, but which may also be seen in seropositive subjects. However, conditions termed linear gingivitis and necrotising periodontitis may be pathognomonic for HIV infection. It is recommended that the term 'HIV-associated' be dropped in relation to periodontal disease.

Gingivitis↗
PubMed1993

Comparative trial of fluconazole and amphotericin in the treatment of denture stomatitis.

The efficacy of fluconazole and amphotericin in the management of denture stomatitis was investigated in a comparative trial. Patients were assessed clinically, hematologically, and mycologically at the time of entry into the study and at 1, 4, and 12 weeks thereafter. A total of 29 patients were selected at random to receive 50 mg of fluconazole daily for 14 days; 30 patients were selected to receive amphotericin lozenges and cream for 28 days. Clinical response rates were similar in both treatment groups throughout the study. The best mycologic response was noted after 1 week whereas the best clinical response was observed after 4 weeks. Clinical evidence of relapse and recurrence at 12 weeks was a common finding irrespective of treatment. Side effects were uncommon in both groups.

Adult↗
PubMed1993

The prevalence of oral candidiasis in HIV-infected individuals and dental attenders in Edinburgh.

This study prospectively assessed the prevalence of oral candidal carriage and oral candidiasis in known HIV-seropositive individuals (n = 121) and other dental attenders in Edinburgh (n = 614). Candida species were isolated from 57.4% of dental attenders and 93.4% of HIV-seropositive subjects. Clinical evidence of oral candidiasis was observed in 6% and 52% of these groups respectively, erythematous forms of candidiasis being the commonest in both groups.

AIDS-Related Opportunistic Infections↗
PubMed1993

Immunohistochemical study of oral keratoses including lichen planus.

Biopsies of non-ulcerated oral mucosa from 13 patients with oral lichen planus and 12 patients with leukoplakia were immunohistochemically stained using monoclonal antibodies to pan T, pan B, T helper and T suppressor/cytotoxic cells and the stained lymphocytes enumerated using an image analyser. The results show the preponderance of T cells infiltrating both oral lichen planus and leukoplakia. The T helper: T suppressor/cytotoxic cell ratio was the same (1:2) for both oral lichen planus and leukoplakia. A similar proportion of T suppressor/cytotoxic cells was found infiltrating the epithelium. These data indicate that T cell subset analysis is of no value in distinguishing oral lichen planus from other oral keratoses.

Antibodies, Monoclonal↗
PubMed1993

Detection of Epstein-Barr virus and human papillomavirus type 16 DNA in hairy leukoplakia by in situ hybridisation and the polymerase chain reaction.

Demonstration of Epstein-Barr virus (EBV) is considered desirable for the accurate diagnosis of hairy leukoplakia (HL). Previous studies have reported possible associations with human papillomavirus (HPV) infection although this is not a universal finding. Presence of EBV and HPV 16 was examined in biopsy specimens from 18 cases of HL and ten control specimens by in situ hybridisation using digoxigenin-labelled synthetic oligonucleotide probes and by the polymerase chain reaction (PCR). The presence of EBV was demonstrated in 12 cases by both techniques. Of the remaining six cases EBV could be detected in three by in situ hybridisation but not by PCR; EBV was not detected by either method in a further three cases. All samples were negative for HPV 16 by both techniques under conditions of high stringency, although when stringency of in situ hybridisation was reduced, four samples appeared to harbour HPV DNA sequences. This study provides further evidence to support the role of EBV in the pathogenesis of HL and suggests that HPV 16 is not regularly encountered.

DNA Probes↗
PubMed1992

Multifocal hairy leukoplakia associated with Kaposi's sarcoma.

An HIV-seropositive patient presented with multifocal lesions of both hairy leukoplakia and Kaposi's sarcoma, hairy leukoplakia being present in the epithelium covering the Kaposi's sarcoma lesions. The findings suggest that hairy leukoplakia in immunocompromised patients is both more common and more widely distributed than is generally recognised.

Adult↗
PubMed1992

Periodontal bone loss in mice induced by different periodontopathic organisms.

Periodontal bone loss in mice orally inoculated with Peptostreptococcus anaerobius, Pept. magnus and Actinobacillus actinomycetemcomitans was compared to that in sham-inoculated mice. Six-to-8-week-old BALB/c mice were inoculated with 1 x 10(5), 1 x 10(7) or 1 x 10(9) colony-forming units (c.f.u.) of bacteria in 50 microliters of medium. Ten mice received each concentration of bacteria and 10 sham-inoculated mice acted as controls. Five mice from each of the groups were killed 6 weeks after inoculation and the remaining five mice at 12 weeks. Right hemimandibles were defleshed, stained and bone loss was measured using an image analyser. All the organisms tested were associated with bone loss. Animals that had received Pept. anaerobius and Pept. magnus had up to 18% more bone loss than those sham inoculated. In contrast, mice inoculated with A. actinomycetemcomitans had up to 38% more bone loss than the sham-inoculated animals, this amount of loss occurring at the lowest inoculation of 1 x 10(5) c.f.u. These data demonstrate a differential ability of micro-organisms to cause periodontal bone loss in mice.

Actinobacillus Infections↗