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Biomedical subjects

P Robinson

Publications and source records attributed to P Robinson.

At least 181 records · Page 10Linked to original sources

Transmission of HIV in a dental practice--the facts.

There is compelling evidence that six patients of a Florida dentist were infected with HIV at the dental practice. The strain of HIV in the dentist and patients was virtually identical. There is no evidence that either lapses in infection control or deliberate attempts to infect patients were responsible for this cluster of cases. Recent media analyses have emphasised that handpieces should be taken seriously as a potential source of cross infection but no evidence is available to confirm this as the route in the Florida practice. The unusual circumstances leading up to the detection of this cluster suggest that there could be other undetected cases and clusters.

Adolescent↗

Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes.

Insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice results from the T-lymphocyte-mediated destruction of the insulin-producing pancreatic beta-cells and serves as a model for human IDDM. Whereas a number of autoantibodies are associated with IDDM, it is unclear when and to what beta-cell antigens pathogenic T cells become activated during the disease process. We report here that a T-helper-1 (Th1) response to glutamate decarboxylase develops in NOD mice at the same time as the onset of insulitis. This response is initially limited to a confined region of glutamate decarboxylase, but later spreads intramolecularly to additional determinants. Subsequently, T-cell reactivity arises to other beta-cell antigens, consistent with intermolecular diversification of the response. Prevention of the spontaneous anti-glutamate decarboxylase response, by tolerization of glutamate decarboxylase-reactive T cells, blocks the development of T-cell autoimmunity to other beta-cell antigens, as well as insulitis and diabetes. Our data suggest that (1) glutamate decarboxylase is a key target antigen in the induction of murine IDDM; (2) autoimmunity to glutamate decarboxylase triggers T-cell responses to other beta-cell antigens, and (3) spontaneous autoimmune disease can be prevented by tolerization to the initiating target antigen.

Aging↗

Environmental correlates of child copula verb growth.

A recurring result from studies which relate the frequency of input variables to rate of language development, is the link between auxiliary verb growth and yes-no questions addressed to children. Explanations for this relationship usually concentrate on the advantages of hearing stressed and non-contracted auxiliary forms in sentence-initial position over hearing unstressed, contracted forms in medial position in declaratives. If such accounts are correct, then it can be predicted that yes-no questions which place forms of COPULA be in initial position will also increase the rate of growth of children's COPULA verb development. This prediction was tested using a sample of 33 children, carefully matched for stage of language development at 1;9 and 2;0 years; rate of copula verb growth was then measured over the succeeding nine months. Analyses include an examination of the contribution of sub-categories of yes-no question, tag questions, and utterances containing sentence-final copulas to the growth of contracted and full copulas. Results confirm that the frequency of inverted copulas in yes-no questions predicts children's copula development. Nevertheless, caution is urged before interpreting the relationship in terms of a direct causal model.

Acoustic Stimulation↗

The role of nuclear medicine in acute gastrointestinal bleeding.

In most patients with upper gastrointestinal (GI) bleeding endoscopy will locate the site and cause of bleeding, and also provide an opportunity for local therapy. The cause of lower GI bleeding is often difficult to attribute, even when pathology is found by colonoscopy or barium enema. Nuclear medicine techniques can be used to identify the site of bleeding in those patients in whom the initial diagnostic procedures are negative or inconclusive. Methods using transient labelling of blood (e.g. 99Tcm-sulphur colloid) produce a high target-to-background ratio in positive cases, give quick results and localize bleeding sites accurately, but depend upon bleeding being active at the time of injection. Techniques using stable blood labelling (e.g. 99Tcm-labelled red blood cells) may be positive even with intermittent bleeding but may take several hours to produce a result and are less precise in localization. In order for these methods to become more widely accepted by physicians and surgeons, and for them to be cost-effective, patients should be carefully selected. The most useful application is in patients with recurrent or prolonged bleeding, those with inconclusive endoscopy or barium studies, and those who are high-risk surgical candidates.

Acute Disease↗

Patient education for self-referral and on-demand treatment for herpes zoster in lymphoma patients.

The aim of this study is to evaluate the benefit of educating lymphoma patients in early self-diagnosis of zoster and subsequent self-referral for prompt treatment. Each of 337 patients attending an out-patient lymphoma clinic was given an explanatory leaflet and photograph about shingles when they first presented with lymphoma. One to two years following the completion of therapy for lymphoma an assessment was made on these patients using a combination of questionnaire survey and retrospective analysis of case notes. Fifty-six (16.6%) of the study population developed zoster following the diagnosis of lymphoma; 29 had had zoster prior to the diagnosis (8.6%). There was an increased incidence of herpes zoster in patients with Hodgkin's disease as compared to those with non-Hodgkin's lymphoma (P < 0.01). Patients who remembered having received the shingles education leaflets were more likely to make self-referral to hospital for prompt treatment (P < 0.001). Long-term complications, eg post-herpetic neuralgia, were less prevalent in patients presenting to hospital for prompt on-demand therapy, compared to those treated in the community. Education of lymphoma patients regarding awareness of early features of zoster is beneficial in preventing complications, but the shingles information episode needs subsequent reinforcement for maximum benefit.

Acyclovir↗

Nasal packing after routine nasal surgery--is it justified?

Ninety-five patients undergoing routine nasal surgery were enrolled into a randomized, prospective trial to investigate the efficacy and morbidity of nasal packing. The patients were randomized to receive a bismuth iodoform paraffin paste (BIPP) pack, a Telfa pack or no pack. Patients for septal surgery were randomized between the BIPP and Telfa groups only. They were independently randomized to receive or not receive, a silastic nasal splint for the first post-operative week. Post-operative pain levels were analysed using a visual analogue scale. Mean pain scores were increased 50 per cent by the use of nasal packs and pack removal, particularly BIPP which, was a most painful event (p < 0.001). Reactionary haemorrhage occurred in only two patients (2.1 per cent), both of whom had packs in situ. Vestibulitis was unique to the patients with a silastic splint, who were packed with BIPP, occurring in 21 per cent of them. Similarly septal perforation was unique to this group. There was no significant difference in the incidence of adhesions between the groups which received packs and those who did not. Routine nasal packing, especially with BIPP, would seen difficult to justify in view of the increased pain levels and increased complications which occur without any demonstrable benefit in the majority of patients. Therefore packing should be reserved for cases where there is concern about persistent haemorrhage. In these cases Telfa would be preferable to BIPP.

Adult↗

Deactivation of visual transduction without guanosine triphosphate hydrolysis by G protein.

G proteins couple receptors to their target enzymes in many signal transduction cascades. It has generally been thought that deactivation of such cascades cannot occur without the hydrolysis of guanosine triphosphate (GTP) by G protein. This requirement has now been reexamined in both vertebrate and invertebrate phototransduction. Results indicate that GTP hydrolysis is not required for deactivation. Evidence is presented for an alternative model in which the target enzyme is deactivated by an inhibitory factor that is available even when GTP hydrolysis is blocked.

Animals↗

A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. The NIAID AIDS Clinical Trials Group and Mycoses Study Group.

BACKGROUND: After primary treatment for cryptococcal meningitis, patients with the acquired immunodeficiency syndrome (AIDS) require some form of continued suppressive therapy to prevent relapse. METHODS: We conducted a multicenter, randomized trial that compared fluconazole (200 mg per day given orally) with amphotericin B (1 mg per kilogram of body weight per week given intravenously) in patients with AIDS who had completed primary therapy for cryptococcal meningitis with amphotericin B (greater than or equal to 15 mg per kilogram). To be eligible, patients had to have at least two negative cultures of cerebrospinal fluid immediately before randomization. The primary end point was relapse of cryptococcal disease as confirmed by biopsy or culture. RESULTS: Of 218 patients initially enrolled, 119 were assigned to fluconazole and 99 to amphotericin B. Twenty-three patients were found not to have met the entry criteria; six other patients assigned to amphotericin B did not receive it and were lost to follow-up. Of the remaining 189 patients, after a median follow-up of 286 days 14 of 78 receiving amphotericin B (18 percent) and 2 of 111 assigned to fluconazole (2 percent) had relapses of symptomatic cryptococcal disease (P less than 0.001 by Fisher's exact test). There was a difference of 19 percent in the estimated probability of remaining relapse-free at one year between the fluconazole group (97 percent) and the amphotericin B group (78 percent) (95 percent confidence interval, 7 percent to 31 percent; P less than 0.001). Serious drug-related toxicity was more frequent in the amphotericin B group (P = 0.02), as were bacterial infections (P = 0.004) and bacteremia (P = 0.002). CONCLUSIONS: Fluconazole taken by mouth is superior to weekly intravenous therapy with amphotericin B to prevent relapse in patients with AIDS-associated cryptococcal meningitis after primary treatment with amphotericin B.

Acquired Immunodeficiency Syndrome↗

Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. The NIAID Mycoses Study Group and the AIDS Clinical Trials Group.

BACKGROUND: Intravenous amphotericin B, with or without flucytosine, is usually standard therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS). Fluconazole, an oral triazole agent, represents a promising new approach to the treatment of cryptococcal disease. METHODS: In a randomized multicenter trial, we compared intravenous amphotericin B with oral fluconazole as primary therapy for AIDS-associated acute cryptococcal meningitis. Eligible patients, in all of whom the diagnosis had been confirmed by culture, were randomly assigned in a 2:1 ratio to receive either fluconazole (200 mg per day) or amphotericin B. Treatment was considered successful if the patient had had two consecutive negative cerebrospinal fluid cultures by the end of the 10-week treatment period. RESULTS: Of the 194 eligible patients, 131 received fluconazole and 63 received amphotericin B (mean daily dose, 0.4 mg per kilogram of body weight in patients with successful treatment and 0.5 mg per kilogram in patients with treatment failure; P = 0.34). Treatment was successful in 25 of the 63 amphotericin B recipients (40 percent; 95 percent confidence interval, 26 percent to 53 percent) and in 44 of the 131 fluconazole recipients (34 percent; 95 percent confidence interval, 25 percent to 42 percent) (P = 0.40). There was no significant difference between the groups in overall mortality due to cryptococcosis (amphotericin vs. fluconazole, 9 of 63 [14 percent] vs. 24 of 131 [18 percent]; P = 0.48); however, mortality during the first two weeks of therapy was higher in the fluconazole group (15 percent vs. 8 percent; P = 0.25). The median length of time to the first negative cerebrospinal fluid culture was 42 days (95 percent confidence interval, 28 to 71) in the amphotericin B group and 64 days (95 percent confidence interval, 53 to 67) in the fluconazole group (P = 0.25). Multivariate analyses identified abnormal mental status (lethargy, somnolence, or obtundation) as the most important predictive factor of a high risk of death during therapy (P less than 0.0001). CONCLUSIONS: Fluconazole is an effective alternative to amphotericin B as primary treatment of cryptococcal meningitis in patients with AIDS. Single-drug therapy with either drug is most effective in patients who are at low risk for treatment failure. The optimal therapy for patients at high risk remains to be determined.

Acquired Immunodeficiency Syndrome↗

Rare non-mosaic trisomies in chorionic villus tissue not confirmed at amniocentesis.

This paper reports eight cases of non-mosaic, rare, and typically lethal trisomies diagnosed in chorionic villi and not confirmed by amniocentesis. Four cases were 47,XX,+16; two cases were 47,XX,+2; one was 47,XX,+12; and one was 47,XY,+7. There have been no known complications in any of these gestations. These eight cases were found in a series of approximately 12,000 samples processed in our laboratory (0.07 per cent). We conclude that (1) rare non-mosaic trisomy not reflecting the fetal condition is an occasional source of diagnostic ambiguity in chorionic villus sampling; and (2) when encountered, a follow-up amniocentesis should be recommended to the patient to confirm or rule out the abnormality. We propose the term 'confined placental abnormality' to describe non-mosaic trisomies and other related abnormalities found only in chorionic tissue.

Adult↗

Distribution of CCK binding sites in the human hippocampal formation and their alteration in schizophrenia: a post-mortem autoradiographic study.

The distribution of cholecystokinin binding sites has been visualized and quantified by quantitative autoradiography in the human hippocampus from post-mortem brains of 11 controls and 11 schizophrenics. CCK receptors were localized to subiculum and parahippocampal gyrus. In the cortical areas there was a particularly dense lamination of receptors. In the schizophrenic material a similar overall pattern was seen, but there were significant losses of receptors in CA1 subiculum and cortex. These findings confirm the distribution of CCK receptors in the retrohippocampal areas in man and also provide further support for earlier homogenate studies which have also shown a loss of CCK binding sites in schizophrenia. This effect was localized primarily to parahippocampal gyrus suggesting that CCK plays some role in the genesis of developmental abnormalities in this region.

Adult↗

Transfection of HLA-DR-expressing DAP.3 cells with a cDNA clone encoding the glycosyl phosphatidylinositol-linked form of lymphocyte function associated antigen-3: biochemical features and functional consequences.

Structural and functional aspects of the accessory molecule lymphocyte function associated antigen (LFA)-3 (CD58) have been examined following the transfection of DAP.3 and P815 cells with a cDNA clone encoding the glycosyl phosphatidylinositol (GPI)-linked form of human LFA-3. Despite earlier observations that DAP.3 cells are deficient in GPI anchoring LFA-3 was expressed efficiently on DAP.3, as well as on P815 cells. Immunoprecipitation of LFA-3 from 35S-labelled cells revealed that the molecule expressed on the DAP.3 cells had a molecular weight intermediate between the transmembrane and GPI-linked forms expressed by human B cells. This suggests that the DAP.3 cells have a default pathway whereby the RNA transcript which encodes the GPI-linked form of the molecule can also encode an integral membrane protein. Functionally, expression of LFA-3 by DAP.3 which had previously been transfected with the genes encoding HLA-DR1 led to a marked augmentation of the proliferative response of five out of eight anti-DR1 human T cell clones. This effect was not reproduced when DR1 and LFA-3 were expressed by separate populations of DAP.3 cells, suggesting that the ligands for CD2 and for the T cell's receptor must be expressed on the same cell membrane. Expression of human LFA-3 also led to a substantial increase in the proliferative response of human peripheral blood T cells to a DR alloantigen. Separation of T cells into CD45RO+ and CD45RO- populations revealed that the augmentation was more marked for the memory than the virgin population. The mechanisms responsible for these differences are discussed.

Animals↗

The morbidity from nasal splints in 105 patients.

The results of a randomized prospective trial investigating the morbidity from intranasal splints in 105 patients, were analysed. Intranasal splints are associated with considerable morbidity (significantly greater post-operative pain and a higher incidence of septal perforation and vestibulitis) and although they significantly reduce the likelihood of developing intranasal adhesions, a similar benefit can be obtained by careful nasal toilet at one week.

Adult↗