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Biomedical subjects

S Shaunak

Publications and source records attributed to S Shaunak.

At least 37 records · Page 2Linked to original sources
PubMed1998

Urgent neurology out-patient referrals from primary health care physicians.

We retrospectively analysed patients seen in a rapid referral clinic to identify those with abnormalities genuinely requiring urgent assessment, and to evaluate the impact of the clinic on routine services. After advertising the availability of the service, 25% of telephone referrals from primary-care physicians led to identification of patients considered suitable for urgent evaluation. We assessed 350 patients over an 18-month period. After neurological review, relevant abnormalities were identified in 73%, and 33% were considered to have warranted urgent assessment. In addition, 74% required radiological evaluation and 14% had a neurophysiological procedure; 19.4% were admitted on the same day, 13% underwent CSF analysis and 34% required some form of therapeutic intervention. In retrospect, patients with a clinical history of > 11 days rarely warranted urgent referral. Visual failure and diplopia provided the highest correlation with patients deemed to require urgent assessment, and syncope and headache the lowest. Despite the number of patients reviewed, no effect was demonstrated on waiting times for standard out-patient review.

Adolescent↗
PubMed1997

Anti-HIV type 1 activity of sulfated derivatives of dextrin against primary viral isolates of HIV type 1 in lymphocytes and monocyte-derived macrophages.

The anti-HIV-1 activity of sulfated derivatives of dextrin was tested in activated peripheral blood mononuclear cells and in monocyte-derived macrophages using low-passage syncytium-inducing and non-syncytium-inducing primary viral isolates of HIV-1. All four compounds blocked infection in a dose-dependent manner. Dextrin 2-sulfate blocked infection with a 90% inhibitory concentration (IC90) of 69 microg ml(-1). The IC90 for dextrin 3-sulfate was 50 microg ml(-1) and for dextrin 6-sulfate was 14 microg ml(-1). Increasing the number of sulfate groups to three per glucan molecule (dextrin 2-, 3-, and 6-sulfate) did not reduce the IC90 further (13 microg ml(-1)) compared to dextrin 6-sulfate. There was no significant difference in the concentration required to block infection of activated peripheral blood mononuclear cells when compared with monocyte-derived macrophages, irrespective of whether low-passage syncytium-inducing or non-syncytium-inducing primary viral isolates of HIV-1 were used. Dextrin 2-sulfate and dextrin 6-sulfate also reduced the transmission of HIV-1 in experiments performed using peripheral blood mononuclear cells from HIV-1-positive patients by 6- to 251-fold in a limiting dilution tissue culture infectious dose assay. Sulfated dextrins were not toxic to either primary lymphocytes or macrophages at the concentrations tested. Having previously shown that the cell surface binding of sulfated dextrins is dependent on the position of the negatively charged sulfate groups, we now show that their anti-HIV-1 activity in primary lymphocytes and macrophages is also dependent on the same arrangement. A phase I/II clinical trial of dextrin 2-sulfate is now in progress.

Anti-HIV Agents↗
PubMed1997

Abnormalities of predictive saccades in Parkinson's disease.

Saccades of patients with mild Parkinson's disease (PD) are said to be abnormal in the absence of a concurrently visible target or when they are part of a rapid sequence of eye movements. We tested this hypothesis using a predictive saccade paradigm in which target visibility is withdrawn for a period. Three rates of target alternation were used (0.25 Hz, 0.5 Hz and 1.0 Hz). Withdrawal of target visibility brought out the extremes of primary saccade gain for both the controls and the patients with PD, most undershoot being displayed at the lowest frequency, whereas the gain was greatest at the highest frequency, actually overshooting the target location. These results demonstrate that the spatial error of parkinsonian saccades does not invariably take the form of hypometria when part of a rapid sequence of eye movements.

Adult↗
PubMed1997

Cerebral nocardia abscesses in a patient with AIDS: correlation of magnetic resonance and white cell scanning images with neuropathological findings.

We present a case of cerebral nocardiosis in a patient with AIDS. Space-occupying lesions were identified using magnetic resonance imaging (MRI) and white cell scanning. Nocardia asteroides was isolated from blood cultures. The patient's response to treatment with amikacin, imipenem and ceftriaxone was followed clinically and radiologically. When he died 6 months later, N. asteroides was isolated at post-mortem from a cerebral abscess. Although cerebral infections associated with the infiltration of neutrophils are rare in patients with AIDS, this case demonstrates that indium-labelled neutrophils can be used to identify a brain abscess and monitor its response to antimicrobial therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Circular forms of unintegrated human immunodeficiency virus type 1 DNA and high levels of viral protein expression: association with dementia and multinucleated giant cells in the brains of patients with AIDS.

Thirty-one histologically abnormal brains from patients with AIDS were studied in order to establish the relationship between multinucleated giant cells, viral protein expression, the various forms of human immunodeficiency virus type 1 (HIV-1) DNA, and clinical evidence of dementia. Unintegrated HIV-1 DNA of 2 to 8 kb was found in 22 of the 31 brains. Multinucleated giant cells without any other pathology were found in 14 cases; unintegrated 1-long terminal repeat (1-LTR) circular forms of HIV-1 DNA and strongly positive immunohistochemistry for gp41 and p24 were found in most of these brains. Most of these patients had a clinical diagnosis of HIV-1-associated dementia and cerebral atrophy. In all the other brains studied, 1-LTR circles were absent and immunohistochemistry for gp41 and p24 was usually negative. Very few of these patients had a clinical diagnosis of dementia. Sequence comparison of the LTR region from integrated HIV-1 DNA with that from unintegrated 1-LTR circular forms of HIV-1 DNA in 12 cases showed no significant differences. A further comparison of these brain-derived LTR sequences with LTR sequences derived directly from lymphoid tissue also showed strong sequence conservation. The V3 loop of the virus from the brain was sequenced in 6 cases and had a non-syncytium inducing-macrophage-tropic genotype. Our results show that (i) although unintegrated HIV-1 DNA was present in most brains from patients with AIDS, molecular evidence of high levels of viral replication was associated with the presence of multinucleated giant cells and dementia, and that (ii) the HIV-1 LTR is not a determinant of neurotropism. These observations suggest that replication of HIV-1 and not just the presence of HIV-1 DNA within giant cells makes the important contribution to central nervous system damage.

AIDS Dementia Complex↗
PubMed1996

Combining specialist and primary health care teams for HIV positive patients: retrospective and prospective studies.

OBJECTIVE: To develop and evaluate a model of health care for HIV positive patients involving specialist, hospital based teams and primary health care teams. DESIGN: One year retrospective and a 2 1/2 year prospective study. SETTING: Two hospitals in West London and 88 general practitioners in 72 general hospitals. SUBJECTS: 209 adults with HIV infection. INTERVENTION: General practitioners enrolled in the project were faxed structured outpatient clinic summaries. When hospital inpatients were discharged, a brief discharge summary was faxed. General practitioners had access to consultant physicians skilled in HIV medicine through a 24 hour mobile telephone service. An HIV/AIDS management and treatment guide containing relevant local information was produced. Quarterly discussion forums for general practitioners were held, and a regular newsletter was produced. MAIN OUTCOME MEASURES: Hospital attendance and general practitioner consultations; perceived benefits and problems of patients and general practitioners. RESULTS: The average length of a hospital inpatient stay was halved for those patients who had participated in the project for two years, and the average number of visits to the outpatient clinic per month fell for patients with AIDS. There was a substantial increase in the number of visits to general practitioners by patients with AIDS and symptomatic HIV infection. Patients and general practitioners both felt that the standard of health care provided had improved. CONCLUSIONS: This model of health care efficiently and effectively utilised existing teams of hospital and primary health care professionals to provide care for HIV positive patients. Simple, prompt, and regular communication systems which provided information relevant to the needs of general practitioners were central to its success.

Adult↗
PubMed1995

Extra-nuclear location of histones in activated human peripheral blood lymphocytes and cultured T-cells.

Dextrin-2-sulphate (D2S) is a sulphated polysaccharide which inhibits human immunodeficiency virus type 1 infection of T-cells by binding to the cell surface. During our investigations of the nature of this interaction, a cell membrane fraction was prepared by ultracentrifugation from the T-cell line, HPB-ALL. Separation of membrane proteins by sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis and analysis for binding proteins using ligand blotting showed that 3H-D2S bound, in a saturable and displaceable manner, to two regions corresponding to molecular weights of 14,000-18,000 and 28,000-32,000. The N-terminal sequences of two of the major protein components in the 14,000-18,000 region were consistent with those of histones H2B and H3. The presence of histone H2B in the cell membrane preparation was confirmed by immunoblotting and enzyme-linked immunosorbent assay using a specific antibody. Histone standards were used to determine the level of each histone in the cell membrane fraction. In addition, the binding of 3H-D2S to purified histone standards was quantified. These results show that all of the binding of 3H-D2S to proteins in the 14,000-18,000 region of the cell membrane preparation can be attributed to the histones present. In contrast to HPB-ALL cells, a cell membrane fraction from freshly isolated human peripheral blood lymphocytes contained very low levels of histones. However, after culture with phytohaemagglutinin for 3 days the cell membrane fraction contained greatly increased levels of histones. To exclude the possibility of contamination of the cell membrane preparation with histones derived from the nucleus, cell membranes were also prepared using an affinity-based method using polyethyleneimine-cellulose. Immunoblotting of adsorbed plasma membranes showed the presence of histone H2B. SDS-polyacrylamide gels stained for protein also indicated that the preparation contained histones H1, H2A, H3 and H4. In further experiments whole cells were used to avoid contamination from nuclear proteins. Lactoperoxidase mediated 125I labelling, a method specific for radiolabelling cell surface proteins, confirmed the presence of histones H2B, H3 and H4 on the surface of HPB-ALL cells. Also, incubation of HPB-ALL cells or phytohaemagglutinin-activated peripheral blood lymphocytes with D2S caused displacement of histones from the cell surface into the supernatant without altering cell viability. In addition, immunocytochemistry of freshly isolated peripheral blood lymphocytes showed that histone H2B was located predominantly in the nucleus. However, in phytohaemagglutinin-activated peripheral blood lymphocytes immunoreactive material was also prominent in the endoplasmic reticulum and on the plasma membrane.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1995

Oculomotor function in amyotrophic lateral sclerosis: evidence for frontal impairment.

Saccadic eye movements, fixation, and smooth pursuit were recorded in 17 subjects with amyotrophic lateral sclerosis (ALS) and 11 age-matched controls using a magnetic scleral search coil. Reflexive, remembered and antisaccades, and smooth pursuit at four target velocities were studied. Subjects with ALS showed significantly elevated error rates (distractibility) and latency in the antisaccade and remembered saccade paradigms but no abnormality of reflexive saccades. The frequency of small saccades that intruded on steady fixation (square-wave jerks) was also increased in ALS subjects. Peak velocity gain of smooth pursuit and performance on the Wisconsin Card Sort Test did not differ significantly between the two groups. These findings are consistent with prefrontal dysfunction in ALS and provide an independent source of support for the thesis that the pathology of this condition invades frontal cortex.

Adult↗
PubMed1995

Eye movements.

Explore the source record for details and available documents.

Electronystagmography↗
PubMed1995

Treatment of adenoviral pneumonitis with intravenous ribavirin and immunoglobulin.

A 67 year old woman developed a severe adenoviral pneumonitis whilst receiving immunosuppressive therapy. She showed clinical and radiological evidence of a response to treatment with nebulised and intravenous ribavirin and intravenous pooled normal human immunoglobulin. To our knowledge this is the first time that such a therapeutic approach has been used in the treatment of a condition which normally carries a very high mortality.

Adenoviridae Infections↗
PubMed1995

Polymerase chain reaction in situ: an appraisal of an emerging technique.

Polymerase chain reaction (PCR) in situ is a new technique which promises to enhance considerably our ability to detect a few copies of target nucleic acid sequences in fixed tissues and cells. It has an enormous potential for application in diagnostic histopathology of viral diseases and in the study of gene expression. PCR in situ is, however, technically difficult, and amplification of the target DNA is only 30-300 fold. In this article we present an overview of PCR in situ techniques used to amplify both DNA and RNA targets (RT-PCR in situ). We also identify problems which can reduce the efficiency of the technique or which can give rise to false-positive results. They include (1) the inhibitory effects of cross-linking of histones to DNA or PCR amplification, (2) abstraction of PCR reagents by tissue-bonding agents which are used to coat glass slides, (3) poor denaturation of target DNA and subsequent DNA renaturation due to extensive cross-linking of histones to DNA, or because of incorrect temperature regulation of thermal cyclers, (4) false-positive results which arise from end-labelling of DNA strand breaks by Taq polymerase, and (5) diffusion of PCR products into and out of cells leading to false-positive results. We present some of the approaches that have been used to overcome some of these difficulties and suggest new avenues for investigation to improve this technique further.

Animals↗
PubMed1995

PCR in situ: aspects which reduce amplification and generate false-positive results.

PCR in situ promises the ability to amplify and detect very low levels of target nucleic acid in tissues. Despite considerable effort, the technique is still technically difficult and has not yet proved to be reliable or reproducible. We have now identified a number of factors which can contribute to the poor amplification of the target DNA and to the generation of false-positive signals. These factors include the effects of fixation, reagent abstraction, DNA degradation, DNA end-labelling and product diffusion. We present evidence to show that formaldehyde fixation cross-links histones to DNA and thus restricts the subsequent amplification of target sequences by PCR. End-labelling of DNA occurs when direct incorporation is used to detect amplified products and this gives rise to false-positive signals. Amplified products can also diffuse out of cells and into neighbouring cells which do not contain target sequences. They can undergo re-amplification within these cells giving rise to false-positive signals. We believe considerable caution should be exercised in the interpretation of results generated using PCR in situ.

Autoradiography↗
PubMed1994

Infection by HIV-1 blocked by binding of dextrin 2-sulphate to the cell surface of activated human peripheral blood mononuclear cells and cultured T-cells.

1. Structural analogues of a sulphated polysaccharide, dextrin sulphate, were synthesized and tested for their ability to block infection by HIV-1. Using the T-cell lines, C8166 and HPB-ALL, and the laboratory adapted strains of HIV-1.MN, HIV-1.IIIb and HIV-1.RF, dextrin 2-sulphate (D2S) combined the best combination of high anti-HIV-1 activity (95% inhibitory concentration (IC95) = 230 nM) and low anticoagulant activity. It also blocked infection of activated peripheral blood mononuclear (PBMN) cells by five primary viral isolates at an IC95 of 230-3700 nM depending upon the primary viral isolate tested. 2. In saturation binding studies, [3H]-D2S bound to a cell surface protein on HPB-ALL cells in a specific and saturable manner with a Kd of 82 +/- 14 nM and a Bmax of 4.8 +/- 0.3 pmol/10(6) cells. It bound to other human T-cell lines in a similar manner. 3. There was very little binding of [3H]-D2S to freshly isolated PBMN cells (Bmax 0.18 +/- 0.03 pmol/10(6) cells) and these cells could not be infected by HIV-1. Culture of PBMN cells in lymphocyte growth medium (LGM) containing IL-2 did not significantly change the Bmax of [3H]-D2S. In contrast, PBMN cells which had been cultured with phytohaemagglutinin (PHA; 5 micrograms ml-1) for 72 h had a Bmax of [3H]-D2S binding of 7.2 +/- 0.1 pmol/10(6) cells and these cells could be infected by HIV-1. Removal of the PHA and further culture of the PBMN cells in LGM containing IL-2 resulted in a fall in the Bmax to 2.0 +/- 0.1 pmol/10(6) cells. The Kd of binding did not change significantly during the course of these experiments.4. [3H]-D2S did not bind to freshly isolated erythrocytes or to erythrocytes which had been cultured in PHA for 72 h.5. These results suggest that there is a relationship between the expression of the [3H]-D2S binding protein on the plasma membrane of PBMN cells and the susceptibility of these cells to infection by HIV- 1.

Anticoagulants↗