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Biomedical subjects

J Sheldon

Publications and source records attributed to J Sheldon.

At least 37 records · Page 2Linked to original sources

Dendritic cells derived from bone marrow and CD34+ selected blood progenitor cells of myeloma patients, cultured in serum-free media, do not contain the Kaposi sarcoma herpesvirus genome.

The aim of our study was to test if dendritic cells contain the KSHV genome. CD34+ peripheral blood progenitor cells (PBPC) and bone marrow mononuclear cells were cultured in X-VIVO 15 medium supplemented with GM-CSF and TNF-alpha in gas-permeable containers. Dendritic cells were identified morphologically and immunophenotypically. The KSHV genome was not identified in any of the cases using a nested primer PCR approach. Serological analysis corroborated the molecular findings: no antibodies for KSHV were found in any of the multiple myeloma patients. These data are of importance when considering use of DC for therapeutic approaches in multiple myeloma.

Antigens, CD34↗

C-reactive protein as an indicator of resolution of sepsis in the intensive care unit.

OBJECTIVE: To investigate the value of decreasing plasma C-reactive protein (CRP) concentrations as an indicator or resolution of microbiologically-proven sepsis. DESIGN: Retrospective analysis of CRP concentrations measured during episodes of microbiologically-proven sepsis. A receiver-operating characteristic (ROC) curve was used to assess the usefulness of CRP as a test for resolution of sepsis. SETTING: The intensive care unit (ICU) of a teaching hospital. PATIENTS AND PARTICIPANTS: 32 episodes of microbiologically-proven sepsis occurring in 18 patients were followed from diagnosis until resolution. MEASUREMENTS AND RESULTS: Daily routine observations and blood testing were performed prospectively. The daily presence or absence of systemic inflammatory response syndrome (SIRS) was prospectively determined according to standard definitions. Concentrations of CRP were analysed retrospectively once the patients had left the ICU. A decrease in CRP by 25% or more from the previous day's level was a good indicator of resolution of sepsis, with a sensitivity of 97%, specificity of 95% and predictive value of 97%. In 13 cases (46%), a decrease in CRP preceded clinical resolution of sepsis; this was more likely to occur in patients with less severe sepsis than in those with severe sepsis or septic shock. CONCLUSION: Daily measurement of CRP is useful for monitoring the course of microbiologically-proven sepsis in ICU patients, and may be used to indicate successful treatment.

Biomarkers↗

Radiation therapy of external iliac lymph nodes with lateral pelvic portals: identification of patients at risk for inadequate regional coverage.

PURPOSE: To determine whether "standard" lateral pelvic radiation therapy portals provide adequate margins for treating the external iliac lymph nodes (EILNs). MATERIALS AND METHODS: With computed tomographic (CT) data and a computerized algorithm, the course of the EILN chain was reconstructed in 48 patients. The marginal distance between a consistently localized portion of the EILNs and the anterior field border that was placed at the front of the pubic symphysis was recorded for each patient. RESULTS: The EILNs were covered adequately in only 50% of both men and women. More adequate EILN margins were observed in (a) women older than 68 years, (b) women with small anteroposterior separations, (c) men older than 70 years, and (d) men and women with a low central obesity index. Less adequate margins were observed in men who were obese or men with large anteroposterior separations. In the study population, no correlation was observed for sex, race, or tumor site. CONCLUSION: The authors recommend portals that are designed specifically for patients rather than standard portals that may inadequately cover the intended targets.

Adult↗

Role of infused CD8+ cells in the induction of peripheral tolerance.

The CD8 molecule when present on a cell recognized by a mature T cell has been shown to have an inhibitory effect on the development of an in vitro immune response by that T cell. To test whether CD8 has a role in the induction of peripheral tolerance in vivo, we have studied tolerance induction in B6 female mice carrying a transgenic TCR specific to male H-Y Ag. Previous studies have shown that male Ag reactive cells are inactivated in these mice after the i.v. injection of viable male lymphoid cells. Here, B6 female transgenic mice were injected with B6 male lymph node cells from CD4 or CD8 gene knockout mice, and the fate of male Ag-specific T cells was followed in vivo. Our results indicate that injection of male CD4 knockout (express CD8) lymphoid cells but not CD8 knockout (do not express CD8) lymphoid cells induced a significant reduction of male H-Y Ag reactive cells in the periphery, suggesting that CD8 plays an important role in the induction of peripheral tolerance of class I-restricted T cells. These results imply that peripheral tolerance can be induced not just by absence of signals required for activation but by the presence of additional signals.

Animals↗

Evaluation of a thicker condom for use as a prophylactic against HIV transmission.

In an evaluation of the breakage rate of a thicker condom when used for anal intercourse, one hundred and eight gay men volunteered to use condoms which were 30% thicker than standard condoms. Of the 772 condoms used, 14 broke during anal sex, representing a breakage rate of 1.8%. When one subject was removed from the sample because of inappropriate use of the condom, the overall breakage rate was 1.6%. This compares favorably with the breakage rates reported for condom use during anal sex in other investigations, and is similar to the breakage rate for condom use during vaginal intercourse.

Adult↗

Low-dose tumour necrosis factor alpha and melphalan in hyperthermic isolated limb perfusion.

Nine patients with soft tissue tumours of the lower limb not amenable to treatment other than by isolated limb perfusion or amputation underwent hyperthermic isolated limb perfusion at the level of the superficial femoral vessels, using a combination of recombinant tumour necrosis factor (TNF) alpha and melphalan. In seven patients with superficial tumours, necrosis and sloughing was apparent within 48 h of perfusion. All patients experienced a complete tumour response. There were no systemic side-effects associated with the use of TNF-alpha although local side-effects, particularly oedema, were pronounced. Three patients ultimately required amputation because of the large soft tissue defects that resulted from necrosis of the tumour and overlying skin.

Adult↗

The involvement of general practitioners in the care of patients with human immunodeficiency virus infection: current practice and future implications.

The objective was to determine the current use of their general practitioner (GP) by patients with human immunodeficiency virus (HIV) infection and whether such patients would be interested in having 'shared care' between a specialist HIV clinic and their GP. A questionnaire was administered to 203 HIV-positive men attending the HIV outpatient clinic of a central London teaching hospital. The main outcome measures were patient characteristics, numbers of patients registered with a GP, numbers of patients with a GP aware of their diagnosis, contacts with the GP in the last year and level of interest and shared care. Eighty-five per cent of patients were registered with a GP of whom 67% knew of the diagnosis. Those diagnosed for more than 2 years were significantly more likely to have an informed GP. A total of 73% of those registered had visited their GP in the previous year although only 27% had visited for an HIV-related problem. Only 19% had a GP actively involved in their HIV care. In all 51% of the patients indicated an interest in having shared care between the clinic and their GP. A high proportion of HIV patients are registered with and attend a GP although they rarely consult for HIV-related problems. A significant proportion of patients expressed interest in having shared care suggesting that there is the potential for increased GP involvement in the care of patients with HIV infection.

Adolescent↗

C-reactive protein and its cytokine mediators in intensive-care patients.

C-reactive protein (CRP) is an acute-phase protein produced by the liver during bacterial infections and inflammation. The cytokines interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF) are widely reported to induce synthesis of CRP by hepatocytes both in vitro and in vivo. We investigated the relation between CRP and its cytokine mediators in 64 critically ill patients during their treatment in the intensive-care unit. Plasma CRP and IL-6 concentrations were significantly lower in patients without any evidence of infection than in those with clinical infection; plasma IL-1 beta concentrations showed no significant difference between any of the groups, but plasma TNF concentrations were lower in patients with evidence of infection. Significant correlation was seen between plasma concentrations of CRP and IL-6 when the latter was measured by bioassay; however, IL-6 showed, at best, only a 50% predictive value for a change in CRP concentration.

Bacterial Infections↗

Neuroanatomic differences between dyslexic and normal readers on magnetic resonance imaging scans.

The areas of six bilateral brain segments in the right and left hemispheres, on a horizontal brain section, and the area of subdivisions of the corpus callosum, on a midsagittal brain section, were measured on magnetic resonance images obtained from 21 dyslexic and 29 control subjects. In the entire group, the frontal half of the horizontal brain section showed asymmetry, with the right side being larger, whereas posteriorly only the occipital polar segment was asymmetrical, with the left side being larger. Dyslexic subjects exhibited asymmetry, with the right side greater than the left side, in contrast to the relatively symmetrical pattern that is normally observed in the midposterior segment that corresponds to the angular gyrus. In the corpus callosum, dyslexic subjects were found to have a larger splenium than nondyslexic subjects, and dyslexic female subjects were found to have a larger splenium than dyslexic male subjects. Because transcallosal pathways connecting the left and right angular gyrus regions traverse through the splenium of the corpus callosum, the above findings in dyslexic subjects suggest an anatomic abnormality in the angular gyrus region.

Adult↗

Cytokine induction of neopterin production.

The pteridine neopterin is a marker of immunological activation and has been shown to be a useful marker of graft-versus-host disease (GVHD) in bone marrow transplant patients. High levels of both neopterin and interferon-gamma (IFN-gamma) were produced in vitro during mixed lymphocyte responses, which may be considered to be a model of the primary events leading to GVHD. Neopterin was shown to be produced by monocytes in response to stimulation with IFN-gamma, but not other cytokines. However, the interleukins IL-1 alpha, IL-1 beta, IL-2, and tumour necrosis factor (TNF) alpha and beta, but not IL-6, stimulated neopterin production by unfractionated peripheral blood mononuclear cells (PBMC), and culture supernatants from PBMC stimulated with IL-1 alpha, IL-1 beta, IL-2 and IL-6, but not TNF-alpha or TNF-beta induced neopterin production following transfer to fresh monocyte cultures. It therefore appears that cytokines may generate neopterin by induction of IFN-gamma, by synergy with low levels of induced IFN-gamma, or by non-IFN-gamma-dependent mechanisms.

Biopterins↗

Overestimation of monoclonal immunoglobulin by immunochemical methods.

A comparison of paraprotein estimation by scanning densitometry with corresponding immunoglobulin concentration measured by rate immunonephelometry, fixed-time immunonephelometry and kinetic immunoturbidimetry using a large number of sera has indicated overestimation of the immunoglobulin by liquid phase immunoassays in the presence of a monoclonal component. The effect was seen with all three major immunoglobulin isotypes but was most marked with IgM paraproteins when measured by kinetic nephelometry. The overestimations could not be explained by presence of rheumatoid factors or immune complexes in the serum samples, or by non-parallelism, over a range of dilutions, of the reaction of sample and calibrant with the antiserum. The source and species of antiserum used was a major contributory factor.

Antibodies, Monoclonal↗

C-reactive protein as a diagnostic test of sepsis in the critically ill.

Changes in the plasma concentration of C-reactive protein were assessed as a diagnostic test for sepsis in critically ill patients. Forty-nine episodes of secondary sepsis were identified in 31 patients. In 43 out of the 49 episodes there was a 25% or greater change in the concentration of C-reactive protein on the day that sepsis was diagnosed but in six episodes of sepsis the change was less than 25%. A 25% rise in the plasma concentration of C-reactive protein in the absence of other non-infective causes of a raised C-reactive protein, such as inflammation, tissue injury or surgery, is highly suggestive of infection, but failure of the C-reactive protein to rise does not eliminate a diagnosis of sepsis.

Bacterial Infections↗