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Biomedical subjects

S Croft

Publications and source records attributed to S Croft.

At least 19 recordsLinked to original sources
PubMed2006

Do delays between diagnosis and surgery in resectable oesophageal cancer affect survival? A study based on West Midlands cancer registration data.

This retrospective study investigates if delays between the diagnosis of cancer of the oesophagus and surgical resection influence long-term survival. Data held by the West Midlands Cancer Intelligence Unit on 800 patients who underwent oesophagectomy for a diagnosis of cancer of the oesophagus or oesophagogastric junction between 1995 and 2000 were reviewed. Six hundred and thirty-two patients treated with curative intention and who had not received neo-adjuvant treatment in the form of radio- or chemotherapy were included in the analysis. The time interval between histological diagnosis and surgical resection was stratified into four groups: less than 3, 3-6, 6-9 and more than 9 weeks. The Cox proportional hazard model was used to test for the independent effect of delays. The results showed no difference in long-term survival according to the delay between histological diagnosis and surgical resection. On multivariate analysis adverse prognostic factors were advanced age, incomplete resection and lymph node involvement. Patients with a longer delay had a higher rate of complete tumour resection suggesting that they were more appropriately selected for the surgical treatment approach. In conclusion we have found no evidence that shorter delays from the date of histological diagnosis to surgical resection are beneficial to long-term survival.

Age Factors↗
PubMed2006

Miltefosine: issues to be addressed in the future.

Future issues that need to be addressed for miltefosine are efficacy against non-Indian visceral leishmaniasis, efficacy in HIV-coinfected patients, efficacy against the many forms of cutaneous and mucosal disease, effectiveness under clinical practice conditions, generation of drug resistance and the need to provide a second antileishmanial agent to protect against this disastrous event, and the ability to maintain reproductive contraceptive practices under routine clinical conditions.

Abnormalities, Drug-Induced↗
PubMed2005

The on-line characterization of a radium slurry by gamma-ray spectrometry.

We have developed an in-line monitor to directly measure the (226)Ra concentration in a nuclear waste stream using quantitative gamma-ray spectrometry applied to the 186keV emission. The waste stream is in the form of a slurry composed of the solid waste material mixed with water. The concentration measurement includes a self-attenuation correction factor determined from a transmission measurement using the 122keV gamma from (57)Co. Presented here is the model for the measurement system and results from some initial tests.

Industrial Waste↗
PubMed2005

Uncertainty in rate loss corrections based on counting a periodic pulser.

Tomographic gamma scanning of waste produces three-dimensional transmission and emission images. These are used to derive item-specific attenuation correction factors that improve the accuracy of non-destructive waste assay. For each vertical layer, data grabs of short duration are acquired as the waste item is rotated and translated. The image reconstruction demands accurate rate loss corrections to minimize assay bias. For this application a pulser was used to perform the necessary rate loss corrections. In this work, we summarize the benefits of the pulser approach and review the basic principles on which the method is based. We extend the treatment to include a derivation of the expression for the uncertainty in the net pulser peak area in the presence of an underlying continuum. We report experimental results, taken using a Canberra model WM2900 Tomographic Gamma Scanner, over a broad range of count-rates and peak-to-continuum ratios. Repeat counts under controlled conditions allowed the correction factor and its variance to be determined and compared against expectations. These results confirm the validity of the correction factor formula and the corresponding expression for its uncertainty. The rate loss analysis has been built into a Monte Carlo Replicate engine to allow the uncertainty to be propagated into the total measurement uncertainty of the final assay.

Gamma Rays↗
PubMed2004

Mast cells at the host-pathogen interface: host-protection versus immune evasion in leishmaniasis.

Infection of a susceptible host with Leishmania, a protozoan parasite, causes the disease leishmaniasis, which is characterized by neutrophil, eosinophil, macrophage, lymphocyte and mast cell infiltration into the infected tissue followed by parasite growth. Although the roles played by other cells in leishmaniasis are known, the role of mast cells remains to be ascertained. Here, we demonstrate that Leishmania regulates mast cell infiltration to the site of infection, mast cell production and mast cell function resulting in differential growth of the parasite in resistant (C57BL/6 or CBA/T6T6) and susceptible (BALB/c) macrophages. An interleukin-3-dependent augmentation in mast cell committed progenitors is observed in BALB/c but not in C57BL/6 mice during Leishmania infection. The mast cell supernatants inhibit IFN-gamma-dependent restriction of Leishmania growth in macrophages in BALB/c mice whereas the reverse phenomenon occurs in C57BL/6 mice. Our data reveals a different facet of host-pathogen interaction.

Animals↗
PubMed1999

In vitro antitrypanosomal activity of Moringa stenopetala leaves and roots.

The leaves and the root extracts of Moringa stenopetala were tested in vitro against trypomastigotes of Trypanosoma brucei, Trypanosoma cruzi and L. donovani amastigotes. The fresh root wood ethanol extract and the dried leaves acetone extract were found to be active against T. brucei with an ED(50) value of 9.2 microg/mL and 10.0 microg/mL respectively. All the other extracts were inactive against all the tested parasite forms.

Animals↗
PubMed1999

The measurement of U, Th and K concentrations in building materials.

A shielded high purity germanium detector has been used to measure the abundance of U, Th and K in aggregate, sand and cement. The measurements were performed in order to demonstrate that the materials contained less than 10 ppm U and less than 20 ppm Th and were therefore suitable for the construction of a low background shielding enclosure. A particular feature of this work is the simplicity of the absolute efficiency calibration. In brief the relative U and Th contents of each sample were derived by first determining the relative detection efficiency curve for each sample using the known relative gamma-ray emission probabilities of the U- and Th-decay series lines from the radionuclides naturally present. To obtain the true activities, the relative efficiency curves for each sample were scaled so that they passed through the absolute efficiency value measurement at 1461 keV using a sample containing KCl bought as an analytical reagent and requiring no special radiological handling precautions. A small experimentally estimated correction was applied for the difference in self absorption between the KCl and building materials due to the differences in material density. The 40K content of the unknown samples was obtained directly from the density adjusted KCl calibration. The measurements are believed to be accurate to approximately +/- 5% absolute.

Calibration↗
PubMed1999

SPECT monitoring of improved cerebral blood flow during long-term treatment of elderly patients with nootropic drugs.

PURPOSE: In normal aging persons, oxygen and glucose consumption progressively decreases with reduced cerebral blood flow (CBF), which could be responsible for age-related changes in cognitive functions. A data processing model with the use of Tc-99m SPECT of the human brain has been developed and found to be sensitive for monitoring the effects of drugs that increase CBF. In this study, the effect of two vasodilator drugs (the combination of pentifylline and nicotinic acid versus piracetam) was compared with the effect of placebo on CBF. MATERIALS AND METHODS: Thirty elderly volunteers had three different procedures using the Peelproc method to spatially standardize and compare CBF patterns by SPECT before and after drug intervention. The 30 patients were divided into five groups of six persons each who were randomly assigned in a 1:1 ratio to the treatment sequences consisting of three phases: the combination of pentifylline and nicotinic acid (C), piracetam (N), and placebo (P), or C-N-P; P-N-C; P-C-N; N-C-P; C-P-N; or N-P-C. Phases 1 to 3 each consisted of a baseline recording of parameters (day 0), treatment for 60 days (days 1 to 60), and recording of parameters after treatment (day 61). RESULTS: In elderly human volunteers (ages, 52 to 70 years), after 2 months of oral treatment with a combination of pentifylline and nicotinic acid (800 mg pentifylline, 200 mg nicotinic acid daily), SPECT results for the Peel-proc program indicated a statistically significant improvement in CBF of the total brain, with a more pronounced improvement in the cerebellum and frontal regions, where a definite shift from abnormal to normal blood flow was detected. Spontaneous communication from most of the volunteers suggested that they experienced an improvement in memory and general well-being from the combination treatment. After 2 months of oral treatment with piracetam (2.4 g daily) in elderly human volunteers, SPECT results indicated a regional improvement in CBF, particularly in the cerebellum. However, no beneficial effects with this drug were spontaneously reported. CONCLUSION: The in vivo method to quantitatively monitor the progress of long-term drug therapy on CBF described here could be useful to assess and even direct changes in therapy.

Administration, Oral↗
PubMed1998

Targeted radiotherapy with Sm-153-EDTMP in nine cases of canine primary bone tumours.

Nine dogs with primary bone tumours were treated with Samarium-153-EDTMP (Sm-153-EDTMP). Conventional treatment protocols were precluded by the size of the dogs and the owners' refusal of limb amputation. All the tumours were of the appendicular skeleton; 4 were confirmed osteosarcomas. The other 5 tumours were radiologically suspect for osteosarcoma. Bone scans were performed on all dogs using Technetium-99m-methylene diphosphonate (Tc-99m-MDP) before administration of Sm-153-EDTMP. Regions of interest were identified over the contralateral limb at the same site as the tumour and counts per pixel were recorded for the tumour and contralateral limb and expressed as a ratio. The dogs were given 1 injection of 37 MBq/kg (1 mCi/kg) of Sm-153-EDTMP intravenously. Thoracic and primary tumour site radiographs were taken at monthly or 2-monthly intervals to monitor progression of the primary tumour and search for evidence of metastasis. Two dogs showed no response to treatment, with an increase in bone pain, and were euthanased within 1 month. In 1 dog, a tumour of the scapula underwent complete involution and the dog is considered free of disease at 20 months post Sm-153-EDTMP treatment. The overall tumourcidal effect of a single dose of Sm-153-EDTMP on primary bone tumours was difficult to evaluate in this group of dogs, as, with one exception, all the primary tumours progressed over time and the dogs were euthanased. Pain control, for which Sm-155-EDTMP is used in man, was not evident, except in the dog that responded completely to treatment.

Age Factors↗
PubMed1996

Characterisation of protein isoprenylation in procyclic form Trypanosoma brucei.

Protein modification by isoprenylation is essential in mammals and other eukaryotes, but has not been demonstrated in the parasitic protozoa of the order kinetoplastida. A key regulatory enzyme of the mevalonate pathway, hydroxymethylglutaryl-coenzyme A reductase (HMG-R), and end products of the path, including dolichols, are present in Trypanosoma brucei. By metabolical labelling of procyclic form trypanosomes in the presence of compactin, an efficient inhibitor of HMG-R, followed by one-dimensional gel electrophoresis, we demonstrate that protein isoprenylation indeed takes place in this organism and at least 14 polypeptides bear the modification. Further characterization of labelled isoprenyl groups by methyl iodide cleavage and high pressure liquid chromatography identified both the farnesyl and geranylgeranyl moieties found covalently attached to proteins in other eukaryotes. The latter moiety was more abundant, as found in mammalian systems. Prolonged incubation with compactin grossly affected cell morphology and altered a number of subcellular structures as seen by electron microscopy. High concentrations of compactin were toxic, whilst lower concentrations were cytostatic. The primary morphological lesion is distinct from that of synvinolin, another inhibitor of HMG-R. The morphological changes correlated with a complete inhibition of HMG-R activity by compactin. Surprisingly there was a complete lack of HMG-R activity in procyclic cells grown for 1 or several days in 100 microM compactin, suggesting that degradation of the enzyme had occurred and compensatory upregulation mechanisms could not be successfully exploited by the parasite to overcome HMG-R inhibition. Subsequent alterations to the overall cell shape are seen after 3 days of compactin exposure. Overall these data indicate that T. brucei has an essential protein isoprenylation pathway that is conserved with the higher eukaryotes. Additionally, products of the MVA pathway are implicated in maintenance of cell architecture.

Animals↗
PubMed1995

A vaccine conjugate of 'ISCAR' immunocarrier and peptide epitopes of the E7 cervical cancer-associated protein of human papillomavirus type 16 elicits specific Th1- and Th2-type responses in immunized mice in the absence of oil-based adjuvants.

TraT protein, known as ISCAR (= Immunostimulatory Carrier), is one of a family of integral membrane proteins (Imps) of Escherichia coli representing powerful carrier molecules which when injected into experimental animals generate substantial antibody and T proliferative responses to molecules conjugated to it. We extend these findings to show that ISCAR functions to stimulate Th1- and Th2-type responses, including specific cytotoxic T cells and tumour protection. We report here that by conjugating to ISCAR a 19mer peptide containing linear B epitopes, a T helper (Th) epitope, and a H-2b-restricted T cytotoxic (CTL) epitope of E7 protein of human papillomavirus type 16 (HPV16), and immunizing C57B1/6 (H-2b) mice, we elicited (i) specific IgG2a and IgG1 antibodies; (ii) IL-2 and IL-4 production by specifically recalled lymph node cells in vitro; (iii) cytotoxic T lymphocytes which specifically killed both E7 peptide-pulsed, and whole E7 gene-transfected tumour target cells; and (iv) in vivo protection against an E7 gene-transfected tumour cell inoculum. These findings have implications for the design of vaccines to stimulate immune responses to endogenously processed target antigens (e.g. tumour-associated antigens) without the unwanted side effects of oil-based adjuvants. In addition they support the case for a E7-targeted therapeutic vaccine for HPV-associated human cervical cancer.

Adjuvants, Immunologic↗
PubMed1993

Augmentation of HIV-specific lymphoproliferation in HIV-infected individuals by TraT: a novel T-cell immunopotentiating agent.

OBJECTIVE: To evaluate the potential of TraT to restore HIV-specific cell-mediated immunity. DESIGN: CD4+ T cell-associated antiviral and recall antigen-specific lymphoproliferative responses are generally impaired or absent in HIV-infected individuals. METHODS: Using peripheral blood mononuclear cells (PBMC) from a group of asymptomatic and symptomatic HIV-infected individuals, we compared the immunomodulatory effects of exogenous interleukin-2 (IL-2) with the effects elicited by the bacterial integral membrane protein, TraT. RESULTS: Exogenous IL-2 enhanced lymphoproliferation induced by an immunodominant synthetic HIV gp41 analogue, gp41[8] (amino acids 593-604), in four out of 10 asymptomatics and six out of 19 symptomatics. In contrast, TraT acted synergistically with gp41[8] to augment HIV-specific proliferation with higher frequency and greater magnitude than exogenous IL-2. Moreover, this TraT-mediated enhancement of HIV-specific lymphoproliferation occurred in the majority of HIV-infected individuals, irrespective of CD4+ T-cell count in peripheral blood or disease status, and thus appears not to be major histocompatibility complex-restricted. TraT also augmented lymphoproliferation induced by well-known recall antigens and other less immunodominant HIV analogues. CONCLUSIONS: These findings suggest that TraT, in combination with HIV-derived peptides, could be used to maintain or restore cell-mediated immune functions of HIV-infected individuals, as well as cellular immune functions in individuals suffering from other immunodeficiency disorders.

Adjuvants, Immunologic↗
PubMed1992

An E.S.R. investigation of the reactive intermediate generated in the reaction between FeII and H2O2 in aqueous solution. Direct evidence for the formation of the hydroxyl radical.

The technique of E.S.R. spectroscopy, when employed in conjunction with a continuous flow system, provides direct evidence for the nature of free radicals formed from organic substrates in the presence of FeII and H2O2 in aqueous solution. It is shown, both via the identification of hydroxyl-radical adducts to alkenes and via the observed site-selectivity of radical attack, that the hydroxyl radical is formed as the reactive intermediate in the presence of various chelators (e.g. EDTA, DTPA). This approach also allows the rate constants for the FeII-H2O2 reaction in the presence of the different chelates to be determined; values obtained are in reasonable agreement with most of those measured by other methods. Examples of radical oxidation (by FeIII) and reduction (by FeII) are revealed.

Electron Spin Resonance Spectroscopy↗
PubMed1991

TraT: a powerful carrier molecule for the stimulation of immune responses to protein and peptide antigens.

A number of integral membrane proteins (Imps) isolated from Escherichia coli have been examined for their ability to generate serum antibody responses in the absence of adjuvant. These proteins were found to stimulate high titers of serum antibody when injected into rabbits or mice in saline. The antibody titers elicited were not significantly increased by the addition of a powerful adjuvant such as IFA. Covalent conjugation of BSA, of the DNP group, and of a peptide Ag from Plasmodium falciparum to these protein carriers resulted in a significant enhancement of the immune response to the conjugated material in comparison with the response elicited when the immunogen was injected without adjuvant or was not conjugated to Imps. The antibody response to these conjugates could not be significantly increased by the addition of IFA. Thus, the Imps of E. coli represent powerful carrier molecules which, when injected into mice and rabbits, are not only capable of generating high titers of antibody to themselves, but also to molecules conjugated to them. Immunization with immunogens coupled to these proteins results in the production of high titers of antibody without the need for oil-based adjuvants, thereby avoiding the unwanted side effects of such adjuvants.

Adjuvants, Immunologic↗