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Biomedical subjects

J Gibson

Publications and source records attributed to J Gibson.

At least 37 records · Page 2Linked to original sources

Stroke in Devon: knowledge was good, but action was poor.

BACKGROUND AND AIM: Effective implementation of early treatment strategies for stroke requires prompt admission to hospital. There are several reasons for delayed admission. Good awareness should facilitate early admission. We identified local targets for education. METHODS: Four groups, each of 40 people, completed questionnaires to determine their knowledge of stroke symptoms and risk factors, and the action they took or would take in the event of a stroke. The groups were: patients with a diagnosis of stroke or TIA (within 48 hrs of admission); patients at risk of stroke; the general population; and nurses. RESULTS: Forty per cent of stroke patients identified their stroke. Median time from onset of symptoms to seeking medical help was 30 minutes. Medical help was sought by the patient themselves in only 15% of cases. In 80% of cases the GP was called rather than an ambulance. Of the at risk group, 93% were able to list at least one symptom of acute stroke, as were 88% of the general population. An ambulance would be called by 73% of the at risk group in the event of a stroke. Patients with self reported risk factors for stroke were largely unaware of their increased risk. Only 7.5% of at risk patients acquired their stroke information from the medical profession. CONCLUSIONS: Public knowledge about stroke is good. However, stroke patients access acute services poorly. At risk patients have limited awareness of their increased risk. A campaign should target people at risk, reinforcing the diagnosis of stroke and access to medical services.

Aged↗

Dental management considerations for the patient with an acquired coagulopathy. Part 2: Coagulopathies from drugs.

Dental patients often give a medical history that suggests the possibility of a coagulopathy from drugs, with a corresponding risk for prolonged bleeding during and following an invasive procedure. Identification of patients who may be prone to oral bleeding requires specific medical history information and the proper use of laboratory tests. Some NSAIDs are reported to cause prolonged oral bleeding, but scientific evidence is lacking. Likewise, the risk of oral bleeding from anticoagulants such as warfarin is often over stated, and unnecessary adjustment of NSAID or warfarin dosage puts patients at risk for significant morbidity and mortality. Some commonly employed laboratory tests such as the prothrombin time provide helpful information when used in the appropriate setting, but others, such as the bleeding time test, provide little or no predictive value in the determination of patients at risk for oral bleeding. Dental management of patients with potential coagulopathies from medications requires an understanding of basic principles of coagulation. The vast majority of these patients can be managed in the community setting without risk and without alteration of anticoagulant drug regimes.

Alcohol Drinking↗

The role of primary healthcare professionals in oral cancer prevention and detection.

AIM: To investigate current knowledge, examination habits and preventive practices of primary healthcare professionals in Scotland, with respect to oral cancer, and to determine any relevant training needs. SETTING: Primary care. METHOD: Questionnaires were sent to a random sample of 357 general medical practitioners (GMPs) and 331 dental practitioners throughout Scotland. Additionally, focus group research and interviews were conducted amongst primary healthcare team members. RESULTS: Whilst 58% of dental respondents reported examining regularly for signs of oral cancer, GMPs examined patients' mouths usually in response to a complaint of soreness. The majority of GMPs (85%) and dentists (63%) indicated that they felt less than confident in detecting oral cancer, with over 70% of GMPs identifying lack of training as an important barrier. Many practitioners were unclear concerning the relative importance of the presence of potentially malignant lesions in the oral cavity. A high proportion of the GMPs indicated that they should have a major role to play in oral cancer detection (66%) but many felt strongly that this should be primarily the remit of the dental team. CONCLUSION: The study revealed a need for continuing education programmes for primary care practitioners in oral cancer-related activities. This should aim to improve diagnostic skills and seek to increase practitioners' participation in preventive activities.

Clinical Competence↗

Mapping of quantitative trait loci controlling trypanotolerance in a cross of tolerant West African N'Dama and susceptible East African Boran cattle.

Trypanosomosis, or sleeping sickness, is a major disease constraint on livestock productivity in sub-Saharan Africa. To identify quantitative trait loci (QTL) controlling resistance to trypanosomosis in cattle, an experimental cross was made between trypanotolerant African N'Dama (Bos taurus) and trypanosusceptible improved Kenya Boran (Bos indicus) cattle. Sixteen phenotypic traits were defined describing anemia, body weight, and parasitemia. One hundred seventy-seven F2 animals and their parents and grandparents were genotyped at 477 molecular marker loci covering all 29 cattle autosomes. Total genome coverage was 82%. Putative QTL were mapped to 18 autosomes at a genomewise false discovery rate of <0.20. The results are consistent with a single QTL on 17 chromosomes and two QTL on BTA16. Individual QTL effects ranged from approximately 6% to 20% of the phenotypic variance of the trait. Excluding chromosomes with ambiguous or nontrypanotolerance effects, the allele for resistance to trypanosomosis originated from the N'Dama parent at nine QTL and from the Kenya Boran at five QTL, and at four QTL there is evidence of an overdominant mode of inheritance. These results suggest that selection for trypanotolerance within an F2 cross between N'Dama and Boran cattle could produce a synthetic breed with higher trypanotolerance levels than currently exist in the parental breeds.

Anemia↗

Micropuncture cholecystectomy vs conventional laparoscopic cholecystectomy: a randomized controlled trial.

BACKGROUND: The aim of this study was to compare micropuncture laparoscopic cholecystectomy (MPLC), with three 3.3-mm cannulas and one 10-mm cannula with conventional laparoscopic cholecystectomy (CLC). METHODS: Patients were randomized to undergo either CLC or MPLC. The duration of each operative stage and the procedure were recorded. Interleukin-6 (IL-6), adrenocorticotropic hormone (ACTH), and vasopressin were sampled for 24 h. Visual analogue pain scores (VAPS) and analgesic consumption were recorded for 1 week. Pulmonary function and quality of life (EQ-5D) were monitored for 4 weeks. Statistical analysis was performed using the Mann-Whitney test or Fisher's exact test. Results are expressed as median (interquartile range). RESULTS: Forty-four patients entered the study, but four were excluded due to unsuspected choledocholithiasis (n = 3) or the need to reschedule surgery (n = 1). The groups were comparable in terms of age, duration of symptoms, and indications for surgery. Total operative time was similar (CLC, 63 [52-81] min vs MPLC 74 [58-95] min; p = 0.126). However, time to place the cannulas after skin incision (CLC, 5:42 [3:45-6:37] min vs MPLC, 7:38 [5:57-10:15] min; p = 0.015) and to clip the cystic duct after cholangiography (CLC, 1:05 [0:40-1:35] min vs MPLC, 3:45 [2:26-7:49] min; p <0.001) were significantly longer for MPLC. Six CLC patients and one MPLC patient required postoperative parenteral opiates (p = 0.04). Oral analgesic consumption was similar in both groups (p = 0.217). Median VAPS were lower at all time points for MPLC, but this finding was not significant (p = 0.431). There were no significant differences in postoperative stay, IL-6, ACTH or vasopressin responses, pulmonary function, or EQ-5D scores. CONCLUSIONS: The thinner instruments did not significantly increase the total duration of the procedure. MPLC reduced the use of parenteral analgesia postoperatively, which may prove beneficial for day case patients, but it did not have a significant impact on laboratory variables, lung function or quality of life.

Adrenocorticotropic Hormone↗

T cells in myeloma.

The current trend to develop immunotherapy strategies for patients with myeloma and other B cell malignancies has stimulated considerable interest in the functional state of the T cell population in these patients. Expanded clones of T cells exist in many patients with myeloma and their presence is associated with an improved survival. However, isolating T cells with tumour specificity has proven to be a difficult task and clinical immunization trials have so far failed to achieve a significant response. There is now evidence that tumour specific T cells are either tolerized or deleted following antigen presentation and that idiotype-derived, immunodominant tumour peptides may not exist in all patients. In order to develop more effective immunotherapy strategies for patients with myeloma, further studies are urgently required to identify the most appropriate tumour antigen, the nature of the interactions which take place during antigen presentation, and how to promote the cytotoxicity of autologous T cells.

CD4-Positive T-Lymphocytes↗

Successful mobilization of peripheral blood stem cells after addition of ancestim (stem cell factor) in patients who had failed a prior mobilization with filgrastim (granulocyte colony-stimulating factor) alone or with chemotherapy plus filgrastim.

This study assessed the ability of recombinant human stem cell factor (rHuSCF) to mobilize stem cells in 44 patients who had failed a prior mobilization (CD34(+) yield 0.5-1.9 x 10(6)/kg BW) with filgrastim-alone or chemotherapy-plus-filgrastim. The same mobilization regimen was used with the addition of rHuSCF. In the filgrastim-alone group (n=13), rHuSCF 20 microg/kg was started 3 days before filgrastim and continued for the duration of filgrastim. In the chemotherapy-plus-filgrastim group (n=31), rHuSCF 20 microg/kg/day plus filgrastim 5-10 microg/kg/day were administered concurrently. Leukaphereses were continued to a maximum of four procedures or a target of >or=3 x 10(6) CD34(+) cells/kg. In both groups, CD34(+) yield (x 10(6)/kg BW) of the study mobilization was higher than that of the prior mobilization (median: 2.42 vs 0.84 P=0.002 and 1.64 vs 0.99 P=<0.001, respectively). In all 54 and 45% of patients in the filgrastim-alone group and chemotherapy-plus-filgrastim group, respectively, reached the threshold yield of 2 x 10(6)/kg. The probability of a successful mobilization was the same in those with a CD34+ yield of 0.5-0.75 x 10(6)/kg BW in the prior mobilization as in those with 0.76-1.99 x 10(6)/kg BW. Downmodulation of c-kit expression and a lower percentage of Thy-1 positivity in the mobilized CD34(+) cells were noted in the successful mobilizers compared with those in the poor mobilizers. This study shows that rhuSCF is effective in approximately half the patients who had failed a prior mobilization and allows them to proceed to transplant. It also points to the likely role of the SCF/c-kit ligand pair in mobilization.

Adult↗

Autologous stem cell transplantation in multiple myeloma patients <60 vs >/=60 years of age.

The role of autologous stem cell transplantation (AuSCT) in older multiple myeloma patients is unclear. Using data from the Autologous Blood and Marrow Transplant Registry, we compared the outcome of 110 patients >/=the age of 60 (median 63; range 60-73) years, undergoing AuSCT with that of 382 patients <60 (median 52; range 30-59) years. The two groups were similar except that older patients had a higher beta(2)-microglobulin level at diagnosis (P=0.016) and fewer had lytic lesions (P=0.007). Day 100 mortality was 6% (95% confidence interval 4-9) and 1-year treatment-related mortality (TRM) was 9% (6-13) in patients <60 years, compared with 5% (2-10) and 8% (4-14), respectively, in patients >/=60 years. The relapse rate, progression-free survival (PFS) and overall survival (OS) in the two groups were also similar. Multivariate analysis of all patients identified only an interval from diagnosis to AuSCT >12 months and the use of two prior chemotherapy regimens within 6 months of AuSCT as adverse prognostic factors. Our results indicate that AuSCT can be safely performed in selected older patients: the best results were observed in patients undergoing AuSCT relatively early in their disease course.

Adult↗

Chasing the genes that control resistance to gastrointestinal nematodes.

The host-protective immune response to infection with gastrointestinal (GI) nematodes involves a range of interacting processes that begin with recognition of the parasite's antigens and culminate in an inflammatory reaction in the intestinal mucosa. Precisely which immune effectors are responsible for the loss of specific worms is still not known although many candidate effectors have been proposed. However, it is now clear that many different genes regulate the response and that differences between hosts (fast or strong versus slow or weak responses) can be explained by allelic variation in crucial genes associated with the gene cascade that accompanies the immune response and/or genes encoding constitutively expressed receptor/signalling molecules. Major histocompatibility complex (MHC) genes have been recognized for some time as decisive in controlling immunity, and evidence that non-MHC genes are equally, if not more important in this respect has also been available for two decades. Nevertheless, whilst the former have been mapped in mice, only two candidate loci have been proposed for non-MHC genes and relatively little is known about their roles. Now, with the availability of microsatellite markers, it is possible to exploit linkage mapping techniques to identify quantitative trait loci (QTL) responsible for resistance to GI nematodes. Four QTL for resistance to Heligmosomoides polygyrus, and additional QTL affecting faecal egg production by the worms and the accompanying immune responses, have been identified. Fine mapping and eventually the identification of the genes (and their alleles) underlying QTL for resistance/susceptibility will permit informed searches for homologues in domestic animals, and human beings, through comparative genomic maps. This information in turn will facilitate targeted breeding to improve resistance in domestic animals and, in human beings, focused application of treatment and control strategies for GI nematodes.

Alleles↗

CMRF44+ dendritic cells from peripheral blood stem cell harvests of patients with myeloma as potential cellular vectors for idiotype vaccination.

The optimal conditions required to harvest dendritic cells (DC) for immunotherapy were investigated in a series of preliminary investigations using peripheral blood stem cell (PBSC) harvests and blood from patients with myeloma. There was no difference in the number of DC (CMRF44+, CD19-, CD14-) in PBSC mobilized with G-CSF (mean 0.28%, n = 7) compared with GM-CSF (mean 0.24%, n = 6) and apheresis itself did not concentrate DC. In longitudinal studies (n = 10), the peak DC count (day 12 post PBSC harvest) did not correlate with the peak CD34+ cell count or white cell count. A simple affinity purification of DC resulted in a mean 63-fold purification. Affinity enriched suspensions from normal blood contained more DC (mean = 18.8%; n = 5) than those from patients with myeloma (mean = 9.9%; n = 13). The percentage of DC with a lymphoid phenotype (CD11c-, CDw123hi+) was significantly higher in G-CSF mobilized PBSC harvests (22.7%; n = 6) than in peripheral blood samples from patients with myeloma (7.0%; n = 13; p = 0.01). DC endocytosis was normal and did not change throughout the course of the disease. Neither DC numbers nor subsets changed significantly between days 1 and 3 of culture. Current mobilization procedures, optimized for PBSC, need to be altered when harvesting DC.

Antibodies, Monoclonal↗

Grading and disease management in national screening for diabetic retinopathy in England and Wales.

AIMS: A National Screening Programme for diabetic eye disease in the UK is in development. We propose a grading and early disease management protocol to detect sight-threatening diabetic retinopathy and any retinopathy, which will allow precise quality assurance at all steps while minimizing false-positive referral to the hospital eye service. METHODS: Expert panel structured discussions between 2000 and 2002 with review of existing evidence and grading classifications. PROPOSALS: Principles of the protocol include: separate grading of retinopathy and maculopathy, minimum number of steps, compatible with central monitoring, expandable for established more complex systems and for research, no lesion counting, no 'questionable' lesions, attempt to detect focal exudative, diffuse and ischaemic maculopathy and fast track referral from primary or secondary graders. Sight-threatening diabetic retinopathy is defined as: preproliferative retinopathy or worse, sight-threatening maculopathy and/or the presence of photocoagulation. In the centrally reported minimum data set retinopathy is graded into four levels: none (R0), background (R1), preproliferative (R2), proliferative (R3). Maculopathy and photocoagulation are graded as absent (M0, P0) or present (M1, P1). DISCUSSION: The protocol developed by the Diabetic Retinopathy Grading and Disease Management Working Party represents a new consensus upon which national guidelines can be based leading to the introduction of quality-assured screening for people with diabetes.

Clinical Protocols↗

Clinical and functional results of open operative repair for Achilles tendon rupture in a non-specialist surgical unit.

We followed up 25 patients (average age 47.9 years, range 22 to 77) after open repair of their Achilles tendon rupture. All had been operated on by a single general surgeon using an end-to-end reabsorbable suture, and immobilised in a plaster of Paris cast for six weeks. All patients had been discharged from follow up by 18 weeks from the operation. At an average of 3.4 years (range six months to 9.25 years), 18 had "excellent", six (24%) "good" and one (4%) "satisfactory" results. All but one patient were able to walk on tiptoes, and 20 of the 22 patients examined directly walked without a limp. Ultrasonography showed the injured tendons to be on average 2.3 times thicker in the antero-posterior diameter and 1.7 times thicker in the transverse diameter. In the hands of a single non-specialist but fully trained general surgeon, this management regimen produced full return to pre-operative activities in the majority of patients, and a low rate of local complications. The macroscopic and ultrasonographic appearance of the operated tendon remained abnormal, but this was not associated with any overt clinical disturbance

Achilles Tendon↗

Diaminoindanes as microsomal triglyceride transfer protein inhibitors.

The synthesis and biological activities of biarylamide-substituted diaminoindanes as microsomal triglyceride transfer protein (MTP) inhibitors are described. One of the more potent compounds, 8aR, inhibited both the secretion of apoB from Hep G2 cells and the MTP-mediated transfer of triglycerides between synthetic acceptor and donor liposomes with IC(50) values of 0.7 and 70 nM, respectively. In normolipidemic rats and dogs, oral administration of 8aR dose-dependently reduced both plasma triglycerides and total cholesterol. Moreover, in rats and dogs, 8aR also prevented the postprandial rise in plasma triglycerides following a bolus administration of a fat load. Because MTP inhibitors decrease very low density lipoprotein assembly in the liver, the potential for hepatic lipid accumulation was evaluated. In normolipidemic rats, hepatic cholesterol and triglyceride contents were dose-dependently increased by 8aR. However, hepatic lipid accumulation resulted in negligible change in total liver weight and was reversible after withdrawal of the compound.

Animals↗

Dendritic cells from patients with myeloma are numerically normal but functionally defective as they fail to up-regulate CD80 (B7-1) expression after huCD40LT stimulation because of inhibition by transforming growth factor-beta1 and interleukin-10.

Limited response to idiotype vaccination in patients with myeloma suggests that there is a need to develop better immunotherapy strategies. It has been determined that the number of high-potency CMRF44+CD14-CD19- dendritic cells (DCs) in the blood of patients with myeloma (range, 0.03%-0.8% of mononuclear cells [MNCs]; n = 26) was not significantly different from that in controls (range, 0.05%-0.8% of MNCs; n = 13). Expression of the costimulatory molecules CD80 and CD86 on DCs from these patients (mean, 29%+/-17% of MNCs and 85%+/-10% of MNCs, respectively) was also normal (mean, 29%+/-17% and 86%+/-16% of MNCs, respectively). Up-regulation of CD80 expression in response to stimulation by human huCD40LT + interleukin (IL)-2 was significantly reduced on the DCs of patients with myeloma during stable disease (n = 9) and was absent during progressive stages (n = 7) of disease. Similar effects were seen on B cells but not on monocytes of the same group of patients. CD86 expression on DCs was high before (86%) and after (89%) stimulation. Inhibition of CD80 up-regulation was neutralized by either anti-transforming growth factor (TGF)-beta1 or anti-IL-10. Up-regulation of CD80 on DCs of controls was inhibited by rTGF-beta1 in a dose-dependent manner. Serum TGF-beta1 and IL-10 levels were normal in most patients studied. Cytoplasmic TGF-beta1 was increased in plasma cells during progressive disease. Thus patients with myeloma have normal numbers of DCs, but CD80 expression may fail to be up-regulated in the presence of huCD40LT because of tumor-derived TGF-beta1 or IL-10. Autologous high-potency DCs may have to be tested for CD80 up-regulation and biologically modified ex vivo before idiotype priming for immunotherapy.

Antibodies, Monoclonal↗

Clonal cytotoxic T cells are expanded in myeloma and reside in the CD8(+)CD57(+)CD28(-) compartment.

The occurrence of clonal T cells in multiple myeloma (MM), as defined by the presence of rearrangements in the T-cell receptor (TCR)-beta chains detected on Southern blotting, is associated with an improved prognosis. Recently, with the use of specific anti-TCR-variable-beta (anti-TCRV(beta)) antibodies, the presence in MM patients of expanded populations of T cells expressing particular V(beta) regions was reported. The majority of these T-cell expansions have the phenotype of cytotoxic T cells (CD8(+)CD57(+) and perforin positive). Since V(beta) expansions can result from either a true clonal population or a polyclonal response, the clonality of CD8(+)TCRV(beta)(+) T cells was tested by TCRV(beta) complementarity-determining region 3 length analysis and DNA sequencing of the variable region of the TCR. In this report, the CD57(+) and CD57(-) subpopulations within expanded TCRV(beta)(+)CD8(+) cell populations are compared, and it is demonstrated that the CD57(+) subpopulations are generally monoclonal or biclonal, whereas the corresponding CD57(-) cells are frequently polyclonal. The oligoclonality of CD57(+) expanded CD8(+) T cells but not their CD57(-) counterparts was also observed in age-matched controls, in which the T-cell expansions were mainly CD8(-). The CD8(+)CD57(+) clonal T cells had a low rate of turnover and expressed relatively lower levels of the apoptotic marker CD95 than their CD57(-) counterparts. Taken together, these findings demonstrate that MM is associated with CD57(+)CD8(+) T-cell clones, raising the possibility that the expansion and accumulation of activated clonal CD8(+) T cells in MM may be the result of persistent stimulation by tumor-associated antigens, combined with a reduced cellular death rate secondary to reduced expression of the apoptosis-related molecule CD95.

Adult↗

Direct-Sun column ozone retrieval by the ultraviolet multifilter rotating shadow-band radiometer and comparison with those from Brewer and Dobson spectrophotometers.

A methodology for direct-Sun ozone retrieval using the ultraviolet multifilter rotating shadow-band radiometer (UV-MFRSR) is presented. Total vertical column ozone was retrieved in three stations: Mauna Loa, Hawaii, in the U.S., and Regina, Saskatchewan, and Toronto, Ontario, in Canada, from direct solar irradiances of the UV-MFRSR at 325-, 305-, 332-, and 311-nm channels (2-nm FWHM). The total uncertainty of ozone retrievals in this study is +/-2.0%. For Mauna Loa the mean ratios of the UV-MFRSR column ozone retrievals to the collocated Dobson and Brewer were 0.998 and 0.986 between May and September of 1999. The mean ratio of UV-MFRSR retrievals to the collocated Brewer retrievals was 1.012 in Toronto between April and August of 1999, and the mean ratio of retrievals of the UV-MFRSR to the collocated Brewer was 0.988 in Regina between June and September of 1999. Total vertical column ozone values for solar zenith angles of >70 degrees were not considered, because of the signal-to-noise ratio and the angular response of the instruments, and were not used in the evaluation. The advantages of total vertical column ozone retrieval using UV-MFRSR include relatively low cost, computer-controlled operation, automated calibration stability checks, and minimal maintenance. It allows for the real-time measurement of total vertical column ozone. The UV-MFRSR is being used at 28 sites across the United States and 2 sites in Canada that form the U.S. Department of Agriculture UV-B Radiation Monitoring and Research Program. This constitutes a unique network of total vertical colunm ozone measurement.

Journal Article↗