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Biomedical subjects

J Gibson

Publications and source records attributed to J Gibson.

At least 91 records · Page 5Linked to original sources
PubMed1999

Acute promyelocytic leukaemia complicating multiple myeloma: evidence of different cell lineages.

The association of leukemia and multiple myeloma is well described usually as a complication of chemotherapy but also in the absence of chemotherapy or at diagnosis. Such leukemias are typically acute myeloid leukemia (AML), particularly myelomonocytic subtype, and cases of acute promyelocytic leuke (APL) are rarely reported. Controversy exists as to whether myeloma and AML originate from a single haematopoietic progenitor or arise from different cell lineages. We report a case of a 58 year old female who developed APL 10 months following diagnosis of nonsecretory light chain (kappa) myeloma which had been treated with local spinal irradiation and low dose oral melphalan and prednisone. Clonality had originally been demonstrated by light chain restriction (kappa) of her bone marrow plasma cells whilst immunoglobulin heavy chain and T cell receptor genes were germ line. At development of APL cytogenetics revealed t(15;17) and PML-RAR fusion gene was detected by RT-PCR. The patient was treated with all-trans retinoic acid (ATRA) and received 2 cycles of consolidation chemotherapy with Idarubicin. Following this therapy the t(15;17) and PML-RAR were both undetectable whilst the clonal population of kappa staining plasma cells persisted. This particular patient represents a rare case of APL complicating multiple myeloma with persistence of the myeloma clone but disappearance of PML-RAR alpha RNA following therapy. This case study appears to support the argument that the APL and myeloma originated from distinct cell lineages.

Antibiotics, Antineoplastic↗
PubMed1999

Effect of clarithromycin and omeprazole therapy on the diversity and stability of genotypes of Helicobacter pylori from duodenal ulcer patients.

The genotypes of multiple isolates of Helicobacter pylori from 17 duodenal ulcer patients in the United Kingdom were compared to determine reasons for treatment failure. Isolates were from antrum and corpus biopsies taken before and after dual therapy with clarithromycin and omeprazole. All isolates were tested for antibiotic resistance and characterised by a novel scheme combining polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the ureA + ureB and 23S rRNA genes, vacA signal and midregion genotypes, and PCR detection of cagA. Combined genotypes of paired pre- and post-treatment isolates from 8 patients showed an infection with a single strain of H. pylori that had acquired resistance to clarithromycin. In 4 other patients, acquisition of clarithromycin resistance was associated with the presence of different strain types of H. pylori. The remaining 5 patients had clarithromycin-sensitive isolates. Overall, H. pylori from different patients had diverse genotypes, yet most (70%) were colonized by the same predominant and stable strain in both the antrum and corpus. There was no link between the emergence of in vitro clarithromycin resistance and a particular strain genotype for these UK isolates. It was concluded that colonization with a clarithromycin-resistant H. pylori was due to selection of a resistant strain or clonal variant within the infecting population. Present genomic markers had low predictive value for emergence of resistance.

Anti-Bacterial Agents↗
PubMed1999

Comparison of icodextrin and glucose solutions for the daytime dwell in automated peritoneal dialysis.

BACKGROUND: The sustained ultrafiltration achieved by icodextrin is more suited for the daytime dwell in automated peritoneal dialysis (APD) than glucose solutions. METHODS: Seventeen patients receiving APD underwent assessment using three different solutions for the daytime dwell: 2.27% glucose, 3.86% glucose and 7.5% icodextrin. Patients were then observed on icodextrin for a 6 month period. RESULTS: Daytime ultrafiltration was greater for 3.86% glucose (median 0.10, IQR 0.01 to 0.321) P<0.01 and icodextrin (median 0.26, IQR 0.14 to 0.361) P<0.001 than 2.27% glucose (median -0.19, IQR -0.54 to -0.081), with 3.86% glucose and icodextrin not being significantly different. Positive ultrafiltration occurred in 3/17 patients with 2.27% glucose, 13/17 patients with 3.86% glucose and 16/17 patients with icodextrin (chi2 P<0.0001). The difference in ultrafiltration of icodextrin and 3.86% glucose correlated with the 4 h dialysate/plasma creatinine ratio in a PET test (r = 0.51, P<0.05). Daytime Kt/V urea was greater for 3.86% glucose (median 0.27, IQR 0.20 to 0.48 per week, P<0.01) and icodextrin (median 0.31, IQR 0.27 to 0.49 per week, P<0.0001) than for 2.27% glucose (median 0.22, IQR 0.15 to 0.38 per week), with the difference between 3.86% glucose and icodextrin not reaching statistical significance (P = 0.06). Daytime creatinine clearance was greater for 3.86% glucose (median 10.2, IQR 6.9 to 13.61/week/1.73 m2, P<0.02) and icodextrin (median 12.1, IQR 9.3 to 15.71/week/1.73 m2, P<0.005) than for 2.27% glucose (median 8.8, IQR 4.9 to 11.91/week/1.73 m2). Daytime creatinine clearance was greater for icodextrin than for 3.86% glucose (P<0.005). The effects of icodextrin were sustained for the 6 month observation period. CONCLUSIONS: Icodextrin produced enhanced ultrafiltration and clearances compared with 2.27% glucose, without the exposure of the peritoneum to hypertonic glucose solutions.

Adult↗
PubMed1999

Brain tissue oxygenation during hemorrhagic shock, resuscitation, and alterations in ventilation.

OBJECTIVES: Recently developed polarographic microelectrodes permit continuous, reliable monitoring of oxygen tension in brain tissue (PbrO2). The aim of this study was to investigate the feasibility and utility of directly monitoring PbrO2 in cerebral tissue during changes in oxygenation or ventilation and during hemorrhagic shock and resuscitation. We also sought to develop a model in which treatment protocols could be evaluated using PbrO2 as an end point. METHODS: Licox Clark-type polarographic probes were inserted in the brain tissue of 16 swine to monitor PbrO2. In eight swine, changes in PbrO2 were observed over a range of fractional concentrations of inspired O2 (FiO2) as well as during periods of hyperventilation and hypoventilation. In eight other swine, PbrO2 was monitored during a graded hemorrhage of up to 70% estimated blood volume and during the resuscitation period. RESULTS: When FiO2 was elevated to 100%, PbrO2 increased from a baseline of 15+/-2 mm Hg to 36+/-11 mm Hg. Hyperventilation while breathing 100% oxygen resulted in a 40% decrease in PbrO2 (p < 0.05), whereas hypoventilation increased PbrO2 to 88 mm Hg (p < 0.01). A graded hemorrhage to 50% estimated blood volume significantly reduced PbrO2, mean arterial pressure, and intracranial pressure (p < 0.01). Continued hemorrhage to 70% estimated blood volume resulted in a PbrO2 of 2.9+/-1.5 mm Hg. After resuscitation, PbrO2 was significantly elevated, reaching 65+/-13 mm Hg (p < 0.01), whereas mean arterial pressure and cerebral perfusion pressure simply returned to baseline. CONCLUSION: Directly measured PbrO2 was highly responsive to changes in FiO2, ventilatory rate, and blood volume in this experimental model. In particular, hypoventilation significantly increased PbrO2, whereas hyperventilation had the opposite effect. The postresuscitation increase in PbrO2 may reflect changes in both O2 delivery and O2 metabolism. These experiments set the stage for future investigations of a variety of resuscitation protocols in both normal and injured brain.

Animals↗
PubMed1999

Long-term interferon-alpha 2A does not induce sustained hematologic remission in younger patients with essential thrombocythemia.

The ability of Interferon alpha (alpha-IFN) to alter the natural history of essential thrombocythemia (ET) and induce sustained hematologic remission would provide further impetus to consider this agent in younger patients with this disease and may influence the decision to commence treatment in asymptomatic patients. This study has failed to demonstrate any sustained hematologic remissions after cessation of long-term (2 years) alpha-IFN administration in a group of 34 female patients with a median age of 41 years (range 14-68) who were considered at intermediate to high risk of thrombotic complications. In the twenty-one patients completing two years of therapy, 13 (62%) had complete hematological responses (CHR; platelet count <400 x 10(9)/L), 7 (33%) partial hematological responses (PHR; platelet count 400-600 x 10(9)/L) and no thrombotic or hemorrhagic complications occurred. In all patients who discontinued alpha-IFN at 2 years, platelet counts rose above the normal range within 1-4 months and the majority required reinstitution of some form of therapy. The inability of long-term alpha-IFN to induce sustained, unmaintained hematologic remission argues strongly against any significant effect on the neoplastic clone at the doses used in this study. This study does, however, confirm the efficacy of long-term alpha-IFN in younger female patients with ET, a group not previously well represented in clinical trials of the agent.

Adolescent↗
PubMed1999

Prevalence of leg wound complications after coronary artery bypass grafting: determination of risk factors.

BACKGROUND: The reported prevalence of leg wound complications after coronary artery bypass grafting is 2% to 24%. Decreased length of hospital stay for patients who have this surgical procedure poses new care requirements in both acute care and community settings. OBJECTIVE: To determine the prevalence of postoperative leg wound complications in patients undergoing coronary artery bypass grafting and the risk factors associated with these complications. METHOD: In this prospective, observational study, 547 consecutive patients who had coronary artery bypass grafting alone or in combination with other cardiac surgical procedures were examined for evidence of leg wound complications each day after surgery during hospitalization. After discharge, problems were detected by home care nurses. RESULTS: The prevalence of leg wound complications was 6.8%. Factors significant by multiple logistic regression included preoperative hospitalization, use of an Ace elastic bandage in the operating room, the length of time the leg incision remained open in the operating room, and administration of nicardipine intravenously in the intensive care unit. Odds ratios were calculated for each variable. Premorbid factors such as diabetes or peripheral vascular disease were not predictive of complications. On average, most problems occurred on postoperative day 10, when many patients were at home. CONCLUSIONS: The results highlight the need to detect complications early, in both the hospital and the community settings. The determination of factors related to poor outcomes may assist clinicians in improving healthcare delivery.

Aged↗
PubMed1998

Longitudinal analysis of circulating myeloma cells detected by allele specific mRNA in situ hybridization.

Individual myeloma cells in the peripheral blood of 7 patients with multiple myeloma were detected by mRNA in situ hybridization (ISH) using biotinylated antisense oligonucleotide probes to non-germline sequences of the CDR3 region of the immunoglobulin heavy chain gene. Peripheral blood samples from these patients were studied over a period of 2-3 years. The number of circulating myeloma cells varied from 0.1-23% of the mononuclear cell population. Longitudinal studies showed that the highest number of circulating myeloma cells were present during escape phase and thus the percentage of mRNA ISH+ cells correlated with the clinical state of the patient. This technique is the most accurate means of monitoring and quantitating individual myeloma cells in the peripheral blood of patients with myeloma and provides insight into the relevance of circulating myeloma cells.

Adult↗
PubMed1998

1H MR spectroscopy of the basal ganglia in childhood: a semiquantitative analysis.

Proton MR spectra of the basal ganglia were obtained from 28 patients, 24 male and 14 female, median age 16.3 months (5 weeks to 31 years). They included 17 patients with normal MRI of the basal ganglia without metabolic disturbance (control group) and 11 patients with various metabolic diseases: one case each of high serum sodium and high serum osmolarity, cobalamin C deficiency, Leigh disease, Galloway-Mowat syndrome, Pelizaeus-Merzbacher disease, hemolytic-uremic syndrome and Wilson disease and two cases of Alagille syndrome and methylmalonic acidemia with abnormal MRI of the basal ganglia or blood or urine analysis (abnormal group). The MR spectrum was measured by using STEAM. The MR-visible water content of the region of interest was obtained. Levels of myoinositol, choline, creatine and N-acetylaspartate were measured using a semiquantitative approach, with absolute reference calibration. In the control group, there was a gradual drop of water content over the first year of life; N-acetylaspartate, creatine and myoinositol levels showed no significant change with age, in contrast to the occipital, parietal and cerebellar regions. Choline showed a gradual decrease for the first 2 years of life and then remained fairly constant. In the abnormal group the water content was not significantly different. N-Acetylaspartate was decreased in patients with high serum sodium and high serum osmolarity, cobalamin C deficiency, Leigh disease and one case of methylmalonic acidemia. Decreased creatine was also found in Leigh disease, and decreased choline in Galloway-Mowat syndrome and Wilson disease. Myoinositol was elevated in the patient with abnormally high serum sodium, and decreased in the hemolytic-uremic syndrome.

Adolescent↗
PubMed1998

Fluconazole-resistant Candida species in the oral flora of fluconazole-exposed HIV-positive patients.

The purpose of this study was to examine the effect of preceding fluconazole treatment on the oral mycologic flora and on the sensitivity of oral Candida albicans isolates to fluconazole. Saline oral rinses were collected from 89 HIV-positive patients, of whom 48 had been exposed to fluconazole and 41 were fluconazole-naive. The rinses were cultured on Sabouraud's and Pagano Levin agars, and yeasts were identified by standard methods. Fluconazole sensitivity of C. albicans isolates was measured by disk diffusion assay. C. albicans was isolated from 69% of patients who had received fluconazole and from 93% of the patients who were fluconazole-naive (p < 0.05). Nine other species of yeasts were also isolated, most commonly C. glabrata. Five patients previously exposed to fluconazole harbored fluconazole-resistant C. albicans, whereas no resistance was detected among the patients who were fluconazole-naive (p < 0.01). Sixteen of the patients who were fluconazole-exposed carried yeasts other than C. albicans, compared with only five patients in the fluconazole-naive group (p < 0.01). All of the fluconazole-resistant strains were isolated from patients with low CD4 counts (less than 100 cells/ml) and after lengthy fluconazole exposures. Nevertheless, patients in Charlotte, N.C., who had a greater mean fluconazole exposure time (10.25 +/- 1.41 months) than patients in Glasgow, UK, (0.65 +/- 0.18 months; p < 0.005), did not develop significantly more in vitro resistance or species diversity. This study indicates that long-term fluconazole treatment can have significant effects on the yeast flora of the mouth, particularly in a patient with a CD4 count of less than 100 cells/ml.

Adult↗
PubMed1998

Carotid artery Doppler ultrasonography in retinal macroaneurysms.

It is postulated that retinal arterial macroaneurysms (RAMs) occur at the site of incomplete embolic occlusion of a branch retinal artery. Embolic events of the retinal vessels are related to the state of the carotid artery tree and therefore Doppler ultrasonography of the carotid arteries in these patients is of particular interest. We have examined 13 patients with retinal artery macroaneurysms with carotid artery Doppler ultrasonography (CADU). Eight of these patients (61.5%) exhibited atheromatous plaques on the same side as the RAM with a moderate degree of arterial narrowing. Although our group of patients did not show advanced carotid artery disease, alterations of the arterial wall found at the level of the carotid artery were higher than expected in a similar hypertensive population. To our knowledge this is the first study of the carotid arterial tree in these patients. Our results support the theory that RAMs may be of embolic origin. Furthermore they demonstrate that CADU is a useful investigation in patients with RAMs.

Aged↗
PubMed1998

B-cell chronic lymphocytic leukaemia with CD8 expression: report of 10 cases and immunochemical analysis of the CD8 antigen.

We report 10 cases of B-cell chronic lymphocytic leukaemia (B-CLL) with expression of the T-cell antigen CD8. The majority of patients had typical B-cell CLL with stable and non-progressive stage A(O) disease except for more common expression of lambda light chain and CD25. Two patients had progressive disease and required therapy, one with atypical morphological and phenotypic features. The incidence of CD8 expression was approximately 0.5% of B-CLL patients from our institutions. Immunoprecipitation of the CD8 antigen from four of these B-CLLs showed identity to the CD8 antigen expressed on T cells with precipitation of CD8alpha bands of molecular weight approximately 34 kD. In view of the known intracellular signalling mechanism of CD8 using the tyrosine kinase p56-lck, we studied p56-lck expression by Western blot and found lack of consistent expression of the CD8 surface antigen, with most lacking p56-lck. Our report indicates that CD8 expression in B-CLL is probably underrecognized but is not a marker of disease progression. The CD8 on the B-CLL surface is immunochemically identical to the antigen on T cells, but is not accompanied by its usual signalling mechanism of p56-lck tyrosine kinase and therefore is unlikely to be a functionally active receptor.

Aged↗
PubMed1998

Aggressive natural killer cell leukemia/lymphoma.

A 32 year old Caucasian male presented with fever, massive hepatosplenomegaly and lymphadenopathy. Peripheral blood and bone marrow findings were consistent, both morphologically and immunophenotypically, with a natural killer cell leukemia/lymphoma. The disease was rapidly progressive and was fatal within five days after presentation.

Adult↗
PubMed1998

Autosomal dominant juvenile recurrent parotitis.

Juvenile recurrent parotitis is a common cause of inflammatory salivary gland swelling in children. A variety of aetiological factors has been proposed for the condition. Here we present a family where four members had juvenile recurrent parotitis and where two other family members may have had an atypical form of the condition. The segregation pattern in the family is consistent with autosomal dominant inheritance with incomplete penetrance and this suggests that, at least in some cases, genetic factors may be implicated in juvenile recurrent parotitis.

Child↗
PubMed1998

The expression of T cell related costimulatory molecules in multiple myeloma.

Presentation of tumour antigen by malignant cells not expressing costimulatory molecules is considered to be a major cause of the failure of the host's immune response against tumours. This study has determined the expression of the B7 family of costimulatory molecules on malignant plasma cells and the expression of the counter receptor molecules, CD28 and CD152 (CTLA-4), on T cells of patients with multiple myeloma. CD28 expression was present on most CD4 cells but was lower on CD8 cells especially from those patients who also showed evidence of expanded T cell clones (median 40%. z=2.4; p<0.02). CD152 expression was increased in 50% (9/18) of patients with myeloma. CD80 (B7-1) expression was present on the plasma cells of only 1 of 27 samples but CD86 (B7-2) expression within the normal range was present on the plasma cells of 14 of 27 samples. Primitive plasma cells (CD38++ CD45++) had a higher expression of CD86 (median 78%) than mature plasma cells (CD38++ CD45-) (median 19%, z=3.7; p<0.01). Thus patients with expanded T cell clones have a downregulated T cell CD28 expression and lack B7-1 expression on their malignant plasma cells. These results are consistent with the concept that engagement of the T cell receptor by tumour antigen on B7-1 deficient malignant plasma cells would result in T cell anergy rather than productive immunity.

Abatacept↗
PubMed1998

Leptin levels in pregnancy: marker for fat accumulation and mobilization?

BACKGROUND: Leptin, an adipose tissue-derived signalling factor encoded by the obese gene has been shown to be present as a 16-kDa protein in the blood of mice and humans. Resistance to leptin occurs in human obesity. Leptin has also been shown to associate with plasma insulin concentrations and there is currently considerable debate about the potential link between insulin resistance and resistance to leptin. In non-pregnant individuals, circulating leptin concentrations associate strongly with both total body fat mass and body mass index (BMI). In normal human pregnancy, the maternal fat stores increase to a peak in the late second trimester, before declining towards term as fat stores are mobilized to support the rapidly growing fetus. Insulin resistance increases during late pregnancy and is believed to be further enhanced in pregnancies complicated by pre-eclampsia. The aim of this study was to examine if leptin levels were altered in pregnancy and, if so, whether the pattern of change in circulating leptin related to previously established changes in fasting insulin concentrations or fat mass. METHODS: We measured third trimester plasma leptin concentrations in 12 uncomplicated pregnant women, nine women with pre-eclampsia matched for age and booking BMI, and 18 non-pregnant women similarly matched. We also examined the longitudinal course of leptin concentrations occurring throughout gestation (from 10 weeks gestation and at five week intervals thereafter), in five normal pregnancies and two women with gestational-onset diabetes. RESULTS: Leptin concentrations were significantly higher in the normal pregnant women (37.1 microg/L, [15.4-117.0], geometric mean, [range]; p=0.049), and women with pre-eclampsia (45.3 microg/L, [21.3-98.4]; p=0.001), than in non-pregnant controls (17.85 microg/L, [1.3-36.5]), however, there was no significant difference between uncomplicated and pre-eclamptic pregnancies (p=0.22). On examination of the longitudinal course of leptin concentrations occurring throughout gestation, in all seven women plasma leptin concentrations initially increased relative to booking (10 weeks) concentrations, but did so by varying amounts (ranging between 30-233%). Significantly, however, in all seven women plasma leptin concentrations peaked at around 20-30 weeks of gestation before declining towards term. CONCLUSION: On the basis of these observations, we postulate that plasma leptin levels increase significantly in human pregnancies and that the pattern of change in circulating leptin parallels the process of fat accumulation and mobilization.

Adult↗
PubMed1998

Progress in the development of Helicobacter pylori strain typing methods.

Helicobacter pylori is very different from other Gram negative bacteria that inhabit the human gastroduodenal tract. Its success in adapting to colonise and persist in the stomach is reflected in key features such as unique chemical structure and architecture of lipopolysaccharide, sheathed flagella, genomic diversity, and potent urease activity. Strain diversity within the species is well established and so the challenge is to exploit variations in these features for developing relevant epidemiological typing methods.

DNA, Bacterial↗