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Biomedical subjects

J Gill

Publications and source records attributed to J Gill.

At least 37 records · Page 2Linked to original sources

Etiology and natural history of neutropenia in human immunodeficiency virus disease: a prospective study.

The objective of this prospective, observational study was to define the natural history of neutropenia in human immunodeficiency virus (HIV) disease. Eighty-seven consecutive patients developing neutropenia (absolute neutrophil count [ANC], <1000 cells/mm(3)) were recruited and closely followed for the duration of the episode. Episodes lasted a median of 13 days, with a mean ANC nadir of 660 cells/mm(3). Presumed or proven infection occurred in 12 (17%) of 71 evaluable subjects, and culture-proven infection occurred only in 6 (8%) of 71. Most of the episodes of neutropenia were brief, mild to moderate in nadir, and self-limiting without complications. Myelosuppressive therapies were implicated in almost all episodes. Serious infections occurred infrequently and were associated with low ANC nadirs but not with duration of the neutropenic episode. Low CD4(+) cell counts also increased the risk of infection complicating an episode of neutropenia.

Adult↗

Atrial flutter ablation: efficacy and cost-effectiveness of a single decapolar electrode to demonstrate bidirectional isthmus block.

AIMS: To evaluate whether a single decapolar electrode is a reliable and cost-effective substitute for the 'Halo' catheter to map the circuit and detect bidirectional isthmus block during atrial flutter (AFL) ablation. METHODS AND RESULTS: Twenty-four patients underwent AFL ablation by using the decapolar electrode in the infero-lateral wall of right atrium (group A) while a 'Halo' catheter was used in 11 patients (group B). Both groups had similar clinical characteristics. Anti-clockwise rotation (20 patients), clockwise (3 patients) or both forms of AFL (1 patient) were detected in group A. All patients in group B had anti-clockwise AFL. Bidirectional isthmus block was completed in 22 patients of group A and in 9 of group B (P=NS) while incomplete isthmus block was detected in 2 patients in each group (P=NS). Mean fluoroscopy and procedure time was 27 +/- 47 min, 107 +/- 36 min in group A and 14 +/- 19 min, 114 +/- 65 min in group B (P=NS). AFL relapsed in 3 patients of group A (follow-up 7 +/- 4 months) and in 2 of group B (4 +/- 2 months). CONCLUSION: A single decapolar electrode is a reliable method to map the circuit and demonstrate bidirectional isthmus block during AFL ablation. The cost of the decapolar electrode is a quarter of that of the 'Halo' catheter. This represents a significant saving particularly for centres with a substantial number of AFL ablations.

Adult↗

Clinicopathologic and molecular analysis of high-grade dysplasia and early adenocarcinoma in short- versus long-segment Barrett esophagus.

Barrett esophagus, especially dysplastic Barrett mucosa, has been regarded as a preneoplastic lesion for esophageal adenocarcinoma. However, the etiology and pathogenesis of dysplasia and early adenocarcinoma in short- (SSBE) and long- (LSBE) segment Barrett esophagus have not been studied in detail. The aims of this study were to clarify clinicopathologic and genetic differences between high-grade dysplasia (HGD) and early adenocarcinoma in SSBE versus LSBE. We analyzed the clinicopathologic features from 47 patients (19 SSBE [<3 cm] and 28 LSBE [> or =3 cm]) with esophagectomy for HGD/T1 adenocarcinoma. Allelic losses on chromosomes 3p (FIHT), 5q (APC), 9p (p16), and 17p (p53) were compared in 12 HGD and 9 T1 tumors from 19 cases of SSBE and in 23 HGD and 15 T1 tumors from 28 cases of LSBE. Patients with SSBE were more likely to be smokers than were patients with LSBE (94.7% v 57.1%; P =.004). HGD or T1 tumors arising from SSBE were less likely to show adjoining nondysplastic Barrett mucosa than those from LSBE (73.6% v 100%; P =.02). LSBE more frequently showed a circumferential pattern of Barrett mucosa than did SSBE (96.4% v 47.3%; P =.0002). Chromosomal allelic losses on 3p, 5q, 9p, and 17p were detected in 19% (4 of 21), 43% (15 of 35), 40% (14 of 35), and 48% (16 of 33) of HGD, respectively, and 26% (5 of 19), 35% (8 of 23), 35% (8 of 23), and 57% (13 of 23) of T1 tumor, respectively. There were no significant differences in allelic loss of 3p, 5q, 9p, or 17p in HGD or T1 tumors from SSBE versus LSBE. These results suggest that both HGD and early adenocarcinoma in SSBE and LSBE may occur through similar genetic alterations, whereas there are some clinicopathologic differences between SSBE and LSBE. HUM PATHOL

Aged↗

Trunk sway measures of postural stability during clinical balance tests: effects of age.

BACKGROUND: The major disadvantage of current clinical tests that screen for balance disorders is a reliance on an examiner's subjective assessment of equilibrium control. To overcome this disadvantage we investigated, using quantified measures of trunk sway, age-related differences of normal subjects for commonly used clinical balance tests. METHODS: Three age groups were tested: young (15-25 years; n = 48), middle-aged (45-55 years; n = 50) and elderly (65-75 years; n = 49). Each subject performed a series of fourteen tasks similar to those included in the Tinetti and Clinical Test of Sensory Interaction in Balance protocols. The test battery comprised stance and gait tasks performed under normal, altered visual (eyes closed), and altered proprioceptive (foam support surface) conditions. Quantification of trunk sway was performed using a system that measured trunk angular velocity and position in the roll (lateral) and pitch (fore-aft) planes at the level of the lower back. Ranges of sway amplitude and velocity were examined for age-differences with ANOVA techniques. RESULTS: A comparison between age groups showed several differences. Elderly subjects were distinguished from both middle-aged and young subjects by the range of trunk angular sway and angular velocity because both were greater in roll and pitch planes for stance and stance-related tasks (tandem walking). The most significant age group differences (F = 30, p <.0001) were found for standing on one leg on a normal floor or on a foam support surface with eyes open. Next in significance was walking eight tandem steps on a normal floor (F = 13, p <.0001). For gait tasks, such as walking five steps while rotating or pitching the head or with eyes closed, pitch and roll velocity ranges were influenced by age with middle-aged subjects showing the smallest ranges followed by elderly subjects and then young subjects (F = 12, p <.0001). Walking over a set of low barriers also yielded significant differences between age groups for duration and angular sway. In contrast, task duration was the only variable significantly influenced when walking up and down a set of stairs. An interesting finding for all tasks was the different spread of values for each population. Population distributions were skewed for all ages and broadened with age. CONCLUSIONS: Accurate measurement of trunk angular sway during stance and gait tasks provides a simple way of reliably measuring changes in balance stability with age and could prove useful when screening for balance disorders of those prone to fall.

Adolescent↗

Saquinavir soft gelatin capsule: a comparative safety review.

The HIV-1 protease inhibitor (PI) saquinavir is available as a soft gelatin capsule (SGC) formulation. At the recommended dosage of saquinavir SGC (1200mg 3 times daily), this formulation provides around 8-fold greater exposure than the established hard gelatin capsule (HGC) formulation at the recommended dosage of 600mg 3 times daily. As with the HGC formulation, the most common adverse events seen with saquinavir SGC are gastrointestinal symptoms (e.g. diarrhoea, abdominal discomfort and nausea). Some of these may occur with a slightly higher frequency with the SGC than with the HGC formulation. Saquinavir SGC has only a minimal effect on nonfasting serum lipid and cholesterol levels. Like other PIs, saquinavir is metabolised by the cytochrome P450 (CYP) 3A4 isoenzyme and is susceptible to interactions with inducers (e.g. rifabutin and rifampicin) and inhibitors (e.g. clarithromycin and ketoconazole) of this enzyme. Ritonavir, nelfinavir, indinavir and delavirdine, all CYP3A4 inhibitors, greatly increase saquinavir plasma concentrations and the therapeutic implications of these interactions continue to be evaluated. While saquinavir is the least potent CYP 3A inhibitor among the PIs, several drugs (notably terfenadine, astemizole and cisapride) should not be given in combination with saquinavir. Therefore, although the SGC formulation enhances saquinavir exposure, it has a similar safety profile to the HGC formulation.

Animals↗

Tuberculosis notifications in Australia, 1998.

Since the inception of the National Mycobacterial Surveillance System (NMSS) in 1991, annual crude notification rates for tuberculosis have remained stable at between 5 and 6 per 100,000 population. In 1998, there was a total of 923 TB notifications in Australia of which 884 were new TB cases, and 39 relapsed cases. The corresponding annual crude notification rate for new and relapsed TB was 4.72 and 0.21 per 100,000 respectively. Seventy-seven percent of notifications that had a country of birth reported were overseas born. In keeping with trends observed over recent reporting years, the populations for which notified TB rates are highest include the overseas born from high prevalence countries and Indigenous Australians. The lowest rates of disease have continued to be reported in the non-Indigenous, Australian born population. Surveillance reports over the last seven years indicate that the rate of disease in this population is gradually declining.

Adolescent↗

Cardiac risk factors and the use of cardioprotective medications in patients with chronic renal insufficiency.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality among patients with chronic renal insufficiency (CRI). beta-Adrenergic blockers, acetylsalicylic acid (ASA), angiotensin-converting enzyme (ACE) inhibitors, and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) all reduce CVD mortality, but little is known about the extent to which these medications are used in patients with CRI. This study, a prospective cross-sectional study of consecutive patients seen by nephrologists in four Canadian centers for follow-up of progressive CRI in 1999, was performed to investigate the prevalence of coronary risk factors and use of cardioprotective medications among patients with CRI. Patients had creatinine clearances of 75 mL/min or less but were not on dialysis therapy. Three hundred four consecutive patients meeting the inclusion criteria were enrolled. Mean age was 60.8 +/- 15.7 years, mean creatinine clearance was 30.3 +/- 18 mL/min, and the case mix of kidney diseases was similar to that in the Canadian Organ Replacement Registry data. One hundred seventeen of 304 patients (38.5%) had a history of previous CVD, and the prevalence of CVD was greater in patients with more severe CRI. Two hundred forty-three patients (79.9%) had a history of hypertension, 132 patients (43.4%) had hyperlipidemia, 114 patients (37.5%) had diabetes mellitus, and 71 patients (27.3%) were smokers. Thirty-five percent of the patients with CVD had blood pressures greater than 140/90 mm Hg; 103 patients (33.9%) were administered beta-blockers; 196 patients (64.5%), ACE inhibitors or angiotensin-receptor blockers; 83 patients (27.3%), ASA; and 56 patients (18.4%), statins. Patients with diabetes were not more likely than those without diabetes to be prescribed cardioprotective medications. CVD is common in the predialysis population, and its prevalence increases with more severe kidney failure. Despite this, the use of cardioprotective medications is relatively low, and many patients had suboptimal blood pressure control. Given the high burden of disease in these patients, beta-blockers and ACE inhibitors should be used to control hypertension and/or for cardioprotection, and the increased use of ASA and statins should be considered.

Adult↗

Loss of CD4+ T cell proliferative ability but not loss of human immunodeficiency virus type 1 specificity equates with progression to disease.

In this study, we compared human immunodeficiency virus (HIV) type 1-specific proliferative responses with HIV-1-induced intracellular cytokine production in a cohort of clinically nonprogressing patients and individuals with progressive HIV-1 infection. We found strong HIV-1-specific proliferative responses in the clinical nonprogressor cohort that correlated with significant numbers of circulating HIV-1-specific CD4(+) T cells. In contrast, HIV-1-specific proliferative responses were absent in most individuals with progressive HIV-1 infection, even though interferon-gamma-producing HIV-1-specific CD4(+) T cells were detectable by flow cytometry. The implication of these data is that the important dysfunction seen in most HIV-positive patients from very early in disease may be an inability of HIV-1-specific CD4(+) memory T cells to proliferate in response to HIV antigens rather than an absolute loss of circulating virus-specific CD4(+) T cells.

Antigens, Viral↗

Human Kaposi's sarcoma cell-mediated tumorigenesis in human immunodeficiency type 1 tat-expressing transgenic mice.

BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) transactivator (Tat) protein has been linked to the development and course of Kaposi's sarcoma (KS) associated with acquired immunodeficiency disease syndrome (AIDS-KS). Tat is an 86-101 amino-acid protein encoded by two exons. To evaluate the growth-promoting effects of Tat in AIDS-KS in vivo, we developed transgenic mice expressing the one-exon-encoded 72 amino-acid protein (Tat(72)) and the two-exon-encoded 86 amino-acid protein (Tat(86)). METHODS: Human KS SLK cells were injected subcutaneously into CD4(+) T-cell-depleted male mice, and the tumors that formed after 3-4 weeks were recovered and analyzed for the expression of Tat protein(s), different cytokine messenger RNAs (mRNAs), and matrix metalloproteinases (MMPs). All statistical tests were two-sided. RESULTS: The average tumor weight was maximum in Tat(86) mice ( approximately 600 mg) compared with Tat(72) ( approximately 200 mg) and nontransgenic ( approximately 100 mg) mice (P<.005). Histologic examination of tumors showed spindle-shaped SLK cells with prominent infiltrates of inflammatory cells. All of the tumors from Tat mice expressed abundant Tat mRNA, suggesting that the infiltrating mouse cells actively expressed Tat. A comparison of the growth-promoting cytokines in the tumors from Tat(86)-transgenic and nontransgenic mice showed that the expression of the following cytokines was substantially increased in the tumors of the Tat(86) mice: tumor necrosis factor-alpha, interleukin 6, interleukin 8, granulocyte-macrophage colony-stimulating factor, and basic fibroblast growth factor. Furthermore, these tumors showed abundant expression of a 105-kd MMP activity associated with infiltrates of host leukocytes in the lesions. CONCLUSION: Our in vivo data clearly suggest that extracellular Tat can contribute to the growth and tumorigenesis of human KS cells.

Animals↗

Complete genome sequence of Neisseria meningitidis serogroup B strain MC58.

The 2,272,351-base pair genome of Neisseria meningitidis strain MC58 (serogroup B), a causative agent of meningitis and septicemia, contains 2158 predicted coding regions, 1158 (53.7%) of which were assigned a biological role. Three major islands of horizontal DNA transfer were identified; two of these contain genes encoding proteins involved in pathogenicity, and the third island contains coding sequences only for hypothetical proteins. Insights into the commensal and virulence behavior of N. meningitidis can be gleaned from the genome, in which sequences for structural proteins of the pilus are clustered and several coding regions unique to serogroup B capsular polysaccharide synthesis can be identified. Finally, N. meningitidis contains more genes that undergo phase variation than any pathogen studied to date, a mechanism that controls their expression and contributes to the evasion of the host immune system.

Antigenic Variation↗

Deliberate self-poisoning in adolescence: why does a brief family intervention work in some cases and not others?

In a randomized trial of a brief family intervention with adolescents who had deliberately poisoned themselves, we have previously reported that, within the group of patients who did not have major depression, the family intervention was significantly superior to routine care in reducing suicidal thinking. The present paper examined whether efficacy was related to changes in family functioning or other possible mediating variables. Potential mediators included family functioning, hopelessness, depression, adolescent problem-solving and compliance with treatment. The efficacy of the family intervention in reducing suicidal ideation within the non-depressed sub-group was probably not mediated by changes in these variables. The implications of this finding are discussed.

Adolescent↗

Reactivation of coagulation after stopping infusions of recombinant hirudin and unfractionated heparin in unstable angina and myocardial infarction without ST elevation: results of a randomized trial. OASIS Pilot Study Investigators. Organization to Assess Strategies for Ischemic++ Syndromes.

AIMS: To compare effects of heparin and hirudin on biochemical markers of coagulation. METHODS AND RESULTS: Patients (n=395) with unstable angina or myocardial infarction without ST elevation were randomized to a 72-h infusion of one of three regimens: unfractionated heparin (bolus of 5000 IU followed by an infusion of 1200 IU. h(-1)), low-dose hirudin (HBW 023; 0.2 mg. kg(-1)bolus followed by 0.10 mg. kg(-1). h(-1)) or medium-dose hirudin (0.4 mg. kg(-1)bolus followed by 0.15 mg. kg(-1). h(-1)). Infusions were adjusted to maintain an activated partial thromboplastin time of between 60-100 s. Activated partial thromboplastin time, prothrombin fragment 1.2 (F1.2), thrombin antithrombin III complex and D-dimer were measured before, during and after the infusion. Median activated partial thromboplastin time was similar in the two groups early on, but was significantly lower in the heparin group than in the combined hirudin group 48 h after starting the infusion (53 s and 75 s, respectively;P<0.001), and 6 h after stopping (31 s and 46 s, respectively;P<0.001). Median F1.2 levels were not significantly different between the groups during the infusion. Median thrombin antithrombin III levels in the heparin and hirudin groups were 2.8 microg. l(-1)and 2.3 microg. l(-1), respectively, at 6 h (P<0.001), and 3.0 microg. l(-1)and 2.3 microg. l(-1), respectively, at 48 h (P<0.001). Median D-dimer levels were 320 ng. ml(-1)and 260 ng. ml(-1)48 h after starting the infusion in the heparin and hirudin groups, respectively (P<0.001), and 415 ng. ml(-1)and 280 ng. ml(-1), respectively (P<0.001) 6 h after stopping. D-dimer levels were significantly elevated above baseline values in both groups 24-48 h after stopping the infusions. CONCLUSIONS: The greater reduction of thrombin antithrombin III and D-dimer during the hirudin infusion supports the hypothesis that hirudin is a more potent antithrombin agent than heparin. Increased D-dimer levels after stopping heparin or hirudin suggest that there is an ongoing pro-coagulant state. These results point to the greater efficacy of hirudin in preventing early clinical events (death, myocardial infarction and refractory ischaemia) compared with heparin that have been observed in large randomized trials. Persistent activation of coagulation afterstopping infusions in our study suggests that a longer course of antithrombotic treatment may be needed to pacify the thrombus.

Angina, Unstable↗

Segmentation of carotid artery in ultrasound images: method development and evaluation technique.

Segmentation of carotid artery lumen in two-dimensional and three-dimensional ultrasonography is an important step in computerized evaluation of arterial disease severity and in finding vulnerable atherosclerotic plaques susceptible to rupture causing stroke. Because of the complexity of anatomical structures, noise as well as the requirement of accurate segmentation, interactions are necessary between observers and the computer segmentation process. In this paper a segmentation process is described based on the deformable model method with only one seed point to guide the initialization of the deformable model for each lumen cross section. With one seed, the initial contour of the deformable model is generated using the entropy map of the original image and mathematical morphology operations. The deformable model is driven to fit the lumen contour by an internal force and an external force that are calculated, respectively, with geometrical properties of deformed contour and with the image gray level features. The evaluation methodology using distance-based and area-based metrics is introduced in this paper. A contour probability distribution (CPD) method for calculating distance-based metrics is introduced. The CPD is obtained by generating contours of the lumen using a set of possible seed locations. The mean contour can be compared to a manual outlined contour to provide accuracy metrics. The variance computed from the CPD can provide metrics of local and global variability. These metrics provide a complete performance evaluation of an interactive segmentation algorithm and a means for comparing different algorithm settings.

Algorithms↗

The molecular genetics of human herpesvirus 8.

Epidemiological evidence from the early 1990s suggested that a sexually transmitted infectious agent other than the HIV virus was associated with the development of Kaposi's sarcoma in patients with HIV. A novel gamma herpesvirus was identified in Kaposi's sarcoma lesions. The molecular genetics of this virus are reviewed in this article.

AIDS-Related Opportunistic Infections↗

Surveillance of pneumococcal disease in Australian states and territories.

Information on pneumococcal disease, including immunisation programs, and optimum future surveillance in each Australian State and Territory were discussed at the Pneumococcal Disease in Australia Workshop on 26-27 March 1999. Workshop participants further expanded on the surveillance aspects of the Workshop in this report. Most participants favoured notification by laboratories of pneumococcal isolates from sterile sites, to provide baseline surveillance data before immunisation programs are fully implemented. It was also thought that trends in antimicrobial resistance should be notified.

Australia↗

Epstein-Barr virus RNA detection and glandular differentiation in nasopharyngeal carcinoma: report of 2 cases.

Most tumors arising in the nasopharynx are either squamous cell carcinoma or so-called undifferentiated carcinoma of the nasopharyngeal type. Primary adenocarcinomas of the nasopharynx are rare, and glandular differentiation in undifferentiated carcinoma of the nasopharyngeal type has not been reported to date. We report 2 cases of undifferentiated carcinoma of the nasopharyngeal type that show distinct glandular differentiation by light microscopy, histochemistry, immunohistochemistry, and ultrastructure. Both tumors showed equal positivity for Epstein-Barr virus latent membrane protein and in situ hybridization for Epstein-Barr virus genome in the undifferentiated areas of the tumor and those featuring glandular differentiation.

Adenocarcinoma↗

Acceptability of health status questionnaire screening and vaccination among Kosovar refugees.

During 1999, following the war in Kosovo, thousands of Kosovar refugees were received by different countries. The public health reception protocols for these refugees varied widely between and within reception countries. We surveyed a group of Kosovar refugees received in Bolton to assess the acceptability of vaccination and health status questionnaire screening. We also examined the refugees' opinions about the confidentiality of their medical history and their willingness to take part in research. Fifteen out of 29 people responded. Most respondents were happy with the interventions.

Adult↗