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D Gill

Publications and source records attributed to D Gill.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of glycosylated recombinant human granulocyte colony-stimulating factor after high-dose cytarabine-based induction chemotherapy for adult acute myeloid leukaemia.

The Australian Leukaemia Study Group (ALSG) investigated whether G-CSF would accelerate haemopoietic recovery after induction treatment for acute myeloid leukaemia (AML) intensified with high-dose cytarabine, and therefore improve response rates and survival. Patients were randomised to receive lenograstim (glycosylated recombinant human G-CSF) 5 microg per kg body weight subcutaneously daily from day 8 after starting chemotherapy, or no cytokine, following chemotherapy with cytarabine 3 g/m2 every 12 h on days 1, 3, 5, and 7, together with idarubicin 9 or 12 mg/m2 on days 1, 2, and 3, plus etoposide 75 mg/m2 on days 1 to 7 inclusive. Patients had untreated AML, and were aged 16 to 60 years. Overall, 54 evaluable patients were randomised to receive lenograstim and 58 to no cytokine. Patients in the lenograstim arm had a significantly shorter duration of neutropenia <0.5 x 10(9)/l compared to patients in the no cytokine arm (median 18 vs 22 days; P = 0.0005), and also shorter duration of total leucopenia <1.0 x 10(9)/l (17 vs 19 days; P = 0.0002), as well as a reduction in duration of treatment with therapeutic intravenous antibiotics (20 vs 24 days; P= 0.015) and a trend to reduced number of days with fever >38.0 degrees C (9 vs 12 days; P = 0.18). There were no differences between the two groups in platelet recovery, red cell or platelet transfusions, or non-haematological toxicities. For patients achieving CR after their first induction course, a reduction in the time to the start of the next course of therapy was observed in the lenograstim arm, from a median of 40.5 days to a median of 36 days (P = 0.082). The overall complete response rates to chemotherapy were similar, 81% in the lenograstim arm vs 75% for the no cytokine arm (P = 0.5), and there was no significant difference in the survival durations. We conclude that the granulopoietic stimulating effect of G-CSF is observed after induction therapy for AML intensified by high-dose cytarabine, resulting in an improvement in a number of clinically important parameters with no major adverse effects.

Acute Disease↗
PubMed2001

Bullous lesions in Bazex syndrome and successful treatment with oral psoralen phototherapy.

A 59-year-old man presented with a psoriasiform dermatitis with associated bullae and destructive nail dystrophy of the hands and feet. He had lost 10 kg weight over 6 months and a mass in the neck was noted. He was provisionally diagnosed with Bazex syndrome (acrokeratosis paraneoplastica) and subsequent investigations revealed a squamous cell carcinoma in the right piriform fossa. His skin lesions were treated with oral psoralen and ultraviolet A phototherapy and this cleared the cutaneous changes, but the nail changes have persisted at 18 months follow up.

Acrodermatitis↗
PubMed2001

Evidence for the microbicidal activity of a chlorine dioxide-containing oral rinse formulation in vivo.

The ability of an oral rinse preparation, containing an admixture of the oxohalogen oxidants chlorite anion and chlorine dioxide, to diminish salivary levels of Streptococcus mutans, lactobacilli and Candida albicans was investigated in a group of 33 dental patients. Patients underwent oral rinsing episodes with the above product (20 ml for a period of 60 seconds, three times daily) for a total of 14 days, and subsequently repeated this exercise with mineral water in place of the oral rinse formulation. A group of 10 dental student volunteers, conducting the same oral rinsing regimens with mineral water in place of the oral health care product, served as a control group. Salivary microorganism levels were determined both prior and subsequent to the above trial period. The results demonstrated that biocidal oxohalogen oxidants present in the oral rinse formulation tested gave rise to a substantial reduction in salivary S. mutans and lactobacilli levels (p < 0.001 and 0.005, respectively), although the decrease observed in C. albicans failed to reach statistical significance. As expected, mineral water employed as an oral rinsing system by the same group of patients, or the student control group, exerted no influence on the salivary levels of each of these microorganisms. The therapeutic, microbial and biochemical ramifications of the results obtained are discussed.

Adult↗
PubMed2000

Modeling of the inhibition of retroviral integrases by styrylquinoline derivatives.

Styrylquinoline derivatives, known to be potent inhibitors of HIV-1 integrase, have been experimentally tested for their inhibitory effect on the disintegration reaction catalyzed by catalytic cores of HIV-1 and Rous sarcoma virus (RSV) integrases. A modified docking protocol, consisting of coupling a grid search method with full energy minimization, has been specially designed to study the interaction between the inhibitors and the integrases. The inhibitors consist of two moieties that have hydroxyl and/or carboxyl substituents: the first moiety is either benzene, phenol, catechol, resorcinol, or salicycilic acid; the hydroxyl substituents on the second (quinoline) moiety may be in the keto or in the enol forms. Several tautomeric forms of the drugs have been docked to the crystallographic structure of the RSV catalytic core. The computed binding energy of the keto forms correlates best with the measured inhibitory effect. The docking procedure shows that the inhibitors bind closely to the crystallographic catalytic Mg(2+) dication. Additional quantum chemistry computations show that there is no direct correlation between the binding energy of the drugs with the Mg(2+) dication and their in vitro inhibitory effect. The designed method is a leading way for identification of potent integrase inhibitors using in silico experiments.

Algorithms↗
PubMed2000

The prevalence of seborrheic keratoses in people aged 15 to 30 years: is the term senile keratosis redundant?

BACKGROUND: Seborrheic keratoses (SKs) are common skin lesions that have been shown to occur with increasing age, although the age of onset is not well recorded. OBJECTIVE: To determine the prevalence, nature, and distribution of SKs in young people. METHODS: One hundred seventy people aged 15 to 30 years were given a total body examination during which the presence, number, site, and size of SKs were recorded. Biopsy specimens were taken from the first 22 people who had lesions clinically diagnosed as SKs. Data on age, skin type, eye color, and hair color were recorded for all respondents. RESULTS: Forty (23.5%) of 170 respondents had at least one SK, with no significant difference between the sexes. There was an increase in prevalence with age from 15.7% in 15- to 19-year-olds to 32.3% in those aged 25 to 30 years. The size of the SKs also increased with age. A total of 77.5% of SKs were found on the trunk and 22.5% on the limbs, head, and neck. There was no correlation between SKs and any particular hair and eye color or skin type. CONCLUSIONS: These findings confirm that SKs are common lesions in young Australians, appearing in a substantial proportion of people younger than 30 years. The term senile keratosis is no longer appropriate for these lesions.

Adolescent↗
PubMed2000

Antidepressants for depression in people with physical illness.

OBJECTIVES: To determine whether antidepressants are clinically effective and acceptable for the treatment of depression in people who also have a physical illness. SEARCH STRATEGY: Medline, Cochrane Library Trials Register and Cochrane Depression and Neurosis Group Trials Register were all systematically searched, supplemented by hand searches of two journals and reference searching. SELECTION CRITERIA: All relevant randomised trials comparing any antidepressant drug (as defined in the British National Formulary) with placebo or no treatment, in patients of either sex over 16, who have been diagnosed as depressed by any criterion, and have a specified physical disorder (for example cancer, myocardial infarction). "Functional" disorders where there is no generally agreed physical pathology (e.g. irritable bowel syndrome) were excluded. The main outcome measures are numbers of individuals who recover/improve at the end of the trial and, as a proxy for treatment acceptability, numbers who complete treatment. DATA COLLECTION AND ANALYSIS: Data was extracted independently by the reviewers onto data collection forms and differences settled by discussion. MAIN RESULTS: 18 studies were included, covering 838 patients with a range of physical diseases (cancer 2, diabetes 1, head injury 1, heart 1, HIV 5, lung 1, multiple sclerosis 1, renal 1, stroke 3, mixed 2). Depression was diagnosed clinically in 3 studies, otherwise by structured interview or checklist. Only 5 studies described how they performed randomisation. 1 study compared drug with no treatment, and the rest with placebo: all of the latter said they were double blind. 6 studies used SSRIs, 3 atypical antidepressants, and the remainder tricyclics. Patients treated with antidepressants were significantly more likely to improve than those given placebo (13 studies, OR 0.37, 95% CI 0.27-0.51) or no treatment (1 study, OR 3.45, 95% CI 11.1-1.10). About 4 patients would need to be treated with antidepressants to produce one recovery from depression which would not have occurred had they been given placebo (NNT 4.2, 95% CI 3.2-6.4). Most antidepressants (tricyclics and SSRIs together, 15 trials ) produced a small but significant increase in dropout (OR 1.66, 95% CI 1.14-2.40. NNH 9.8, 95% CI 5.4-42.9). The "atypical" antidepressant mianserinproduced significantly less dropout than placebo. Only 2 studies used numerical scales designed to measure effects on function and quality of life; in HIV (Karnofsky scale), drug was better than no treatment; in lung disease (Sickness Impact Profile), drug was not significantly different from placebo. Only 7 studies reported looking for changes in the physical disease. Antidepressants produced no change in immune function in HIV relative to placebo (2 studies) or no treatment (1 study). Relative to placebo, antidepressants produced no change in cardiovascular function in heart disease, in respiratory function in lung disease, or in vital signs or laboratory tests in cancer (1 study each). Nortriptyline produced worse control in diabetes. Trends towards tricyclics being more effective than SSRIs, but also more likely to produce dropout were noted, but these are based on non-randomised comparisons between trials. REVIEWER'S CONCLUSIONS: The review provides evidence that antidepressants, significantly more frequently than either placebo or no treatment, cause improvement in depression in patients with a wide range of physical diseases. About 4 patients would need to be treated with antidepressants to produce one recovery from depression which would not have occurred had they been given placebo (NNT 4.2, 95% CI 3.2-6.4). Antidepressants seem reasonably acceptable to patients, in that about 10 patients would need to be treated with antidepressants to produce one dropout from treatment which would not have occurred had they been given placebo (NNH 9.8, 95% CI 5.4-42.9). (ABSTRACT TRUNCATED)

Antidepressive Agents↗
PubMed2000

Molecular remission without blood product support using all-trans retinoic acid (ATRA) induction and combined arsenic trioxide/ATRA consolidation in a Jehovah's Witness with de novo acute promyelocytic leukaemia.

Arsenic trioxide has recently been used in the treatment of both relapsed and de novo acute promyelocytic leukaemia (APML). Molecular remissions have been attained using arsenic trioxide with minimal associated haematological toxicity, making protocols utilizing this drug an attractive option for Jehovah's Witnesses with APML. A 62-year-old female Jehovah's Witness with de novo APML was treated with all-trans retinoic acid induction followed by combined arsenic trioxide/ATRA consolidation, and achieved molecular remission with minimal haematological toxicity and no blood product support.

Antineoplastic Agents↗
PubMed2000

Population-based surveys on the frequency of common skin diseases in adults--is there a risk of response bias?

Population-based surveys on the frequency of common skin diseases are important in determining the health needs of a community. As they rely on voluntary presentation, there is a risk of response bias which may compromise the quality of the data obtained. The aim was to determine in what way and to what degree response bias may occur in a population-based survey on the frequency of common skin diseases in adults. A follow-up study was conducted on 1043 out of 2500 adults who did not attend for examination as part of a randomized population-based survey on the frequency of common skin diseases amongst adults in Maryborough, Central Victoria, Australia. Nonrespondents were more likely to be at the extremes of age, retired, unemployed and less likely to report that they had a history of skin disease than the respondents. Subsequent examination of a sample of the nonrespondents revealed they were more likely to have skin cancers and Campbell de Morgan angiomas than the respondents. These differences cannot be fully explained on the basis of an age-related response bias alone. Response bias is a risk in population-based surveys of common skin diseases which rely on voluntary presentation. Some attempt should be made to sample the nonrespondents in these surveys to determine the nature and extent of any bias and to adjust for it, if necessary.

Adult↗
PubMed2000

Mesangioproliferative glomerulonephritis with IgM deposition: clinical characteristics and outcome.

The significance of IgM on immunofluorescence in renal biopsy specimens remains unclear. This retrospective case study was conducted to define the clinical features, response to therapy and outcome of patients with Mesangioproliferative Glomerulonephritis (MGN) with diffuse IgM deposition. Of 1919 native renal biopsies performed over a ten-year period, 139 (7.2%) had light microscopic features of MGN and manifested IgM as the dominant immunoglobulin. When exclusion criteria (more than a trace of IgA or IgG, segmental IgM, evidence of SLE, vasculitis, FSGS or Alport's syndrome and pregnant patients) were applied, 60 patients (3.1%) remained. Follow-up data were available for 54 cases with a mean age of 26.5 years (range 1.7-63). Mean follow-up period was 7.4 years (range 4.7-22.2). Forty-one per cent presented with nephrotic syndrome (NS), 26% with asymptomatic proteinuria (>250mg/24hr), 18% with macroscopic hematuria and 15% with isolated microscopic hematuria. Twenty-one percent of patients were hypertensive at presentation. Creatinine was initially <120 (mol/L in all but one patient. Only four patients (7.4%), all nephrotic, suffered a decline in renal function despite treatment; all 4 developed ESRF after a mean of 5.6 years (range 2-8.3). Two of these were subsequently re-biopsied and found to have FSGS. No patients with isolated microscopic / macroscopic hematuria or asymptomatic proteinuria suffered a decline in renal function. Protein excretion rate fell into the normal range in 63% of those receiving steroids, with 82% becoming steroid dependent. Of those treated with cyclosporine (48%) or cyclophosphamide (52%) only 9.5% and 14.5% respectively remained in prolonged remission after discontinuing treatment. It is concluded that MGN with IgM deposition carries a very favorable prognosis except in patients with NS who develop FSGS. However there is a high incidence of steroid dependence and resistance in the proteinuric group.

Adolescent↗
PubMed2000

IFN-alpha1a gene is the major variant in the North American population.

Thirteen interferon (IFN)-alpha functional genes have been reported. A number of these genes have allelic members (variants). In the case of IFN-alpha1, two variants, IFN-alpha1a and IFN-alpha1b, are known. The variants differ from each other by one base change in the coding region, leading to a single change in amino acid sequence and the presence of a restriction site. We have developed oligonucleotide primers for amplification of IFN-alpha1 gene(s) using polymerase chain reaction (PCR). Genomic DNA, obtained from over 23,000 normal healthy individuals and from four human cell lines, were used as templates in PCR to amplify the IFN-alpha1 gene sequences. The resulting PCR products were analyzed by restriction endonuclease digestion and DNA sequencing to identify the presence of variant sequences. The results show that IFN-alpha1a is predominant in the genomic DNA of the population examined. Among the cell lines studied, IFN-alpha1a is the only variant found in U-937 and Namalwa cells, whereas KG-1 cells have only IFN-alpha1b, and EB-3 cells have both IFN-alpha1a and IFN-alpha1b in the genome.

Alleles↗
PubMed2000

Genetic heterogeneity of the Coppock-like cataract: a mutation in CRYBB2 on chromosome 22q11.2.

PURPOSE: To identify the genetic defect for the Coppock-like cataract (CCL) affecting a Swiss family, which defect was unlinked to the chromosome 2q33-35 CCL locus. METHODS: A large family was characterized for linkage analysis by slit lamp examination or by the review of drawings made before cataract extraction. The affection status was attributed before genotyping, and the genotyping was masked to the affection status. Two-point and multipoint linkage analyses were performed using the MLINK and the LINKMAP components of the LINKAGE program package (ver. 5.1), respectively. Mutational analysis of candidate genes was performed by a combination of direct cycle sequencing and an amplification refractory mutation system assay. RESULTS: Ten individuals were affected with the CCL phenotype. The disease was autosomal dominant and appeared to be fully penetrant. A new CCL locus was identified on chromosome 22q11.2 within a 11.67-cM interval (maximum lod score [Zmax] = 4.14; theta = 0). Mutational analysis of the CRYBB2 candidate gene identified a disease-causing mutation in exon 6. This sequence change was identical with that previously described to be associated with the cerulean cataract, a clinically distinct entity. CONCLUSIONS: The CCL phenotype is genetically heterogeneous with a second gene on chromosome 22q11.2, CRYBB2. The CCL and the cerulean cataract are two distinct clinical entities associated with the same genetic defect. This work provides evidence for a modifier factor that influences cataract formation and that remains to be identified.

Adolescent↗
PubMed2000

Tautomers of styrylquinoline derivatives containing a methoxy substituent: computation of their population in aqueous solution and their interaction with RSV integrase catalytic core.

8-Hydroxy-2-[2-(3-hydroxy-4-methoxyphenyl)ethenyl]-7-quinoline carboxylic acid and 8-hydroxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethenyl]-7-quinoline carboxylic acid inhibit the processing and strand transfer reactions catalyzed by HIV-1 integrase with an IC50 of 2 microM. Some of their spectral properties are briefly reported. Their fluorescence is so weak that it is of no use in an experimental determination of the binding to the protein and we resorted to computer simulation. Both styrylquinoline derivatives, in their monoanionic form, have several dozens of tautomers and each of these forms has four planar rotamers. In this work computer simulations have been performed to determine which tautomer is the most abundant in aqueous solution and which binds to the Rous sarcoma virus (RSV) integrase catalytic core. As the substituents on the quinoline moiety are the same as on salicylic acid, the energies of hydroxy benzoic acid tautomers were also computed both in vacuo and embedded in a continuous medium which had the dielectric constant of bulk water, using the recent CPCM technique. The CPCM method was then applied to the two integrase inhibitors to estimate the tautomer population in water. The binding site of the compounds on the RSV integrase catalytic core was determined through a docking protocol, consisting of coupling a grid search method with full energy minimization. The designed method is a way leading to identification of potent integrase inhibitors using in silico experiments.

Avian Sarcoma Viruses↗
PubMed2000

Renal transplantation in pre-school children.

This short report describes the outcome of 13 renal transplants in 11 children under 5 years of age. Nine (82%) of the 11 recipients are alive; 2 children died with functioning grafts. Approximately 50% of grafts are functioning at 5 years post transplantation. Children with congenital kidney malformations can be successfully managed to transplantation.

Child, Preschool↗
PubMed1999

Role of donor leukocyte chimerism in establishing the etiology of neutropenia after liver transplantation.

BACKGROUND: The quantitation of donor leukocyte chimerism may aid in establishing the etiology of neutropenia after liver transplantation. METHODS: The incidence and clinical and laboratory characteristics of severe neutropenia were studied in adults who have undergone liver transplantation at our institution over the last 4 years. RESULTS: Severe neutropenia developed in 5 of 156 patients (3%). The clinical and pathological features were nonspecific. In two patients with a delayed diagnosis of graft-versus-host disease (GVHD), donor leukocytes comprised > or = 50% of the circulating peripheral blood mononuclear cells. In a third patient, an earlier diagnosis of GVHD was suspected on the basis of a donor leukocyte count of 3-10% in the peripheral blood. In contrast, donor leukocyte chimerism was < or = 0.01% in two patients with probable drug-induced neutropenia CONCLUSIONS: The determination of donor leukocyte chimerism has an important role in the investigation of neutropenia after liver transplantation, allowing early diagnosis and treatment of GVHD.

Adult↗
PubMed1999

Presentation, management and course of angina and suspected angina in primary care.

Previous surveys may have underestimated both prevalence and incidence of ischemic heart disease in general practice. Case identification is difficult, as many patients presenting with chest pain turn out not to have ischemic heart disease, although their outcome is unclear otherwise. In this work we aimed to: (1) estimate prevalence and incidence of angina in one Oxford general practice; (2) describe the processes of assessment, investigation, and management of suspected angina; and (3) describe the 2-year symptomatic and functional outcome of angina patients, compared with patients whose provisional diagnosis of suspected ischemic heart disease (IHD) was not subsequently sustained (NCCP). A retrospective survey of patients was undertaken (aged 45-74 years) by hand searching paper and electronic medical records to find, as of 1 January 1992, all patients in the practice with continuing treatment of angina diagnosed before 1989, or those having a new diagnosis of angina being assessed (suspected angina) in the 3 year 1989-1991. Two years later, a postal questionnaire survey compared the symptomatic and functional outcome of confirmed IHD and NCCP. On 1 January 1992, the diagnosis of angina was recorded in the notes of 11.1% of patients aged 45-74 years, and the diagnosis was considered correct in 7.4%. Over a 3-year period, 129 people was suspected of suffering from angina, but in 71 (55%) the diagnosis was not confirmed; 76 (59%) were either referred to a specialist out-patient clinic or had an emergency admission. A 2-year follow-up found that similar proportions of patients with angina and noncardiac chest pain had a poor outcome in terms of symptoms, mental state, quality of everyday life, and continuing consultation. The clinical burden of ischemic heart disease in general practice has been underestimated by earlier methodological approaches using less complete ascertainment strategies. The adequacy of current diagnostic and management arrangements for patients with suspected angina merits review, at both the primary and secondary care levels.

Aged↗
PubMed1999

Frequent consulters in general practice: a systematic review of studies of prevalence, associations and outcome.

We conducted a systematic review of the observational literature on frequent consulters in general practice. Electronic searching identified 34 studies which met our inclusion criteria. Frequent consulters were identified in a wide range of primary health care settings, confirming that a small proportion of patients is responsible for a disproportionate number of consultations. A cutoff of 9-14 consultations per annum was used to define a frequent consulter in most studies. Studies have examined a variety of associated characteristics, and indicate that frequent consulters are highly heterogeneous, and have high rates of physical disease, psychiatric illness and social difficulties. Few are likely to conform to the "heartsink" stereotype. These patients are likely to have multiple, complex problems, often including chronic physical disease, with or without psychological and social problems. The natural history of frequent consulting behavior seems to be to persist in many cases. Implications for management are discussed.

Family Practice↗