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Biomedical subjects

J Dixon

Publications and source records attributed to J Dixon.

At least 109 records · Page 6Linked to original sources

Indeterminate adrenal mass in patients with cancer: evaluation at PET with 2-[F-18]-fluoro-2-deoxy-D-glucose.

PURPOSE: To evaluate the ability of positron emission tomography (PET) to characterize adrenal masses in patients with cancer. MATERIALS AND METHODS: Twenty-four adrenal masses (size range, 1.5-10.0 cm [mean, 2.8 cm]) in 20 patients (13 men and seven women) with cancer (lung [n = 10], colon [n = 3], lymphoma [n = 3], miscellaneous [n = 4]) were evaluated. PET was performed in fasting patients 45 minutes after infusion of 5-10 mCi (185-370 MBq) of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG). PET images were correlated with findings at computed tomography (CT), surgery, and/or percutaneous biopsy. RESULTS: Fourteen adrenal masses were proved malignant at surgery (n = 4), biopsy (n = 7), or follow-up (n = 3). Ten lesions were proved benign at biopsy (n = 4) or follow-up CT (n = 6). PET helped correct differentiation of benign from malignant adrenal lesions in all patients. A statistically significant difference (P < .001) was seen between mean tumor-to-background ratios for malignant (mean, 7.4; range, 2.9-16.6; median, 6.9) versus benign (mean, 0.8; range, 0.2-1.2; median, 0.6) adrenal lesions. CONCLUSION: PET helped correct differentiation of benign from malignant adrenal lesions.

Adrenal Gland Diseases↗

Mitochondrial encephalomyopathy associated with a single nucleotide pair deletion in the mitochondrial tRNALeu(UUR) gene.

The investigation of pathogenic mitochondrial DNA (mtDNA) mutations has revealed a complex relation between patient genotype and phenotype. For unknown reasons, some mtDNA mutations produce specific clinical manifestations such as chronic progressive external ophthalmoplegia; myoclonic epilepsy and ragged-red fiber disease (MERRF); and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). To enhance our understanding of the association between genotype and phenotype, we investigated a patient with mitochondrial encephalomyopathy and severe cerebral calcifications for a mtDNA mutation. There was a deletion of one of three T:A nucleotide pairs in the tRNALeu(UUR) gene of the mtDNA involving positions 3271 to 3273. Pedigree analysis suggested that this mutation may have occurred spontaneously in the proband. This analysis represents the smallest mtDNA deletion observed to date and is the first deletion identified within a mitochondrial tRNA. This observation emphasizes the importance of delineating the precise mutation responsible for an oxidative phosphorylation disease for patient diagnosis as well as for genetic counseling of maternal lineage relatives.

Adult↗

Distribution of NHS funds between fundholding and non-fundholding practices.

OBJECTIVES: To estimate the amount spent on specific hospital care by health agencies in 1993-4 and compare it with the resources allocated to patients registered with fundholding practices for the same type of care. To investigate whether fundholding practices and health agencies pay different amounts for inpatient care. DESIGN: Examination of hospital episode statistics, 1991 census data, and family health services authority and health agency records. SETTING: Health agencies and fundholding practices in the former North West Thames Regional Health Authority. MAIN OUTCOME MEASURES: Amount per capita allocated to inpatient and outpatient care for patients registered with fundholding and non-fundholding practices. Average specialty cost per finished consultant episode for health agencies and fundholding practices. RESULTS: The ratio of per capita funding for patients in non-fundholding practices to those in fundholding practices ranged from 59% to 87% for inpatient and day case care and from 36% to 106% for outpatient care. Average specialty costs per episode were similar for fundholding practices and health agencies. CONCLUSIONS: Fundholding practices seem to have been funded more generously than non-fundholding practices in North West Thames.

Budgets↗

Can there be fair funding for fundholding practices?

Most regional health authorities set budgets for fundholding practices according to the amount of care used by the practice population. This article explains why this funding method can only lead to an inequitable allocation of resources between fundholding and non-fundholding practices. Using the experience of North West Thames region, the efforts made to make funding fairer are discussed. The steps that health authorities could take to investigate and reduce the problem are also outlined. In the absence of a capitation formula for funding fundholding practices, the paper suggests that health authorities should do much more to investigate the amount of money they spend on non-fundholding practices. Regions could develop and use other methods to set budgets rather than rely on activity recorded by practices. Regions and the Department of Health should resolve urgently if and how far the budgets for fundholders should be compensated for increases in provider prices.

Budgets↗

Drug use and HIV risk-taking behaviour among injecting drug users not currently in treatment in Sydney, Australia.

This study investigated the drug use patterns and HIV risk-taking behaviour of 200 injecting drug users (IDU) not currently in treatment in Sydney, Australia. Although there was low HIV seroprevalence, unsafe injecting and sexual practices were common. Variables that were predictive of injecting risk-taking were higher level of heroin use, sexual relationship with an IDU and greater polydrug use. Two variables were predictive of sexual risk-taking: higher level of hallucinogen use and sexual relationship with an IDU. Female subjects were significantly more likely to have an IDU sexual partner. A higher level of cannabis use was associated with greater polydrug use and a higher level of amphetamine use was associated with greater use of opiates other than heroin. The findings are discussed in terms of the need for interventions aimed towards reducing sexual risk-taking among users of hallucinogens and towards reducing injecting and sexual risk-taking among IDU and their sexual partners. The potential difficulty in producing behaviour change among polydrug users is highlighted.

Adolescent↗

Controlled evaluation of a brief intervention for HIV prevention among injecting drug users not in treatment.

This study evaluated the effectiveness of a brief intervention (BI), a one-session motivational interview, in reducing HIV risk-taking behaviour among injecting drug users (IDU) not enrolled in any form of treatment for drug dependence. IDU were randomly assigned to either BI or a non-intervention control condition (NIC). One hundred and twenty-one subjects were successfully contacted for a 3-month follow-up and 88 subjects were followed up at 6 months. There were significant reductions for the sample as a whole for injecting risk-taking subscale scores on the HIV Risk-taking Behaviour Scale between pre-treatment and follow-up. There was no significant change in sexual risk-taking behaviour. There were no significant differences between groups on any measure at 3- and 6-month follow-up. There are a number of possible reasons why the sample as a whole showed significant improvements from initial to follow-up assessments. It is possible that, having had their attention directed to their risk-taking behaviour, subjects attempted to reduce their injecting risk-taking behaviour. If this is the case and subjects in the NIC condition can be considered as having received a BI, this suggests that BIs involving a personal risk assessment are effective in reducing risk behaviours associated with injecting. However, this suggestion could only be confirmed by comparison with a non-assessment control group.

Adolescent↗

Comparison of goat and horse blood as culture medium supplements for isolation and identification of Haemophilus influenzae and Streptococcus pneumoniae from upper respiratory tract secretions.

The results of this study show that goat blood as a culture medium supplement is as supportive as horse blood for the isolation and identification of Haemophilus influenzae and Streptococcus pneumoniae from clinical material. Care is required in the preparation of goat blood chocolate agar to ensure that a thermolabile growth inhibitor of NAD-dependent Haemophilus species is eliminated.

Animals↗

Expression of aminopeptidase-n (CD 13) in normal tissues and malignant neoplasms of epithelial and lymphoid origin.

AIMS: To provide a detailed knowledge of the distribution of the CD13 molecule, also known as the protease aminopeptidase-N, on both normal tissues and malignant neoplasms of epithelial and lymphoid origin. METHODS: CD13 antigen was examined by immunocytochemistry, using a recently produced antibody (VS5E) alongside a commercially available anti-CD13 monoclonal antibody. The VS5E recognising CD13 was produced by immunising a doxorubicin resistant breast cancer cell line (MCF-7-ADr). A striking feature of this antibody was that it stained the doxorubicin resistant cells but not the parental cell line. Both antibodies were tested on a broad range of normal tissues and three common types of epithelial malignancy (colon n = 28, lung n = 30, breast n = 35), and 12 cases of Hodgkin's and 52 of non-Hodgkin's lymphomas. RESULTS: CD13 was expressed on many tissue and cell types outside the haematopoietic system. In particular it was present on breast epithelium and in 20% (seven of 35) of breast carcinomas, but absent in normal and neoplastic colonic and bronchial tissues and lymphomas. CONCLUSIONS: This study provides not only detailed information about the expression of the CD13 antigen, but also raises the important possibility that CD13 expression may correlate with drug resistance in breast carcinomas.

Antigens, CD↗

Mammalian osteoclasts express a transient potassium channel with properties of Kv1.3.

Previous studies have revealed that expression of K+ channels in osteoclasts correlates with cell morphology and is influenced by interaction with the extracellular matrix. In this study, we investigated the electrophysiological properties of an outwardly rectifying K+ channel in rat and mouse osteoclasts using patch-clamp techniques. Cell-attached patch recordings revealed a channel of approximately 14 pS conductance that opened upon depolarization, and had a reversal potential close to that predicted for a K+ channel. Channel activity was transient; inactivation of ensemble currents, like that of whole-cell currents, occurred as a single exponential process. Both single-channel and macroscopic currents exhibited use-dependent inactivation in response to repetitive depolarizations. Two scorpion toxins, margatoxin and charybdotoxin, blocked this transient K+ channel, with half-maximal inhibition at 200 pM and 5 nM, respectively. In contrast, dendrotoxin (500 nM) had little effect. In summary, the outwardly rectifying K+ channel in osteoclasts resembles the Shaker-related K+ channel, Kv1.3. When membrane potential was recorded in whole-cell configuration, charybdotoxin (50 nM) caused a depolarization of 5 to 10 mV from resting levels of -50 mV or more positive; therefore this K+ channel contributes to the membrane potential of osteoclasts under some conditions. To investigate the molecular nature of osteoclast K+ channels, we performed RT-PCR on osteoclast RNA using primers for Kv1.3 and the inward rectifier, IRK1. mRNA encoded by Kv1.3 and IRK1 was detected and message identity confirmed by restriction enzyme digestion and sequence analysis. We conclude that osteoclasts exhibit, in addition to the previously described inward rectifier, an outwardly rectifying K+ conductance with properties of the Kv1.3. channel.

Animals↗

Upper airway carriage by Haemophilus influenzae and Streptococcus pneumoniae in Australian aboriginal children hospitalised with acute lower respiratory infection.

When nasopharyngeal secretions from 171 Australian Aboriginal children hospitalized with acute lower respiratory tract infections (ALRI) were cultured selectively for Streptococcus pneumoniae and Haemophilus influenzae, 136 (79.5%) and 151 (88.3%) children yielded 166 and 254 isolates of S. pneumoniae and H. influenzae, respectively. In colonized subjects multiple populations of S. pneumoniae (20% of carriage-positive patients) and H. influenzae (55%) were common. Pneumococci belonging to 27 types or groups were identified. H. influenzae serotype b colonized 16.4% of all children studied. More than one half of 152 children tested were excreting antibiotics at the time of admission to hospital. Significantly fewer children with serum antibiotic residues were colonized with S. pneumoniae than were antibiotic free children. Antibiotic usage had no measurable impact on the isolation rate of H. influenzae.

Acute Disease↗

Exogenous VLDL stimulates apolipoprotein B secretion from HepG2 cells by both pre- and post-translational mechanisms.

Previous studies have suggested that oleic acid (OA), by increasing availability of triglyceride (TG) and/or cholesteryl ester (CE), increases the secretion of apolipoprotein B (apoB) from HepG2 cells. The present studies were conducted to determine the effect of exogenous very low density lipoproteins (VLDL), which can provide TG and cholesterol to cells and be returned to the liver after secretion, in the regulation of hepatic apoB secretion. Addition of exogenous VLDL (50 micrograms protein/ml) to culture media was found to significantly stimulate apoB secretion from HepG2 cells. This effect was observed consistently with VLDL isolated from either normal or hyperlipidemic subjects. The effects of addition of VLDL were compared to that of OA, which was previously shown to stimulate apoB secretion by a posttranslational mechanism. VLDL appeared to increase apoB secretion by two mechanisms; the dominant one being posttranslational. Thus, VLDL protected newly synthesized apoB from rapid intracellular degradation in a manner similar to OA. Although treatment with VLDL increased the mass of both TG and CE, 3-fold and 2.6-fold, respectively, it appeared that the increase in TG was the critical factor associated with increased apoB secretion. Triacsin D, which is a potent inhibitor of TG synthesis, significantly inhibited the VLDL-induced stimulation of apoB secretion. Inhibition of apoB secretion by Triacsin D was associated with the loss of the protective effect of VLDL on newly synthesized apoB. In addition to its posttranslational effects, exogenous VLDL also regulated apoB secretion at the pretranslational level. Thus, we also observed that VLDL treatment consistently increased synthesis of apoB protein by 20-30%, an effect that is not observed after treatment of HepG2 cells with OA. A sensitive solution hybridization/RNase protection assay indicated that the increased apoB synthesis was associated with a 20-30% increase in apoB mRNA in VLDL-treated HepG2 cells. OA treatment had no effect on apoB mRNA levels. We conclude that VLDL treatment stimulates apoB secretion in HepG2 cells primarily by supplying fatty acids for TG synthesis. However, 20-30% of the stimulatory effect was due to a second mechanism that appeared to be pretranslational. Based on studies with OA, it appears that some component of VLDL other than TG-derived fatty acid was responsible for this effect.

Apolipoproteins B↗

A YAC contig encompassing the Treacher Collins syndrome critical region at 5q31.3-32.

Treacher Collins syndrome (TCOF1) is an autosomal dominant disorder of craniofacial development the features of which include conductive hearing loss and cleft palate. Previous studies have localized the TCOF1 locus between D5S519 (proximal) and SPARC (distal), a region of 22 centirays as estimated by radiation hybrid mapping. In the current investigation we have created a contig across the TCOF1 critical region, using YAC clones. Isolation of a novel short tandem repeat polymorphism corresponding to the end of one of the YACs has allowed us to reduce the size of the critical region to approximately 840 kb, which has been covered with three nonchimeric YACs. Restriction mapping has revealed that the region contains a high density of clustered rare-cutter restriction sites, suggesting that it may contain a number of different genes. The results of the present investigation have further allowed us to confirm that the RPS14 locus lies proximal to the critical region and can thereby be excluded from a role in the pathogenesis of TCOF1, while ANX6 lies within the TCOF1 critical region and remains a potential candidate for the mutated gene.

Annexin A6↗

Treacher Collins syndrome: correlation between clinical and genetic linkage studies.

Treacher Collins syndrome (TCOF1) is an autosomal dominant disorder of craniofacial development in which there is considerable variability in the clinical manifestations. The TCOF1 locus has previously been mapped to chromosome 5q32-33.2 and markers flanking the disease locus identified. In the current investigation we have analysed eight short tandem repeat polymorphisms for linkage to TCOF1 in a large family with multiple affected individuals. Linkage analysis suggested that TCOF1 in this family was linked to markers in the region 5q32-33.2. We have used the results to make diagnostic predictions in certain mildly affected and apparently unaffected individuals.

Chromosome Mapping↗

Discovery and synthesis of methyl 2,5-dimethyl-4-[2- (phenylmethyl)benzoyl]-1H-pyrrole-3-carboxylate (FPL 64176) and analogues: the first examples of a new class of calcium channel activator.

Methyl 2,5-dimethyl-4-[2-(phenylmethyl)benzoyl]-1H-pyrrole-3-carboxylate, FPL 64176 (1), is the first example of a new class of calcium channel activator (CCA) that does not act on any of the well-defined calcium channel modulator receptor sites, as typified by verapamil, diltiazem, and the dihydropyridines. The potent activity of 1, having the 2-(phenylmethyl)benzoyl substituent, was predicted using QSAR on an initial set of less potent benzoylpyrroles. When compared to the CCA Bay K 8644, 1 has similar potency on calcium uptake into GH3 cells (both have EC50 approximately 0.015 microM) but is appreciably more potent functionally at increasing contractility in a guinea pig atria preparation (1 has EC50 = 0.049 microM vs Bay K 8644 EC50 = 1.95 microM). 1 is an achiral, pharmacologically clean agonist with no demonstrable partial agonist properties and possesses appreciably higher efficacy than Bay K 8644. It should therefore become a useful biochemical and pharmacological tool for the study of calcium channels in many cell types.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Proteus syndrome with cardiomyopathy and a myocardial mass.

Proteus syndrome is an overgrowth syndrome principally affecting cutaneous and skeletal tissues, accompanied by subcutaneous hamartomas. We report on a patient with predominantly skeletal and visceral involvement, including a cardiac mass and thickening of the myocardial septum affecting cardiac conduction and contraction.

Adult↗

Lessons from Lithuania: rethinking public health training.

Lithuania faces stark problems that are familiar to most countries in the former Soviet Union: high morbidity and mortality rates, pollution, an unstable economy, and rapid changes in the financing and organisation of health care. In this environment Moore and Dixon visited Kaunas Medical Academy to help identify how training in public health medicine could contribute towards improving the health of the population. Although over 200 hours are devoted to public health training for medical undergraduates, teaching is unfocused, fragmented, and includes little epidemiology--the core subject for public health physicians. Teaching is mainly through long lectures with few group discussions. Student participation and motivation are low. As well as recommending redesign of the curriculum, Moore and Dixon suggested training in teaching methods for teachers. They also suggested that postgraduate training in public health should begin and should be targeted at hospital managers, teaching staff, and existing public health physicians.

Curriculum↗

An outbreak of serotype 1 Streptococcus pneumoniae infection in central Australia.

An outbreak of serotype 1 Streptococcus pneumoniae infection involving both adults and children occurred in central Australia during the winter months of 1991. Eighteen patients, mainly Aboriginal men, presented with culture-positive serotype 1 bacteraemic pneumonia. In this group, 11 of 12 adults for whom medical records were available were alcohol dependent. Thirteen children who were separately studied were hospitalised with acute lower respiratory tract infection: none had bacteraemia but all had upper airway colonisation by type 1 pneumococci. Antibiotics taken by 8 of the 13 children before admission to hospital may have compromised the isolation of type 1 pneumococci from blood cultures. Since the availability of antibiotics, epidemic pneumococcal infection is infrequent and has not been reported in Australia. In three outbreaks of type 1 disease recorded elsewhere crowding and alcoholism were identified as contributory factors. In the 16 month period before this outbreak none of 162 strains of pneumococci isolated from blood (32 strains) and nasopharyngeal secretions (130 strains) from Aborigines with acute lower respiratory tract infection and meningitis in the Alice Springs region were serotype 1 organisms.

Adult↗