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Biomedical subjects

J Thomas

Publications and source records attributed to J Thomas.

At least 55 records · Page 3Linked to original sources
PubMed2004

The rationale behind autologous autoimmune hematopoietic stem cell transplant conditioning regimens: concerns over the use of total-body irradiation in systemic sclerosis.

Hematopoietic stem cell transplantation (HSCT) is becoming an increasingly recognized indication for treatment of autoimmune diseases and severe immune-mediated disorders. However, multicenter registry data have demonstrated higher than anticipated early toxicity, approximately 10% for autoimmune diseases in general, and 20-27% for diffuse systemic sclerosis (scleroderma). If uncorrected, this high treatment-related mortality will hinder development of stem cell therapy for immune-mediated diseases. In order to develop safer regimens, we address some pitfalls and concepts involved in design and selection of conditioning regimens for autoimmune diseases in general, and because it is associated with the highest regimen-related toxicity, scleroderma in specific.

Autoimmune Diseases↗
PubMed2004

Findings in an independent sample support an association between bipolar affective disorder and the G72/G30 locus on chromosome 13q33.

Markers near the nested genes G72 and G30 on chromosome 13q33 have been implicated in the etiology of schizophrenia and, recently, bipolar affective disorder (BPAD). Hattori et al (2003) reported that single-nucleotide polymorphisms (SNPs) near the G72/G30 locus were associated with BPAD in a sample of 22 pedigrees, and that SNP haplotypes were associated in a second, larger sample of triads. The present study attempts to replicate this finding in an independent case-control sample. Six SNPs near the G72/G30 locus, including the most strongly associated markers in the previous study, were tested in 139 cases and 113 ethnically matched controls. Significant association was detected between BPAD and two adjacent SNPs (smallest P=0.007; global P=0.024). Haplotype analysis produced additional support for association (smallest P=0.004; global P=0.004). Analysis of 31 unlinked microsatellite markers detected no population stratification in the cases or controls studied. Although the associated alleles and haplotypes differ from those previously reported, these new results provide further evidence, in an independent sample, for an association between BPAD and genetic variation in the vicinity of the genes G72 and G30.

Bipolar Disorder↗
PubMed2004

A critical evaluation of the relationship between serum vitamin B, folate and total homocysteine with cognitive impairment in the elderly.

BACKGROUND: Serum homocysteine increases with age and is also considered a marker for low serum vitamin B(12) and folate. Furthermore, raised serum total homocysteine has been associated with atrophic changes in the brain. An association between serum vitamin B(12)/folate and cognitive impairment would be of considerable public health importance in view of the increasing numbers of elderly people. AIM: To systematically review published studies on the relationship between serum vitamin B(12), folate and total homocysteine and cognitive function in the elderly. DESIGN AND DATA SOURCES: A systematic review was undertaken of published evidence in English, examining the association between low serum vitamin B(12)/folate and raised total homocysteine with cognitive impairment (as indicated by low scores on neuropsychological testing) in subjects aged over 60 years. Sixteen electronic databases and cited articles were searched. Of 383 potential articles, six fulfilled the eligibility criteria: three case control and three cohort studies were identified. 'The Cochrane Non-Randomized Studies Methods Group' guidelines were used for assessment and extraction of data from these studies. RESULTS: All three case control studies found that serum total homocysteine was significantly higher in cases when compared with controls, and there was wide variation for both serum vitamin B(12) and folate in both groups of participants. The relationship of serum folate and vitamin B(12) status with cognitive impairment was heterogeneous and one case control study reported decreasing cognitive scores with increasing serum vitamin B(12). In the cohort studies, although serum total homocysteine could predict the rate of decline in neuropsychological testing, the overall odds ratio/relative risk (RR) of developing cognitive impairment in relation to levels of serum B(12) and serum folate were not significant. Although one study reported a significant RR of developing Alzheimer's disease when both serum folate and B(12) levels were low. One cohort study reported an increased prevalence of Alzheimer's type dementia in subjects who had normal serum vitamin B(12) at baseline. CONCLUSION: Serum total homocysteine is negatively correlated with neuropsychological tests scores. But the evidence does not support a correlation between serum vitamin B(12) or folate and cognitive impairment in people aged over 60 years. Hence, there is little evidence to justify treating cognitive impairment with vitamin B(12) or folate supplementation. This is consistent with the findings from recent systematic reviews of randomized double-blind trials, which have not found any evidence of potential benefit of vitamin supplementation. Further research is required in order to establish whether raised serum total homocysteine is a cause or consequence of disease.

Aged↗
PubMed2004

Short shrift for the sane? The hospital management of self-harm patients with and without mental illness.

In recent years the British government has sought to target service provision both on people with severe enduring mental illness and on those considered to be at risk of suicide. The study reported here suggests these policies may have had unforeseen repercussions on services for people who self-harm but have no identifiable mental illness. This paper compares the hospital management of self-harm patients with and without mental illness. Over the years 1996-2000, a total of 4,329 self-harm patient attendances were recorded at the accident and emergency department of a British hospital. Whilst patients in 63.7% of attendances could reasonably have been considered to have some form of mental illness, we found that in the remaining 36.3% of attendances (where patients had no indicator of mental illness) a particularly poor standard of service was given. We suggest that if government targets for a reduction in the suicide rate are to be met, it is crucial that there should be marked improvements in services for all self-harm patients presenting at accident and emergency departments. However, in improving services we must be vigilant to the danger that targeting those with a mental illness may mean we fail to provide even basic levels of care for others.

Community Mental Health Services↗
PubMed2004

Chemoradiation therapy is effective for the palliative treatment of malignant dysphagia.

Between 1993 and 2001, 106 patients with esophageal cancer were reviewed at a multidisciplinary clinic and treated with palliative intent by chemoradiation therapy. This study assesses the palliative benefit on dysphagia and documents the toxicity of this treatment. The study population comprised 72 men and 34 women with a median age of 69 years. Patients were treated with a median radiation dose of 35 Gy in 15 fractions with a concurrent single course of 5 FU-based chemotherapy. Dysphagia was measured at the beginning and completion of treatment and at monthly intervals until death, using a modified DeMeester (4-point) score. Treatment was well tolerated, with only 5% of patients failing to complete therapy. The treatment-related mortality was 6%. The median survival for the study population was 7 months. The median baseline score at presentation was 2 (difficulty with soft food). Following treatment, 49% of patients were assessed as having a dysphagia score of 0 (no dysphagia). Seventy-eight per cent had an improvement of at least one grade in their dysphagia score after treatment. Only 14% of patients showed no improvement with treatment. Fifty-one per cent maintained improved swallowing until the time of last follow-up or death. This single-institution study shows that chemoradiation therapy administered for the palliation of malignant dysphagia is well tolerated and produces a sustainable normalization in swallowing for almost half of all patients.

Adult↗
PubMed2004

Population based study of late onset cerebellar ataxia in south east Wales.

OBJECTIVE: To determine the prevalence and causation of late onset cerebellar ataxia (LOCA) in south east Wales, United Kingdom. METHODS: A population based study of LOCA was conducted in a defined geographical region with a total population of 742,400. Multiple sources of ascertainment were used to identify all cases prevalent on 1 January 2001. The inclusion criteria were: a predominantly progressive cerebellar ataxia with onset of symptoms at age > or = 18 years; and disease duration of > or = 1 year. Cases with known acquired ataxias, ataxic syndromes with associated prominent autonomic dysfunction and/or atypical parkinsonism suggestive of multiple system atrophy and disorders with ataxia as a minor feature were excluded. RESULTS: We identified 76 index cases of LOCA, of whom 63 were sporadic, idiopathic LOCA (ILOCA) and 13 were familial LOCA, of whom six had either spinocerebellar ataxia type 6, Friedreich's ataxia or dominant episodic ataxia. The mean annual incidence rate for the period 1999-2001 was 0.3/100,000 population/year. The crude prevalence rates were 8.4 per 100,000 (95% CI 7.2 to 11.6) for ILOCA and 1.8 per 100,000 (95% CI 0.8 to 2.7) for inherited LOCA. Of the 54/63 (85.7%) patients with ILOCA who were assessed, mean (SD) age at onset of symptoms was 53.8 (14.1) years (range 19 to 78) with a male:female ratio of 2.1:1. The mean disease duration was 8.7 (6.3) years (range 1 to 31). The most frequent presenting complaint was disturbance in gait (90.7%). One-third had a relatively pure cerebellar syndrome (33.3%) and two-thirds (66.7%) had additional extracerebellar neurological features. The majority (92%) were ambulant but only 9.3% were independently self-caring. CONCLUSION: This population based study provides insight into LOCA within a defined region and will inform decisions about the rational use of healthcare resources for patients with LOCA.

Adult↗
PubMed2004

Growth hormone deficiency associated with methylmalonic acidemia.

Poor growth is a common finding in patients with organic acidemias. Growth hormone (GH) therapy has been considered in the management of these disorders as a mode to enhance anabolism and lower the high levels of methylmalonic acid. We report two patients with methylmalonic acidemia (mut(o)) and GH deficiency. Both patients had persistently elevated serum concentrations of methylmalonic acid, which failed to respond to conventional therapy. In anticipation of using GH therapy to reduce high methylmalonic acid concentrations, the first patient underwent GH testing utilizing a provocative glucagon stimulation test and was found to be deficient. He was subsequently treated with GH and demonstrated improved growth, but his methylmalonic acid concentrations remain elevated. The second patient was also found to be GH deficient. These findings suggest that GH deficiency may be an etiologic factor in the poor growth seen in patients with organic acidemia.

Acidosis↗
PubMed2004

Homocysteine, Alzheimer genes and proteins, and measures of cognition and depression in older men.

The epsilon4 allele of apolipoprotein E (APOE), and the plasma levels of APOE, amyloid beta-protein precursor, amyloid beta1-40 (Abeta40) and homocysteine (Hcy) have all been correlated with the presence of dementia. Mutations in the methylnetetrahydrofolate reductase enzyme (MTHFR) have been associated with elevated levels of Hcy. This study explored the association of these factors with cognition and depression in community dwelling older men. Two hundred and ninety-nine men, mean age 78.9 years (SD 2.8), were studied in this cross-sectional survey. Mean plasma Hcy was 13.5 (SD 5.3) micromol/L. The MTHFR genotype had no obvious impact on Hcy levels. Ln Hcy and Ln Abeta40 were both inversely correlated with calculated glomerular filtration rate (cGFR), r = -0.41 (p < 0.001) and r = -0.28 (p < 0.001), respectively. There was a positive correlation between Ln Hcy and Ln Abeta40, r = 0.19 (p < 0.001), which remained significant after adjusting for cGFR, with a doubling of Hcy associated with a 24% increase of Abeta40. The e4 allele was associated with increased depressive symptoms as measured by the Geriatric Depression Scale-15, Odds ratio (OR) = 2.59 (95%CI 1.06-6.34) and poorer performance on the Clock Drawing Test, OR = 2.32 (95% CI: 1.25-4.29). There was a positive association between Abeta40 and Hcy, even after adjustment for cGFR in this sample of well, community dwelling older men. This association may help elucidate the link between elevated levels of Hcy and Alzheimer's disease.

Aged↗
PubMed2004

Cancer control in Africa: a call for action.

Cancer is an emerging public health problem in Africa especially with increasing frequency of HIV-associated malignancies and exposure to environmental carcinogens. This review attempts to highlight steps that can be taken to achieve effective control programmes in low-resource areas of Africa. The author reviews the areas of importance in cancer control programmes based on local experience. To implement cancer control programmes, steps must be taken to improve the data collection on incidence and trends of common cancers with the establishment of local cancer registries. There is the necessity to increase the level of awareness of the population about common cancers, to dispel the cultural taboos and myths, and teach basic preventive health measures. These can be achieved by well-organized sustained educational programmes extended to the grass-roots with community participation. The training of personnel at community level to recognize the early signs and symptoms coupled with provision of primary health care facilities and basic sustained well-planned referral system will be necessary to accommodate the fall-out of educational programmes and anti-cancer campaign. The integration of cancer control activities into the existing health care structure would make it easier to sustain these programmes. The cost-effectiveness of prevention and early diagnosis of cancer cannot be over-emphasized in Africa. With government investment in national health and provision of facilities for early diagnosis and treatment, effective cancer control can be achieved.

Africa↗
PubMed2003

Measurement of the perfection of nanoscale multilayers.

In modern materials science the characterisation of nanostructures is becoming increasingly important. For measurement of the quality of nanoscale multilayer arrangement with high spatial resolution a method is described that is based on the broadening of the spots in the Fourier transformation of transmission electron microscopic images of multilayer cross-sections. Using this method on Si/Ge superlattices with periodic lengths between 4 and 12 nm it could be quantitatively shown that the layer perfection decreases with increasing periodic length. The transition from elastic to plastic deformation between the Si and Ge layers at larger periodic lengths can be the reason for this behaviour.

Journal Article↗
PubMed2003

Effects of palytoxin on cation occlusion and phosphorylation of the (Na+,K+)-ATPase.

Palytoxin (PTX) inhibits the (Na(+) + K+)-driven pump and simultaneously opens channels that are equally permeable to Na+ and K+ in red cells and other cell membranes. In an effort to understand the mechanism by which PTX induces these fluxes, we have studied the effects of PTX on: 1) K+ and Na+ occlusion by the pump protein; 2) phosphorylation and dephosphorylation of the enzyme when a phosphoenzyme is formed from ATP and from P(i); and 3) p-nitro phenyl phosphatase (p-NPPase) activity associated with the (Na+, K+)-ATPase. We have found that palytoxin 1) increases the rate of deocclusion of K+(Rb+) in a time- and concentration-dependent manner, whereas Na+ occluded in the presence of oligomycin is unaffected by the toxin; 2) makes phosphorylation from P(i) insensitive to K+, and 3) stimulates the p-NPPase activity. The results are consistent with the notion that PTX produces a conformation of the Na+, K(+)-pump that resembles the one observed when ATP is bound to its low-affinity binding site. Further, they suggest that the channels that are formed by PTX might arise as a consequence of a perturbation in the ATPase structure, leading to the loss of control of the outside "gate" of the enzyme and hence to an uncoupling of the ion transport from the catalytic function of the ATPase.

4-Nitrophenylphosphatase↗
PubMed2003

Placental site trophoblastic tumor masquerading as an ovarian ectopic pregnancy.

The vast majority of pregnancies of unknown location (PUL) will be failing pregnancies and early intrauterine or ectopic pregnancies (EPs) that are too early to visualize on transvaginal scan. Very rarely, a positive pregnancy test in the presence of a negative scan will reflect an underlying human chorionic gonadotropin (hCG)-secreting tumor. We report a case in which elevated serum hCG led to the initial diagnosis of an EP which was subsequently found to be a placental site tumor of the ovary. This case shows that a misinterpretation of signs of EP can result in a delay in accurate diagnosis.

Adult↗
PubMed2003

An audit of the management of induced abortion in England and Wales.

OBJECTIVES: To assess the quality of care provided to women undergoing induced abortion. METHODS: The design was a single round audit questionnaire aimed at the providers of abortion services throughout England and Wales (NHS hospitals, clinics under NHS, agency agreements and private units. The levels of care were assessed against agreed audit criteria. RESULTS: Responses were received from 240 (74%) of the 324 units providing abortion care in England and Wales. These units undertook 80% of the 176,000 termination procedures. Generally standards of care were appropriate, but there were clear areas for improvement including choice of method, infection screening, and delays in referral. A number of unnecessary investigations were still evident, including cross-matching, while lower doses and alternative drug regimens might reduce costs. Only half of the units audited procedures and complications. CONCLUSIONS: This audit was carried out prior to the publication of the RCOG evidence-based guideline and a further round of audit to assess the impact of the guideline should now be considered.

Abortion Applicants↗
PubMed2003

Endometrioid adenocarcinoma of the uterus with a minimal deviation invasive pattern.

AIMS: Minimal deviation adenocarcinoma of endometrioid type is a rare pathological entity. We describe a variant of typical endometrioid adenocarcinoma associated with minimal deviation adenocarcinoma of endometrioid type. METHODS AND RESULTS: One 'pilot' case of minimal deviation adenocarcinoma of endometrioid type associated with typical endometrioid adenocarcinoma was encountered at our institution in 2001. A second case of same type was received in consultation. We reviewed 168 consecutive hysterectomy specimens diagnosed with 'endometrioid adenocarcinoma' specifically to identify areas of minimal deviation adenocarcinoma of endometrioid type. Immunohistochemistry was done with the following antibodies: MIB1, p53, oestrogen receptor (ER), progesterone receptor (PR), cytokeratin 7 (CK7), cytokeratin 20 (CK20), carcinoembryonic antigen (CEA), and vimentin (VIM). Four additional cases of minimal deviation adenocarcinoma of endometrioid type were identified. All six cases of minimal deviation adenocarcinoma of endometrioid type were associated with superficial endometrioid adenocarcinoma. In two cases with a large amount of minimal deviation adenocarcinoma of endometrioid type, the cervix was involved. The immunoprofile of two representative cases was ER+, PR+, CK7+, CK20-, CEA-, VIM+. MIB1 immunostaining of four cases revealed little proliferative activity of the minimal deviation adenocarcinoma of endometrioid type glandular cells (0-1%) compared with the associated 'typical' endometrioid adenocarcinoma (20-30%). The same four cases showed no p53 immunostaining in minimal deviation adenocarcinoma of endometrioid type compared with a range of positive staining in the associated endometrioid adenocarcinoma. CONCLUSIONS: Minimal deviation adenocarcinoma of endometrioid type more often develops as a result of differentiation from typical endometrioid adenocarcinoma than de novo. Due to its deceptively benign microscopic appearance, minimal deviation adenocarcinoma of endometrioid type may be overlooked and may lead to incorrect assessment of tumour depth and pathological stage. There was a tendency for tumour with a large amount of minimal deviation adenocarcinoma of endometrioid type to invade the cervix.

Aged↗
PubMed2003

Advances in EELS spectroscopy by using new detector and new specimen preparation technologies.

First results obtained with a Gatan UHV Enfina system, which was attached to a VG HB 501 UX dedicated STEM, are reported. The Enfina system is based on a CCD detector and offers, compared to the previously used photodiode array, a narrower point-spread function, higher sensitivity, and faster read-out capabilities. These improvements are demonstrated with electron energy-loss measurements on various oxides, such as Al2O3, TiO2 and SrTiO3. It is shown that a better energy resolution is achieved and that acquisition of high-energy absorption edges with a reasonable signal-to-noise ratio becomes possible. Furthermore, we report on the influence of the TEM specimen quality on the energy-loss spectra. Thin amorphous layers at the specimen surfaces, which are induced by ion-milling processes, can modify specific electron energy-loss near-edge structure features. We found that for the investigated ceramics the use of low-energy ion-milling systems is highly recommended, since the loss of energy-loss near-edge structure details by the presence of the amorphous layers is considerably reduced. This is especially true for very thin specimens.

Journal Article↗
PubMed2003

Validation of a six-graded faces scale for evaluation of postoperative pain in children.

BACKGROUND: The faces pain scales are often used for self-report assessment of paediatric pain. The aim of this study was to evaluate the validity of a six-graded faces pain scale after surgery by comparing the level of agreement between the children's report of faces pain scores and experienced nurses' assessment of pain by observation of behaviour. The faces pain scores before, at and after administration of analgesics were analysed. The study was performed in two South African hospitals, one with a mainly rural population and the other with an urban population. METHODS: A total of 110 children aged 4-12 years, scheduled for inguinal surgery in the two South African hospitals, were included in the study. The anaesthetic technique was standardized. All patients received a caudal block preoperatively. Postoperative pain assessments were made every hour for 8 h after the caudal block was performed. A designated nurse assessed pain by using a four-graded descriptive scale (no, mild, moderate or severe pain) and thereafter the child reported pain by using the six-graded faces pain scale. RESULTS: A high correlation was found between the two methods of assessment (tau = 0.76, P < 0.0001). The correlation between methods was high in both hospital populations and in all age groups. The weakest correlation was found in children aged 8-12 years (tau = 0.56, P < 0.01). Significantly lower faces pain scores were found after administration of analgesics compared with pain rating before analgesics (P < 0.0001). The proportion of patients with pain scores above 2 decreased from 86% to 31% (P < 0.001). CONCLUSIONS: The findings support this six-graded faces pain scale as a useful and valid instrument for measuring pain in the postoperative period in children aged 4-12 years.

Amides↗
PubMed2003

The packaging signal of simian immunodeficiency virus is upstream of the major splice donor at a distance from the RNA cap site similar to that of human immunodeficiency virus types 1 and 2.

Deletion mutation of the RNA 5' leader sequence of simian immunodeficiency virus (SIV) was used to localize the virus packaging signal. Deletion of sequences upstream of the major splice donor (SD) site produced a phenotype most consistent with a packaging defect when analysed by both RNase protection assay and RT-PCR. Sequences downstream of the SD were deleted and produced varying effects but did not affect packaging: a large downstream deletion had little effect on function, whereas a nested deletion produced a profound replication defect characterized by reduced protein production. Secondary structure analysis provided a potential explanation for this. The major packaging signal of SIV appears to be upstream of the SD in a region similar to that of human immunodeficiency virus type 2 (HIV-2) but unlike that of HIV-1; however, the packaging signal of all three viruses are at a similar distance from their respective cap sites. This conserved positioning suggests that it is more important in the virus life cycle than the position of the signal relative to the SD.

5' Untranslated Regions↗