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Biomedical subjects

J Stewart

Publications and source records attributed to J Stewart.

At least 37 records · Page 2Linked to original sources

Atypical development of Sertoli cells and impairment of spermatogenesis in the hypogonadal (hpg) mouse.

Testes of hypogonadal (hpg) mice show arrested postnatal development due to congenital deficiencies of gonadotrophin-releasing hormone (GnRH) and gonadotrophin synthesis and secretion. Follicle-stimulating hormone (FSH), androgen or oestrogen treatment restore qualitatively normal spermatogenesis in hpg testes. Understanding the cellular and molecular changes accompanying hormone-induced spermatogenesis in hpg mice requires detailed morphological analyses of the germ cells and Sertoli cells in the untreated hpg testis. We compared seminiferous epithelial cytology in adult hpg, immature and adult wild-type mice using unbiased optical disector-based stereology, immunolocalization of Sertoli cell microtubules (MT), espin (a component of the blood-testis barrier), markers of Sertoli cell maturity (p27(kip1) and WT-1), and electron microscopy. Hpg testes had marked reductions in weight, seminiferous cord volume and length, and severe spermatogenic impairment with germ cells per testis < 1% of adult wild-type testes. Sertoli cell nuclei expressed WT-1 in hpg testes, but often were centrally located, similar to 9-14-day-old wild-type testes, and they expressed p27(kip1), indicating that hpg Sertoli cells were post-mitotic. Hpg testes had significantly (P < 0.05) reduced Sertoli cells per testis (0.56 million) compared with 10-day wild-type (1.15 million) and adult wild-type testes (2.06 million). Immunofluorescence labelling of normal adult Sertoli cells showed supranuclear MT columns and basally located espin, but these features were absent in 10-day-old and hpg Sertoli cells. Hpg Sertoli cells showed pleomorphic nuclear ultrastructure with mature-type nucleoli, similar to normal adult-type Sertoli cells, but hpg Sertoli cells exhibited incomplete tight junctions that lacked ectoplasmic specializations. We conclude that in hpg mice, chronic gonadotrophin insufficiency restrains Sertoli cell proliferation and maturation, forming pseudo-adult-type Sertoli cells that are incapable of supporting germ cell proliferation and maturation.

Animals↗

Idiopathic osteoarthritis and contracture: causal implications.

OBJECTIVE: To use the known association of idiopathic osteoarthritis with contracture as a means of searching for its cause. There are currently two theories concerning this association, one assuming that the contracture is a consequence of the osteoarthritis and the other that it precedes and causes the osteoarthritis. This study tested both theories. METHODS: Flexion ranges in the 12 finger joints were obtained by goniometric measurement in two samples of normal female subjects, one group with a mean age of 22 years (25 subjects) and one with a mean age of 45 years (50 subjects). The results were compared with the known regional prevalence of osteoarthritis in the finger joints of women. RESULTS: The older group showed evidence of reduced flexion range consistent with development of contracture in the extensor mechanism of the fingers. The distribution of the contracture showed a strong negative correlation with the regional prevalence of osteoarthritis. CONCLUSIONS: An early dorsal contracture develops in the fingers of normal subjects, but it is neither a consequence of nor the cause of digital osteoarthritis. The most parsimonious explanation for the association is that both contracture and idiopathic osteoarthritis are independent consequences of failure to use the full movement range. If this hypothesis is correct, the disease could be preventable.

Adult↗

A paediatric case of a solitary fibrous tumour of the parotid gland.

Solitary fibrous tumours are rare and they were first described in the pleura of the lungs. However this rare tumour is being increasingly recognised in the oro-facial region and other extra-pleural sites among adults. We present a paediatric case of a solitary fibrous tumour of the parotid gland in an 11-year-old girl who was also diagnosed as having type I neurofibromatosis.

Child↗

Collaborative management of HIV infection in the community: an effort to improve the quality of HIV care.

Our hospital led a multidisciplinary community team to improve the quality of care delivered to HIV-infected clients utilizing a disease management approach in a US metropolitan community of 150,000 people. Community needs assessment and client and community surveys were used to define the problems. Patient care flowcharting and the creation of an electronic patient database facilitated patient tracking across the entire community. Clinical guidelines and a consultation and referral immunology clinic standardized care practices. Measurable improvements in the quality of care were noted in multiple areas. Flowchart completion rates rose from 44% to 100%; medication adherence assessment rose from 82% to 100%; immunization rates rose from a mean of 72% to a mean of 87%; PPD screening rose from a low of 35% to a high of 87%; perinatal transmission rates fell from 31% to 4%; and Emergency Department utilization decreased. Two essential components of the effort were the establishment of a full-time leadership position in the form of a clinical nurse practitioner and the creation of an electronic database with flowcharting to standardize the measurement, delivery and tracking of care. The programme has become an example of successful disease management through hospital-community collaboration.

Adult↗

Influence of subinhibitory concentrations of plant essential oils on the production of enterotoxins A and B and alpha-toxin by Staphylococcus aureus.

The data presented show the ability of subinhibitory concentrations of plant essential oils to influence the production of enterotoxins A and B and alpha-toxin by Staphylococcus aureus. Subinhibitory concentrations of the oils of bay, clove, cinnamon, nutmeg and thyme had no significant effect on the overall quantity of extracellular protein produced. Haemolysis due to alpha-toxin was significantly reduced after culture with all five plant essential oils. This reduction was greatest with the oils of bay, cinnamon and clove. These three oils also significantly decreased the production of enterotoxin A; the oils of clove and cinnamon also significantly decreased the production of enterotoxin B.

Enterotoxins↗

There is no evidence of an association in children and teenagers between the apolipoprotein E epsilon4 allele and post-traumatic brain swelling.

Traumatic brain injury (TBI) is an important cause of mortality and disability in children and teenagers. A particular feature of the neuropathology at post-mortem is brain swelling. The cause of the swelling in some cases is not known, while in others it is associated with traumatic axonal injury or hypoxia. Apolipoprotein E (APOE) epsilon4 allele is known to be an important genetic determinant of outcome in children after TBI. We hypothesized a relationship between possession of APOEepsilon4 and diffuse traumatic brain swelling. A total of 165 cases aged between 2 and 19 years were identified from the department's tissue archive. APOE genotype was determined by polymerase chain reaction (PCR) in 106 cases. Bilateral swelling was present in 44 cases (11 with APOEepsilon4), unilateral swelling in 25 cases (7 with APOEepsilon4) and in 36 cases (9 with APOEepsilon4) there was no evidence of brain swelling. There was no significant relationship between possession of APOEepsilon4 and the presence of cerebral swelling (chi(2) = 0.09, df = 2, P = 0.96). The 95% confidence interval for difference in proportions with swelling in those with and without the APOE epsilon4 is -19% to 22%. Thus, a significant relationship was not found between diffuse brain swelling and possession of APOEepsilon4, and in this cohort of patients there was an identifying cause of the brain swelling in all cases.

Adolescent↗

Medfly (Diptera: Tephritidae) genetic sexing: large-scale field comparison of males-only and bisexual sterile fly releases in Guatemala.

The effect of releases of bisexual (males and female) and unisexual (male only) sterilized medflies was compared in three large field evaluations over a 3-yr period (1995-1997) in southwestern Guatemala. The two strains tested were a genetic sexing strain, Vienna-4/Tol-94, carrying the temperature sensitive tsl gene to eliminate females in the egg stage, and the standard bisexual Petapa strain. Flies were mass-reared, sterilized by irradiation as pupae, shipped to a field center, and released by air as young adults over 2 km by 2 km core areas in the centers of separate 6 km by 6 km test plots. Strain performance was monitored weekly by trapping sterile and wild male adults in core and buffer areas and by collecting eggs from coffee berries to determine induced sterility. Results indicated a several-fold advantage for the males-only strain as measured by the level of induced sterility, especially at the very high release ratios of 100:1 recorded in 1997. During that final test year, sterile-fly release rates were increased to provide high sterile:wild (S:W) fly ratios in the field, and egg sterility reached levels in excess of 70% in plots were the male-only strain was used. However, in the plots where the bisexual strain was released, induced sterility only reached 12% despite S:W ratios above 1,000:1.

Agriculture↗

Modified de Gramont with oxaliplatin in the first-line treatment of advanced colorectal cancer.

We previously reported high activity for oxaliplatin and a modified de Gramont regimen (OxMdG) in a single centre study of patients with metastatic colorectal cancer. We now report results with a further 56 patients treated at 14 centres. Low rates of grade 3 and 4 toxicity were seen, with no toxic deaths. Objective response rates were CR/PR=53%; NC=34.7%; PD=12.2%. Median time to progression was 8.3 months and overall survival was 14.5 months. This regimen is more convenient than those based around the conventional de Gramont regimen but is highly active and well tolerated; it forms part of a current UK MRC phase 3 trial.

Adult↗

Association between interleukin-1A polymorphism and cerebral amyloid angiopathy-related hemorrhage.

BACKGROUND AND PURPOSE: It has been suggested that the interleukin-1A (IL-1A) allele 2 is a risk factor for Alzheimer's disease (AD). Because cerebral amyloid angiopathy-related hemorrhage (CAAH) often coexists with AD, we examined the IL-1A polymorphism in CAAH. METHODS: In a case-control study, patients with pathologically verified CAAH, AD patients without intracerebral hemorrhage, and neuropathologically normal control subjects were studied. DNA was extracted from brain tissue, and IL-1A was genotyped. Logistic regression was used to examine the IL-1A polymorphism in CAAH patients with and without AD compared with AD and non-AD control subjects. RESULTS: There were 42 patients with CAAH, 232 AD patients, and 167 non-AD control subjects. In age-adjusted analyses, there was no association between possession of IL-1A allele 2 and risk of CAAH compared with AD control subjects (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.45 to 1.97; P=0.87) or non-AD control subjects (OR, 0.94; 95% CI, 0.47 to 1.87; P=0.86). Stratifying for the presence of apolipoprotein E epsilon2 or epsilon4 demonstrated the known increased risk of CAAH from these lipoprotein E alleles. Subgroup analyses demonstrated a nonsignificant excess of the IL-1A 2,2 genotype in patients with CAAH and AD compared with those CAAH patients who did not have histological evidence indicating AD (OR, 2.17; 95% CI, 0.15 to 122.3; P=0.64). Comparisons between CAAH patients with AD and AD control subjects and between CAAH patients without AD and non-AD control subjects did not demonstrate an association between CAAH and possession of either the IL-1A allele 2 or the 2,2 genotype. CONCLUSIONS: The IL-1A allele 2 or 2,2 genotype does not appear to be a major risk factor for CAAH.

Aged↗

Effects of sex and hormonal status on astrocytic basic fibroblast growth factor-2 and tyrosine hydroxylase immunoreactivity after medial forebrain bundle 6-hydroxydopamine lesions of the midbrain dopamine neurons.

We examined astrocytic basic fibroblast growth factor immunoreactivity (FGF-2-IR) and tyrosine hydroxylase immunoreactivity (TH-IR) in the cell-body region of midbrain dopaminergic neurons after unilateral infusions of the neurotoxin 6-hydroxydopamine into the medial forebrain bundle in male and female rats. In addition, to determine whether neonatal exposure to gonadal hormones has consequences on the expression of astrocytic FGF-2 and cell loss in response to injury in adulthood, we studied the effects of these lesions in adult male and female rats that had been exposed or not to testosterone in the neonatal period. In both males and females there was a progressive loss of TH-expressing cells that peaked 5 weeks after the lesions. Females showed less loss of TH-expressing cells than males, but this effect was not estrogen dependent. Lesions led to an increase in expression of astrocytic FGF-2 that was greater in males than in females. Finally, it was found that, regardless of genetic sex, rats exposed to testosterone neonatally showed greater astrocytic FGF-2 expression after lesions than those not exposed, and that among those not exposed to testosterone, estrogen treatment had a modest protective effect. Analysis of behavior and striatal dopamine content showed that the percent of striatal dopamine depletion 14 days after the lesion correlated with the amount of behavioral asymmetry displayed by animals on all tests conducted after lesioning. In groups killed 2 and 5 weeks after the lesion, the amount of behavioral asymmetry correlated with the percent loss of TH-IR cells and with the percent increase in FGF-2-IR cells in the midbrain. These relationships were not evident in groups killed 3 and 7 days after the lesion, possibly because the changes in the number of FGF-2- and TH-IR cells were not fully manifested. The present findings show that hormonal events early in life can alter the response of midbrain dopamine neurons to insult and injury in adult life and suggest that the slow degeneration of these neurons may release signals triggering a sustained activation of adjacent astrocytes which, in turn, may lead to induction of astrocytic FGF-2.

Animals↗

Phenotypic switching of VEGF and collagen XVIII during hypoxia in head and neck squamous carcinoma cells.

The present study sought to determine the potential role of stress activated MAPK and phosphatidylinositol 3-kinase (PI3K) signaling pathways in mediating phenotypic switching between angiogenic and angiostatic elements among squamous cell carcinoma (SCC) cell lines. In particular, we investigated the effects of hypoxia and those of cobalt chloride (CoCl(2)), which mimics the hypoxic response including the production of reactive oxygen species, on such phenotypic shifts. The expression and production of collagen XVIII, and CBP2/Hsp47 provided a measure of an angiostatic phenotype, while vascular endothelial growth factor (VEGF) expression was used to assess potential angiogenic states. These studies revealed that hypoxia produced a slight up-regulation of collagen XVIII and CBP2/Hsp47 that was inhibited by the stress kinase inhibitor SB203580 but was unaffected by N-acetylcysteine (NAC). In addition, VEGF expression was increased following hypoxia and this effect was reversed with inhibition of by SB203580. Conversely, CoCl(2) significantly diminished the expression of both collagen XVIII and CBP2/Hsp47 and enhanced VEGF expression. These changes were reversed by the PI3K inhibitor wortmannin and by treating cells with NAC. These studies show that phenotypic switching between collagen XVIII and VEGF is controlled by stress activated kinases under hypoxia, and PI3K signaling pathways as well as reactive oxygen species (ROS) following CoCl(2) treatment. Furthermore, modulation of the angiogenic switch is most profound during Akt activation than during activation of stress activated kinases.

Acetylcysteine↗

A review of social housing regeneration in the London Borough of Brent.

Council high-rise estates sprang up rapidly during the 1960s and 1970s, with cross-governmental support to resolve the nation's housing crisis. It soon became apparent that many such new estates, designed by remote architects, and sometimes constructed rapidly and unsatisfactorily, did not provide the ideal living initially perceived. Many estates had early problems with architecture, construction and design. They proved an inhumane environment for many residents and there were frequent problems with communal features. Such estates were soon stigmatised and difficult to let as increasingly residual households were placed there, creating majority welfare-dependent estates. This created a downward spiral that traditional, and remote, housing management found difficult to address, and was too wide-scale to rectify financially within existing regimes. Prior to the 1980s, there were no specific government policies to tackle housing regeneration on high-rise estates. Problems became wider than traditional housing management and poor housing environments, encompassing social and economic exclusion. This paper, based on historical and contemporary literature as well as estate visits, reviews regeneration policy in three council housing estates within the London Borough of Brent. It traces successive government approaches since the 1980s from one that challenged the very status of council housing--notably at Stonebridge Park and Chalkhill, to one of partnership with the local authority--at South Kilburn. Housing policy is now concerned with more than just housing--it is about moving toward social inclusion, which requires initiative, flair, resource and commitment. It is about new accountabilities--not just numbers of bricks and mortar constructions, but about the lives, opportunities and health of those who live in an area. This fundamentally involves a partnership approach with residents at the centre of regeneration. This paper finds that sustainable estate regeneration policies are about continued improvements in both housing policy and social development.

Adolescent↗

Thick vs thin loop transurethral resection of the prostate: a double-blind prospective trial of early morbidity.

OBJECTIVE: To compare blood loss, irrigation requirements and hospital stay between standard transurethral resection of the prostate (TURP) and resection incorporating vaporization, i.e. transurethral vaporization resection (TUVRP). PATIENTS AND METHODS: Seventy patients were prospectively randomized in a blinded fashion between TURP with a standard resection loop (thin loop) or resection with a roller cutting electrode (thick loop). The outcome was assessed as the change in haemoglobin at 30 min and 24 h after the resection finished. Secondary outcome measures were irrigation requirements, length of catheterization, hospital stay, changes in serum sodium, and complications. The nursing staff and surgical registrar managing the patients after surgery were unaware of the resection technique used. RESULTS: Data were available for 65 patients (36 thin loop and 29 thick loop resections). The mean decrease in haemoglobin after TURP was 14.8 g/L at 30 min and 11.8 g/L at 24 h; for TUVRP the corresponding values were 14.6 and 14.2 g/L (P = 0.69). In addition, there was no difference in irrigation requirements, changes in serum sodium, length of catheterization, hospital stay or bleeding complications. CONCLUSION: The use of a thick loop at higher cutting current settings during TUVRP offers no advantage over standard thin-loop TURP.

Aged↗

Ultrasonic debridement of contaminated facial wounds.

Contaminated facial wounds can be debrided with the Piezon ultrasonic scaler. The fine scaler tip provides efficient, rapid, precise and thorough removal of ingrained subdermal dirt and grit without the loss of viable facial tissue.

Adolescent↗

Inhibition of listeriolysin O and phosphatidylcholine-specific production in Listeria monocytogenes by subinhibitory concentrations of plant essential oils.

Successful infection by Listeria monocytogenes is dependent upon a range of bacterial extracellular proteins including a cytolysin termed listeriolysin O and phosphatidylcholine-specific phospholipase C. Five plant essential oils--bay, clove, cinnamon, nutmeg and thyme--significantly reduced the production of listeriolysin O by L. monocytogenes. The greatest change was observed after culture with oil of thyme, which reduced haemolysis to 52.1 haemolytic units (HU)/ml compared with 99.8 HU/ml observed with the control. Oil of clove was the only oil that also significantly reduced phosphatidylcholine-specific phospholipase C activity. These changes were observed despite the oils causing no change to the final bacterial concentration or total extracellular protein concentration.

Bacterial Toxins↗

Incidence and case fatality rates of stroke subtypes in a multiethnic population: the South London Stroke Register.

OBJECTIVE: To identify sociodemographic differences in the incidence of the subtypes of first ever stroke in a multiethnic population. METHODS: A prospective community stroke register (1995-8) was developed using multiple notification sources and pathological and clinical classifications of stroke. Standardisation of rates was to European and World populations and adjusted for age, sex and socioeconomic status in multivariate analyses. A multiethnic population of 234 533 in south London, of whom 21% are black was studied. RESULTS: A total of 1254 cases were registered. The average age of stroke was 71.7 years with black patients being 11.3 years younger than white patients (p<0.0001). The incidence rate/1000 population was 1.33 (crude) (95% CI 1.26 to 1.41), 1.28 (European adjusted) (95% CI 1.2 to 1.35) with a 2.18 (95% CI 1.86 to 2.56) (p<0.0001) age and sex adjusted incidence rate ratio in the black population. Radiological diagnosis was confirmatory in 1107 (88.3%) with 862 (68.7%) infarction, 168 (13.4%) primary intracerebral haemorrhage, and 77 (6.2%) subarachnoid haemorrhage. Of the cerebral infarction cases 189 (21.9%) were total anterior circulatory, 250 (29%) partial anterior, 141 (16.4%) posterior (POCI) and 282 (32.7%) lacunar infarcts. The black group had a significantly higher incidence of all subtypes of stroke except for POCI and unclassified strokes. The incidence rate ratio (IRR) for men compared with women was 1.34 (95% confidence interval (95% CI) 1.19 to 1.50; p<0.001). The IRR for manual versus non-manual occupations in those aged 35-64 years was 1.64 (95%CI 1.22 to 2.23; p<0.0001). There was a borderline significant increase in adjusted survival at 6 months in the black group 95% (CI 0.61 to 1.03, p=0.078) with a hazard ratio of 0.79 after adjustment and stratification. CONCLUSIONS: Although the black population is at increased risk of stroke and most subtypes of stroke, this is not translated into significant differences in survival. Hence black/white differences in mortality are mainly driven by incidence of stroke. There are striking demographic inequalities in the risk of stroke in this multiethnic inner city population that need to be tackled through interagency working. Although the reasons for the increased risk in the black population are unclear, demographic factors such as socioeconomic status do seem to play a significant independent part.

Adolescent↗

Community self-help and the homeless poor in Latin America.

Finding realistic housing solutions that are able to respond to the realities of poverty in the developing, or newly industrializing, world are frequently distinct from those suited to the developed world due to levels of poverty and differing welfare regimes. This requires a different understanding of the concept of housing and shelter for developing and developed countries. Population increase and emerging habitation patterns in parts of Latin America have required that policy-makers review traditional 'top down' approaches to the way the homeless poor are treated and how self-help or 'bottom up' schemes are increasingly seen as a sustainable way forward in providing affordable housing options to both governments and communities. Over the last decades, mass in-migration to cities has put pressure on governments to provide public housing--but two major problems arose: firstly, governments found it difficult to finance the increasing demand for public housing, and secondly, the nature of employment and the informal economy in the developing world meant that this new housing was often too costly for the urban poor, in some cases increasing homelessness still further. Recent policy developments tend to favour supporting what the poor are and have been able to achieve for themselves, with appropriate government support. Upgrading shack settlements is now recognised as a community driven and cost-effective response that can, if appropriately supported, offer an initial and sustainable solution to urban housing need by tapping into additional non-governmental sources of funding. In the absence of a major public sector housing stock to meet demand, governments are also recognising that self-help housing schemes for families able to access funding and resources offer a further innovative approach to meeting housing need. The nature of housing and shelter in the developing world requires a unique response so that it remains attainable and affordable to the poor. Neo-liberal policies, increasingly adopted in Latin America, are not able to provide suitable, sustainable and affordable housing delivery and alternatives need to be explored. This paper traces some developments in Latin American housing policy and explores some of the challenges that are faced in responding to the unique housing needs of the urban poor.

Developing Countries↗

Prevalence of Shiga toxin-producing Escherichia coli in ground beef and cattle feces from King County, Washington.

Shiga toxin-producing Escherichia coli (STEC) is increasingly recognized as a common cause of diarrhea. STEC infection is a major public health threat because of its ability to cause serious and potentially life-threatening illnesses. The main reservoirs of STEC are believed to be the intestinal tracts of animals. Several studies have investigated the prevalence of STEC in various food items. The objective of this study was to determine the prevalence of STEC in the Seattle ground beef supply. In addition, the relative amount of STEC contamination between stores was compared, and possible differences between types of ground beef based on fat content (9, 16, and 23%) were investigated. A survey of Stx-I and/or Stx-II genes in fecal samples from cattle at a local slaughterhouse was also conducted. Of 296 ground beef samples tested from area retail grocery stores, 16.8% were positive for the presence of the toxin genes. Our data showed that there was no statistically significant difference (P > 0.05) in the prevalence of STEC between the ground beef samples of different fat contents and between grocery store chains. Of the 103 cattle fecal samples tested, 19 (18.4%) were found positive for the presence of Stx-I and/or Stx-II genes. The presence of a rather high percentage of STEC in the food supply in the absence of large number of cases suggests that not all STEC lineages are pathogenic for humans.

Animals↗