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Biomedical subjects

S Jackson

Publications and source records attributed to S Jackson.

At least 109 records · Page 6Linked to original sources
PubMed1999

Immunization with envelope MN rgp120 vaccine in human immunodeficiency virus-infected pregnant women.

Twenty-six human immunodeficiency virus (HIV)-infected pregnant women participated in a placebo-controlled study of immunogenicity and safety of multiple doses of MN rgp120 vaccine over the last half of pregnancy. The women had CD4 lymphocyte counts>400/mm3, no AIDS-defining illness and normal pregnancies. Vaccination was well tolerated, with no significant local or systemic reactions in the women and no adverse outcomes in the infants attributable to the vaccine. Vaccination did not alter plasma RNA reverse transcriptase-polymerase chain reaction copy number; moreover, immunization was not associated with changes in CD4 counts or HIV binding and neutralization antibody titers. Infants were followed up until 18 months of age. Five of 26 infants (19%) were HIV infected, with infection occurring in children of both vaccinated and placebo women. Analysis of factors that influence transmission did not disclose associations with immunization status, viral load, CD4 count, or maternal viral neutralization titers.

AIDS Vaccines↗
PubMed1999

Oromandibular reconstruction with the radial-forearm osteocutaneous flap: experience with 60 consecutive cases.

One of the more difficult problems in reconstructive surgery of the head and neck is replacement of bone and soft tissue lost because of injury, osteomyelitis, or malignancy. The radial-forearm osteocutaneous flap is an accepted choice for oromandibular reconstruction. This study was undertaken to review one center's experience with 60 consecutive cases of oromandibular reconstruction with the radial-forearm osteocutaneous flap. Records of the 38 men and 22 women (mean age, 60 years; range, 26 to 86 years) were reviewed for tumor location, defect and bone length, flap failure rate, recipient- and donor-site complications, length of surgery, and hospital stay. Cancer resection was the reason for 97 percent of reconstructions; 33 percent of flaps were used to reconstruct a lateral defect of the mandible, 40 percent a lateral-central defect, and 27 percent a lateral-central-lateral defect. Mean skin flap size was 55 cm2 (range, 15 to 117 cm2) and mean bone length, 9.4 cm (range, 5 to 14 cm). The microvascular success rate was 98.3 percent. Complications included fracture of the donor radius (15 percent), nonunion of the mandible (5 percent), and hematoma (8.3 percent). These results are comparable to results reported in the literature with other radial forearm flaps. The free radial osteocutaneous flap is a safe and reliable choice for mandibular reconstruction. It offers sufficient bone to reconstruct large defects and can provide adequate pedicle length for vessel anastomosis to the contralateral side of the neck. The above attributes make the radial forearm osteocutaneous flap one of the "first line" flap choices for oromandibular reconstruction.

Carcinoma, Squamous Cell↗
PubMed1999

Achieving a culture of continuous improvement by adopting the principles of self-assessment and business excellence.

Following a brief description of the inception of self-assessment and the European Foundation for Quality business excellence model, this article describes how one clinical directorate in an NHS Trust used the principles of both to secure a culture of continuous improvement. The journey from a mainly hierarchical, bureaucratic, individualist culture to one where the norms, values and beliefs reflected teamwork, involvement and empowerment is described. The highs, lows and learning points are all included, in an attempt to enlighten other healthcare organisations considering the benefits and pitfalls of using the business excellence model to improve the quality of their healthcare delivery.

Commerce↗
PubMed1999

Exploring the possible reasons why the UK Government commended the EFQM (European Foundation for Quality Management) excellence model as the framework for delivering governance in the new NHS.

A brief introduction into recent developments of the EFQM Excellence Model and the United Kingdom (UK) Government's agenda for ensuring that quality is at the heart of all decision making is given. In view of the Government explicitly commending the use of the EFQM Excellence Model to all organisations within the National Health Service, the author decides to explore the possible reasons behind the commendation. When comparing the EFQM Excellence Model with the Government's vision for quality, the former emerges as a more than ideal tool for any organisation wishing to commence or strengthen their journey on the road to quality and/or excellence; particularly as the EFQM Excellence Model is based on the principles of self-assessment, continuous improvement, learning and innovation, teamwork and a culture totally focused on the customer. Finally, ten possible reasons behind the Government commending the use of the Model are given.

Benchmarking↗
PubMed1999

Depolarising the 'broadened' and 'back-to-basics' relief models.

Prompted by the calls in recent years to link relief practice to peace-building, development, or both, several conferences and papers have recently mounted a strong critique, seeing these 'broadenings' of relief as 'eroding' or 'corrupting' core humanitarian principles and playing into neo-isolationist agendas to slash humanitarianism. This paper argues that whereas these critiques have important goals in mind when they encourage a concentration on the basics of relief, there has been a loss of subtlety in the ensuing debate. Considering each element of the debate in turn, the paper argues that there is more common ground between 'new' and 'old', 'broadened' and 'basics' relief than at first appears. In concluding, it is argued that further research on key questions, and an openness to hear all perspectives will get us further than entrenched positions and rallying cries.

Altruism↗
PubMed1999

Pure stress leakage symptomatology: is it safe to discount detrusor instability?

OBJECTIVE: To determine whether the combination of a urological history and urinary diary, with rigorous selection criteria, can be used to define a group of women on whom urodynamic assessment is unnecessary prior to offering surgery for urinary stress incontinence. DESIGN: Retrospective review of the urodynamic records of women attending for assessment between January 1992 and December 1996. SETTING: Urodynamic Department, Southmead Hospital, Bristol. POPULATION: 5193 women who attended the urodynamic clinic during the five year study period. METHODS: Self-completion of a urinary diary in the preceding week before urodynamic assessment and a detailed urological history before undergoing cystometry by all women in the study period. Data were entered onto a computer database. Women reporting stress incontinence in the absence of bladder filling symptoms, with a normal urinary diary showing daytime frequency of seven times or less and nocturia of no more than once, had the results of their filling cystometry analysed. RESULTS: Of 5193 women, 555 had symptoms of pure stress incontinence and a normal urinary diary. Incontinence was confirmed objectively in 81%, with 9% having incontinence secondary to detrusor instability; 5% had detrusor instability as the sole cause of their incontinence with 4% having a mixed picture of detrusor instability incontinence and urethral sphincter weakness. CONCLUSION: Genuine stress incontinence cannot be diagnosed reliably from a urological history, even when rigorous selection criteria are used in combination with a normal urinary diary. Without cystometry, incontinence secondary to detrusor instability will be missed.

Female↗
PubMed1999

The effect of oestrogen supplementation on post-menopausal urinary stress incontinence: a double-blind placebo-controlled trial.

OBJECTIVE: To investigate the effect of hormone replacement therapy on post-menopausal urinary stress incontinence. DESIGN: Double-blind, placebo-controlled, randomised trial. SETTING: University associated teaching hospital. POPULATION: Post-menopausal women with genuine stress incontinence, not taking hormone replacement therapy. METHODS: Randomisation to six months therapy with oestradiol valerate 2 mg daily or placebo. Assessment prior to treatment and upon study completion with the SF-36 health status questionnaire, the Bristol Female Lower Urinary Tract Symptoms questionnaire, a one week urinary diary, one hour perineal pad test, cystometry and urethral profilometry. RESULTS: Sixty-seven women consented to participate, 33 were randomised to receive oestradiol. Mean age was 63 years. Five women failed to undergo repeat assessment, three of whom were receiving oestrogen. Six women receiving oestradiol experienced breakthrough bleeding during the six months and were subsequently treated with additional monthly progestogen. No significant effect of oestrogen over placebo was observed for any subjective or objective clinical outcome. CONCLUSIONS: This trial is one of the largest controlled studies yet reported, with the longest duration of treatment. No improvement in post-menopausal stress incontinence was demonstrated after six months therapy with oestradiol. This concurs with another study reported recently; it seems unlikely that oestrogen has a significant role to play in this condition.

Double-Blind Method↗
PubMed1999

Subtypes of human immunodeficiency virus type 1 and disease stage among women in Nairobi, Kenya.

In sub-Saharan Africa, where the effects of human immunodeficiency virus type 1 (HIV-1) have been most devastating, there are multiple subtypes of this virus. The distribution of different subtypes within African populations is generally not linked to particular risk behaviors. Thus, Africa is an ideal setting in which to examine the diversity and mixing of viruses from different subtypes on a population basis. In this setting, it is also possible to address whether infection with a particular subtype is associated with differences in disease stage. To address these questions, we analyzed the HIV-1 subtype, plasma viral loads, and CD4 lymphocyte levels in 320 women from Nairobi, Kenya. Subtype was determined by a combination of heteroduplex mobility assays and sequence analyses of envelope genes, using geographically diverse subtype reference sequences as well as envelope sequences of known subtype from Kenya. The distribution of subtypes in this population was as follows: subtype A, 225 (70.3%); subtype D, 65 (20.5%); subtype C, 22 (6.9%); and subtype G, 1 (0.3%). Intersubtype recombinant envelope genes were detected in 2.2% of the sequences analyzed. Given that the sequences analyzed represented only a small fraction of the proviral genome, this suggests that intersubtype recombinant viral genomes may be very common in Kenya and in other parts of Africa where there are multiple subtypes. The plasma viral RNA levels were highest in women infected with subtype C virus, and women infected with subtype C virus had significantly lower CD4 lymphocyte levels than women infected with the other subtypes. Together, these data suggest that women in Kenya who are infected with subtype C viruses are at more advanced stages of immunosuppression than women infected with subtype A or D. There are at least two models to explain the data from this cross-sectional study; one is that infection with subtype C is associated with a more rapid disease progression, and the second is that subtype C represents an older epidemic in Kenya. Discriminating between these possibilities in a longitudinal study will be important for increasing our understanding of the role of specific subtypes in the transmission and pathogenesis of HIV-1.

Base Sequence↗
PubMed1999

Neuropsychological impairment in stroke, carotid stenosis, and peripheral vascular disease, A comparison with healthy community residents.

BACKGROUND AND PURPOSE: An increasing body of literature suggests a role for clinically "silent" cerebrovascular disease in the pathogenesis of cognitive impairment. Such pathology commonly occurs in the absence of stroke. The main aim of the study was to examine neuropsychological impairment associated with cerebrovascular and peripheral vascular disease (PVD) and to compare cognitive deficits with a nonvascular control group. The main hypothesis was that older people with both transient ischemic attack (TIA) and PVD would demonstrate greater cognitive impairment than controls. METHODS: A battery of neuropsychological tests was administered to 4 groups of community residents older than 65 years. The groups comprised 25 patients with carotid stenosis and TIA, 25 nonamputees with PVD, 25 patients with stroke, and 25 matched (with the stroke group) controls. RESULTS: Stroke patients showed greater impairment than controls in all tests. PVD patients did not perform significantly worse (P<0.05 after Bonferroni correction) than control subjects on any of the neuropsychological tests. However, 25% of PVD patients had scores lying within the bottom 5% of control group scores for attention, calculation, and 1 test of frontal lobe function. TIA patients were more impaired in general intellectual impairment and frontal lobe function than controls. Frontal lobe impairment, suicidal thinking, and age were all independent predictors of global cognitive impairment in the TIA group. Frontal lobe impairment was the only predictor of global cognitive impairment in the PVD group. CONCLUSIONS: TIA and PVD patients showed similar patterns of neuropsychological impairment, but TIA may result in more prolonged cognitive impairment, particularly in frontal lobe function. This group may be at increased risk of vascular dementia as well as impulsivity and suicide.

Aged↗
PubMed1999

Reversal of human neutrophil survival by leukotriene B(4) receptor blockade and 5-lipoxygenase and 5-lipoxygenase activating protein inhibitors.

Persistent neutrophilia is a feature of chronic obstructive pulmonary disease (COPD). Leukotriene synthesis inhibitors and cysteinyl leukotriene receptor antagonists have shown efficacy in the treatment of asthma. Antagonism of leukotriene (LT)B(4) receptors is being considered as a mode of treating COPD. We examined the capacity for inhibition of leukotriene synthesis and LTB(4) receptor antagonism to reduce survival of neutrophils from patients with COPD and those from normal subjects. The basal apoptosis level of these cells was 55.4 +/- 2.4% (mean +/- SEM) of total cells. Separate exposure to lipopolysaccharide (LPS), granulocyte-macrophage colony-stimulating factor (GM-CSF), dexamethasone (DEX), and LTB(4) increased neutrophil survival (p < 0. 001). The LTB(4) receptor antagonist SB201146 abolished LPS-induced survival in a concentration-dependent manner (10 pmol to 0.1 microM), with an IC(50) of 1.9 nM. Combined exposure to SB201146 and to the cysteinyl leukotriene antagonist SKF104353 did not have a greater effect on survival than did exposure to SB201146 alone. Inhibition of 5-lipoxygenase (5-LO) with BWA4C and of 5-LO-activating protein (FLAP) with MK886 abolished GM-CSF- and DEX-induced neutrophil survival. BWA4C and MK886 abolished GM-CSF- induced neotrophil survival in a concentration-dependent manner (1 nM to 10 microM), with IC(50) values of 182.0 nM and 63.1 nM, respectively. These findings demonstrate reversal of LPS-, GM-CSF-, and DEX-induced neutrophil survival by LTB(4) receptor antagonism and inhibitors of 5-LO and FLAP. They also suggest a potential additional antiinflammatory mode of action of these compounds through reduction of cell survival.

5-Lipoxygenase-Activating Proteins↗
PubMed1999

Primitive reflexes in cerebrovascular disease: a community study of older people with stroke and carotid stenosis.

OBJECTIVES: To determine the prevalence of primitive reflexes (frontal release signs) in elderly community residents with cerebrovascular disease and to examine their relationship with neuropsychological and mood-related variables. METHODS: Three groups of 25 people over 65 with anterior circulation stroke, transient ischaemic attack (TIA) and a control group were assessed using measures of generalized cognitive impairment, frontal lobe dysfunction, frontal release signs and mood-related variables. Predictors of cerebrovascular disease were examined further in stroke and TIA groups. RESULTS: Both stroke and TIA groups showed a higher mean score on the Frontal Release Signs Scale and a higher prevalence of most reflexes than the control group. Verbal fluency and DSM-IV depressive disorder were independent predictors of frontal release signs. CONCLUSION: TIAs may predispose to subtle neurological impairment, which may be mediated by frontal lobe damage. Their role in the pathogenesis of depression in later life requires further exploration.

Affect↗
PubMed1998

Human and nonhuman primate lymphocytes engrafted into SCID mice reside in unique mesenteric lymphoid structures.

The present study compares the location and phenotype of B lineage lymphocytes in tissues from SCID mice engrafted with PBMC of human, chimpanzee, and pig-tailed macaque origin. In mice repopulated with both human and nonhuman primate lymphocytes, plasma cells were found in the peritoneal cavity in vascularized structures located in the mesentery near the pancreas, intestines, and spleen. The predominant isotype of the plasma cells was IgG; IgM and IgA cells were also present. Kappa and lambda light chains were expressed by 62% and 38% of the Ig-containing cells, respectively. J chain expression occurred in most cells irrespective of the Ig isotype. In the SCID mice engrafted with human lymphocytes, a few IgM-containing cells were found in the spleen; plasma cells were not found in other tissues, including the intestine. The aggregation of plasma cells did not appear to be a result of infection with EBV. T cells were rarely found in the lymphoid aggregates but were recovered from the spleen and peritoneal lavage. Human Ig levels in the serum of engrafted mice reflected the isotype distribution of the cells with IgG > IgM > or = IgA.

Adult↗
PubMed1998

HIV-1/simian immunodeficiency virus infection of human and nonhuman primate lymphocytes results in the migration of CD2+ T cells into the intestine of engrafted SCID mice.

Increased lymphocytic infiltration of intestinal tissues has been observed in patients infected with HIV-1 and in SIV-infected rhesus macaques. To determine whether HIV-1 and SIV infections influence the homing of human and nonhuman primate PBMC to intestinal tissues, we engrafted SCID mice with human or nonhuman primate PBMC and infected them with either cell-free or cell-associated HIV-1 or SIV. In mice that received both PBMC and virus, human or nonhuman primate CD2+ T cells were found in intestinal tissues, primarily in the intraepithelial lymphocyte compartment and lamina propria. Immunomagnetic sorting revealed that these cells were derived from the CD4+ population. Using gag-specific primers, PCR analysis of these tissues detected the presence of HIV-1 proviral DNA. However, in SCID mice that were engrafted with either human or nonhuman primate PBMC and no HIV-1 or SIV, CD2+ T cells were not detected in intestinal tissues. These results indicate that HIV-1 and SIV can modulate the migratory properties of human and nonhuman primate T cells in the SCID mouse model.

Animals↗
PubMed1998

Hydroxamate-based inhibitors of low affinity IgE receptor (CD23) processing.

A series of hydroxamic acids related to the non-selective matrix metalloprotease inhibitor Batimastat is described, which inhibits the proteolytic cleavage of the low affinity IgE receptor from cell membrane preparations. Limited SAR studies suggest that the structural requirements for effective inhibition are distinct from those required for the inhibition of collagenase.

Humans↗
PubMed1998

Selective inhibition of low affinity IgE receptor (CD23) processing.

A series of hydroxamic acids related to the non-selective matrix metalloproteinase inhibitor Batimastat has been prepared, some members of which are potent inhibitors of the processing of the low affinity IgE receptor (CD 23). Increased activity is obtained by appropriate substitution at the alpha-position, whilst selectivity is gained by use of a P1' benzyl group in conjunction with a C-terminal primary amide.

Hydroxamic Acids↗