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R Fox

Publications and source records attributed to R Fox.

At least 109 records · Page 6Linked to original sources

Functional mapping of the cytoplasmic region of intercellular adhesion molecule-3 reveals important roles for serine residues.

Intercellular adhesion molecule-3 (ICAM-3), a ligand for beta2 integrins, elicits a variety of activation responses in lymphocytes. We describe a functional mapping study that focuses on the 37-residue cytoplasmic region of ICAM-3. Carboxyl-terminal truncations delineated portions involved in T cell antigen receptor costimulation, homotypic aggregation, and cellular spreading. Truncation of the membrane distal 25 residues resulted in loss of T cell antigen receptor costimulation as determined by interleukin 2 secretion. Aggregation and cell spreading were sensitive to truncation of the membrane distal and proximal thirds of the cytoplasmic portion. Phosphoamino acid analysis revealed that ICAM-3 from activated cells contained phosphoserine and phosphopeptide mapping identified Ser489 as a site of phosphorylation in vivo. Mutation of Ser489 or Ser515 to alanine blocked interleukin 2 secretion, aggregation and cell spreading, while mutation of other serine residues affected only a subset of functions. Ser489 was a phosphorylation site in vitro for recombinant protein kinase Ctheta. Finally, treatment of Jurkat cells with chelerythrine chloride, a protein kinase C inhibitor, prevented ICAM-3-triggered spreading. This study delineates separable regions and amino acid residues within the cytoplasmic portion of ICAM-3 that are important for T cell function.

Amino Acid Sequence↗

Left main intervention revisited: early and late outcome of PTCA and stenting.

We reviewed our experience with 28 unselected, consecutive patients undergoing left main coronary artery (LMCA) angioplasty who had been considered unsuitable for coronary artery bypass graft surgery (CABG). Fourteen patients (50%) had a protected LMCA circulation. Balloon angioplasty was performed in 11 patients (39.3%), and stents were implanted in 17 patients (60.7%). The procedure was elective in 22 patients (78.6%) and acute in the setting of myocardial infarction/cardiogenic shock in 6 (21.4%). The mean follow-up duration was 15.9 +/- 12 months. There were 5 early (before hospital discharge) and 4 late deaths (total 32.1%), 1 myocardial infarction (3.6%), 6 repeat angioplasties (21.4%), and 3 subsequent CABG (10.7%). All 5 early deaths occurred in patients with cardiogenic shock and unprotected circulation. The results of our study suggest that when patients have prohibitive surgical risks, elective LMCA angioplasty and/or stenting may be undertaken with a high procedural success rate. However, our data do not support intervention in the presence of acute myocardial infarction/cardiogenic shock.

Aged↗

Comparison of bailout versus elective stenting: time to reassess our benchmarks of outcome.

The aim of this study was to compare the clinical outcome of elective and bailout stenting in an era of improved stent deployment techniques and antithrombotic therapy. We retrospectively analysed 136 consecutive patients undergoing stent implantation over a 15 mo period. There was no significant difference in the follow-up duration, length of hospital stay, or the total incidence of major complications between the two groups. Bailout stenting, as compared to elective stenting, was not associated with an increased incidence of in-hospital (no death vs. 1.4%, 4.6% non-Q myocardial infarction vs. 0%, 7.7% vascular complications vs. 7.0%) or late complications (no death vs. 1.4%, no non-Q myocardial infarction vs. 2.8%, 3.1% repeat angioplasty vs. 5.6%, 1.5% coronary artery bypass surgery vs. 1.4%). Stents can be implanted in cases of failed angioplasty with a success rate similar to that of elective stent implantation with a low incidence of complications and equivalent clinical outcome.

Adult↗

Increased incidence of psychotic disorders in migrants from the Caribbean to the United Kingdom.

BACKGROUND: Several studies have replicated the finding of increased incidence of schizophrenia and related psychoses in first and second generation migrants from the Caribbean. The finding has remained consistent in studies employing different methods, but concern has been expressed about indirect methods of calculating the population at risk. This study aims to overcome these short-comings. METHOD: A further prospective study was undertaken in Nottingham assembling an inception cohort of psychotic patients (N = 168) presenting from a defined catchment area. The 1991 census, which includes codings for self-ascribed ethnic origin, was used to calculate the denominator, employing correction factors for potential under-enumeration. Case-ascertainment was based upon all service contacts and subjects had in-depth assessments including the SCAN. Collateral history was obtained from informants. RESULTS: Subjects born in the Caribbean, or who had one or both parents born in the Caribbean, had a greatly elevated risk (incidence ratios above 7) for all psychotic disorders and for ICD-10 (DCR)-defined F20 Schizophrenia. CONCLUSIONS: The size of the increase and the methodological safeguards employed support the validity of this now highly replicated finding. A personal or family history of migration from the Caribbean is a major risk factor for psychosis; the consistency of this finding justifies a systematic evaluation of potential aetiological factors. Any hypothesis derived from the evidence so far must explain: increased incidence in first and second generation migrants; increased risk for all psychoses (including affective psychoses); and an effect specifically associated with a migration history from the Caribbean to Northern Europe.

Adolescent↗

Intra-amniotic debris identified at ultrasound scanning: a feature of congenital ichthyosis.

A case is described in which intra-amniotic debris was identified during an ultrasound scan in a woman with polyhydramnios at 33 weeks' gestation. At delivery the neonate was found to have severe ichthyosis involving the whole of her head, trunk and limbs, with large plaques of hyperkeratotic skin on the palms of her hands and the soles of her feet. The finding of excessive debris in association with polyhydramnios should raise the possibility of an exfoliative skin disorder.

Adult↗

Definitions of genital ulcer disease and variation in risk for prevalent human immunodeficiency virus infection.

OBJECTIVES: Although genital ulcer disease (GUD) has been associated with human immunodeficiency virus (HIV) infection in a number of studies, definitions of genital ulceration have varied. The authors hypothesized that the association of GUD with prevalent HIV infection may vary according to the definition of GUD that is used. METHODS: As part of a prospective cohort study, 863 patients were interviewed and examined who presented to a sexually transmitted disease (STD) clinic for new symptom evaluation and who agreed to HIV testing to determine demographic and behavioral risk associated with prevalent HIV infection. To determine the association between GUD and prevalent HIV, the following definitions of GUD were used: observed ulcers, history of syphilis, serologic evidence of syphilis, observed culture-proven genital herpes, and serologic evidence of herpes simplex virus type II (HSV-2) infection. RESULTS: Of 481 men and 382 women enrolled, prevalent HIV infection was detected in 12.5% and 5.2%, respectively. In multivariate analyses controlling for known HIV risk behaviors, prevalent HIV infection was associated with observed GUD (odds ratio [OR] = 2.0, 95% confidence intervals (CI) = 1.0-3.9), a history of syphilis (OR = 6.0, CI = 2.8-12.7), and serologic evidence of syphilis (OR = 3.7, CI = 1.9-7.0), but not with serologic evidence of HSV-2 (OR = 1.2, CI = 0.7-2.1), nor with observed HSV-2 culture-positive genital ulcerations (OR = 1.0, CI = 0.4-4.2). Factors contributing to different strengths of association between HIV infection and a history of syphilis or serologic evidence of syphilis included the presence of underdiagnosed syphilis infection in people with reactive serologic tests and the absence of serologic reactivity in people with a positive history. CONCLUSIONS: Although GUD is strongly associated with prevalent HIV, the strength of the association depends on the definition of GUD used. For accurate evaluation of people at risk for HIV, clinicians and researchers should use multiple definitions of GUD.

Adolescent↗

Multiple cycles of aggressive chemotherapy prior to autologous peripheral stem cell transplantation for lymphoma.

BACKGROUND: Based on in vitro evidence of synergy between certain chemotherapeutic agents and of improved efficacy of cytotoxics administered as continuous infusions we devised a novel chemotherapy regimen for use in patients with lymphoma. AIMS: To assess the efficacy and tolerability of this regimen alone and in combination with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory lymphoma. METHODS: The regimen consisted of cytosine arabinoside and etoposide given as five day continuous infusions, bolus doses of methotrexate and cyclophosphamide and four days of oral dexamethasone (MADEC), together with prophylactic G-CSF. Fifty-one patients aged 17 to 65 years (median 43) were treated; 34 had intermediate or high grade non-Hodgkin's lymphoma and 17 had Hodgkin's disease. Patients with responsive disease received a second cycle. RESULTS: Eleven patients (22%) achieved a complete response and 19 patients (38%) achieved a partial response, eight of whom were gallium negative. Previous chemosensitivity was highly predictive for response; minimal response was seen in patients with primary refractory disease. The probability of survival and event-free survival at 40 months for the entire group is 46% (+/- 8% SEM) and 26 +/- 8% respectively. Thirty-one patients proceeded to ASCT; the probability of survival of the transplanted group is 65 +/- 11% at 40 months. The regimen caused significant myelosuppression. The majority of cycles were complicated by febrile neutropenia and the requirement for platelet and red cell transfusions. Non-haematological toxicity was predominantly mucositis and was generally mild. CONCLUSIONS: MADEC is a highly active regimen in patients with relapsed lymphoma. Patients responding to MADEC who proceed to ASCT have a good chance of achieving a durable remission.

Adolescent↗

Ovarian response to purified FSH in infertile women with long-standing hypogonadotrophic hypogonadism.

It has previously been proposed that all anovulatory women requiring exogenous gonadotrophin therapy could be treated by purified FSH alone in the follicular phase. We have studied the ovarian response to purified FSH in 5 amenorrhoeic women with low endogenous LH production as a result of long-standing hypothalamic amenorrhoea. Follicles developed in all of the women but the rise in oestradiol was very slow. As a consequence of the HCG injection being delayed to allow the follicles to become functionally mature, too many follicles attained a preovulatory size. After the treatment was changed to more conventional preparations containing both FSH and LH, the women had improved ovarian responses and 3 of them conceived. It is clear that FSH alone will promote follicular growth but that LH is needed to stimulate follicular function. We conclude that LH does play an important role in follicular maturation and that it is a critical component of exogenous gonadotrophin therapy for women with prolonged hypogonadotrophic hypogonadism.

Adult↗

Incidence of schizophrenia in Nottingham. A comparison of two cohorts, 1978-80 and 1992-94.

BACKGROUND: Several studies have reported a decline of up to 50% in the incidence of schizophrenia over recent decades. We aimed to measure changes in the incidence and diagnostic patterns of first-episode psychosis by comparing two Nottingham cohorts, identified in two equal periods separated by 14 years. METHOD: Two prospectively ascertained cohorts of first-episode psychotic disorder were identified over the time periods 1978-80 and 1992-94. The earlier cohort was of the World Health Organization Determinants of Outcome of Severe Mental Disorder (DOSMD) ten-country study. The later cohort was obtained using similar methodology. Both groups were diagnosed using ICD-10 diagnostic criteria and age-standardised incidence rates were compared. RESULTS: The standardised incidence rate for all psychotic disorders rose slightly from 2.49 to 2.87 per 10000 population per year, but the F20 classification fell significantly by over a third (1.41 to 0.87 per 10000 per year). The second study group (1992-1994) included a greater diversity of psychotic diagnoses compared with the first, in particular an increased proportion of acute and drug-related psychoses. CONCLUSIONS: Methodological considerations call for caution in interpreting such data, but we conclude that the significant fall in the narrowly defined diagnostic category of schizophrenia reflects a real change in the syndromal presentation of psychotic disorders.

Adolescent↗

Reduced Anticoagulation with Antiplatelet Therapy Alone is Safe and Effective after "Bail-Out" Stenting for Failed Angioplasty.

The aim of this retrospective study was to compare the safety and efficacy of antiplatelet therapy alone with conventional anticoagulation with warfarin after Òbail-outÓ coronary stenting for failed balloon angioplasty at a tertiary referral centre. Eighty-two consecutive patients undergoing Òbail-outÓ stenting over a 22-month-period were studied. Forty patients received antiplatelet therapy alone with aspirin and ticlopidine and 42 patients received anticoagulation with warfarin for 30 days. The main outcome measures examined were death, myocardial infarction, coronary artery bypass surgery, repeat angioplasty, and significant vascular complications. The angiographic procedural success rate was 100% in both groups. At six weeks there were no deaths and no patient required emergency coronary artery bypass surgery in either group. There were three (7.1%, p = NS) stent thromboses and two (4.8%, p = NS) Q-wave myocardial infarctions in the warfarin group as compared to none in the antiplatelet group. There was a significantly higher incidence of vascular complications in the warfarin group (21.4% vs. 0%, p = 0.004). The length of hospital stay was significantly shorter in the antiplatelet group [3.4 (2.0) vs. 7.8 (2.6) days, p < 0.001]. This study suggests that reduced anticoagulation with antiplatelet therapy alone after Òbail-outÓ stenting is an effective and safe strategy which reduces vascular complications and hospital stay without increasing the rate of stent thrombosis.

Journal Article↗