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Biomedical subjects

S Cross

Publications and source records attributed to S Cross.

At least 55 records · Page 3Linked to original sources
PubMed1997

A case report: immune responses and clinical course of the first human use of granulocyte/macrophage-colony-stimulating-factor-transduced autologous melanoma cells for immunotherapy.

The first use of granulocyte/macrophage-colony-stimulating-factor-transduced, lethally irradiated, autologous melanoma cells as a therapeutic vaccine in a patient, with rapidly progressive, widely disseminated malignant melanoma resulted in the generation of a novel antitumour immune response associated with partial, albeit temporary, clinical benefit. An initially negative reaction to non-transduced, autologous melanoma cells was converted to a delayed-type hypersensitivity (DTH) reaction of increasing magnitude following successive vaccinations. While intradermal vaccine sites showed prominent dendritic cell accrual, DTH sites revealed a striking influx of eosinophils in addition to activated/memory T lymphocytes and macrophages, recalling the histology of challenge tumour cell rejection in immune mice. Cytotoxic T lymphocytes (CTL) reactive with autologous melanoma cells were detectable at high frequency after vaccination, not only in limiting-dilution analysis, but also in bulk culture without added cytokines. Clonal analysis of CTL showed a conversion from a purely CD8+ response to a high proportion of CD4+ clones following vaccination. A prominent acute-phase response manifested by a five- to tenfold increase in C-reactive protein was observed, as was a systemic eosinophila. Vaccination resulted in the regression of axillary lymphatic metastases, stabilisation of pulmonary metastases, and a dramatic, reversible increase in cerebral oedema associated with multiple central nervous system metastases: however, lesions in the adrenal glands, pancreas and spleen proved refractory. The antitumour effects and immune response were not detectable 2 months following the last vaccination. Irradiation of the extensive cerebral metastases resulted in rapid deterioration and death of the patient.

Autopsy↗
PubMed1997

Blood pressure and cognitive decline in healthy old people.

Both hypertension and cognitive decline are common in old age. We sought to examine the effects of blood pressure (BP) on rates of cognitive decline in a longitudinal study of community-resident healthy old people. A total of 603 initially healthy old people aged over 69 years were visited at home. Subject's age, years of full-time education, Social Occupational Classification, health status and medication use were recorded. Sitting systolic and diastolic BP was measured, and the Mini-Mental State Examination (MMSE) and National Adult Reading Test (NART) administered. Follow-up was planned after 4 years: 69 subjects were dead, 15 were too unwell and 12 had moved away; 78 subjects either refused or failed to reply. Psychometric tests were administered to the remaining 429 (71.1%) after a median period of 4.20 years. Forty-two subjects had significant sensory impairment or interrupted testing. No significant differences in cognitive decline were found between those who had started medication (n = 163) and those remaining untreated (n = 224). Mean MMSE score change was 0.44 points (s.d. 2.07, P < 0.001). Entering all baseline variables into a stepwise regression analysis significant positive effects were found for initial MMSE score (beta = 0.50, P < 0.001), age (beta = 0.17, P < 0.001), systolic BP (beta = 0.16, P < 0.001) and period between testing (beta = 0.14, P = 0.004), and negative effect for NART-predicted IQ (beta = -0.16, P = 0.003).). We conclude that (1) older people exhibit faster age-associated cognitive decline as measured by MMSE; (2) people with higher NART-predicted IQs are relatively protected; (3) people with high systolic BPs are at greater risk of cognitive decline.

Aged↗
PubMed1997

Age-associated cognitive decline in healthy old people.

BACKGROUND: disease often confounds the identification of risk factors for age-associated cognitive decline in elderly subjects. If the cognitive effects of ageing are to be distinguished from those of disease, healthy people need to be studied. METHODS: we examined the effects of incident disease and drug prescription on cognitive change in a sample of initially healthy old people in a longitudinal study and related these to age, education, social class and blood pressure. We screened general practice case notes of 10,000 patients aged 70 years and over resident in Edinburgh to identify potentially healthy subjects. We visited 1467 potential subjects at home and enquired directly about health problems and medications, administered the Mini-Mental State Examination (MMSE) and National Adult Reading Test and recorded educational attainment, occupation and blood pressure. RESULTS: 603 subjects (237 male, 366 female), mean age 75.7 years (range 70-88 years), reported no health problems and were taking no regular medications. Four years after the initial visit we determined the outcome of all 603 subjects and retested available survivors. Psychometric tests were then administered to the 429 (71.1%) available survivors after a median period of 4.2 years (69 subjects were dead, 15 were too unwell, 12 had moved away and 78 either refused or failed to reply). Forty-two subjects had significant sensory impairment or interrupted testing, 195 remained in good health, 29 reported or had documented disease but were on no regular medication and 163 were on regular medication for diseases diagnosed during the follow-up period. MMSE score declined by 0.3 points in the healthy group (P < 0.048). However, once a single outlier whose MMSE score fell from 29 to 22 was excluded, the mean decline for the remainder was non-significant at 0.2 points (P = 0.079). There was no significant difference in cognitive decline between those who had and those who had not started medication (P = 0.59). CONCLUSIONS: the study fails to support the hypothesis that cognitive decline can be attributed to age alone in healthy old people. If such a decline exists, we consider that it is unlikely to account for loss of more than 0.1 MMSE point per year.

Aged↗
PubMed1997

Risk factors for developing multiple sclerosis after childhood optic neuritis.

We reviewed the records of all children (younger than 16 years of age) who presented with a diagnosis of optic neuritis (ON) identified through the comprehensive records-linkage system at the Mayo Clinic and identified 94 cases between 1950 and 1988 with a documented history of idiopathic ON. Detailed follow-up information was available on 79 patients, with a median length of follow-up of 19.4 years. Life-table analysis showed that 13% of the 79 patients with isolated ON had progressed to clinically or laboratory-supported definite multiple sclerosis (MS) by 10 years of follow-up, 19% by 20 years, 22% by 30 years, and 26% by 40 years. Gender, age, funduscopic findings, visual acuity, or family history of either ON or MS did not predict the development of MS. The presence of bilateral sequential or recurrent ON increased the risk of developing MS (p = 0.002; hazard ratio = 5.09), whereas the presence of infection within 2 weeks before the onset of ON decreased the risk of developing MS (p = 0.060; hazard ratio = 0.24). This study of childhood ON supports the lower risk of recurrence and progression to MS compared with adults.

Adolescent↗
PubMed1997

Revised guidelines on asthma management.

The revised guidelines on asthma separate the management of children under five from that of adults and older children. A 'step' approach to treatment is advocated; with the recommendation that patients begin on the lowest level of medication that can control symptoms.

Adult↗
PubMed1997

The management of acute asthma.

Health professionals likely to come into contact with people experiencing an acute episode of asthma, such as school nurses, ambulance personnel and A&E staff, need clear guidelines on management. The British Thoracic Society guidelines, revised this year, advise on the categorisation of asthma, assessment and treatment.

Acute Disease↗
PubMed1997

Self-management of asthma.

Many patients with asthma are able to monitor and manage their condition successfully with support. Monitoring of peak expiratory flow can help provide information on an individual's condition. Information and education are vital in reducing mortality and morbidity in asthma.

Asthma↗
PubMed1997

Mould spores: the unusual suspects in hay fever.

Microfungi are microscopic plants that lack chlorophyll and depend on plant or animal material for nourishment. Moulds will only proliferate in a humid atmosphere. Moulds produce vast numbers of small spores, varying in diameter from 2 to 5 microns, which become airborne. Some common moulds in the UK include Cladosporium, Alternaria and Aspergillus, of which several species are pathogenic to humans. The frequency of mould allergy is uncertain, but it appears to be higher in children than in adults. Wet weather favours mould growth, and sunny, windy weather favours spore release, while snow reduces both considerably. In warm, humid climates, fungi are present in large quantities all the year round. In temperate zones, spore counts are highest during the late summer. Indoor exposure largely depends upon the level of humidity. Mould growth can be immense in badly constructed houses and can contribute to sick-house syndrome. Occupational exposure can occur during manufacture of bread, cheese, beer and wine. In recent years, the use of moulds has been extended to include antibiotic, enzyme and steroid manufacture. Inhalation of small quantities of mould spores can evoke an IgE response and asthma. Massive exposure to some moulds growing in the airway can evoke an IgE and IgG response in people with bronchopulmonary aspergillosis. The inhalation of large amounts of mould antigen in organic dust can cause an IgG response and extrinsic allergic alveolitis

Antigens, Fungal↗
PubMed1996

Identification of type B-specific and cross-reactive cytotoxic T-lymphocyte responses to Epstein-Barr virus.

Persistent Epstein-Barr virus (EBV) infection is primarily controlled by HLA class I-restricted memory cytotoxic T-cell (CTL) responses which can be reactivated in vitro by stimulation of peripheral blood lymphocytes with autologous lymphoblastoid cell lines. During an investigation of a donor infected by both type A and type B EBV, CTL specific for type B EBV were isolated. The CTL were found to recognize an epitope encoded by the EBNA-6B gene. The minimal epitope sequence was identified as QNGALAINTF, corresponding to residues 213 to 222 in the EBNA-6B protein, and presentation of this epitope was shown to be via HLA B62 (B15). This is the first report of the characterization of an epitope that is EBV type B specific. CTL recognizing sequences common to type A and type B EBV were identified as well. A cross-reactive epitope recognized by these CTL was encoded within the EBNA-6 gene of both type A and type B. This minimal sequence for this epitope was LLDFVRFMGV (residues 284 to 293 in both types), and the epitope was restricted through HLA A*0201. This second epitope sequence overlaps with a published EBV B44-restricted epitope (EENLLDFVRF). The implications of these findings are discussed with respect to the design and efficacy of epitope-based vaccines.

Adolescent↗
PubMed1995

Skin closure and the incidence of groin wound infection: a prospective study.

Groin wound infection is a dreaded complication of vascular surgery and may jeopardize an underlying graft. A variety of skin closures have been used and the object of this study was to prospectively determine the relationship between skin closure and wound infection. One hundred fourteen consecutive patients (70 men and 44 women) undergoing bypass surgery with a groin incision (n = 173) were randomly assigned to skin closure with subcuticular Maxon, interrupted nylon, continuous nylon, or clips following a standard two-layer closure of subcutaneous tissue. Fourteen (12%) patients had diabetes and 50 (44%) had digital ulceration and gangrene. Aortofemoral bypass was performed in 25% of the patients and infrainguinal bypass in the remaining 75%. Perioperative wound cultures were obtained before closure. Wounds were inspected and cultures repeated on postoperative days 3, 5, 7, 10, and 14. Infection was defined as a positive culture. Groin wound infection occurred in 3% of the population and graft infection in 0.6%. The type of suture did not influence the incidence of infection. This study failed to demonstrate a significant difference in the incidence of wound infection with the use of different suture materials. We conclude that suture material should be selected on the basis of surgeon preference and costs.

Aged↗
PubMed1995

Objective measurement of changes in regional wall motion characteristics following coronary artery bypass grafting using tomographic radionuclide ventriculography.

Difficulties arise when using non-invasive methods to measure changes in regional left ventricular function. With the increasing recognition of the entity of hibernating myocardium, and the known asymmetric effects of coronary artery disease, this is an important problem, as it prevents detailed investigation of the effects of revascularization upon ventricular function. We investigated the use of tomographic radionuclide ventriculography in assessing such changes. Twenty consecutive patients (18 males, 2 females, mean age 60 years), undergoing elective coronary artery bypass surgery, were identified and imaged prior to and after surgery. The mean global left ventricular ejection fraction was 42 and 45% pre- and post-surgery, respectively. Following revascularization, it was improved in 9 patients, unchanged in 3 and deteriorated in 8. By comparison with pooled normal data from 25 subjects, 10 patients were noted to have overall resting phase values within normal limits. After surgery, an improvement was seen in 5 patients, no significant change in 11 and a deterioration in 4. With respect to regional ejection fraction, 24 of 80 segments improved, 25 remained unchanged and 31 deteriorated. For regional phase analysis, 26 improved, 45 remained unchanged and 9 deteriorated. confirmed that important regional changes in left ventricular function occur following revascularization, even without a change in global ejection fraction.

Aged↗
PubMed1995

Studies of DNA methylation in animals.

We have been studying the evolution and function of DNA methylation in vertebrate animals using three related approaches. The first is to further characterise proteins that bind to methylated DNA. Such proteins can be viewed as 'receptors' of the methyl-CpG 'ligand' that mediate downstream consequences of DNA modification. The second approach involves CpG islands. These patches of non-methylated DNA coincide with most gene promoters, but their origin and functional significance have only recently become the subject of intensive study. The third approach is to trace the evolution of DNA methylation. Genomic methylation patterns of vertebrates are strikingly different from those of invertebrates. By studying methylation in animals that diverged from common ancestors near to the invertebrate/vertebrate boundary, we will assess the possibility that changes in DNA methylation contributed causally to the evolution of the complex vertebrate lineage.

Animals↗
PubMed1995

Diverting managed care Medicaid patients from pediatric emergency department use.

OBJECTIVE: To evaluate the health outcomes of managed care Medicaid children with non-emergent conditions who were not authorized to be seen in the Pediatric Emergency Department (PED) by their primary care provider. DESIGN: Consecutive case surveillance from 6/29/92 to 2/2/93. SETTING: University based PED (17,500 visits/year) in inner city Baltimore. PARTICIPANTS: Cases were MAC children denied authorization to be seen for non-emergent conditions in the PED. Age and complaint matched MAC children were selected from the university based Pediatric Ambulatory Center (PAC) and from non-emergent PED visits (PED-seen) in order to compare utilization rates after denial. INTERVENTION: The Maryland Access to Care (MAC) Medicaid program (started in 12/91) emphasizes primary care and appropriate health care utilization by incorporating the following elements of managed care: assignment to primary care provider, gatekeeping, mandatory enrollment and fee for service. METHODS: Consecutive case surveillance from 6/29/92 to 2/2/93 was used to evaluate the health outcomes of MAC children denied authorization for non-emergent care in a university based PED. One week following denial, a pediatric nurse practitioner contacted the patient's caretaker and the MAC provider to ascertain health outcome. Medicaid claims data was used to compare the six month health care utilization of the denied group to age and complaint matched children seen in the PED (PED-seen) or in a primary care clinic (PAC). RESULTS: 216 MAC patients were not authorized for a PED visit by their MAC providers. 123 (57%) saw their MAC provider within one week of the denied PED visit. 40 (18%) were not seen because their presenting complaint had resolved completely. No adverse health outcomes occurred because of delay in health care delivery. The subsequent ER utilization rate of the denied group was the same as the PED-seen comparison group, and significantly higher than that of the PAC group (P = .002). The denied group was hospitalized at a significantly higher rate relative to these comparison groups (P = .003). CONCLUSIONS: Diverting Medicaid children classified as non-emergent in an ER to their MAC providers can be a safe practice short-term. However, denial of a PED visit has no impact on subsequent ER utilization by Medicaid participants and may be associated with higher hospitalization rate. Gatekeeping in this setting does not necessarily change the health care seeking behavior of these patients.

Baltimore↗
PubMed1994

Second locus for Hirschsprung disease/Waardenburg syndrome in a large Mennonite kindred.

We have studied a large Mennonite kindred in which 20 members were affected with Hirschsprung disease (HSCR), 5 of whom had one or more manifestations of Waardenburg syndrome (WS) type II (WS2). Eleven additional relatives had signs of WS2 without HSCR. Since HSCR and WS2 each represent perturbations of neural crest migration/differentiation, this large pedigree with apparent cosegregation of HSCR and WS2 offered an opportunity to search for linkage between these loci, candidate genes, and random DNA markers, particularly in view of recent discoveries of genes for Waardenburg syndrome type I (WS1) and Hirschsprung disease (c-ret). We have examined the following possible linked markers in 69 relatives in this family: the c-ret gene (HSCR); the human PAX3 gene (HuP2) on chromosome 2q (WS1) and placental alkaline phosphatase (ALPP) on chromosome 2q (linked to WS1); argininosuccinate synthetase (ASS) on chromosome 9q, close to ABO blood groups which have shown weak linkage to WS; and the beta 1 GABA receptor gene (GABARB1) on chromosome 4q13-11, close to c-kit, deletions of which cause piebaldism. Linkage between any of these loci and HSCR/WS in this kindred was excluded, demonstrating that there is at least one further locus for HSCR other than c-ret.

Christianity↗