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Biomedical subjects

L Spencer

Publications and source records attributed to L Spencer.

At least 19 recordsLinked to original sources

Description of the outbreak of equine influenza (H3N8) in the United Kingdom in 2003, during which recently vaccinated horses in Newmarket developed respiratory disease.

Between March and May 2003, equine influenza virus infection was confirmed as the cause of clinical respiratory disease among both vaccinated and unvaccinated horses of different breeds and types in at least 12 locations in the UK. In the largest outbreak, 21 thoroughbred training yards in Newmarket, with more than 1300 racehorses, were affected, with the horses showing signs of coughing and nasal discharge during a period of nine weeks. Many of the infected horses had been vaccinated during the previous three months with a vaccine that contained representatives from both the European (A/eq/Newmarket/2/93) and American (A/eq/Newmarket/1/93) H3NN8 influenza virus lineages. Antigenic and genetic characterisation of the viruses from Newmarket and elsewhere indicated that they were all closely related to representatives of a sublineage of American viruses, for example, Kentucky/5/02, the first time that this sublineage had been isolated in the uk. In the recently vaccinated racehorses in Newmarket the single radial haemolysis antibody levels in acute sera appeared to be adequate, and there did not appear to be significant antigenic differences between the infecting virus and A/eq/Newmarket/1/93, the representative of the American lineage virus present in the most widely used vaccine, to explain the vaccine failure. However, there was evidence for significantly fewer infections among two-year-old horses than older animals, despite their having similar high levels of antibody, consistent with a qualitative rather than a quantitative difference in the immunity conveyed by the vaccination.

Amino Acid Sequence↗

A highly immunogenic trivalent T cell receptor peptide vaccine for multiple sclerosis.

BACKGROUND: T cell receptor (TCR) peptide vaccination is a novel approach to treating multiple sclerosis (MS). The low immunogenicity of previous vaccines has hindered the development of TCR peptide vaccination for MS. OBJECTIVE: To compare the immunogenicity of intramuscular injections of TCR BV5S2, BV6S5 and BV13S1 CDR2 peptides in incomplete Freunds adjuvant (IFA) with intradermal injections of the same peptides without IFA. METHODS: MS subjects were randomized to receive TCR peptides/IFA, TCR peptides/saline or IFA alone. Subjects were on study for 24 weeks. RESULTS: The TCR peptides/IFA vaccine induced vigorous T cell responses in 100% of subjects completing the 24-week study (9/9) compared with only 20% (2/10) of those receiving the TCR peptides/saline vaccine (P =0.001). IFA alone induced a weak response in only one of five subjects. Aside from injection site reactions, there were no significant adverse events attributable to the treatment. CONCLUSIONS: The trivalent TCR peptide in IFA vaccine represents a significant improvement in immunogenicity over previous TCR peptide vaccines and warrants investigation of its ability to treat MS.

Adult↗

Class I topical corticosteroid use by psoriasis patients in an academic practice.

BACKGROUND: Psoriasis is a chronic skin disorder that can have a profound impact on the quality of life of patients. The treatment of psoriasis is complicated by the availability of numerous topical agents, systemic agents, and phototherapy. Of the topical preparations available, the ultra-high potency, or Class I steroids, have an important role in treating psoriasis. Their use is most appropriate for the treatment of plaques in regions excluding the face, axilla, groin and genitals. OBJECTIVE: The purpose of this study was to examine the prescribing patterns of Class I topical corticosteroids within a large academic dermatology practice for patients with all types of psoriasis. METHODS: A retrospective chart review of 650 patients with psoriasis from an academic dermatology practice was performed. Class I steroid use was defined as those patients who were observed to be currently using clobetasol propionate, halobetasol propionate, diflorasone, or augmented betamethasone dipropionate. RESULTS: A total of 79% of patients were prescribed topical steroids of any class while 46% of patients were prescribed a Class I steroid. In all, 58% of patients who received topical steroid therapy received a Class I agent; 11% of patients prescribed Class I steroids also received systemic therapy for their psoriasis. Conversely, 35% of patients who received systemic therapy were also receiving Class I topical therapy. DISCUSSION: In our department, Class I topical steroids are commonly used in the treatment of psoriasis. The superpotent topicals are often used as an adjunct to systemic therapy and will likely remain a mainstay of psoriasis therapy.

Administration, Topical↗

T cells are required for host protection against Brugia malayi but need not produce or respond to interleukin-4.

T cells are known to be required for host protection in mouse models of Brugia malayi infection. Several independent studies in murine models have also highlighted the rapid induction of Th2-like responses after infection with B. malayi or B. pahangi. Previous data from our laboratory have described a significant increase in permissiveness in the absence of interleukin-4 (IL-4), the "prototypical" Th2 cytokine, involved in both the induction and maintenance of Th2 responses. These observations led to our hypothesis that T cells involved in murine host protection would respond to IL-4 signaling and differentiate into cells of the "type 2" phenotype. As such, these cells would presumably also act as major sources of IL-4. To investigate these hypotheses, we performed several adoptive transfers in which we controlled the cell population(s) able to produce or respond to IL-4. We show here that, in contrast to our original hypotheses, IL-4 production and IL-4 receptor expression by T cells are both dispensable for T-cell-mediated host protection. Instead, our data imply that T cells may be required for eosinophil accumulation at the site of infection.

Animals↗

Histopathologic and histochemical characterization of calcified structures in hamsters inoculated with Paracoccidioides brasiliensis.

In pathogenicity studies of 31 Paracoccidioides brasiliensis isolates preserved using Castellani's method we intraperitoneally inoculated 104 young adult hamsters and found laminated concentric structures and calcified appearance that resembled Schaumann bodies, in 43 of them, especially in animals with apparently good condition. We characterized these structures histologically and histochemically using different stains (PAS, Grocott, haematoxylin-eosin, Von Kossa). The Von Kossa staining revealed calcium in these structures. Similar structures have been described in patients with sarcoidosis and also in hamsters inoculated with P. brasiliensis. We found no correlation between the presence of these calcifications and serum calcium levels.

Animals↗

Might patients benefit from oral iron therapy following operative treatment of breast carcinoma?

AIMS: To assess the changes in blood haemoglobin concentration and serum iron indices as a consequence of breast operations for cancer in our unit. METHODS: Haematological parameters were measured in 109 patients undergoing definitive operative treatment for breast carcinoma. RESULTS: A mean fall in haemoglobin of 2.1 g (P=0.001) occurred in patients undergoing mastectomy and axillary clearance and of 1.3 g (P<0.001) in patients undergoing wide local excision and axillary clearance. The transferrin saturation (serum iron/total iron binding capacity) in both sets of patients after surgery fell on average to levels that would be expected to impair subsequent red cell production. CONCLUSION: The changes in iron indices that occurred were unrelated to the degree of blood loss consistent with a possible inflammatory effect of the operation. Oral iron therapy is unlikely to be of benefit to operative breast patients if they have normal pre-operative iron stores.

Anemia, Iron-Deficiency↗

Palliative care in the community for children with cancer in South East England.

In-depth interviews and discussions were held with 40 different professionals in South East England involved in managing palliative care for children with cancer in the community. Participants included paediatric oncologists and outreach nurse specialists in tertiary centres, paediatricians in shared care units, children's community nurses, general practitioners, social workers and child psychologists. The research examined palliative care services available in the region, exploring attitudes to both current provision and possible service improvements. Providing palliative care in the community involves multi-agency collaboration and the study highlighted a range of different approaches to case management with the diversity of resources available. Key improvements proposed by health-care professionals included: better communication and liaison between all the professionals involved; clearer allocation of roles and responsibilities; 24-hour availability of specialist advice on palliative care for children with cancer; faster access to social work and psychology services at the community level; continuity of nursing and respite care. The provision of specialist local palliative care services for children with cancer was generally rejected. The participants favoured improving community palliative care for all children with life-limiting or life-threatening conditions with community nursing teams providing continuity of care and outreach nurses providing specialist advice and support.

Journal Article↗

Interleukin-4 receptor-Stat6 signaling in murine infections with a tissue-dwelling nematode parasite.

Interleukin-4 (IL-4) has been shown to be crucial in parasite expulsion in several gastrointestinal nematode infection models. Data from both epidemiological studies with humans and experimental infections in animals imply a critical role for the type II helper response, dominated by IL-4, in host protection. Here we utilized inbred mice on two distinct backgrounds to document the involvement of IL-4 in the clearance of a primary infection of Brugia from the murine host. Our data from infections of IL-4 receptor(-/-) and Stat6(-/-) mice further indicate that IL-4 exerts its effects by activating the Stat6 molecule in host target cells, a finding which links clearance requirements of a gastrointestinal tract-dwelling nematode with those of a tissue-dwelling nematode. Additionally, we show that the requirements for IL-4 receptor binding and Stat6 activation extend to accelerated clearance of a secondary infection as well. The data shown here, including analysis of cell populations at the site of infection and infection of immunoglobulin E (IgE)(-/-) mice, lead us to suggest that deficiencies in eosinophil recruitment and isotype switching to IgE production may be at least partially responsible for slower parasite clearance in the absence of IL-4.

Animals↗

Invasive serotype a Haemophilus influenzae infections with a virulence genotype resembling Haemophilus influenzae type b: emerging pathogen in the vaccine era?

OBJECTIVE: Haemophilus influenzae type b causes severe disease in nonimmune infants and young children; other serotypes are uncommon pathogens and thought to have low virulence. Some have hypothesized that with the virtual elimination of H influenzae type b, other serotypes might acquire virulence traits and emerge as important pathogens of children. We describe the clinical, epidemiologic, and molecular biologic features of 5 cases of severe disease attributable to Haemophilus influenzae type a. METHODS: After observing 4 cases of invasive disease caused by H influenzae type a, we reviewed microbiology records at 3 reference laboratories that perform all serotyping in Utah and surveillance databases. Strains of H influenzae type a and control strains were examined by Southern blotting with the use of the cap probe pUO38 and by pulsed-field gel electrophoresis. The putative virulence mutation, the IS1016-bexA deletion, was detected by polymerase chain reaction amplification and sequencing. RESULTS: During a 10-month period, we observed 5 children with severe invasive disease caused by H influenzae type a. No isolates of H influenzae type a had been submitted to the reference laboratories between 1992 and 1998. The median age of patients was 12 months (range: 6-48 months). Four of 5 had meningitis and bacteremia; 1 had purpura fulminans. Three isolates, representing 1 of 2 pulsed-field gel electrophoresis patterns, contained the IS1016-bexA deletion and were associated with particularly severe disease. CONCLUSIONS: We describe an unusual cluster of severe disease caused by H influenzae type a that resembles the clinical and epidemiologic features of H influenzae type b disease. Our data support the hypothesis that the IS1016-bexA deletion may identify more virulent strains of H influenzae. Haemophilus influenzae, epidemiology, virulence, serotyping, pathogenicity.

Base Sequence↗

Thrombospondin-1 suppresses wound healing and granulation tissue formation in the skin of transgenic mice.

The function of the endogenous angiogenesis inhibitor thrombospondin-1 (TSP-1) in tissue repair has remained controversial. We established transgenic mice with targeted overexpression of TSP-1 in the skin, using a keratin 14 expression cassette. TSP-1 transgenic mice were healthy and fertile, and did not show any major abnormalities of normal skin vascularity, cutaneous vascular architecture, or microvascular permeability. However, healing of full-thickness skin wounds was greatly delayed in TSP-1 transgenic mice and was associated with reduced granulation tissue formation and highly diminished wound angiogenesis. Moreover, TSP-1 potently inhibited fibroblast migration in vivo and in vitro. These findings demonstrate that TSP-1 preferentially interfered with wound healing-associated angiogenesis, rather than with the angiogenesis associated with normal development and skin homeostasis, and suggest that therapeutic application of angiogenesis inhibitors might potentially be associated with impaired wound vascularization and tissue repair.

Animals↗

What's best? Clinical indicators of quality in residential aged care facilities.

This paper reports on the views of 36 registered nurses (RNs) in Phase One of a three stage study, Quality of Care for Residents in Aged Care Facilities. Case studies were conducted in nine residential aged care facilities and data were collected from informants using semi-structured interviews, participant observation and document analysis and review. Of the 36 RNs, almost three quarters (n=26) provided care at the bedside and ten held managerial positions. Each volunteered to participate. When asked to nominate the major clinical indicators of high quality residential aged care, all 26 RNs who worked at the bedside stated that the absence of decubitis ulcers was the pre-eminent measurable factor. While five managerial RNs also mentioned low rates of pressure ulcers, only two ranked it as the most important clinical indicator of high quality care. Hydration management was the clinical indicator nominated most frequently by managerial nurses. The one indicator of equal importance to both groups, but for different reasons, was that of poly pharmacy. The differences in priorities between each group were statistically significant.

Aged↗

Hepatitis B immunity in high risk health care workers. Seven years post vaccination.

The purpose of this descriptive, quantitative study was to examine hepatitis B immunity in high risk health care workers 7 years post immunization. The study related immunity to age and site of injection, and also described titer results. The study sample was composed of 42 health care workers from areas with frequent blood exposure. The study found that 21% of the health care workers had nonreactive titers 7 or more years post immunization. No significant differences existed in the percentages of the reactive participants according to injection site, although it is recommended the injection be given intramuscularly in the deltoid. No statistically significant relationship was revealed by comparing titer results to age. The low power (.24) displays the need for larger sample sizes which could be obtained by using multicenter data sites. Future research with national collaboration and standard performance measurement systems could provide crucial information related to hepatitis B immunity in health care workers.

Adult↗

Reactivity of ferulic acid and its derivatives toward hydrogen peroxide and peracetic acid.

The reactions of ferulic acid and its derivatives with hydrogen peroxide and peracetic acid in lignin-retaining bleaching conditions have been investigated to determine their susceptibility to oxidative degradation. The conjugated side chain of ferulic acid and its etherified or esterified derivative was shown to be fairly stable, especially to hydrogen peroxide. The major reaction was trans-cis isomerization that possibly involved a radical mechanism but did not cause bond cleavage. The peracetic acid reaction increased the rate of trans-cis isomerization and was also accompanied by a minor cleavage of the side chain. Esterification did not have a substantial effect on the reactivity of ferulic acid, but 4-O-etherification significantly stabilized it against these two oxidants. By contrast, aldehyde substitution tremendously enhanced the susceptibility of the cinnamyl side chain to oxidative degradation, as evidenced by an intensive degradation of coniferaldehyde.

Coumaric Acids↗

A comparison of language achievement in children with cochlear implants and children using hearing aids.

English language achievement of 29 prelingually deaf children with 3 or more years of cochlear implant (CI) experience was compared to the achievement levels of prelingually deaf children who did not have such CI experience. Language achievement was measured by the Rhode Island Test of Language Structure (RITLS), a measure of signed and spoken sentence comprehension, and the Index of Productive Syntax (IPSyn), a measure of expressive (signed and spoken) English grammar. When the CI users were compared with their deaf age mates who contributed to the norms of the RITLS, it was found that CI users achieved significantly better scores. Likewise, we found that CI users performed better than 29 deaf children who used hearing aids (HAs) with respect to English grammar achievement as indexed by the IPSyn. Additionally, we found that chronological age highly correlated with IPSyn levels only among the non-CI users, whereas length of CI experience was significantly correlated with IPSyn scores for CI users. Finally, clear differences between those with and without CI experience were found by 2 years of post-implant experience. These data provide evidence that children who receive CIs benefit in the form of improved English language comprehension and production.

Achievement↗

Good symptom relief with palliative MVP (mitomycin-C, vinblastine and cisplatin) chemotherapy in malignant mesothelioma.

PURPOSE: To evaluate the therapeutic impact of a simple combination chemotherapy regimen on symptoms related to malignant mesothelioma. MATERIALS AND METHODS: Between October 1986 and June 1997, 39 patients with advanced inoperable malignant mesothelioma were treated with palliative MVP (mitomycin-C 8 mg/m2 q. six weeks, vinblastine 6 mg/m2 q. three weeks and cisplatin 50 mg/m2 q. three weeks) chemotherapy and assessed for objective response and relief of symptoms. RESULTS: Eight of 39 patients (20%) achieved an objective partial response with a median duration of nine months: only five patients had progression of disease during chemotherapy. Twenty-four of 39 (62%) had an overall improvement in their symptomology with particularly good responses for pain (79%). These benefits were independent of performance status. Resolution of symptoms was achieved in all responding patients within two treatment cycles. There was no statistically significant difference in duration and incidence of symptom response in those patients achieving radiological PR compared with those with no change and more than 60% of patients with radiological no change obtained useful symptom control. The treatment was well tolerated with only four patients developing grade 3 leucopenia and three with grade 3 nausea. CONCLUSIONS: MVP is a well tolerated regimen and its use in malignant mesothelioma provides useful symptomatic benefit. These results should be the basis for further trials of MVP in the management of mesothelioma with symptom control as a principal endpoint.

Aged↗

A pilot study of MVP (mitomycin-C, vinblastine and cisplatin) chemotherapy in small-cell lung cancer.

MVP chemotherapy (mitomycin C 8 mg m(-2), courses 1, 2, 4 and 6, vinblastine 6 mg m(-2), cisplatin 50 mg m(-2)) is an active low-toxicity regimen in non-small-cell lung cancer (NSCLC). Based on the single-agent activity of these agents in SCLC, we have conducted a phase II trial of MVP in SCLC. Fifty chemo-naive patients with SCLC were entered in this trial. There were 33 men and 17 women with median age 66 years (range 46-83 years); 18 patients had limited disease (LD) and 32 extensive disease (ED). WHO performance status (PS) was: three patients PS 0, 33 patients PS 1, ten patients PS 2, four patients PS 3. A maximum of six cycles was given in responding patients. On completion of chemotherapy, patients with LD obtaining complete response (CR)/good partial response (PR) received thoracic irradiation and those obtaining CR were offered entry into the ongoing MRC Prophylactic Cranial Irradiation Trial. The overall response was 79% with 17% CR and 62% PR. For LD patients, 38% obtained CR but for ED only one patient achieved CR. Median response duration for LD patients was 8 months and for ED patients 5 months. Median survival was 10 months for LD patients and 6 months for ED patients. There was complete resolution of symptoms in 24%, partial improvement in 68%, no change in 2% and progressive symptoms in 6%. As regards toxicity, 24% developed WHO grade 3/4 neutropenia, 16% grade 3/4 thrombocytopenia and 6% significant hair loss. Two patients died during the first week of treatment with neutropenic infection. Quality of life using the EORTC questionnaire (QLC-C30) with lung cancer module demonstrated significant improvements from baseline levels in emotional and cognitive functioning, global QOL, of pain, dyspnoea and cough. MVP, an effective palliative regimen for NSCLC, is also active against SCLC with low toxicity and merits comparison with more toxic conventional schedules.

Aged↗

Listening to migrant voices: focus groups on health issues in south Georgia.

This qualitative study utilized focus groups to invite Latino migrant farm workers to express ideas about their health and service needs. Four focus groups composed of Latino men and women were conducted on four different evenings in the same county. Three themes emerged: health care issues, living and working conditions, and social and community issues. Specific needs of the community were also identified by the participants. For the first time, migrant farm workers in Georgia had the opportunity to lend their own voice regarding their concerns and ideas about health and social conditions. The findings from this study are congruent with other studies and provide the basis for developing interventions to enhance the health of migrant farm workers. In addition, the findings have implications for community health nursing and the proposed Vision of 2010: Healthy People in Healthy Communities, whose goals include increased years of healthy life and the elimination of health disparities.

Adolescent↗

Hmong/medicine interactions: improving cross-cultural health care.

BACKGROUND AND OBJECTIVES: There are now more than 100,000 Hmong (Southeast Asian) refugees in the United States. This study examined interactions between Hmong patients and their health care providers and identified specific factors that either enable or obstruct health care delivery. METHODS: We used semistructured interview techniques to investigate patients' and providers' experiences, looking for attitudes, ideas, or behaviors that could be modified to improve health care delivery. Interviews with 23 Hmong patients, 18 health care providers, and six translators were audiotaped, transcribed, and analyzed by a multidisciplinary team. Methods included text analysis, theme identification, rank ordering, participant observation, immersion-crystallization, and open-ended discussion. RESULTS: Hmong patients and their US-trained health care providers have different health belief systems. Both linguistic and cultural translation were seen as problematic. Additionally, an overwhelming number of patients identified kindness, caring, and a positive attitude as important provider characteristics. Providers noted difficulties in understanding Hmong conceptions of acute versus chronic diseases, illness prevention, and pain, both physical and psychological. Many respondents gave suggestions for improvement: 1) learn more about each other's cultures, 2) be patient, kind, and positive, 3) avoid negative statements or predictions, 4) improve translation quality, 5) explain medical terms using visual aids, 6) respect Hmong family-centered decision making, 7) increase the time allotted for translated clinical encounters, and 8) train Hmong health care providers. CONCLUSIONS: Many basic issues in relations between clinicians and Hmong patients must be addressed to improve health care communication.

Asia, Southeastern↗