Anti-T-cell-antibody prophylaxis in children: success with a novel combination strategy of mycophenolate mofetil and antithymocyte serum.
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Adolescent↗
Biomedical subjects
D Campbell
Publications and source records attributed to D Campbell.
Survival strategies of Entamoeba histolytica: Modulation of cell-mediated immune responses.
Tissue invasion and disease associated with the protozoan Entamoeba histolytica has long been connected with suppression of host cellular immunity. Dampening of the host's defences may facilitate survival of amoebae in extraintestinal sites and development of the characteristic amoebic abscesses. In recent years, several studies have begun to clarify, at the cellular level, the specific effects E. histolytica has on immune cell accessory and effector cell functions. Here, Darren Campbell and Kris Chadee discuss the parasite's multiple modulatory effects on macrophages and T cells and how this manipulation of immune defences may enable the parasite to remain viable in the host. They suggest the putative amoebic molecules involved and potential modulation by the cytokines: interleukins IL-4 and IL-10 and transforming growth factor-beta.
Journal Article↗
Prochlorothrix hollandica PCC 9006: genomic properties of an axenic representative of the chlorophyll a/b-containing oxyphotobacteria.
Prochlorothrix hollandica is an oxygenic photosynthetic prokaryote that differs from the cyanobacteria in having chlorophyll a/b-protein complexes instead of phycobilisomes as major light-harvesting antennae. We report the isolation and culturing of an axenic strain of P. hollandica, available from the Pasteur Culture Collection of Cyanobacteria as strain PCC 9006. The strain has a mean DNA base composition of 51.6 +/- 0.1 mol% G+C and a genomic complexity of 3.37 +/- 0.17 x 10(9) daltons (5,505 kb). A reiterated DNA sequence represents approximately 4.4% of the genome. Restriction enzyme isoschizomers with different sensitivities to base methylation were used to demonstrate that most A residues in the sequence GATC are methylated in P. hollandica DNA and that this methylation increases with culture age. Furthermore, some C residues are methylated, although the specificity of the C methylation system does not match that of well-characterized C methylases. Nucleotide analysis showed that up to approximately 3.5% of both dA and dC residues are methylated in P. hollandica DNA.
Base Pairing↗
Interleukin (IL)-2, IL-4, and tumor necrosis factor-alpha responses during Entamoeba histolytica liver abscess development in gerbils.
To determine cytokine production patterns during hepatic amebiasis, gerbils were infected with Entamoeba histolytica in the liver. Then spleen and hepatic lymph node cell proliferation and interleukin (IL)-2 (a Th1 marker), IL-4 (a Th2 marker), and tumor necrosis factor-alpha (TNF-alpha) production in response to concanavalin A and amebic antigen in vitro were quantified. Early abscess development (day 5 after inoculation) coincided with IL-2, IL-4, and low TNF-alpha production and strong lymphoproliferative responses, whereas suppression of IL production and lymphoproliferation occurred during acute disease (day 20). Proliferative responses and IL-2 production increased at days 30 and 60 after inoculation, but IL-4 levels remained low. Animals drug-treated at day 20 after inoculation demonstrated high IL-2 and low IL-4 production and resistance to reinfection. While acute hepatic amebiasis in gerbils is accompanied by transient immunosuppression, late infection and resistance to reinfection are associated with IL-2 production but low IL-4 and TNF-alpha production (Th-1-like response).
Animals↗
Sexual negotiation in the AIDS era: negotiated safety revisited.
OBJECTIVE: To test the safety of the 'negotiated safety' strategy-the strategy of dispensing with condoms within HIV-seronegative concordant regular sexual relationships under certain conditions. METHOD: Data from recently recruited cohort of homosexually active men (Sydney Men and Sexual Health cohort, n = 1037) are used to revisit negotiated safety. The men were surveyed using a structured questionnaire and questions addressing their sexual relationships and practice their own and their regular partner's serostatus, agreements entered into by the men concerning sexual practice within and outside their regular relationship, and contextual and demographic variables. RESULTS: The findings indicate that a significant number of men used negotiated safety as an HIV prevention strategy. In the 6 months prior to interview, of the 181 men in seroconcordant HIV-negative regular relationships, 62% had engaged in unprotected anal intercourse within their relationship, and 91% (165 men) had not engaged in unprotected anal intercourse outside their relationship. Of these 165 men, 82% had negotiated agreements about sex outside their relationship. The safety of negotiation was dependent not only on seroconcordance but also on the presence of an agreement; 82% of the men who had not engaged in unprotected anal intercourse outside their regular relationship had entered into an agreement with their partner, whereas only 56% of those who had engaged in unprotected anal intercourse had an agreement. The safety of negotiation was also related to the nature of the safety agreement reached between the men and on the acceptability of condoms. Agreements between HIV-negative seroconcordant regular partners prohibiting anal intercourse with casual partners or any form of sex with a casual partner were typically complied with, and men who had such negotiated agreements were at low risk of HIV infection. CONCLUSIONS: The adoption of the strategy of negotiated safety among men in HIV-seronegative regular relationships may help such men sustain the safety of their sexual practice.
Adolescent↗
Chronic subclinical hypothermia: home care alert.
Chronic subclinical hypothermia poses a serious challenge to home health nurses because the condition may negatively impact the plan of care for very old and frail clients. This article provides a review of age-associated changes in thermoregulation, discusses the ways in which these changes may affect an elderly client's response to care, and offers home care interventions for individuals with chronic subclinical hypothermia.
Aged↗
The value of the lipid-laden macrophage index in the assessment of aspiration pneumonia.
BACKGROUND: A semi-quantitative index of lipid-laden macrophages on broncho-alveolar lavage (BAL) has been reported to be highly sensitive but only moderately specific for aspiration in adults. There has been little published literature evaluating this technique since the original report. AIMS: To assess the value of a lipid-laden macrophage index (LLMI) of greater than 100 to confirm the clinical diagnosis of aspiration in patients with abnormal radiological investigations. METHODS: Prospective evaluation of 80 adult patients with abnormal radiology was undertaken using BAL and the LLMI. A diagnosis of aspiration was made prior to bronchoscopy if the patient had one or more of: clinically witnessed aspiration, positive barium swallow or speech pathology assessment; or an upper gastrointestinal endoscopy showed severe reflux oesophagitis and the patient had a history consistent with aspiration. RESULTS: Eighteen patients were diagnosed with aspiration. Of these, 17 had an index > 100, and one had an index of 94 (mean 157, 99% CI 127-187, range 94-238). Of the other 62 subjects, seven had an index > 100 (mean 46, 99% CI 22-70, range 0-303). There was a significant difference between index scores for the two groups (p = 0.002). For aspiration, an index > 100 had a sensitivity of 94% and a negative predictive value of 98%. The specificity was 89%, with a positive predictive value of 71%. CONCLUSIONS: The LLMI is a sensitive indicator for aspiration causing radiological lung disease in adults. Its lack of specificity means it cannot be the sole means of diagnosis, but it can allow better targeting of other investigations in those patients in whom bronchoscopy is undertaken to investigate radiological abnormalities.
Adult↗
Asthma prevalence, morbidity and management practices in South Australia, 1992-1995.
BACKGROUND: The Spring South Australian Health Omnibus Survey (SSAHOS) has been used to monitor trends in asthma prevalence, asthma morbidity and asthma management practices between 1992 and 1995. AIMS: To determine if self-reported asthma prevalence and availability of asthma action plans were increasing. To identify deficiencies in asthma management and opportunities for intervention. METHODS: Representative population survey by trained interviewers using a multistage, systematic, clustered area sample of 4200 households in South Australia where people aged 15 years or more are living. RESULTS: Over 3000 interviews were conducted each year. Between 1992 and 1995 the self-reported prevalence of asthma in those aged 15 years or more increased significantly from 15.7% to 20.3% (p < 0.0005), and the prevalence of current asthma increased from 9.3% to 11.4% (p < 0.05). The self-reported availability of individual asthma action plans increased from 21.9% in 1992 to 42.2% in 1995 (p < 0.0005). In 1992, 21% had a nebuliser at home, and 10.5% had a peak flow meter. In 1993, 61.4% were using preventive medications, and 35% thought bronchodilators were 'preventer' medications. In 1994 and 1995, between 12.5% and 15.6% had nocturnal awakening weekly or more often, and 31.4% had morning asthma symptoms weekly or more often. Between 20.1% and 20.8% had lost days from usual activities during the last year. Those on incomes below $20,000 had more symptoms, had more admissions to hospital, and required more medication than those on higher incomes. CONCLUSIONS: Self-reported asthma prevalence has increased. There remains a gap between current asthma management and that recommended by the National Asthma Campaign.
Adolescent↗
Risk factors for repeat attendance at hospital emergency departments among adults and children with asthma.
BACKGROUND: Acute asthma attacks are frequent causes of attendance at hospital Emergency Departments (EDs) and a subgroup of these patients repeatedly present for such treatment. AIMS: This study sought to characterise patients who were repeat attenders at EDs, to assist the targetting of appropriate future interventions aimed at reducing avoidable presentation. METHODS: A cross-sectional survey was undertaken of patients presenting with an asthma attack to the EDs of six teaching hospitals in Adelaide, South Australia between 14 May and 30 June 1994. Patients were interviewed within six weeks of their attendance about aspects of their asthma history, severity, medications, self-management, attitudes and environment. Repeat attenders, defined as two or more visits over the course of the preceding year, were compared with those who reportedly attended on one occasion only, using logistic regression analyses. RESULTS: Sixty-two per cent of 272 patients aged under 15 years and 40% of 165 patients aged 15 years or more reported having attended two or more times over the course of the preceding year. Among adults, the variables independently associated with repeat attendance principally related to asthma severity. Among children, repeat attendance was associated with parental attitudinal variables relating to appraisal of their child's asthma severity, management of asthma attacks and parental worry. CONCLUSIONS: The factors underlying repeated presentations at EDs differ between adults and children and interventions to minimise avoidable presentation will require different emphasis for these patient subgroups.
Adolescent↗
Mental health practices of Ontario family physicians: a study using qualitative methodology.
OBJECTIVE: To obtain descriptions of how family physicians detect and manage mental health problems commonly encountered in their practices and how they function in their role as mental health care providers. Also, to elicit their perceptions of barriers to the delivery of optimal mental health care. METHOD: Focus groups with standardized questions were used to elicit descriptive data, opinions, attitudes, and terminology. Convenience samples of 10 to 12 physicians were chosen in each of Ontario's 7 health care planning regions, with a mixture of rural, urban, and university settings. Discussions were audiotaped, transcribed, analyzed, and recurring themes were extracted. RESULTS: Family physicians' descriptions of the range of problems commonly encountered and their detection and management highlight the unique nature of mental health care in the primary care setting. The realities of family medicine, the undifferentiated nature of presenting problems, the long-term physician-patient relationship, and the frequent overlap of physical and mental health problems dictate an approach to diagnosis and treatment that differs from mental health care delivery in other settings. Difficulties in the relationship with local psychiatric services--accessing psychiatric care (especially for emergencies), poor communication with mental health care providers, and cumbersome intake procedures of many mental health services--were consistently identified as barriers to the delivery of optimal mental health care. CONCLUSIONS: This study confirms the importance of the family physician in the detection and management of mental health problems. It offers insights into how family physicians function in their role as mental health care providers and how they deal with diagnostic and management challenges that are specific to primary care. It also identifies barriers to the optimal delivery of mental health care in the primary care setting, including difficulties at the clinical interface between psychiatry and family medicine. Further studies are needed to explore these issues in greater depth.
Appointments and Schedules↗
A risk screening questionnaire for adult asthmatics to predict attendance at hospital emergency departments. South Australian Asthma Reference Panel.
STUDY OBJECTIVES: To develop a practical screening tool that could identify adult patients highly likely to attend a hospital emergency department (ED) in a 1-year period. DESIGN: Retrospective case-control study of patients who did and did not attend a hospital ED for asthma in the past year. SETTING: Adelaide, South Australia. PARTICIPANTS: One hundred sixty-five adults attending an ED for asthma were compared with 260 adults with asthma from a community survey who had not attended an ED in the previous year. MEASUREMENTS AND RESULTS: The following variables were independently related to ED attendance: having been woken from sleep by asthma in past month; having been admitted to hospital because of asthma in the past year; having seen more than one general practitioner for asthma in the last 12 months; a moderate or severe self-rating of asthma in the last month; and having taken oral steroid medication for asthma in past month. A risk screening questionnaire using the weighted responses to these five variables with a cutoff score of 30/100 demonstrated a sensitivity of 90% and specificity of 88%. CONCLUSIONS: These findings agree with those of previous studies that markers of asthma severity and discontinuity of care are risk factors for adverse asthma outcomes. Validation of the risk screening questionnaire is required in a prospective study.
Adolescent↗
Prognosis of very low-birthweight babies.
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Humans↗
The Belfast Cord Blood Bank.
The first cord blood bank in the British Isles was established in Belfast in June 1993. Cord blood (CB) is rich in haematopoietic progenitor cells and has been used successfully as a substitute for bone marrow transplants in over 200 patients world-wide. Most have received CB from a histocompatible sibling, but reports include several unrelated HLA matched transplants. In addition to the cryopreservation of 400 units of donated CB in the Cord Blood Bank, we have stored eight CB collections from siblings of children with leukaemia in Northern Ireland. A pilot study in collaboration with the maternity unit in the Mater Infirmorum Hospital confirmed the feasibility of a CB banking programme and highlighted many issues relating to Good Manufacturing Practice (GMP). The authors describe experience of collecting 824 units of CB over three years and discuss a few of the wider implications of this innovation in the management of patients requiring myeloablative therapy.
Adult↗
The nurse executive and the physician: ally or adversary?
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Communication↗
Biochemical and genetic characterization of multiple splice variants of the Flt3 ligand.
We have performed a comprehensive analysis of cell lines and tissues to compare and contrast the expression patterns of Flt3 ligand (FL), c-Kit ligand (KL), and macrophage colony-stimulating factor as well as their receptors, Flt3, c-Kit, and c-Fms. The message for FL is unusually ubiquitous, whereas that of its receptor is quite restricted, apparently limiting the function of the ligand to fetal development and early hematopoiesis. We have also sequenced a mouse FL genomic clone, revealing how the three splice variant FL mRNAs that we have isolated arise. The chromosomal location of the FL gene has been mapped, by in situ hybridization, to chromosome 7 in mouse and chromosome 19 in human. Natural FL protein has been purified from a stromal cell line and shown to be a 65 kD nondisulfide-linked homodimeric glycoprotein comprised of 30 kD subunits, each containing 12 kD of N- and O-linked sugars. Pulse-chase experiments show that one of the splice variants (T110) is responsible for producing the bulk of soluble FL, but only after it has first been expressed at the cell surface as a membrane-bound form. The other splice-variant forms produce molecules that are either obligatorily soluble (T169) or membrane-bound but released only very slowly (T118). Finally, even though most cell lines express some amount of FL mRNA, we found that very little FL protein is actually made, with T cells and stromal cells being the major producers. The data suggests that FL plays its roles over very short distances, perhaps requiring cell-cell contact.
Amino Acid Sequence↗
Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway.
The JAK-STAT signaling pathway has been implicated in mediating biological responses induced by many cytokines. However, cytokines that promote distinct cellular responses often activate identical STAT proteins, thereby raising the question of how specificity is manifest within this signaling pathway. Here we report the generation and characterization of mice deficient in STAT1. STAT1-deficient mice show no overt developmental abnormalities, but display a complete lack of responsiveness to either IFN alpha or IFN gamma and are highly sensitive to infection by microbial pathogens and viruses. In contrast, these mice respond normally to several other cytokines that activate STAT1 in vitro. These observations document that STAT1 plays an obligate and dedicated role in mediating IFN-dependent biologic responses and reveal an unexpected level of physiologic specificity for STAT1 action.
Animals↗
flk2/flt3 ligand is a potent cofactor for the growth of primitive B cell progenitors.
We have investigated the role of flk2/flt3 ligand (FL) in B cell lymphopoiesis. The ability of FL to stimulate the growth of immature B cells was assessed using distinct populations: CD43lowB220+ pre-B cells, CD43+B220+ pro-B cells, and CD43+B220low progenitors. FL failed to affect the growth of the pro-B or pre-B cells whether used alone or in combination with stem cell factor (SCF) or IL-7. In striking contrast, FL was a potent cofactor for the CD43+B220low progenitor cells, interacting with either IL-7 and/or SCF to stimulate their growth. The combination of FL with IL-7 plus SCF stimulated maximum expansion of these cells, albeit, less than that stimulated in stromal cell cultures. When the CD43+B220low progenitors were divided based on expression of heat stable Ag (CD24) into a CD24- and a CD24+ subset, the FL-responsive cells were contained only within the CD24- subset. FL interacted with SCF or with IL-7 to stimulate their growth resulting in a 20- and 50-fold increase in cellularity, respectively. Since the CD24- subset was the most immature of the B cell populations studied, our data suggest that FL costimulates the expansion of very primitive B cell progenitors.
Animals↗
Detection of Mycoplasma mycoides subspecies mycoides by monoclonal antibody-based sandwich ELISA.
Monoclonal antibodies (MAbs) were produced from a mouse immunised with Mycoplasma mycoides subsp. mycoides small colony (MmmSC) antigen and their use to detect and differentiate strains within the Mycoplasma mycoides cluster investigated in an antigen capture ELISA format. The MAbs produced could not distinguish between MmmSC and M. mycoides subsp. mycoides large colony (MmmLC) strains. However, the sandwich ELISAs developed were able to specifically distinguish these two biotypes from the other four members of the M. mycoides cluster, and from all other mycoplasma or bacteria species examined. The most sensitive application of the test was a combination of enrichment and capture by overnight or 48-h incubations of samples inoculated into mycoplasma broth in antibody-coated microtiter wells.
Animals↗