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BACKGROUND: Palliative care (PC) can reduce symptom distress and improve quality of life for patients and their families experiencing life-threatening illness. While the need for PC in Kenya is high, PC service delivery and research is limited. Qualitative research is needed to explore potential areas for PC research and support needed to enable that research. This insight is critical for informing a national PC research agenda and mobilizing limited resources for conducting rigorous PC research in Kenya. OBJECTIVES: To explore perceptions of priority areas for PC research and support needed to facilitate rigorous research from the perspective of Kenyan PC providers and leaders. METHODS: Focus groups (FGs) were conducted in November and December of 2018 using a semi-structured interview guide. FGs were audio-recorded, transcribed, and analyzed using a thematic content analysis approach. RESULTS: Three FGs were conducted (n = 22 participants). Ten themes related to PC research emerged, including research on: 1) beliefs about death, disease, and treatment to inform PC; 2) awareness about PC, 3) integration of PC within the health system; 4) understanding caregiver experiences and needs; 5) community health volunteers (CHVs) and volunteer programs; 6) evaluation of costs and benefits of PC; 7) treatment approaches, including complementary and alternative medicine (CAM) and advanced diagnostics at end of life; 8) other suggestions for research, 9) populations in need of PC research; and 10) resources for enabling research. CONCLUSIONS: Kenyan PC providers and leaders identified key areas requiring increased scientific inquiry and critical resources needed to enable this research. These findings can help to focus future PC research in Kenya and encourage funding agencies to prioritize the issues identified.
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Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Cuidados Paliativos , Humanos , Quênia , Qualidade de Vida , Grupos FocaisRESUMO
BACKGROUND: There are significant challenges in ensuring sufficient clinician participation in quality improvement training. Clinician capability has been identified as a barrier to the delivery of evidence-based care. Clinician training is an effective strategy to address this barrier, however, there are significant challenges in ensuring adequate clinician participation in training. This study aimed to assess the extent of participation by antenatal clinicians in evidence-based training to address alcohol consumption during pregnancy, and to assess differences in participation by profession. METHODS: A 7-month training initiative based on six evidence-based principles was implemented in a maternity service in New South Wales, Australia. Descriptive statistics described participation in training (% attending: any training; six evidence-based principles of training; all principles). Regression analyses examined differences by profession. RESULTS: Almost all antenatal clinicians participated in some training (182/186; 98%); 69% participated in ≥1 h of training (µ = 88.2mins, SD:56.56). The proportion of clinicians participating in training that satisfied each of the six principles ranged from 35% (training from peers and experts) to 82% (training was educational and instructional). Only 7% participated in training that satisfied all principles. A significantly higher proportion of midwifery compared to medical clinicians participated in training satisfying five of the six training principles. CONCLUSIONS: A training initiative based on evidence-based principles resulted in almost all clinicians receiving some training and 69% participating in at least 1 h of training. Variability between professions suggests training needs to be tailored to such groups. Further research is required to determine possible associations with care delivery outcomes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, No. ACTRN12617000882325 (date registered: 16/06/2017).
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Tocologia , Melhoria de Qualidade , Consumo de Bebidas Alcoólicas , Austrália , Feminino , Humanos , New South Wales , GravidezRESUMO
BACKGROUND: Health disparities for children with intellectual disabilities can be challenging to measure due to many other factors that can impact health and healthcare use. The aim of the current study was to use longitudinal cohort data to compare children with intellectual disability (ID) in Ireland between 2006 and 2014 on healthcare utilisation and unmet need, at ages 9 and 13, using a propensity score matching (PSM) approach. METHODS: Using data from the Growing up in Ireland study, PSM was used to identify an appropriate control sample to compare with a sample of children with ID (n = 124). Participants were matched on variables that are known to influence healthcare utilisation to reduce the impact of confounding variables between groups so that differences between the groups can be estimated. Logistic regression was used to estimate effects at ages 9 and 13. RESULTS: Children with ID were no more likely to have visited a general practitioner or emergency department in the past 12 months than children without ID. They did have a greater likelihood of visiting a doctor in a hospital in the past 12 months and of having an overnight stay in hospital by age 9. Primary caregivers of children with ID were more likely to report unmet health needs at ages 9 and 13. CONCLUSIONS: This approach is a novel means of comparing healthcare use in this population by balancing the impact of other factors that may result in inequities, to which children with ID may be more vulnerable.
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Deficiência Intelectual , Adolescente , Criança , Estudos de Coortes , Serviço Hospitalar de Emergência , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/terapia , Aceitação pelo Paciente de Cuidados de Saúde , Pontuação de PropensãoRESUMO
AIM: Attending routine outpatient clinic appointments is a central self-management behaviour of individuals living with Type 1 diabetes. A large number of young adults with Type 1 diabetes disengage from diabetes services, which may contribute to poor psychosocial and diabetes outcomes. The aim of this study is to elicit preferences from young adults with Type 1 diabetes regarding clinic-related services to inform service delivery. METHODS: A discrete choice experiment was developed to understand the preferences of young adults with Type 1 diabetes for clinic-related services. RESULTS: Young adults recruited from young adult Type 1 diabetes clinics in 2016 completed the experiment (n = 105). Young adults with Type 1 diabetes showed a preference for shorter waiting times, seeing a nurse and a consultant, relative to a nurse alone, and a flexible booking system compared with fixed appointment times. Results suggest no preference for a nurse and a doctor, relative to a nurse alone, or other optional services (e.g. seeing dietitians or psychologists), type of HbA1c test and digital blood glucose diaries over paper-based diaries. CONCLUSION: This study highlights aspects of routine clinic appointments that are valued by young adults living with Type 1 diabetes, namely shorter waiting times at clinic, the option to see both a nurse and consultant at each visit and a flexible clinic appointment booking system. These findings suggest young adults with Type 1 diabetes value convenience and should help services to restructure their clinics to be more responsive to the needs of young adults.
Assuntos
Comportamento de Escolha , Diabetes Mellitus Tipo 1/terapia , Preferência do Paciente , Adolescente , Adulto , Instituições de Assistência Ambulatorial , Glicemia/análise , Automonitorização da Glicemia/instrumentação , Automonitorização da Glicemia/métodos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/psicologia , Feminino , Grupos Focais , Humanos , Masculino , Preferência do Paciente/psicologia , Preferência do Paciente/estatística & dados numéricos , Satisfação do Paciente/estatística & dados numéricos , Relações Profissional-Paciente , Inquéritos e Questionários , Fatores de Tempo , Listas de Espera , Adulto JovemRESUMO
There are now over 104,000 people living in Ireland with a cancer diagnosis. Using The Irish Longitudinal Study on Ageing (TILDA), healthcare utilisation of cancer survivors (aged 50 +) was compared with those without a history of cancer across service providers. Our cancer variable was stratified by time since diagnosis (2-5, 6-10, 11+ years) and type (breast, prostate, colorectal and a miscellaneous group of other cancers). While the probability of cancer survivors accessing GP services was not significant different to respondents without a history of cancer, the probability of an outpatient specialist office visit was 19.5, 11.8 and 14.0 percentage points higher, respectively for those 2-5years, 6-10 years and 11 years or more after their cancer diagnosis and was statistically significant. In Ireland, the pattern of GP and specialist use appears less well defined compared to other European countries. This suggests an overarching policy response is required for cancer survivorship care.
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The objective of the current study was to quantify the effects of exposure to Salmonella, Neospora caninum, and Leptospira interrogans serovar Hardjo (L. hardjo) on dairy farm profitability and to simulate the effect of vaccination for Salmonella and L. hardjo on dairy farm profitability. The production effects associated with exposure to each of these pathogens in study herds were defined under 3 categories: (1) milk production effects, (2) reproduction effects (including culling), and (3) mortality effects. The production effects associated with exposure to Salmonella, N. caninum, and L. hardjo were incorporated into the Moorepark Dairy Systems Model. In the analysis, herds negative for exposure to Salmonella, N. caninum, and L. hardjo were assumed baseline herds, with all results presented relative to this base. In simulations examining the effect of vaccination for Salmonella and L. hardjo on farm profitability, vaccinated herds (vaccination costs included) were considered as baseline herds and results were presented relative to this base. Total annual profits in unvaccinated herds were reduced by 77.31, 94.71, and 112.11 per cow at milk prices of 0.24, 0.29, and 0.34/L, respectively, as a result of exposure to Salmonella. In the current study, herds positive for exposure to Salmonella recorded a 316-kg reduction in milk yield, whereas no association was detected between exposure to N. caninum or L. hardjo and milk production. Exposure to both N. caninum and L. hardjo was associated with compromised reproductive performance. Herds positive for exposure to N. caninum and Salmonella had greater rates of adult cow mortality and calf mortality, respectively. Vaccination for both Salmonella and L. hardjo was associated with improved performance in study herds. Exposure to N. caninum resulted in a reduction in annual farm profits of 11.55, 12, and 12.44 per cow at each milk price, whereas exposure to L. hardjo resulted in a reduction in annual farm profits of 13.83, 13.78, and 13.72 per cow at each milk price. Herds that tested positive for exposure to Salmonella and L. hardjo were compared with herds vaccinated for the respective pathogens. Herds vaccinated for Salmonella generated 67.09, 84.48, and 101.89 per cow more profit at each milk price compared with herds positive for exposure. Similarly, herds vaccinated for L. hardjo generated 9.74, 9.69, and 9.63 per cow more profit compared with unvaccinated exposed herds. However, herds that tested negative for exposure to Salmonella and L. hardjo generated additional profits of 10.22 and 4.09 per cow, respectively, compared with vaccinated baseline herds.
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Doenças dos Bovinos/microbiologia , Coccidiose/veterinária , Leptospirose/veterinária , Salmonelose Animal/microbiologia , Animais , Anticorpos Antibacterianos , Bovinos , Doenças dos Bovinos/economia , Doenças dos Bovinos/epidemiologia , Coccidiose/epidemiologia , Feminino , Irlanda/epidemiologia , Leptospira interrogans/classificação , Leptospirose/epidemiologia , Leptospirose/microbiologia , Leite/economia , Neospora , Reprodução , Salmonella , Salmonelose Animal/epidemiologiaRESUMO
BACKGROUND: An ageing population leads to increasing prevalence of age-related chronic conditions that present challenges to the health-care services. Despite this, in countries including Ireland, little is known about the health-care impact of conditions such as osteoarthritis or rheumatoid arthritis amongst older adults. METHODS: A series of count models are developed to investigate the incremental health-care usage of individuals with either osteoarthritis or rheumatoid arthritis on the use of general practitioners (GP) services, outpatients' services, accident and emergency visits and inpatient nights. RESULTS: Both types of arthritic conditions lead to increased usage of GP and outpatients' services but not other hospital services. Differences in entitlements to care, as captured by the presence of a medical card in Ireland, lead to different health-care usage among arthritis sufferers. Translating the additional utilization into cost suggests a combined incremental annual cost of both types of arthritis of 13.6 million. CONCLUSIONS: Osteoarthritis and rheumatoid arthritis present challenges to health-care services in the context of an ageing population. In the case of Ireland the burden falls predominantly on primary health-care and outpatient services. Within the context of changing health-care service provision in Ireland, the results of this study have implications for future planning of service delivery.
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Artrite Reumatoide/terapia , Atenção à Saúde/estatística & dados numéricos , Osteoartrite/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/economia , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Irlanda/epidemiologia , Masculino , Pessoa de Meia-Idade , Osteoartrite/economiaRESUMO
UNLABELLED: 13q deletion is a rare cause of ambiguous genitalia in the male newborn, and can be associated with mental retardation of varying degree, retinoblastoma, and malformations of the brain, eye, genitourinary and gastrointestinal tract, depending on the level of the deletion. We present a male neonate with ambiguous genitalia and IUGR with a 13q33.2 deletion, and a paternal balanced translocation. Microarray analysis found the genes involved to be on chromosome 13 in the region 102989254bp-109214509bp. This deletion encompasses the EFNB2 gene, which has been implicated in genital malformations in 13q deletion cases. CONCLUSIONS: We find a link between haploinsufficiency of the EFNB2 gene and the presence of ambiguous genitalia and hypospadia in patients with a 13q.33 deletion. This work emphasizes the importance of early diagnosis of this condition due to the link with mental retardation and the need for follow up and management.
Assuntos
Anormalidades Múltiplas/genética , Deleção Cromossômica , Cromossomos Humanos Par 13 , Retardo do Crescimento Fetal/genética , Genitália Masculina/anormalidades , Deficiência Intelectual/genética , Mapeamento Cromossômico , Anormalidades Congênitas/genética , Humanos , Recém-Nascido , Cariotipagem , Masculino , Análise em Microsséries , Translocação GenéticaRESUMO
Sex reversal due to duplication of the Xp21 dosage-sensitive sex reversal locus results in XY females with gonadal dysgenesis. Pure Xp disomy (without a concurrent loss of genetic material) can occur by translocation or interstitial duplication. The case reported here is the rare form with a t(Xp;Yp). The combination of conventional clinical cytogenetic techniques, microsatellite analysis and high-density microarrays identified the X-chromosome breakpoint as centromeric of the NR0B1 gene and its control elements. Cytogenetics and array technology complemented each other in characterizing the translocation event and the extent of the dosage-sensitive sex reversal critical region on the derivative Y-chromosome. The implications of this analysis also lie in genetic counseling that highlight the likely de novo nature of a paternal meiotic event.
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Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Transtornos do Desenvolvimento Sexual , Pré-Escolar , Feminino , Humanos , CariotipagemRESUMO
BACKGROUND: The transition from medical school to internship can be daunting for newly qualified doctors. High rates of stress and burnout have been reported, with negative impacts on patient care and physician wellbeing. AIMS: We surveyed interns in our hospital group to evaluate rates of stress and burnout, as well as identify the causative factors and propose potential solutions to these. METHODS: A hundred and one interns working in four different hospitals over a 2-year period were invited to participate in an anonymous survey. The survey collected basic demographic details and surveyed aspects of mental health using the burnout scale, Maslach Burnout Inventory (MBI) and the stress scale and 12-item General Health Questionnaire (GHQ-12). Interns were also asked to rate a variety of workplace factors on a Likert scale based on the degree of stress caused. Finally, they were surveyed on their awareness of support services available to them. RESULTS: Our results showed that 37% of interns met the criteria for psychological distress, high levels of emotional exhaustion, high depersonalisation and a low sense of personal accomplishment were reported in 55.4, 51.5 and 41.6%, respectively. Inadequate preparation for practice, financial worries, poor role definition and sleep deprivation were reported as significant stressors. Most were unaware of available support services and expressed interest in leaving Ireland after internship. CONCLUSIONS: Burnout and stress are significant problems amongst doctors in Irish hospitals. Ensuring better preparation for clinical practice and awareness of support services is vital to tackle this issue.
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Esgotamento Profissional/psicologia , Hospitais/normas , Internato e Residência/normas , Médicos/psicologia , Estresse Psicológico/etiologia , Adulto , Estudos Transversais , Feminino , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
The identification of an association between polymorphisms of the prion protein (PrP) gene and susceptibility to scrapie has enabled the development of breeding programmes to increase natural resistance to scrapie. It is, however, imperative to identify if such selection would affect important reproduction and production traits. The objective of this study was to determine if there is a relationship between polymorphisms at codons 136, 154 and 171 of the PrP gene and ovulation rate or litter size in sheep. Data were collected from a mixed-aged flock of Belclare ewes, over a 9-year period. Ovulation rate was determined annually using laparoscopy by counting the number of corpora lutea at each of two consecutive oestrous cycles, one immediately before and one after mating (2418 records from 366 ewes). Litter size was recorded at parturition (875 records from 353 ewes). The five common PrP alleles were present in the population and 14 PrP genotypes were represented among the animals studied. There was no significant overall effect of PrP genotype on ovulation rate or litter size and pairwise comparisons among genotypes did not reveal any significant differences for either trait. These data suggest that breeding programmes based on selection for specific polymorphisms of the PrP gene will not influence ovulation rate or litter size, at least in the breed studied.
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Tamanho da Ninhada de Vivíparos , Ovulação/genética , Proteínas PrPSc/genética , Ovinos/fisiologia , Animais , Feminino , Frequência do Gene , Genótipo , Polimorfismo Genético , GravidezRESUMO
The objective of this study was to determine if there is an association between tenderness in bovine M. longisimus dorsi (LD) and polymorphisms in the bovine calpain I (exons 9 & 14), calpain II (regulatory subunit) or growth hormone (intron 3) genes. Genomic DNA was isolated from bovine LD (n=281) on which quality attributes (Warner Bratzler shear force (WBSF), sarcomere length and composition) were also characterised. DNA polymorphisms were analysed using polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis. Association analyses were performed between genotypes at the four polymorphic loci and day 14 WBSF values. It was found that the calpain 1 exon 9 genotypes had an association with WBSF such that animals with the GA genotype exhibited decreased WBSF and increased tenderness when compared to animals with the GG genotype (P<0.05). This observation concurs with that of earlier studies, suggesting that this polymorphism is a functional marker for beef tenderness.
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Human islets were macroencapsulated in permselective hollow fiber membrane devices and successfully allotransplanted subcutaneously with > 90% viability after 2 weeks in situ. Recipients were patients with type I or type II diabetes and normal control subjects; none was immunosuppressed. Between 150 and 200 islet equivalents were implanted in each of the nine patients. No adverse patient complications were observed. Biocompatibility of devices was excellent. Insulin-positive beta-cells were confirmed in encapsulated islets recovered from the implanted devices in all patient populations including the type I diabetic patients. Glucose-stimulated insulin release could be demonstrated in vitro from recovered islets. These data demonstrate that macroencapsulated human islets can survive at the subcutaneous site and that permselective membranes can be designed to protect against both allogeneic immune responses as well as the autoimmune component of type I diabetes.
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Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Insulina/metabolismo , Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/metabolismo , Materiais Biocompatíveis , Glicemia/metabolismo , Sobrevivência Celular , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Glucose/farmacologia , Humanos , Terapia de Imunossupressão , Insulina/análise , Secreção de Insulina , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/efeitos dos fármacos , Transplante das Ilhotas Pancreáticas/fisiologia , Membranas Artificiais , Teofilina/farmacologiaRESUMO
Patient length of hospitalization was examined in a private short-term therapeutic community unit using a longitudinal, multimethod, -ultivariate approach, with data analyzed separately by patient sex. Patient data were entered into stepwise linear regression analyses for weeks 1, 2, and 4 of an average seven-week hospitalization for male and female patients separately. Results for men were not specifically replicated among the women. Longer-staying men were diagnosed more frequently as "personality disorders," tended to be somewhat aloof, perceived the ward as encouraging denial, facade, order, and organization. Among women, verbal behavior, interpersonal relations, discontentedness with family, and other variables were related to length of hospitalization. Shorter-staying male and female patients tended to exhibit characteristics at the "feminine" end of a hypothetical masculinity-femininity continuum. Conforming, accepting behavior seemed reinforced for all patients.
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Tempo de Internação , Comportamento Social , Comunidade Terapêutica , Adulto , Feminino , Identidade de Gênero , Humanos , Estudos Longitudinais , Masculino , Relações Profissional-Paciente , Escalas de Graduação Psiquiátrica , Autoimagem , Fatores Sexuais , Conformidade Social , Desejabilidade Social , Percepção Social , Comportamento VerbalRESUMO
This report explores two theoretical positions regarding psychiatric inpatient self-labeling processes over time. One position suggests that acceptance of the deviant label "mentally ill" is benign; the other suggests that such label acceptance may be harmful to patients. Employing empirical, longitudinal data from a sample of 43 inpatients, three complex, but discernible, patterns of "acceptance," "rejection," or "denial" of the "deviant" label of mental patient emerged over time within a short-term hospital setting. The three patient groups varied on Minnesota Multiphasic Personality Inventory scales, staff behavioral ratings over time, involvement in approved ward activities, and length of hospitalization. Results were discussed in terms of patient-staff interaction and its possible relation to patient self-labeling.
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Hospitais Psiquiátricos , Transtornos Mentais , Pacientes , Autoimagem , Autoavaliação (Psicologia) , Adulto , Análise de Variância , Feminino , Humanos , Tempo de Internação , MMPI , Masculino , Relações Profissional-Paciente , Comunidade TerapêuticaRESUMO
Ezetimibe is intestinally active cholesterol absorption inhibitor used to reduce low-density lipoprotein-cholesterol levels. This case report describes a novel side effect with this agent: ezetimibe-induced hyperlipidaemia in a patient with statin intolerance and familial combined hyperlipidaemia. Ezetimibe therapy induced an asymptomatic 770% increase in triglycerides (TGs) (3.51-27.1 mmol/l) and a 190% increase in total cholesterol (9.8-18.5 mmol/ 1) secondary to an increase (4.6-25.9 micromol/l; 560%) in hepatic cholesterol (lathosterol) synthesis. This lipid profile resolved 9 months after cessation of ezetimibe therapy. This report shows that ezetimibe may have long-lasting effects in man far exceeding its plasma half-life and that ezetimibe monotherapy can induce a large increase in hepatocyte very-low-density lipoprotein synthesis in rare individuals with a consequent mixed hyperlipidaemia or possibly hypercholesterolaemia depending on the metabolism and clearance of TG-rich lipoproteins.
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Anticolesterolemiantes/efeitos adversos , Azetidinas/efeitos adversos , Hiperlipidemias/induzido quimicamente , Colesterol/sangue , Ezetimiba , Feminino , Humanos , Hiperlipidemia Familiar Combinada/sangue , Hiperlipidemia Familiar Combinada/tratamento farmacológico , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
Bovine viral diarrhoea virus (BVDV) and bovine herpesvirus 1 (BoHV-1) are contagious bovine viral agents. The objectives of this study were to use quarterly bulk milk and 'spot' testing of unvaccinated youngstock to establish the national prevalence of exposure to BVDV and/or BoHV-1 in Irish dairy herds. Seasonality of bulk milk ELISA results was also examined. From a geographically representative population of 305 dairy herds, 88% and 80% of herds yielded mean annual positive bulk milk readings for BVDV and BoHV-1, respectively. Of these, 61% were vaccinated against BVDV and 12% against BoHV-1. A total of 2171 serum samples from weanlings having a mean age of 291 days yielded 543 (25%) seropositive for BVDV, and 117 (5.4%) seropositive for BoHV-1. A significant seasonal trend in bulk milk antibody ELISA readings and herd status was recorded for BVDV, with more herds categorised as positive in the latter half of the year.
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Doença das Mucosas por Vírus da Diarreia Viral Bovina/epidemiologia , Vírus da Diarreia Viral Bovina/isolamento & purificação , Herpesvirus Bovino 1/isolamento & purificação , Rinotraqueíte Infecciosa Bovina/epidemiologia , Animais , Anticorpos Antivirais/sangue , Doença das Mucosas por Vírus da Diarreia Viral Bovina/virologia , Bovinos , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Rinotraqueíte Infecciosa Bovina/virologia , Irlanda/epidemiologia , Leite/virologia , Prevalência , Estações do AnoRESUMO
p21WAF1/CIP1 is a nucleoprotein that was initially characterized by its ability to be regulated transcriptionally by p53 and by its ability to mediate growth arrest by binding to cyclin-dependent kinases. Although p21WAF1/CIP1 is thought to mediate the effects of p53 in causing growth arrest, p21WAF1/CIP1 is also regulated in a p53-independent manner, e.g., during terminal differentiation of some cell lines. Growth factors including epidermal growth factor also induce p21WAF1/CIP1 through p53-independent pathways. Because the epidermal growth factor signaling pathway is abnormal in psoriatic epidermis, we studied p21WAF1/CIP1 expression, using in situ hybridization and immunohistochemistry, in psoriasis. Both p21WAF1/CIP1 mRNA and protein were significantly elevated in untreated psoriatic plaques compared with uninvolved psoriatic skin (p < 0.0001), with the up-regulation of p21WAF1/CIP1 being predominantly suprabasal. This increase was accompanied by a small increase in p53 protein expression of uncertain significance. Furthermore, p21WAF1/CIP1 expression was induced in skin after sellotape stripping and by the application of agents, such as dithranol, that are capable of inducing hyperproliferation. The pattern of p21WAF1/CIP1 expression observed is consistent with a role in induction and maintenance of differentiation. Our experiments, however, cannot determine whether the abnormalities of p21WAF1/CIP1 epidermal expression in psoriasis and after insult are independent of changes in p53 expression.
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Ciclinas/metabolismo , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Irritantes/farmacologia , Psoríase/metabolismo , Antralina/farmacologia , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/genética , Humanos , Estimulação Física , Psoríase/patologia , RNA Mensageiro/metabolismo , Dodecilsulfato de Sódio/farmacologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
This study was designed to assess the potential benefit of hydroxyurea (HU) on virological and immunological markers in heavily pretreated human immunodeficiency virus (HIV)-infected patients. A total of 118 patients received hydroxyurea as treatment added to their current antiviral therapy ('add' group), or as treatment added together with a switched nucleoside reverse transcriptase inhibitor or protease inhibitor or with the introduction of an additional antiviral agent ('add and switch' group). Efficacy of HU was also compared among patients receiving didanosine- and non-didanosine-containing regimens. Results showed that HU was not associated with a significant decline in plasma HIV-1 RNA, and no significant difference in plasma HIV-1 RNA changes was noted between patients who did and did not receive didanosine. The absolute number of CD4 cells, but not the CD4 percentage, declined significantly from baseline. Significantly more grade 3-4 neutropenia occurred among patients receiving HU combined with zidovudine, although the discontinuation rate for haematological toxicity was similar in zidovudine- and non-zidovudine-treated patients.
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Fármacos Anti-HIV/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hidroxiureia/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Didanosina/administração & dosagem , Didanosina/uso terapêutico , Quimioterapia Combinada , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Feminino , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Hidroxiureia/administração & dosagem , Hidroxiureia/efeitos adversos , Masculino , RNA Viral/sangue , Inibidores da Transcriptase Reversa/administração & dosagem , Resultado do TratamentoRESUMO
PURPOSE: To define the clinical characteristics and determine the gene localization for a previously undescribed form of congenital fibrosis of the extraocular muscles (CFEOM), referred to as CFEOM type 3 (CFEOM3). METHODS: A large family with CFEOM was identified, and participating individuals underwent ophthalmologic examination and donated blood for genetic analysis. The family's disorder was tested for linkage to the known CFEOM loci, followed by a genome-wide search and linkage refinement using polymorphic DNA markers. RESULTS: Thirty-eight members of this Canadian family participated in the study. Affected individuals are born with a nonprogressive eye movement disorder characterized by variable expression of ptosis and restrictive external ophthalmoplegia. Severely affected individuals have ptosis, primary gaze fixed in a hypo- and exotropic position, and marked restriction of eye movement bilaterally. Mildly affected individuals have normally positioned globes with a limitation of vertical gaze. Moderately affected individuals have asymmetrical involvement with one eye severely and one eye mildly affected. The disorder is autosomal dominant with variable expression and probable incomplete penetrance. Genetic analysis reveals linkage to markers on 16q24.2q24.3. A maximum lod score of 5.8 occurs at markers D16S3063 and D16S689, and the CFEOM3 disease gene is located within a 5.6-cM region flanked by D16S486 and D16S671. CONCLUSIONS: These data establish that CFEOM3 is a phenotypically variant and genotypically distinct form of CFEOM with linkage to chromosome 16qter. The authors have previously demonstrated that CFEOM1 results from a developmental absence of the superior division of the oculomotor nerve. The authors hypothesize that CFEOM3 results from a defect analogous to, but distinct from CFEOM1.