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1.
Psychol Med ; 53(2): 559-566, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-34140050

RESUMO

BACKGROUND: Offspring of parents with major mood disorders (MDDs) are at increased risk for early psychopathology. We aim to compare the rates of neurodevelopmental disorders in offspring of parents with bipolar disorder, major depressive disorder, and controls. METHOD: We established a lifetime diagnosis of neurodevelopmental disorders [attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disabilities, specific learning disorders, and motor disorders] using the Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version in 400 participants (mean age 11.3 + s.d. 3.9 years), including 93 offspring of parents with bipolar disorder, 182 offspring of parents with major depressive disorder, and 125 control offspring of parents with no mood disorder. RESULTS: Neurodevelopmental disorders were elevated in offspring of parents with bipolar disorder [odds ratio (OR) 2.34, 95% confidence interval (CI) 1.23-4.47, p = 0.010] and major depressive disorder (OR 1.87, 95% CI 1.03-3.39, p = 0.035) compared to controls. This difference was driven by the rates of ADHD, which were highest among offspring of parents with bipolar disorder (30.1%), intermediate in offspring of parents with major depressive disorder (24.2%), and lowest in controls (14.4%). There were no significant differences in frequencies of other neurodevelopmental disorders between the three groups. Chronic course of mood disorder in parents was associated with higher rates of any neurodevelopmental disorder and higher rates of ADHD in offspring. CONCLUSIONS: Our findings suggest monitoring for ADHD and other neurodevelopmental disorders in offspring of parents with MDDs may be indicated to improve early diagnosis and treatment.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Transtorno Bipolar , Filho de Pais com Deficiência , Transtorno Depressivo Maior , Humanos , Criança , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno Depressivo Maior/epidemiologia , Depressão , Filho de Pais com Deficiência/psicologia , Pais/psicologia
2.
Psychol Med ; 50(6): 1050-1056, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31120010

RESUMO

BACKGROUND: Children of parents with mood and psychotic disorders are at elevated risk for a range of behavioral and emotional problems. However, as the usual reporter of psychopathology in children is the parent, reports of early problems in children of parents with mood and psychotic disorders may be biased by the parents' own experience of mental illness and their mental state. METHODS: Independent observers rated psychopathology using the Test Observation Form in 378 children and youth between the ages of 4 and 24 (mean = 11.01, s.d. = 4.40) who had a parent with major depressive disorder, bipolar disorder, schizophrenia, or no history of mood and psychotic disorders. RESULTS: Observed attentional problems were elevated in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia (effect sizes ranging between 0.31 and 0.56). Oppositional behavior and language/thought problems showed variable degrees of elevation (effect sizes 0.17 to 0.57) across the three high-risk groups, with the greatest difficulties observed in offspring of parents with bipolar disorder. Observed anxiety was increased in offspring of parents with major depressive disorder and bipolar disorder (effect sizes 0.19 and 0.25 respectively) but not in offspring of parents with schizophrenia. CONCLUSIONS: Our results suggest that externalizing problems and cognitive and language difficulties may represent a general manifestation of familial risk for mood and psychotic disorders, while anxiety may be a specific marker of liability for mood disorders. Observer assessment may improve early identification of risk and selection of youth who may benefit from targeted prevention.


Assuntos
Transtorno Bipolar/psicologia , Filho de Pais com Deficiência/psicologia , Transtorno Depressivo Maior/psicologia , Psicologia do Esquizofrênico , Adolescente , Ansiedade/psicologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pais , Escalas de Graduação Psiquiátrica , Psicopatologia , Fatores de Risco , Esquizofrenia , Adulto Jovem
3.
BJOG ; 127(13): 1628-1635, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32437082

RESUMO

OBJECTIVE: To assess pain symptoms before and after hysterectomy in women with endometriosis. DESIGN: A population-based registry study. SETTING: Sweden. POPULATION: Women aged 18-45 years who underwent hysterectomy for endometriosis between 2010 and 2015. METHODS: Pain symptoms before hysterectomy and 12 months after surgery were collected from the Swedish National Quality Register for Gynaecological Surgery (GynOp). Pain symptoms were also assessed by follow-up surveys after a median follow-up period of 63 months. MAIN OUTCOME MEASURES: Pelvic or lower abdominal pain after hysterectomy. RESULTS: The study included 137 women. The proportion of women experiencing pain of any severity decreased by 28% after hysterectomy (P < 0.001). The proportion of women with severe pain symptoms decreased by 76% after hysterectomy (P < 0.001). The majority of women (84%) were satisfied with the surgical result. Presence of severe pain symptoms after the hysterectomy was associated with less satisfaction (P < 0.001). Pain symptoms after surgery, patient satisfaction and the patient's perceived improvement were not significantly different between women whose ovarian tissue was preserved and women who underwent bilateral oophorectomy. CONCLUSIONS: We observed a significant, long-lasting reduction in pain symptoms after hysterectomy among women with endometriosis. Hysterectomy, with the possibility of ovarian preservation, may be a valuable option for women with endometriosis who suffer from severe pain symptoms. TWEETABLE ABSTRACT: Hysterectomy is a valuable option for women with endometriosis and severe pain symptoms.


Assuntos
Endometriose/complicações , Endometriose/cirurgia , Histerectomia , Dor Pélvica/etiologia , Dor Pélvica/cirurgia , Doenças Uterinas/complicações , Doenças Uterinas/cirurgia , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Índice de Gravidade de Doença , Suécia , Adulto Jovem
4.
Brain Behav Immun ; 81: 272-279, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31228612

RESUMO

OBJECTIVE: To our knowledge, this is the first study assessing brain activation in response to painful stimulation over disease-relevant (finger joint) vs. neutral area (thumb nail) in patients suffering from rheumatoid arthritis (RA) compared to healthy controls (HC). METHOD: Thirty-one RA patients and 23 HC underwent functional magnetic resonance imaging (fMRI) while stimulated with subjectively calibrated painful pressures corresponding to a pain sensation of 50 mm on a 100 mm VAS scale (P50) at disease-affected finger joint and thumbnail (left hand), and corresponding sites in HC. RESULTS: Compared to controls, RA patients had significantly increased pain sensitivity (lower P50) at the inflamed joints but not at the thumbnail. RA patients exhibited significantly less activation in regions related to pain- and somatosensory processing (S1, M1, anterior insula, S2, SMG and MCC) during painful joint stimulation, compared to HC. No group difference in cerebral pain processing was found for the non-affected thumbnail. Within RA patients, significantly less brain activation was found in response to painful stimulation over disease-affected joint compared to non-affected thumbnail in bilateral S1, bilateral S2, and anterior insula. Further, RA patients exhibited a right-sided dlPFC deactivation, psycho-physiologically interacting (PPI) with the left dlPFC in response to painful stimulation at disease-affected joints. CONCLUSION: The results indicate normal pain sensitivity and cerebral pain processing in RA for non-affected sites, while the increased sensitivity at inflamed joints indicate peripheral/spinal sensitization. Brain imaging data suggest that disease-relevant pain processing in RA is marked by aberrations and a failed initiation of cortical top-down regulation.


Assuntos
Artrite Reumatoide/fisiopatologia , Córtex Cerebral/fisiopatologia , Dor/fisiopatologia , Adulto , Idoso , Artrite Reumatoide/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico por imagem , Limiar da Dor/fisiologia
5.
BJOG ; 123(4): 608-16, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25601143

RESUMO

OBJECTIVE: To study the association between duration of second stage of labour and risks of maternal complications (infection, urinary retention, haematoma or ruptured sutures) in the early postpartum period. DESIGN: Population-based cohort study. SETTING AND SAMPLE: We included 72 593 mothers with singleton vaginal deliveries at ≥37 weeks of gestation in cephalic presentation, using the obstetric database from the Stockholm-Gotland region in Sweden, 2008-12. METHODS: Logistic regression analysis. Odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated and adjustments were made for maternal age, body mass index, height, smoking, cohabitation, gestational age, labour induction, epidural analgesia and oxytocin augmentation. RESULTS: Rates of any complication varied by parity from 7.3% in parous women with previous caesarean section, 4.8% in primiparas and 1.7% in parous women with no previous caesarean section. Compared with a second stage <1 hour, the adjusted ORs for any complication (95% CI) in primiparas were for 1 to <2 hours 1.28 (1.11-1.47); 2 to <3 hours 1.54 (1.32-1.79), 3 to <4 hours 1.63 (1.38-1.93) and ≥4 hours 2.08 (1.74-2.49). The corresponding adjusted ORs for parous women without previous caesarean were 2.27 (1.78-2.90), 2.97 (2.09-4.22), 3.65 (2.25-5.94) and 3.16 (1.44-6.94), respectively. The adjusted ORs for women with previous caesarean were for 1 to <2 hours 1.62 (1.13-2.32); 2 to <3 hours 1.56 (1.00-2.43), 3 to <4 hours 2.42 (1.52-3.87), and ≥4 hours 2.31 (1.25-4.24). CONCLUSIONS: Risks of maternal complications in the postpartum period increase with duration of second stage of labour also after accounting for maternal, pregnancy and delivery characteristics. Special attention has to be given to parous women with previous caesarean deliveries.


Assuntos
Cesárea/estatística & dados numéricos , Parto Obstétrico/efeitos adversos , Segunda Fase do Trabalho de Parto , Período Pós-Parto , Infecção Puerperal/epidemiologia , Retenção Urinária/epidemiologia , Adulto , Peso ao Nascer , Parto Obstétrico/estatística & dados numéricos , Feminino , Humanos , Recém-Nascido , Trabalho de Parto Induzido , Razão de Chances , Gravidez , Prevalência , Fatores de Risco , Suécia/epidemiologia , Fatores de Tempo
6.
J Intern Med ; 278(6): 645-59, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26096600

RESUMO

Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.


Assuntos
Doenças Cardiovasculares , Doença Pulmonar Obstrutiva Crônica , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/terapia , Feminino , Técnicas Genéticas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteômica/métodos , Saúde Pública/métodos , Saúde Pública/estatística & dados numéricos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/terapia , Fatores de Risco , Fatores Socioeconômicos , Suécia/epidemiologia
7.
Hum Reprod ; 27(2): 388-93, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22128294

RESUMO

BACKGROUND: Misoprostol has been shown to be an effective agent for cervical ripening and termination of early pregnancy especially when administered vaginally. Our objective was to evaluate whether bacterial vaginosis (BV) affected the pharmacokinetics of vaginally administered misoprostol during early pregnancy. METHODS: Ten women with BV and 10 healthy women requesting medical abortion up to 9 weeks of pregnancy were administered 200 mg mifepristone followed 24-48 h later by a single dose of 800 µg misoprostol vaginally. Blood samples were taken before (0 h) and 0.5, 1, 2, 3 and 4 h after misoprostol administration. Misoprostol acid was determined in serum samples using liquid chromatography/tandem mass spectrometry. RESULTS: All women with BV had a vaginal pH > 4.7. The mean bioavailability measured as the area under the curve (AUC) and maximum concentration (C(max)) appeared higher in the control than in the BV group (1458.7 versus 878.1 pg h/ml) and (630.7 versus 342.5 pg/ml), respectively, but did not achieve statistical significance and there was no other significant difference in the pharmacokinetics between the two groups. However, if two women with vaginal pH > 4.7 were excluded from the control group the difference in AUC240 (1359 versus 878.1 pgh/ml) reached statistical significance (P = 0.048). CONCLUSIONS: BV had an effect on pharmacokinetics of vaginally administered misoprostol in early pregnancy. However, the results should be interpreted with caution due to the small sample size and marked individual variations.


Assuntos
Abortivos não Esteroides/farmacocinética , Misoprostol/farmacocinética , Complicações Infecciosas na Gravidez/metabolismo , Vaginose Bacteriana/metabolismo , Abortivos não Esteroides/administração & dosagem , Aborto Induzido , Administração Intravaginal , Adolescente , Adulto , Disponibilidade Biológica , Biotransformação , Estudos de Casos e Controles , Feminino , Humanos , Concentração de Íons de Hidrogênio , Misoprostol/administração & dosagem , Misoprostol/análogos & derivados , Misoprostol/sangue , Gravidez , Complicações Infecciosas na Gravidez/sangue , Primeiro Trimestre da Gravidez , Estudos Prospectivos , Vaginose Bacteriana/sangue , Adulto Jovem
8.
BJOG ; 119(13): 1648-56, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23078516

RESUMO

OBJECTIVE: To investigate risk of recurrence of labour dystocia and mode of delivery in second labour after taking first labour and fetal and maternal characteristics into account. DESIGN: A population-based cohort study. SETTING: The Swedish Medical Birth Register from 1992 to 2006. POPULATION: A total of 239 953 women who gave birth to their first and second singleton infants in cephalic presentation at ≥ 37 weeks of gestation with spontaneous onset of labour. METHODS: We used logistic regression analysis to estimate crude and adjusted odds ratios. MAIN OUTCOME MEASURES: Labour dystocia and mode of delivery in second labour. RESULTS: Overall labour dystocia affected only 12% of women with previous dystocia. Regardless of mode of first delivery, rates of dystocia in the second labour were higher in women with than without previous dystocia, but were more pronounced in women with previous caesarean section (34%). Analyses with risk score groups for dystocia (risk factors were long interpregnancy interval, maternal age ≥ 35 years, obesity, short maternal stature, not cohabiting and post-term pregnancy) showed that risk of instrumental delivery in second labour increased with previous dystocia and increasing risk score. Among women with trial of labour after caesarean section with previous dystocia and a risk score of 3 or more, 66% had a vaginal instrumental or caesarean delivery (17 and 49%, respectively). In women with trial of labour after caesarean section without previous dystocia and a risk score of 0, corresponding risk was 32% (14 and 18%, respectively). CONCLUSION: Previous labour dystocia increases the risk of dystocia in subsequent delivery. Taking first labour and fetal and maternal characteristics into account is important in the risk assessments for dystocia and instrumental delivery in second labour.


Assuntos
Cesárea/estatística & dados numéricos , Distocia/etiologia , Extração Obstétrica/estatística & dados numéricos , Adulto , Estudos de Coortes , Distocia/epidemiologia , Feminino , Humanos , Modelos Logísticos , Razão de Chances , Paridade , Gravidez , Recidiva , Sistema de Registros , Fatores de Risco , Suécia/epidemiologia
9.
Child Care Health Dev ; 37(5): 727-33, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21198777

RESUMO

BACKGROUND: There is little available information about what children and parents would like to know about a forthcoming hospitalization and what they currently receive. METHODS: The current study was a survey of 102 children between the ages of 6 and 10 years and their parents recruited either from the Recovery Unit following day surgery or from the wards following overnight admissions at Sydney Children's Hospital, Australia. Information was obtained about each child's experience in hospital, the nature and format of information that they had received prior to the admission, and what information the child/parent thought would be helpful to receive. RESULTS: Parents recorded a total of 163 questions asked by children prior to their admission. Questions related to timing (e.g. duration of admission, length of procedure), pain, procedural information, anaesthesia, needles, whether parents can be present, activities to do in hospital, seeking explanations ('Why' questions), hospital environment, seeking reassurance and miscellaneous questions. Children who were satisfied with the amount of information they received before coming to hospital subsequently reported that they would be significantly less scared should they need to come back to hospital for a future procedure. A total of 46.7% of children received information about their hospitalization from their parent(s) and a further 12% from a doctor and parent. CONCLUSIONS: Children were found to have many questions about a forthcoming hospitalization. Parents were found to have a major role as information providers. Further research is needed to assess parental confidence and competence to meet their child's information needs.


Assuntos
Criança Hospitalizada/psicologia , Pais/psicologia , Educação de Pacientes como Assunto/métodos , Estresse Psicológico , Adaptação Psicológica , Ansiedade , Criança , Comunicação , Coleta de Dados , Feminino , Humanos , Masculino
10.
J Perinatol ; 37(3): 236-242, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27929527

RESUMO

OBJECTIVE: The associations between duration of second stage of labor, pushing time and risk of adverse neonatal outcomes are not fully established. Therefore, we aimed to examine such relationships. STUDY DESIGN: A population-based cohort study including 42 539 nulliparous women with singleton infants born in cephalic presentation at ⩾37 gestational weeks, using the Stockholm-Gotland Obstetric Cohort, Sweden, and the Swedish Neonatal Quality Register, 2008 to 2013. Poisson regression was used to analyze estimated adjusted relative risks (RRs), with 95% confidence intervals (CIs). Outcome measures were umbilical artery acidosis (pH <7.05 and base excess <-12), birth asphyxia-related complications (including any of the following conditions: hypoxic ischemic encephalopathy, hypothermia treatment, neonatal seizures, meconium aspiration syndrome or advanced resuscitation after birth) and admission to neonatal intensive care unit (NICU). RESULTS: Overall rates of umbilical artery acidosis, birth asphyxia-related complications and admission to NICU were 1.08, 0.63 and 6.42%, respectively. Rate of birth asphyxia-related complications gradually increased with duration of second stage: from 0.42% at <1 h to 1.29% at ≥4 h (adjusted RR 2.46 (95% CI 1.66 to 3.66)). For admission to NICU, corresponding rates were 4.97 and 9.45%, and adjusted RR (95% CI) was 1.80 (95% CI 1.58 to 2.04). Compared with duration of pushing <15 min, a duration of pushing ⩾60 min increased rates of acidosis from 0.57 to 1.69% (adjusted RR 2.55 (95% CI 1.51 to 4.30)). CONCLUSION: Prolonged durations of second stage of labor and pushing are associated with increased RRs of adverse neonatal outcomes. Clinical assessment of fetal well-being is essential when durations of second stage and pushing increases.


Assuntos
Acidose/epidemiologia , Asfixia Neonatal/epidemiologia , Segunda Fase do Trabalho de Parto/fisiologia , Complicações do Trabalho de Parto/epidemiologia , Resultado da Gravidez , Adulto , Estudos de Coortes , Bases de Dados Factuais , Parto Obstétrico/métodos , Feminino , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal/organização & administração , Admissão do Paciente , Gravidez , Pressão/efeitos adversos , Análise de Regressão , Fatores de Risco , Suécia , Fatores de Tempo , Contração Uterina , Adulto Jovem
11.
Cancer Res ; 35(11 Pt. 2): 3308-16, 1975 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1192404

RESUMO

Sideropenic anemia with epithelial lesions (Plummer-Vinson syndrome) was previously very common among women in northern Sweden. The incidence of this condition is decreasing, however, because of better nutrition and improved health care. Plummer-Vinson syndrome as a sequela of previous sideropenic anemia still influences the pattern of hypopharyngeal and oral cancer in northern Sweden where the female/male ratio in these diseases is remarkably high and where cancer in the postcricoid part of the hypopharynx is relatively common. In Sweden as a whole, a decreasing trend in the incidence of hypopharyngeal cancer in women can be demonstrated, which is probably due to diminished prevalence of Plummer-Vinson syndrome.


Assuntos
Transtornos de Deglutição/epidemiologia , Neoplasias Faríngeas/epidemiologia , Síndrome de Plummer-Vinson/epidemiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/epidemiologia , Fenômenos Fisiológicos da Nutrição , Síndrome de Plummer-Vinson/complicações , Lesões Pré-Cancerosas/etiologia , Fumar , Suécia
12.
J Mol Biol ; 303(3): 423-32, 2000 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-11031118

RESUMO

A high precision NMR structure of oxidized glutaredoxin 3 [C65Y] from Escherichia coli has been determined. The conformation of the active site including the disulphide bridge is highly similar to those in glutaredoxins from pig liver and T4 phage. A comparison with the previously determined structure of glutaredoxin 3 [C14S, C65Y] in a complex with glutathione reveals conformational changes between the free and substrate-bound form which includes the sidechain of the conserved, active site tyrosine residue. In the oxidized form this tyrosine is solvent exposed, while it adopts a less exposed conformation, stabilized by hydrogen bonds, in the mixed disulfide with glutathione. The structures further suggest that the formation of a covalent linkage between glutathione and glutaredoxin 3 is necessary in order to induce these structural changes upon binding of the glutathione peptide. This could explain the observed low affinity of glutaredoxins for S-blocked glutathione analogues, in spite of the fact that glutaredoxins are highly specific reductants of glutathione mixed disulfides.


Assuntos
Escherichia coli/química , Ressonância Magnética Nuclear Biomolecular , Oxirredutases , Proteínas/química , Proteínas/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , Sequência Conservada , Cisteína/metabolismo , Dissulfetos/química , Dissulfetos/metabolismo , Glutarredoxinas , Glutationa/análogos & derivados , Glutationa/metabolismo , Glutationa/farmacologia , Ligação de Hidrogênio , Modelos Moleculares , Dados de Sequência Molecular , Oxirredução , Oxigênio/metabolismo , Ligação Proteica , Conformação Proteica/efeitos dos fármacos , Substâncias Redutoras/metabolismo , Substâncias Redutoras/farmacologia , Alinhamento de Sequência , Solventes , Especificidade por Substrato , Termodinâmica , Tirosina/metabolismo
13.
Neuroscience ; 298: 112-9, 2015 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-25862586

RESUMO

Previous results have shown that the substance P (SP) N-terminal fragment SP1-7 may attenuate hyperalgesia and produce anti-allodynia in animals using various experimental models for neuropathic pain. The heptapeptide was found to induce its effects through binding to and activating specific sites apart from any known neurokinin or opioid receptor. Furthermore, we have applied a medicinal chemistry program to develop lead compounds mimicking the effect of SP1-7. The present study was designed to evaluate the pharmacological effect of these compounds using the mouse spared nerve injury (SNI) model of chronic neuropathic pain. Also, as no comprehensive screen with the aim to identify the SP1-7 target has yet been performed we screened our lead compound H-Phe-Phe-NH2 toward a panel of drug targets. The extensive target screen, including 111 targets, did not reveal any hit for the binding site among a number of known receptors or enzymes involved in pain modulation. Our animal studies confirmed that SP1-7, but also synthetic analogs thereof, possesses anti-allodynic effects in the mouse SNI model of neuropathic pain. One of the lead compounds, a constrained H-Phe-Phe-NH2 analog, was shown to exhibit a significant anti-allodynic effect.


Assuntos
Analgésicos/uso terapêutico , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Limiar da Dor/efeitos dos fármacos , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/uso terapêutico , Substância P/química , Substância P/uso terapêutico , Animais , Área Sob a Curva , Sítios de Ligação/efeitos dos fármacos , Modelos Animais de Doenças , Hiperalgesia/tratamento farmacológico , Masculino , Camundongos , Medição da Dor , Ligação Proteica/efeitos dos fármacos , Estatísticas não Paramétricas , Fatores de Tempo
14.
AIDS ; 4(11): 1081-5, 1990 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-2282180

RESUMO

A population-based survey was carried out in the Kagera region of the United Republic of Tanzania in 1987 to determine the magnitude of HIV-1 infection and to study associated risk factors. The region was divided into one urban and three rural zones. A multistage cluster sampling technique was adopted. Antibodies to HIV-1 were determined by enzyme-linked immunosorbent assay and confirmed by Western blot analysis. A total of 2,475 adults (aged 15-54 years) and 1,961 children (aged 0-14 years) was studied. The overall prevalence of HIV-1 infection among adults was 9.6%, with a higher prevalence in the urban zone (24.2%) than in the three rural zones (10.0, 4.5 and 0.4%, respectively). The corresponding figures for children were 1.3% overall: 3.9% in the urban area and for the rural areas 1.2, 0.8 and 0.0%, respectively. The age-specific seroprevalence for adults was highest in the age group 25-34 years. The age-standardized sex-specific prevalence was higher among women than men in the urban zone, while it was the same in the rural zones. Change of sexual partners among adults was associated with an increased risk of HIV-1 seropositivity. Travelling outside the region but within the country was also found to be associated with increased risk of HIV-1 infection but only in the rural population.


Assuntos
Infecções por HIV/epidemiologia , Soroprevalência de HIV , HIV-1 , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , População Rural , Estudos de Amostragem , Fatores Sexuais , Tanzânia/epidemiologia , Viagem , População Urbana
15.
AIDS ; 12(13): 1707-14, 1998 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-9764792

RESUMO

OBJECTIVE: To assess the present level of HIV-2 infection in an adult population in Bissau and to evaluate sex and age-specific changes in HIV-2 prevalence and incidence between 1987 and 1996. DESIGN AND METHODS: Sex and age-specific changes in HIV-2 prevalence were evaluated comparing a survey from 1987 in a sample of 100 houses with a survey performed in 1996 in an independent sample of 212 houses from the same study area. HIV-2 incidence rates were examined in an adult population (age > or = 15 years) from 100 randomly selected houses followed with four consecutive HIV serosurveys from 1987 to 1996. RESULTS: The HIV-2 prevalence in 1996 was 6.8% (men, 4.7%; women, 8.4%). Compared with the 1987 survey there was a significant decrease in prevalence among men [age-adjusted relative risk (RR), 0.50; 95% confidence interval (CI), 0.31-0.83], whereas it remained unchanged in women (RR, 1.00; 95% CI, 0.67-1.48). The male-to-female RR decreased from 0.99 (95% CI, 0.61-1.61) in 1987 to 0.51 (95% CI, 0.34-0.76) in 1996. The overall annual incidence rate was 0.54 per 100 person-years of observation (PYO), being higher in women (0.72 per 100 PYO) than in men (0.31 per 100 PYO). With the observation time divided into an early and a late period, there was a decrease in incidence with time among men (0.66 to 0.00 per 100 PYO), but no major change among women (0.59 to 0.85 per 100 PYO). The two trends differed significantly (P = 0.03). We observed a higher annual incidence rate amongst older women aged > 44 years (1.77 per 100 PYO) than among younger women (0.55 per 100 PYO; P = 0.05). CONCLUSION: There are no signs of an epidemic spread of HIV-2 in Bissau even though the HIV-1 prevalence is increasing rapidly. A significant reduction in the male HIV-2 prevalence and incidence rates has resulted in a major shift in the pattern of spread of HIV-2, from being equally distributed to being predominantly a female infection. Currently, older women in particular seem to have a high risk of getting infected.


Assuntos
Soroprevalência de HIV , HIV-2 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Guiné-Bissau/epidemiologia , Soronegatividade para HIV , HIV-1 , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Saúde da População Urbana
16.
Artigo em Inglês | MEDLINE | ID: mdl-1910083

RESUMO

In Dar es Salaam, Tanzania, 200 children with severe malnutrition and controls matched for age, sex, and area of residence were screened for serological evidence of infection with the human immunodeficiency virus type 1 (HIV-1) over 5 months in 1988. The prevalence of HIV-1 antibodies in the malnourished group was 25.5% (51 of 200) compared with 1.5% (three of 200) in the controls. The seroprevalence rate was equally high in malnourished children above the age of 18 months (26 of 102; 25.5%), as in those below this age (25 of 98; 25.5%). The prevalence rate was higher in children with marasmus (38.2%) as compared to children with marasmic-kwashiorkor (12.3%) or kwashiorkor (12.2%). The prevalence of clinical features known to be associated with AIDS was higher in the HIV seropositive malnourished children as compared to the seronegative children. The modified World Health Organization clinical case definition of AIDS in children was also evaluated and found to have a low sensitivity and positive predictive value (62.8 and 57.1%, respectively) but a fairly high specificity (83.9%). It is recommended to routinely rule out HIV infection in malnourished children, especially those with marasmus.


Assuntos
Síndrome da Imunodeficiência Adquirida/epidemiologia , Soropositividade para HIV , HIV-1 , Kwashiorkor/complicações , Desnutrição Proteico-Calórica/complicações , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/fisiopatologia , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Kwashiorkor/epidemiologia , Kwashiorkor/fisiopatologia , Masculino , Prevalência , Desnutrição Proteico-Calórica/epidemiologia , Desnutrição Proteico-Calórica/fisiopatologia , Tanzânia , População Urbana
17.
Am J Med Genet ; 77(4): 261-7, 1998 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-9600732

RESUMO

While loss-of-function mutations in Gsalpha are invariably associated with the short stature and brachydactyly of Albright hereditary osteodystrophy (AHO), the association with hormone resistance (to parathyroid hormone and thyrotropin) typical of pseudohypoparathyroidism type Ia (PHP-Ia) is much more variable. Observational studies and DNA polymorphism analysis suggest that maternal transmission of the Gsalpha mutation may be required for full expression of clinical hormone resistance. To test this hypothesis, we studied transmission of a frameshift mutation in Gsalpha through three generations of a pedigree affected by AHO and PHP-Ia. While all family members carrying this loss-of-function mutation in one Gsalpha allele had AHO, neither the presence of the mutation nor the degree of reduction of erythrocyte Gsalpha bioactivity allowed prediction of phenotype (AHO alone versus AHO and PHP-Ia). Paternal transmission of the mutation (from the patriarch of the first generation to three members of the second generation) was not associated with concurrent PHP-Ia, but maternal transmission (from two women in the second generation to four children in the third generation) was invariably associated with PHP-Ia. No expansion of an upstream short CCG nucleotide repeat region was detected, nor was there evidence of uniparental disomy by polymorphism analysis. This report, the first to document the effects across three generations of both paternal and maternal transmission of a specific Gsalpha mutation, strongly supports the hypothesis that a maternal factor determines full expression of Gsalpha dysfunction as PHP-Ia.


Assuntos
Displasia Fibrosa Poliostótica/genética , Mutação da Fase de Leitura , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Pseudo-Hipoparatireoidismo/genética , Sondas de DNA , Eletroforese em Gel de Poliacrilamida , Membrana Eritrocítica/metabolismo , Feminino , Displasia Fibrosa Poliostótica/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Genes Recessivos , Humanos , Marcação por Isótopo , Masculino , Hibridização de Ácido Nucleico , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo Genético , Pseudo-Hipoparatireoidismo/metabolismo , Análise de Sequência de DNA
18.
APMIS ; 96(11): 979-90, 1988 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3196478

RESUMO

Survival rates during a follow-up period of more than seven years were analyzed in 1,349 women with breast cancer in relation to the histo-pathological classification of female breast cancer proposed by Ackerman and to other commonly used histo-pathological criteria, including the axillary node status. The information was collected prospectively during a case-control study. Major emphasis was placed on multivariate evaluation. In analyses based on the histo-pathological findings in the mastectomy specimen alone, the Ackerman grouping was found to be of prognostic value, but apart from nuclear polymorphism the other recorded characteristics (histo-pathological type, histological grading, lymphocyte infiltration, and sinus histiocytosis) did not give any prognostic information. When the axillary node status was included in the multivariate models, the presence of axillary metastases correlated well with the prognosis and the Ackerman classification provided no significant additional information. The results indicate that in cases where the histopathological axillary status is known, little additional prognostic information can be gained from traditional histo-pathological evaluation over and above this status. However, the Ackerman classification and the degree of nuclear polymorphism separate distinct prognostic groups with the same degree of difference in observed survival rates as one discriminated by the axillary node status.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Feminino , Seguimentos , Humanos , Polimorfismo Genético , Prognóstico , Estudos Prospectivos
19.
Int J Epidemiol ; 24(6): 1071-7, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8824846

RESUMO

BACKGROUND: A cohort of employees at a smelter in Northern Sweden has been updated with the addition of information regarding smoking habits to evaluate the role of smoking in the occurrence of lung cancer in various job categories and employment cohorts. An updated analysis of earlier studies of the interaction between roaster work and smoking is also reported. The cohort members first employed during the period 1928-1979 have been followed up to 1 January 1988. Information regarding smoking habits for 69% of the cohort was gathered in a questionnaire study. RESULTS: The prevalence of daily smoking decreased during the study period and was lower for salaried employees. The figures were, however, comparable with national figures for similar social and occupational strata. Adjustment for smoking did not alter the lung cancer gradient between employment cohorts or between job categories. CONCLUSIONS: The interaction between smoking and roaster work was confirmed and the benefits from ceasing to smoke shown to be greater among the roaster workers.


Assuntos
Neoplasias Pulmonares/epidemiologia , Doenças Profissionais/epidemiologia , Fumar/tendências , Adulto , Feminino , Humanos , Incidência , Neoplasias Pulmonares/etiologia , Masculino , Metalurgia , Pessoa de Meia-Idade , Fatores de Risco , Fumar/efeitos adversos , Suécia/epidemiologia
20.
Int J Epidemiol ; 22(3): 528-36, 1993 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8359971

RESUMO

The results of a population-based follow-up study are presented. The baseline study which started in August 1987, was carried out to determine the prevalence of human immunodeficiency virus (HIV-1) infection in the Kagera region of Tanzania. A multistage cluster sampling technique was adopted in the selection of the study population. In the follow-up survey which started in June 1988, members of the same study population were revisited and studied in order to determine the incidence of HIV-1 infection among those who were HIV seronegative in the initial survey. HIV serology was conducted by using enzyme-linked immunosorbent assay and all positive sera were confirmed by the Western blot technique. A total population of 1316 adults aged 15-54 years was studied, constituting an average follow-up response rate of 69% in the rural areas and of 59% in the urban area. The overall incidence of HIV-1 infection among the adult population sample was 13.7 per 1000 person-years at risk with the highest incidence in the urban zone (47.5 per 1000 person-years at risk) and the lowest incidence in one of the three rural zones (4.9 per 1000 person-years at risk). The age-specific annual incidence was highest in the age group 25-34 years for males and in the age group 15-24 for females. From these results it was estimated that the number of newly infected adults in the region each year is about 8200 with a range between 5400 and 11,000 corresponding to the 95% confidence limits on the overall incidence.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Síndrome da Imunodeficiência Adquirida/epidemiologia , Soropositividade para HIV/epidemiologia , HIV-1 , Adolescente , Adulto , Análise por Conglomerados , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Tanzânia/epidemiologia
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