RESUMO
OBJECTIVE: To examine if oral metformin is as effective as insulin in the prevention of fetal macrosomy in pregnancies complicated with gestational diabetes mellitus (GDM). DESIGN: Open-label prospective randomised controlled study. SETTING: Maternity outpatient clinics in a secondary and tertiary level hospital in Finland. SAMPLE: One hundred women with GDM who did not attain euglycaemia with diet. METHODS: Women were randomised to therapy with insulin (n = 50) or oral metformin (n = 50). MAIN OUTCOME MEASURES: Incidence of large-for-gestational-age (LGA) infants and neonatal morbidity. RESULTS: There were no statistically significant differences in the incidence of LGA (8.5 versus 10.0%, P = 0.97), mean birthweight, mean cord artery pH or neonatal morbidity between the insulin and metformin groups. Fifteen (31.9%) of the 47 women randomised to metformin needed supplemental insulin. They were more obese (with a body mass index of 36 versus 30 kg/m(2), P = 0.002), had higher fasting blood glucose levels in an oral glucose tolerance test (6.1 versus 5.0 mmol/l, P = 0.001) and needed medical treatment for GDM earlier (26 versus 31 gestational weeks, P = 0.002) than women who were normoglycemic with metformin. There was a tendency to a higher rate of caesarean sections in the metformin group than in the insulin group (RR 1.9; 95% CI 0.99-3.71). CONCLUSIONS: Metformin seems to be suitable for the prevention of fetal macrosomy, especially in lean or moderately overweight women developing GDM in late gestation. Women with considerable obesity, high fasting blood glucose and an early need for pharmacological treatment may be more suitable for insulin therapy.
Assuntos
Diabetes Gestacional/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Metformina/uso terapêutico , Adulto , Índice de Massa Corporal , Feminino , Macrossomia Fetal/prevenção & controle , Humanos , Obesidade/complicações , Pacientes Ambulatoriais , Gravidez , Estudos Prospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: Primary hyperparathyroidism (PHPT), a common endocrine condition, is usually caused by sporadically occurring parathyroid adenoma. A subset of patients carry germline mutations in genes such as MEN1 (multiple endocrine neoplasia type 1), HRPT2 (hyperparathyroidism 2), and CASR (calcium-sensing receptor) predisposing to syndromic forms of PHPT or familial isolated hyperparathyroidism (FIHP). Recently, germline mutations in two novel genes AIP (aryl hydrocarbon receptor-interacting protein) and CDKN1B (cyclin-dependent kinase inhibitor 1B) have been found to be associated with endocrine tumors. The purpose of this study was to evaluate the role of MEN1, HRPT2, CASR, AIP, and CDKN1B genes in PHPT patients with clinical features suggestive of genetic predisposition. PATIENTS AND DESIGN: Medical records of patients treated for PHPT from 1974 to 2001 at Oulu University Hospital were reviewed. Patients with multiglandular or recurrent/persistent disease, other MEN1- related manifestations, aged 40 yr or younger at onset or with a family history of PHPT/MEN1-related tumor were invited to the study. Twenty patients with previously diagnosed MEN1 were excluded. Participants were interviewed and blood samples obtained for biochemical screening and mutation analysis of MEN1, HRPT2, CASR, AIP, and CDKN1B. RESULTS: Of the 56 invited patients, 29 took part in the study. One patient was found to carry the c. 1356_1367del12 MEN1 founder mutation. Mutations in other genes were not detected. CONCLUSIONS: Apart from MEN1, mutations in other genes predisposing to PHPT seem to be rare or non-existing in Northern Finnish PHPT patients. No evidence was found for a role of AIP or CDKN1B in PHPT predisposition.
Assuntos
Hiperparatireoidismo Primário/genética , Neoplasias das Paratireoides/genética , Adulto , Inibidor de Quinase Dependente de Ciclina p27 , DNA/química , DNA/genética , Feminino , Finlândia , Predisposição Genética para Doença , Variação Genética , Humanos , Hiperparatireoidismo Primário/patologia , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Neoplasias das Paratireoides/patologia , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas/química , Proteínas Proto-Oncogênicas/genética , Receptores de Detecção de Cálcio/química , Receptores de Detecção de Cálcio/genética , Estudos Retrospectivos , Análise de Sequência de DNA , Proteínas Supressoras de Tumor/química , Proteínas Supressoras de Tumor/genética , Adulto JovemRESUMO
OBJECTIVE: The existence of genotype-phenotype correlation in multiple endocrine neoplasia type 1 (MEN1) is controversial. Two founder mutations of the MEN1 gene in Northern Finland gave us an opportunity to compare clinical features among heterozygotes of different mutations. DESIGN AND METHODS: Study cohort included 82 MEN1 heterozygotes who were tested for MEN1 during the years 1982-2001. Medical records were reviewed for manifestations of MEN1, other tumours and cause of death by the end of August 2003. Logistic regression analysis was used in evaluating the impact of age, gender and mutational status of affected heterozygotes on the likelihood of developing manifestations of MEN1. RESULTS: Founder mutations 1466del12 and 1657insC were found in 39 and 29 individuals, and D418N, G156R and R527X mutations in 9, 3 and 2 individuals respectively. Except for pituitary adenoma and nonfunctional pancreatic tumour (NFPT), age was a risk factor for all the disease manifestations. For NFPT, frameshift/nonsense mutations (1657insC, R527X) gave an odds ratio (OR) of 3.26 (95% confidence intervals (CI), 1.27-8.33; P = 0.014) compared with in-frame/missense mutations (1466del12, D418N, G156R); including the founder mutation carriers (n = 68) only, the 1657insC mutation gave an OR of 3.56 (CI, 1.29-9.83; P = 0.015). For gastrinoma, in-frame/missense mutations predicted the risk with an OR of 6.77 (CI, 1.31-35.0; P = 0.022), and in the founder mutations group the 1466del12 mutation gave an OR of 15.09 (CI, 1.73-131.9, P = 0.014). CONCLUSIONS: In this study population, NFPT was more common in the frameshift/nonsense or 1657insC mutation carriers, whereas gastrinoma was more common in the in-frame/missense or 1466del12 mutation carriers.
Assuntos
Neoplasia Endócrina Múltipla Tipo 1/genética , Neoplasia Endócrina Múltipla Tipo 1/mortalidade , Proteínas Proto-Oncogênicas/genética , Adolescente , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/mortalidade , Adulto , Idoso , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/mortalidade , Criança , Códon sem Sentido , Feminino , Finlândia/epidemiologia , Efeito Fundador , Mutação da Fase de Leitura , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/mortalidade , Genótipo , Humanos , Hiperparatireoidismo Primário/genética , Hiperparatireoidismo Primário/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Fenótipo , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/mortalidade , Fatores de RiscoRESUMO
OBJECTIVE: To assess whether there are any differences in genetic, autoimmune, or clinical features between type 1 diabetes presenting in childhood and that diagnosed later. RESEARCH DESIGN AND METHODS: We studied 352 individuals (252 children and adolescents <20 years of age and 100 adults > or =20 years of age) manifesting clinical signs of type 1 diabetes over a period of 7.5 years at a university hospital in northern Finland with a primary catchment area population of approximately 300,000. The patients were analyzed for susceptible and protective HLA-DQB1 alleles (*02, *0302, *0301, *0602, *0603, and *0604), islet cell antibodies (ICA), insulin autoantibodies, and antibodies to GAD and IA-2 (IA-2A). Their clinical symptoms and signs were recorded at diagnosis. RESULTS: The adult patients carried the high-risk DQB1*02/0302 genotype less frequently than the children and more often had protective genotypes. They also had a decreased frequency of all 4 single autoantibody specificities and of multiple (> or =3) autoantibodies. The proportion of patients testing negative for all autoantibodies was lower among the children than among the adults. IA-2A were associated with the DQB1*0302/x genotype in both the children and adults, and the same held true for ICA among the adults. The adults were characterized by a higher proportion of males, a longer duration of symptoms, and a lower frequency of infections during the preceding 3 months. In addition, they had a higher relative body weight on admission and milder signs of metabolic decompensation (higher pH, base excess, and bicarbonate concentrations) and a lower glycated hemoglobin level at diagnosis than the children. CONCLUSIONS: Clinical manifestation of type 1 diabetes before the age of 20 years is associated with a strong HLA-defined genetic disease susceptibility, an intensive humoral immune response to various beta-cell antigens, a higher frequency of preceding infections, and a shorter duration of symptoms and more severe metabolic decompensation at diagnosis. Taken together, these observations suggest that the age at clinical onset of type 1 diabetes is determined by the intensity of the beta-cell-destructive process, which is modulated by both genetic and environmental factors.
Assuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/genética , Adolescente , Adulto , Idade de Início , Alelos , Glicemia/análise , Peso Corporal , Peptídeo C/sangue , Criança , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Finlândia , Glutamato Descarboxilase/imunologia , Hemoglobinas Glicadas/análise , Antígenos HLA-DQ/genética , Cadeias beta de HLA-DQ , Antígenos de Histocompatibilidade Classe II/imunologia , Hospitais Universitários , Humanos , Ilhotas Pancreáticas/imunologia , MasculinoRESUMO
Estimation of mortality and the natural course of a disease is usually based on information of carefully studied individuals with or at risk for a specific disease. Genealogical information has rarely been accurate enough for such studies. With the help of church records and multiple endocrine neoplasia type 1 (MEN1) family information of the two founder MEN1 mutations in Northern Finland (1466del12 and 1657insC), we could trace back common ancestors born in the beginning of the 1700s (1466del12) and approximately 1850 (1657insC) and find 67 probable gene carriers born between 1728 and 1929, which were identified among their offspring. Information was gathered from 34 obligatory MEN1 gene carriers and 31 spouses. The mean age (+/- sd) of death of affected males (n = 16) was 61.1 +/- 12.0 yr vs. 65.8 +/- 15.3 yr for unaffected males (n = 16) and for affected females (n = 16) was 67.2 +/- 10.7 yr vs. 67.7 +/- 14.7 yr for unaffected females (n = 13). The ages of death of the obligatory heterozygotes did not differ from that of the spouses in sex groups or from the sex-matched life expectancy estimates derived from Finnish national statistics. Causes of death differed significantly between female probands and spouses. In conclusion, obligatory MEN1 gene carrier status did not show a harmful effect on survival in this retrospective analysis tracing back to almost 300 yr.
Assuntos
Efeito Fundador , Neoplasia Endócrina Múltipla Tipo 1/genética , Neoplasia Endócrina Múltipla Tipo 1/mortalidade , Mutação , Proteínas Proto-Oncogênicas/genética , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Feminino , Finlândia , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: The magnitude of the influence of the apolipoprotein (apo) E genotype on the lipid response to different cholesterol-lowering diet modifications has been controversial. OBJECTIVE: The aim of the study was to investigate the effect of apo E genotype on serum lipid response to the separate modification of dietary fat and cholesterol. DESIGN: A prospective study design with the 3 main apo E genotype groups (3/3, 3/4, and 4/4; n = 15 in each group) was used. Groups were matched for sex, age, body mass index, menopausal status, and baseline serum cholesterol concentration. Subjects followed 3 different diets in fixed order: 1) a standardized baseline diet (38% fat, 300 mg cholesterol/d), 2) a modified National Cholesterol Education Program (NCEP) diet (34% fat, 265 mg cholesterol/d), and 3) the modified NCEP diet + cholesterol (566 mg cholesterol/d). Subjects were middle-aged (50.9 +/- 8.0 y) and mildly hypercholesterolemic (6.55 +/- 1.05 mmol/L). RESULTS: The genotype groups differed in their total cholesterol response to the NCEP diet; the mean (95% CI) decrease being greatest, -14.1% (-19.8%, -8.6% ), in subjects with apo E genotype 4/4 (P = 0.03, analysis of variance). The increase in total cholesterol after addition of 300 mg cholesterol was also greatest in subjects with apo E 4/4 [10.4% (5.8%, 15.1%)] (P = 0.03, analysis of variance). CONCLUSIONS: Apo E genotype modified the lipid response to changes in both dietary fat and cholesterol in mildly hypercholesterolemic subjects; the response was greatest in subjects with apo E genotype 4/4 and even a moderate increase in dietary cholesterol resulted in a 10% elevation in serum total cholesterol in them.
Assuntos
Apolipoproteínas E/genética , Colesterol na Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Lipídeos/sangue , Polimorfismo Genético , Adulto , Apolipoproteína A-I/metabolismo , Colesterol/sangue , HDL-Colesterol/sangue , Ácidos Graxos/sangue , Feminino , Genótipo , Humanos , Hipercolesterolemia/genética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Triglicerídeos/sangueRESUMO
We have examined the usefulness of ultrasound (US) in the detection of Achilles tendon (AT) xanthomata in heterozygous familial hypercholesterolemia. Our study is based on 30 adult subjects with heterozygous familial hypercholesterolemia (FH) (16 men, 14 women), 27 subjects with other non-familial forms of severe hypercholesterolemia (non-FH) with serum total cholesterol levels > or = 8 mmol/l (13 men and 14 women) and 31 subjects without marked hypercholesterolemia of the same age (control group; serum total cholesterol < 8 mmol/l) (15 men, 16 women). The three groups were comparable with respect to age, sex and body mass index. In the control group the mean sagittal thickness of AT was 4.5 mm (95% CI 3.2, 5.9 mm) and the mean coronal breadth of AT 11.0 (95% CI 9.0, 13.0 mm). Mean thickness of AT was 4.9 (range 4-7) mm in the non-FH group and 11.1 (5-16) mm in the FH group. The mean breadth of AT was in these groups 12.0 (10-17) mm and 19.2 (12-27) mm, respectively. Using the upper 95% confidence interval cut-off point in the control group as a criterion for normal AT thickness and breadth, 6 (22%) of non-FH and 29 (97%) of FH patients had increased AT thickness and 5 (19%) vs. 26 (87%) patients had increased AT breadth, respectively. The sensitivity of AT thickness for identifying FH was 0.97, specificity 0.78 and positive predictive value 0.83. The sensitivity of AT breadth in identifying FH was 0.87, specificity 0.81 and positive predictive value 0.84. None of the control subjects and none of the non-FH patients showed structural abnormalities of AT in the US, whereas 89% of FH-patients showed hypoechogenicity of AT. FH-score obtained by summing up the number of abnormal US findings gave a sensitivity of 0.93, a specificity of 0.96 and a positive predictive value of 0.96 for AT US in discriminating FH from non-FH. In conclusion, US examination of AT is a useful method in the detection of AT xanthomata and thus of help in the diagnosis of heterozygous FH.
Assuntos
Tendão do Calcâneo/diagnóstico por imagem , Hiperlipoproteinemia Tipo II/complicações , Xantomatose/diagnóstico por imagem , Adulto , Feminino , Heterozigoto , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Masculino , Doenças Musculares/complicações , Doenças Musculares/diagnóstico por imagem , Sensibilidade e Especificidade , Ultrassonografia , Xantomatose/complicaçõesRESUMO
Hypercholesterolemia clustering in families not explained by either low density lipoprotein (LDL)-receptor mutations producing familial hypercholesterolemia (FH), or the apolipoprotein B (apo B) Arg3500-->Gln mutation with familial defective apo B (FDB), is common in the Finnish population. In search of previously unknown apo B mutations, we screened exons 26 to 29 of the apo B gene in 68 Finnish severely hypercholesterolemic (> or = 8 mmol/l) non-FH, non-FDB patients, using a single-strand conformation polymorphism analysis based screening method. Four rare and two polymorphic previously unreported DNA variations were detected. The rare variants were a three-nucleotide deletion, with the deletion of Asp2186, an A11961-->G change leading to a Thr3918-->Ala change, a T12922-->G change causing a Val4238-->Ala substitution, and a neutral T12935-->C change leading to a new RsaI cutting site. The polymorphic G12937-->C and G13569-->A changes leading to Arg4243-->Thr and Ala4454-->Thr substitutions, respectively, had minor allele frequencies of 0.03 and 0.02. None of these variants seemed to explain the hyperlipidemia in these patients. A major Finnish mutation causing severe hypercholesterolemia is unlikely to exist in the 3' two-thirds of the coding area of the apo B gene.
Assuntos
Apolipoproteínas B/genética , Código Genético , Testes Genéticos , Variação Genética , Hipercolesterolemia/genética , Sequência de Bases , Éxons , Finlândia , Frequência do Gene , Haplótipos , Humanos , Lipídeos/sangue , Linhagem , Polimorfismo Genético , Polimorfismo Conformacional de Fita SimplesRESUMO
BACKGROUND: Clozapine has been reported to be effective in diminishing violence toward others in psychotic patients. This article describes the impact of clozapine on severe self-mutilation among patients with the dual diagnoses of borderline personality disorder and persistent psychoses. METHOD: Seven subjects known to the authors were selected for careful chart audits. These subjects had been admitted to 2 state psychiatric hospitals owing to severe self-mutilation and/or violence and subsequently treated with clozapine. A mirror-image design anchored to the start date of clozapine treatment and extending in either direction to a maximum of 1 year was used to extract data. Data extracted included incidents of self-mutilation (restraint), seclusion, the as and when needed (p.r.n.) use of medications, injuries to staff and peers, hospital privileges, and Global Assessment of Functioning (GAF) scores. RESULTS: The subjects were all white women with a mean age of 37 years. All subjects carried DSM-III-R or DSM-IV borderline personality disorder diagnoses and an Axis I disorder diagnosis. They had received trials of several psychotropic agents, often in combination and mostly without benefit. After clozapine treatment, there were statistically significant reductions in incidents of self-mutilation (restraint), seclusion, the use of p.r.n. antianxiety medications, and injuries to staff and peers. These subjects received higher levels of hospital privileges, and their GAF scores nearly doubled following clozapine treatment. Four subjects were subsequently discharged from hospital. CONCLUSION: These preliminary but nonetheless favorable results suggest that clozapine deserves careful consideration for a controlled study in patients with borderline personality disorder and psychoses, especially if the clinical issues include severe self-mutilation, aggression, and violence. Until such studies are done, the risk-to-benefit ratio of clozapine treatment needs to be carefully evaluated on an individualized basis in such subjects.
Assuntos
Agressão/efeitos dos fármacos , Antipsicóticos/uso terapêutico , Transtorno da Personalidade Borderline/tratamento farmacológico , Clozapina/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Automutilação/prevenção & controle , Adulto , Antipsicóticos/farmacologia , Transtorno da Personalidade Borderline/epidemiologia , Transtorno da Personalidade Borderline/psicologia , Clozapina/farmacologia , Comorbidade , Esquema de Medicação , Feminino , Hospitalização , Humanos , Prontuários Médicos , Pessoa de Meia-Idade , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/psicologia , Restrição Física , Medição de Risco , Índice de Gravidade de Doença , Isolamento Social , Resultado do TratamentoRESUMO
Several commercially available spirometers use unheated ceramic elements as flow sensors to determine flow and calculate volume of air. The usual method of correcting the resulting flow and volume values to body temperature pressure saturated (BTPS) is to apply a constant factor approximately equal to 30 percent of the full BTPS correction factor. To evaluate the usual BTPS correction factor technique, we tested several sensors with a mechanical pump using both room air and air heated to 37 degrees C and saturated with water vapor. The volume signals used to test the sensors were volume ramps (constant flow) and the first four American Thoracic Society (ATS) standard waveforms. The percent difference in FEV1 obtained using room vs heated-humidified air (proportional to the magnitude of the BTPS correction factor needed) ranged from 0.3 percent to 6.2 percent and varied with the number of maneuvers previously performed, the time interval between maneuvers, the volume of the current and previous maneuvers, and the starting temperature of the sensor. The temperature of the air leaving the sensor (exit temperature) showed a steady rise with each successive maneuver using heated air. When six subjects performed repeated tests over several days (each test consisting of at least three maneuvers), a maneuver order effect was observed similar to the results using the mechanical pump. These results suggest that a dynamic, rather than static, BTPS correction factor is needed for accurate estimations of forced expiratory volumes and to reduce erroneous variability between successive maneuvers. Use of exit air temperature provides a means of estimating a dynamic BTPS correction factor, and this technique may be sufficient to provide an FEV1 accuracy of less than +/- 3 percent for exit air temperatures from 5 degrees to 28 degrees C.
Assuntos
Temperatura Corporal , Ventilação Pulmonar , Espirometria/instrumentação , Cerâmica , Volume Expiratório Forçado , Humanos , Capacidade VitalRESUMO
In connection with a population-based study on familial and non-familial determinants of serum total cholesterol an interviewer-administered short questionnaire, including 21 food items, and a qualitative fat index based on four questions were developed. Subjects for the validation study, 51 women and 31 men, aged 16-71 years, were selected from the population-based study (n = 892). The short questionnaire and the qualitative fat index were validated with a 3 day food record as the reference method. The short questionnaire captured 90-97% of the mean intakes of total fat, saturated, monounsaturated and polyunsaturated fatty acids and cholesterol. The Pearson correlation coefficients between the fat intakes based on the questionnaire and the diet records were strongest for the intake of total fat (r = 0.80). The qualitative fat index was based on four questions concerning type of fat: the higher the scores the higher the intakes of polyunsaturated fatty acids. The Spearman correlation coefficients between the qualitative fat index and the intakes based on the diet records were -0.55 for saturated, 0.34 for monounsaturated and 0.52 for polyunsaturated fatty acids. The respective correlation for the P/S ratio (total amounts of polyunsaturated fatty acids/saturated fatty acids) and the PM/S ratio (total amounts of polyunsaturated and monounsaturated fatty acids/saturated fatty acids) were 0.50 and 0.53. An inverse association between serum total cholesterol and the qualitative fat index was found in the whole study population, suggesting the impact of dietary fat on serum cholesterol in this study population. In conclusion, the short questionnaire proved to be accurate in measuring the intake of different fatty acids at the group level, whereas the simpler fat index measured the quality of fat quite well.
Assuntos
Registros de Dieta , Gorduras na Dieta , Adolescente , Adulto , Idoso , Colesterol na Dieta , Ingestão de Energia , Ácidos Graxos Insaturados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Gestational diabetes mellitus (GDM) is associated with an increased risk of subsequent diabetes and metabolic syndrome (MS). The independent significance of overweight, often associated with GDM, is controversial. This study was aimed to investigate the prevalence of MS and carotid intima-media thickness (CIMT) values in normal and overweight women with previous insulin-treated GDM and control without GDM 19 years after the index pregnancy. METHODS: The study group consisted of 61 women with prior GDM and 55 controls who gave birth in Oulu University Hospital between 1988 and 1993. These women were further divided into subgroups according to pre-pregnancy BMI (<25 or ≥25âkg/m(2)). In 2008-2010, anthropometrics and blood pressure were measured, blood samples were taken, and an oral glucose tolerance test was performed to investigate the components of MS. CIMT was measured by Doppler ultrasound. RESULTS: Total prevalence of MS was 62% in the GDM group and 31% in the control group (P=0.001); it was highest (86%) in GDM women with pre-pregnancy overweight. CIMT was significantly thicker (0.67 vs 0.56âmm, P=0.007) and more often abnormal (71.7 vs 45.3%, P=0.004) in the GDM group compared with the controls. In logistic regression analysis, the strongest factor predicting MS in the whole study population was pre-pregnancy overweight. CONCLUSIONS: Pre-pregnancy overweight was the strongest predictive factor for later MS, whereas GDM indicated increased risk of subsequent diabetes and subclinical atherosclerosis. The risk of MS was highest when both of these factors were present.
Assuntos
Complicações do Diabetes/epidemiologia , Diabetes Gestacional/epidemiologia , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Adulto , Antropometria , Aterosclerose/complicações , Aterosclerose/epidemiologia , Glicemia/metabolismo , Pressão Sanguínea/fisiologia , Espessura Intima-Media Carotídea , Diabetes Mellitus Tipo 2/epidemiologia , Dislipidemias/epidemiologia , Feminino , Finlândia/epidemiologia , Seguimentos , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Modelos Logísticos , Pessoa de Meia-Idade , Paridade , Gravidez , Fatores de RiscoRESUMO
Context. The literature concerning the health-related quality of life (HRQoL) of patients with surgically treated PA is controversial. Objective. To describe the long-term HRQoL of surgically treated patients in all PA classes. Design and subjects. The 15D, a generic HRQoL instrument producing a 15-dimensional profile and a single 15D index score (a difference ≥0.03 on a 0-1 scale is considered clinically important), was used to assess the HRQoL of a 13-year surgical cohort of PA patients in Northern Finland. Results and Conclusion. Nighty-eight eligible consecutive patients with surgically treated PA were studied at an average of 6.3 years after their latest pituitary operation. The average postoperative 15D profiles in patients with non-functioning PA and in acromegalics without GH-suppressive medical treatment were similar to those of the age-standardized general population. However, after this rather long followup, the mean 15D score and the number of statistically significant 15D dimension impairments, compared with those of their reference population, were 0.11 and 9/15, 0.10 and 3/15, and 0.08 and 7/15 for Cushing's disease, acromegalics needing somatostatin analog, and prolactinoma patients, respectively. Hypopituitarism with replacement medication was not associated with impaired HRQoL. The somatostatin-analog-associated HRQoL finding warrants further clinical research.
Assuntos
Efeito Fundador , Neoplasia Endócrina Múltipla Tipo 1/genética , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas , Cromossomos Humanos Par 11/genética , DNA/química , DNA/genética , Análise Mutacional de DNA , Saúde da Família , Feminino , Finlândia , Genótipo , Haplótipos , Humanos , Masculino , Repetições de Microssatélites , Neoplasia Endócrina Múltipla Tipo 1/patologia , Mutação , LinhagemAssuntos
Genes Supressores de Tumor , Mutação em Linhagem Germinativa/genética , Hiperparatireoidismo/genética , Mutação/genética , Proteínas/genética , Adulto , Idoso , Sequência de Aminoácidos , Criança , Análise Mutacional de DNA , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Mosaicismo/genética , Linhagem , Proteínas/química , Proteínas Proto-Oncogênicas/genética , Receptores de Detecção de Cálcio/genética , Proteínas Supressoras de TumorRESUMO
120 patients (64 men, 56 women) aged 19-66 years with primary hypercholesterolaemia (mean serum total cholesterol 10.1 mmol/l, range 6.5-16.3 mmol/l) with normal or moderately raised concentrations of serum triglycerides were randomised after four weeks' diet and four weeks' diet+placebo phase either to cholestyramine (40 patients) or lovastatin (80 patients) treatments for the succeeding 12 weeks. The maximal daily doses were 24 g of cholestyramine and 80 mg of lovastatin. The baseline data of the treatment groups were comparable with the exception of HDL-cholesterol concentrations, which were lower in the lovastatin group. The mean reductions in total serum cholesterol concentrations were 24.3% for cholestyramine (P less than or equal to 0.01) and 33.4% for lovastatin (P less than or equal to 0.01) (P less than or equal to 0.01 between the treatment groups), in LDL-cholesterol 32.1% (P less than or equal to 0.01) and 40.7% (P less than or equal to 0.01) (P less than or equal to 0.05 between the treatment groups) and in apolipoprotein B 23.3% (P less than or equal to 0.01) and 33.3% (P less than or equal to 0.01) (P less than or equal to 0.01 between the treatment groups), respectively. Lovastatin was the only drug to reduce serum triglyceride concentrations, it did so by 26.0%. HDL-cholesterol increased by 7.7% (P = NS) when cholestyramine was taken and by 13.5% (P less than or equal to 0.05) with lovastatin (P = NS between the treatment groups). Apolipoprotein A1 remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Resina de Colestiramina/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Lovastatina/uso terapêutico , Adulto , Idoso , Apolipoproteína A-I/efeitos dos fármacos , Apolipoproteína A-I/metabolismo , Apolipoproteínas B/sangue , Apolipoproteínas B/efeitos dos fármacos , HDL-Colesterol/sangue , HDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , Resina de Colestiramina/efeitos adversos , Feminino , Humanos , Hipercolesterolemia/sangue , Hiperlipoproteinemia Tipo II/sangue , Lovastatina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
Sixty-two patients (34 men and 28 women) aged 19-64 years, half of whom had familial hypercholesterolemia, treated initially for 18 weeks with lovastatin alone were randomly allocated either to lovastatin (L) and cholestyramine (16 g/day) or lovastatin and guar gum (L + GG 20 g/day) treatment for 18 additional weeks to compare the hypocholesterolemic effects of these two combination therapies. The patients were selected for this study from a larger study of patients (n = 120) with severe hypercholesterolemia [serum total cholesterol (serum Chol) 6.5-16.3 mM before treatment], and only those patients in whom serum Chol after lovastatin alone (dose 80 mg/day) remained greater than or equal to 5.2 mM were eligible for evaluation of combination therapies. Serum Chol decreased from 10.6 +/- 1.6 to 5.9 +/- 1.3 mM (mean +/- SD) (p less than 0.001) and low-density lipoprotein cholesterol (LDL Chol) from 8.5 +/- 1.8 to 4.1 +/- 1 mM (p less than 0.001) in patients treated with L + GG (values before the beginning of lovastatin and at the end of the combination therapy). The respective changes were from 10.9 +/- 2.2 to 5.5 +/- 1.2 mM (p less than 0.001) and from 8.7 +/- 2.3 to 3.5 +/- 1.2 mM (p less than 0.001) in patients treated with lovastatin and cholestyramine (L + C). At the end of the study, both serum Chol (p less than 0.005) and LDL Chol (p less than 0.01) were significantly lower with L + C than with L + GG.(ABSTRACT TRUNCATED AT 250 WORDS)