RESUMO
UNLABELLED: The study demonstrates that wintertime surgeries are associated with impaired fracture healing and increases the risk of conversion to hip arthroplasty after osteosynthesis of femoral neck fracture. Furthermore, the results raise the possibility of association between seasonal changes in vitamin D levels and impaired fracture healing of femoral neck fracture. INTRODUCTION: Although the changes of vitamin D level and calcitropic hormones influencing bone metabolism are seasonal, the effect of seasons on hip fracture healing is unknown. We assessed the effects of seasonal periodicity on conversion to hip arthroplasty after primary osteosynthesis of femoral neck fracture. METHODS: This nationwide retrospective observational cohort study involved 2779 patients aged ≥ 60 years who underwent internal screw fixation for primary femoral neck fracture and were discharged in 2000. Cases requiring conversion to arthroplasty during the 8-year follow-up derived from the Hungarian health insurance database were registered. Risk factors assessed included sex, age, fracture type, season of primary surgery and surgical delay. Competing-risks regression analysis was used for data analyses. RESULTS: During the observation period, 190 conversions to hip arthroplasty (6.8%) were identified, yielding an overall incidence of 19.5 per 1000 person-years. The crude incidence rates of conversions after osteosynthesis in winter, spring, summer and fall were 28.6, 17.8, 16.9 and 14.7 per 1000 person-years, respectively. Besides younger age, female sex and intracapsular fracture displacement, wintertime primary osteosynthesis significantly increased the risk of conversion (fall vs. winter, hazard ratio (HR): 0.50, 95% confidence interval [95% CI 0.33-0.76]; spring vs. winter, HR: 0.63, [95% CI 0.44-0.92]; summer vs. winter, HR: 0.62, [95% CI 0.42-0.91]). CONCLUSIONS: Our study demonstrate that wintertime primary osteosynthesis increases the risk of conversion surgeries. The results may help improving the outcome of primary fixation of femoral neck fractures.
Assuntos
Artroplastia de Quadril/estatística & dados numéricos , Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas/estatística & dados numéricos , Consolidação da Fratura , Estações do Ano , Idoso , Idoso de 80 Anos ou mais , Parafusos Ósseos , Feminino , Fixação Interna de Fraturas/métodos , Humanos , Incidência , Masculino , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
SUMMARY: LCT 13910 CC genotype is associated with lactose intolerance, a condition often resulting in reduced milk intake. Women with the CC genotype were found to have decreased serum calcium and reduced bone mineral density. INTRODUCTION: The CC genotype of the 13910 C/T polymorphism of the LCT gene is linked to lactose intolerance and low calcium intake. METHODS: We studied 595 postmenopausal women, including 267 osteoporotic, 200 osteopenic, and 128 healthy subjects. Genotyping, osteodensitometry, and laboratory measurements were carried out. RESULTS: Frequency of aversion to milk consumption was 20% for CC genotype and 10% for TT + TC genotypes (p = 0.03). The albumin-adjusted serum calcium was 2.325 +/- 0.09 mmol/L for CC genotype and 2.360 +/- 0.16 mmol/L for TT + TC genotypes (p = 0.031). Bone mineral density (BMD; Z score) was lower in the CC than TT + TC genotypes, respectively, at the radius (0.105 +/- 1.42 vs 0.406 +/- 1.32; p = 0.038), at the total hip (-0.471 +/- 1.08 vs -0.170 +/- 1.09; p = 0.041), and at the Ward's triangle (-0.334 +/- 0.87 vs -0.123 +/- 0.82; p = 0.044). CONCLUSION: LCT 13910 C/T polymorphism is associated with decreased serum calcium level and lower BMD in postmenopausal women.
Assuntos
Densidade Óssea/genética , Doenças Ósseas Metabólicas/etiologia , Cálcio/sangue , Lactase-Florizina Hidrolase/genética , Intolerância à Lactose/complicações , Absorciometria de Fóton/métodos , Idoso , Antropometria , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/fisiopatologia , Feminino , Genótipo , Humanos , Intolerância à Lactose/sangue , Intolerância à Lactose/genética , Intolerância à Lactose/fisiopatologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/etiologia , Osteoporose Pós-Menopausa/fisiopatologia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Down-regulation of the Drosophila ribosomal protein S21 gene (rpS21) causes a dominant weak Minute phenotype and recessively produces massive hyperplasia of the hematopoietic organs and moderate overgrowth of the imaginal discs during larval development. Here, we show that the S21 protein (RpS21) is bound to native 40S ribosomal subunits in a salt-labile association and is absent from polysomes, indicating that it acts as a translation initiation factor rather than as a core ribosomal protein. RpS21 can interact strongly with P40, a ribosomal peripheral protein encoded by the stubarista (sta) gene. Genetic studies reveal that P40 underexpression drastically enhances imaginal disc overgrowth in rpS21-deficient larvae, whereas viable combinations between rpS21 and sta affect the morphology of bristles, antennae, and aristae. These data demonstrate a strong interaction between components of the translation machinery and showed that their underexpression impairs the control of cell proliferation in both hematopoietic organs and imaginal discs.
Assuntos
Proteínas de Drosophila , Drosophila melanogaster/metabolismo , Proteínas de Insetos/metabolismo , Fatores de Iniciação de Peptídeos/metabolismo , Proteínas Ribossômicas/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar , Regulação para Baixo , Drosophila melanogaster/crescimento & desenvolvimento , Dosagem de Genes , Humanos , Proteínas de Insetos/genética , Larva , Dados de Sequência Molecular , Fatores de Iniciação de Peptídeos/genética , Fenótipo , Proteínas Ribossômicas/genética , Homologia de Sequência de AminoácidosRESUMO
Calcium-sensing receptor (CaSR) is an attractive candidate gene for osteoporosis susceptibility. The CaSR "A986S" genotype has been shown to have an effect on serum calcium. Recently, an association has been reported between the CaSR gene A986S polymorphism and bone mineral density in healthy white girls. In this study, we examined whether CaSR gene A986S polymorphism is associated with decreased bone mass in 230 Hungarian postmenopausal women. From this cohort, 108 osteoporotic patients were compared with 122 healthy control women. Bone mineral density (BMD) was measured at the lumbar spine (L2-4) and femoral neck using dual-energy X-ray absorptiometry. Allele-specific polymerase chain reaction was used to amplify A986S polymorphisms of the CaSR gene. We found no difference in the distribution of different alleles or genotypes between groups (p = 0.762). No significant effect of CaSR genotype on BMD was observed either in the whole population or in the subgroups. Our data do not support the idea that CaSR gene A986S polymorphism has an impact on bone mass.
Assuntos
Substituição de Aminoácidos/genética , Densidade Óssea/genética , Cálcio/metabolismo , Osteoporose Pós-Menopausa/genética , Polimorfismo Genético/genética , Receptores de Superfície Celular/genética , Idoso , Alanina/genética , Alelos , Análise de Variância , Estudos de Coortes , Feminino , Fêmur/fisiologia , Genótipo , Humanos , Hungria/epidemiologia , Vértebras Lombares/fisiologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/epidemiologia , Receptores de Detecção de Cálcio , Serina/genéticaRESUMO
The major determinant for risk of osteoporosis in later life is bone mineral density (BMD) attained during early adulthood. Bone mineral density is a complex trait that is presumably influenced by multiple genes. Interleukin-1 receptor antagonist protein (IL-1RN) is an attractive candidate gene for osteoporosis susceptibility, because IL-1RN completely inhibits the stimulatory effects of interleukin-1 (IL-1) on bone resorption in organ cultures and has been implicated in the pathogenesis of osteoporosis. In addition, the IL-1RN gene contains a variable-number tandem repeat polymorphism (VNTR) in intron 2 with three potential protein-binding sites. Recently, an association has been found between this polymorphism and postmenopausal bone loss in the spine. In this study, we use the previously described IL-1RN polymorphism to test for an association between this polymorphism and bone mineral density in our population of postmenopausal women. There was no correlation between alleles or genotypes and BMD in the 286 subjects. Dividing subjects into osteoporotic and healthy groups (osteoporotics and controls), we found no difference in the distribution of alleles or genotypes between groups. We found no association between IL-1RN alleles or genotypes and BMD either at the lumbar spine or the femoral neck within groups. Our data do not support the hypothesis that this IL-1RN gene VNTR polymorphism has an impact on bone mass in postmenopausal women.
Assuntos
Densidade Óssea/genética , Polimorfismo Genético , Pós-Menopausa , Sialoglicoproteínas/genética , Adulto , Idoso , Feminino , Genótipo , Humanos , Proteína Antagonista do Receptor de Interleucina 1 , Pessoa de Meia-Idade , Repetições MinissatélitesRESUMO
Oestrogen/oestrogen receptor (ER) and vitamin D/vitamin D receptor (VDR) systems have been implicated in the pathogenesis of colorectal cancers. The expression of erbB-2 and epidermal growth factor receptor (EGFR) in colorectal cancers has been suggested to have diagnostic and prognostic significance. In our study, XbaI and PvuII polymorphisms of the ER gene and the BsmI polymorphism of the VDR gene were studied in 56 Caucasian patients with rectal cancer. The relationship between the ER and VDR genotypes and the expression of oncogenes was also investigated. The presence of the x allele of ER gene significantly correlated with the overexpression of the erbB-2 and EGFR oncogenes. Significantly increased erbB-2 expression was observed in patients with the VDR B allele. The XXbb allelic combination of the ER/VDR genes was associated with a significantly lower erbB-2 expression, whereas in the other genotypes significantly higher oncogene expression was seen. Our data raise the possibility that ER/VDR gene polymorphisms accompanied by variable oncogene expression might influence the pathogenetic processes of colorectal cancers.
Assuntos
Receptores ErbB/genética , Genes erbB-2/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Receptores de Estrogênio/genética , Neoplasias Retais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Neoplasias Retais/metabolismo , Mapeamento por RestriçãoRESUMO
OBJECTIVE: We studied the significance of BsmI restriction enzyme polymorphism of the vitamin D receptor (VDR) gene and the XbaI and PvuII polymorphisms of the estrogen receptor (ER) gene in patients with type 2 diabetes (n=49), android type obesity with normal carbohydrate metabolism (n=29) and healthy controls (n=138). METHODS: The distribution of genotypes in the study groups, as well as their relationship to fasting and 1 h postprandial serum C-peptide levels were analyzed. RESULTS: Postprandial serum C-peptide levels of BB genotypes were significantly higher in the diabetes and obese groups (6.18+/-5.09 ng/ml) compared with other genotypes (2.71+/-2.45 vs. 1.72+/-1.97 ng/ml, respectively, P=0.05). Among patients with type 2 diabetes and obese subjects, the XX allelic variant of the ER gene was more frequent (P=0.00015). Postprandial C-peptide levels of subjects exhibiting XX genotype were significantly lower compared with those with Xx genotype (1.67+/-2.16 vs. 3.8+/-3.72 ng/ml, P=0.021). The BBXx allelic combination of the VDR/ER receptor genes was less frequent in diabetic patients than in healthy subjects or in obese patients. The BBXx genotype was associated with significantly elevated postprandial C-peptide levels in all subjects compared with other combinations (9.65+/-3.14 vs. 1.35+/-2.82 ng/ml, P=0.003). No difference was found in the distribution of the PvuII polymorphism of the ER gene or in the association with the C-peptide levels among study groups. CONCLUSION: Polymorphisms of the VDR/ER receptor genes might play a role in the pathogenesis of type 2 diabetes by influencing the secretory capacity of beta-cells.
Assuntos
Diabetes Mellitus Tipo 2/genética , Obesidade/genética , Receptores de Estrogênio/genética , Vitamina D/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Peptídeo C/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The mechanism by which thyroid hormones promote bone growth has not yet been elucidated. In vitro, thyroid hormones stimulate insulin-like growth factor-I (IGF-I) production by osteoblasts, which is important for the anabolic effects of the hormone on bone. To determine whether the IGF-I/IGF binding protein (IGFBP) profile is affected when thyroid hormone production is altered in vivo, we studied 36 women who had recently been diagnosed with hyperthyroidism (age: 29-67 years; 19 with Graves' disease, 17 with toxic nodular goiter) and 36 age-matched healthy women as controls. Serum IGF-I, and its binding proteins (IGFBP-3, IGFBP-4, and IGFBP-5), as well as bone mineral density (BMD) at the lumbar spine, femoral neck, and radius midshaft were measured before and 1 year after antithyroid (methimazole) treatment. Serum IGF-I levels were significantly increased in the hyperthyroid patients before treatment (214 +/- 18.2 ng/mL vs. 145 +/- 21.3 ng/mL; p < 0.05). There was no difference in IGF-I levels of patients with Graves' disease and toxic nodular goiter. Serum IGF-I concentrations returned to normal after treatment with methimazole. Serum IGFBP-3 and IGFBP-4 values were significantly elevated in the hyperthyroid group before treatment (3960 +/- 220 ng/mL and 749.7 +/- 53.1 ng/mL vs. 2701 +/- 180 ng/mL and 489.9 +/- 32.4 ng/mL; p < 0.05 and p < 0.01, respectively) and were reduced to those of controls after treatment. Serum IGFBP-5 of hyperthyroid subjects was not different from that of controls either before or after therapy. Serum free thyroxine showed a positive correlation with serum levels of IGF-I (r = 0.73, p < 0.05), IGFBP-3 (r = 0.59, p < 0.05), and IGFBP-4 (r = 0.67, p < 0.05) but not IGFBP-5. BMD at the radius midshaft was significantly lower in hyperthyroid patients at the start of the study and showed a positive correlation with serum IGF-I (r = 0.58; p < 0.001) and a negative correlation with IGFBP-4 (r = -0.61; p < 0.05). Radius BMD showed a 7.2% increase in the hyperthyroid group after 1 year of methimazole treatment, and the correlation between BMD and serum IGF-I disappeared. Our data indicate that thyroid hormones may influence the IGF-I/IGFBP system in vivo in hyperthyroidism. The anabolic effects of increased levels of IGF-I may be limited in hyperthyroidism due to the increases of inhibitory IGFBPs that can counteract the anabolic effects and contribute to the observed net bone loss.
Assuntos
Densidade Óssea , Hipertireoidismo/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Adulto , Idoso , Antitireóideos/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Feminino , Humanos , Hipertireoidismo/sangue , Hipertireoidismo/tratamento farmacológico , Metimazol/uso terapêutico , Pessoa de Meia-Idade , Rádio (Anatomia)/metabolismo , Valores de ReferênciaRESUMO
The role of tumor necrosis factor-alpha in insulin resistance has been studied in 59 patients with Type 2 diabetes, 28 with android type obesity and 35 healthy lean controls. Immunoreactive concentrations and bioactivity of serum tumor necrosis factor-alpha have repeatedly been determined in 8 weeks intervals for 12 months, five times per patients, by using ELISA and L929 cell cytotoxicity bioassay. Significantly higher immunoreactive tumor necrosis factor-alpha concentrations and bioactivity have been found in both, the Type 2 diabetic and obese groups as compared to the healthy persons. Tumor necrosis factor-alpha concentrations and bioactivity have showed a significant positive linear correlation with the elevated basal serum C-peptide levels and body mass indexes in both groups of patients. According to these data the cytokine might play a role in insulin resistance in obesity as well in Type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus/sangue , Obesidade/sangue , Fator de Necrose Tumoral alfa/metabolismo , Tecido Adiposo/anatomia & histologia , Idoso , Biomarcadores/sangue , Índice de Massa Corporal , Peptídeo C/sangue , Diabetes Mellitus/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Glucagon/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Valores de Referência , Fator de Necrose Tumoral alfa/análiseRESUMO
OBJECTIVE: To determine the incidence and risk factors of potential adverse drug interactions occurring in patients in the emergency department. DESIGN: Survey of a random sample of medical records of elderly persons and other adults seeking care at an emergency department. The interactions were determined by a computer programme, reviewed using explicit criteria, and excluded if of uncertain or trivial clinical significance. SETTING: University Hospital Medical Emergency Department. PATIENTS: A total of 423 randomly selected adults seeking care at a university hospital emergency department. Attendances made by 195 persons over age 60 and 228 younger adults were evaluated. All subjects were treated on an outpatient basis. MAIN OUTCOME MEASURES: Seventy percent of attendances led to the prescription of an added medication. In 5.4% of the attendances in which at least one medication was added, the new medication introduced a potential adverse interaction. The number of medications used at attendance was the best predictor of whether a potential interaction would occur. Additional medications prescribed in the emergency department that accounted for most of the added interactions were theophylline, macrolid antibiotics, digitalis glycosides, nonsteroidal anti-inflammatory agents, angiotensin converting-enzyme inhibitors and calcium antagonists. CONCLUSIONS: Potential adverse drug interactions were more common in elderly patients because of the higher number of concurrent medications rather than age-based factors. Safeguards need to be introduced to prevent patients from receiving medications in the emergency departments that have the potential to cause adverse interactions.
Assuntos
Toxidermias/epidemiologia , Interações Medicamentosas , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Benzodiazepinas/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Serviço Hospitalar de Emergência , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Análise de Regressão , Fatores de RiscoRESUMO
OBJECTIVE: We report two Hungarian patients with familial hypocalciuric hypercalcemia (FHH) caused by a mutation of the calcium-sensing receptor (CaSR) at codon 55. The proband and her father were heterozygous for this mutation. DESIGN: We performed detailed clinical and laboratory assessments of this family to characterize the effects of CaSR mutation on several endocrine organs expressing CaSR. RESULTS: Interestingly, we could not detect any failure in the function of any tissues we examined, except in serum calcium levels. CONCLUSIONS: To our knowledge, this has been the first report from Eastern and Central Europe showing P55 L mutation of the CaSR, as well as the first publication discussing the effect of this mutation on several endocrine systems containing CASR.
Assuntos
Cálcio/metabolismo , Cálcio/urina , Glândulas Endócrinas/fisiopatologia , Genes Dominantes , Hipercalcemia/fisiopatologia , Adulto , Sequência de Bases , Densidade Óssea , Códon , Feminino , Heterozigoto , Humanos , Hipercalcemia/genética , Hipercalcemia/metabolismo , Hipercalcemia/urina , Masculino , Pessoa de Meia-Idade , Mutação , Receptores de Detecção de Cálcio/genéticaRESUMO
In 1997 in western Austria, 9.9% of Pseudomonas aeruginosa strains from patients of general practitioners were resistant to imipenem as well as 18.2% of the isolates from hospitals and 20.2% of the strains at a university teaching hospital. Within the hospital the imipenem resistance varied from 9.9% among out-patients to 28.7% in isolates from intensive care units. In medical/surgical words, up to 15.1% of P. aeruginosa strains were resistant to imipenem. The incidence of imipenem-resistant P. aeruginosa strains correlates to the use of carbapenems. In June 1997, 10 consecutive isolates from 8 patients were obtained and typed using restriction fragment length polymorphism analysis (RFLP) and Pyocin typing. All 10 isolates were resistant to meropenem as well as to imipenem. The finding (by RFLP and Pyocin typing) of individual bacterial types in each isolate strongly contradicts the spread of infection by cross infection. However, all patients were proven to have been treated with imipenem during the 3 months prior to testing. In 1997, 13,880 g of imipenem were used at the university hospital in Innsbruck. The use of carbapenems appears to be the main cause for the increased incidence of imipenem-resistant P. aeruginosa strains.
Assuntos
Infecção Hospitalar/tratamento farmacológico , Imipenem/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Áustria/epidemiologia , Técnicas de Tipagem Bacteriana , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Resistência Microbiana a Medicamentos , Humanos , Meropeném , Polimorfismo de Fragmento de Restrição , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/microbiologia , Tienamicinas/uso terapêuticoRESUMO
In this study, the Xbal polymorphisms of the estrogen-, the Bsml polymorphism of the vitamin D- as well as the A986S polymorphism of the calcium-sensing receptor genes were investigated in 56 patients with colorectal cancer. The expression of erbB-2, epidermal growth factor receptor, ras, p53 and their relationship to estrogen-, vitamin D- and calcium-sensing receptor genotypes were also studied. In subjects exhibiting XX genotype of the estrogen receptor gene or bb genotype of the vitamin D receptor gene, erbB-2 expression was significantly lower compared to those with xx, Xx or BB, Bb (6/56 and 11/56 vs. 31/56 and 26/56; p = 0.0043 and 0.041). The presence of the XX alleles of estrogen receptor gene significantly correlated with the overexpression of the epidermal growth factor receptor expression in tumors, whereas in xx and Xx genotypes, significantly higher expression was seen (7/56 vs. 30/56; p = 0.049). Analyzing the combinations of the two gene allelic variants, we have found XXbb genotype to be associated with a significantly lower erbB-2 expression, compared to other combinations (Xxbb, XxBb, XXBb) (2/7 vs. 7/7, 4/5, 4/5; p = 0.0011). Patients with AA calcium-sensing receptor genotype were in higher UICC stages at the time of discovery of their disease than those with AS genotype. The AA allelic variant of the calcium-sensing gene was more frequent among patients with colorectal cancer compared to controls (36/56 vs. 36/112; p = 0.0004). Our observations raise the possibility that estrogen-, and vitamin D receptor gene polymorphisms accompanied with variable oncogene expression might influence the pathogenic processes resulting in the development of colorectal cancer. The A986S polymorphism of calcium-sensing receptor might also be a prognostic marker of the disease.
Assuntos
Proteínas de Ligação ao Cálcio/genética , Neoplasias Colorretais/genética , Receptores de Calcitriol/genética , Receptores de Estrogênio/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Primers do DNA , Receptores ErbB/biossíntese , Feminino , Regulação Neoplásica da Expressão Gênica , Genes erbB-2/genética , Genes ras/genética , Genótipo , Humanos , Immunoblotting , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Polimorfismo Genético , Proteína Supressora de Tumor p53/biossínteseRESUMO
Fever is not the most frequent symptom in rheumatology; however, its occurrence always draws attention to a severe underlying pathologic process. The rheumatologic assessment of febrile patients usually takes place for three reasons: the patient's fever is associated with known rheumatic disease or musculoskeletal symptoms, or rheumatologic cause is suggested as the underlying cause of fever of unknown origin. The primary task of the rheumatologist is to rule out infections and autoimmune processes. In addition to the musculoskeletal and accompanying symptoms, the information about the course of fever and the observation of the continuity or periodicity of fever provide help to establish the diagnosis. A summarising discourse about this issue is rarely published in this speciality; therefore, we found it important to provide an overview of rheumatological diseases accompanied by fever.
Assuntos
Doenças Autoimunes/diagnóstico , Febre de Causa Desconhecida/etiologia , Febre/etiologia , Doenças Reumáticas/diagnóstico , Doenças Autoimunes/complicações , Diagnóstico Diferencial , Febre/diagnóstico , Febre de Causa Desconhecida/diagnóstico , Humanos , Doenças Reumáticas/complicaçõesAssuntos
Peptídeo C/sangue , Endotelina-1/sangue , Obesidade/sangue , Obesidade/classificação , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Ensaio de Imunoadsorção Enzimática , Jejum , Feminino , Humanos , Masculino , Obesidade/fisiopatologia , Período Pós-Prandial , Radioimunoensaio , Valores de Referência , Fator de Necrose Tumoral alfa/análiseRESUMO
25-hydroxyvitamin D3 24-hydroxylase (CYP24A1), the catabolizing enzyme of the active vitamin D3, is often overexpressed in solid tumors. The unbalanced high levels of CYP24A1 seem to be a determinant of vitamin D resistance in tumors. Splice variants of CYP450 enzymes are common. Existence of CYP24A1 isoforms has been reported recently. We have investigated the presence of CYP24A1 splicing variants (SV) in human colon cancer cell lines and tissue samples. Using a set of primer combination we have screened the entire coding sequence of CYP24A1 and identified three splice variants in colon cancer cell lines. The presence of these SVs in human colon tissue samples showed a correlation with histological type of the tissue and gender of patients. The sequencing of the alternatively spliced fragments showed that two have lost the mitochondrial target domain, while the third lacks the heme-binding domain. All SVs retained their sterol binding domain. Translation of these variants would lead to a dysfunctional enzyme without catalytic activity that still binds its substrates therefore they might compete for substrate with the synthesizing and catabolizing enzymes of vitamin D.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/metabolismo , Esteroide Hidroxilases/biossíntese , Esteroide Hidroxilases/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Processamento Alternativo , Linhagem Celular Tumoral , Colo/metabolismo , Primers do DNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Esteróis/química , Vitamina D3 24-HidroxilaseRESUMO
The CYP3A7 enzyme metabolizes some steroid hormones, including dehydroepiandrosterone sulfate (DHEAS). The age-related decline of serum DHEAS levels is believed to contribute to osteoporosis. Previously, the CYP3A7*1C polymorphism has been shown to cause a persistent high CYP3A7 enzyme activity, resulting in lower levels of DHEAS in men. We hypothesized that the CYP3A7*1C polymorphism might contribute to bone loss through decreased levels of serum DHEAS in postmenopausal women. Postmenopausal women (n = 319) were divided into two subgroups: 217 with osteoporosis and 102 healthy controls. Genotyping, serum DHEAS measurement, and osteodensitometry of the lumbar spine and femoral neck were carried out in all subjects. Homozygous CYP3A7*1C carriers had significantly lower BMD at the lumbar spine compared to wild types (T score -3.27 +/- 1.02 in CYP3A7*1C homozygous mutants vs. -1.35 +/- 1.53 in wild types, P = 0.041). This association remained significant after adjustment for menopausal age, serum DHEAS level, alcohol consumption, steroid intake, smoking habits, and previous fractures. No association was found between genotypes and serum DHEAS levels in the total study population or in the subgroups. Serum DHEAS levels correlated positively with bone mineral density at the lumbar spine (r = 0.59, P = 0.042) after correction for age. Our data suggest that the CYP3A7 polymorphism might have an influence on bone mass at the lumbar spine independently of serum DHEAS concentrations.
Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Sulfato de Desidroepiandrosterona/sangue , Polimorfismo Genético , Idoso , Densidade Óssea , Osso e Ossos/patologia , Citocromo P-450 CYP3A , Densitometria , Feminino , Variação Genética , Genótipo , Homozigoto , Humanos , Vértebras Lombares/patologia , Pessoa de Meia-Idade , Pós-MenopausaRESUMO
OBJECTIVES: The significance of genetic polymorphisms in the development of Paget's disease of bone is unclear at present. METHODS: We analysed the BsmI polymorphism of the vitamin D receptor (VDR) gene, the PvuII and XbaI polymorphisms of the oestrogen receptor-alpha (ER alpha) gene, and the A986S polymorphism of the calcium-sensing receptor (CaSR) gene in 69 pagetic patients and 120 healthy subjects. We also examined the relationship of these polymorphisms with lumbar spine and femoral neck BMD as well as with biochemical parameters (serum alkaline phosphatase, osteocalcin and parathyroid hormone) in Paget's disease. RESULTS: The XbaI and PvuII genotype distributions of the ER alpha gene were significantly different between patients with Paget's disease and control subjects (P<0.001). Also, the CaSR A986S genotype frequency was significantly different between pagetic patients and controls (P<0.01). No significant effect of gene polymorphisms on BMD or biochemical parameters of bone turnover was observed. CONCLUSION: Our results suggest that the ER alpha PvuII/XbaI and CaSR A986S polymorphisms may contribute to genetic susceptibility to Paget's disease. However, further studies are required to investigate the underlying pathomechanism and to replicate the associations.
Assuntos
Densidade Óssea , Osteíte Deformante/genética , Polimorfismo Genético , Receptores de Detecção de Cálcio/genética , Receptores de Esteroides/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Receptor alfa de Estrogênio , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Osteíte Deformante/sangue , Osteíte Deformante/fisiopatologia , Receptores de Calcitriol/genética , Receptores de Estrogênio/genéticaRESUMO
We studied the effect of alphacalcidol (1-alpha-hydroxycholecalciferol) on bone metabolism in patients who were placed on glucocorticoid therapy. We selected 41 women (age: 32-52 yrs) who were recently diagnosed with systemic lupus erythematodes, multiple sclerosis, rheumatoid arthritis or asthma bronchiale. Patients did not have other disease or take drugs known to influence bone metabolism. Patients were randomly enrolled into two groups and were given 5-25 mg prednisone daily. After 4 weeks, group A (n = 21) received 0.5-1.0 microgram (mean = 0.54 +/- 0.03 microgram) alphacalcidol and group B (control; n = 20) was given 500 mg calcium daily for three years. There were no significant differences in age and steroid doses between groups. Serum calcium (Ca), osteocalcin (OC), collagen I C-terminal propeptide (PICP), parathyroid hormone (PTH), and urinary calcium and deoxypyridinoline crosslink excretion (DPD) were measured before corticosteroid administration, and before alphacalcidol or calcium treatment as well as 6 weeks, 6 months, and 1, 2, and 3 years later. Bone mineral density (BMD) was examined before treatment and 6 months, 1, 2, and 3 years later by DEXA and SPA. OC and PICP decreased significantly after 4 weeks on steroid in both groups and increased in group A but not in group B after 6 weeks of treatment with alphacalcidol and remained unchanged for 3 years. Serum PTH increased in both groups after 4 weeks of glucocorticoid treatment and was reduced in group A, but not in group B, after 6 weeks on alphacalcidol. Serum Ca, urinary Ca, and DPD did not change significantly in either group during the study period. Lumbar spine and femoral neck BMD were significantly reduced in group B after 6 months and 1 year, respectively, and continued to decrease during the study, while no significant change in group A was observed. BMD of the radius did not change in either group for 2 years but there was a significant reduction by the third year in group B. Based on these results, alphacalcidol treatment appears to be effective in preventing glucocorticoid-induced bone loss in these patients by reducing secondary hyperparathyroidism and stimulating bone formation.