RESUMO
OBJECTIVE: The objective of this study was to develop a simple tool for the assessment of possible dental treatment needs (DTN) for non-dental professionals (Mini Dental Assessment, MDA). To keep the assessment universal, we aimed to base it on the patient's history and a simple chewing efficiency test (CET) as the dental status is a known determinant for chewing efficiency. MATERIALS & METHODS: The assessment was developed using data from 169 patients from two sites (University Hospital Giessen, St. Bonifatius Hospital Lingen, both Germany). In all patients, a dental examination was performed, the denture status was evaluated (based on the California Dental Association criteria; CDA criteria), and the DTN was determined. In addition, the time since the patient's last visit to a dentist (TLVD) and denture age (DA) were assessed. Furthermore, a CET was carried out and the comminution score was determined (CETS). RESULTS: In total, 108 patients required dental treatment. The mean value (±SD) was 2.9 ± 0.9 score points for the DTN, 2.5 ± 3.8 years for the TLVD, and 10.8 ± 8.9 years for the DA. There was a significant correlation (Spearman, P < .05) between the DTN and degree of comminution (3.4 ± 1.8). Based on the results of the statistical analysis, the intended assessment tool was developed using the variables CETS, TLVD, and DA weighed by their respective regression coefficients (10:3:1). Subsequently, the resulting MDA score (51.32 ± 28.14) was calculated. A sensitivity/specificity analysis was conducted and a receiver operating characteristic curve was calculated (SPSS 17.0, area under curve 0.805; 95 % CI 0.738-0.873). CONCLUSION: It can be concluded that the dental status of elderly patients is reflected in the outcome of the MDA. However, ongoing validation is needed. TRIAL REGISTRATION: DRKS00003219.
Assuntos
Assistência Odontológica , Avaliação Geriátrica , Necessidades e Demandas de Serviços de Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha , Humanos , Masculino , Mastigação/fisiologia , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeAssuntos
Diabetes Mellitus Tipo 1/complicações , Oftalmopatia de Graves/complicações , Poliendocrinopatias Autoimunes/complicações , Poliendocrinopatias Autoimunes/diagnóstico , Dermatopatias/complicações , Antitireóideos/uso terapêutico , Carbimazol/uso terapêutico , Glucocorticoides/uso terapêutico , Oftalmopatia de Graves/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Mixedema/etiologia , Poliendocrinopatias Autoimunes/tratamento farmacológico , Prednisona/uso terapêutico , Resultado do TratamentoRESUMO
Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Of the numerous organ manifestations, involvement of the upper and lower gastrointestinal tract (GIT) appears to be the most frequent with regard to the clinical symptoms. However, as the frequency and clinical relevance of GI involvement in patients with SSc are not known in detail, the German network of the systemic sclerosis (DNSS) has developed a detailed questionnaire to evaluate the extent and profile of gastrointestinal involvement in SSc patients. The multi-symptom questionnaire was used at baseline and after 1 year in registered patients of the DNSS. In addition, the results were compared with gastrointestinal disorders in patients with SSc and other rheumatic diseases, as well as with the medical history of the patients. In total, 90 patients were included in the study. The results of the study show that in reality, a much higher (nearly all) percentage of (98,9%) patients than expected suffer from GI-symptoms, regardless of the stage of their disease. Of these, meteorism (87,8%) was the most common followed by coughing/sore voice (77,8%), heartburn (daytime 68,9%, nighttime 53,3%), diarrhea (67,8%), stomach ache (68,9%) and nausea (61,1%). Although SSc patients were treated according to the respective recommendations, only limited improvements with regard to GI-symptoms could be achieved after 1 year of follow-up. In addition, the study revealed that the multi-symptom questionnaire is a useful tool to contribute to identify the gastrointestinal sequelae in systemic sclerosis.
Assuntos
Gastroenteropatias/epidemiologia , Doença Mista do Tecido Conjuntivo/epidemiologia , Esclerodermia Difusa/epidemiologia , Esclerodermia Limitada/epidemiologia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Seguimentos , Gastroenteropatias/diagnóstico , Gastroenteropatias/terapia , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença Mista do Tecido Conjuntivo/diagnóstico , Doença Mista do Tecido Conjuntivo/terapia , Prognóstico , Sistema de Registros , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/terapia , Esclerodermia Limitada/diagnóstico , Esclerodermia Limitada/terapia , Índice de Gravidade de Doença , Inquéritos e Questionários , Fatores de TempoRESUMO
BACKGROUND: Diabetes mellitus secondary to pancreatic diseases is a condition seldom thought of in clinical practice. Yet, a high percentage of exocrine pancreatic insufficiency has been reported for the general population and especially for diabetic subjects. Thus, we investigated the prevalence of diabetes mellitus due to pancreatic diseases. METHODS: In this study, we investigated 1868 patients diagnosed with diabetes mellitus who had been admitted to our hospital during the last 24 months. Patient data were diligently studied, and patients were reclassified according to the diabetes classification as proposed by the American Diabetes Association. RESULTS: Among 1868 subjects, 172 patients could be classified as type 3c diabetes mellitus (9.2%). Among these were 135 diagnosed with chronic pancreatitis (78.5%), 12 with hereditary haemochromatosis, 14 with pancreatic cancer and 7 with cystic fibrosis. Thus, diabetes mellitus due to chronic pancreatitis occurred in this collective in 7.2% of all diabetic subjects. Misclassification of these patients was very common. Only 51.2% (88/172) were initially classified correctly. Most type 3 diabetes patients were initially misclassified as type 2 diabetes (69/84). CONCLUSIONS: Diabetes mellitus secondary to pancreatic diseases (especially chronic pancreatitis) seems more common than generally believed with a prevalence of 9.2% among the subjects studied here. Because the awareness of this diabetes type is poor, misclassification is quite frequent. A common problem seems to be the differentiation between type 2 and type 3. Yet, the right classification of diabetes mellitus is important, because there are special therapeutic options and problems in patients with diabetes secondary to pancreatic diseases.
Assuntos
Diabetes Mellitus/epidemiologia , Pancreatopatias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Diabetes Mellitus/etiologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatopatias/complicações , Prevalência , Estudos Retrospectivos , Estatísticas não Paramétricas , Adulto JovemRESUMO
Intraportal islet transplantation suffers from low efficiency caused by substantial islet mass loss after transplantation. How this process is regulated is still unclear. Here, we show that NF-κB activation was detectable in islet grafts shortly after transplantation of porcine islets to diabetic NMRI nu/nu mice, and systemic NF-κB inhibition in transplanted animals significantly prolonged islet graft survival. Proinflammatory cytokines alone did not cause evident cell death in pancreatic islet within 24 h, while the combination of cytokines with hypoxia resulted in a strong induction of cell death that could be blocked dose-dependently by a selective IKK-ß inhibitor. Under hypoxia, NF-κB activity impaired expression of antiapoptotic gene BCL-xL, c-FLIP and survivin. NF-κB activation in isolated islets was reduced by hypoxia in a time-dependent manner, accordingly, NF-κB activation in transplanted islets diminished by time. Our data indicate that, while NF-κB has an antiapoptotic role under normoxia, low oxygen conditions decrease its activity and transform it to a proapoptotic transcription factor in pancreatic islets. We conclude that NF-κB inhibition represents a potential strategy to improve islet transplantation efficiency.
Assuntos
Quinase I-kappa B/antagonistas & inibidores , Transplante das Ilhotas Pancreáticas/métodos , NF-kappa B/metabolismo , Oxigênio/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Apoptose/fisiologia , Citocinas/farmacologia , Diabetes Mellitus Experimental/cirurgia , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/fisiologia , Hipóxia/patologia , Hipóxia/fisiopatologia , Imidazóis/farmacologia , Transplante das Ilhotas Pancreáticas/patologia , Transplante das Ilhotas Pancreáticas/fisiologia , Masculino , Camundongos , Camundongos Nus , NF-kappa B/antagonistas & inibidores , Veia Porta , Quinoxalinas/farmacologia , Proteínas Recombinantes/farmacologia , Suínos , Transplante HeterólogoRESUMO
BACKGROUND: New-onset diabetes mellitus after organ transplantation (PTDM) significantly impairs patient and organ survival. Published rates of PTDM range from 2% to 54%, depending on the definition. OBJECTIVES: To analyze incidence of PTDM after renal transplantation according to recent guidelines and to evaluate implementation of a prospective standardized screening protocol. PATIENTS AND METHODS: Data for all consecutive patients who underwent transplantation from 2000 to 2006 were analyzed retrospectively for PTDM. In a prospective pilot trial all candidates for living related donor transplantation underwent a 75-g oral glucose tolerance test at evaluation prior to renal transplantation and at 3, 6, and 12 months thereafter. RESULTS: Data for 181 out of 271 consecutive patients were analyzed. Of these patients, 36 (19.9%) developed PTDM. Age, body mass index, pretransplantation fasting glucose concentration, and number of HLA mismatches were significant predictive risk factors. Posttransplantation diabetes mellitus occurred more frequently in patients receiving a cadaver organ compared with a living donor organ and in those receiving tacrolimus therapy vs cyclosporine therapy. Preliminary results demonstrated a 55.5% incidence of PTDM at 3 months in patients who received a living donor organ, much higher than expected. CONCLUSIONS: With an incidence of approximately 20%, PTDM is a frequent complication of transplantation. Prospective screening using oral glucose tolerance testing is a more sensitive method for detection of impaired glucose metabolism and PTDM. Relevance and therapeutic consequences must be determined in large-scale prospective studies.
Assuntos
Diabetes Mellitus/epidemiologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Glicemia/metabolismo , Cadáver , Feminino , Teste de Tolerância a Glucose , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Humanos , Incidência , Transplante de Rim/imunologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de Tecidos , Adulto JovemRESUMO
OBJECTIVE: Recently it has been shown that there is not only endocrine insufficiency in diabetic patients, but a frequent co-morbidity of both, the endocrine and exocrine pancreas. The present study was performed to further analyse the determinants of exocrine pancreatic function in patients with diabetes mellitus. METHODS: The records of 1992 patients with diabetes mellitus who had been treated in our hospital during a 2-year period were re-evaluated. Defined parameters were documented in standardized data sheets. Records were further checked for the results of imaging procedures of the pancreas. In 307 patients FEC had been performed and documented. Only these patients were included in further evaluation. RESULTS: FEC was inversely correlated with diabetes duration and HbA1c-levels but not with age. C-peptide levels correlated positively with FEC. BMI and FEC were also significantly correlated. There was no correlation between diabetes therapy and exocrine pancreatic function as there was no correlation with any concomitant medication. The presence of diabetes-associated antibodies was not related to FEC. According to the documented data 38 were classified as type-1 diabetes (12.4%), 167 as type-2 (54.4%), and 88 patients met the diagnostic criteria of type-3 (28.7%). Fourteen patients could not be classified because of lacking information (4.6%). CONCLUSIONS: Exocrine insufficiency might be explained as a complication of diabetes mellitus. However, it is more likely that type-3 diabetes is much more frequent than previously believed. Consequently the evaluation of exocrine function and morphology should be included into the clinical workup of any diabetic patient at least at the time of manifestation.
Assuntos
Diabetes Mellitus/enzimologia , Insuficiência Pancreática Exócrina/metabolismo , Fezes/enzimologia , Pâncreas Exócrino/metabolismo , Elastase Pancreática/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Peptídeo C/sangue , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/fisiopatologia , Insuficiência Pancreática Exócrina/diagnóstico , Insuficiência Pancreática Exócrina/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas Exócrino/patologia , Pâncreas Exócrino/fisiopatologia , Testes de Função Pancreática , Adulto JovemRESUMO
Alterations of bone metabolism have been observed in numerous studies of HIV-infected patients. Sex steroids are known to profoundly influence bone mass and bone turnover. Hypogonadism is common in HIV-infection. Therefore, we performed a cross sectional study of 80 male HIV-infected patients without wasting syndrome, and 20 healthy male controls, in whom we analyzed urine and serum samples for both calciotropic hormones and markers of bone metabolism and of endocrine testicular function. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry both in the lumbar spine and Ward's triangle of the left hip. None of the patients received highly-active-antiretroviral-therapy (HAART). Compared to eugonadal HIV-infected patients, subjects with hypogonadism (n = 32; 40%) showed statistically significant decrease of serum osteocalcin (p < 0.05) and elevated urinary excretion of crosslinks (p < 0.05). However, we found 13 and 15, respectively, patients with osteopenia (t-score -1.0 to -2.5 SD below normal) of the lumbar spine. The dissociation between bone formation and resorption and the reduction of of BMD (p < 0.05) is stronger expressed in patients with hypogonadism. Habitual hypogonadism appears to be of additional relevance for bone metabolism of male HIV-positive patients prior to HAART.
Assuntos
Densidade Óssea , Infecções por HIV/metabolismo , HIV-1 , Hipogonadismo/metabolismo , Adulto , Terapia Antirretroviral de Alta Atividade , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/metabolismo , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Hipogonadismo/complicações , Hipogonadismo/epidemiologia , Masculino , Pessoa de Meia-Idade , Osteocalcina/sangue , Osteocalcina/metabolismo , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/metabolismo , Prevalência , Testosterona/sangue , Testosterona/metabolismo , Adulto JovemRESUMO
BACKGROUND: There are still too few conclusive reports about conspicuous parathormone (PTH) and Vitamin D metabolism in patients with fecal elastase 1 deficiency or any connection of the calcium metabolism to the severity of exocrine pancreas insufficiency. METHODS: Between March 1998 and September 2002, we investigated on 240 female patients with fecal elastase 1 deficiency at an average age of approx. 56.4 years and suffering from meteorism and weight loss as well as on age matched 80 healthy female controls. Serum levels of PTH, total calcium, D subset3-vitamins, calcitriol and calcefediol, as well as the concentration of fecal elastase 1 were determined in patients and controls. RESULTS: In 240 female patients with deficiency of fecal elastase 1 only two patients show milder cases of new diagnosed primary hyperparathyroidism. Calcitriol was markedly decreased (14.3 +/- 6.1 and 20.7 +/- 9.4 pg/ml) compared to controls (41.8 +/- 8.3 pg / ml) ( p < 0.01). Calcefediol was not significantly different within the various elastase-groups (p = 0.07). Nevertheless, vitamin D subset3 and fecal elastase 1 in patients correlated significantly (p < 0.01) and, compared to controls, both were extremely low (means in patients. Both D subset3-vitamins in patients were significantly lower when elastase 1 in feces was under 200 microg/g compared to the others (for calcitriol p < 0.05, for calcefediol p < 0.05). CONCLUSION: In female patients elastase 1 in feces confirm the grade of vitamin D supply, and thus show a vitamin D subset3-deficiency, depending on the loss of stool content. There seems to be a connection here between the loss of exocrine function and may be even the characteristic of sterol-binding of elastase 1 in the pancreas, which seems to be relevant for vitamin D-supply.
Assuntos
Fezes/enzimologia , Elastase Pancreática/análise , Hormônio Paratireóideo/sangue , Vitamina D/metabolismo , Adulto , Idoso , Calcifediol/sangue , Calcitriol/sangue , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The aim of this study was to characterize the GH-IGF-I axis of patients with HIV-1-infection without any symptoms of AIDS-associated wasting. A special emphasis was placed on determine bone mineral density (BMD) and biochemical markers of bone metabolism. Therefore 42 male fasting HIV-1-infected outpatients were included and estimation of serum GH, IGF-I, IGFBP-1 and 3, osteocalcin, TNF-alpha, 1,25dihydroxycholecalciferol, and endocrine markers of the gonad function by commercially available RIA's performed. DEXA-measurements of the lumbar spine and the Ward's triangle of the left hip were done. The GH, IGF-1, IGFBP-1 and 3 serum levels were within the normal range Performing Spearman-correlation test, we established significance between IGF-I serum levels and BMD lumbar spine and Ward's triangle (p < 0.01, p < 0.05), CD4 cell-count (p < 0.05), 1,25dihydroxycholecalciferol (p < 0.05), osteocalcin (p < 0.05), TNF-alpha (p < 0.05), body mass index (BMI) (p < 0.05) and total testosterone (p < 0.01). IGFBP-1 correlates both inversely significantly with CD4 cell-count (p < 0.05) and serum-calcium (p < 0.05). The IGFBP-3 correlates with BMI (p < 0.05) and serum osteocalcin (p < 0.05). Correlation both with markers of bone metabolism and vitamin D metabolites showed the important role of GH/IGF-I axis in modulating the availability of calcium in chronic conditions. This axis may be in a part responsible for the manifestation of the HIV-associated osteopenia.
Assuntos
Densidade Óssea , Doenças Ósseas Metabólicas/metabolismo , Doenças Ósseas Metabólicas/virologia , Infecções por HIV/metabolismo , HIV-1 , Hormônio do Crescimento Humano/sangue , Adulto , Biomarcadores/sangue , Contagem de Linfócito CD4 , Cálcio/metabolismo , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Osteocalcina/sangueRESUMO
AIM: Efficacy and safety of benfotiamine in treatment of diabetic polyneuropathy. METHODS: Double blind, placebo-controlled, phase-III-study. 181 patients were screened. 165 patients with symmetrical, distal diabetic polyneuropathy were randomised to one of three treatment groups entering the wash-out phase and 133/124 patients were analysed in the ITT/PP analysis: Benfotiamine 600 mg per day (n=47/43), benfotiamine 300 mg per day (n=45/42) or placebo (n=41/39). RESULTS: After 6 weeks of treatment, the primary outcome parameter NSS (Neuropathy Symptom Score) differed significantly between the treatment groups (p=0.033) in the PP (per protocol) population. In the ITT (intention to treat) population, the improvement of NSS was slightly above significance (p=0.055). The TSS (Total Symptom Score) showed no significant differences after 6 weeks of treatment. The improvement was more pronounced at the higher benfotiamine dose and increased with treatment duration. In the TSS, best results were obtained for the symptom "pain". Treatment was well tolerated in all groups. CONCLUSION: Benfotiamine may extend the treatment option for patients with diabetic polyneuropathy based on causal influence on impaired glucose metabolism. Further studies should confirm the positive experiences.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Neuropatias Diabéticas/tratamento farmacológico , Tiamina/análogos & derivados , Adulto , Idoso , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Segurança , Limiar Sensorial/efeitos dos fármacos , Tiamina/efeitos adversos , Tiamina/uso terapêuticoRESUMO
To evaluate ex vivo/in vitro the binding and dissociation characteristics and the level of crossreactivity of insulin antibodies and insulin autoantibodies directed to three different insulin molecules (human, bovine and porcine insulin). In this study sera from 17 diabetic patients were included, who were exclusively treated with s.c. human insulin, but presenting with severe insulin antibody mediated, immunological insulin resistance (i.e., insulin antibodies, IA). In addition, we included serum from one female patient, previously diagnosed with insulin autoimmune syndrome (no exposure to exogenous insulin treatment, i.e., insulin autoantibodies, IAA). Antibody concentrations and a binding/dissociation analysis was performed by using J(125)-labelled (position: A-14) human, porcine and bovine insulin according to the protocol described recently. In the patient with insulin autoimmune syndrome (IAA) we observed total crossreactivity between human, bovine and porcine insulin. By contrast, in the group of s.c. insulin treated diabetic patients with antibody-mediated insulin resistance (IA) we detected only partial crossreactivity. In these patients, there was a significantly higher level in the inital insulin binding (P < 0.05) directed to human insulin (median: 34%, IQR: 21.0-62.0), compared to porcine (median: 29.5%, IQR: 18.3-61.0) and bovine insulin (29%, IQR: 20.3-61.5), respectively. Here, we demonstrate different binding characteristics between IAA and IA, suggesting different epitope specificities. The observation of a significantly lower insulin binding to the "natural insulin analogs" (bovine and porcine insulin) compared to human insulin in the IA-group is in support of the concept that insulin analogs are eventually less immunogenic.
Assuntos
Reações Antígeno-Anticorpo , Anticorpos Anti-Insulina/imunologia , Insulina/análogos & derivados , Insulina/imunologia , Administração Cutânea , Adulto , Animais , Reações Antígeno-Anticorpo/imunologia , Doenças Autoimunes/sangue , Doenças Autoimunes/imunologia , Bovinos , Reações Cruzadas/imunologia , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/imunologia , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/imunologia , Insulina/administração & dosagem , Insulina/efeitos adversos , Anticorpos Anti-Insulina/sangue , Projetos Piloto , Especificidade da Espécie , Suínos , SíndromeRESUMO
BACKGROUND: Type-1 diabetic individuals differ with regard to both, the formation of circulating insulin antibodies, and the incidence of severe hypoglycaemia. AIM OF THE STUDY: To assess the association of insulin binding to antibodies with the incidence of severe hypoglycaemia. PATIENTS AND METHODS: In a cross sectional study, 73 children with type-1 diabetes mellitus (median age 14 years, duration of diabetes 6 years) were investigated, 22 of whom had experienced severe hypoglycaemia during the past 18 months, and 51 had never experienced severe hypoglycaemia. Of the patients with severe hypoglycaemia 16 had experienced severe unexplained hypoglycaemias, and 6 had experienced severe hypoglycaemias which were explicable (by missed meals, unplanned physical exercise etc.). Insulin binding was measured in a blinded central laboratory by radioimmunoassay, and expressed as ratio bound/unbound insulin; a binding >15% was considered relevant insulin binding. RESULTS: A total of 38 patients displayed relevant insulin binding (17 of whom had experienced severe hypoglycaemia), and 35 patients did not (5 of whom had experienced severe hypoglycaemia; p=0.0055, Fisher's exact test). Patients with relevant insulin binding were younger (12.2 vs 14.5 years, p=0.006) than patients without relevant insulin binding. From the 16 patients with inexplicable severe hypoglycaemia, 15 displayed relevant insulin binding, compared to 2 of the 6 patients with explicable severe hypoglycaemia (p=0.009). The association of any severe hypoglycaemia, and of inexplicable severe hypoglycaemia, with relevant insulin binding was significant (odds ratio 4.8 (95%CI 1.5-15.2), and 22.1(95%CI 2.7-179.6), p<0.006). Patients with/without relevant insulin binding, or with/without severe hypoglycaemia, did not differ significantly regarding sex, duration of diabetes, number of insulin injections per day, HbA1c and C-peptide levels (ANOVA). CONCLUSION: Insulin binding to antibodies >15% appears to be a strong risk factor for inexplicable severe hypoglycaemias in type-1 diabetic children.
Assuntos
Anticorpos/metabolismo , Diabetes Mellitus Tipo 1/complicações , Hipoglicemia/etiologia , Insulina/imunologia , Insulina/metabolismo , Adolescente , Estudos de Casos e Controles , Criança , Estudos Transversais , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Humanos , Masculino , Ligação Proteica , Fatores de RiscoRESUMO
BACKGROUND: There are still too few conclusive reports about conspicuous vitamin D-deficiency in young female patients with chronic pancreatitis, or any connection of the deficiency to the severity of the disease. Therefore the aim of this study was to examine marker of vitamin D3 metabolism in female patients with episode of biliary pancreatitis to determine if increased severity of the disease would correlate with impaired vitamin D3 metabolism. METHODS: Between 1996 and 2003, we investigated 53 premenopausal patients with an average age of approximately 33 years suffering from an episode of chronic pancreatitis, as well as 30 female healthy controls with an average age of 32.4 years. The severity of chronic pancreatitis in patients was determined via endoscopic retrograde cholangiopancreaticography (ERCP) and assigned to 1 of 3 grades based on the Cambridge classification. Additional parameter assessed were demographics, smoking, consumption of alcohol and CD-transferrin, fasting metabolic parameters, biochemical markers of vitamin D3 metabolism and fecal elastase 1. None of the patients received hormone replacement therapy, Vitamin D or Calcium-supplementation. RESULTS: The serum levels of 1,25-dihydroxyvitamin D [1,25(OH2)D] were significantly reduced compared to female healthy controls. Fecal elastase 1 correlated with this classification of severity of chronic pancreatitis (p < 0.01). Furthermore, fecal elastase 1 of patients correlated the same way with both D-vitamins (p <0.01). The level of both D3 vitamins in patients were significantly lowered when the content of fecal elastase 1 was under 200 microg/g compared to the others [for 1,25-(OH2)D3 p < 0.01; 25-OH- D3 p < 0.01]. CONCLUSION: Premenopausal patients with chronic pancreatitis are at risk of developing decreased levels of 1,25(OH2)D3. This fact may contribute to a negative calcium balance and alteration of bone metabolism. Therefore, ERCP and fecal elastase 1 verify the severity grade of a chronic pancreatitis, and thus show a vitamin D3 deficiency in young women, depending on the progress of disease.
Assuntos
Colecalciferol/sangue , Pancreatite Crônica/sangue , Deficiência de Vitamina D/sangue , Adulto , Calcifediol/sangue , Estudos Transversais , Fezes/enzimologia , Feminino , Alemanha/epidemiologia , Humanos , Elastase Pancreática/metabolismo , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/epidemiologia , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/epidemiologiaRESUMO
In diabetic patients, mycotic infections may increase the risk of developing diabetic foot syndrome. However, little data are available on the prevalence of fungal foot infections in patients with diabetes. In a first study published using data obtained during a conference attended by patients with long-term diabetes mellitus type 1 (DM1), 78/95 patients (82.1%) showed probable pedal fungal infections, of which 84.6% (66/78) were mycologically confirmed by direct microscopy and/or culture. The dermatophyte Trichophyton rubrum was the most common (69.2% of isolates). Significant correlation was found between infection and the gender (men more frequently affected) and the age of the patients. Marked mycoses on the soles of the feet were often considered to be dry skin by the patients. In a second study, 174 [31 DM1, 112 DM2 and 29 healthy accompanying persons (HAP), family members without DM] participants at a regional patients' symposium on diabetes took part in an examination for fungal infections and neuropathy of the feet. In addition to the items of the first study, we gathered data on the quality of blood glucose control (HbA1c), peripheral neuropathy (neuropathy symptome and deficit score) and measurement of sudomotoric activity by Neuropad. Mean duration of disease was 23.6 (DM1) and 11.2 (DM2) years, mean HbA1c 7.56% (DM1) and 6.89% (DM2) and fungal foot infections were confirmed at 35.5% (DM1), 53.1% (DM2) and 37.9% (HAP) respectively. In DM2, the prevalence of positive fungal samples is significantly higher for participants with less controlled blood glucose (higher HbA1c) (P = 0.04). Mycotic foot infection is also correlated with age, gender and duration of diabetes disease. Of special interest is the finding of relatively high numbers of black fungi ('Dematiaceae') (n = 10), Phialophora europea (n = 3) being the most common one. The sudomotoric activity was impaired in a very high number of participants [107/171 (61.5%)], and was found positively correlated with the prevalence of fungal foot infection in DM2 but not in DM1 and HAP. The high prevalence of fungal infections detected in DM1 as well as in DM2 diabetics is remarkable, especially considering this highly motivated collective. Therefore, it appears that the feet of diabetics require more diagnostic, therapeutic and preventive care in terms of mycotic infections and sudomotoric dysfunction than previously thought.
Assuntos
Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Dermatoses do Pé/epidemiologia , Micoses/epidemiologia , Onicomicose/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia , Pé Diabético/prevenção & controle , Feminino , Dermatoses do Pé/microbiologia , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/microbiologia , Onicomicose/microbiologia , Phialophora/isolamento & purificação , Prevalência , Inquéritos e Questionários , Sudorese/fisiologia , Trichophyton/isolamento & purificaçãoRESUMO
AIMS/HYPOTHESIS: The Krüppel-like factor 11 (KLF11; TIEG2), a pancreas-enriched Sp1-like transcription factor, is a known negative regulator of pancreatic exocrine cell growth. A recent study indicated KLF11-induced activation of the human proinsulin promoter (hInsP). MATERIALS AND METHODS: We investigated the functional role of KLF11 in pancreatic beta cells. RESULTS: Endogenous KLF11 mRNA expression was found in whole rat pancreas, human pancreatic islets and INS-1E beta cells and was profoundly reduced by high glucose in INS-1E. Cotransfections of INS-1E and beta-TC3 beta cells with a human (h)KLF11 expression plasmid and an hInsP-driven reporter plasmid resulted in a substantial dose-dependent and glucose-independent inhibition of proinsulin promoter activity. 5'-deletion of hInsP demonstrated that hKLF11 acts via DNA sequences upstream of -173 and requires the beta cell-specific transcription machinery, since hKLF11-mediated inhibition of promoter activity was abolished in HEK293 cells. Besides a previously described GC box, we further identified a CACCC box within the hInsP, both putative KLF11-binding motifs. Electrophoretic mobility shift analysis (EMSA) verified binding of in vitro translated hKLF11 to the GC box, but neither hKLF11-induced inhibition nor basal hInsP activity was altered by mutation or 5'-deletion of the GC box. In contrast, CACCC box mutation substantially reduced basal promoter activity and partially diminished hKLF11 inhibition, although binding of in vitro translated hKLF11 to the CACCC box could not be verified by EMSA. CONCLUSIONS/INTERPRETATION: In rodent beta cell lines, we demonstrate hKLF11overexpression-mediated inhibition [corrected] of human proinsulin gene expression and characterise a prominent role for the CACCC box in maintaining basal proinsulin promoter activity.
Assuntos
Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proinsulina/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteínas Reguladoras de Apoptose , Sítios de Ligação , Linhagem Celular , Regulação da Expressão Gênica , Glucose/metabolismo , Humanos , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/citologia , Mutação , Plasmídeos/metabolismo , Proinsulina/biossíntese , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Fator de Transcrição Sp1RESUMO
HISTORY AND CLINICAL FINDINGS: A 69-year-old man was admitted to our hospital with severe headache, recurrent episodes of fever and deterioration of general health. He returned from a vacation in Tuscany (Italy) a few days before admission. Physical examination revealed slight nuchal rigidity and an elevated body temperature of 37.8 C but was otherwise unremarkable. INVESTIGATIONS: Differential blood count showed a lymphocytopenia. Other abnormal laboratory findings included an elevated blood sedimentation rate and a slightly increased C-reactive protein value. Abdominal sonography demonstrated a marginally enlarged spleen. DIAGNOSIS, TREATMENT AND CLINICAL COURSE: A lumbar puncture was performed. Cerebrospinal fluid analysis revealed a lymphocytic meningitis. Serological examination of a blood sample showed specific IgM-antibodies against sandfly fever Naples virus (SFNV), subtype Toscana virus (TOSV). After this diagnosis had been made initially instituted intravenous administration of antibiotics and antiviral medication were discontinued. The patient's symptoms improved rapidly under symptomatic treatment. Slight headaches without episodes of fever persisted for a few weeks without residual neurological symptoms. CONCLUSIONS: A history of travel should always be sought in patients with clinical signs for meningitis. Considering the increasing spread and incidence of SFNV and its subtype Toscana in mediterranean countries, such virus should be kept in mind when treating patients who present such symptoms after returning from those countries during the summer season.
Assuntos
Febre de Causa Desconhecida/etiologia , Meningite Viral/diagnóstico , Febre por Flebótomos/diagnóstico , Vírus da Febre do Flebótomo Napolitano , Viagem , Aciclovir/uso terapêutico , Idoso , Antivirais/uso terapêutico , Ceftriaxona/uso terapêutico , Diagnóstico Diferencial , Quimioterapia Combinada , Alemanha , Humanos , Masculino , Meningite Viral/tratamento farmacológico , Meningite Viral/transmissão , Febre por Flebótomos/tratamento farmacológico , Febre por Flebótomos/transmissãoRESUMO
INTRODUCTION: The aim of the study was to determine the prevalence of vitamin D deficiency, secondary hyperparathyroidism (sHPT), generalized bone pain and predictors of vitamin D deficiency in a cohort of 994 healthy adult urban residents (589 males, 405 females; age range: 16-69 years) consisting of 101 Germans, 327 Turkish residents of Turkey and 566 Turkish immigrants living in Germany. METHODS: The mean (+/- standard deviation) for 25-hydroxyvitamin D [25(OH)D] and biointact parathyroid hormone (BioPTH) for the German men and women was 68.4 nmol/l and 26.7 pg/ml, respectively. Turkish residents of Turkey had a mean 25(OH)D and BioPTH of 40.6 nmol/l and 27.5 pg/ml, respectively, whereas Turkish residents of Germany had a 25(OH)D of 38.1 nmol/l and a BioPTH of 35.6 pg/ml. RESULTS: Vitamin D insufficiency was common among Turkish nationals independent of whether they lived in Turkey or Germany; 75% had 25(OH)D levels of <50 nmol/l. Turkish females had a higher prevalence of 25(OH)D deficiency (<25 nmol/l) than Turkish males: 30 and 19% of Turkish females living in Germany and Turkey were severely vitamin D deficient compared to 8% and 6% of Turkish males living in Germany and Turkey, respectively. With respect to BioPTH levels, 31% of Turkish females and 21% of Turkish males had elevated BioPTH levels in contrast to only 15% of females and 4% of males living in Turkey. Unconditional logistic regression analysis identified the most important predictors for low 25(OH)D levels as sex, body mass index, lack of sun exposure and living at a higher latitude. Additionally, wearing a scarf and number of children were found to be an independent risk factor for vitamin D deficiency in Turkish women living in Turkey and Germany. A strong correlation between low 25(OH)D levels and higher rates and longer duration of generalized bone and/or muscle aches and pains (often diagnosed as fibromyalgia) was observed. CONCLUSION: Secondary hyperparathyroidism and vitamin D deficiency was found to be common among Turkish immigrants living in Germany, especially in veiled women. Therefore, the monitoring of vitamin D status--i.e. 25(OH)D and PTH--in Turkish immigrants is warranted and once a deficiency is identified, it should be appropriately treated.
Assuntos
Emigração e Imigração , Fibromialgia/epidemiologia , Hiperparatireoidismo Secundário/epidemiologia , Osteomalacia/epidemiologia , Deficiência de Vitamina D/epidemiologia , Adolescente , Adulto , Idoso , Cálcio/sangue , Estudos Transversais , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Prevalência , Fatores de Risco , Turquia , Vitamina D/análogos & derivados , Vitamina D/sangueRESUMO
The long-term normalization of glucose metabolism - a prerequisite for the prevention of secondary complications in patients with diabetes mellitus - is only possible by transplantation of a whole pancreas or a reasonable number of islets. An absolute indication for pancreas grafting is given in type 1 diabetic patients with end-stage renal disease. The 1-year survival after simultaneous kidney/pancreas transplantation is, according to the international registry, 94-100% for patients, 89-92% for kidneys and 85-87% for the pancreas. The high success rate with long lasting normalization of glucose metabolism leads to a stabilization and/or amelioration of secondary complications, to an increase in quality of life and, most importantly, to a significant reduction in mortality when compared to diabetic kidney recipients. The indications for islet transplantation are similar to those for pancreatic grafting. Islet grafting is only a minor surgical procedure, but islet isolation is difficult. The 1-year survival for the recipients is 98%, for the islets 82% and for insulin-independency 42%. There is a significant decline of islet function to 10% 5 years after transplantation. Stem cell therapy would provide a definitive treatment solution not only for patients with type 1 diabetes. So far, this therapeutic option is still at an early stage of development.