RESUMO
Periodontitis has low-prevalence, highly severe disease manifestations with an early onset and rapid progression. The diagnosis is based on severe destruction of the alveolar bone in adolescents and young adults. Genetic susceptibility variants and smoking are well-established risk factors, but their interactions in modifying disease susceptibility have not been studied. We aimed to identify genetic risk variants of early-onset periodontitis that unmask their effects on tobacco smoke exposure. To this end, we analyzed 79,780,573 common variants in 741 northwest Europeans diagnosed to have >30% bone loss at >2 teeth before 35 y of age, using imputed genotypes of the OmniExpress BeadChip. Never versus ever smokers were compared in a logistic regression analysis via a case-only approach. To explore the effect of tobacco smoke on the expression of the G×S-associated genes, cultures of primary gingival fibroblasts (n = 9) were exposed to cigarette smoke extract, and transcripts were quantified by reverse transcription polymerase chain reaction. We identified 16 loci for which our analysis suggested an association with G×S increased disease risk (P < 5 × 10-5). Nine loci had previously been reported to be associated with spirometric measures of pulmonary function by an earlier G×S genome-wide association study. Genome-wide significant cis expression quantitative trait loci were reported for G×S-associated single-nucleotide polymorphisms at ST8SIA1 and SOST, indicating a causal role of these genes in tobacco-related etiopathology. Notably, SOST is a negative regulator of bone growth, and ST8SIA1 has a role in tissue remodeling. Cigarette smoke extract significantly altered the expression of 2 associated genes: SSH1 (P = 5 × 10-07), which is required for NF-κB activation and innate immune responses to bacterial invasion, and ST8SIA1 (P = 0.0048). We conclude that the genetic predisposition to early-onset periodontitis is in part triggered by smoking and that tobacco smoke directly affects the expression of genes involved in bone homeostasis, tissue repair, and immune response.
Assuntos
Periodontite Agressiva/genética , Fumar/efeitos adversos , Adolescente , Idade de Início , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Fosfoproteínas Fosfatases/genética , Fatores de Risco , Sialiltransferases/genética , Fumaça/efeitos adversos , Adulto JovemAssuntos
Resistência Microbiana a Medicamentos/efeitos dos fármacos , Prostatectomia , Infecções Urinárias/microbiologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Bactérias/isolamento & purificação , Bacteriúria/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/complicações , Cateterismo Urinário/efeitos adversos , Infecções Urinárias/etiologiaAssuntos
Úlcera Duodenal/tratamento farmacológico , Secretina/uso terapêutico , Adulto , Ensaios Clínicos como Assunto , Preparações de Ação Retardada , Avaliação de Medicamentos , Feminino , Suco Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Gastrinas/sangue , Humanos , Mucosa Intestinal/enzimologia , Mucosa Intestinal/ultraestrutura , Masculino , Pessoa de Meia-Idade , Suco Pancreático/metabolismo , Antro Pilórico/ultraestrutura , Testes Cutâneos , Fatores de TempoRESUMO
PURPOSE: Population-based data about patterns and prevalence of antidepressant drug use is limited in Europe and presently unavailable for Germany. Therefore, we have identified patterns and prevalence of antidepressant use among outpatients on a population-based scale in the German state of Baden-Wuerttemberg. METHODS: We conducted a historical cohort study using a computerised prescription database referring to all members of the major German public health insurance company AOK. We assessed the prevalence of antidepressant drug use over a 3-year period, calculated the number of prescription items purchased per patient and compared first-line and second-line treatments. RESULTS: The 1-year prevalence of antidepressant drug use among more than 4,000,000 health insurance members was 7.4% (male: 4.3%; female: 10.2%). Importantly, almost 40% of the patients received only a single prescription item from 2000 to 2002. Though the use of serotonin-reuptake inhibitors (SSRIs) markedly increased by about 65% within the study period, these are primarily used as second-line drugs and still much less frequently than St. John's wort or tricyclic antidepressants such as amitryptiline or doxepin. CONCLUSIONS: The prevalence of antidepressant drug use is higher than previously reported for other European countries. The preferred use of St. John's wort and tricyclics over SSRIs and other modern-type antidepressants in Germany is quite unique in Europe and different from the US. The identified drug use pattern leaves a major room for improvement in view of the numerous single prescription items purchased.
Assuntos
Antidepressivos/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Estudos de Coortes , Depressão/epidemiologia , Feminino , Alemanha , Humanos , Masculino , PrevalênciaRESUMO
A malnourished M. Crohn-patient developed severe symptoms similar to those of an acute polyneuropathy associated with a period of marked decrease of serum phosphate concentration during intravenous high-caloric infusions. After the serum phosphate concentration was normalized recovery from all neurologic symptoms followed within a few days. Based on this observation the possible consequences of severe hypophosphatemia are discussed.
Assuntos
Doenças do Sistema Nervoso/etiologia , Nutrição Parenteral/efeitos adversos , Fosfatos/deficiência , Adulto , Doença de Crohn/dietoterapia , Feminino , Humanos , Fosfatos/sangueRESUMO
Corafusin, an infusion solution containing lidocaine, electrolytes and sorbitol, was tested during 4-day continuous infusion of patients with myocardial infarction. The serum sodium level remained constant within the normal range whereas initially reduced serum potassium and magnesium concentration increased to normal within 24 hours. Both sodium and water balance were generally equilibrated during the entire test period. Testing of lactate and non-esterified fatty acids revealed a significant decrease within the first 24 hours. On the basis of these findings it can be concluded that the infusion solution tested is suited for lidocaine infusion therapy of patients with myocardial infarction.
Assuntos
Eletrólitos/metabolismo , Lidocaína/administração & dosagem , Infarto do Miocárdio/tratamento farmacológico , Homeostase , Humanos , Infusões Parenterais , Lidocaína/uso terapêutico , Magnésio/metabolismo , Potássio/metabolismo , Sódio/metabolismo , Sorbitol/metabolismoRESUMO
Shock is to define by clinical symptoms, measurable haemodynamic and metabolic changes, clotting failure and disorders of fluid, electrolyte and acid-base balance. It is essential to remove hypovolemia, acidosis, cardiovascular failure, pulmonary and renal insufficiency. Quite a lot of proved and controversial pharmacological substances are placed at physician's disposal. However, the mortality of cardiogenic shock and gram-negative septic shock is more than 80% respectively 30%, often caused by shock lung or irreversible injury to the kidneys. Shock due to depletion of extracellular fluid, poisoning and acute pancreatitis require specific treatment.
Assuntos
Choque/tratamento farmacológico , Bicarbonatos/uso terapêutico , Desidratação/tratamento farmacológico , Di-Hidroergotoxina/uso terapêutico , Furosemida/uso terapêutico , Glucagon/uso terapêutico , Humanos , Metilprednisolona/uso terapêutico , Diálise Peritoneal , Substitutos do Plasma , Choque Cardiogênico/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Espironolactona/uso terapêutico , Simpatomiméticos/uso terapêutico , Teofilina/análogos & derivados , Teofilina/uso terapêuticoRESUMO
85 women undergoing vacuum aspiration following miscarriage were studied. At the time of vacuum aspiration, immunofluorescent stainings for detection of C. trachomatis proved positive in 5.9% of the patients. Group B streptococci were isolated in 7.5%, coliforms in 3.5%, and Gardnerella vaginalis in 51% of the patients. The overall frequency of postabortal pelvic inflammatory disease (PID) was 3.5%, whereas 40% of chlamydia-positive women contracted postabortal PID (p less than 0.05). No significant relation between other microorganisms and postabortal PID was observed. The duration of postabortal bleeding was unrelated to the genital microbiologic flora. Based on anamnestic information about previous pregnancies and duration of preoperative bleeding it was possible to define subgroups at risk of harboring C. trachomatis and coliforms. The clinical significance of this is unknown.
Assuntos
Aborto Espontâneo/microbiologia , Colo do Útero/microbiologia , Dilatação e Curetagem , Curetagem a Vácuo , Vagina/microbiologia , Adolescente , Adulto , Feminino , Imunofluorescência , Humanos , Doença Inflamatória Pélvica/etiologia , Doença Inflamatória Pélvica/microbiologia , Gravidez , Estudos Prospectivos , Hemorragia Uterina/etiologia , Hemorragia Uterina/microbiologiaRESUMO
Salivary, gastric, and pancreatic secretory responses to intravenous 13-norleucine-motilin (13-nle-motilin), a synthetic analog of motilin and biologically equivalent to the natural polypeptide, were studied in healthy volunteers. 13-nle-Motilin in doses of 100 ng/kg body wt/hr significantly stimulated gastric pepsin output, while H + secretion and serum gastrin levels remained unchanged. Enhanced pepsin secretion was not accompanied by an increase in gastric secretion of cyclic 3', 5'-adenosine monophosphate, nor did gastric mucosal levels of the cyclic nucleotide rise. A dose of 13-nle-motilin, which stimulated gastric pepsin output, did not exert any significant effect on salivary and pancreatic secretions.