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Evidence-based reviews of drugs causing medication-induced salivary gland dysfunction, such as xerostomia (sensation of oral dryness) and subjective sialorrhea are lacking. To compile a list of medicaments that influence salivary gland function, electronic databases were searched for relevant articles published up to June 2013. A total of 269 papers out of 3,867 records located satisfied the inclusion criteria (relevance, quality of methodology, strength of evidence). A total of 56 active substances with a higher level of evidence and 50 active substances with a moderate level of evidence of causing salivary gland dysfunction are described in this article. While xerostomia was a commonly reported outcome, the objective effect on salivary secretion was rarely measured. Xerostomia was, moreover, mostly reported as a negative side effect instead of the intended effect of that drug. A comprehensive list of medications having documented effects on salivary gland function or symptoms was compiled, which may assist practitioners in assessing patients who complain of dry mouth while taking medications.
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Glândulas Salivares/efeitos dos fármacos , Xerostomia/etiologia , HumanosRESUMO
Disorders of sex development (DSD), are a group of rare congenital conditions. Unlike 46, XX DSD where the cause is usually clear, identification of a cause of XY DSD is often unclear and may be attributed to a disorder of gonadal development, androgen synthesis or androgen action. Reaching a firm diagnosis is challenging and requires expertise within a framework that abides by the highest standards of clinical care. Whilst conditions associated with altered sex development have improved our fundamental understanding of sex and gonadal development, it is debatable whether this improvement in our understanding has improved the lives of people with DSD. Thus, there is a need for more emphasis on showing that a firm diagnosis for conditions associated with DSD is associated with a change in clinical practice that benefits the patient. With the rapid advances in diagnostic technology, there is also a need for clearer guidance on the relative merits of biochemical vs genetic evaluation. The standardization and harmonization of complex genetic and biochemical analyses for rare conditions are issues that require further guidance and it is probably that international networks and registries for rare conditions will facilitate the development of this framework.
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Transtornos do Desenvolvimento Sexual/diagnóstico , Transtornos do Desenvolvimento Sexual/genética , Gônadas/crescimento & desenvolvimento , Desenvolvimento Sexual/genética , Androgênios/genética , Transtornos do Desenvolvimento Sexual/patologia , Feminino , Humanos , MasculinoRESUMO
STUDY QUESTION: What is the likelihood of identifying genetic or endocrine abnormalities in a group of boys with 46, XY who present to a specialist clinic with a suspected disorder of sex development (DSD)? SUMMARY ANSWER: An endocrine abnormality of the gonadal axis may be present in a quarter of cases and copy number variants (CNVs) or single gene variants may be present in about half of the cases. WHAT IS KNOWN ALREADY: Evaluation of 46, XY DSD requires a combination of endocrine and genetic tests but the prevalence of these abnormalities in a sufficiently large group of boys presenting to one specialist multidisciplinary service is unclear. STUDY, DESIGN, SIZE, DURATION: This study was a retrospective review of investigations performed on 122 boys. PARTICIPANTS/MATERIALS, SETTING, METHODS: All boys who attended the Glasgow DSD clinic, between 2010 and 2015 were included in the study. The median external masculinization score (EMS) of this group was 9 (range 1-11). Details of phenotype, endocrine and genetic investigations were obtained from case records. MAIN RESULTS AND THE ROLE OF CHANCE: An endocrine abnormality of gonadal function was present in 28 (23%) with a median EMS of 8.3 (1-10.5) whilst the median EMS of boys with normal endocrine investigations was 9 (1.5-11) (P = 0.03). Endocrine abnormalities included a disorder of gonadal development in 19 (16%), LH deficiency in 5 (4%) and a disorder of androgen synthesis in 4 (3%) boys. Of 43 cases who had array-comparative genomic hybridization (array-CGH), CNVs were reported in 13 (30%) with a median EMS of 8.5 (1.5-11). Candidate gene analysis using a limited seven-gene panel in 64 boys identified variants in 9 (14%) with a median EMS of 8 (1-9). Of the 21 boys with a genetic abnormality, 11 (52%) had normal endocrine investigations. LIMITATIONS, REASONS FOR CAUTION: A selection bias for performing array-CGH in cases with multiple congenital malformations may have led to a high yield of CNVs. It is also possible that the yield of single gene variants may have been higher than reported if the investigators had used a more extended gene panel. WIDER IMPLICATIONS OF THE FINDINGS: The lack of a clear association between the extent of under-masculinization and presence of endocrine and genetic abnormalities suggests a role for parallel endocrine and genetic investigations in cases of suspected XY DSD. STUDY FUNDING/COMPETING INTEREST(S): RN was supported by the James Paterson Bursary and the Glasgow Children's Hospital Charity Summer Scholarship. SFA, RM and EST are supported by a Scottish Executive Health Department grant 74250/1 for the Scottish Genomes Partnership. EST is also supported by MRC/EPSRC Molecular Pathology Node and Wellcome Trust ISSF funding. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: None.
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Transtorno 46,XY do Desenvolvimento Sexual/diagnóstico , Testes Genéticos/métodos , Hormônios Esteroides Gonadais/sangue , Biomarcadores/sangue , Criança , Pré-Escolar , Hibridização Genômica Comparativa , Transtorno 46,XY do Desenvolvimento Sexual/sangue , Transtorno 46,XY do Desenvolvimento Sexual/epidemiologia , Transtorno 46,XY do Desenvolvimento Sexual/genética , Genótipo , Humanos , Lactente , Masculino , Fenótipo , Prevalência , Estudos RetrospectivosRESUMO
The aim of this paper was to perform a systematic review of the pathogenesis of medication-induced salivary gland dysfunction (MISGD). Review of the identified papers was based on the standards regarding the methodology for systematic reviews set forth by the World Workshop on Oral Medicine IV and the PRISMA statement. Eligible papers were assessed for both the degree and strength of relevance to the pathogenesis of MISGD as well as on the appropriateness of the study design and sample size. A total of 99 papers were retained for the final analysis. MISGD in human studies was generally reported as xerostomia (the sensation of oral dryness) without measurements of salivary secretion rate. Medications may act on the central nervous system (CNS) and/or at the neuroglandular junction on muscarinic, α-and ß-adrenergic receptors and certain peptidergic receptors. The types of medications that were most commonly implicated for inducing salivary gland dysfunction were those acting on the nervous, cardiovascular, genitourinary, musculoskeletal, respiratory, and alimentary systems. Although many medications may affect the salivary flow rate and composition, most of the studies considered only xerostomia. Thus, further human studies are necessary to improve our understanding of the association between MISGD and the underlying pathophysiology.
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Doenças das Glândulas Salivares/induzido quimicamente , Glândulas Salivares/efeitos dos fármacos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Medicina Bucal/métodos , Doenças das Glândulas Salivares/patologia , Glândulas Salivares/patologiaRESUMO
An investigation is made of the influence of subglottal boundary conditions on the prediction of voiced sounds. It is generally assumed in mathematical models of voicing that vibrations of the vocal folds are maintained by a constant subglottal mean pressure pI, whereas voicing is actually initiated by contraction of the chest cavity until the subglottal pressure becomes large enough to separate the vocal folds. The problem is reformulated to determine voicing characteristics in terms of a prescribed volumetric flow rate Qo of air from the lungs-the evolution of the resulting time-dependent subglottal mean pressure p[overline]-(t) is then governed by glottal mechanics, the aeroacoustics of the vocal tract, and the influence of continued contraction of the lungs. The new problem is analyzed in detail for an idealized mechanical vocal system that permits precise specification of all boundary conditions. Predictions of the glottal volume velocity pulse shape are found to be in good general agreement with the traditional constant-pI theory when pI is set equal to the time averaged value of p[overline]-(t). But, in all cases examined the constant-pI approximation yields values of the mean flow rates Qo and sound pressure levels that are smaller by as much as 10%.
Assuntos
Glote/fisiologia , Pulmão/fisiologia , Fonação , Voz , Fenômenos Biomecânicos , Simulação por Computador , Humanos , Modelos Biológicos , Contração Muscular , Análise Numérica Assistida por Computador , Pressão , Músculos Respiratórios/fisiologia , Fatores de Tempo , VibraçãoRESUMO
The voice source is dominated by aeroacoustic sources downstream of the glottis. In this paper an investigation is made of the contribution to voiced speech of secondary sources within the glottis. The acoustic waveform is ultimately determined by the volume velocity of air at the glottis, which is controlled by vocal fold vibration, pressure forcing from the lungs, and unsteady backreactions from the sound and from the supraglottal air jet. The theory of aerodynamic sound is applied to study the influence on the fine details of the acoustic waveform of "potential flow" added-mass-type glottal sources, glottis friction, and vorticity either in the glottis-wall boundary layer or in the portion of the free jet shear layer within the glottis. These sources govern predominantly the high frequency content of the sound when the glottis is near closure. A detailed analysis performed for a canonical, cylindrical glottis of rectangular cross section indicates that glottis-interior boundary/shear layer vortex sources and the surface frictional source are of comparable importance; the influence of the potential flow source is about an order of magnitude smaller.
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Glote/anatomia & histologia , Acústica da Fala , Voz/fisiologia , Feminino , Glote/fisiologia , Humanos , Masculino , Modelos Biológicos , Pressão , Reologia , Prega Vocal/anatomia & histologia , Prega Vocal/fisiologiaRESUMO
An analysis is made of the fluid-structure interactions necessary to support self-sustained oscillations of a single-mass mechanical model of the vocal folds subject to a nominally steady subglottal overpressure. The single-mass model of Fant and Flanagan is re-examined and an analytical representation of vortex shedding during 'voiced speech' is proposed that promotes cooperative, periodic excitation of the folds by the glottal flow. Positive feedback that sustains glottal oscillations is shown to occur during glottal contraction, when the flow separates from the 'trailing edge' of the glottis producing a low pressure 'suction' force that tends to pull the folds together. Details are worked out for flow that can be regarded as locally two-dimensional in the glottal region. Predictions of free-streamline theory are used to model the effects of quasi-static variations in the separation point on the glottal wall. Numerical predictions are presented to illustrate the waveform of the sound radiated towards the mouth from the glottis. The theory is easily modified to include feedback on the glottal flow of standing acoustic waves, both in the vocal tract beyond the glottis and in the subglottal region.
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BACKGROUND: Children's oral health-related quality of life (COHQoL) measures are well known and widely used. However, rigorous systematic reviews of these measures and analyses of their quality are in absence. OBJECTIVES: To systematically review and quantitatively assess the quality of COHQoL measures through a scoping review. DATA SOURCES: Systematic literature search of PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), EMBASE (Excerpta Medica database), HaPI (Health and Psychosocial Instruments), and DOSS (Dentistry and Oral Sciences Source). STUDY ELIGIBILITY: The measure's focus was COHQoL; the child age ranged from 5 to 14 years; the publication was either a research article or a systematic review and related to caries; and it was written in English or had an English abstract. Two authors independently selected the studies. Disagreements were reconciled by group discussions with a third author. APPRAISAL: The International Society for Quality of Life Research minimum standards for patient-reported outcome measures were used for quality appraisal. SYNTHESIS: Descriptive analysis. RESULTS: We identified 18 measures. Their quality scores ranged from 9.5 to 15.0 on a scale of 16. The quality appeared to bear no relationship to the citation and use of these measures. However, elements of these measures might be more useful than others, depending on the age-specific use and primary quality concerns. LIMITATIONS: Some of the information on the minimum standards of the 18 measures cannot be found in the existing literature. Measures published without English abstract were not searched. CONCLUSIONS: The quality of these measures is suboptimal. Researchers and practitioners in this field should exercise caution when choosing and using these measures. Efforts at improving the quality of the COHQoL measures, such as refining existing ones or developing new measures, are warranted. KNOWLEDGE TRANSFER STATEMENT: Researchers, clinician scientists, and clinicians can use the results of this study when deciding which oral health-related quality of life measure they wish to use in children.
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Cárie Dentária , Qualidade de Vida , Adolescente , Criança , Pré-Escolar , Família , Humanos , Saúde BucalRESUMO
The differential diagnosis of differences or disorders of sex development (DSD) belongs to the most complex fields in medicine. It requires a multidisciplinary team conducting a synoptic and complementary approach consisting of thorough clinical, hormonal and genetic workups. This position paper of EU COST (European Cooperation in Science and Technology) Action BM1303 'DSDnet' was written by leading experts in the field and focuses on current best practice in genetic diagnosis in DSD patients. Ascertainment of the karyotpye defines one of the three major diagnostic DSD subclasses and is therefore the mandatory initial step. Subsequently, further analyses comprise molecular studies of monogenic DSD causes or analysis of copy number variations (CNV) or both. Panels of candidate genes provide rapid and reliable results. Whole exome and genome sequencing (WES and WGS) represent valuable methodological developments that are currently in the transition from basic science to clinical routine service in the field of DSD. However, in addition to covering known DSD candidate genes, WES and WGS help to identify novel genetic causes for DSD. Diagnostic interpretation must be performed with utmost caution and needs careful scientific validation in each DSD case.
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Transtornos do Desenvolvimento Sexual/diagnóstico , Sequenciamento do Exoma , Cariótipo , Sequenciamento Completo do Genoma , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/genética , Variações do Número de Cópias de DNA , Transtornos do Desenvolvimento Sexual/genética , União Europeia , Disgenesia Gonadal/diagnóstico , Disgenesia Gonadal/genética , Humanos , Biologia Molecular , Técnicas de Diagnóstico Molecular , Guias de Prática Clínica como Assunto , Análise de Sequência de DNARESUMO
All inbred strains of mice carry the Ren-1 structural gene, which encodes the renin-1 isozyme, the classical renin activity found in kidneys. In addition, some strains carry a second renin structural gene, Ren-2, which encodes the predominantly expressed submaxillary gland renin isozyme, renin-2. Ren-1 and Ren-2 exhibit markedly different patterns of tissue-specific expression. In an effort to understand the molecular basis for this differential expression, detailed analysis of the genomic sequences corresponding to the Ren-1 and Ren-2 genes, and the transcripts originating from these loci, was undertaken. Sequence analysis of regions proximal to the structural genes indicated the presence of eucaryotic consensus sequences for transcription. These sequence motifs were strongly conserved between Ren-1 and Ren-2. Approximately 150 bases upstream from the major transcription initiation site, significant differences between these genes were apparent, including the presence of a repetitive DNA element in the Ren-2 copy as well as other breaks in homology and sequence curiosities. Strong homology between Ren-1 and Ren-2 resumed at a point ca. 200 bases further upstream on Ren-1. S1 analysis of submaxillary gland and kidney RNA populations indicated that the majority of transcripts initiate at homologous positions on Ren-1 and Ren-2. On a per cell basis, the accumulation of Ren-1 transcripts in the kidney and Ren-2 transcripts in the submaxillary gland are probably equivalent. These results suggest that it is tissue-specific utilization of the homologous start sites that is critical to their differential patterns of expression. Models which can account for this observation are presented. Interestingly, we found a minor fraction of transcripts initiating 5' to the major transcription start site. These transcripts encoded an open reading frame which may add an additional 23 amino acids to the N-terminus of the renin precursor.
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Renina/genética , Animais , Sequência de Bases , Clonagem Molecular , Regulação da Expressão Gênica , Genes , Camundongos , Camundongos Endogâmicos BALB C/genética , Camundongos Endogâmicos DBA/genética , Modelos Genéticos , Transcrição GênicaRESUMO
It is commonly assumed that cats actively avoid eliminated materials (especially in multi-cat homes), suggesting regular litter box cleaning as the best defense against out-of-box elimination. The relationship between previous use and litter box appeal to familiar subsequent users is currently unknown. The purpose of this study was to investigate the relationship between previous litter box use and the identity of the previous user, type of elimination, odor, and presence of physical/visual obstructions in a multi-cat household scenario. Cats preferred a clean litter box to a dirty one, but the identity of the previous user had no impact on preferences. While the presence of odor from urine and/or feces did not impact litter box preferences, the presence of odorless faux-urine and/or feces did - with the presence of faux-feces being preferred over faux-urine. Results suggest neither malodor nor chemical communication play a role in litter box preferences, and instead emphasize the importance of regular removal of physical/visual obstructions as the key factor in promoting proper litter box use.
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Comportamento Animal/fisiologia , Gatos/psicologia , Defecação/fisiologia , Comportamento Social , Animais , Fezes , Feminino , Masculino , OdorantesRESUMO
Fetuses were examined to produce a developmental profile of renin expression in the kidneys and adrenal glands in single renin gene and two renin gene strains of mice. Sites of renin expression were detected by in situ hybridization using an 35S-labeled antisense RNA probe complimentary to the renin cDNA. Accumulation of renin transcripts in the adrenal gland reached a maximum at 15.5 days post coitum for all strains examined, but declined to undetectable levels by birth in one gene strains, while in two gene strains, the levels of renin transcripts lessened and by birth became limited to the developing inner cortex. Kidney renin transcripts were first detected at 14.5 days post coitum in the newly developing arteries in fetuses of both genotypes of mice. As the renal arterial tree developed, renin mRNA containing cells were progressively localized to more distal blood vessels and finally to the specialized cells of the afferent arteriole (juxtaglomerular cells). These results were confirmed by examining the localization of immunoreactive T antigen in transgenic fetuses. These mice carried a transgene which placed the SV40 T antigen structural gene under control of renin regulatory elements. Expression of T antigen occurred at the same sites in the kidneys and adrenal glands as renin mRNA. Furthermore, in strains with two renin genes, primer extension analysis indicated transcripts from both genes were present in equal proportion in combined kidney and adrenal gland extracts of total RNA. These transcripts were full length in size. The transient localization of renin mRNA in cells of the fetal intrarenal arteries is consistent with the notion that renin may be a useful marker for the developing renal vasculature.
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Desenvolvimento Embrionário e Fetal/genética , Feto/metabolismo , Renina/genética , Glândulas Suprarrenais/citologia , Glândulas Suprarrenais/metabolismo , Animais , Antígenos Transformantes de Poliomavirus/genética , Antígenos Transformantes de Poliomavirus/metabolismo , Feto/citologia , Feto/fisiologia , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/fisiologia , Imuno-Histoquímica , Rim/citologia , Rim/metabolismo , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Renina/metabolismo , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/fisiologiaRESUMO
The aims of this paper are three-fold: (1) to summarize the current epidemiological data on oral cancer in Libya as reported in the published literature and as compared to other national oral cancer rates in the region; (2) to present both the history of the early development, and future goals, of population-based oral cancer tumor registries in Libya as they partner with the more established regional and international population-based cancer tumor registries; and, (3) to offer recommendations that will likely be required in the near future if these nascent, population-based Libyan oral cancer registries are to establish themselves as on-going registries for describing the oral cancer disease patterns and risk factors in Libya as well as for prevention and treatment. This comprehensive literature review revealed that the current baseline incidence of oral cancer in Libya is similar to those of other North Africa countries and China, but is relatively low compared to the United Kingdom, the United States, and India. The recently established Libyan National Cancer Registry Program, initiated in 2007, while envisioning five cooperating regional cancer registries, continues to operate at a relatively suboptimal level. Lack of adequate levels of national funding continue to plague its development and the accompanying quality of service that could be provided to the Libyan people.
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OBJECTIVE: To determine the efficacy and safety of interventions for mucous membrane pemphigoid (MMP). STUDY DESIGN: We conducted a systematic review from 2003 to 2013 according to the Cochrane Collaboration methodology. Randomized controlled trials (RCTs) or controlled clinical trials and observational studies were included, with diagnosis confirmed by clinical, histopathologic, and immunofluorescence criteria. The primary outcome was lesion remission or healing; several relevant secondary outcomes were also included. RESULTS: In the final analysis, 1 RCT and 32 observational studies were included. The one included RCT with a high risk of bias in multiple domains found limited evidence that pentoxifylline, combined with corticosteroid and cyclophosphamide, was more effective than standard therapy (corticosteroid + cyclophosphamide alone) for ocular MMP. We summarize here the outcomes from 32 observational studies examining 242 patients across 19 unique treatments. Interventions that show promise include rituximab and intravenous immunoglobulin. CONCLUSIONS: This systematic review is the most recent since 2003-2009. There is still lack of high-quality research providing evidence-based MMP treatments.
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Penfigoide Mucomembranoso Benigno/tratamento farmacológico , Anti-Infecciosos/uso terapêutico , Ciclofosfamida/uso terapêutico , Dapsona/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
This narrative review of the functions of saliva was conducted in the PubMed, Embase and Web of Science databases. Additional references relevant to the topic were used, as our key words did not generate references which covered all known functions of saliva. These functions include maintaining a moist oral mucosa which is less susceptible to abrasion, and removal of micro-organisms, desquamated epithelial cells, leucocytes and food debris by swallowing. The mucins form a slimy coating on all surfaces in the mouth and act as a lubricant during such processes as mastication, formation of a food bolus, swallowing and speaking. Saliva provides the fluid in which solid tastants may dissolve and distributes tastants around the mouth to the locations of the taste buds. The hypotonic unstimulated saliva facilitates taste recognition. Salivary amylase is involved in digestion of starches. Saliva acts as a buffer to protect oral, pharyngeal and oesophageal mucosae from orally ingested acid or acid regurgitated from the stomach. Saliva protects the teeth against acid by contributing to the acquired enamel pellicle, which forms a renewable lubricant between opposing tooth surfaces, by being supersaturated with respect to tooth mineral, by containing bicarbonate as a buffer and urea and by facilitating clearance of acidic materials from the mouth. Saliva contains many antibacterial, antiviral and antifungal agents which modulate the oral microbial flora in different ways. Saliva also facilitates the healing of oral wounds. Clearly, saliva has many functions which are needed for proper protection and functioning of the human body.
Assuntos
Saliva/fisiologia , Cariogênicos , Humanos , Lubrificação , Mucosa Bucal/fisiologia , Percepção Olfatória/fisiologia , Saliva/química , Saliva/metabolismo , Proteínas e Peptídeos Salivares/fisiologia , Taxa Secretória , Percepção Gustatória/fisiologia , Doenças Dentárias/prevenção & controle , Cicatrização/fisiologiaRESUMO
OBJECTIVE: To determine the efficacy and safety of interventions for pemphigus vulgaris (PV). STUDY DESIGN: We conducted a systematic review from 2003 to 2013 according to the Cochrane Collaboration methodology. Randomized controlled trials (RCTs) or controlled clinical trials (CCTs) and observational studies were conducted along with diagnosis confirmed by clinical, histopathologic, and immunofluorescence criteria. Primary outcomes were disease remission and mortality; several relevant secondary outcomes were also included. RESULTS: Fourteen RCTs or CCTs and 110 observational studies were included in the final analyses. RCTs or CCTs demonstrated considerable heterogeneity in outcome measures, and all had a high risk of bias for at least 1 of 8 domains. Of the studies, 96.8% (120) described the use of oral corticosteroids. Azathioprine and mycophenolate-mofetil were the most commonly cited treatments. An increasing number of studies described biologic therapies (rituximab, intravenous immunoglobulin [IVIg]). Evidence supporting recent comprehensive treatment guidelines was reviewed. CONCLUSIONS: We found persisting wide variations in treatment practice and inadequate quality of research supporting optimal PV treatment.
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Doenças da Boca/tratamento farmacológico , Pênfigo/tratamento farmacológico , Humanos , Doenças da Boca/diagnóstico , Doenças da Boca/epidemiologia , Pênfigo/diagnóstico , Pênfigo/epidemiologia , Indução de RemissãoRESUMO
Several experimental procedures produce dramatic alterations in kidney renin production, leading to increased plasma renin levels with attendant hypertension in animal model systems. The pattern of changes for kidney renin messenger RNA (mRNA) levels relative to changes for tissue and plasma renin activity was studied in Sprague-Dawley rats made hypertensive by either coarctation of the aorta between the two renal arteries or clipping of the left renal artery. In both models, the renin mRNA content of the contralateral hypertrophied kidney transiently decreased to undetectable levels while the ischemic kidney exhibited transient increases in renin mRNA. In aorta-coarctated rats ischemic kidney renin mRNA increased 10-fold to 16-fold during the first 3 days after coarctation but returned to the level observed in sham-operated rats 14 days after operation. However, differences between the time course and magnitude of changes in renin mRNA levels and the pattern of alteration in tissue and plasma renin activities were observed. Thus, although the kidney renin mRNA transiently increased in hypertensive animals, the extent of this increase was insufficient to account for the 30-fold to 50-fold increases in plasma renin activity. Similarly, the transient increase in kidney renin mRNA was inconsistent with only a twofold increase in tissue renin enzyme activity of the ischemic kidney. These data indicate that in addition to alterations in the kidney renin mRNA pool, posttranslational processing and/or release of renin from the kidney are cocontributors in regulating the plasma renin levels in these experimental models.
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Hipertensão Renovascular/genética , Processamento de Proteína Pós-Traducional , RNA Mensageiro/metabolismo , Renina/metabolismo , Animais , DNA Recombinante , Hipertensão Renovascular/metabolismo , Rim/metabolismo , Masculino , Ratos , Ratos Endogâmicos , Renina/genéticaRESUMO
The Ren-1 locus of mice encodes the protease renin, which with converting enzyme processes angiotensinogen to the potent vasopressor angiotensin II. Some strains of mice appear to carry a duplication of the renin structural gene (Ren-2) near the Ren-1 locus. Strains with the gene duplication can exhibit as much as 100-fold higher levels of submaxillary gland renin compared to strains with a single gene copy. In contrast, kidney renin levels appear to be unaffected by the gene duplication. Sequence analysis of a 319 bp renin cDNA recombinant isolated from a kidney library from the two-gene strain DBA/2Ha corresponds to a transcript of the Ren-1 gene. Moreover, a single base substitution of A for G at residue #996 in the kidney renin mRNA creates a potential glycosylation recognition site that may, in part, account for the differential glycosylation of kidney and submaxillary gland renins. In addition, our tissue surveys indicate that mature mRNAs from the Ren loci are detectable in adrenal gland and testes, as well as sublingual and parotid salivary glands, and reveal length variation for the renin transcripts in at least the submaxillary gland.
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Camundongos/genética , Renina/genética , Animais , Aberrações Cromossômicas , Genes Reguladores , Rim/metabolismo , Camundongos/metabolismo , Renina/biossínteseRESUMO
PURPOSE: To evaluate prospectively the prevalence and pathophysiology of anorectal dysfunction following radiation therapy (RTH) for localized carcinoma of the prostate. METHODS AND MATERIALS: The following parameters of anorectal function were evaluated in each of 35 patients (aged 55-82 years) with localized prostatic carcinoma treated with RTH either to a dose of 55 Gy/20 fractions/4 weeks (18 patients) or 64 Gy/32 fractions/6.5 weeks (17 patients), before RTH and 4-6 weeks and at a mean (+/- SD) of 1.4 (+/- 0.2) years after its completion: (1) anorectal symptoms (questionnaire), (2) anorectal pressures at rest and in response to voluntary squeeze and increases in intra-abdominal pressure (multiport anorectal manometry), (3) rectal sensation (balloon distension) and (4) anal sphincteric morphology (endoanal ultrasound). RESULTS: All but 1 patient completed three series of measurements. RTH had no effect on anal sphincteric morphology. The increase in frequency of defecation and fecal urgency and incontinence scores previously reported in the patients 4-6 weeks after RTH were sustained 1 year later (p < 0.001, p < 0.001, and p < 0.05, cf. baseline, respectively). At this time, 56% (19 of 34), 50% (17 of 34) and 26% (9 of 34) of the patients had increased frequency of defecation, fecal urgency, and incontinence, respectively. Decreases in anal sphincteric pressures at rest and in response to voluntary squeeze recorded in the patients 4-6 weeks after RTH were not sustained 1 year later but the volumes of rectal distension associated with perception of the stimulus and desire to defecate were lower compared with baseline volumes (p < 0.01 and p < 0.05, respectively), reflecting heightened rectal sensitivity in the patients. There was no difference in measurements between the two radiation dose regimens. Univariate logistical regression analysis was performed on patients who had experienced increased symptom scores or decreases in recorded motor and sensory manometric parameters at 1 year, cf. baseline. The predictor variables used included individual patient tumor and treatment characteristics as well as individual patient symptom scores and parameters of anorectal motor and sensory function at baseline and 4-6 weeks after RTH. The results of the univariate logistical regression analysis showed that (1) frequency of defecation at 4-6 weeks and (2) rectal volumes at baseline both for (a) perception (p < 0.001) and (b) desire to defecate (p < 0.001), predicted significantly for the patients who had symptoms and signs of anorectal dysfunction at 1 year. Individual patient tumor and treatment-related variables tested, in contrast, had no predictive significance. CONCLUSIONS: Anorectal symptoms following RTH for prostatic carcinoma are common and persist at least until 1 year after its completion and are associated with objective evidence of heightened rectal sensitivity.
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Canal Anal/efeitos da radiação , Defecação/efeitos da radiação , Incontinência Fecal/etiologia , Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Canal Anal/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Pressão , Estudos Prospectivos , Dosagem Radioterapêutica , Análise de Regressão , Sensação , Fatores de TempoRESUMO
Noninvasive myocardial imaging with potassium-43 and rubidium-81 has been used successfully to identify areas of infarction and exercise-induced ischemia as regions of decreased radioactivity. The image defects observed are believed to be due to a decreased radionuclide uptake in regions of myocardial scar or to heterogeneous myocardial accumulation of tracer as a result of regional ischemia. Of 27 patients with left bundle branch block studied with noninvasive imaging at rest and during exercise, 25 manifested at rest reduced radioactivity in the region of the interventricular septum. This pattern is similar to that seen in patients with anteroseptal myocardial infarction. Sixteen of the 27 patients underwent diagnostic coronary arteriography and left ventriculography. Only five of these patients had evidence of either previous infarction or significant obstructive coronary artery disease as assessed with clinical or angiographic criteria, or both. Although the image defect was routinely demonstrated at rest in patients with left bundle branch block, this defect was generally normalized or less distinct with exercise in patients with no anatomic heart disease. In contrast, a larger, more distinct or new image defect with exercise correctly identified the presence of significant obstructive coronary artery disease in patients with left bundle branch block. In the clinical application of noninvasive myocardial imaging, these image defects observed at rest can lead to the false pasitive radionuclide interpretation of anteroseptal myocardial infarction.