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1.
J Laryngol Otol ; 136(12): 1296-1303, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35791976

RESUMO

OBJECTIVE: To study unusual presentations of coronavirus-associated mucormycosis that are rarely seen in sinonasal mucormycosis cases. METHOD: The data of 400 rhino-orbito-cerebral mucormycosis patients admitted to Sawai Man Singh Hospital, Jaipur, from May 2021 to June 2021, were retrospectively collected. The diagnosis of mucormycosis was made by histological examination of biopsy samples. RESULTS: Out of 400 patients, 62 had symptoms other than common symptoms of rhino-orbito-cerebral mucormycosis. Thirty-four patients had facial palsy, 19 complained of gum ulcers, 6 developed a cheek abscess, 2 complained of maggots in the nose along with common rhino-orbito-cerebral mucormycosis symptoms, and 1 had a cerebellar infarct. CONCLUSION: Mucormycosis is a disease with various presentations, and coronavirus-associated mucormycosis has added unusual presentations to the existing list of manifestations of rhino-orbito-cerebral mucormycosis. In this coronavirus disease era, mucormycosis should always be considered as a diagnosis in patients with these unusual presentations.


Assuntos
Coronavirus , Mucormicose , Doenças Orbitárias , Humanos , Masculino , Mucormicose/complicações , Mucormicose/diagnóstico , Estudos Retrospectivos
2.
J Laryngol Otol ; 135(5): 442-447, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33827722

RESUMO

OBJECTIVE: To study the possible association between invasive fungal sinusitis (mucormycosis) and coronavirus disease. METHODS: A prospective observational study was conducted at a tertiary care centre over four months, involving all patients with mucormycosis of the paranasal sinuses suffering from or having a history of coronavirus disease infection. RESULTS: Twenty-three patients presented with mucormycosis, all had an association with coronavirus disease 2019. The ethmoids (100 per cent) were the most common sinuses affected. Intra-orbital extension was seen in 43.47 per cent of cases, while intracranial extension was only seen in 8.69 per cent. Diabetes mellitus was present in 21 of 23 cases, and was uncontrolled in 12 cases. All patients had a history of steroid use during their coronavirus treatment. CONCLUSION: New manifestations of coronavirus disease 2019 are appearing over time. The association between coronavirus and mucormycosis of the paranasal sinuses must be given serious consideration. Uncontrolled diabetes and over-zealous use of steroids are two main factors aggravating the illness, and both of these must be properly checked.


Assuntos
COVID-19/microbiologia , Mucorales/isolamento & purificação , Mucormicose/microbiologia , Seios Paranasais/microbiologia , Administração Intravenosa , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/virologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/microbiologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Mucorales/efeitos dos fármacos , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Mucormicose/etiologia , Pandemias , Seios Paranasais/diagnóstico por imagem , Estudos Prospectivos , SARS-CoV-2 , Sinusite/diagnóstico , Sinusite/microbiologia , Esteroides/efeitos adversos , Esteroides/uso terapêutico
3.
J Laryngol Otol ; 133(5): 368-375, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31064425

RESUMO

OBJECTIVE: To propose a new classification of inner-ear anomalies that is more clinically oriented and surgically relevant: the SMS (Sawai Man Singh) classification of cochleovestibular malformations. METHODS: A retrospective multicentric study was conducted of 436 cochlear implantations carried out in 3 Indian tertiary care institutes. Patients with anomalous anatomy were included and classified, as per the new SMS classification, into cochleovestibular malformation types I, II, III and IV, based on cochlear morphology, modiolus and lamina cribrosa. RESULTS: There were 19, 23, 8 and 4 patients with cochleovestibular malformation types I, II, III and IV, respectively. Two-year post-operative Meaningful Auditory Integration Scale scores were statistically analysed. CONCLUSION: This new classification for inner-ear anomalies is a simpler, more practical, outcome-oriented classification that can be used to better plan the surgery. These merits make it a more uniform classification for recording results.


Assuntos
Tomada de Decisão Clínica/métodos , Cóclea/anormalidades , Implante Coclear/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/classificação , Vestíbulo do Labirinto/anormalidades , Criança , Pré-Escolar , Feminino , Perda Auditiva Neurossensorial/congênito , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/cirurgia , Humanos , Índia , Masculino , Estudos Retrospectivos , Centros de Atenção Terciária
4.
J Laryngol Otol ; 132(6): 540-543, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30019665

RESUMO

OBJECTIVE: The study primarily aimed to calculate the orientation of the cochlea pre-operatively, using high-resolution computed tomography of the temporal bone, and predict the ease of electrode insertion. METHODS: Pre-operatively, high-resolution computed tomography scans were conducted on children scheduled for cochlear implantation, and two angles, α and ß, were calculated. The values of α and ß were then correlated with intra-operative difficulty in insertion of the electrode array. RESULTS: Ninety-six children were included in the study. Of the seven patients who had an α angle of less than 50 degrees, the surgeon experienced difficulties in electrode insertion. However, there were four patients with an α angle of more than 50 degrees for whom the surgeon also experienced difficulties in electrode insertion. In all these patients, the ß angle was more than 20 degrees. CONCLUSION: Calculation of cochlear orientation and its angle with the surgical axis (α and ß) can aid the planning of surgery, particularly with regard to the cochleostomy site and preservation of residual hearing.


Assuntos
Cóclea/diagnóstico por imagem , Implante Coclear/métodos , Perda Auditiva Neurossensorial/cirurgia , Osso Temporal/diagnóstico por imagem , Pré-Escolar , Cóclea/anatomia & histologia , Implantes Cocleares , Eletrodos Implantados , Feminino , Humanos , Lactente , Masculino , Cuidados Pré-Operatórios , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
5.
J Chem Phys ; 148(5): 054310, 2018 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-29421878

RESUMO

This work presents the analysis of non-equilibrium energy transfer and dissociation of nitrogen molecules (N2(Σg+1)) using two different approaches: the direct molecular simulation (DMS) method and the coarse-grain quasi-classical trajectory (CG-QCT) method. The two methods are used to study thermochemical relaxation in a zero-dimensional isochoric and isothermal reactor in which the nitrogen molecules are heated to several thousand degrees Kelvin, forcing the system into strong non-equilibrium. The analysis considers thermochemical relaxation for temperatures ranging from 10 000 to 25 000 K. Both methods make use of the same potential energy surface for the N2(Σg+1)-N2(Σg+1) system taken from the NASA Ames quantum chemistry database. Within the CG-QCT method, the rovibrational energy levels of the electronic ground state of the nitrogen molecule are lumped into a reduced number of bins. Two different grouping strategies are used: the more conventional vibrational-based grouping, widely used in the literature, and energy-based grouping. The analysis of both the internal state populations and concentration profiles show excellent agreement between the energy-based grouping and the DMS solutions. During the energy transfer process, discrepancies arise between the energy-based grouping and DMS solution due to the increased importance of mode separation for low energy states. By contrast, the vibrational grouping, traditionally considered state-of-the-art, captures well the behavior of the energy relaxation but fails to consistently predict the dissociation process. The deficiency of the vibrational grouping model is due to the assumption of strict mode separation and equilibrium of rotational energy states. These assumptions result in errors predicting the energy contribution to dissociation from the rotational and vibrational modes, with rotational energy actually contributing 30%-40% of the energy required to dissociate a molecule. This work confirms the findings discussed in Paper I [R. L. Macdonald et al., J. Chem. Phys. 148, 054309 (2018)], which underlines the importance of rotational energy to the dissociation process, and demonstrates that an accurate non-equilibrium chemistry model must accurately predict the deviation of rovibrational distribution from equilibrium.

6.
Artigo em Inglês | MEDLINE | ID: mdl-28872760

RESUMO

BACKGROUND: Wireless motility capsule (WMC) findings are incompletely defined in suspected gastroparesis. We aimed to characterize regional WMC transit and contractility in relation to scintigraphy, etiology, and symptoms in patients undergoing gastric emptying testing. METHODS: A total of 209 patients with gastroparesis symptoms at NIDDK Gastroparesis Consortium centers underwent gastric scintigraphy and WMCs on separate days to measure regional transit and contractility. Validated questionnaires quantified symptoms. KEY RESULTS: Solid scintigraphy and liquid scintigraphy were delayed in 68.8% and 34.8% of patients; WMC gastric emptying times (GET) were delayed in 40.3% and showed 52.8% agreement with scintigraphy; 15.5% and 33.5% had delayed small bowel (SBTT) and colon transit (CTT) times. Transit was delayed in ≥2 regions in 23.3%. Rapid transit was rarely observed. Diabetics had slower GET but more rapid SBTT versus idiopathics (P ≤ .02). GET delays related to greater scintigraphic retention, slower SBTT, and fewer gastric contractions (P ≤ .04). Overall gastroparesis symptoms and nausea/vomiting, early satiety/fullness, bloating/distention, and upper abdominal pain subscores showed no relation to WMC transit. Upper and lower abdominal pain scores (P ≤ .03) were greater with increased colon contractions. Constipation correlated with slower CTT and higher colon contractions (P = .03). Diarrhea scores were higher with delayed SBTT and CTT (P ≤ .04). CONCLUSIONS & INFERENCES: Wireless motility capsules define gastric emptying delays similar but not identical to scintigraphy that are more severe in diabetics and relate to reduced gastric contractility. Extragastric transit delays occur in >40% with suspected gastroparesis. Gastroparesis symptoms show little association with WMC profiles, although lower symptoms relate to small bowel or colon abnormalities.


Assuntos
Endoscopia por Cápsula/métodos , Esvaziamento Gástrico , Gastroparesia/diagnóstico por imagem , Cintilografia , Endoscopia por Cápsula/instrumentação , Feminino , Gastroparesia/fisiopatologia , Humanos , Masculino , Pressão , Estudos Prospectivos
7.
Chem Commun (Camb) ; 53(54): 7624-7627, 2017 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-28640293

RESUMO

Traditional methods for deriving computationally-generated collision cross sections for comparisons with ion mobility-mass spectrometry data require 3-dimensional energy-minimized structures and are often time consuming, preventing high throughput implementation. Here, we introduce a method to predict ion mobility collision cross sections of lipids and peptide analogs important in prebiotic chemistry and other fields. Using less than 100 2-D molecular descriptors this approach resulted in prediction errors of less than 2%.

8.
Artigo em Inglês | MEDLINE | ID: mdl-28066953

RESUMO

BACKGROUND: Animal studies have increasingly highlighted the role of macrophages in the development of delayed gastric emptying. However, their role in the pathophysiology of human gastroparesis is unclear. Our aim was to determine changes in macrophages and other cell types in the gastric antrum muscularis propria of patients with diabetic and idiopathic gastroparesis. METHODS: Full thickness gastric antrum biopsies were obtained from patients enrolled in the Gastroparesis Clinical Research Consortium (11 diabetic, 6 idiopathic) and 5 controls. Immunolabeling and quantitative assessment was done for interstitial cells of Cajal (ICC) (Kit), enteric nerves protein gene product 9.5, neuronal nitric oxide synthase, vasoactive intestinal peptide, substance P, tyrosine hydroxylase), overall immune cells (CD45) and anti-inflammatory macrophages (CD206). Gastric emptying was assessed using nuclear medicine scintigraphy and symptom severity using the Gastroparesis Cardinal Symptom Index. RESULTS: Both diabetic and idiopathic gastroparesis patients showed loss of ICC as compared to controls (Mean [standard error of mean]/hpf: diabetic, 2.28 [0.16]; idiopathic, 2.53 [0.47]; controls, 6.05 [0.62]; P=.004). Overall immune cell population (CD45) was unchanged but there was a loss of anti-inflammatory macrophages (CD206) in circular muscle (diabetic, 3.87 [0.32]; idiopathic, 4.16 [0.52]; controls, 6.59 [1.09]; P=.04) and myenteric plexus (diabetic, 3.83 [0.27]; idiopathic, 3.59 [0.68]; controls, 7.46 [0.51]; P=.004). There was correlation between the number of ICC and CD206-positive cells (r=.55, P=.008). Enteric nerves (PGP9.5) were unchanged: diabetic, 33.64 (3.45); idiopathic, 41.26 (6.40); controls, 46.80 (6.04). CONCLUSION: Loss of antral CD206-positive anti-inflammatory macrophages is a key feature in human gastroparesis and it is associates with ICC loss.


Assuntos
Complicações do Diabetes/metabolismo , Gastroparesia/metabolismo , Lectinas Tipo C/metabolismo , Macrófagos/metabolismo , Lectinas de Ligação a Manose/metabolismo , Antro Pilórico/metabolismo , Receptores de Superfície Celular/metabolismo , Adulto , Complicações do Diabetes/patologia , Sistema Nervoso Entérico/metabolismo , Feminino , Fibrose , Gastroparesia/patologia , Humanos , Células Intersticiais de Cajal/metabolismo , Células Intersticiais de Cajal/patologia , Masculino , Receptor de Manose , Pessoa de Meia-Idade , Antro Pilórico/patologia , Adulto Jovem
9.
Aliment Pharmacol Ther ; 44(6): 576-82, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27444134

RESUMO

BACKGROUND: Infectious enteritis is a commonly identified risk factor for irritable bowel syndrome (IBS). The incidence of Clostridium difficile infection (CDI) is on the rise. However, there is limited information on post-infectious IBS (PI-IBS) development following CDI and the host- and infection-related risk factors are not known. AIM: To determine the incidence and risk factors for PI-IBS following CDI. METHODS: A total of 684 cases of CDI identified from September 2012 to November 2013 were surveyed. Participants completed the Rome III IBS questionnaire and details on the CDI episode. Predictive modelling was done using logistic regression to evaluate risk factors for PI-IBS development. RESULTS: A total of 315 CDI cases responded (46% response rate) and 205 were at-risk (no pre-CDI IBS) for PI-IBS development. A total of 52/205 (25%) met the Rome III criteria for IBS ≥6 months following CDI. IBS-mixed was most common followed by IBS-diarrhoea. In comparison to those without subsequent PI-IBS, greater percentage of PI-IBS patients had CDI symptoms >7 days, nausea, vomiting, abdominal pain during CDI, anxiety and a higher BMI. Using logistic regression, CDI symptoms >7 days [Odds ratio (OR): 2.96, P = 0.01], current anxiety (OR: 1.33, P < 0.0001) and a higher BMI (OR: 1.08, P = 0.004) were independently associated with PI-IBS development; blood in the stool during CDI was protective (OR: 0.44, P = 0.06). CONCLUSIONS: In this cohort study, new-onset IBS is common after CDI. Longer CDI duration, current anxiety and higher BMI are associated with the diagnosis of C. difficile PI-IBS. This chronic sequela should be considered during active management and follow-up of patients with CDI.


Assuntos
Clostridioides difficile/fisiologia , Infecções por Clostridium/complicações , Infecções por Clostridium/epidemiologia , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/microbiologia , Dor Abdominal/complicações , Dor Abdominal/epidemiologia , Dor Abdominal/microbiologia , Adulto , Estudos de Coortes , Diarreia/epidemiologia , Diarreia/microbiologia , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
10.
Neurogastroenterol Motil ; 28(7): 1114-9, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26914765

RESUMO

BACKGROUND: Gastrointestinal (GI) and non-GI disorders are associated with altered intestinal permeability, which can be measured in vivo by urinary excretion after oral lactulose and mannitol ingestion. Inadvertent dietary consumption of (12) Carbon ((12) C, regular) mannitol in food or from other sources may interfere with the test's interpretation. (13) Carbon ((13) C) constitutes 1% of carbon in nature and (13) C mannitol is a stable isotope. Our aim was to determine the performance of (13) C mannitol for measurement of intestinal permeability. METHODS: Ten healthy volunteers underwent intestinal permeability assay using coadministered (12) C mannitol, (13) C mannitol and lactulose, followed by timed urine collections. Urinary sugar concentrations were measured using tandem high performance liquid chromatography-mass spectrometry. KEY RESULTS: We found that (13) C mannitol can be distinguishable from (12) C mannitol on tandem mass spectrometry. In addition, (13) C mannitol had ~20-fold lower baseline contamination compared to (12) C mannitol. We describe here the (13) C mannitol assay method for the measurement of intestinal permeability. CONCLUSIONS & INFERENCES: In conclusion, (13) C mannitol is superior to (12) C mannitol for measurement of intestinal permeability. It avoids issues with baseline contamination and erratic excretions during the testing period.


Assuntos
Isótopos de Carbono/metabolismo , Isótopos de Carbono/urina , Absorção Intestinal/fisiologia , Manitol/metabolismo , Manitol/urina , Biomarcadores/metabolismo , Biomarcadores/urina , Isótopos de Carbono/administração & dosagem , Humanos , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Masculino , Manitol/administração & dosagem , Pessoa de Meia-Idade , Permeabilidade/efeitos dos fármacos , Espectrometria de Massas em Tandem/métodos
12.
BMJ Glob Health ; 1(1): e000066, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28588929

RESUMO

BACKGROUND: Environmental enteric dysfunction (EED) is an asymptomatic intestinal disorder affecting populations living in conditions of poor sanitation and hygiene. The study tested intestinal barrier function in infants with EED. METHODS: We prospectively studied an advanced high-performance liquid chromatography mass spectrometry assay of urine collected after oral intake of the monosaccharide, L-rhamnose and the disaccharide, lactulose, in 112 children from three continents. FINDINGS: Compared to the US cohort (n=27), the cohorts of children from Peru (n=19) and Zambia (n=85) were older with evidence of growth impairment. The median (range) of age (months) was 8.0 (2.0 to 13.0), 27.0 (15.0 to 29.0) and 21.0 (12.0 to 36.0), respectively. The median (range) of height for age Z score was -0.1 (-1.8 to 2.4), -1.8 (-3.3 to -0.2) and -2.3 (-8.5 to 1.2), respectively. Among children with valid sugar data (n=22 USA, n=19 Peru, n=73 Zambia), there were no significant differences in the median rhamnose urine concentrations between the three groups. The median (range) lactulose concentration (µg/mL) was 6.78 (0.29 to 31.90), 47.60 (4.23 to 379.00) and 75.40 (0.67 to 873.00) in the US, Peruvian and Zambian cohorts, respectively (p<0.001). The lactulose/rhamnose ratio (LRR) was higher in cohorts from Peru (0.75, 0.15, 5.02) and Zambia (2.26, 0.08, 14.48) compared to the US (0.14, 0.06, 1.00) cohort (p<0.001). In a multivariate effect modification model, higher weight-for-age z scores were associated with lower post-dose lactulose when rhamnose excretion was constant (p=0.003). CONCLUSIONS: This non-invasive two saccharide permeability protocol measures changes in intestinal permeability in children with EED and permits the identification of individuals for interventional trials.

13.
Neurogastroenterol Motil ; 27(11): 1580-6, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26303310

RESUMO

BACKGROUND: Gastrointestinal infections are risk factors for irritable bowel syndrome (IBS) and functional dyspepsia (FD). We investigated whether non-enteric infections and antibiotic exposure are also associated with the development of functional gastrointestinal disorders (FGIDs). METHODS: In a nested case-control study, random samples of Olmsted County, MN, were mailed valid self-report questionnaires from 1988 through 1994, and then follow-up questionnaires from 1995 through 2003. Survey responders who did not report any FGID symptoms at baseline, but then reported such symptoms in at least one subsequent survey, were classified as new-onset cases. Age-matched controls were individuals who did not have symptoms at either the initial or subsequent surveys. KEY RESULTS: The overall response rate was 78% to the initial survey and 52% to the follow-up survey. Based on the responses, 316 participants had a new onset of an FGID (43 IBS constipation, 95 IBS diarrhea, 25 IBS mixed, and 153 other FGIDs, including FD) and 250 did not (controls). Around 76% (241/316) of cases reported a non-enteric infection vs 66% (166/250) of the controls. The frequency of enteric infections was similar between the two groups. Of the new FGID cases, 83% had a non-enteric infection that was treated with antibiotic. In a logistic regression model, treatment with antibiotics for a non-gastrointestinal infection was associated with the development of an FGID (odds ratio = 1.90; 95% CI: 1.21-2.98; p = 0.005), after adjusting for age and sex. CONCLUSIONS & INFERENCES: Based on a case-control study, treatment of a non-gastrointestinal infection with antibiotics appears to be a risk factor for development of an FGID.


Assuntos
Antibacterianos/efeitos adversos , Gastroenteropatias/epidemiologia , Infecções/tratamento farmacológico , Infecções/epidemiologia , Adulto , Distribuição por Idade , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Distribuição por Sexo , Inquéritos e Questionários , Adulto Jovem
14.
Neurogastroenterol Motil ; 26(6): 745-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24860967

RESUMO

The alterations in resident gut microbiota seen in chronic gastrointestinal disorders have led to an increasing interest in the role of gut bacteria in maintaining intestinal barrier function. While acute alterations in colonic secretomotor function in response to pathogens have been well described, the effect of commensal bacteria on intestinal barrier function and colonic secretomotor function still remains poorly understood. Germ-free mice represent a model system to study effect of gut microbes on host gastrointestinal physiology. The study by Lomasney et al. represents an important step in this direction by demonstrating that the colonic secretomotor function is largely preserved in germ-free mice, hence making them a suitable model to study effect of gut microbiota on host function.


Assuntos
Trato Gastrointestinal/microbiologia , Vida Livre de Germes , Microbiota/fisiologia , Modelos Animais , Animais , Camundongos
15.
Neurogastroenterol Motil ; 26(2): 156-67, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24438587

RESUMO

BACKGROUND: Gastrointestinal (GI) infections resulting from bacterial, viral, and parasitic pathogens predispose to postinfectious irritable bowel syndrome (PI-IBS) and other functional GI disorders. Existing literature supports the role of enterochromaffin cell hyperplasia, serotonin synthesis and reuptake, impaired barrier function, altered immune activation, and potentially mast cell activation in the pathophysiology of PI-IBS. PURPOSE: The objective of this review was to summarize from the literature the characteristics of the pathogens commonly implicated in PI-IBS, their acute enteritis phases, and the changes seen in the postinfectious phase that may contribute toward development of IBS. A limitation of our current understanding is that the postinfectious GI sequelae reported in prior studies followed epidemic diarrheal outbreaks often involving more than one pathogen, or the studies focused on highly selected, tertiary referral patients. Understanding the mechanisms, natural history, and optimized management of individuals suffering PI-IBS following the more typical sporadic infection requires larger studies of PI-IBS following GI infections encountered in community settings. These studies should include genetic, physiological, and molecular studies to provide more generalizable information that can ultimately be used to diagnose, manage, and potentially prevent the development of PI-IBS.


Assuntos
Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/parasitologia , Infecções por Campylobacter/complicações , Campylobacter jejuni/patogenicidade , Giardia lamblia/patogenicidade , Giardíase/complicações , Humanos , Norovirus/patogenicidade
16.
Osteoporos Int ; 24(8): 2253-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23443412

RESUMO

UNLABELLED: To achieve an efficient molecular diagnosis of osteogenesis imperfecta (OI), Ehlers-Danlos syndrome (EDS), and osteopetrosis (OPT), we designed a next-generation sequencing (NGS) platform to sequence 34 genes. We validated this platform on known cases and have successfully identified the causative mutation in most patients without a prior molecular diagnosis. INTRODUCTION: Osteogenesis imperfecta, Ehlers-Danlos syndrome, and osteopetrosis are collectively common inherited skeletal diseases. Evaluation of subjects with these conditions often includes molecular testing which has important counseling and therapeutic and sometimes legal implications. Since several different genes have been implicated in these conditions, Sanger sequencing of each gene can be a prohibitively expensive and time-consuming way to reach a molecular diagnosis. METHODS: In order to circumvent these problems, we have designed and tested a NGS platform that would allow simultaneous sequencing on a single diagnostic platform of different genes implicated in OI, OPT, EDS, and other inherited conditions, leading to low or high bone mineral density. We used a liquid-phase probe library that captures 602 exons (~100 kb) of 34 selected genes and have applied it to test clinical samples from patients with bone disorders. RESULTS: NGS of the captured exons by Illumina HiSeq 2000 resulted in an average coverage of over 900X. The platform was successfully validated by identifying mutations in six patients with known mutations. Moreover, in four patients with OI or OPT without a prior molecular diagnosis, the assay was able to detect the causative mutations. CONCLUSIONS: In conclusion, our NGS panel provides a fast and accurate method to arrive at a molecular diagnosis in most patients with inherited high or low bone mineral density disorders.


Assuntos
Densidade Óssea/genética , Doenças do Desenvolvimento Ósseo/diagnóstico , Doenças do Desenvolvimento Ósseo/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Adulto , Doenças do Desenvolvimento Ósseo/fisiopatologia , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/genética , Síndrome de Ehlers-Danlos/fisiopatologia , Biblioteca Gênica , Predisposição Genética para Doença , Testes Genéticos/métodos , Humanos , Masculino , Mutação , Osteogênese Imperfeita/diagnóstico , Osteogênese Imperfeita/genética , Osteogênese Imperfeita/fisiopatologia , Osteopetrose/diagnóstico , Osteopetrose/genética , Osteopetrose/fisiopatologia , Análise de Sequência de DNA/métodos
18.
Neurogastroenterol Motil ; 24(9): 844-52, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22650155

RESUMO

BACKGROUND: Emerging evidence suggests that "fibroblast-like cells" (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are ultrastructurally distinct from other interstitial cells, including interstitial cells of Cajal (ICC), and express small-conductance Ca(2+) -activated K(+) channels (SK3). In mice, platelet-derived growth factor receptor α (PDGFRα) antibody has also been shown to label FLC. The aims of this study were to determine the morphology and distribution of PDGFRα-immunoreactive (ir) FLC in human gastric muscle and to determine if FLC are altered in gastroparesis, where ICC are reduced. METHODS: Full thickness gastric body biopsies from five healthy subjects, 10 diabetic, and 10 idiopathic gastroparesis patients were immunolabeled using SK3 and PDGFRα staining for FLC and Kit staining for ICC. Intramuscular FLC and ICC were quantified. KEY RESULTS: Intramuscular PDGFRα-ir cells had slender cell bodies and long, thin processes and were more abundant in the longitudinal compared with the circular muscle. In the region of myenteric plexus, FLC had smaller, rounder cell bodies with 3-4 processes and formed networks, often around ganglia. All SK3-ir cell structures showed complete overlap with PDGFRα-ir. FLC were in close proximity to ICC, but their cell bodies did not overlap. No differences were seen in the distribution, morphology, or overall numbers of FLC in gastroparesis patients. CONCLUSIONS & INFERENCES: In conclusion, PDGFRα identifies FLC in human gastric smooth muscle. FLC were not altered in distribution or overall numbers in gastroparesis. Additional studies are required to determine their role in human GI function.


Assuntos
Complicações do Diabetes/metabolismo , Mucosa Gástrica , Gastroparesia/metabolismo , Músculo Liso , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Estômago , Adulto , Estudos de Casos e Controles , Feminino , Esvaziamento Gástrico , Mucosa Gástrica/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Músculo Liso/citologia , Músculo Liso/metabolismo , Plexo Mientérico/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo , Estômago/citologia
19.
Neurogastroenterol Motil ; 24(7): 597-603, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22626059

RESUMO

Gastroparesis is often divided into subsets based on etiology and pathophysiology; however, the utility of these subsets in the diagnosis and treatment of gastro-paresis is not well defined. The objectives are to consider the subsets of gastroparesis from the perspectives of etiology and pathogenesis, pathophysiology, histopathology, and clinical associations, with particular focus on similarities and differences between diabetic and idiopathic gastroparesis and consideration of the potential subset of painful gastroparesis. We conclude that idiopathic and diabetic gastroparesis has similar initial presentations and manifestations, except that idiopathic gastroparesis tends to be associated more frequently with pain. Myopathic disorders are uncommon. Extrinsic denervation was considered the most common etiology; however, with the decline in surgery for peptic ulceration and in-depth study of full-thickness gastric biopsies, the most common intrinsic defects are being recognized in the interstitial cells of Cajal (ICC-opathy) and with immune infiltration and neuronal changes (intrinsic neuropathic gastroparesis). Histomorphological differences at the microscopic level between diabetic and idiopathic gastroparesis are still of unclear significance. Two gastroparesis subsets worthy of special mention, because they are potentially reversible with identification of the cause, are postviral gastroparesis, which has a generally good prognosis, and iatrogenic gastroparesis, especially in patients with non-surgical gastroparesis, such as diabetics exposed to incretins such as pramlintide and exenatide.


Assuntos
Gastroparesia/diagnóstico , Gastroparesia/etiologia , Gastroparesia/classificação , Humanos
20.
Neurogastroenterol Motil ; 24(6): 531-9, e249, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22339929

RESUMO

BACKGROUND: Cellular changes associated with diabetic (DG) and idiopathic gastroparesis (IG) have recently been described from patients enrolled in the Gastroparesis Clinical Research Consortium. The association of these cellular changes with gastroparesis symptoms and gastric emptying is unknown. The aim of this study was to relate cellular changes to symptoms and gastric emptying in patients with gastroparesis. METHODS: Earlier, using full thickness gastric body biopsies from 20 DG, 20 IG, and 20 matched controls, we found decreased interstitial cells of Cajal (ICC) and enteric nerves and an increase in immune cells in both DG and IG. Here, demographic, symptoms [gastroparesis cardinal symptom index score (GCSI)], and gastric emptying were related to cellular alterations using Pearson's correlation coefficients. KEY RESULTS: Interstitial cells of Cajal counts inversely correlated with 4 h gastric retention in DG but not in IG (r = -0.6, P = 0.008, DG, r = 0.2, P = 0.4, IG). There was also a significant correlation between loss of ICC and enteric nerves in DG but not in IG (r = 0.5, P = 0.03 for DG, r = 0.3, P = 0.16, IG). Idiopathic gastroparesis with a myenteric immune infiltrate scored higher on the average GCSI (3.6 ± 0.7 vs 2.7 ± 0.9, P = 0.05) and nausea score (3.8 ± 0.9 vs 2.6 ± 1.0, P = 0.02) as compared to those without an infiltrate. CONCLUSIONS & INFERENCES: In DG, loss of ICC is associated with delayed gastric emptying. Interstitial cells of Cajal or enteric nerve loss did not correlate with symptom severity. Overall clinical severity and nausea in IG is associated with a myenteric immune infiltrate. Thus, full thickness gastric biopsies can help define specific cellular abnormalities in gastroparesis, some of which are associated with physiological and clinical characteristics of gastroparesis.


Assuntos
Sistema Nervoso Entérico/patologia , Gastroparesia/patologia , Estômago/patologia , Adulto , Idoso , Sistema Nervoso Entérico/fisiopatologia , Feminino , Esvaziamento Gástrico/fisiologia , Gastroparesia/fisiopatologia , Humanos , Células Intersticiais de Cajal/patologia , Células Intersticiais de Cajal/fisiologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Estômago/fisiopatologia , Inquéritos e Questionários
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