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1.
J Am Anim Hosp Assoc ; 58(6): 283-287, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36315861

RESUMO

A 2 yr old castrated male shih tzu was presented for assessment of worsening chronic snoring since first detected at 3 mo of age. An upper respiratory endoscopic examination and a computed tomographic scan showed a well-circumscribed, fluid-filled nasopharyngeal mass located in the median plane on the nasal side of the soft palate. This lesion was removed using a ventral approach to the nasopharynx by blunt-sharp dissection from the submucosal tissues of the soft palate. Histopathology revealed a cystic lesion lined by a single layer of a pseudostratified columnar ciliated epithelium, characteristic of a pharyngeal cyst. Follow-up 5 mo after surgery revealed complete resolution of the clinical signs with no evidence of local recurrence. Pharyngeal cysts are developmental abnormalities of the branchial apparatus. Most derive from the second branchial arch and cause cysts, sinuses, and fistulae to develop in the neck region. In our case, the lesion was located in the nasopharynx, leading to snoring and exercise intolerance. This condition should be included in the differential diagnosis of suspected nasopharyngeal obstruction.


Assuntos
Branquioma , Doenças do Cão , Masculino , Cães , Animais , Branquioma/diagnóstico , Branquioma/patologia , Branquioma/veterinária , Região Branquial/patologia , Ronco/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia , Nasofaringe/cirurgia , Nasofaringe/patologia
2.
Res Vet Sci ; 136: 408-415, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33799171

RESUMO

Acquired pyloric narrowing is a rare and poorly-documented condition in cats, but the endoscopic appearance of pyloric narrowing has never previously been reported. The objectives of this study were to describe the clinical, endoscopic and histological features in cats with gastrointestinal signs where the pylorus could not be passed during endoscopy, and to compare these data with a control group. Medical files of cats that underwent upper GI endoscopy by the same operator between 2006 and 2015 were reviewed. Cats for which the pylorus could not be passed were assigned to the case group, whilst those with an easily-passable pylorus were assigned to the control group. The case group comprised 27 cats and control group comprised 35 cats. Median age and weight were not different between groups, but there were more Siamese cats in the case group (6/27) compared with the control group (1/35; P = 0.04). Chronic vomiting was the main clinical sign in both groups, but the vomitus was more likely to contain food in case group (23/25) than in cats in control group (17/30; P < 0.01). Endoscopic findings confirmed gastric inflammation in both groups, whilst histological findings revealed similar lymphoplasmacytic infiltration of the gastric mucosa and the duodenum in most cases, neoplastic features being infrequent. Acquired pyloric narrowing is probably an underdiagnosed condition in adult cats. A possible association between pyloric narrowing and gastrointestinal inflammatory disease requires further study but, for now, it is recommended that multiple gastric, pyloric, and duodenal biopsies be acquired during the endoscopy.


Assuntos
Doenças do Gato/diagnóstico por imagem , Gastroscopia/veterinária , Estenose Pilórica/veterinária , Piloro/diagnóstico por imagem , Animais , Biópsia/veterinária , Peso Corporal , Gatos , Estudos de Coortes , Feminino , Masculino , Estenose Pilórica/complicações , Estenose Pilórica/diagnóstico por imagem , Estudos Retrospectivos , Vômito/etiologia , Vômito/veterinária
3.
J Feline Med Surg ; 23(12): 1140-1148, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33749374

RESUMO

OBJECTIVES: The aim of this study was to develop an algorithm capable of predicting short- and medium-term survival in cases of intrinsic acute-on-chronic kidney disease (ACKD) in cats. METHODS: The medical record database was searched to identify cats hospitalised for acute clinical signs and azotaemia of at least 48 h duration and diagnosed to have underlying chronic kidney disease based on ultrasonographic renal abnormalities or previously documented azotaemia. Cases with postrenal azotaemia, exposure to nephrotoxicants, feline infectious peritonitis or neoplasia were excluded. Clinical variables were combined in a clinical severity score (CSS). Clinicopathological and ultrasonographic variables were also collected. The following variables were tested as inputs in a machine learning system: age, body weight (BW), CSS, identification of small kidneys or nephroliths by ultrasonography, serum creatinine at 48 h (Crea48), spontaneous feeding at 48 h (SpF48) and aetiology. Outputs were outcomes at 7, 30, 90 and 180 days. The machine-learning system was trained to develop decision tree algorithms capable of predicting outputs from inputs. Finally, the diagnostic performance of the algorithms was calculated. RESULTS: Crea48 was the best predictor of survival at 7 days (threshold 1043 µmol/l, sensitivity 0.96, specificity 0.53), 30 days (threshold 566 µmol/l, sensitivity 0.70, specificity 0.89) and 90 days (threshold 566 µmol/l, sensitivity 0.76, specificity 0.80), with fewer cats still alive when their Crea48 was above these thresholds. A short decision tree, including age and Crea48, predicted the 180-day outcome best. When Crea48 was excluded from the analysis, the generated decision trees included CSS, age, BW, SpF48 and identification of small kidneys with an overall diagnostic performance similar to that using Crea48. CONCLUSIONS AND RELEVANCE: Crea48 helps predict short- and medium-term survival in cats with ACKD. Secondary variables that helped predict outcomes were age, CSS, BW, SpF48 and identification of small kidneys.


Assuntos
Doenças do Gato , Insuficiência Renal Crônica , Algoritmos , Animais , Doenças do Gato/diagnóstico por imagem , Gatos , Creatinina , Aprendizado de Máquina , Prognóstico , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/veterinária
4.
J Am Vet Med Assoc ; 256(8): 906-913, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32223711

RESUMO

OBJECTIVE: To compare clinical, endoscopic, and histopathologic features between dogs with chronic gastritis (CG) with and without lymphofollicular hyperplasia (LFH). ANIMALS: 64 and 56 dogs with CG with (cases) and without (controls) LFH, respectively. PROCEDURES: The medical record database of a referral clinic was searched to identify dogs that underwent endoscopic examination of the upper portion of the gastrointestinal tract and were subsequently determined to have CG with or without LFH between October 2006 and February 2011. Signalment and clinical, endoscopic, and histologic findings were compared between cases and controls. Logistic regression was used to identify factors associated with CG with LFH. RESULTS: Compared with controls, cases were significantly younger and more likely to be of a brachycephalic phenotype. The proportions of dogs with a poor body condition or diarrhea were significantly lower and the proportions of dogs with inspiratory dyspnea, exercise intolerance, or hyperemia and discoloration of the gastric mucosa were significantly higher for the case group, compared with the control group. Inspiratory dyspnea, gastric mucosal hyperemia, and gastritis severity were positively associated, whereas poor body condition was negatively associated, with CG with LFH on multivariable logistic regression. CONCLUSIONS AND CLINICAL RELEVANCE: The strong positive association between inspiratory dyspnea and CG with LFH suggested that the condition may be a consequence of an increase in negative intrathoracic pressure rather than a distinct clinical entity. Prospective studies are warranted to elucidate the mechanism by which inspiratory dyspnea contributes to the development of CG with LFH.


Assuntos
Doenças do Cão , Gastrite/veterinária , Animais , Cães , Endoscopia/veterinária , Hiperplasia/veterinária , Modelos Logísticos , Estudos Prospectivos
5.
J Am Anim Hosp Assoc ; 55(5): 261-265, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31433228

RESUMO

A 4 mo old female Staffordshire bull terrier puppy was presented with chronic Escherichia coli cystitis. Ultrasound and cystoscopic examination revealed innumerable, intraluminal, finger-like proliferations arising from the dorsal urinary bladder (UB) wall. Histological examination of mucosal biopsies obtained by cystoscopy was suggestive of granulomatous cystitis. The proliferative lesions were removed surgically and submitted for histological examination. The UB submucosa was heavily infiltrated by macrophages with periodic acid-Schiff-positive cytoplasm exhibiting rare Michaelis-Gutmann bodies, leading to the diagnosis of malakoplakia. The puppy was prescribed with sulfamethoxazole-trimethoprim. The urinary signs disappeared despite the persistent UB wall thickening revealed by abdominal ultrasound. Urine culture performed during the ninth week of treatment showed a persistent infection by E coli resistant to sulfamethoxazole-trimethoprim. The dog was switched to doxycycline but was then lost to follow-up. Malakoplakia is a chronic granulomatous inflammation well documented in humans. Its pathophysiology is not fully understood, but bacterial infection, immunodepression, and a defective lysosomal function may lead to the intracytoplasmic accumulation of partially degraded bacteria that can subsequently mineralize to form the Michaelis-Gutmann bodies. Malakoplakia should be suspected when UB mass lesions are identified in a young dog with bacterial cystitis.


Assuntos
Malacoplasia/veterinária , Doenças da Bexiga Urinária/veterinária , Animais , Antibacterianos/uso terapêutico , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/veterinária , Cistite/microbiologia , Cistite/veterinária , Doenças do Cão , Cães , Feminino , Malacoplasia/patologia , Doenças da Bexiga Urinária/patologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/patologia , Infecções Urinárias/veterinária
6.
J Feline Med Surg ; 19(4): 484-492, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26534945

RESUMO

Case series summary Six cats were diagnosed with renal abscesses. Common clinical findings were lethargy, dehydration, abdominal pain and nephromegaly. Fever was noted in half of the cases. Diagnosis was established by ultrasonography, cytological examination and bacterial culture of abscess aspirates. At least one possible contributing factor could be identified in all cases. Antibiotics were consistently used and in two cats the abscess was surgically drained. The short-term outcome was fair but the long-term outcome was dependent on the underlying condition. Relevance and novel information The results of this small case series suggest that renal abscess should be considered when nephromegaly and/or abdominal discomfort are noted. Diagnosis of renal abscess is straightforward when ultrasonography and fine-needle aspirate analysis can be performed. Medical treatment is assumed to be preferable but surgical treatment may be warranted on a case-by-case basis. Given that almost every affected cat was diagnosed with at least one comorbidity, a thorough evaluation is recommended for all cats with renal abscesses.


Assuntos
Abscesso/veterinária , Doenças do Gato/diagnóstico , Nefropatias/veterinária , Dor Abdominal/etiologia , Dor Abdominal/veterinária , Abscesso/complicações , Abscesso/diagnóstico , Animais , Antibacterianos/uso terapêutico , Biópsia por Agulha Fina/veterinária , Doenças do Gato/diagnóstico por imagem , Doenças do Gato/patologia , Gatos , Diagnóstico Diferencial , Feminino , Febre/etiologia , Febre/veterinária , Nefropatias/complicações , Nefropatias/diagnóstico , Masculino , Estudos Retrospectivos , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/etiologia , Infecções Urinárias/veterinária
8.
J Feline Med Surg ; 18(2): 118-28, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25722348

RESUMO

OBJECTIVES: Many cats with gastrointestinal signs have coexisting abnormalities in the intestine, liver and pancreas. Investigations typically involve clinicopathological tests, diagnostic imaging and biopsy, either at coeliotomy or by non-invasive means. While exploratory coeliotomy enables all organs to be sampled simultaneously, it is invasive and might not be necessary. The aim of the current study was to assess the performance of preliminary clinical information in predicting the histopathological presence of abnormalities in alimentary tract organs in cats. METHODS: The records of 38 cats with alimentary tract signs, which had ultimately undergone exploratory coeliotomy and surgical biopsy, were reviewed. The clinical signs, clinicopathological findings, diagnostic imaging findings and histopathology results were reviewed. RESULTS: On histopathological analysis, lesions were detected in 29/37 (78%) liver biopsies, in 29/35 (83%) gastrointestinal biopsies and in 17/37 (46%) pancreatic samples, the majority of which were inflammatory in nature. Clinical signs were generally poor markers of the presence of lesions in the alimentary tract. Further, while liver enzyme activity was relatively specific (88-100%) for detecting histopathological abnormalities in the liver, sensitivity was poor (11-50%). Pancreatic histopathological abnormalities were present in 1/3 of the cats with a positive pancreas-specific lipase result, and in 6/8 cats with a negative result. While relatively specific (57-100%) for both intestinal (57-100%) and hepatic (71-80%) histopathological abnormalities, abdominal ultrasonography lacked sensitivity for both organs (intestine 50-80%; liver 20-25%). In contrast, ultrasonography was relatively sensitive (50-80%), but not specific (17-22%) for detecting pancreatic lesions. CONCLUSIONS AND RELEVANCE: Clinical signs, and clinicopathological and ultrasonographic abnormalities lack precision for hepatic and pancreatic histopathological lesions in cats with alimentary tract signs, and cannot reliably predict from which organs biopsies should be collected. Arguably, therefore, exploratory coeliotomy is necessary to determine the site of histopathological abnormalities in feline alimentary tract disorders.


Assuntos
Doenças do Gato/diagnóstico por imagem , Doenças do Gato/patologia , Endoscopia Gastrointestinal/veterinária , Gastroenteropatias/veterinária , Animais , Gatos , Intestino Delgado/patologia , Rim/diagnóstico por imagem , Fígado/diagnóstico por imagem , Pâncreas/diagnóstico por imagem , Radiografia Abdominal/veterinária , Estudos Retrospectivos , Gastropatias/veterinária , Ultrassonografia
9.
Opt Express ; 22(11): 13507-14, 2014 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-24921544

RESUMO

We outline a full-vectorial three-dimensional multi-mode matching technique in a cylindrical coordinate system that addresses the mutual coupling among multiple modes co-propagating in a perturbed whispering gallery mode microcavity. In addition to its superior accuracy in respect to our previously implemented single-mode matching technique, this current technique is suitable for modelling waveguide-to-cavity coupling where the influence of multi-mode coupling is non-negligible. Using this methodology, a robust scheme for hybrid integration of a microcavity onto a silicon-on-insulator platform is proposed.

10.
Vet Q ; 34(1): 37-40, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24593857

RESUMO

A 16-year-old domestic shorthaired cat with chronic kidney disease was presented with a subacute history of weakness and anorexia. Severe hypercalcaemia was identified and attributed to a cervical mass, diagnosed as a parathyroid carcinoma after surgery. Renal function, as evaluated by plasma creatinine, initially worsened during hypercalcaemia but fully returned to previously documented values two months post-operatively.


Assuntos
Doenças do Gato/cirurgia , Hipercalcemia/veterinária , Hiperparatireoidismo Primário/veterinária , Neoplasias das Paratireoides/veterinária , Animais , Doenças do Gato/etiologia , Gatos , Hipercalcemia/complicações , Hipercalcemia/cirurgia , Hiperparatireoidismo Primário/etiologia , Hiperparatireoidismo Primário/cirurgia , Masculino , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/cirurgia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/veterinária , Resultado do Tratamento
11.
BMC Vet Res ; 9: 250, 2013 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-24330630

RESUMO

BACKGROUND: Cimicoxib is a new coxib anti-inflammatory drug for use in the dog. To determine a preclinical dosage regimen for cimicoxib in dog, a reversible model of kaolin-induced paw inflammation was used. Dosage regimens were established using pharmacokinetic/pharmacodynamic (PK/PD) modeling approach (indirect response model). RESULTS: Analgesic, anti-inflammatory and antipyretic endpoints investigated with the inflammation model established the efficacy of cimicoxib at a dose of 2 mg/kg administered orally (single dose) in 12 beagle dogs.For both the oral and IV route of administration two groups of dogs to be identified namely Poor Metabolizers (PM) and Extensive Metabolizers (EM).The terminal half-life after oral administration was 8.0 ± 0.6 h for the PM and 4.6 ± 2.6 h for the EM groups, with the corresponding values after the IV route being 5.6 ± 1.7 h and 2.7 ± 0.9 h (mean ± SD).The main pharmacodynamic parameters (potency, efficacy, and sensitivity) were estimated for four endpoints (body temperature, creeping speed, ground vertical reaction force and clinical lameness score). The plasma concentration corresponding to half the maximum of the indirect effect were 239 µg/L for creeping speed, 284 µg/L for the lameness score, 161 µg/L for the ground reaction vertical force and 193 µg/L for the body temperature.To document possible polymorphism of the cimicoxib disposition in the target dog population, cimicoxib was administered by the intravenous route to 40 dogs (four different sized breeds). The cimicoxib half-lives in these 40 dogs were of same order of the magnitude as those of the EM beagle dogs. Thus pharmacokinetic and pharmacodynamic parameters obtained from the EM beagle dogs were selected to simulate the dose-effect relationship of cimicoxib after an oral administration allowing a dosage regimen to be selected for confirmation by a clinical trial. CONCLUSIONS: Cimicoxib was an efficacious anti-inflammatory, antipyretic and analgesic drug and a dosage regimen of 2 mg/kg daily was determined for confirmatory clinical trials.


Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacocinética , Imidazóis/farmacocinética , Sulfonamidas/farmacocinética , Administração Oral , Animais , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Doenças do Cão/tratamento farmacológico , Cães/metabolismo , Meia-Vida , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/veterinária , Injeções Intravenosas/veterinária , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico
12.
Am J Vet Res ; 73(11): 1841-7, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23106473

RESUMO

OBJECTIVE: To compare pharmacokinetics and clearances of creatinine and iohexol as estimates of glomerular filtration rate (GFR) in dogs with various degrees of renal function. ANIMALS: 50 Great Anglo-Francais Tricolor Hounds with various degrees of renal function. PROCEDURES: Boluses of iohexol (40 mg/kg) and creatinine (647 mg/kg) were injected IV. Blood samples were collected before administration and 5 and 10 minutes and 1, 2, 4, 6, and 8 hours after administration. Plasma creatinine and iohexol concentrations were assayed via an enzymatic method and high-performance liquid chromatography, respectively. A noncompartmental approach was used for pharmacokinetic analysis. Pharmacokinetic variables were compared via a Bland-Altman plot and an ANOVA. RESULTS: Compared with results for creatinine, iohexol had a significantly higher mean ± SD plasma clearance (3.4 ± 0.8 mL/min/kg vs 3.0 ± 0.7 mL/min/kg) and a significantly lower mean volume of distribution at steady state (250 ± 37 mL/kg vs 539 ± 73 mL/kg), mean residence time (80 ± 31 minutes vs 195 ± 73 minutes), and mean elimination half-life (74 ± 20 minutes vs 173 ± 53 minutes). Despite discrepancies between clearances, especially for high values, the difference was < 0.6 mL/min/kg for 34 (68%) dogs. Three dogs with a low GFR (< 2 mL/min/kg) were classified similarly by both methods. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma iohexol and creatinine clearances can be used interchangeably for screening patients suspected of having chronic kidney disease (ie, low GFR), but large differences may exist for dogs with a GFR within or above the reference range.


Assuntos
Meios de Contraste/farmacocinética , Creatinina/farmacocinética , Doenças do Cão/metabolismo , Iohexol/farmacocinética , Nefropatias/veterinária , Animais , Creatinina/sangue , Cães , Feminino , Taxa de Filtração Glomerular , Nefropatias/metabolismo , Nefropatias/patologia , Masculino
13.
Appl Opt ; 47(9): 1215-22, 2008 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-18709067

RESUMO

We present an improved, high-resolution method for the measurement of phase retardation induced by the material birefringence of optical fibers. Such a method can be used to retrieve information about the spatial distribution of refractive index anisotropy in the fiber by comparing the accumulated phase of a polarization component oriented along the fiber transmission axis and another located in the transverse plane. The method is based on the nonlinear regression of a phase modulated signal of known modulation amplitude altered by the sample. Experimental results obtained with our method for a standard telecommunications fiber (the Corning SMF-28) as well as photosensitive fibers (Fibercore PS1250 and PS1500) are presented with a noise-limited phase resolution below 10(-4) radians and a spatial resolution below 1 microm. An analysis of the limitation of such measurement methods is also presented including diffraction by the fibers.

14.
Opt Express ; 16(6): 4228-36, 2008 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-18542518

RESUMO

We present the results of a comprehensive analysis optimizing the performance of DPSK systems with increased FSR and narrow optical filtering, establishing improved chromatic dispersion tolerance of NRZ-DPSK by 20%, RZ-DPSK by 71% and CSRZ-DPSK by 74% approximately. Transmitting a 40Gb/s signals on a spectrally efficient 50GHz DWDM grid still exhibit improvements of 7% for NRZ-DPSK, 37% for RZ-DPSK and 22% for CSRZ-DPSK, relative to a typical DPSK receiver. The optimized delay and optical filtering scale with the amount of chromatic dispersion. We also demonstrate the impact of limited transmitter bandwidth on optimal optical filtering and bit delay parameters.


Assuntos
Cor , Comunicação , Modelos Teóricos , Óptica e Fotônica , Processamento de Sinais Assistido por Computador , Simulação por Computador , Sensibilidade e Especificidade
15.
J Am Anim Hosp Assoc ; 44(2): 51-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18316440

RESUMO

Pediatric devices based on a capillary system may provide an alternative to vacuum tubes for canine blood sampling. The potential advantages are absence of vein collapse, limited blood volume sampled, and improved safety. The aim of this study was to compare routine plasma and hematological variables in seven healthy dogs using both techniques. Five biochemical analytes were measured, and a complete hematological examination and plasma exogenous creatinine clearance test were performed. No clinically relevant difference between the two techniques was observed for any variable or functional test assessed.


Assuntos
Coleta de Amostras Sanguíneas/veterinária , Cães/sangue , Animais , Análise Química do Sangue/veterinária , Coleta de Amostras Sanguíneas/instrumentação , Coleta de Amostras Sanguíneas/métodos , Creatinina/farmacocinética , Estudos Cross-Over , Feminino , Testes Hematológicos/veterinária , Masculino , Distribuição Aleatória , Valores de Referência
16.
J Feline Med Surg ; 9(5): 382-6, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17498993

RESUMO

Using paediatric devices to collect venous blood from a cephalic vein in cats offers numerous practical advantages over traditional jugular venepuncture and vacuum closed systems: minimal restraint is required; there is minimal risk of serious injury to the cat; the discomfort associated with venepuncture is reduced by the use of small diameter (25 gauge) needles; very small volumes (200 microl) of blood are extracted; and the risk of vein collapse or haematoma is low. The aim of this study was to compare the haematological and plasma chemistry results obtained from six healthy cats using the two sampling techniques. Five plasma biochemical analytes were measured and a complete haematological examination was performed on each specimen. No clinically relevant difference between the two blood sampling techniques was observed for any variable, indicating that paediatric devices provide a useful alternative to vacuum tubes for venous blood collection in the cat.


Assuntos
Contagem de Células Sanguíneas/veterinária , Coleta de Amostras Sanguíneas/veterinária , Gatos/sangue , Animais , Coleta de Amostras Sanguíneas/instrumentação , Desenho de Equipamento , Feminino , Masculino
17.
Am J Ophthalmol ; 140(4): 760-2, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16226543

RESUMO

PURPOSE: To ascertain whether there is a common disease haplotype for the Q368STOP mutation of the myocilin gene in Australian and Canadian families with primary open-angle glaucoma (POAG). DESIGN: Family pedigree study. METHODS: A disease haplotype for the Q368STOP mutation of the myocilin gene has previously been identified in 15 Tasmanian families with POAG. The four microsatellite markers that constitute this 0.14-megabase (Mb) disease haplotype were genotyped in individuals from a large French Canadian family with POAG (family CT) and two unrelated French Canadian individuals with ocular hypertension. RESULTS: The Tasmanian Q368STOP disease haplotype was identified in affected individuals from family CT, and the same alleles were shared at the four microsatellite markers in the two unrelated French Canadian individuals. CONCLUSION: The same disease haplotype for the Q368STOP mutation of the myocilin gene was found in both the Tasmanian and French Canadian populations, supporting the view that this mutation arose from a common Caucasian founder.


Assuntos
Códon de Terminação/genética , Proteínas do Citoesqueleto/genética , Proteínas do Olho/genética , Glaucoma de Ângulo Aberto/genética , Glicoproteínas/genética , Haplótipos/genética , Mutação Puntual , Austrália , Canadá , Análise Mutacional de DNA , Feminino , Efeito Fundador , Genótipo , Glaucoma de Ângulo Aberto/epidemiologia , Humanos , Masculino , Repetições de Microssatélites , Linhagem
18.
Hum Mol Genet ; 11(18): 2077-90, 2002 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-12189160

RESUMO

Primary open-angle glaucoma (POAG) is a complex disorder characterized by a progressive and treatable degeneration of the optic nerve. TIGR/myocilin (MYOC) gene mutations are found in approximately 4% of all POAG patients. Populations with frequent founder effects, such as the French-Canadians, offer unique advantages to implement genetic testing for the disorder. To assess molecular diagnosis for POAG in this population, we determined the prevalence of TIGR/MYOC mutations in 384 unrelated glaucoma patients, 38 ocular hypertensive subjects and 18 affected families (180 patients). We further analyzed the clinical features associated with these variations. Nine coding sequence variants were defined as mutations causing mostly, but not exclusively, POAG. Four families segregated distinct mutations (Gly367Arg, Gln368Stop, Lys423Glu and Pro481Leu), while 14 unrelated glaucoma patients harbored six known mutations (Thr293Lys, Glu352Lys, Gly367Arg, Gln368Stop, Lys423Glu and Ala445Val) and two novel (Ala427Thr and Arg126Trp). The frequencies of these mutations were respectively 3.8% and 22.2% in the unrelated and family studies. The Gly367Arg and Lys423Glu variants caused the earliest ages at onset. When achievable, assessment of relatives of unrelated mutation carriers showed the Arg126Trp and Gly367Arg to be familial. Characteristic allele signatures, indicative of specific founder effects, were observed for five of the six mutations conveyed by at least two patients. Recombination probability estimates suggested that the French-Canadian population had most probably inherited these six mutations from 7-10 Québec settlers. Our data demonstrated that genetic screening for TIGR/MYOC mutations should be offered to glaucoma families and to close relatives of unrelated patients aware of a family history for the disorder.


Assuntos
Proteínas do Olho/genética , Efeito Fundador , Glaucoma de Ângulo Aberto/genética , Glicoproteínas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Criança , Proteínas do Citoesqueleto , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Fenótipo , Polimorfismo Genético , Quebeque , População Branca
19.
Hum Mol Genet ; 11(11): 1333-42, 2002 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-12019215

RESUMO

The opticin (OPTC) gene encodes a protein that is a member of the small leucine-rich repeat protein (SLRP) family. OPTC is located on chromosome 1q31-q32 within an age-related macular degeneration (AMD) susceptibility locus. We have developed an affinity-purified N-terminal anti-opticin antibody and used it to examine opticin expression in human eye tissues. The antibody was also used for opticin protein localization in human eye sections. Immunoblots of human eye tissues detected a predominant band of approximately 62 kDa in size in iris, trabecular meshwork/ciliary body, retina, vitreous, and optic nerve. Immunohistochemical experiments revealed that opticin is specifically localized in human cornea, iris, ciliary body, vitreous, choroid and retina. Due to opticin's protein profile in the eye, we have also screened OPTC for mutations in individuals with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG) or AMD. We identified four sequence variations, all of which were observed in normal controls except for the Arg229Cys change. Three amino acid substitutions (Ile182Thr, Arg229Cys and Arg325Trp) were in residues conserved in dog, mouse, pig and human. The Arg229Cys alteration was present in a homozygous state in one individual with neovascular AMD. Examination of the other AMD afflicted family members showed that the OPTC Arg229Cys variant did not segregate with the disorder within the family. The protein localization pattern of opticin and our preliminary screen of AMD patients suggest that a larger AMD patient screen may be warranted.


Assuntos
Proteínas da Matriz Extracelular/análise , Olho/metabolismo , Proteoglicanas/análise , Idoso , Sequência de Aminoácidos , Animais , Células COS , DNA Complementar , Cães , Proteínas da Matriz Extracelular/genética , Feminino , Testes Genéticos , Variação Genética , Glaucoma/genética , Glaucoma/metabolismo , Glaucoma de Ângulo Aberto/genética , Glaucoma de Ângulo Aberto/metabolismo , Humanos , Immunoblotting , Imuno-Histoquímica , Degeneração Macular/genética , Degeneração Macular/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Especificidade de Órgãos , Linhagem , Proteoglicanas/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Suínos
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