RESUMEN
BACKGROUND: The finding that exposure to general anesthetics (GAs) in childhood may increase rates of learning disabilities has raised a concern that anesthetics may interfere with brain development. The generation of neuronal circuits, a complex process in which axons follow guidance cues to dendritic targets, is an unexplored potential target for this type of toxicity. METHODS: GA exposures were conducted in developing neocortical neurons in culture and in early postnatal neocortical slices overlaid with fluorescently labeled neurons. Axon targeting, growth cone collapse, and axon branching were measured using quantitative fluorescence microscopy. RESULTS: Isoflurane exposure causes errors in Semaphorin-3A-dependent axon targeting (n = 77 axons) and a disruption of the response of axonal growth cones to Semaphorin-3A (n = 2,358 growth cones). This effect occurs at clinically relevant anesthetic doses of numerous GAs with allosteric activity at γ-aminobutyric acid type A receptors, and it was reproduced with a selective agonist. Isoflurane also inhibits growth cone collapse induced by Netrin-1, but does not interfere branch induction by Netrin-1. Insensitivity to guidance cues caused by isoflurane is seen acutely in growth cones in dissociated culture, and errors in axon targeting in brain slice culture occur at the earliest point at which correct targeting is observed in controls. CONCLUSIONS: These results demonstrate a generalized inhibitory effect of GAs on repulsive growth cone guidance in the developing neocortex that may occur via a γ-aminobutyric acid type A receptor mechanism. The finding that GAs interfere with axon guidance, and thus potentially with circuit formation, represents a novel form of anesthesia neurotoxicity in brain development.
Asunto(s)
Anestésicos por Inhalación/farmacología , Axones/efectos de los fármacos , Isoflurano/farmacología , Neuronas/efectos de los fármacos , Receptores de GABA/efectos de los fármacos , Análisis de Varianza , Anestesia General/métodos , Animales , Encéfalo/efectos de los fármacos , Células Cultivadas , Quimiotaxis/efectos de los fármacos , Conos de Crecimiento/efectos de los fármacos , Técnicas In Vitro , Ratones , Ratones Endogámicos C57BL , Microscopía Fluorescente/métodos , Factores de Crecimiento Nervioso/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
Numerous studies from the clinical and preclinical literature indicate that general anesthetic agents have toxic effects on the developing brain, but the mechanism of this toxicity is still unknown. Previous studies have focused on the effects of anesthetics on cell survival, dendrite elaboration, and synapse formation, but little attention has been paid to possible effects of anesthetics on the developing axon. Using dissociated mouse cortical neurons in culture, we found that isoflurane delays the acquisition of neuronal polarity by interfering with axon specification. The magnitude of this effect is dependent on isoflurane concentration and exposure time over clinically relevant ranges, and it is neither a precursor to nor the result of neuronal cell death. Propofol also seems to interfere with the acquisition of neuronal polarity, but the mechanism does not require activity at GABAA receptors. Rather, the delay in axon specification likely results from a slowing of the extension of prepolarized neurites. The effect is not unique to isoflurane as propofol also seems to interfere with the acquisition of neuronal polarity. These findings demonstrate that anesthetics may interfere with brain development through effects on axon growth and specification, thus introducing a new potential target in the search for mechanisms of pediatric anesthetic neurotoxicity.
Asunto(s)
Anestésicos/toxicidad , Polaridad Celular/efectos de los fármacos , Corteza Cerebral/citología , Corteza Cerebral/efectos de los fármacos , Neuronas/efectos de los fármacos , Anestésicos Intravenosos/toxicidad , Animales , Axones/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Células Cultivadas , Femenino , Inmunohistoquímica , Isoflurano/toxicidad , Ratones , Ratones Endogámicos C57BL , Microscopía Fluorescente , Embarazo , Propofol/toxicidadRESUMEN
OBJECTIVE: To compare recurrence of signs of lower urinary tract disease (LUTD) in cats with idiopathic cystitis that were fed the dry or canned formulation of a commercial diet designed to result in production of an acidic urine. DESIGN: Prospective trial. ANIMALS: 54 client-owned cats with idiopathic cystitis that was diagnosed on the basis of a history of abnormal micturition, abnormal results on urinalysis, radiography, or cystoscopy, and lack of an alternative diagnosis. PROCEDURE: Cats were assigned to be fed the canned or dry formulation of the diet. Reevaluations conducted at 2 and 16 weeks, and at 6 and 12 months included a physical examination, CBC and serum biochemical analysis (except week 2), blood gas analysis, and urinalysis. Regular telephone contacts were also made. The study was discontinued after 12 months or if signs of LUTD recurred. RESULTS: Signs of LUTD did not recur in 16 of 18 cats fed the canned diet, and 17 of 28 cats fed the dry diet (chi 2, P < 0.05). Seven cats were reevaluated at recurrence. Owners of remaining cats in which signs of LUTD recurred declined to have their pets reexamined. A different problem (bacterial urinary tract infection) was identified in only 1 cat on reevaluation. Eight cats were lost to follow-up evaluation. CLINICAL IMPLICATIONS: Feeding this commercial canned urinary acidifying diet may reduce the proportion of cats with idiopathic cystitis that will have recurrence of signs of LUTD within a 12-month period.
Asunto(s)
Alimentación Animal , Enfermedades de los Gatos/dietoterapia , Cistitis/veterinaria , Dieta/veterinaria , Orina/química , Animales , Recuento de Células Sanguíneas/veterinaria , Análisis Químico de la Sangre/veterinaria , Gatos , Cistitis/dietoterapia , Femenino , Concentración de Iones de Hidrógeno , Masculino , Estudios Prospectivos , Recurrencia , Gravedad Específica , Urinálisis/veterinariaRESUMEN
OBJECTIVE: To evaluate the safety and efficacy of amitriptyline hydrochloride in the treatment of severe recurrent idiopathic cystitis (IC) in cats. DESIGN: Prospective study. ANIMALS: 15 cats with IC that failed to respond to other treatments. PROCEDURE: Each cat received 10 mg of amitriptyline, PO, every 24 hours in the evening for 12 months or until signs recurred. Urinalysis, CBC, serum biochemical analysis, urine bacteriologic culture, and cystoscopy were performed initially, and after 6 and 12 months in responders. Severity scores of owner-observed signs of lower urinary tract (bladder and urethra) disease were recorded. RESULTS: During the first 6 months of treatment, 11 of the 15 cats had no owner-observed signs of lower urinary tract disease. During the next 6 months, 9 of 15 cats remained free of signs of cystitis. Despite clinical improvement, cystoscopic abnormalities persisted in all cats at the 6- and 12-month evaluations. Hematuria and proteinuria were decreased at the 12-month evaluation compared with the initial evaluation. Two of 15 cats initially appeared somnolent after amitriptyline treatment. Of 9 cats completing the study, 7 had increased body weight and 8 had decreased coat quality compared with the initial evaluations. Four cats developed small cystic calculi during the first 6 months of the study. Serum biochemical or hematologic abnormalities were not detected during the study. CLINICAL IMPLICATIONS: Amitriptyline treatment successfully decreased clinical signs of severe recurrent IC in 9 of 15 cats treated. Somnolence, weight gain, decreased grooming, and transient cystic calculi were observed during treatment in some cats.
Asunto(s)
Inhibidores de Captación Adrenérgica/uso terapéutico , Amitriptilina/uso terapéutico , Antidepresivos Tricíclicos/uso terapéutico , Enfermedades de los Gatos/tratamiento farmacológico , Cistitis/veterinaria , Animales , Gatos , Cistitis/tratamiento farmacológico , Femenino , Masculino , Estudios Prospectivos , Recurrencia , Resultado del TratamientoRESUMEN
OBJECTIVE: To identify the underlying cause of clinical signs in cats with nonobstructive diseases of the bladder and urethra. DESIGN: Prospective case series. SAMPLE POPULATION: 109 cats examined by the urology service of The Ohio State University's veterinary teaching hospital because of stranguria, hematuria, pollakiuria, or urination in inappropriate locations. PROCEDURE: History was obtained and a CBC, serum biochemical analyses, serologic tests for FeLV and feline immunodeficiency virus, urinalysis, bacterial culture of urine, and contrast radiography or urethrocystoscopy (females only) were performed. RESULTS: 16 cats had cystic calculi: 8 had struvite uroliths, 7 had calcium oxalate uroliths, and 1 had a urolith of unknown composition in conjunction with an anatomic defect. Anatomic defects, including diverticulae, urethral strictures, and a malpositioned urethra, were identified in 12 cats. A urinary tract infection was identified in 1 cat, and neoplasia was diagnosed in 2. One of the cats with neoplasia also had a struvite urolith. The remaining 80 cats did not have an anatomic defect, urolith, or tumor. Ten of these cats also did not have radiographic or cystoscopic abnormalities and were presumed to have a behavioral disorder. The remaining 70 cats had radiographic or cystoscopic abnormalities, and idiopathic cystitis was diagnosed. In 14 of the cats with idiopathic cystitis, results of a urinalysis were normal. Cats with idiopathic cystitis were significantly more likely to eat dry food exclusively (59%) than were cats in the general population (19%). CLINICAL IMPLICATIONS: Results suggest that idiopathic cystitis occurs commonly in cats with stranguria, hematuria, pollakiuria, or inappropriate elimination and is associated with consumption of dry foods. Contrast radiography or cystoscopy is necessary for differentiating idiopathic cystitis from behavioral disorders in some cats.
Asunto(s)
Enfermedades de los Gatos/diagnóstico , Enfermedades Urológicas/veterinaria , Alimentación Animal/efectos adversos , Alimentación Animal/clasificación , Animales , Gatos , Cistitis/diagnóstico , Cistitis/veterinaria , Cistoscopía/veterinaria , Divertículo/diagnóstico , Divertículo/veterinaria , Femenino , Hematuria/diagnóstico , Hematuria/veterinaria , Concentración de Iones de Hidrógeno , Compuestos de Magnesio/análisis , Masculino , Fosfatos/análisis , Estudios Prospectivos , Proteinuria/diagnóstico , Proteinuria/veterinaria , Gravedad Específica , Estruvita , Uretra/anomalías , Estrechez Uretral/diagnóstico , Estrechez Uretral/veterinaria , Cálculos de la Vejiga Urinaria/química , Cálculos de la Vejiga Urinaria/diagnóstico , Cálculos de la Vejiga Urinaria/veterinaria , Enfermedades de la Vejiga Urinaria/diagnóstico , Enfermedades de la Vejiga Urinaria/veterinaria , Orina/química , Enfermedades Urológicas/diagnósticoRESUMEN
This article discusses the utility and limitations of urethroscopy and cystoscopy in both male and female cats. The special equipment and techniques necessary to adequately visualize the urethra and bladder of female cats are described in some detail. The emerging ability to visualize the male urethra is introduced. Photographs taken through the cystoscope are used to illustrate both normal anatomy and lesions likely to be encountered with cats with lower urinary tract disease. Cystoscopy is an important diagnostic tool for an inclusionary and exclusionary diagnosis of interstitial cystitis (sterile idiopathic inflammation).
Asunto(s)
Biopsia/veterinaria , Gatos/anatomía & histología , Cistoscopía/veterinaria , Sistema Urinario/patología , Anestesia/veterinaria , Animales , Biopsia/métodos , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/patología , Cistoscopía/métodos , Endoscopía/métodos , Endoscopía/veterinaria , Femenino , Masculino , Uretra/patología , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/patología , Infecciones Urinarias/veterinaria , Fenómenos Fisiológicos del Sistema Urinario , Enfermedades Urológicas/diagnóstico , Enfermedades Urológicas/patología , Enfermedades Urológicas/veterinariaRESUMEN
Cholecystectomy is the most common surgical procedure in the elderly. Published reports on this operation suffer from small sample sizes, crude analyses, erroneous conclusions, and unsupported recommendations. The authors reviewed all first operations for cholelithiasis at the North Carolina Memorial Hospital from 1973 to 1982 to assess factors associated with postoperative morbidity in patients aged 70 years or older after biliary tract surgery. These elderly patients (n = 142) had more frequent postoperative complications (26.1% vs. 12.0%, p less than 0.0001), and greater mortality (9.2% vs. 2.7%, p less than 0.005) than did 839 younger patients. Patients with preoperative cardiac, renal or neurologic problems had more frequent postoperative complications whether they were old or young. Postoperative complications were more frequent in the elderly for non-emergency surgery (21.2% vs. 9.7%) but not for emergency surgery (44.8% vs. 42.4%). Logistic regression analysis was used to determine independent predictors of postoperative complications. Age greater than or equal to 70 years was associated with an increase in risk that was not statistically significant.