RESUMEN
Boucher-Neuhäuser syndrome (BNHS) is characterized by chorioretinal dystrophy, hypogonadotropic hypogonadism, and cerebellar dysfunction and atrophy. The disorder has been associated with biallelic pathogenic variants in the patatin-like phospholipase domain-containing protein 6 (PNPLA6) gene. We present an individual with a clinical diagnosis consistent with BNHS who lacked any PNPLA6 variants but on quartet family exome sequencing had a de novo variant in the hexokinase 1 (HK1) gene (NM_000188.2 [GRCh37/hg19]: g.71139826G>A, c.1240G>A, p.Gly414Arg), suggesting genetic heterogeneity for BNHS. Longitudinal follow-up indicated neurological deterioration, neuropsychiatric symptoms, and progressive cerebellar atrophy. The BNHS phenotype overlaps and expands the known HK1 genotypic and phenotypic spectrum. Individuals with variants in HK1 should undergo evaluation for hypogonadotropic hypogonadism, potentially amenable to treatment.
Asunto(s)
Hipogonadismo , Síndrome de Klinefelter , Ataxias Espinocerebelosas , Humanos , Hexoquinasa/genética , Ataxias Espinocerebelosas/genética , Hipogonadismo/diagnóstico , Hipogonadismo/genética , AtrofiaRESUMEN
Phasic contractile activity in rat portal vein is more sensitive to the rate of change in length than to absolute length and this response is widely assumed to be a general characteristic of myogenic behaviour for vascular smooth muscle. Previously, we found that rat lymphatic vessels exhibit phasic contractile behaviour similar to that of portal vein. In the present study, we hypothesized that lymphatic muscle would exhibit rate-sensitive contractile responses to stretch. The hypothesis was tested on rat mesenteric lymphatics (90-220 microm, i.d.) using servo-controlled wire- and pressure-myograph systems to enable ramp increases in force or pressure at different rates. Under isometric conditions in wire-myograph preparations, both the amplitude and the frequency of phasic activity were enhanced at more optimal preloads, but superimposed upon this effect were bursts of contractions that occurred only during fast preload ramps. In such cases, the ratio of contraction frequency during the ramp to that at the subsequent plateau (at optimal preload) was > 1. Further, the frequency ratio increased as a function of the preload ramp speed, consistent with a rate-sensitive mechanism. In contrast, the amplitude ratio was < 1 and declined further with higher ramp speeds. Downward preload ramps produced corresponding rate-sensitive inhibition of contraction frequency but not amplitude. Similar findings were obtained in pressurized lymphatics in response to pressure ramps and steps. Our results suggest that lymphatics are sensitive to the rate of change in preload/pressure in a way that is different from portal vein, possibly because the pacemaker for generating electrical activity is rate sensitive but lymphatic muscle is not. The behaviour may be widely present in collecting lymphatic vessels and is probably an important mechanism for rapid adaptation of the lymphatic pump to local vascular occlusion.
Asunto(s)
Vasos Linfáticos/fisiología , Animales , Contracción Isométrica/fisiología , Masculino , Músculo Liso/fisiología , Miografía , Especificidad de Órganos , Vena Porta/fisiología , Presión , Ratas , Ratas Sprague-Dawley , Estrés MecánicoRESUMEN
PURPOSE: To describe a case of chronic exogenous Exophiala dermatitidis endophthalmitis. METHODS: Retrospective chart review and case report. RESULTS: A 60-year-old man with history of chronic herpes zoster keratitis complicated by secondary fungal keratitis treated with penetrating keratoplasty presented with a white cataract, chronic anterior uveitis, and counting fingers vision in the left eye. Combined cataract extraction and diagnostic vitrectomy revealed positive cultures and polymerase chain reaction-based testing for E. dermatitidis-the same organism responsible for the keratitis. The patient was treated with multiple oral, intravenous, and intravitreal antifungal agents. Ultimately, the corneal infection recurred and the patient elected to undergo enucleation. Filamentous fungi consistent with E. dermatitidis infection were identified in the cornea of the enucleation specimen. CONCLUSION: Although rare, Exophiala species can cause exogenous endophthalmitis. Chronic endophthalmitis should be suspected in patients who develop persistent intraocular inflammation after infectious keratitis.
Asunto(s)
Endoftalmitis/microbiología , Infecciones Fúngicas del Ojo/microbiología , Feohifomicosis/diagnóstico , Enfermedad Crónica , Humanos , Queratitis/microbiología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
We tested the hypothesis that lymphatics would exhibit myogenic constrictions and dilations to intraluminal pressure changes. Collecting lymphatic vessels were isolated from rat mesentery, cannulated, and pressurized for in vitro study. The lymphatic diameter responses to controlled intraluminal pressure steps of different magnitudes were tested in the absence and presence of the inflammatory mediator substance P, which is known to enhance lymphatic contractility. Myogenic constriction, defined as a time-dependent decrease in end-diastolic diameter over a 1- to 2-min period following pressure elevation (after initial distension), was observed in the majority of rat mesenteric lymphatic vessels in vitro and occurred over a relatively wide pressure range (1-15 cmH2O). Myogenic dilation, a time-dependent rise in end-diastolic diameter following pressure reduction, was observed in over half the vessels equilibrated at a low baseline pressure. Myogenic constrictions were independent of the cardiac-like and time-dependent compensatory decline in end-systolic diameter and increase in amplitude observed in almost all vessels following pressure elevation. Substance P increased the percentage of vessels exhibiting myogenic constriction, the magnitude and rate of constriction, and the pressure range over which constriction occurred. Our results demonstrate that myogenic responses occur in collecting lymphatic vessels and suggest that the response may aid in preventing vessel overdistension during inflammation/edema.