Administration Of Anticholinergic Agents Research Articles

TH17 cells mediate inflammation in a novel model of spontaneous experimental autoimmune lacrimal keratoconjunctivitis with neural damage

Dry eye disease (DED) affects one third of the population worldwide. In prior studies, experimental autoimmune lacrimal keratoconjunctivitis (EALK) induced by desiccating stress in mice has been used as a model of DED. This model is complicated by a requirement for exogenous epithelial cell injury and administration of anticholinergic agents with broad immunologic effects. We sought to develop a novel mouse model of EALK and to demonstrate the responsible pathogenic mechanisms. CD4+CD45RBhigh naive T cells with and without CD4+CD45RBlow regulatory T cells were adoptively transferred to C57BL/10 recombination-activating gene 2 (Rag2)-/- mice. The eyes, draining lymph nodes, lacrimal glands, and surrounding tissues of mice with and without spontaneous keratoconjunctivitis were evaluated for histopathologic changes, cellular infiltration, and cytokine production in tissues and isolated cells. Furthermore, the integrity of the corneal nerves was evaluated using whole-tissue immunofluorescence imaging. Gene-deficient naive T cells or RAG2-deficient hosts were evaluated to assess the roles of IFN-γ, IL-17A, and IL-23 in disease pathogenesis. Finally, cytokine levels were determined in the tears of patients with DED. EALK developed spontaneously in C57BL/10 Rag2-/- mice after adoptive transfer of CD4+CD45RBhigh naive T cells and was characterized by infiltration of CD4+ T cells, macrophages, and neutrophils. In addition to lacrimal keratoconjunctivitis, mice had damage to the corneal nerve, which connects components of the lacrimal functional unit. Pathogenic T-cell differentiation was dependent on IL-23p40 and controlled by cotransferred CD4+CD45RBlow regulatory Tcells. TH17 rather than TH1 CD4+ cells were primarily responsible for EALK, even though levels of both IL-17 and IFN-γ were increased in inflammatory tissues, likely because of their ability to drive expression of CXC chemokines within the cornea and the subsequent influx of myeloid cells. Consistent with the findings of this model, the tears of patients with DED had increased levels of inflammatory cytokines, including IL-17A and TNF-α. We describe a novel model of spontaneous EALK that supports a role for TH17cells in disease pathogenesis and that will contribute to our understanding of autoimmune lacrimal keratoconjunctivitis in many human eye diseases, including DED.

Transient Asystole During Surgery for Posterior Fossa Meningioma Caused by Activation of the Trigeminocardiac Reflex -Three Case Reports-

Three patients undergoing surgery for cerebello-pontine angle meningioma suffered transient episodes of asystole. All patients exhibited return to the previous heart rate with cessation of surgical manipulations and administration of anticholinergic agents. These reactions were apparently elicited by activation of the trigeminocardiac reflex (TCR) by direct stimulation of the trigeminal nerve or branches in the dura mater or cerebellar tentorium. Remifentanil was used in all three cases as an anesthetic agent, so may be a cause of the TCR. The possibility of activation of the TCR should be considered during surgical manipulation around the trigeminal nerve or the distribution of the trigeminal nerve branches. Transient bradycardia, hypotension, or asystole can occur regardless of whether there is pressure on the brainstem during posterior fossa meningioma surgery.

Risk Management for Gastrointestinal Endoscopy in Elderly Patients: Questionnaire for Patients Undergoing Gastrointestinal Endoscopy

More elderly patients now undergo gastrointestinal endoscopy following recent advances in endoscopic techniques. In this study, we conducted a high-risk survey of endoscopies in Japan, using a questionnaire administered prior to upper gastrointestinal tract endoscopy (UGITE), and identified anticholinergic agents and glucagon preparations as high-risk premedication. We also evaluated the cardiovascular effects of anticholinergic agents and glucagon through measurements of plasma levels of human atrial natriuretic peptide (hANP) and human brain natriuretic peptide (hBNP). The subjects were 1480 patients who underwent UGITE. Nurses administered a pre-endoscopy questionnaire, questioning subjects regarding heart disease, hypertension, glaucoma, and urinary difficulties as risk factors for anticholinergic agents, and Diabetes mellitus as a risk factor for glucagon preparations. Evaluation of subjects divided into under 65 and over 65 age groups revealed that in subjects aged 65 and over, risk factors for anticholinergic agents were significantly more high than those for glucagon. Analysis of the cardiovascular effects of anticholinergic agents and glucagon, in the elderly patients showed that hANP levels were significantly higher following administration of anticholinergic agents, but the change was not significant for glucagon premedication. Taking a detailed history before UGITE with the aid of a questionnaire at the same time as informed consent is obtained, is extremely useful in terms of risk management and selection of the appropriate premedication.

The effect of desmopressin (DDAVP) in patients complaining of nocturia

The mechanism of increased nocturnal urine production in adult patients complaining of nocturia has seldom been reported. The objective of this clinical study is to investigate the circadian rhythm of both urine production and plasma arginine-vasopressin (AVP) level, and the efficacy of intranasal instillation of 1-deamino-8-D-arginine-vasopressin (DDAVP) in adult patients complaining of nocturia. Eight patients (seven men, one woman) who ranged in age from 44 to 77 years (mean 64.1 years) were examined. Three of them suffered from Shy-Drager syndrome, and no patient had shown any improvement of symptoms in spite of administration of anti-cholinergic agents and restriction of water intake. Nocturnal urine volume was more than bladder capacity in all patients, and no patient showed normal elevation of nocturnal plasma AVP level. Intranasal administration of DDAVP of 5 or 10 micrograms revealed marked decrease in nocturia, and nocturnal urine volume (p < 0.01). There were mild side effects (headache, nasal obstruction, and hyponatremia) not requiring any treatment. In conclusion, DDAVP is a safe and effective treatment for adult patients complaining of nocturia due to hyperproduction of nocturnal urine and inappropriate nocturnal secretion of AVP.

無抑制膀胱と逆流防止術

A retrospective study on antireflux surgery for primary vesicoureteral reflux at Hokkaido University Hospital was performed. One hundred and seventy-nine patients (299 ureters) underwent antireflux surgery in these 17 years and 7 months. When the period was divided into 3, success rate was 96.5, 93.8 and 100 per cent, respectively. Overall success rate was 96.6 per cent. There was a combined failure or complication in 9 patients. The records of these 9 were reviewed in detail. Three were believed to be a technical error: 2 stricture and one persistent reflux. The remaining 6 were all children except one and had no clear reason for failure: 2 persistent reflux and 4 contralateral appearance of reflux ("missing VUR"). Four of these 6 patients were characterized by voiding dysfunction, namely uninhibited bladder. In 3 patients reflux disappeared spontaneously by administration of anticholinergic agent. In many of these, vesical diverticulum formation was also noted to precede or to coincide with recurrence or appearance of reflux. Thus other 3 patients with diverticulum formation after antireflux surgery were added and re-evaluated. All 3 children had voiding dysfunction with uninhibited bladder. Diverticulum formation was believed to be related to uninhibited bladder in at least one child. It seems that the child with uninhibited bladder and reflux is particularly at risk for failure or complication of antireflux surgery. Patients with symptoms of voiding dysfunction deserve a complete evaluation, including cystoscopy and urodynamics.