PubMed Health⌕ Search

Biomedical subjects

F Casellas

Publications and source records attributed to F Casellas.

At least 37 records · Page 2Linked to original sources

[Patient assessment of the long-term benefits of surgery in inflammatory bowel disease].

UNLABELLED: The objective of surgical treatment in ulcerative colitis (UC) and Crohn's disease (CD) differs. Surgery in UC is more aggressive and potentially curative whereas in CD it is more conservative and palliative. OBJECTIVE: To assess the opinion of patients with inflammatory bowel disease who underwent surgery in the distant past about the results and timing of surgery. MATERIAL AND METHODS: A total of 50 surgical patients (36 with CD and 14 with UC) who had undergone an intestinal surgical procedure at least one year before. The clinical characteristics of patients and details of surgery procedures were recorded. Also, a personal interview was conducted. Patients were asked about their current clinical status, surgical consequences and their opinion about the appropriate timing of surgery. RESULTS: Surgery for UC was total proctocolectomy in 85% of patients and it was on an emergency basis in 43% of them. Surgery for UC was partial intestinal or colonic resection, and it was on an emergency basis in 22% of them. Postsurgical complications were more common in UC than CD patients (50% versus 20%; p < 0.05). In CD surgery, recurrence of disease occurred in 78% of patients within a 2.6 years interval. Among UC and CD patients, 71% and 50%, respectively, reported that their presurgical expectatives had been fulfilled (p = 0.17). CONCLUSIONS: Surgery for UC is associated with an appreciable rate of complications; however, most patients had their expectatives fulfilled with surgery as long-term symptoms were controlled. As for CD, the patient's satisfaction degree was lower than or UC.

Adult↗

Improved screening for intestinal villous atrophy by D-xylose breath test.

The hydrogen breath test (H2BT) with D-xylose has proven valid in both early recognition and follow-up of intestinal malabsorption. To further evaluate the specificity of the H2BT with D-xylose in the diagnosis of intestinal malabsorption as compared to the conventional urinary D-xylose test, we analyzed the result in 49 patients referred to our unit with a clinical diagnosis of intestinal malabsorption. These patients had an abnormal 25-g D-xylose H2BT but a normal conventional urinary D-xylose test. Jejunal biopsy with Watson capsule was performed in all patients. H&E staining was prepared from each biopsy specimen, and histological changes were classified according to the Marsh criteria. Jejunal biopsy showed mucosal atrophy in 5 patients (10%), hyperplastic lesion in 11 (22.5%), infiltrative lesion in 14 (28.5%), and normal appearance in 19 (39%). G. lamblia infection was additionally diagnosed in two patients. Histological changes were independent of the presence of diarrhea, weight loss, abdominal pain, or anemia. H2 excretion, assessed as increase over baseline and area under the curve, was similarly independent of the histological pattern. In conclusion, performance of a D-xylose H2BT in patients with a normal urinary test reveals a significant number of patients with intestinal mucosal atrophy who might otherwise remain undiagnosed.

Adolescent↗

Helicobacter pylori eradication prevents recurrence from peptic ulcer haemorrhage.

BACKGROUND: Successful eradication of Helicobacter pylori infection clearly modifies the natural history of peptic ulcer disease and prevents further recurrences of duodenal and gastric ulcers. However, there are few prospective studies about actual rates of rebleeding after H. pylori eradication, a highly relevant aspect of management as re-infection, relapse of ulcer disease for other reasons (i.e. anti-inflammatory agents) or idiopathic ulcers unrelated to H. pylori may develop and cause further bleeding episodes. OBJECTIVE: To determine the incidence of bleeding episodes after eradication of H. pylori infection in patients who had bled from an H. pylori-positive peptic ulcer. PARTICIPANTS AND INTERVENTIONS: H. pylori-positive patients who bled from a gastric or duodenal ulcer were treated with appropriate triple and/or quadruple therapy. H. pylori eradication was confirmed by urea breath test 4 weeks after treatment. Patients received no further treatment but were followed clinically and additional urea breath tests were performed every 6 months. Endoscopy with antral and corpus biopsies and urea breath test were repeated as soon as patients manifested any dyspeptic symptoms that might signal recurrence. RESULTS: A total of 103 patients with bleeding duodenal ulcer were included in the study; H. pylori was successfully eradicated in 93 of these patients, who were followed for a median interval of 27 months. The yearly re-infection rate was calculated to be 0.6%. There were no instances of rebleeding in any patients during the follow-up period. CONCLUSIONS: Even after prolonged follow-up, successful H. pylori eradication prevents rebleeding.

Adult↗

Impact of surgery for Crohn's disease on health-related quality of life.

OBJECTIVE: When patients with Crohn's disease (CD) express concerns about their disease, they emphasize worries about surgery. However, most studies about the impact of surgery in CD on health-related quality of life (HRQOL) have compared postsurgical changes on HRQOL relative to HRQOL before surgery, not taking into account the influence of CD activity on HRQOL. Our aim was to assess whether surgical treatment of CD modifies HRQOL, compared with inactive CD, active CD, or healthy controls. METHODS: Outcomes of 29 CD patients in remission with a previous bowel resection were compared with those from 42 clinically active CD patients and 48 patients with medically induced remission. A reference control group of 63 healthy individuals was also studied. HRQOL was measured by the Inflammatory Bowel Disease Questionnaire (IBDQ), the Psychological General Well Being Index (PGWBI), and the EuroQol. RESULTS: Active CD patients scored the lowest on the IBDQ. Both operated and nonoperated inactive CD patients had lower HRQOL scores than controls in overall IBDQ and in all five domains. However, neither global score, digestive, systemic, emotional, social, or functional dimensions differed significantly between operated and nonoperated inactive CD patients. PGWBI and the visual analog scale of the EuroQol were also similar in both groups of inactive CD patients (103 [range, 94-107] vs. 103 [97-106] and 90 [73-87] vs. 82 [76-84]), but significantly higher than in active CD. CONCLUSIONS: HRQOL is impaired in active CD, and improves during remission irrespective of whether it had been achieved medically or surgically. Our results suggest that to improve HRQOL it is more important to achieve remission than the approach, drugs or surgery, chosen.

Adult↗

Genetic heterogeneity within ulcerative colitis determined by an interleukin-1 receptor antagonist gene polymorphism and antineutrophil cytoplasmic antibodies.

BACKGROUND: Although there is strong evidence implicating genetic predisposition in the pathogenesis of the chronic inflammatory bowel diseases, the number and identity of susceptibility genes remain uncertain. Cytokine genes are tentative candidate loci, but data regarding association studies in different populations are conflicting. AIMS: To determine potential associations of interleukin-1 receptor antagonist (IL-1ra), tumour necrosis factor alpha (TNF alpha), and tumour necrosis factor beta (TNF beta) gene polymorphisms with ulcerative colitis or subsets of ulcerative colitis in a Spanish population. METHODS: Genotyping for IL-1ra, TNF alpha and TNF beta gene polymorphisms was performed by the polymerase chain reaction in 95 patients with ulcerative colitis and 74 healthy controls. A variable number of tandem repeats (VNTR) in the IL-1ra gene, and a single base pair polymorphism in the TNF alpha gene promoter region (-308) and in the first intron of the TNF beta gene were analysed. Anti-neutrophil cytoplasmic antibodies (ANCA) were detected using an indirect immunofluorescence assay. RESULTS: There were no significant differences between ulcerative colitis patients and controls in either polymorphism analysed, nor between ulcerative colitis subgroups as a function of the clinical disease pattern. However, when stratified by their ANCA status, perinuclear ANCA (p-ANCA) ulcerative colitis showed an increased frequency of the genotype 1,2 of the IL-1ra gene compared with ANCA-negative ulcerative colitis (52% versus 28%; P = 0.02, Pcorr = 0.1). Furthermore, p-ANCA ulcerative colitis had a statistically significant increase of this genotype compared with cytoplasmic ANCA (c-ANCA)/ANCA-negative ulcerative colitis (52% versus 26.5%; P = 0.01, Pcorr = 0.05). CONCLUSIONS: In the Spanish population studied, the polymorphisms analysed in the IL-1ra, TNF alpha and TNF beta genes are unlikely to be important in the overall susceptibility to ulcerative colitis. However, the combination of a subclinical (p-ANCA) and a genetic (IL-1ra gene) marker identified a distinct ulcerative colitis subgroup (p-ANCA; IL-1ra genotype 1,2). These findings provide further evidence of genetic heterogeneity within ulcerative colitis, and support the concept that ANCA may represent a subclinical marker of genetic heterogeneity.

Adolescent↗

The impact of delaying gastric emptying by either meal substrate or drug on the [13C]-urea breath test.

OBJECTIVE: Optimal [13C]-urea breath test (UBT) conditions for diagnosis of Helicobacter pylori infection are still being fine-tuned. In the present study we investigated the impact of delaying gastric emptying by different meal substrates or L-DOPA, a drug known to induce gastric stasis, on the performance of the [13C]-UBT. METHODS: A total of 115 patients participated in the study. On two consecutive days, participants ingested [13C]-urea (100 mg) 10 min after either 270 ml of a mixed formula meal (1 Kcal/ml) or an equivalent amount of tap water. In 11 participants two additional tests were performed with or without oral 500 mg L-DOPA given 30 min before [13C]-urea load. The 13C/12C ratio in a basal breath sample was compared with ratios in samples collected 30 and 60 min after [13C]-urea. Histological assessment of H. pylori presence in antral biopsy served as reference standard. RESULTS: Formula UBT showed excellent specificity (100% at 30 and 60 min) and good sensitivity (97% at both time intervals), whereas water UBT had the same specificity but slightly lower sensitivity (94% at 30 min and 73% at 60 min). In formula UBT, 13C/12C ratios were higher at 60 min than at 30 min (21.7+/-2 vs 17.7+/-1.8 per thousand respectively, p < 0.01, whereas in water UBT 13C/12C ratios were higher at 30 min than at 60 min (13.9+/-1.5 vs 8.4+/-0.09 per thousand respectively, p < 0.01). Pretreatment with L-DOPA did not modify either the sensitivity or the specificity of the UBT. CONCLUSIONS: The performance of the [13C]-urea with a formula meal may not be improved by pharmacologically delaying gastric emptying. A short, water-based test may be a sensible approach to worldwide standardization of the [13C]-UBT for H. pylori infection.

Adult↗

Validation of the spanish version of the inflammatory bowel disease questionnaire on ulcerative colitis and Crohn's disease.

The objective of this study is to validate the Spanish translation of the Inflammatory Bowel Disease Questionnaire (SIBDQ) on ulcerative colitis and Crohn's disease by assessing its convergence validity, discriminatory power, reliability and sensitivity to change. For that purpose, 211 patients with inflammatory bowel disease (116 with ulcerative colitis and 95 with Crohn's disease) completed the SIBDQ, the Psychological General Well-Being Index and the EuroQol. SIBDQ was repeated in those patients who remained in stable remission and in those with changes in clinical activity. Clinical activity was assessed by the Rachmilewitz and Harvey-Bradshaw indices. Correlations among scores of SIBDQ, EuroQol, Psychological General Well-Being Index and clinical indices of activity were all positive and comparable for both diseases (r = -0. 50 to r = -0.70, p < 0.01). Analysis of variance showed that SIBDQ discriminates between different clinical degrees of activity. Cronbach's alpha was 0.96 in ulcerative colitis and Crohn's disease. SIBDQ was also highly reliable when it was repeated in clinically stable patients with ulcerative colitis (intraclass correlation coefficient = 0.82) and Crohn's disease (intraclass correlation coefficient = 0.86). SIBDQ was sensitive to clinical changes in ulcerative colitis and in Crohn's disease, whether patients entered remission (effect size -1.88 and -1.81, respectively) or relapsed (effect size 1.70 and 8.04, respectively). In conclusion, the Spanish version of the IBDQ has proven to be a valid, reliable and sensitive instrument to detect clinical changes in patients with ulcerative colitis and Crohn's disease.

Adolescent↗

Impact of inflammatory bowel disease on health-related quality of life.

Health-related quality of life (HRQOL) has a recognized importance to evaluate, manage and follow patients. Different types of instruments for measuring HRQOL have recently been introduced to evaluate HRQOL in patients with inflammatory bowel disease. Most questionnaires suggest that inflammatory bowel disease has a significant impact in HRQOL. It seems that ulcerative colitis has less profound effects on HRQOL than Crohn's disease and that some differences in HRQOL status are related to some factors such as the severity of the disease. When patients express their concerns, most important worries are related to surgery. Effective medical treatment appears to improve HRQOL. Effects of surgery on HRQOL can probably be different depending on the type of surgical technique and if it is curative or not. Recent studies suggest that inflammatory bowel disease not only impacts on patient's HRQOL but also on their caregivers. Features such as the impact on HRQOL of different disease variables, such as complications or patient personality, the role of medical or surgical treatments on different dimensions of HRQOL, the cost-utility evaluation of therapy are some of the fields that will probably focus the protagonism in the next years.

Colitis, Ulcerative↗

Hydrogen breath test with glucose in exocrine pancreatic insufficiency.

The present study was designed to investigate the prevalence of bacterial overgrowth in patients with exocrine pancreatic insufficiency by using the hydrogen breath test with glucose. Thus, in 30 patients with exocrine pancreatic insufficiency (in 15 due to chronic pancreatitis and in 15 associated to primary immunodeficiency), established by quantifying trypsin output before and after stimulation with cerulein using a duodenal perfusion technique, a glucose test was performed by administering 50 g of glucose and quantifying H2 in the breath by gas chromatography. The glucose test was positive in six of 15 patients with chronic pancreatitis but in only one of 15 immunodeficient patients (p < 0.05). Age, sex, etiology, time of evolution, associated diabetes, pancreatic calcifications, duodenal pH, or duodenal trypsin output did not differ between patients with and those without bacterial overgrowth. Previous gastroduodenal surgery was more common in chronic pancreatitis patients with overgrowth (six of six vs. four of nine; p < 0.05). Five patients with a positive glucose test were treated with antibiotics for 2 weeks and became negative in two of them. These results suggest that a positive glucose test indicating overgrowth is relatively common in exocrine pancreatic insufficiency due to chronic pancreatic, especially in patients with previous gastroduodenal surgery.

Adolescent↗

Antiinflammatory effects of enterically coated amoxicillin-clavulanic acid in active ulcerative colitis.

The inflammatory activity of colonic mucosal lesions may be stimulated by intraluminal bacteria. Our aim was to investigate whether administration of broad-spectrum antibiotics decreases inflammatory activity in ulcerative colitis. To this end, we performed a randomized, 5-day study with either oral enterically coated amoxicillin-clavulanic acid (1 g + 250 mg, t.i.d.); i.v. methylprednisolone (40 mg/day) and oral placebo (t.i.d.); or both i.v. methylprednisolone and oral amoxicillin-clavulanic acid as above, in 30 patients with clinically active ulcerative colitis. Before and after 5 days of treatment, intestinal inflammation was assessed by the quantification of mucosal release of eicosanoids and interleukin-8 by rectal dialysis in each patient. Breath H2 excretion after oral lactulose was determined as an index of metabolic activity of colonic flora. The total release of (IL-8) interleukin-8 and eicosanoids significantly decreased in patients treated with antibiotic or steroids and antibiotic. Antibiotic treatment, but not steroids, markedly inhibited breath H2 excretion. In conclusion, short-term treatment with enteric-coated amoxicillin-clavulanic acid decreases the intraluminal release of IL-8 and other inflammatory mediators.

Adolescent↗

Influence of the smoking habit in the surgery of inflammatory bowel disease.

UNLABELLED: The smoking habit is a key factor in the development of inflammatory bowel disease (IBD), but little information exists as to the relationship between smoking habit, the need of surgery and its complications. OBJECTIVES: To investigate the relationship between smoking habit, the need of surgery, their complications and clinical recurrence after surgery in Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We studied a group of 62 patients (22 with UC and 40 with CD) with previous surgery. We analyzed the clinical and surgical characteristics of the disease. Smoking habit was established by a personal interview. This group of patients was compared with another control group of 202 patients (133 with UC and 69 with CD) with IBD without previous surgery. RESULTS: Smoking habit was similar between operated and non-operated patients for both UC (73% and 80% non-smokers) and CD (67% and 63% smokers) The number and type of complications after surgery were not related with smoking habit. In CD patients, although the recurrences did not depend on the smoking habit, they did occur earlier in smokers than in non smokers (83.6 +/- 21 vs 155 +/- 50 weeks, p = ns). CONCLUSIONS: The smoking habit does not seem to influence significantly the need of surgery and post surgical development of IBD, although in CD the smokers seems to present recurrence before non smokers.

Adult↗

Effects of smoking on the presentation and clinical course of inflammatory bowel disease.

OBJECTIVE: To evaluate the influence of regular smoking on the presentation and clinical course of inflammatory bowel disease. METHODS: We performed a case-control study interviewing 160 inflammatory bowel disease patients (63 with Crohn's disease (CD) and 97 with ulcerative colitis (UC)) and 140 first-degree relatives as controls. The risk of developing the disease relative to a smoking habit was calculated as the odds ratio. Furthermore, to evaluate the influence of smoking on the subsequent course of inflammatory bowel disease, we performed a multivariate analysis that included pertinent variables such as the need for surgery, number of hospitalizations and relapses. RESULTS: The pattern of smoking in UC patients was different from that in CD patients. In UC there was a significant predominance of non-smokers and ex-smokers (P = 0.02), whereas smoking habits in CD were not different from those in controls. Giving up smoking was a risk factor to develop UC (odds ratio: 3.2, P = 0.02). In UC, non-smokers and specially ex-smokers need surgery more frequently than smokers (P < 0.01). Otherwise the relapse/year index was not influenced by smoking. In CD there was a non-significant association between smoking habits and the various clinical parameters analysed. UC patients who begin smoking after diagnosis of the disease present a significant reduction in the number of recurrences. CONCLUSION: Smoking habit significantly affects the presentation and clinical course of UC, whereas in CD, a smoking habit does not have any apparent influence on the disease.

Adult↗

Usefulness of rectal dialysis to determine intrarectal eicosanoids release in ulcerative colitis.

The quantification of the local production of eicosanoids is of interest because it has been implicated in the mucosal damage of ulcerative colitis. In situ production of eicosanoids is not reflected by its urinary or seric levels, requiring invasive examinations. Thus, new non-invasive techniques such as rectal dialysis have been investigated. The purpose of this study was to assess whether the determination of the intrarectal eicosanoid levels measured by rectal dialysis is useful in detecting the presence of rectal inflammation in patients with ulcerative colitis. Thirty one patients with clinically active colitis and 7 controls with irritable bowel syndrome have been studied. A 10 cm long dialysis bag was placed in the rectum for 1 hour. To determine the variability of the technique, the dialysis was repeated the next day in 6 controls. To detect intrarectal eicosanoids release in inactive colitis, rectal dialysis was performed in another group of 15 patients with clinical and endoscopically inactive colitis and compared with 9 patients with active colitis. PGE2, TXB2, and LTB4 were measured in rectal dialysates by immunospecific RIA. Dialysis was well tolerated by all participants. Intrarectal level of every eicosanoid was much higher in active colitis than in controls (p < 0.05) and in inactive colitis (p < 0.001). The mean coefficient of variation of duplicated dialysis ranged from 15 to 28%. In conclusion, rectal dialysis is a non-invasive technique that allows to prove the presence of active inflammation in ulcerative colitis patients.

Adolescent↗

Seasonal influence in exacerbations of inflammatory bowel disease.

Several epidemiological studies have suggested a possible seasonality in the presentation and course of inflammatory bowel disease. Our aim was to investigate whether in our area there is a seasonality in the presentation and evolution of inflammatory bowel disease. In this retrospective evaluation 255 patients were included, of whom 141 patients were diagnosed with ulcerative colitis and 114 with Crohn's disease according to conventional criteria, with histological confirmation in 225 patients. Relapse was defined as the development of symptoms that required an increase or change in the usual treatment. Periods of activity were related to the month and grouped within one of four seasonal periods: December to February, March to May, June to August and September to November. Bouts of ulcerative colitis and Crohn's disease were most frequently diagnosed in the period June to August (p < 0.05). Both diseases showed similar seasonality, and analysis of the 305 attacks did not show any significant trend. In conclusion, inflammatory bowel disease begins more frequently in the period June to August, but its course does not show consistent seasonal variations.

Adolescent↗

Follow-up of celiac disease with D-xylose breath test.

Hydrogen breath tests (H2-BT) are commonly used to diagnose carbohydrate malabsorption. Specifically, the H2-BT with D-xylose has been shown to be as valid as the traditional urinary test for the recognition of intestinal malabsorption. We have now investigated the H2-BT with D-xylose in the follow-up of patients with celiac disease. Seventeen patients with celiac disease established clinically and confirmed by jejunal biopsy were studied. H2-BT was performed before and after treatment with a gluten-free diet for at least five months. Alveolar breath samples were obtained before administering orally 25 g of D-xylose and thereafter at 30 min intervals for 5 hr. Samples were analyzed for H2 by chromatography. Simultaneously, the 5-hr urinary excretion of D-xylose was determined by colorimetry. Gluten removal significantly decreased the H2 delta change (from 56.5 +/- 5.9 ppm to 32.2 +/- 8.8, P < 0.05). A similar decrease was observed in the area under the curve (P < 0.05). Conversely, urinary D-xylose excretion increased significantly (P < 0.05). Eleven of the 17 celiacs clinically improved after treatment. The H2-BT normalized in every patient who entered remission on the gluten-free diet, whereas the urinary D-xylose excretion remained abnormal in six of them. In the six nonresponder patients the H2-BT remained high in five, whereas urinary D-xylose excretion paradoxically normalized in 2. We conclude that H2-BT with D-xylose is a useful and practical test for the follow-up of celiac disease and is simpler and more reliable than the urinary D-xylose test.

Adolescent↗

Bowel habit after cholecystectomy: physiological changes and clinical implications.

BACKGROUND & AIMS: Scarce data suggest that cholecystectomy may alter bowel habit. The aim of this study was to determine whether cholecystectomy modifies gut transit. METHODS: Five experimental groups were studied: 29 patients with uncomplicated gallstones before and 1 month after elective cholecystectomy, 22 patients 4 years after elective cholecystectomy, 14 patients with postcholecystectomy diarrhea, 5 patients with acute infectious diarrhea (disease controls), and 13 patients before and 1 month after other elective surgery (surgical controls). All participants underwent measurement of colonic transit by a modified radiopaque pellet method and orocecal transit by the standard lactulose breath H2 test. RESULTS: One month postoperatively, cholecystectomy had substantially accelerated total colonic transit (51 +/- 5 hours before vs. 38 +/- 5 hours after; P < 0.05) and delayed slightly orocecal transit (80 +/- 4 minutes before vs. 103 +/- 8 minutes after; P = 0.05). Similar colonic and orocecal transit times were measured 4 years after cholecystectomy (40 +/- 4 hours and 105 +/- 8 minutes, respectively). Colonic transit times in patients with the postcholecystectomy diarrhea syndrome were accelerated as much as in patients with infectious diarrhea, who served as controls (19 +/- 3 hours and 15 +/- 4 hours, respectively). Surgery per se had no effect on gut transit. CONCLUSIONS: Cholecystectomy shortens gut transit by accelerating colonic passage. These sequelae develop early and persist at least 4 years after cholecystectomy. The postcholecystectomy diarrhea syndrome probably represents a magnification of the above colonic sequelae.

Adult↗

Bile acid induced colonic irritation stimulates intracolonic nitric oxide release in humans.

AIM: To measure the intracolonic release of nitric oxide end products (nitrates plus nitrites) and eicosanoids in response to intraluminal irritation with deoxycholic acid (DCA). PATIENTS: Seven patients with irritable bowel syndrome. METHODS: The left colon was perfused with a solution with or without 3 mM deoxycholic acid. Aspirates were assayed for eicosanoids by specific radioimmuno-assay, and for nitrates plus nitrites by the Griess reaction. To confirm that stimulated colonic mucosa can produce nitric oxide (NO), ancillary studies were performed in vitro using samples of normal mucosa obtained from five surgically resected colons. Samples were incubated for 30 minutes in Kreb's solution, 3 mM DCA or DCA with 1 mM L-nitro-arginine-methyl-ester (L-NAME) to inhibit the NO synthase. Finally, NO synthase activity was measured in five samples of human colonic mucosa. RESULTS: Intracolonic release of nitrates plus nitrites was basally undetectable in six of seven patients. Bile acid considerably increased the release of prostaglandin E2 and nitrates plus nitrites (p < 0.01). By contrast, no increase in thromboxane and leukotriene was seen. In vitro mucosal incubation with DCA increased the production of NO synthase products, which was blocked by L-NAME. Activity of Ca+2 independent NO synthase was detectable in four of five samples of human colonic mucosa. CONCLUSION: The human colonic mucosa responds to bile acid induced irritation by a surge in NO generation via NO synthase.

Adolescent↗