Predictors of symptom trajectory in newly diagnosed ulcerative colitis: a 3-year follow-up cohort study.

BACKGROUND AND AIMS: Psychological symptoms are associated with poorer ulcerative colitis (UC)-related outcomes. However, the majority of research is cross-sectional. We aimed to identify subgroups based on the longitudinal evolution of GI symptom levels and health-related quality of life (HRQoL), and to disentangle the directionality of effects between GI symptom levels and psychological distress. METHODS: Self-reported GI symptom severity, HRQoL, inflammatory biomarkers and psychological distress were assessed in 98 newly diagnosed UC patients at disease onset and yearly for 3 consecutive years. Latent class growth analysis was used to determine subgroups based on longitudinal trajectories of symptom severity and HRQoL, and baseline predictors of trajectory group membership were determined. Cross-lagged structural equation models were used to disentangle temporal relationships between psychological functioning and symptom severity. RESULTS: Patients with higher initial psychological distress had increased probability of maintaining higher levels of diarrhea and abdominal pain. Conversely, patients with lower initial levels of diarrhea and abdominal pain had higher chances of maintaining lower levels of psychological distress. Higher levels of C-reactive protein at baseline predicted greater improvements in mental health after anti-inflammatory treatment. Reductions in diarrhea and abdominal pain preceded reductions in psychological symptoms over time. CONCLUSIONS: Baseline psychological distress is predictive of increased GI symptom severity and reduced mental HRQoL over time, suggesting early assessment of psychological symptoms may identify patients who may have worse disease trajectories. Abdominal pain predicted increased psychological distress, but not the other way around. Intervening on abdominal pain may help prevent or reduce future psychological distress.

Rehabilitation of severely resorbed maxillae with zygomatic implants: an evaluation of implant stability, tissue conditions, and patients' opinion before and after treatment.

PURPOSE: The aim of the present study was to describe experiences of 11 consecutively treated patients who received zygomatic implants. Patient results were assessed through clinical and radiographic evaluations of tissue conditions, including resonance frequency analysis (RFA). MATERIALS AND METHODS: Eleven patients were treated with implant-retained fixed prostheses. A total of 64 implants were placed, 22 of which were placed in the zygoma. Fixed prostheses were removed to allow clinical and radiographic evaluations at a follow-up visit 18 to 46 months following implant placement. RFA was performed on all implants. A visual analog scale was used to assess patient satisfaction before and after treatment. RESULTS: All patients received implant-supported prostheses. All zygomatic implants demonstrated clinical signs of osseointegration. One anterior implant was lost during follow-up. Mean ISQ values for the zygomatic and anterior implants were 65.9 (range, 42 to 100) and 61.5 (range, 48 to 71), respectively. Twenty-four implants showed moderate inflammation, with 3 exhibiting severe inflammation. Most anterior implants (75.6%) showed a marginal bone recession of 1 thread or less. Four zygomatic implants showed bone loss of 4 to 5 threads, and 5 zygomatic implants exhibited no marginal bone support. Patients described significant improvement in chewing ability and esthetics but did not describe changes in speech. DISCUSSION: The use of zygomatic implants can help the clinician avoid the need for bone grafting and reduce morbidity. In addition, it can shorten the treatment time considerably. CONCLUSION: This preliminary report demonstrates that zygomatic implants can provide posterior support to fixed prostheses in patients who lack bone volume to place conventional implants without encroaching upon the maxillary sinus.

Design, synthesis, and biological evaluation of the first selective nonpeptide AT2 receptor agonist.

The first druglike selective angiotensin II AT(2) receptor agonist (21) with a K(i) value of 0.4 nM for the AT(2) receptor and a K(i) > 10 microM for the AT(1) receptor is reported. Compound 21, with a bioavailability of 20-30% after oral administration and a half-life estimated to 4 h in rat, induces outgrowth of neurite cells, stimulates p42/p44(mapk), enhances in vivo duodenal alkaline secretion in Sprague-Dawley rats, and lowers the mean arterial blood pressure in anesthetized, spontaneously hypertensive rats. Thus, the peptidomimetic 21 exerts a similar biological response as the endogenous peptide angiotensin II after selective activation of the AT(2) receptor. Compound 21, derived from the prototype nonselective AT(1)/AT(2) receptor agonist L-162,313 will serve as a valuable research tool, enabling studies of the function of the AT(2) receptor in more detail.

First reported nonpeptide AT1 receptor agonist (L-162,313) acts as an AT2 receptor agonist in vivo.

In this investigation, it is demonstrated that the first nonpeptide AT(1) receptor agonist L-162,313 (1), disclosed in 1994, also acts as an agonist at the AT(2) receptor. In anesthetized rats, administration of compound 1 intravenously or locally in the duodenum increased duodenal mucosal alkaline secretion, effects that were sensitive to the selective AT(2) receptor antagonist PD-123,319. The data strongly suggest that 1 is an AT(2) receptor agonist in vivo. To the best of our knowledge, this substance is the first nonpeptidic low-molecular weight compound with an agonistic effect mediated through the AT(2) receptor.

The bradykinin BK2 receptor mediates angiotensin II receptor type 2 stimulated rat duodenal mucosal alkaline secretion.

BACKGROUND: This study investigates bradykinin and nitric oxide as potential mediators of AT2-receptor-stimulated duodenal mucosal alkaline secretion. Duodenal mucosal alkaline secretion was measured in methohexital- and alpha-chloralose-anaesthetised rats by means of in situ pH-stat titration. Immunohistochemistry and Western blot were used to identify the BK2 receptors. RESULTS: The AT2 receptor agonist CGP42112A (0.1 microg kg(-1) min(-1)) administered intravenously increased the duodenal mucosal alkaline secretion by approximately 50 %. This increase was sensitive to the selective BK2 receptor blocker HOE140 (100 ng/kg i.v.), but not to luminal administration of the NOS blocker L-NAME (0.3 mM). Mean arterial pressure did not differ between groups during the procedures. Immunohistochemistry showed a distinct staining of the crypt epithelium and a moderate staining of basal cytoplasm in villus enterocytes. CONCLUSION: The results suggest that the AT2-receptor-stimulated alkaline secretion is mediated via BK2 receptors located in the duodenal cryptal mucosal epithelium.