Neurokinin-2 receptor levels correlate with intensity, frequency, and duration of pain in chronic pancreatitis

OBJECTIVE: Generation and maintenance of pain in chronic pancreatitis (CP) have been shown to be partially attributable to neuroimmune interactions, which involve neuropeptides such as substance P (SP). So far, expression of SP receptors NK-2R, NK-3R, the SP-encoding gene preprotachykinin A (PPT-A), and the SP degradation enzyme neutral endopeptidase (NEP) and their relation to pain in CP have not been determined. METHODS: Tissue samples from patients with CP (n = 25) and from healthy donors (n = 20) were analyzed for PPT-A, NK-2R, NK-3R, and NEP expression using quantitative RT-PCR. NEP protein levels were examined by immunoblot analysis and its localization was determined using immunohistochemistry. A scoring system was used to grade the extent of fibrosis on hematoxylin and eosin- and Masson-Trichrome-stained sections. Messenger RNA levels and the extent of pain were analyzed for correlations. RESULTS: In CP tissues, NK-2R and PPT-A expression was increased, whereas NK-3R and NEP mRNA levels were comparable with normal pancreas. Overexpression of NK-2R was related to the intensity, frequency, and duration of pain in CP patients. NK-1R and NEP expression was significantly related to the extent of fibrosis. CONCLUSIONS: Expression of NK-2R and PPT-A is increased in CP and is associated with pain. Failure to up-regulate NEP may contribute to the disruption of the neuropeptides loop balance in CP and thus may exacerbate the severe pain syndrome.

Increase in substance P precursor mRNA in noninflamed small-bowel sections in patients with Crohn's disease

BACKGROUND: Neuropeptides, such as substance P (SP), are mediators of neurogenic inflammation and play an important role in inflammatory disorders. To further investigate the role of the SP pathway in inflammatory bowel disease (IBD), we analyzed the following in normal intestinal tissue specimens and in tissue specimens from patients with Crohn's disease (CD) and ulcerative colitis (UC): neurokinin receptor-1 (NK-1R); its isoforms (NK-1R-L and NK-1R-S); its ligand SP, encoded by preprotachykinin-A (PPT-A); and the SP-degradation enzyme, neutral endopeptidase (NEP). METHODS: Real-time quantitative reverse transcription-polymerase chain reaction was used to simultaneously determine the expression of NK-1R-L, NK-1R-S, and PPT-A. Protein levels of NK-1R and NEP were determined by immunoblot analysis. RESULTS: In noninflamed small-bowel tissue samples of CD patients, PPT-A mRNA expression was significantly increased, whereas there was no difference between inflamed or noninflamed UC and normal intestinal tissue samples. Examining subgroups of diverse intestinal segments from CD and UC samples with various levels of inflammation revealed no differences in NK-1R-L and NK-1R-S mRNA expression, whereas there was a tendency toward overall lower NK-1R-S mRNA copy numbers. Immunoblot analysis showed upregulation of NK-1R protein levels in cases of IBD, with more pronounced enhancement in cases of CD than in UC. For NEP, there were no differences in protein levels in normal, CD, and UC intestinal tissues. COMMENTS: These observations suggest a contribution of SP and its receptor, NK-1R, in the local inflammatory reaction in IBD and particularly in ileal CD. Moreover, significant upregulation of PPT-A mRNA in the noninflamed ileum of these patients suggests an influence of inflamed intestines on their healthy counterparts.

Stability of soft tissue profile after mandibular setback in sagittal split osteotomies: a longitudinal and long-term follow-up study

PURPOSE: The aim of the study was to conduct a long-term prospective follow-up on the stability of soft tissues after bilateral sagittal split osteotomy (BSSO) with rigid internal fixation to set back the mandible. PATIENTS AND METHODS: Seventeen consecutive patients (6 females, 11 males) were re-examined 12.7 years (T5) after surgery. The precedent follow-ups included: before surgery (T1), 5 days (T2) after surgery, 6.6 months (T3) after surgery, and 14.4 months after (T4) surgery. Lateral cephalograms were traced by hand, digitized, and evaluated with the Dentofacial Planner program (Dentofacial Software, Toronto, Canada). The x-axis for the system of coordinates ran through Sella (point 0) and the line NSL -7 degrees. RESULTS: The net effect of the soft tissue chin (soft tissue pogonion) was 79% of the setback at pogonion. At the lower lip (labrale inferior) it was 100% of the setback at lower incisor position. Point B' followed point B to 99%. Labrale inferior and menton' also showed a significant backward, as well as a downward, movement (T5 to T2). Gender correlated significantly (P = .004) with the anterior displacement of point B' and pogonion' (P = .012). The soft tissue relapse 12.7 years after BSSO setback surgery at point B' was 3% and 13% at pogonion'. CONCLUSION: Among the reasons for 3-dimensional long-term soft tissue changes of shape, the surgical technique, the normal process of human aging, the initial growth direction, and remodeling processes must be considered. Growth direction positively influenced the long-term outcome of setback surgery in female compared with male patients because further posterior movement of the mandibular soft tissue occurred.

Stability after bilateral sagittal split osteotomy setback surgery with rigid internal fixation: a systematic review

PURPOSE: The purpose of this systematic review was to evaluate relapse and its causes in bilateral sagittal split setback osteotomy with rigid internal fixation. MATERIALS AND METHODS: Literature research was done in databases such as PubMed, Ovid, the Cochrane Library, and Google Scholar Beta. From the original 488 articles identified, 14 articles were finally included. Only 5 studies were prospective and 9 retrospective. The range of postoperative study records was from 6 weeks to 12.7 years. RESULTS: The horizontal short-term relapse was between 9.9% and 62.1% at point B and between 15.7% and 91.3% at pogonion. Long-term relapse was between 14.9% and 28.0% at point B and between 11.5% and 25.4% at pogonion. CONCLUSIONS: Neither large increase nor decrease of relapse was seen when short-term values were compared with long-term. Bilateral sagittal split osteotomy for mandibular setback in combination with orthodontics is an effective treatment of skeletal Class III and a stable procedure in the short- and long-term. The etiology of relapse is multifactorial: the proper seating of the condyles, the amount of setback, the soft tissue and muscles, remaining growth and remodeling, and gender were identified. Age did not show any correlations. To obtain reliable scientific evidence, further short- and long-term research of bilateral sagittal split osteotomy setback with rigid internal fixation should exclude additional surgery, ie, genioplasty or maxillary surgery, and include correlation statistics.

Diabetic patients treated for unprotected left main coronary artery disease with drug eluting stents: a 3-year clinical outcome study. The diabetes and drug eluting stent for LeFT main registry (D-DELFT)

AIMS: Diabetes mellitus (DM) plays an important role in the development of coronary artery disease. Although previous studies have associated drug-eluting stent (DES) implantation in diabetic patients with favourable clinical and angiographic outcomes, the very long-term efficacy of these devices in diabetic patients undergoing PCI for significant unprotected left main coronary artery (ULMCA) disease has not been established yet. METHODS AND RESULTS: Consecutive diabetic patients (n=100), who underwent elective PCI with DES for de novo lesions in an ULMCA between April 2002 and April 2004 in seven tertiary health care centres, were identified retrospectively and analysed. Consecutive non-diabetic patients (n=193), who underwent elective DES implantation for unprotected ULMCA disease, were selected as a control group. All patients were followed for at least 36 months. At 3-years follow-up, freedom from cardiac death ; myocardial infarction (CDMI), target lesion revascularisation (TLR) and target vessel revascularisation (TVR) did not differ significantly between groups. The adjusted freedom from major adverse cardiac events (MACE, defined as the occurrence of CD, MI or TVR) was 63.4% in the DM group and 77.6% in the controls (p<0.001). When divided into IDDM and NIDDM sub-groups, insulin-dependent DM (IDDM) but not non IDDM (NIDDM) patients had significantly lower freedom from CDMI, TLR, TVR and MACE compared to controls. CONCLUSIONS: These results suggest that major improvements in DES technology and pharmacotherapy are still required to improve clinical outcome and that the decision to perform percutaneous revascularisation in this subset of patients should be taken cautiously and on a case by case basis.

Does hyoid bone resection according to Sistrunk influence normal craniofacial growth? A cephalometric study

PURPOSE: To retrospectively evaluate the influence of hyoid bone resection according to Sistrunk in early age due to a thyroglossal duct cyst on craniofacial growth. MATERIALS AND METHODS: We retrospectively examined 10 patients (2 females and 8 males) having had hyoid bone resection according to Sistrunk due to thyroglossal duct cysts by lateral cephalograms taken before orthodontic treatment (mean, 17.1 years; range, 8.6-31.9 years). Surgery was carried out at a mean age of 4.4 years (range, 0.37-9.8 years). All lateral cephalograms were evaluated and traced by hand. Descriptive statistics were calculated, and data from each patient were compared individually with corresponding standard values (age and gender) from Bathia and Leighton. RESULTS: With regard to sagittal parameters, the SNB angles were by trend too small and the ANB angles were too large. However, the ratio of mandibular to maxillary length showed that the patients had a mandible that was too large or maxilla that was too small. With regard to vertical parameters, large deviations from normal values in both directions (hyperdivergent to hypodivergent pattern) could be detected when we analyzed NSL/ML', NL/ML', and NSL/NL. With regard to dental parameters, the majority of the patients had retroclined upper (IsL/NL, IsL/N-A) and lower (IiL/ML, IiL/N-B) incisors. CONCLUSIONS: Several vertical and horizontal skeletal and dental cephalometric parameters were shown to be different by trend when compared with control values. A possible negative impact on craniofacial growth potential and direction as a result of hyoid resection in early age according to Sistrunk cannot be excluded.

Stability after bilateral sagittal split osteotomy advancement surgery with rigid internal fixation: a systematic review

PURPOSE: The purpose of this systematic review was to evaluate horizontal relapse and its causes in bilateral sagittal split advancement osteotomy (BSSO) with rigid internal fixation of different types. MATERIALS AND METHODS: A search of the literature was performed in the databases PubMed, Ovid, Cochrane Library, and Google Scholar Beta. From 488 articles identified, 24 articles were finally included. Six studies were prospective, and 18 were retrospective. The range of postoperative study records was 6 months to 12.7 years. RESULTS: The short-term relapse for bicortical screws was between 1.5% and 32.7%, for miniplates between 1.5% and 18.0%, and for bioresorbable bicortical screws between 10.4% and 17.4%, at point B. The long-term relapse for bicortical screws was between 2.0% and 50.3%, and for miniplates between 1.5% and 8.9%, at point B. CONCLUSIONS: BSSO for mandibular advancement is a good treatment option for skeletal Class II, but seems less stable than BSSO setback in the short and long terms. Bicortical screws of titanium, stainless steel, or bioresorbable material show little difference regarding skeletal stability compared with miniplates in the short term. A greater number of studies with larger skeletal long-term relapse rates were evident in patients treated with bicortical screws instead of miniplates. The etiology of relapse is multifactorial, involving the proper seating of the condyles, the amount of advancement, the soft tissue and muscles, the mandibular plane angle, the remaining growth and remodeling, the skill of the surgeon, and preoperative age. Patients with a low mandibular plane angle have increased vertical relapse, whereas patients with a high mandibular plane angle have more horizontal relapse. Advancements in the range of 6 to 7 mm or more predispose to horizontal relapse. To obtain reliable scientific evidence, further short-term and long-term research into BSSO advancement with rigid internal fixation should exclude additional surgery, ie, genioplasty or maxillary surgery, and include a prospective study or randomized clinical trial design with correlation statistics.

Regional differences in symptomatic fever management among paediatricians in Switzerland: the results of a cross-sectional Web-based survey

AIMS In symptomatic fever management, there is often a gap between everyday clinical practice and current evidence. We were interested to see whether the three linguistic regions of Switzerland differ in the management of fever. METHODS A close-ended questionnaire, sent to 900 Swiss paediatricians, was answered by 322 paediatricians. Two hundred and fourteen respondents were active in the German speaking, 78 in the French speaking and 30 in the Italian speaking region. RESULTS Paediatricians from the French and Italian speaking regions identify a lower temperature threshold for initiating a treatment and more frequently reduce it for children with a history of febrile seizures. A reduced general appearance leads more frequently to a lower threshold for treatment in the German speaking than in the French and Italian speaking areas. Among 1.5 and 5-year-old children the preference for the rectal route is more pronounced in the German than in the French speaking region. French speaking respondents more frequently prescribe ibuprofen and an alternating regimen with two drugs than German speaking respondents. Finally, the stated occurrence of exaggerated fear of fever was higher in the German and Italian speaking regions. CONCLUSIONS Switzerland offers the opportunity to compare three different regions with respect to management of febrile children. This inquiry shows regional differences in symptomatic fever management and in the perceived frequency of exaggerated fear of fever. The gap between available evidence and clinical practice is more pronounced in the French and in the Italian speaking regions than in the German speaking region.

Vitamin D status among children and adolescents on anticonvulsant drugs in southern Switzerland.

INTRODUCTION It is recognised that vitamin D status is often inadequate (<50 nmol/l) in epileptic children, mainly because some anticonvulsant drugs induce the enzymes responsible for its metabolism. The purpose of the present study was to address vitamin D status among children and adolescents treated with anticonvulsant drugs and control subjects who reside in southern Switzerland, a high solar radiation region. METHODS Between January and May 2013, total serum 25-hydroxyvitamin D was assessed by liquid chromatography-tandem mass spectrometry in 58 children and adolescents with epilepsy and 29 controls residing in southern Switzerland. Dark-skinned individuals, females wearing dress styles covering practically the whole body and subjects with body mass index ≥85th percentile for age and sex were excluded. RESULTS Concentration of serum 25-hydroxyvitamin D was similar in epilepsy patients (48 [37-62] nmol/l; median and interquartile range) and controls (53 [47-64] nmol/l). An inadequate serum 25-hydroxyvitamin D concentration was common both among patients (55%) and control subjects (34%). Serum 25-hydroxyvitamin D was significantly lower among patients treated with anticonvulsant drugs that induce the metabolism of vitamin D (30 [21-51] nmol/l) than among the remaining patients (51 [40-65] nmol/l) and controls. CONCLUSIONS The present study indicates a relevant tendency towards inadequate vitamin D status among children with and without anticonvulsant drug management who reside in southern Switzerland. This tendency is more prominent in patients treated with anticonvulsant drugs that induce the metabolism of 25-hydroxyvitamin D.

Salt intake in children and its consequences on blood pressure.

Sodium is the most abundant extracellular cation and therefore pivotal in determining fluid balance. At the beginning of life, a positive sodium balance is needed to grow. Newborns and preterm infants tend to lose sodium via their kidneys and therefore need adequate sodium intake. Among older children and adults, however, excessive salt intake leads to volume expansion and arterial hypertension. Children who are overweight, born preterm, or small for gestational age and African American children are at increased risk of developing high blood pressure due to a high salt intake because they are more likely to be salt sensitive. In the developed world, salt intake is generally above the recommended intake also among children. Although a positive sodium balance is needed for growth during the first year of life, in older children, a sodium-poor diet seems to have the same cardiovascular protective effects as among adults. This is relevant, since: (1) a blood pressure tracking phenomenon was recognized; (2) the development of taste preferences is important during childhood; and (3) salt intake is often associated with the consumption of sugar-sweetened beverages (predisposing children to weight gain).

Taste acceptability of pulverized brand-name and generic drugs containing amlodipine or candesartan.

Trials with pulverized brand-name antihypertensive drugs suggest that, from the perspective of taste acceptability, crushed candesartan, chlortalidon, hydrochlorothiazide, lercanidipine and lisinopril should be preferred to pulverized amlodipine, atenolol, bisoprolol, enalapril, irbesartan, losartan, ramipril, telmisartan and valsartan. Brand-name antihypertensive drugs and the corresponding generic medicines have never been compared with respect to their taste acceptability. We therefore investigated among healthy health care workers the taste acceptability of a pulverized 1 mg-test dose of the brand-name and two generics containing either the dihydropyridine calcium-channel blocker amlodipine (Norvasc(®), Amlodipin-Mepha(®) and Amlodipin Pfizer(®)) or the angiotensin receptor antagonist candesartan (Atacand(®), Cansartan-Mepha(®) and Pemzek(®)). For this purpose, a smiley-face scale depicting four degrees of pleasure was used. Between November and December 2013, the taste test was performed among 19 nurses (15 female and 4 male subjects) and 12 physicians (5 female and 7 male subjects) aged between 25 and 49 years. Pulverized brand-names and generics containing either amlodipine or candesartan did not differ with respect to their taste acceptability.

Risk Behavior and Reciprocity of Organ Donation Attitudes in Young Men

Background Lack of donor organs remains a major obstacle in organ transplantation. Our aim was to evaluate (1) the association between engaging in high-risk recreational activities and attitudes toward organ donation and (2) the degree of reciprocity between organ acceptance and donation willingness in young men. Methods A 17-item, close-ended survey was offered to male conscripts ages 18 to 26 years in all Swiss military conscription centers. Predictors of organ donation attitudes were assessed in bivariate analyses and multiple logistic regression. Reciprocity of the intentions to accept and to donate organs was assessed by means of donor card status. Results In 1559 responses analyzed, neither motorcycling nor practicing extreme sports reached significant association with donor card holder status. Family communication about organ donation, student, or academic profession and living in a Latin linguistic region were predictors of positive organ donation attitudes, whereas residence in a German-speaking region and practicing any religion predicted reluctance. Significantly more respondents were willing to accept than to donate organs, especially among those without family communication concerning organ donation. Conclusions For the first time, it was shown that high-risk recreational activities do not influence organ donation attitudes. Second, a considerable discrepancy in organ donation reciprocity was identified. We propose that increasing this reciprocity could eventually increase organ donation rates.