Duodeno-jejunal junction dyssynergia： Description of a novel syndrome

AIM： To investigate the hypothesis that duodeno-jejunal dyssynergia existed at the duodeno-jejunal junction.
METHODS： Of 112 patients who complained of epigastric distension and discomfort after meals, we encountered nine patients in whom the duodeno-jejunal junction did not open on duodenal contraction. Seven healthy volunteers were included in the study. A condom which was inserted into the ist duodenum was filled up to 10 mL with saline in increments of 2 mL and pressure response to duodenal distension was recorded from the duodenum, duodeno-jejunal junction and the jejunum.
RESULTS： In healthy volunteers, duodenal distension with 2 and 4 mL did not produce pressure changes, while 6 and up to 10 mL distension effected significant duodenal pressure increase, duodeno-jejunal junction pressure decrease but no jejunal pressure change. In patients, resting pressure and duodeno-jejunal junction and jejunal pressure response to 2 and 4 mL duodenal distension were similar to those of healthy volunteers. Six and up to 10 mL 1^st duodenal distension produced significant duodenal and duodeno-jejunal junction pressure increase and no jejunal pressure change.
CONCLUSION： Duodeno-jejunal junction failed to open on duodenal contraction, a condition we call ＇duodenojejunal junction dyssynergia syndrome＇ which probably leads to stagnation of chyme in the duodenum and explains patients＇ manifestations.     

Novel potential nonsedating H1 antagonists related to the gauche rotamer of PROS-NH-histamine

On the basis of the most stable stereorotameric (R) forms of ^πNH-histamine (2), the trans (1-TR) and gauche (1-GR) forms have both been reported to be involved in potentiation of H₁-receptors. Apart from the known classic models of H₁-antagonists that mostly belong to 1-TR, a new topographic receptor map for 1-GR has been postulated. Twenty-seven new compounds pertaining to novel nonclassic molecular models related to 1-GR have been postulated as potential nonsedating, less toxic H₁-antagonists. Representative members of the new agents were investigated for H₁-blocking activity by using isolated segments from guinea pig ileum. Many of the tested new compounds exhibited activities comparable to that of acrivastine as a reference nonsedating drug. The C log P values of the new agents were lower than that of acrivastine (4.34), which might indicate decreased tendency to cross the blood–brain barrier. The most pronounced activity was displayed by the 5-substituted aminomethylenepyrimidine-2,4,6-triones (21, 23) since they displayed nearly equal 50% inhibition concentrations (IC₅₀) (6.12 × 10⁻⁶ M) and lower C log P values.     

AMP-activated protein kinase: a physiological off switch for murine gastric acid secretion

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) has been shown to be a metabolic energy regulator in various cells. Activation is a direct result of rising AMP concentration coupled with falling adenosine triphosphate (ATP). AMPK activation during metabolic stress consequently reduces cellular ATP consumption. The gastric parietal cell has a large abundance of mitochondria per cell volume due to the numerous energy-dependent transporters and channels responsible for acid secretion. We identified AMPK in the parietal cell as a metabolic energy regulator that can switch acid secretion off as cellular ATP levels fall. AMPK presence in murine gastric glands was evaluated by immunofluorescent localization. We used a digital imaging system to monitor acid secretion as observed by proton efflux from parietal cells in hand-dissected gastric glands loaded with the pH-sensitive dye 2′,7′-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein. Individual murine gastric glands were exposed to histamine, pentagastrin, or carbachol. AMPK was pharmacologically activated with 5-aminoimidazole-4-carboxamide-1-β-d-riboside (AICAR) monophosphate or inhibited with 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine (compound C) or ATP. Acid secretion was evaluated under these conditions as the rate of intracellular pH recovery. In addition, whole-stomach pH measurements were performed. Immunofluorescent localization confirmed the presence of AMPK in gastric mucosa. Exposure to AICAR monophosphate significantly reduced secretagogue-induced acid secretion; addition of compound C or ATP restored acid secretion. Our results indicate that secretagogue-induced acid secretion could be significantly reduced with AMPK activation and restored with its deactivation. We therefore propose the AMPK as a cellular metabolic off switch for gastric acid secretion.     

Validation of MCADD newborn screening

Medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD) represents a potentially fatal fatty acid β‐oxidation disorder. Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has been implemented worldwide, but is associated with unresolved questions regarding population heterogeneity, burden on healthy carriers, cut‐off policies, false‐positive and negative rates. In a retrospective case‐control study, 333 NBS samples showing borderline acylcarnitine patterns but not reaching recall criteria were genotyped for the two most common mutations (c.985A>G/c.199C>T) and compared with genotypes and acylcarnitines of 333 controls, 68 false‐positives, and 34 patients. c.985A>G was more frequently identified in the study group and false‐positives compared to controls (1:4.3/1:2.3 vs. 1:42), whereas c.199C>T was found more frequently only within the false‐positives (1:23). Biochemical criteria were devised to differentiate homozygous (c.985A>G), compound heterozygous (c.985A>G/c.199C>T), and heterozygous individuals. Four false‐negatives were identified because our initial algorithm required an elevation of octanoylcarnitine (C₈) and three secondary markers in the initial and follow‐up sample. The new approach allowed a reduction of false‐positives (by defining high cut‐offs: 1.4 μmol/l for C₈; 7 for C₈/C₁₂) and false‐negatives (by sequencing the ACADM gene of few suspicious samples). Our validation strategy is able to differentiate healthy carriers from patients doubling the positive predictive value (42→88%) and to target NBS to MCADD‐subsets with potentially higher risk of adverse outcome. It remains controversial, if NBS programs should aim at identifying all subsets of all diseases included. Because the natural course of milder variants cannot be assessed by observational studies, our strategy could serve as a general model for evaluation of MS/MS‐based NBS.     

Italian healthcare workers' views on mandatory vaccination

Background  

Mandatory vaccination has contributed to the success of immunisation programmes but voluntary vaccination allows people to be responsible for their own health. There are benefits from both policies and the arguments between them remain subject to debate within and without the scientific community, both nationally and internationally. The aim of this study is to assess the opinions of those who actually work in the Vaccination Service.     

Extraction of a large self-amputated colonic lipoma: A case report

Despite being the most common benign tumor of nonepithelial origin in the colon, colonic lipomas are nonetheless considered a rare occurrence. The minority of patients presenting with symptomatic colonic lipoma are generally treated with resection. We report a case of a symptomatic patient who, on presentation, was found to have a partially obstructing, self-amputated colonic mass on colonoscopy, requiring endoscopic fragmentation to extrude what was later histologically diagnosed to be a lipoma.     

Inguinal canal dilatation: a novel technique for the repair of failed testicular descent despite hormonal treatment

Treatment of the undescended testicle (UT) after it failed to descend on hormonal therapy is surgical. Spermatic cord elongation may impair testicular function, particularly in cases in which cord integuments or veins have to be divided to provide an extra cord length. A factor that might impede testicular descent is presence of a narrowed or obliterated inguinal canal. We investigated the hypothesis that dilatation of a narrowed or obliterated inguinal canal might assist spontaneous testicular descent. Twenty-six boys (age 3.6 +/- 0.8 years) with unilateral UT and failed hormonal treatment, whose UT was located at deep inguinal ring, were included in the study. Through an inguinal incision, the inguinal canal was dilated, spermatic cord adhesions divided, hernial sac, if present, excised, and skin closed. Testicular descent into the scrotum occurred in 22 patients within 4.2 +/- 1.3 months. The remaining four patients were reoperated on by Fowler-Stephens orchiopexy after 14 months. A technique is presented for the treatment of the UT after failure to respond to hormonal treatment. It consisted of clearing the testicular pathway of any adhesions and dilating the narrowed inguinal canal. The technique is simple, easy, and does not interfere with the testicle or spermatic cord.     

Effect of urethral stimulation on vesical contractile activity

BACKGROUND: We investigated the hypothesis that urethral stimulation effects vesical contraction. METHODS: Vesical pressure response to urethral balloon distension with normal saline in increments of 1 mL was recorded in 26 healthy volunteers (17 men, 9 women; mean age, 36.9 +/- 9.7 SD years) before and after individual anesthetization of the urinary bladder and urethra. Urethral distension was effected by a 6F balloon-ended catheter introduced per urethra. Vesical pressure was measured by means of a microtip catheter. RESULTS: Vesical pressure recorded gradual increase on increase of urethral balloon distension. Bladder response was maintained as long as urethral distension was continuous. The response showed no significant difference when we distended different parts of the male or female urethrae. Urethral distension after individual vesical and urethral anesthetization effected no change in the vesical pressure. CONCLUSIONS: Urethral distension produced a vesical pressure increase that presumably denotes vesical contraction. Vesical contraction on urethral stimulation by distension is suggested to be mediated through a "urethrovesical stimulating reflex" that seems to facilitate vesical contraction. Provided further studies to be performed in this respect, the reflex may prove to be of diagnostic significance in micturition disorders.