Parents, physicians, and antibiotic use

BACKGROUND: Emergence of resistant bacterial pathogens has increased concerns about antibiotic prescribing patterns. Parent expectations and pressure may influence these patterns. OBJECTIVE: To understand how parents influence the prescribing patterns of physicians and what strategies physicians believe are important if we are going to reduce inappropriate use of oral antimicrobial agents. DESIGNS AND METHODS: One thousand pediatricians who are members of the American Academy of Pediatrics were asked to complete a semi-structured questionnaire. The physicians were chosen randomly by the American Academy of Pediatrics. RESULTS: Nine hundred fifteen pediatricians were eligible and 610 surveys were analyzable, for a response rate of 67%. The majority of respondents were male (56%), worked in a group practice (51%), saw an average of 114 patients per week and were in practice for 14 years. Forty percent of the pediatricians indicated that 10 or more times in the past month a parent had requested an antibiotic when the physician did not feel it was indicated. Forty-eight percent reported that parents always, most of the time, or often pressure them to prescribe antibiotics when their children are ill but antibiotics are not indicated. In follow-up questions, approximately one-third of physicians reported they occasionally or more frequently comply with these requests. Seventy-eight percent felt that educating parents would be the single most important program for reducing inappropriate oral antibiotic use and 54% indicated that parental pressure, in contrast to concerns about legal liability (12%) or need to be efficient in practice (19%), contributed most to inappropriate use of oral antibiotics. CONCLUSIONS: Pediatricians acknowledge prescribing antimicrobial agents when they are not indicated. Pediatricians believe educating parents is necessary to promote the judicious use of antimicrobial agents.     

Intrahepatic bile duct and portal vein anatomy revisited

Seventeen normal cadaver livers were studied to assess the anatomic relationship of bile ducts to portal veins. The common bile duct, main portal vein, and hepatic artery were cannulated and injected with air, dilute contrast medium, and mineral oil, respectively. The livers were placed in anatomic position and examined with computed tomography. In the lateral segment of the left hepatic lobe, the bile ducts were anterior to the portal vein in seven cases, posterior in seven, and tortuous (ie, both anterior and posterior) in three. In the medial segment of the left lobe, the bile ducts were anterior in four cases, posterior in four, tortuous in three, and not seen in six. In the right lobe, the bile ducts were anterior in nine cases, posterior in five, tortuous in one, and not seen in two. In the porta hepatis, the bile ducts were anterior in ten cases, posterior in one, tortuous in five, and not seen in one. Histologic findings confirmed the anterior and posterior location of the bile ducts relative to the portal veins. These findings contradict the commonly held view of intrahepatic bile ducts being anterior to the portal vein and are clinically significant for techniques such as bile duct drainage.     

Incidence and Predictors of Permanent Pacemaker Requirement after Transcatheter Aortic Valve Implantation with a Self‐Expanding Bioprosthesis

Background: Previous reports have suggested the occurrence of cardiac conduction disorders and permanent pacemaker (PPM) requirement after transcatheter aortic valve implantation (TAVI). Based on a single‐center experience, we aim to assess the incidence of postprocedural conduction disorders, need for PPM, and its determinants after TAVI with a self‐expanding bioprosthesis. Methods: From August 2007 to October 2009, 32 consecutive patients underwent TAVI with the Medtronic CoreValve (MCV) System (Medtronic Inc., Minneapolis, MN, USA). Three patients paced at baseline and two cases of procedure‐related mortality were excluded. We analyzed the 12‐lead electrocardiogram at baseline, immediately after procedure and at discharge. Requirements for PPM were documented and potential clinical, electrophysiological, echocardiographic, and procedural predictors of PPM requirement were studied. Results: After TAVI, eight patients (29.6%) required PPM implantation due to high‐grade atrioventricular (AV) block. The prevalence of left bundle branch block increased from 13.8% to 57.7% directly after implantation (P = 0.001). Need for PPM was correlated to the depth of prosthesis implantation (r = 0.590; P = 0.001). At a cutoff point of 10.1 mm, the likelihood of pacemaker could be predicted with 87.5% sensitivity and 74% specificity and a receiver operator characteristic curve area of 0.86 ± 0.07 (P = 0.003). Of the seven patients with preexisting right bundle branch block (RBBB), four (57.1%) required PPM implantation after TAVI. Conclusions: High‐grade AV block requiring PPM implantation is a common complication following TAVI and could be predicted by a deeper implantation of the prosthesis. Patients with preexisting RBBB also seem to be at risk for the development of high‐grade AV block and subsequent pacemaker implantation. (PACE 2010; 1364–1372)     

AP-811, a novel ANP-C receptor selective agonist

AP-811 is a derivative of the Phe8-Ile15 region of atrial natriuretic peptide (ANP) and is one of the smallest linear ligands for ANP receptors. The binding and agonist activities of AP-811 have been compared with those of other ANP analogs for the ANP-A and ANP-C receptors. AP–811 binds with a high binding affinity to and is a strong agonist for the ANP-C receptor, indicating that the binding and agonist sites for this receptor are the same or near each other in the ANP sequence. In contrast, AP-811 showed no agonistic effect for the ANP-A receptor, although it could bind to this receptor. Comparing the biological activities of AP-811 with those of other ANP analogs, we propose that the binding and agonist sites for the ANP-A receptor may consist of separate regions of ANP. In conclusion, AP-811 is the smallest C-receptor-selective agonist.     

Quantitative structure–activity relationship (QSAR) study of elastase substrates and inhibitors

One hundred Suc-X-Y-Ala-pNA peptides (SUC: succinyl, pNA: p-nitroanilide, X, Y: Gly, Ala, Val, Leu, Ile, Phe, Pro, x-aminobutyric acid, norvaline, norleucine) were synthesized and their reaction constants with porcine pancreatic elastase (K_m, K_cat and K_cat/K_m) were determined. These reaction constants were quantitatively analyzed using the Free–Wilson/Fujita–Ban method. The contribution of amino acid side chains to the reaction constants K_m, K_cat and K_cat/K_m), expressed logarithmically, was found to be additive. On the other hand, 19 elastase inhibitors of the general formula CF₃CO-X-Y-Ala-pNA (X,Y: ten amino acids) were synthesized, and their inhibition constants were compared with the Michaelis constant for the corresponding substrates and analyzed using free-energy-related substituent constants. In the analysis of amino acid side chains in the Y position, the K_i value of the inhibitor was generally correlated to the K_m value of the substrate, which corresponded to the inhibitor, thus confirming the validity of the equation This study may serve as a prototypical approach to unraveling structure–activity relationships of peptide substrates and inhibitors of medicinal or agricultural importance.     

Two-step hard acid deprotection/cleavage procedure for solid phase peptide synthesis

A new two-step deprotection/cleavage procedure for t-butoxycarbonyl (Boc) based solid phase peptide synthesis is reported. First the protective groups are removed from 4-(oxymethyl)-phenylacetamidomethyl (PAM) resin attached peptide with the weak hard acid, trimethylsilyl bromide-thioanisole/trifluoroacetic acid (TFA). In the second step, the peptide is cleaved from the resin with a stronger hard acid such as trimethylsilvl trifluoromethanesulfonate in TFA or with HF. The method is also shown to deformylate Nⁱⁿ-formyltryptophan moiety efficiently. The usefulness of this procedure for practical solid phase peptide synthesis is demonstrated by comparison with other deprotection methods in the synthesis of urotensin II and human endothelin.     

Effect of plant neutrophil elastase inhibitor on leucocyte migration, adhesion and cytokine release in inflammatory conditions

BACKGROUND AND PURPOSE

The serine and cysteine peptidase inhibitor, BbCI, isolated from Bauhinia bauhinioides seeds, is similar to the classical plant Kunitz inhibitor, STI, but lacks disulphide bridges and methionine residues. BbCI blocks activity of the serine peptidases, elastase (K_iapp 5.3 nM) and cathepsin G (K_iapp 160.0 nM), and the cysteine peptidase cathepsin L (K_iapp 0.2 nM). These three peptidases play important roles in the inflammatory process.

EXPERIMENTAL APPROACH

We measured the effects of BbCI on paw oedema and on leucocyte accumulation in pleurisy, both induced by carrageenan. Leucocyte–endothelial cell interactions in scrotal microvasculature in Wistar rats were investigated using intravital microscopy. Cytokine levels in pleural exudate and serum were measured by elisa.

KEY RESULTS

Pretreatment of the animals with BbCI (2.5 mg·kg⁻¹), 30 min before carrageenan-induced inflammation, effectively reduced paw oedema and bradykinin release, neutrophil migration into the pleural cavity. The number of rolling, adhered and migrated leucocytes at the spermatic fascia microcirculation following carrageenan injection into the scrotum were reduced by BbCI pretreatment. Furthermore, levels of the rat chemokine cytokine-induced neutrophil chemo-attractant-1 were significantly reduced in both pleural exudates and serum from animals pretreated with BbCI. Levels of interleukin-1β or tumour necrosis factor-α, however, did not change.

CONCLUSIONS AND IMPLICATIONS

Taken together, our data suggest that the anti-inflammatory properties of BbCI may be useful in investigations of other pathological processes in which human neutrophil elastase, cathepsin G and cathepsin L play important roles.