Convergent synthesis and antibacterial activity of pyrazole and pyrazoline derivatives of diazepam.

Polysubstituted pyrazoles (5)(a-l), pyrazolines (7)(a-c), (8)(a-c) and pyrazolotriazine (10) derivatives of diazepam were synthesized. The structures of hitherto unknown compounds were established by analytical and spectral methods. Some of these compounds were screened to test their antibacterial activity against gram-positive (B. subtilis) and gram-negative (P. aeruginosa). All compounds showed potent activity against these bacteria.     

Tissue distribution and macromolecular interactions of 14[C-ring] melphalan in the rat

Summary The kinetics of uptake and elimination, covalent binding, and macromolecular interactions of ¹⁴[C-ring] melphalan was studied after a single oral dose (20 mg/kg, 0.1 mCi/kg) in normal rats. Peak radioactivity level in tissues was observed at 2–4 h after administration. Uptake of label in most tissues was rapid, with a t_1/2 of less than 1 h. Elimination was biphasic. Tissues of the gastrointestinal tract showed the most rapid rates of elimination, with t_1/2 of 13, 24, 18, and 19 h for stomach, duodenum, and small and large intestines, respectively. Bone marrow also showed a fast rate of elimination of radioactivity, with a t_1/2 of 30 h. Tissues with the slowest rates of elimination were skin, eye, spleen, pancreas, and lung, with t_1/2 of 333, 241, 149, 122, and 109 h, respectively. Covalent binding studies showed that melphalan, or its metabolites, bound irreversibly to all tissue macromolecular fractions. The percentage of covalently bound radioactivity increased with time in all tissues except kidney and eye, reaching up to 70%–80% of the total radioactivity remaining at 72 h. Elimination of covalently bound radioactivity was slower in the DNA fractions of the tissues of the gastrointestinal tract and heart compared with the elimination rate from lipid, protein, or RNA fractions. Slow elimination rates of ¹⁴[C-ring] melphalan equivalents from the protein fraction were observed in the skin, eye, and brain. Accumulation, rather than elimination, of radioactivity in this fraction was most prominent in the pancreas. In the bone marrow accumulation of radioactivity was observed in the lipid fraction.Abbreviations used in this paper are L-Pam Melphalan, l-phenylalanine mustard 4-bis (2-chloroethyl) amino-1-phenylalanine - l-DOH 4-bis (2-hydroxyethyl) amino-1-phenylalanine - l-MOH 4-2 hydroxyethyl 2 chloroethyl amino-1-phenylalanine - HPLC high-pressure liquid chromatography - TCA trichloroacetic acid - AUC area under the curve - GIT gastrointestinal tract     

Problems, obstacles and complications of femoral lengthening with the use of the Italian modification of the Ilizarov device]

The results of femoral lengthening using the Italian modification of the Ilizarov are presented. Mean age of the patients was 14 years (ranging from 7 to 29). The most frequent etiology of limb shortening was femoral hypoplasia (7 patients) and sequelae of septic arthritis of the hip and/or the knee (6 patients). Indications for surgical treatment were limb shortening from 3 to 12 cm (mean 6.5 cm), along with axial deviation ranging from 10 degrees to 40 degrees in 6 patients. Mean follow-up time was 15 months (ranging from 6 to 35 months). The Ilizarov apparatus was based on two distal rings, stabilized by "K" wires, and proximally by a ring connected with an Italian femoral arch, stabilized by a Schanz screw. Planned lengthening (ranging from 3.5 cm to 12 cm) was achieved in all treated patients. The healing index ranged from 0.8 to 2.1 month/cm (mean 1.4). Problems, obstacles and complications were analyzed according to the Paley classification. In all 16 patients without primary knee stabilization, limited knee flexion ranging from 5 degrees to 90 degrees (mean 40 degrees) was noted during the distraction phase, which didn't improve significantly during the consolidation phase. Knee flexion improved to a mean 90 degrees after a 6 month follow-up. Bone regenerate defects (cysts, narrowing) were noted in 4 patients. Secondary knee stabilization was performed in 2 cases. In the first case because of knee pain and a severe limitation of knee motion. In the second, during a revision procedure because of distal femur angulation. Premature consolidation was noted in one patient and was treated by osteotomy. In one case axial deviation during the consolidation phase required osteotomy. In another case a fracture of the femur was treated by a plaster cast. In one case 1.5 years after the lengthening procedure subluxation of the hip was noted. Permanent knee flexion limitation to less than 90 degrees was noted in 6 patients. Femoral lengthening with the use of the Italian modification of the Ilizarov device give a high incidence of knee range of motion limitation, which can be decreased by preserving more than 30 degrees knee flexion during the distraction phase.     

Evaluation of medical and dental visits in New York City: Opportunities to identify persons with and at risk for diabetes mellitus in dental settings

Objective

The identification of persons with or at risk for chronic diseases is a new practice paradigm for oral healthcare. Diabetes mellitus (DM) is a chronic disease of particular importance to oral health providers. This study sought to understand healthcare utilization patterns that would support the introduction of this new practice paradigm.

Methods

The primary and oral healthcare utilization patterns of New York City (NYC) adults were assessed using data collected from the 2013 NYC Community Health Survey. We stratified healthcare utilization patterns by type of provider, insurance, DM diagnosis and DM modifiable risk factors.

Results

Of 6.4 million NYC adults, an estimated 676 000 (10.5%) reported a previous diagnosis of DM, and 3.9 million (69.5%) were identified with one or more modifiable risk factor for DM. Of these at risk individuals, 2.2 million (58.9%) received dental services in the past 12 months, and 545 000 (14.3%) did not see a primary care provider during the same period. Of the approximately 1.16 million adults without health insurance, an estimated 338 000 (26.2%) had a dental visit only.

Conclusion

Healthcare utilization patterns in this urban setting suggest that oral healthcare providers can support the identification of patients with and at risk for DM who may otherwise not have the opportunity for screening.     

Osteomyelitis due to multiple carbapenemase-producing Gram-negative bacteria: The first case report of a GES-13-producing Pseudomonas aeruginosa isolate in Canada

A case of osteomyelitis in an infant following a burn injury sustained in Pakistan caused by a GES-13-producing Pseudomonas aeruginosa (the first reported in Canada) and an OXA-48 producing Klebsiella pneumoniae is described. The present case serves to highlight the importance of international travel as a risk factor for infection with carbapenemase-producing bacteria and the challenges in the laboratory detection of these organisms.     

Efficacy and Safety of Orally Administered Intravenous Midazolam Versus a Commercially Prepared Syrup

Background:

Among different categories of sedative agents, benzodiazepines have been prescribed for more than three decades to patients of all ages. The effective and predictable sedative and amnestic effects of benzodiazepines support their use in pediatric patients. Midazolam is one of the most extensively used benzodiazepines in this age group. Oral form of drug is the best accepted route of administration in children.

Objectives:

The purpose of this study was to compare the efficacy and safety of a commercially midazolam syrup versus orally administered IV midazolam in uncooperative dental patients. Second objective was to determine whether differences concerning sedation success can be explained by child‘s behavioral problems and dental fear.

Patients and Methods:

Eighty eight uncooperative dental patients (Frankl Scales 1,2) aged 3 to 6 years, and ASA I participated in this double blind, parallel randomized, controlled clinical trial. Midazolam was administered in a dose of 0.5 mg/kg for children under the age 5 and 0.2 mg/kg in patients over 5 years of age. Physiologic parameters including heart rate, respiratory rate, oxygen saturation and blood pressure were recorded. Behavior assessment was conducted throughout the course of treatment using Houpt Sedation Rating Scale and at critical moments of treatment (injection and cavity preparation) by North Carolina Scale. Dental fear and behavioral problems were evaluated using Child Fear Schedule Survey-Dental Subscale (CFSS-DS), and Strength and Difficulties Questionnaire (SDQ). Independent t-test, Chi-Square, and Pearson correlation were used for statistical analysis.

Results:

Acceptable overall sedation ratings were observed in 90% and 86% of syrup and IV/Oral group respectively; Chi-Square P = 0.5. Other domains of Houpt Scale including: sleep, crying and movement were also not significantly different between groups. Physiological parameters remained in normal limits during study without significant difference between groups.

Conclusions:

“Orally administered IV midazolam” preparation can be used as an alternative for commercially midazolam syrup.     

Utility of common bile duct measurement in ED point of care ultrasound: A prospective study

Background

Measurement of the common bile duct (CBD) is considered a fundamental component of biliary point-of-care ultrasound (POCUS), but can be technically challenging.