Effects of Chlorpheniramine Maleate on Catheter-Related Bladder Discomfort in Patients Undergoing Ureteroscopic Stone Removal: A Randomized Double-Blind Study

Catheter-related bladder discomfort (CRBD) associated with intraoperative urinary catheterization is a distressing symptom during recovery from anesthesia. Anticholinergics have been used to manage CRBD. Chlorpheniramine maleate (CPM) is a first-generation antihistamine, which also has anticholinergic effects. This study was undertaken to evaluate the efficacy of CPM in preventing CRBD. Seventy-six adults (19-65 years old) with American Society of Anesthesiologists physical status I, II, or III of either sex, undergoing elective ureteroscopic stone removal under general anesthesia were randomized into one of two groups (each n = 38). Group C (control) received a placebo, and group CPM received 8 mg of intravenous CPM before the induction of anesthesia. CRBD was assessed upon arrival in the post-anesthetic care unit at 0, 1, 2, and 6 h. The severity of CRBD was graded as none, mild, moderate, and severe. Tramadol was administered when the severity of CRBD was more than moderate. The incidence rate and overall severity of CRBD did not differ between the groups at any of the time points (р > 0.05). The incidence of moderate CRBD was higher in group C than in group CPM only at 0 h (26.3% vs. 5.3%, р = 0.025). However, fewer patients in the CPM group required rescue tramadol to relieve CRBD after surgery (31.6% vs. 60.5%, р = 0.011). CPM administration before the induction of anesthesia had little effect on the incidence and severity of CRBD after surgery, but it reduced the administration of tramadol required to control CRBD postoperatively.     

Accuracy of Diffusion Tensor Imaging for Diagnosing Cervical Spondylotic Myelopathy in Patients Showing Spinal Cord Compression

ObjectiveTo assess the performance of diffusion tensor imaging (DTI) for the diagnosis of cervical spondylotic myelopathy (CSM) in patients with deformed spinal cord but otherwise unremarkable conventional magnetic resonance imaging (MRI) findings.ResultsThe MD, LD, and RD cut-off values were 1.079 × 10^-3, 1.719 × 10^-3, and 0.749 × 10^-3 mm²/sec, respectively, and that of FA was 0.475. Sensitivity, specificity, positive predictive value and negative predictive value were: 100 (4/4), 44.8 (13/29), 20 (4/20), and 100 (13/13) for MD; 100 (4/4), 27.6 (8/29), 16 (4/25), and 100 (8/8) for FA; 100 (4/4), 58.6 (17/29), 25 (4/16), and 100 (17/17) for MD∩FA; 100 (4/4), 68.9 (20/29), 30.8 (4/13), and 100 (20/20) for LD∩FA; and 75 (3/4), 68.9 (20/29), 25 (3/12), and 95.2 (20/21) for RD∩FA in percentage value. Diagnostic performance comparisons revealed significant differences only in specificity between FA and MD∩FA (p = 0.003), FA and LD∩FA (p < 0.001), FA and RD∩FA (p < 0.001), MD and LD∩FA (p = 0.024) and MD and RD∩FA (p = 0.024).ConclusionFractional anisotropy combined with MD, RD, or LD is expected to be more useful than FA and MD for diagnosing CSM in patients who show deformed spinal cords without signal changes on MRI.     

Hydrolysis of Clavulanate by Mycobacterium tuberculosis β-Lactamase BlaC Harboring a Canonical SDN Motif

Combinations of β-lactams with clavulanate are currently being investigated for tuberculosis treatment. Since Mycobacterium tuberculosis produces a broad spectrum β-lactamase, BlaC, the success of this approach could be compromised by the emergence of clavulanate-resistant variants, as observed for inhibitor-resistant TEM variants in enterobacteria. Previous analyses based on site-directed mutagenesis of BlaC have led to the conclusion that this risk was limited. Here, we used a different approach based on determination of the crystal structure of β-lactamase Bla_MAb of Mycobacterium abscessus, which efficiently hydrolyzes clavulanate. Comparison of Bla_MAb and BlaC allowed for structure-assisted site-directed mutagenesis of BlaC and identification of the G¹³²N substitution that was sufficient to switch the interaction of BlaC with clavulanate from irreversible inactivation to efficient hydrolysis. The substitution, which restored the canonical SDN motif (SDG→SDN), allowed for efficient hydrolysis of clavulanate, with a more than 10⁴-fold increase in k_cat (0.41 s⁻¹), without affecting the hydrolysis of other β-lactams. Mass spectrometry revealed that acylation of BlaC and of its G¹³²N variant by clavulanate follows similar paths, involving sequential formation of two acylenzymes. Decarboxylation of the first acylenzyme results in a stable secondary acylenzyme in BlaC, whereas hydrolysis occurs in the G¹³²N variant. The SDN/SDG polymorphism defines two mycobacterial lineages comprising rapidly and slowly growing species, respectively. Together, these results suggest that the efficacy of β-lactam–clavulanate combinations may be limited by the emergence of resistance. β-Lactams active without clavulanate, such as faropenem, should be prioritized for the development of new therapies.