Calcium channel blocker overdose mimicking an acute myocardial infarction

A 42-year-old man presented with shortness of breath, weakness, and diaphoresis, and developed a new left bundle branch block while under evaluation in the Emergency Department. At emergency cardiac catheterization, he was found to have only insignificant coronary disease, and a hyperdynamic ventricle. Despite these findings, he subsequently developed profound bradycardia and hypotension, which were refractory to standard therapies including pressors, calcium, and transvenous pacing. He gradually improved over several days and made a full recovery, after which he admitted to taking multiple calcium channel blockers (CCBs) in an attempt to self-medicate for symptoms he related to his lifelong paroxysmal supraventricular tachycardia. This is the first report of a CCB overdose mimicking an acute myocardial infarction, and highlights the fact that CCB overdose must be considered in the differential diagnosis of some patients who present with apparent acute myocardial infarction.     

Anaerobic bacteria associated with cervical neoplasia

The possible association between cervical neoplasia and anaerobic bacteria was examined by correlating the histopathology of cervical biopsies with anaerobic cultures obtained from the cervix in 90 patients. Fourteen patients had invasive carcinoma of the cervix (ICC). All but one of them had Stage I or II disease. Severe dysplasia was present in 11 patients, moderate dysplasia in 9, mild dysplasia in 11, and carcinoma in situ in 26. Cultures from patients with ICC were characterized by a relative sparsity of anaerobes. The cultures of 3 of 14 patients with ICC contained anaerobes, in contrast to 53 of 76 patients in the other categories. Further, none of the 14 patients with ICC had anaerobic gram-negative bacilli whereas they were present in 18 of 76 patients in the other categories. ICC was not associated with any specific anaerobic bacteria. These data suggest that anaerobic bacteria are sparse and anaerolic gram-negative bacilli are rare in early invasive carcinoma of the cervix.     

Three-Year Trajectory of Teachers’ Fidelity to a Drug Prevention Curriculum

Little is known about the trajectories over time of classroom teachers’ fidelity to drug prevention curricula. Using the “Concerns-Based Adoption Model” (C-BAM) as a theoretical framework, we hypothesized that teachers’ fidelity would improve with repetition. Participants comprised 23 middle school teachers who videotaped their administration of three entire iterations of the All Stars curriculum. Investigators coded two key curriculum lessons, specifically assessing the proportion of activities of each lesson teachers attempted and whether they omitted, added, or changed prescribed content, or delivered it using new methods. Study findings provided only partial support for the C-BAM model. Considerable variability in teachers’ performance over time was noted, suggesting that their progression over time may be nonlinear and dynamic, and quite possibly a function of their classroom and school contexts. There was also evidence that, by their third iteration of All Stars, teachers tended to regress toward the baseline mean. That is, the implementation quality of those that started out with high levels of fidelity tended to degrade, while those that started out with very low fidelity to the curriculum tended to improve. Study findings suggest the need for ongoing training and technical assistance, as well as “just in time” messages delivered electronically; but it is also possible that some prevention curricula may impose unrealistic expectations or burdens on teachers’ abilities and classroom time.     

Childhood leprosy in an endemic area.

A study was done on 794 new cases of leprosy among children (aged 0-14 years) detected and treated with MDT during 1990-1995 in Gudiyatham Taluk, South India. Incidence rates of leprosy and proportion of multibacillary cases increased with age, while bacillary + tuberculoid was most common. Over 80% had a single patch and most children were detected through surveys. Nearly 30% had history of household contacts with leprosy, mostly parents or grandparents. Reactions and relapses were not uncommon. The findings emphasize the need for more careful surveys for case detection and better follow-up in case management.     

Acute intestinal obstruction due to small gut hemangioma.

A 20-year-old man presented with acute intestinal obstruction due to multiple hemangiomas of small intestine extending into the adjoining mesentery. The diagnosis was made at laparotomy and subsequently confirmed on histology. Occurrence of hemangioma in the small intestine and its presentation as acute intestinal obstruction are rare.     

Successful switch (tOPV to bOPV) in India: Tribute to a resilient health system

In accordance with the end game strategies for polio eradication a synchronized switch plan from tOPV to bOPV was implemented globally in 2016. The National Committee for Polio Eradication (NCCPE) validated the switch activities in India. An expert group of 104 academics conducted field visits in 25 states and 2 Union territories for independent verification (after an initial round of verification by the National Polio Surveillance Project [NPSP]). The objectives were to validate withdrawal and disposal of tOPV by screening cold chain points in public and private sector health facilities in both rural and urban areas; additionally, availability of bOPV and IPV was also documented. 34 filled tOPV and 5 empty vials were detected inside cold chain equipment and 17 outside. The disposal mechanism was found to be reasonably adequate. The key strategies -- ‘throttling’ of vaccine supplies well ahead of the switch date while preventing stock outs at various immunization points, simultaneously working with the regulators to delicense the tOPV on the switch date and helping manufacturers to calibrate vaccine production according to national timelines, and strong and persistent advocacy with professional associations to align with national bOPV and IPV policy facilitated successful accomplishment of the switch process. Effective implementation of the switch strategy in India also bears testimony to the resilience of the health system operating under diverse and heterogeneous governance.     

Stable 5,6-epoxyeicosatrienoic acid analog relaxes coronary arteries through potassium channel activation

5,6-epoxyeicosatrienoic acid (5,6-EET) is a cytochrome P450 epoxygenase metabolite of arachidonic acid that causes vasorelaxation. However, investigations of its role in biological systems have been limited by its chemical instability. We developed a stable agonist of 5,6-EET, 5-(pentadeca-3(Z),6(Z),9(Z)-trienyloxy)pentanoic acid (PTPA), in which the 5,6-epoxide was replaced with a 5-ether. PTPA obviates chemical and enzymatic hydrolysis. In bovine coronary artery rings precontracted with U46619, PTPA (1 nmol/L to 10 micromol/L) induced concentration-dependent relaxations, with maximal relaxation of 86+/-5% and EC50 of 1 micromol/L. The relaxations were inhibited by the cyclooxygenase inhibitor indomethacin (10 micromol/L; max relaxation 43+/-9%); the ATP-sensitive K+ channel inhibitor glybenclamide (10 micromol/L; max relaxation 49+/-6%); and the large conductance calcium-activated K+ channel inhibitor iberiotoxin (100 nmol/L; max relaxation 38+/-6%) and abolished by the combination of iberiotoxin with indomethacin or glybenclamide or increasing extracellular K+ to 20 mmol/L. Whole-cell outward K+ current was increased nearly 6-fold by PTPA (10 micromol/L), which was also blocked by iberiotoxin. Additionally, we synthesized 5-(pentadeca-6(Z),9(Z)-dienyloxy)pentanoic acid and 5-(pentadeca-3(Z),9(Z)-dienyloxy)pentanoic acid (PDPA), PTPA analogs that lack the 8,9 or 11,12 double bonds of arachidonic acid and therefore are not substrates for cyclooxygenase. The PDPAs caused concentration-dependent relaxations (max relaxations 46+/-13% and 52+/-7%, respectively; EC50 1micromol/L), which were not altered by glybenclamide but blocked by iberiotoxin. These studies suggested that PTPA induces relaxation through 2 mechanisms: (1) cyclooxygenase-dependent metabolism to 5-ether-containing prostaglandins that activate ATP-sensitive K+ channels and (2) activation of smooth muscle large conductance calcium-activated K+ channels. PDPAs only activate large conductance calcium-activated K+ channels.     

A p38alpha selective mitogen-activated protein kinase inhibitor prevents periodontal bone loss

In the oral microbial environment, Gram-negative bacterial derived lipopolysaccharide (LPS) can initiate inflammatory bone loss as seen in periodontal diseases. p38 Mitogen-activated protein kinase (MAPK) signaling is critical to inflammatory cytokine and LPS-induced cytokine expression, which may contribute toward periodontal bone loss. The purpose of this proof-of-principle study was to evaluate the ability of an orally active p38alpha MAPK inhibitor (SD-282) to reduce periopathogenic LPS-induced alveolar bone loss in an experimental rat model. Five groups of Sprague-Dawley rats received one of the following treatments: LPS injected to the palatal gingiva adjacent to the maxillary molars three times per week for 8 weeks, LPS plus two doses of SD-282 (15 or 45 mg/kg) twice daily by oral gavage, or control groups given drug vehicle (1% polyethylene glycol) or SD-282 (45 mg/kg) only. Baseline and 8-week alveolar bone loss was assessed by microcomputed tomography (microCT) and histological examination. LPS induced severe bone loss over this time period, whereas control groups were unchanged from baseline measurements. Both doses of SD-282 showed significant protection from LPS-induced bone loss. Bone area and volumetric analysis of maxillas by microCT indicated significant loss of bone volume with LPS treatment, which was blocked with the p38 inhibitor. Histological examination indicated significantly fewer tartate-resistant acid phosphatase-positive osteoclasts and a significant decrease in interleukin (IL)-6, IL-1beta, and tumor necrosis factor alpha expression in p38 inhibitor-treated groups compared with LPS groups by immunostaining. Results from this in vivo study suggest that orally active p38 MAPK inhibitors can reduce LPS-induced inflammatory cytokine production and osteoclast formation and protect against LPS-stimulated alveolar bone loss.