Interleukin-18 Antagonism Improved Histopathological Conditions of Malaria Infection in Mice

Background: Interleukin 18 (IL-18) exerts pleiotropic roles in many inflammatory-related diseases including parasitic infection. Previous studies have demonstrated the promising therapeutic potential of modulating IL-18 bioactivity in various pathological conditions. However, its involvement during malaria infection has yet to be established. In this study, we demonstrated the effect of modulating IL-18 on the histopathological conditions of malaria infected mice. Methods: Plasmodium berghei ANKA infection in male ICR mice was used as a model for malaria infection. Modulation of IL-18 release was carried out by treatment of malarial mice with recombinant mouse IL-18 (rmIL-18) and recombinant mouse IL-18 Fc chimera (rmIL-18Fc) intravenously. Histopathological study and analysis were performed on major organs including brain, liver, spleen, lungs and kidney. Results: Treatment with rmIL-18Fc resulted in significant improvements on the histopathological conditions of the organs in malaria-infected mice. Conclusion: IL-18 is an important mediator of malaria pathogenesis and targeting IL-18 could prove beneficial in malaria-infected host.Key Words: Malaria, Interleukin-18, Plasmodium berghei, Histopathology     

The Potential of β Carbolin Alkaloids to Hinder Growth and Reverse Chloroquine Resistance in Plasmodium falciparum

Background:

Nowadays, scourge of malaria as a fatalistic disease has increased due to emergence of drug resistance and tolerance among different strains of Plasmodium falciparum. Emergence of chloroquine (CQ) resistance has worsened the calamity as CQ is still considered the most efficient, safe and cost effective drug among other antimalarials. This urged the scientists to search for other alternatives or sensitizers that may be able to augment CQ action and reverse its resistance.

Method:

Three β-carbolin derivatives, namely, harmalin, harmol and harmalol were tested for their anti-plasmodial and CQ resistance reversal effects against P. falciparum 3D7 and K1. SYBRE Green-1 based drug sensitivity assay and isobologram analysis were used to screen the mentioned effects respectively.

Results:

All of them showed moderate anti-plasmodium effect and harmalin was the most effective as compared to the others in reversing CQ resistance and tolerance.

Conclusion:

The mentioned phytochemicals are not ideal to be used as conventional antimalarials and only harmalin can be suggested to reverse CQ resistance in P. falciparum K1.     

Electrocardiographic Monitoring During Coloscopy

Electrocardiographic abnormalities were observed in 15 of 23 patients (65%), five with known heart disease, who were monitored for one hour prior to, during and for one hour after coloscopy. In one patient, ischemic S-T depression, 2 mm. below the resting level, persisted during the one hour following coloscopy. In all other patients, the electrocardiographic abnormalities disappeared before the end of the monitoring period.     

Intravenous calcitriol versus paricalcitol in haemodialysis patients with severe secondary hyperparathyroidism

Aim:   Secondary hyperparathyroidism (SHPT) is common among haemodialysis patients. Intensive treatment with calcitriol is often complicated by hypercalcaemia, hyperphosphataemia and elevated calcium phosphorus (Ca X PO₄) product. Paricalcitol is a vitamin D analogue developed to overcome some of the limitations of calcitriol therapy. The study objectives were to compare the response of intact parathyroid hormone (iPTH) and the incidence of hypercalcaemia, hyperphosphataemia and elevated Ca X PO₄ product in patients with severe SHPT treated with either i.v. calcitriol or i.v. paricalcitol.
Methods:   This was a single centre randomized open label study. Patients with serum intact iPTH of 50 pmol/L or more were randomized to receive either i.v. calcitriol (0.01 ug/kg) or i.v. paricalcitol (0.04 ug/kg) during every haemodialysis treatment. Serum iPTH, calcium, phosphorus and alkaline phosphatase were measured at the beginning of the study and every 3 weeks for 12 weeks.
Results:   Twenty-five patients were enrolled into the study – 12 were randomized into the calcitriol group and 13 into the paricalcitol group. There were no differences in the baseline study parameters between both groups. Serum iPTH levels were significantly reduced ( P  = 0.003) only in the paricalcitol group but not in the calcitriol group ( P  = 0.101). On the other hand, serum calcium levels were significantly increased only in the calcitriol group ( P  = 0.004 vs P  = 0.242). Serum phosphorus, alkaline phosphatase and Ca X PO₄ product were not different.
Conclusion:   Intravenous paricalcitol may be superior to i.v. calcitriol for the treatment of severe SHPT in our chronic haemodialysis population. A larger randomized controlled trial is indicated to confirm these initial findings.     

Endovascular Abdominal Aortic Aneurysm Repair by Interventional Cardiologists—A Community‐Based Experience

Introduction: Endovascular repair of abdominal aortic aneurysm (AAA) is a relatively recent technology. In comparison to the conventional open surgical treatment for AAA, endovascular AAA repair (EVAR) combines a less‐invasive approach with lower morbidity and mortality. There have been few studies regarding the performance of this procedure in a community‐based setting. We report our experience of EVAR performed primarily by interventional cardiologists in a community hospital. Methods: In our community hospital setting, between September 2005 and November 2007, we included all patients who underwent EVAR by interventional cardiologists, with available on‐site vascular surgical support. Clinical and serial computed angiographic imaging outcomes were followed by a retrospective chart review. Data collection tools included demographic and clinical characteristics, anatomical aneurysm features, length of stay, peri‐ and postprocedural complications, and mortality. Results: A total of 71 consecutive patients had EVAR attempted. The endovascular stent placement was successful in 67 (93%) patients. Thirty‐day mortality in this study was 1 of 71 (1.4%). All four procedural failures and the single periprocedural mortality occurred in women. Mean follow‐up was 12 months. There were a total of six mortalities and among these four were women (P ≤ 0.001); however, multivariate analysis revealed loss of significant difference in mortality (P = 0.16). Major complications following EVAR were noted in 10 of 71 (14%) patients. Conclusion: EVAR can be successfully performed by experienced interventional cardiologists with vascular surgical support in a community‐based setting. In our experience, there is acceptable rate of complications and mortality in a carefully selected patient population. (J Interven Cardiol 2010;23:485–490)     

His Bundle Extrasystoles Revisited: The Great Electrocardiographic Masquerader

A 74‐year‐old man with past history of near syncope presented with frequent periods of second‐degree atrioventricular block (2° AVB). An electrophysiological study revealed prolonged atrial‐His and His‐ventricular (HV) intervals and frequent His bundle (H) extrasystoles. The latter manifested in the surface electrocardiogram as premature atrial, junctional, or ventricular beats, as well as 2° AVB that mimicked Wenckebach or Mobitz II block. Procainamide markedly suppressed H extrasystole. However, because of the presence of prolonged HV interval and history of presyncope, a permanent pacemaker was inserted. The case illustrates the varied manifestation of H extrasystole and presents guidelines for management. (PACE 2011; e56–e59)     

Mitral Balloon Valvuloplasty as an Outpatient Procedure Using Inoue Balloon Technique

Objective: To evaluate the safety and feasibility of mitral balloon valvuloplasty (MBV) as an outpatient procedure. Background: MBV is usually done as an inpatient procedure, requiring 3–4 days of hospital admission. Only one report is available about MBV as a day case procedure in the English literature. Methods: Between October 1994 and December 1996, 128 patients underwent MBV using an Inoue balloon. Of those, 31 patients (Group I) had the procedure as outpatients and 97 patients (Group II) as inpatients. Their mean age in Group I was 29 ± 9 years and in Group II 32 ± 10 years (P < 0.3). Atrial fibrillation was present in 4 patients in Group I and in 13 patients in Group II (P < 0.99). Results: Hemodynamic study revealed that mitral valve area increased from 0.9 ± 0.2 to 1.9 ± 0.5 cm²* in Group I and from 0.8 ± 0.2 to 1.7 ± 0.5 cm²* in Group II, Left atrial pressure decreased from 24 ± 5 to 15 ±6 mm Hg* in Group I and 24 ± 6 to 16 ± 5 mmHg in Group II.* Mitral valve gradient decreased from 15 + 5 to 5 + 2 mmHg in Group I and 15 + 5 to 6 + 3 mmHg in Group II* (*P < 0.001). Patients in Group I stayed in the Preadmission Unit for a mean period of 9.5 ± 2.5 hours. Patients in Group II stayed for a mean of 2.5 days in the hospital. Severe mitral regurgitation developed in one patient in each Group and needed semiurgent mitral valve replacement without sequela. No death, convulsions, or thromboembolism were encountered, and three patients in both Groups developed minor hematoma and needed no additional treatment. Conclusion: MBV as an outpatient procedure is feasible and safe and could significantly decrease the cost of medical care.     

Evaluation of the Safety and Efficacy of Deep Sedation for Electrophysiology Procedures Administered in the Absence of an Anesthetist

Several procedures performed in the electrophysiology laboratory (EP lab) require surgical manipulation and are lengthy. Patients undergoing such procedures usually receive general anesthesia or deep sedation administered by an anesthesiologist. In 536 consecutive procedures performed in the EP lab, we assessed the safety and efficacy of deep sedation administered under the direction of an electrophysiologist and in the absence of an anesthetist. Patients were monitored with pulse oximetry, noninvasive blood pressure recordings, and continuous ECGs. The level of consciousness and vital signs were evaluated at 5-minute intervals. Deep sedation was induced in 260 patients using midazolam, phenergan, and meperidine, then maintained with intermittent dosing of meperidine at the following mean doses: midazolam 0.031 ± 0.024 mg/kg; phenergan 0.314 ± 0.179 mg/kg; and meperidine 0.391 ± 0.167 mg/kg per hour. In the remaining 276 patients, deep sedation was induced with midazolam and fentanyl and maintained with a continuous infusion of fentanyl at a mean dose of 2.054 ± 1.43 μg/kg per hour. Fourteen patients experienced a transient reduction in oxygen saturation that was readily reversed following administration of naloxone. An additional 11 patients desaturated secondary to partial airway obstruction, which resolved after repositioning the head and neck. Fourteen patients experienced hypotension with fentanyl. All but one returned to baseline blood pressures following an infusion of normal saline. No patient required intubation and no death occurred. Only three patients had recollection of periprocedure events. No patient remembered experiencing pain with the procedure. Hospital stays were not prolonged as a result of the sedation used. In conclusion: (1) deep sedation during EP procedures can be administered safely under the guidance of the electrophysiologist without an anesthetist present; (2) the drugs used should be readily reversible in case of respiratory depression; and (3) this approach may reduce the overall cost of the procedures in the EP lab, maintaining adequate patient comfort.