Phenylephrine Increases Cerebral Blood Flow during Low-flow Hypothermic Cardiopulmonary Bypass in Baboons

Background: Although low-flow cardiopulmonary bypass (CPB) has become a preferred technique for the surgical repair of complex cardiac lesions in children, the relative hypotension and decrease in cerebral blood flow (CBF) associated with low flow may contribute to the occurrence of postoperative neurologic injury. Therefore, it was determined whether phenylephrine administered to increase arterial blood pressure during low-flow CPB increases CBF.

Methods: Cardiopulmonary bypass was initiated in seven baboons during fentanyl, midazolam, and isoflurane anesthesia. Animals were cooled at a pump flow rate of 2.5 l *symbol* min-1 *symbol* m-2 until esophageal temperature decreased to 20 degrees C. Cardiopulmonary bypass flow was then reduced to 0.5 l *symbol* min-1 *symbol* m-2 (low flow). During low-flow CPB, arterial partial pressure of carbon dioxide (PCO2) and blood pressure were varied in random sequence to three conditions: (1) PCO2 30-39 mmHg (uncorrected for temperature), control blood pressure; (2) PCO2 50-60 mmHg, control blood pressure; and (3) PCO2 30-39 mmHg, blood pressure raised to twice control by phenylephrine infusion. Thereafter, CPB flow was increased to 2.5 l *symbol* min-1 *symbol* m-2, and baboons were rewarmed to normal temperature. Cerebral blood flow was measured by washout of intraarterial133 Xenon before and during CPB.

Results: Phenylephrine administered to increase mean blood pressure from 23+/-3 to 46+/-3 mmHg during low-flow CPB increased CBF from 14+/-3 to 31+/-9 ml *symbol* min-1 *symbol* 100 g-1, P < 0.05. Changes in arterial PCO2 alone during low flow bypass produced no changes in CBF.     

Exhaled Nitric Oxide Levels during Acute Asthma Exacerbation

Objectives: Fractional exhaled nitric oxide (FE_NO) has been shown in laboratory settings and trials of patients with stable asthma to correlate with the degree of airway inflammation. The authors hypothesized that the technique of measuring FE_NO would be reproducible in the setting of acute asthma in the emergency department (ED) and that the FE_NO results during ED visits would potentially predict disposition, predict relapse following discharge, and correlate with the National Institutes of Health (NIH) asthma severity scale and peak expiratory flow measurements. Methods: The authors prospectively measured FE_NO in a convenience sample of ED patients with acute exacerbations of asthma, both at the earliest possible opportunity and then one hour later. Each assessment point included triplicate measurements to assess reproducibility. The authors also performed spirometry and classified asthma severity using the NIH asthma severity scale. Discharged patients were contacted in 72 hours to determine whether their asthma had relapsed. Results: The authors discontinued the trial (n= 53) after a planned interim analysis demonstrated reproducibility (coefficient of variation, 15%) substantially worse than our a priori threshold for precision (4%). There was no association between FE_NO response and corresponding changes in spirometry or clinical scores. Areas under the receiver operating characteristic curves for the prediction of hospitalization and relapse were poor (0.579 and 0.713, respectively). Conclusions: FE_NO measurements in ED patients with acute asthma exacerbations were poorly reproducible and did not correlate with standard measures of asthma severity. These results suggest that using existing technology, FE_NO is not a useful marker for assessing severity, response to treatment, or disposition of acute asthmatic patients in the ED.     

In vitro evaluation of the accuracy of five different electronic apex locators for determining the working length of endodontically retreated teeth

The aim of this study was to evaluate the accuracy of five electronic apex locators (EALs) in determining the working length (WL) of teeth after removal of the root canal obturation materials. A total of 32 extracted straight, single-rooted teeth were used. The actual canal length (AL) was determined and the WL was established by subtracting 0.5 mm from the AL. The root canals were instrumented and divided into two groups. One group (n = 6) served as control, while the other group (n = 26) was the experimental group. In the experimental group, the root canals were obturated using vertically compacted gutta-percha with AH 26 sealer. In both groups, the access cavities were restored with a provisional restoration and stored for 15 days at 37 degrees C and 100% humidity. The root canal obturation material was removed, and the teeth were then mounted in an experimental apparatus. Five EALs were used: Dentaport ZX, ProPex, Foramatron D10, Apex NRG and Apit 7. For the electronic measurement of canal length, a size 25 K-file was used. During measurement, the canal was irrigated with 2.5% sodium hypochlorite. The difference (D) between the AL and the electronically determined length (EDL), AL-EDL, was calculated and recorded for each measurement. Data were analysed by two-way anova and Fisher's PLSD test. In both groups, statistically significant differences were found among the EALs (P < 0.01). In conclusion, the Dentaport ZX, ProPex and Foramatron D10 were more accurate than the other two EALs in determining the WL in teeth after removal of the root canal obturation materials. However, the Apex NRG and Apit 7 were also reliable for determination of the WL in the majority of the cases.     

Saudi young patient understanding of information about side effects: Verbal versus numerical expression

Objective

To determine the effect of providing different formats about side effect information (verbal versus numerical) to acne patients in Saudi Arabia that are newly prescribed Roaccutane.

Design

A prospective study assessing patients’ degree of estimation about side effect information.

Participants

One hundred and forty-one acne patients newly prescribed Roaccutane.

Settings

Four dermatology clinics in Riyadh. Two in tertiary hospitals and the other two in private clinics.

Intervention

Each patient received information about two different side effects for Roaccutane. The side effect provided was supplemented with the probability of occurrence, which was written either in words or in numbers. (Dry eye “very common” or “30%”; Loss of hair “rare” or “0.01%”).

Main outcome measures

Patient’s estimation of side effect occurrence. Other outcomes were the likelihood of experiencing the side effect, the severity of the side effect, their perception of risk of the side effects to their general health, their satisfaction with the information provided and, whether the information provided will influence their decision to take the medicine.

Result

The mean estimate for side effect occurrence for the dry eyes was 46% in the verbal group and 41% in the numerical group (p = 0.5); for loss of hair it was 50% in the verbal group and 39% in the numerical group (p = 0.03). There are no significant differences between verbal and numerical groups regarding the remaining measures.

Conclusion

Patients overestimate the probability of occurrence of side effect. Verbal format of probability of occurrence is associated with higher estimation than the numerical format.     

Non-steroidal anti-inflammatory drugs, tumour immunity and immunotherapy

Non-steroidal anti-inflammatory drugs (NSAIDs) have received considerable importance in cancer chemoprevention over the last few years. They are now being considered as prospective candidates in cancer immunotherapy because of their striking immune-enhancing impact on various effector elements of anti-tumour immunity on one hand, and to augment the efficacy of different anti-cancer immunotherapeutic strategies on the other. This review specifically discusses the role of NSAIDs in anti-tumour immunity by describing their immunomodulatory effects on different immune cells including tumour-associated macrophages (TAM), dendritic cells (DC), natural killer (NK) cells, T effector cells, and T regulatory cells (Treg). Secondly, the therapeutic perspective of NSAIDs in combination with different anti-cancer immunotherapeutic approaches, in particular the cancer vaccines, tumour-specific monoclonal antibodies, and cytokine-based therapy, has been outlined. At the end, the impact of anti-inflammatories other than NSAIDs on tumour immunity and immunotherapy, and the immunopharmacological potential of selective E-prostanoid (EP) receptor antagonists with respect to cancer immunity have also been discussed briefly.     

The use of pharmacoeconomic evidence to support formulary decision making in Saudi Arabia: Methodological recommendations

In pharmacoeconomics the costs and consequences of alternative medications are compared. Many countries have begun to use pharmacoeconomic evidence to support decisions on licensing, pricing, reimbursement, or addition to the formulary. In Saudi Arabia, it is not mandatory to submit cost effectiveness evidence to support licensing or addition to the formulary decisions however, data will be considered if submitted. Previous evidence suggests that the use of pharmacoeconomic evidence by Saudi Pharmacy and Therapeutic (P&T) committee members in formulary decisions making process is limited mainly because of lack of expertise and lack of resources. This paper intended to provide Saudi P&T decision makers with a clear set of best practice methodological recommendations to help in increasing the utilisation of pharmacoeconomic evidence in the formulary decisions making process.     

Antimicrobial activity of julifloricine isolated from Prosopis juliflora

Antimicrobial activity of julifloricine, an alkaloid isolated from Prosopis juliflora, was studied in vitro against 40 microorganisms which included 31 bacteria, two Candida species, five dermatophytic fungi and two viruses. Significant inhibitory effect was noted against Gram positive bacteria. The minimal inhibitory concentration (MIC) for Staphylococcus aureus, S. epidermidis, S. citreus, Streptococcus pyogenes and Sarcina lutea was 1 microgram/ml and against S. faecalis, S. pneumoniae, S. lactis, Corynebacterium diphtheriae, C. hofmannii and Bacillus subtilis, 5 micrograms/ml. Its effect was compared with those of identical concentrations of benzyl penicillin, gentamicin and trimethoprim. The inhibitory effect of julifloricine on Gram negative bacteria such as the species of Salmonella, Shigella, Klebsiella, Proteus, Pseudomonas, Enterobacter, Aeromonas and Vibrio was almost insignificant. Julifloricine as compared to micoanzole was found superior against C. tropicalis and responded equally to C. albicans. As compared to econazole, it was found less effective against both C. albicans and C. tropicalis. This alkaloid was found inactive against dermatophytic fungi (up to a dose of 10 micrograms/ml) and viruses which included Herpes simplex 1 and Newcastle disease virus. Julifloricine up to a doses of 1000 micrograms/25 g of mice was found nonlethal.