Drug resistance in malaria

Ever since the discovery of the first case of chloroquine resistance along the Thai-Combodian border in the late 1950s, Southeast Asia has played an important role as a focus for the development of drug resistance in Plasmodium falciparum. Although the first case of quinine resistance had been reported much earlier from South America, the onset of chloroquine resistance marked the beginning of a new chapter in the history of malaria in Southeast Asia and by 1973 chloroquine finally had to be replaced by the combination of sulphadoxine and pyrimethamine (SP) as first line drug for the treatment of uncomplicated malaria in Thailand and more than 10 African countries have also switched their first line drug to SP. In 1985, eventually SP was replaced by mefloquine. The rapid development of resistance to this new drug leads to the introduction of artemisinin as a combination drug in the mid-1990s. It is mandatory to mention here that therapeutic regimens for prevention and treatment of chloroquine-resistant P. falciparum are associated with higher costs and side-effects compared to chloroquine. Additionally, some of these alternative treatments are associated with more side-effects, take longer time for cure and are more difficult to comply with than chloroquine. Urgent efforts are needed to identify effective, affordable, alternative antimalarial regimens. Molecular markers for antimalarial resistance have been identified, including pfmdr-1 and pfcrt polymorphisms associated with chloroquine resistance and dhfr and dhps polymorphisms associated with SP resistance. Polymorphisms in pfmdr-1 may also be associated with resistance to chloroquine, mefloquine and artemisinin. Use of such genetic information for the early detection of resistance foci and future monitoring of drug resistant malaria is a potentially useful epidemiological tool, in conjunction with the conventional in vitro and in vivo drug sensitivity assessments. The purpose of this review is to describe the state of knowledge regarding drug resistant malaria and to outline the changing patterns of drug resistance including its determinants, current status in diverse geographical areas, molecular markers and their implications to limit the advent, spread and intensification of drug resistant malaria.     

"Were-wolf" cutaneous tuberculosis

Lupus vulgaris is a variant of cutaneous tuberculosis. Its more destructive and mutilating clinical forms have become rarer in consonance of a general decline of cutaneous tuberculosis. It is rarely seen now in developed countries due to stringent control measures, improved quality of living and effective therapeutic regimens. Misdiagnosis, neglect, or late diagnosis may result in severe, ulcerative and mutilating "wolf eaten" skin lesions.This paper describes four such cases of "were-wolf" cutaneous tuberculosis. Early diagnosis and treatment is important to prevent much of the disfigurement.     

Improved cardioprotection using a novel stepwise ischemic preconditioning protocol in rabbit heart

Background

The current commonly used cardiac ischemic preconditioning (IPC) protocol, involving three 5-min cycles of ischemia–reperfusion (I/R), may not be clinically beneficial because of its acutely deleterious effects on hemodynamics. This study attempted to assess the effects of a novel stepwise IPC scheme on cardiac function, infarct size, and arrhythmogenesis in a rabbit model of prolonged I/R.

Methods

Anesthetized open-chest rabbits were subjected to 60-min occlusion of a proximal branch of the left coronary artery followed by 180-min reperfusion. Animals were divided into five groups (n = 6 each): (1) control group (no IPC); (2) 2-min IPC group (three cycles of 2-min IPC); (3) 5-min IPC group (three cycles of 5-min IPC); (4) 10-min IPC group (three cycles of 10-min IPC); and (5) stepwise IPC group (2-, 5-, and 10-min I/R).

Results

Compared with control group, 2-, 5-, and 10-min IPC decreased arrhythmia score by 16%, 67%, and 33%, respectively. Remarkably, stepwise IPC resulted in a 78% reduction of arrhythmias. Stepwise IPC also produced the least ventricular infarct size when compared with 2-, 5-, and 10-min IPC groups (16.4% versus 39.3%, 28.1%, and 38.5%, P < 0.05).

Conclusions

These results suggest that stepwise IPC has better cardioprotective effects against prolonged I/R injury and may serve as an acceptable approach to clinical revascularization procedures on the heart, including catheter-based and surgical approaches.     

Are the measurements of water-filled and air-charged catheters the same in urodynamics?

Introduction and hypothesis

The aim of our study was to compare air-charged and water-filled catheters simultaneously in the measurement of the intravesical, abdominal and detrusor pressure during urodynamic investigations.

Methods

Consecutive women with lower urinary tract symptoms, referred for urodynamics were prospectively studied. Readings of intravesical pressure (p_ves), abdominal pressure (p_abd) and detrusor pressure (p_det), recorded by both the air-charged and water-filled catheters, were displayed simultaneously and compared at the end of filling, on standing, on sitting prior to voiding and at the maximum involuntary detrusor contraction. The signals (pressures) recorded by both types of catheter were compared using the Bland–Altman plot and paired samples t test.

Results

Twenty women with a mean age of 49 (range 36–72) were recruited. One patient with normal urodynamics was excluded in view of the poor quality trace. At each of the four comparison points, the air-charged catheters consistently produced higher mean pressures than the water-filled catheters. There were wide variations in the difference between the readings produced by the two types of catheter.

Conclusions

Pressures measured using air-charged catheters are not comparable with water-filled catheters and are therefore not interchangeable. Caution must be used when comparing urodynamic parameters using air-charged and water-filled catheters.     

Isolated adrenal cryptococcosis,diagnosed by fine‐needle aspiration biopsy: A case report

This report documents a case of isolated adrenal gland cryptococcosis without the often reported component of concomitant meningitis or Addison's disease in an immune competent patient. Furthermore, both the patient's lung cancer and adrenal infection with cryptococcus were incidentally discovered during work‐up for syncope in the setting of hyponatremia. This case also underscores the diagnostic value of fine‐needle aspiration biopsy in this unusual presentation. Diagn. Cytopathol. 2014;42:899–901. © 2014 Wiley Periodicals, Inc.