Treatment of malaria in the United States: a systematic review

Context  Many US clinicians and laboratory personnel are unfamiliar with the diagnosis and treatment of malaria. Objectives  To examine the evidence base for management of uncomplicated and severe malaria and to provide clinicians with practical recommendations for the diagnosis and treatment of malaria in the United States. Evidence Acquisition  Systematic MEDLINE search from 1966 to 2006 using the search term malaria (with the subheadings congenital, diagnosis, drug therapy, epidemiology, and therapy). Additional references were obtained from searching the bibliographies of pertinent articles and by reviewing articles suggested by experts in the treatment of malaria in North America. Evidence Synthesis  Important measures to reduce morbidity and mortality from malaria in the United States include the following: obtaining a travel history, considering malaria in the differential diagnosis of fever based on the travel history, and prompt and accurate diagnosis and treatment. Chloroquine remains the treatment of choice for Plasmodium falciparum acquired in areas without chloroquine-resistant strains. In areas with chloroquine resistance, a combination of atovaquone and proguanil or quinine plus tetracycline or doxycycline or clindamycin are the best treatment options. Chloroquine remains the treatment of choice for all other malaria species, with the exception of P vivax acquired in Indonesia or Papua New Guinea, in which case atovaquone-proguanil is best, with mefloquine or quinine plus tetracycline or doxycycline as alternatives. Quinidine is currently the recommended treatment for severe malaria in the United States because the artemisinins are not yet available. Severe malaria occurs when a patient with asexual malaria parasitemia, and no other confirmed cause of symptoms, has 1 or more designated clinical or laboratory findings. The only adjunctive measure recommended in severe malaria is exchange transfusion. Conclusions  Malaria remains a diagnostic and treatment challenge for US clinicians as increasing numbers of persons travel to and emigrate from malarious areas. A strong evidence base exists to help clinicians rapidly initiate appropriate therapy and minimize the major mortality and morbidity burdens caused by this disease.      

Propagation of alloreactive lymphocytes from histologically negative endomyocardial biopsies from heart transplant patients. Association with subsequent histological evidence of allograft rejection

Endomyocardial biopsies from heart transplant patients were cultured in vitro in the presence of Interleukin-2 and irradiated feeder cells to propagate graft-infiltrating lymphocytes. A correlation was seen between the frequency of lymphocyte growth and the degree of cellular infiltration of the biopsies. In this study, 43 of 113 (38%) histologically negative biopsies obtained from 55 patients during the first month post-transplant yielded lymphocyte cultures. The cumulative incidence of subsequent histological rejection was considerably higher in patients with such "grower" biopsies than in patients with "nongrower" biopsies. In the grower group, we were able to obtain data on alloreactivity of 32 lymphocyte cultures assayed by primed lymphocyte testing (PLT). The presence of donor-specific PLT reactivity in the cultured lymphocytes was associated with an additional risk for subsequent histological rejection. These findings suggest that the in vitro culturing of histologically negative endomyocardial biopsies will identify patients at increased risk for developing heart transplant rejection.     

Human vascular endothelial cells with extended life spans: in vitro cell response,protein expression,and angiogenesis

An in vitro angiogenesis system was designed for screening angiogenic agonists and antagonists. In order to obtain large quantities of cells and reproducibility, human endothelial cells with extended life spans were developed by retroviral transfection. The resulting cells grown in a serum-free medium containing endothelial cell growth supplement (ECGS) have a telomerase activity, extended life spans of at least 21 passages, and an endothelial cell phenotype (diI-acetylated-LDL upake, factor VIII-related antigen, VEGFR-1 and R-2, and tissue-type plasminogen activator (tPA)) that resembled that of unaltered primary endothelial cells. Exceptions were (i) a higher expression of tPA, and (ii) a non-significant growth response to FGF-2 or VEGF stimulation. Within three-dimensional fibrin gels, specific cell clones rapidly formed tubular structures in a more reproducible manner than those observed with low-passage primary cells. Tube formation by primary endothelial cells and those with extended life spans was dependent upon FGF-2 and ECGS, respectively. Both cell types produced FGF-2 and VEGF cytokines. Increasing doses of suramin significantly decreased the size of microvessels formed by both cell lines. These functional results indicate that a vascular matrix system containing human cells with extended life spans can be successfully utilized as an in vitro assay for antiangiogenic compounds.     

Spontaneous pneumothorax: an unusual presentation of rheumatoid arthritis

SIR, We read with interest the article by Gotsman et al. [1]describing a case of spontaneous pneumothorax in a rheumatoidarthritis (RA) patient treated with methotrexate. Spontaneouspneumothorax secondary to pulmonary rheumatoid nodules is anuncommon complication of RA. Cases described so far have beenmale patients with longstanding RA [2]. We describe a femalepatient     

Use of the automatic implantable cardioverter-defibrillator in the treatment of malignant ventricular tachyarrhythmias

Since February, 1980 nearly 200 automatic cardioverter - defibrillators have been implanted in patients with malignant ventricular arrhythmias. The currently-employed device weighs 298 grams and occupies a volume of 162 cm3. There are two defibrillation electrodes which also serve as sensors: one, an intravascular catheter placed in the superior vena cava at the level of the right atrium; the other, a flexible rectangular patch placed extrapericardially over the apex of the heart. Additionally, there is a bipolar right ventricular electrode for rate counting and R-wave synchronization which will eventually be used for pacing as well. The unit is powered by lithium batteries with a projected monitoring life of three years, or the capability of discharging approximately 100 times. The arrhythmia detector activates the cardioverter -defibrillator about 15 to 20 seconds after diagnosing a "treatable" arrhythmia, identified on the basis of a striking absence of isoelectric potential segments characteristic of ventricular fibrillation and many ventricular tachycardias. The diagnosis also requires fulfillment of individually-programmed heart rate criteria. If the initial discharge of 25 joules is ineffective, the device will recycle as many as three times with a final pulse of up to 42 joules. Of the twelve nonsurvivors among the initial 52 implantees who underwent implantation through September, 1982, only four deaths were unwitnessed and considered to be sudden and arrhythmic; the other eight deaths were due to heart failure or unrelated causes. Thus, from a predicted mortality of 48% in the same group of patients if the automatic defibrillator had not been implanted, the "sudden death" mortality was reduced to 8.5%.