The role of the coagulation cascade in brain edema formation after intracerebral hemorrhage

Summary The coagulation cascade has a potential role in brain edema formation due to intracerebral hemorrhage. In this study blood and other solutions were injected stereotactically into the right basal ganglia in rats. Twenty-four hours following injection, brain water and ion contents were measured to determine the amount of brain edema. Intracerebral blood resulted in an increase in brain water content. The amount of brain edema surrounding the intracerebral hematoma was reduced by a thrombin inhibitor Na-(2-Naphthalenesulfonylglycyl)-4-amidino-DL-phenylalaninepiperidide, (-NAPAP) infused into the hematoma after the clot had been allowed to solidify. The inhibitor did not alter the actual size of the clot mass. An artificial clot composed of fibrinogen, thrombin, and styrene microspheres also produced brain edema. A fibrin clot led to edema formation even in the absence of mass effect provided by the microspheres. The single component responsible for production of brain edema in all these models was thrombin. The edema was formed in response to a fibrinogen-independent pathway. These results indicate that the coagulation cascade is involved in brain edema that develops adjacent to an intracerebral hematoma.     

Impact of minimal injuries on a level I trauma center.

Overtriage (i.e.; transport of patients with minimal injuries to a trauma center) has been accepted as necessary to avoid missing clinically significant injuries. We reviewed our experience with 344 patients (ISS less than or equal to 4) who were admitted to a level I trauma center during a 2-year period. The trauma team was activated for 209 patients (TA), and emergency department referrals accounted for 135 (ED). One hundred seventy-three patients (TA = 64%, ED = 36%) met American College of Surgeons' Committee on Trauma (ACSCOT) field triage criteria (FTC). Mechanism of injury, especially ejection from a motor vehicle, was the most frequently utilized FTC indicator. We found no differences between the TA and ED groups relative to Trauma Score, Glasgow Coma Scale score, Injury Severity Score, length of stay, or ICU days. Mean total costs were higher for the TA group than for the ED group. The TA group had a higher nursing acuity level than the ED group. Compliance with FTC yields an inherent overtriage of minimally injured patients; however, noncompliance with FTC compounds the overtriage rate. Failure to comply with FTC is costly, labor intensive, and may represent misuse of the trauma system. We propose continual re-education of prehospital personnel, increased responsibility of all hospitals in the trauma center catchment area, and protocols for "downstaging" trauma resuscitation in minimally injured patients.     

Combination chemotherapy with cisplatin, bleomycin, and methotrexate in patients with advanced head and neck cancer

Twenty-six patients with advanced head and neck cancer, 22 of whom had failed prior surgery and/or radiotherapy, were treated with a combination regimen of cis-diamminedichloroplatinum II, bleomycin, and methotrexate. There were no complete responses. Nine patients achieved a partial response (35%). Three of the four (75%) patients without prior therapy achieved a partial response while only 6 of the 22 patients (27%) with prior surgery and/or radiation therapy obtained a partial response. The median response duration was 3 months. Patients with a partial response did not live significantly longer than those who did not live significantly longer than those who did not respond. Toxic reactions were frequent: there were three episodes of sepsis secondary to leukopenia and two cases of bleomycin pulmonary toxicity. Mucositis was noted in 40% and nausea and vomiting in 60% of patients. We conclude that this triple-drug regimen has little value in the treatment of patients with advanced squamous cell carcinoma of the head and neck who have failed prior surgery and radiotherapy.     

The "D circle": closed-circuit operation of the Bain circuit.

A method of converting a Mapleson D (Bain) circuit to closed-circuit operation is presented, utilizing a laboratory air pump and a Waters carbon dioxide absorber canister to recirculate exhaled gas. The elimination of carbon dioxide from the circuit was studied and found to be adequate. The circuit would allow the use of low fresh gas flows for the maintenance of anaesthesia without the danger of carbon dioxide rebreathing. We suggest that such a circuit could provide appropriate conditions of gas humidity and temperature for endotracheal anaesthesia, while realizing the advantage of a circulator in mask anaesthesia is possible. Further design considerations for a "D circle" breathing system for clinical use are discussed.     

Determination of stone composition by noncontrast spiral computed tomography in the clinical setting

OBJECTIVES: Several investigators have evaluated noncontrast computed tomography (NCCT) in predicting stone composition in vitro. We assessed NCCT in predicting stone composition in patients presenting to our emergency room with flank pain and stone disease. METHODS: One hundred twenty-nine patients presenting to our university hospital with flank pain underwent renal colic protocol NCCT scans at the request of the emergency room physicians. A General Electric, high-speed advantage CT scanner was used at 120 kV, 200 mA, and 1.4:1 pitch, with collimation varying between 3 and 5 mm. Ninety-nine patients with predominantly (greater than 50%) calcium oxalate or uric acid composition after either stone passage or stone removal were identified. Each scan was analyzed by one of two radiologists, who determined the predominant attenuation for each stone. Stones once passed or retrieved were analyzed by Urocor Laboratories. The attenuation and attenuation/size ratio (peak attenuation/size in millimeters) were compared with the results of the stone analysis. RESULTS: Eighty-two calculi predominantly composed of calcium oxalate and 17 calculi predominantly composed of uric acid were identified in 99 patients. The calculi ranged in size from 1 to 28 mm. A significant difference (P = 0.017, unpaired t test) was found between the Hounsfield measurement of uric acid calculi (mean 344 +/- 152 HU) and the Hounsfield measurement of calcium oxalate calculi (mean 652 +/- 490 HU). If only the Hounsfield units from stones 4 mm or larger were compared, the data were even more compelling (P = 0.002). However, using an attenuation/size ratio cutoff of greater than 80, the negative predictive value was 99% that a stone would be predominantly calcium oxalate. CONCLUSIONS: Using peak attenuation measurements and the attenuation/size ratio of urinary calculi from NCCT, we were able to differentiate between uric acid and calcium oxalate stones.     

Ischemia-reperfusion injury in renal transplantation is independent of the immunologic background

BACKGROUND: Adhesion molecule expression is important to early transplant failure. However, whether or not adhesion molecule-facilitated inflammation is antigen-dependent is unknown. We tested this hypothesis. METHODS: Rat renal grafts were four-hours cold-preserved in University of Wisconsin (UW) solution, transplanted to syngeneic or allogeneic recipients, and harvested after 2, 6, 12, 24, and 48 hours and after 1 week. The first allogeneic group receive no immunosuppression; two additional groups received either low (1.5 mg/kg) or standard (5 mg/kg) cyclosporine A (CsA). Renal function and morphology were determined; frozen sections were immunostained for P-selectin, L-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1), leukocyte function associated molecule-1 (LFA-1), very late antigen-4 (VLA-4), as well as for neutrophils and monocytes. RESULTS: Selectins increased rapidly at 2 hours and quickly decreased by 12 hours. While P-selectin was expressed on vasculature, L-selectin was found on inflammatory cells. Neutrophil influx and that of LFA-1-positive cells occurred early, peaked between 12 and 24 hours, and paralleled the maximal impairment in renal function. ICAM-1 and PECAM-1 showed similar kinetics and a diffuse distribution. VCAM-1 increased more slowly after 12 hours, peaked at 24 hours, and was localized predominantly on the endothelium of elastic vessels. Between 24 hours and 1 week, all grafts progressively developed dense VLA-4-positive monocytic infiltrates adjacent to vessels expressing VCAM-1. Functional, morphological, and immunohistochemical parameters did not differ between isografts and allografts at one week. However, by day 10, allografts showed severe vascular and cellular rejection, while injury in isografts resolved. Immunosuppression with CsA did not reverse the inflammation induced by ischemia-reperfusion injury. CONCLUSIONS: The early inflammation after ischemia-reperfusion injury is largely independent of the immunologic background. We suggest that initial injury prevention should receive the highest priority.     

Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice

Kevin M. De Cock, MD; Mary Glenn Fowler, MD, MPH; Eric Mercier, MD, MPH; Isabelle de Vincenzi, MD, PhD; Joseph Saba, MD; Elizabeth Hoff, MSc; David J. Alnwick, MSc; Martha Rogers, MD; Nathan Shaffer, MD

JAMA. 2000;283:1175-1182.

Each year, an estimated 590,000 infants acquire human immunodeficiency virus type 1 (HIV) infection from their mothers, mostly in developing countries that are unable to implement interventions now standard in the industrialized world. In resource-poor settings, the HIV pandemic has eroded hard-won gains in infant and child survival. Recent clinical trial results from international settings suggest that short-course antiretroviral regimens could significantly reduce perinatal HIV transmission worldwide if research findings could be translated into practice. This article reviews current knowledge of mother-to-child HIV transmission in developing countries, summarizes key findings from the trials, outlines future research requirements, and describes public health challenges of implementing perinatal HIV prevention interventions in resource-poor settings. Public health efforts must also emphasize primary prevention strategies to reduce incident HIV infections among adolescents and women of childbearing age. Successful implementation of available perinatal HIV interventions could substantially improve global child survival.

     

Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.