CLINICO-EPIDEMIOLOGICAL ALGORITHM FOR PREDICTING SYSTEMIC ARTERIAL HYPERTENSION AT HIGH ALTITUDE THROUGH MATHEMATICAL MODELLING

A population based hybrid design combining element of cohort and cross-sectional approach was used to develop a simple clinical algorithm to predict individual probability of developing hypertension (systolic BP > 140 mm Hg and/or diastolic BP > 90 mmHg). 3615 soldiers initially normotensive at the time of induction into high altitude, were studied by systematic random sampling. Multiple logistic regression analysis showed a high significant association between hypertension and age, body mass index (BMI), tobacco smoking and alcohol consumption. Using the constant/coefficient values obtained from the logistic model and the receiver operating characteristics (ROC) curve analysis, the following predictive rule was developed – To the age in years, add (BMIx 3.86); also add 5.53 if he is a smoker; and add 19.81 if he consumes alcohol. If the total exceeds 142, the individual is at high risk of developing hypertension. This algorithm carries a sensitivity of 68.2% and specificity of 78.5%.KEY WORDS: Hypertension, High altitude     

Effect of trapidil in ischemia/reperfusion injury of peripheral nerves

OBJECTIVE: Ischemia plays an important role in the development of pathological changes in nerve tissue, and restoration of blood flow results in injury (ischemia/reperfusion [I/R] injury) mediated by toxic oxygen free radicals. Trapidil is currently used as a coronary artery vasodilating agent and is also used for the prevention of ischemic symptoms of cerebral vasospasm. The purpose of this study was to determine the effects of trapidil on I/R injury and the ischemic tolerance of rat peripheral nerves. METHODS: Preischemia or prereperfusion administration of trapidil (8 mg/kg) was evaluated in the rat sciatic nerve I/R injury model. Nerve tissue samples from the I/R injury site were assayed for malondialdehyde (MDA), nitrites, and nitrates, as markers of I/R injury, and pathological changes were evaluated by electron microscopy. RESULTS: I/R resulted in an increase in MDA levels, which remained elevated for 2 weeks in control nerves. Rats that received trapidil before ischemia exhibited decreased MDA levels, and rats that received trapidil after the standard 3 hours of ischemia demonstrated increased tolerance to reperfusion, as reflected in significantly decreased MDA levels. Nitrite and nitrate levels in trapidil-treated rats were significantly higher than those in control animals. Histological evaluations of the sciatic nerve segments demonstrated that preischemia and postischemia trapidil treatments had a sparing effect against the myelin damage and axonal edema that are consistently noted in untreated ischemic reperfused nerves. CONCLUSION: The results confirm that pretreatment with trapidil before the ischemic insult or before reperfusion provides marked protection against I/R injury in peripheral nerves.     

Autologous bone marrow transplantation for acute myeloid leukemia using busulfan plus etoposide as a preparative regimen

We have studied the use of a new preparative regimen for the treatment of patients in remission of acute myeloid leukemia (AML) with autologous bone marrow transplantation. Chemotherapy consisted of busulfan 1 mg/kg every 6 hours for 4 days (total dose, 16 mg/kg) on days -7 through -4 followed by an intravenous infusion over 6 to 10 hours of etoposide 60 mg/kg on day -3. Autologous bone marrow, treated in vitro with 100 micrograms/mL of 4-hydroperoxycyclophosphamide, was infused on day 0. We have treated 58 patients up to the age of 60 years, 32 in first remission, 21 in second or third remission, and 5 with primary refractory AML unresponsive to high-dose Ara-C, but achieving remission with aggressive salvage regimens. Of the first remission patients, there has been 1 treatment related death and 5 relapses. With median follow-up of 22 months, the actuarial relapse rate is 22% +/- 9% and disease-free survival is 76% +/- 9% at 3 years. Patients with favorable French-American-British (FAB) subtypes (M3 or M4 EO) did especially well, with no relapses seen in 15 patients observed for a median of 30 months. Actuarial relapse rate at 3 years was 48% for first remission patients with less favorable FAB subtypes. Of patients in second or third remission, there were 5 treatment related deaths and 4 relapses. With median follow-up of 22 months, the actuarial relapse rate is 25% +/- 11% and disease-free survival is 56% +/- 11% at 3 years. Four of five primary refractory patients died during treatment and 1 remains in remission with short follow-up. These preliminary data are very encouraging and, if confirmed, support the use of autologous purged bone marrow transplantation using aggressive preparative regimens as one approach to improve the outcome of adults with AML.