Successful autografting in chronic myelogenous leukaemia using Philadelphia negative blood progenitor cells mobilized with rHuG-CSF alone in a patient responding to alpha-interferon

Several non-randomized studies suggest a possible survival advantage for chronic myelogenous leukaemia (CML) patients treated with an autologous stem-cell transplantation. Due to the possible contribution of residual leukaemic cells present in the inoculum in post-transplant relapse, several methods are being evaluated to eliminate neoplastic cells or to select 'normal' (Ph¹ negative) progenitor cells for autografting. Recently, several studies have shown that Ph¹ negative blood progenitor cells can be mobilized by rHuG-CSF alone in patients who have a cytogenetic response to alpha-interferon (IFN). We describe the first case, as far as we are aware, of a CML patient responding to IFN autografted by using blood progenitor cells collected by rHuG-CSF alone.     

Alpha1-Adrenergic Blockade and Sudden Cardiac Death

Alpha₁-Adrenergic Blockade and Sudden Cardiac Death. Introduction: The primary goal of the present study was to test whether selective pharmacologic blockade of alpha₁ receptors, and specifically of the subtype alpha_1a could prevent ventricular fibrillation (VF) during acute myocardial ischemia. Background: The development of new autonomic interventions is of clinical interest in view of the failure of traditional; antiarrhythmic drugs to prevent sudden death. Experimental evidence indicates that alpha, receptors, and in particular the subtype alpha_1a may he involved in the genesis of malignant arrhythmias during acute myocardial ischemia and reperfusion. Despite this evidence, questions have been raised about the actual antifibrillatorv efficacy of alpha-adrenergic blockade in the acutely ischemic myocardium. The effects of prazosin and of abanoquil (UK 52,046), a highly selective alpha_1a receptor blocker, were tested and compared with propranolol in a conscious animal preparation for sudden death. Methods and Results: Ten dogs with a 1-month-old anterior wall myocardial infarction were studied. These dogs had all developed, in control conditions, VF during a 2-minute occlusion of the circumflex coronary artery while exercising (n=9) or lying on the table (n=1). Afterwards, the dogs underwent additional tests with the following intravenously administered drugs: abanoquil (n=10; 1μg/kg. prazosin (n=9; 0.1 mg/kg), and propranolol (n=10; 1 mg/kg). Internal control analysis was used. All dogs tested had recurrence of VF with both alpha-adrenergic blockers. Propranolol significantly reduced heart rate during ischemia and prevented VF in 5 of 10 dogs tested (P < 0.05). When heart rate was kept constant by atrial pacing (n = 3), 2 of the 3 animals remained protected by propranolol. Just prior to onset of VF, heart rate was not significantly different in the control and in the abanoquil tests (237 ± 45 and 253 ± 34 beats/min, respectively), whereas it was higher (P < 0.05) with prazosin (288 ± 40 beats/min). Conclusions: Alpha, and alpha_1a receptor blockers do not prevent VF secondary to acute myocardial ischemia in the presence of elevated sympathetic activity and heart rate. In the same setting, beta-adrenergic blockade prevents the reflex heart rate increase due to ischemia and provides a significant protection.     

The Andalusian trial on heroin‐assisted treatment: A 2 year follow‐up

Introduction and Aims. In 2003, a randomised controlled trial comparing injected diacetylmorphine and oral methadone was carried out in Andalusia, Spain. The subsequent follow‐up study evaluated the health and drug use status of participants, 2 years after the completion of the trial. Design and Methods. This follow‐up cohort study was carried out between March and August 2006. Data collected included information on socio‐demographics, drug use, health and health‐related quality of life. We compared data collected before randomisation and at 2 years for the following three groups: those currently on heroin‐assisted treatment (C‐HAT), those who have discontinued HAT (D‐HAT), and those who have never received HAT (N‐HAT). Results. From the total 62 randomised participants in 2003, 54 (87%) were interviewed for this study. Participants were distributed as follow: C‐HAT 44.4% (24), N‐HAT 22.2% (12) and D‐HAT 33.3% (18). Illicit heroin use had a statistically significant decrease in the three groups from baseline to 2 years post trial. Mean days of heroin use were 2.42 (SD = 3.02); 6.56 (SD = 9.48) and 13.92 (SD = 12.59) for the C‐HAT, D‐HAT and N‐HAT groups, respectively. Those currently on HAT were the only group that sustained at 2 years, their marked improvement in health after 9 months of treatment during the trial period. Discussion and Conclusions: Patients who received HAT showed better outcomes compared with those not on HAT. The results of this study strengthen the evidence showing that HAT can improve and stabilise the health of long‐term heroin users with severe comorbidities and high mortality.[Oviedo‐Joekes E, March JC, Romero M, Perea‐Milla E. The Andalusian trial on heroin assisted treatment: A 2 year follow‐up. Drug Alcohol Rev 2009]     

Respiratory depression following epidural morphine in an infant of three months of age

Epidural administration of combinations of opioids and a local anaesthetic provides prompt and effective analgesia and is increasingly used in paediatric anaesthesia. However, respiratory depression by rostral spread of opioid in the CSF is by far the greatest concern after epidural morphine. An infant of three months of age underwent portoenterostomy (Kasai's operation) for extrahepatic biliary duct atresia. A median approach at the L₃–L₄ epidural interspace was used and a dose of 1 ml·kg^–1 of 0.125% bupivacaine with adrenaline 1:400 000 mixed with 50 μg·kg^–1 morphine was injected using a 19 gauge Tuohy needle. Six h after epidural morphine, the infant developed respiratory depression with an increase in drowsiness, miosis and decreased respiratory rate. Low arterial saturation ( S pO₂) was detected by pulse oximetry and confirmed by blood gas analysis. An intravenous bolus of 5 μg·kg^–1 naloxone followed by a 3-h infusion of 2 μg·kg^–1·h^–1 resulted in complete reversal of signs and symptoms of respiratory depression. Epidural opioids should be limited to paediatric patients admitted to specialized recovery units for the first postoperative day.     

Hemoglobin Switching in Nonanemic Sheep. III. Evidence for Presumptive Identity between the Ararr C Factor and Erythropoietin

The degree of A C hemoglobin switching following administration of a humanurine erythropoietin preparation to anon-anemic sheep was compared, in thesame animal, with the switching obtainedwith administration of anemic sheepplasma containing known amounts oferythropoietin. A strong correlationemerges between the dosage of erythropoietin given and the degree of A Cswitching observed. This correlation between erythropoietin dose and A Cresponse is maintained despite the use ofmaterials that originated in different species (man and sheep), were assayed forerythropoietin in yet another species(mouse), and had grossly different specific activities (units/mg.) of erythropoietin, so that the specific activity of thehuman urine preparation was approximately 400 to 1600 times that of anemicsheep plasma. We believe these observations provide substantial evidence fora provisional hypothesis of identity between erythropoietin and the A Cswitching factor.

Submitted on December 22, 1969 Revised on June 15, 1970 Accepted on June 24, 1970     

Hirschsprung's Disease Complicating Pregnancy

The first case of uncorrected Hitschsprung's disease complicating pregnancy is reported. The congenital aganglionic megacolon was confirmed by tissue biopsy. Following the completion of her pregnancy, the patient had definitive surgical correction of her malady. A brief discussion of bowel obstruction in pregnancy is included.