In-utero intravascular transfusion of the fetus for the management of severe Rhesus isoimmunization—a reappraisal

Summary. Ten fetuses, severely affected by Rhesus (D) haemolytic disease, received one to three intravascular blood transfusions at between 18 and 30 weeks gestation, with the use of fetoscopically guided needles into one of the umbilical cord vessels. Although the technique was successfully accomplished in all cases, the fetal response to the procedure was varied. Only two fetuses survived beyond the neonatal period, and one child subsequently died principally because of the problems resulting from premature delivery. The reason for the low rate of survival has been explored and the continued use of the method described is now questioned.     

The Usefulness of Head-Up Tilt Testing and Hemodynamic Investigations in the Workup of Syncope of Unknown Origin

To enhance the clinical evaluation of patients suffering from recurrent syncope of unknown origin, the integrity of mechanisms controlling blood pressure was examined in 151 patients utilizing a screening tilt test. Ninety-eight patients had an abnormal blood pressure and/or heart rate response to tilt testing, including provoked syncopal attacks in 63 patients. Whenever indicated, the screening tilt test was followed by blood volume and hemodynamic determinations, as well as autonomic nervous system testing to identify contributing pathophysiological abnormalities (hypovolemia, venous pooling, autonomic dysfunction). Detailed analysis of this battery of tests allowed us to conclude that: (1) The tilt test is commonly a provocative tool in the workup of patients with recurrent syncope due to vasovagal - vasodepressor reactions and other abnormalities of blood pressure regulation; (2) Its usefulness is augmented by associated hemodynamic and blood volume evaluations; (3) The identification of contributory pathophysiological mechanisms of blood pressure control facilitates specific therapeutic interventions.     

Clinical Performance of the Implantable Cardioverter Defibrillator: Electrocardiographic Documentation of 101 Spontaneous Discharges

Records of 105 patients, who received an automatic implantable Cardioverter defibrillator (AICD), were studied to investigate the causes of spontaneous AJCD discharges and to correlate the symptoms with the arrhythmias triggering AJCD discharges. During a follow-up period of 13 ± 8 months, 46/105 (44%) patients had 566 spontaneous AICD discharges. A total of 101 discharges were documented with Holter monitoring in 23 patients. In this study group, there were 8 (8%) AICD discharges for 5 episodes of ventricular fibrillation, and 68 (67%) discharges for 63 episodes of sustained ventricular tachycardia. Patients lost consciousness in all episodes of ventricular fibrillation, but were symptomatic prior to only 36 (53%) discharges in ventricular tachycardia. Non-sustained ventricular tachycardia persisting for a period of 7,5 ± 2 seconds resulted in 20 AICD discharges; patients were symptomatic prior to 13 (65%) discharges. Supraventricular tachycardias triggered three discharges. One patient had two spurious discharges during sinus rhythm. In conclusion, most of the spontaneous AICD discharges were appropriate for the detected rhythms, but only clinically appropriate for the management of arrhythmias in 75% of the cases. A significant portion of the patients with sustained or nonsustained ventricular tachycardias triggering AICD discharges were asymptomatic prior to discharge, which requires further assessment of the physiology of the arrhythmia as a component of the detection algorithm.     

Long-Term Performance of Endocardial Pacing Leads

To assess the performance of endocardial pacemaker leads and to identify factors associated with structural lead failure, medical records of 2,611 endocardial pacing leads (in 1, 5W patients) implanted between 1980 and 1991, having at least 1 month of follow-up, were reviewed. Leads without structural failure had normal function at the last follow-up date, or were discontinued for reasons other than structural failure (patient death, infection, dislodgment, lead-pacemaker incompatibility, operative complication, or abandonment by telemetry not related to failure). Leads with suspected structural failures were invasively or noninvasively disconnected because of clinical malfunction (loss of capture or sensing, oversensing, elevated thresholds, or skeletal muscular stimulation). Leads with verified structural failures met the criteria for suspected lead failure and also had a visible defect seen in the operating room or on chest roentgenograms, a change in the impedance interpreted by the physician as lead disruption, or a manufacturer's return product report that confirmed structural failure. Variables analyzed included patients’ age and gender, paced chamber, venous access, insulation materials, fixation mechanism, coaxial design, polarity, and different lead models. The cumulative lead survival at 5 and 10 years were 97.4% and 92.9%, respectively, for suspected failures; and 98.7% and 97.3%, respectively, for verified failures. Leads in older patients (≥ 65 years old), and leads in atrial position had fewer verified failures (P = 0.014 and P = 0.007, respectively). Unipolar leads also tended to perform better according to the verified definition (P = 0.07). The lead Medtronic 4012 had more suspected (P < 0.05) and more verified failures (P < 0.01), the lead CPI 4010 had more verified failures (P < 0.05) than the entire group of ventricular leads. Conclusions: Endocardial pacing leads implanted in atrial position, and implanted in older patients (> 65 years old) seems to have better long-term survival. Some lead models (Medtronic 4012 and CPI 4010) had poor survival rates, that could not be explained by the analyzed variables. The expected performance of endocardial pacing leads varies according to how failure is defined.     

DDIR Versus VVIR Pacing in Patients with Paroxysmal Atrial Tachyarrhythmias

Patients with sinus node dysfunction (SND) in particular those with tachycardia-bradycardia syndrome and patients undergoing atrioventricular nodal ablation procedures for refractory paroxysmal atrial tachyarrhythmias (PAT), are candidates for single chamber (VVIR mode) or dual chamber rate responsive (DDIR mode) systems. To evaluate the benefits and disadvantages of each pacing mode we retrospectively analyzed 33 patients with a history of frequent PAT who received a VVIR (22 patients); or a DDDR pacemaker (11 patients) programmed to the DDIR mode. The mean follow-up time was 25 and 18 months, respectively. Preimplant left atrial diameter was significantly smaller in the DDIR group. Chronic atrial fibrillation developed in 54% of the VVIR patients and 27% of the DDIR group, but this difference was not significant. Complications of patients with VVIR pacemakers included new mitral and tricuspid insufficiency, stroke, pacemaker inlolerance and aggravated congestive heart failure. Patients with DDIR pacemakers had a lower incidence of symptoms and complications. However, this group received more antiarrhythmic medication, required a closer follow-up, and their pacemakers needed frequent reprogramming. Our findings suggest that VVIR is a poor choice for patients with SND, congestive heart failure, and PAT, and that DDIR may be an acceptable alternative.     

Structure and other chemical characterizations of gila toxin,a lethal toxin from lizard venom

The complete primary structure of a lethal toxin, horridum toxin, from the venom of the lizard, Heloderma horridum horridum, was determined by Edman degradation. The amino acid sequence was deduced by overlapping peptide fragments generated by chemical and enzymatic digestions. Horridum toxin causes hemorrhage in internal organs and particularly in the eye, leading to exophthalmia, an effect that has not been observed for other toxins. It is a glycoprotein with a total of 210 residues. Examination of the primary sequence revealed that horridum toxin has considerable homology to tissue-type kallikrein and trypsin. Furthermore, synthetic substrates for trypsin, such as tosyl-l -arginine methyl ester, benzoyl-l -arginine ethyl ester and other p-nitroanilide substrates, were hydrolyzed. The toxin released bradykinin upon hydrolysis of kininogen. This enzymatic behavior is similar to that of plasma kallikrein; however, the presence of a characteristic “kallikrein-like” loop at 91-100 (GTIYNCNYVN) in the primary structure and other features similar to tissue kallikrein suggest that horridum toxin is more like tissue kallikrein. This toxin degraded all three chains of fibrinogen but did not form a clot, which suggests that it is different from thrombin. Moreover, it differs from another lethal factor from H. horridum horridum, gila toxin, which has 245 amino acid residues and does not cause exophthalmia.     

Species Differnces in the Hydrolysis of Meperdine and its Inhibition by Organophosphate Compounds

Species Differences in the Hydrolysis of Meperidine and ItsInhibition by Organophosphate Compounds. Luttrell, W. E., andCastle, M. C. (1988). Fundam. Appl. Toxicol. 11, 323–332.The hydrolysis of meperidine was assayed in washed, unfortifiedliver microsomal fractions of guinea pig, rat, mouse, dog, andhuman, by following substrate disappearance as quantitated byhigh-performance liquid chromatography. Using the method ofLineweaver-Burk plots, the velocity of the meperidine hydrolysisreaction was not detectable in guinea pig, very low in human,and extremely high in dog. Hydrolysis of p-nitrophenyl acetatewas also monitored in liver microsomal preparations from thesame animal species, with guinea pig showing greatest hydrolyticactivity and rat showing least hydrolytic activity for thissubstrate. The data in the above two assays suggested that meperidinehydrolysis is mediated by a unique esterase not present in guineapig and very low in human, but present with high activity indog liver micro-somes. From these comparative studies we concludedthat liver microsomes from different species may contain differentcarboxylesterases having different affinities for meperidine.To further characterize meperidine carboxylesterase of dog andrat liver microsomes, inhibitory studies in vitro with two organophosphatecompounds—paraoxon (diethyl-p-nitrophenyl phosphate) andsoman (pinacolyl methylphosphonofluoridate)—indicateda varied pattern of enzyme inhibition. These results suggestedthat liver microsomal carboxylesterases are involved in themetabolism of meperidine and that interference with these enzymesby organophosphate compounds may alter pharmacologic and toxicologiceffects of meperidine.