A Comparison of the Physicochemical and Biological Properties of Mirtazapine and Mianserin

Although the chemical structures of the antidepressants mirtazapine and mianserin are closely related there are considerable differences in their biological properties. To find an explanation of this, various physicochemical properties of mirtazapine and mianserin were measured or calculated. Isosteric replacement of CH in mianserin by N in mirtazapine has profound effects on physicochemical properties. The charge distributions as indicated by NMR and calculated by semi-empirical quantum mechanics differ, not only for the changed aromatic A-ring (as expected), but also in other regions of the molecule. The N5 atom in particular, which is conjugated to the changed aromatic ring, is less negatively charged in mirtazapine than in mianserin. Consequently the oxidation potential of mirtazapine is significantly higher than that of mianserin. Another result of this difference in charge distribution is that the (calculated) dipole-moment vectors of the compounds are oriented roughly perpendicular to each other. The dipole moment of mirtazapine is, moreover, three times larger than that of mianserin; mirtazapine is, therefore, more polar than mianserin and this is reflected in a lower retention index. Finally, the basicity of mirtazapine, expressed as the pK_a value, is slightly but significantly lower than that of mianserin. The observed differences between the physicochemical properties of mirtazapine and mianserin result in different interactions of these two antidepressants with macromolecules, such as receptors, transporters and metabolizing enzymes; this might explain the differences observed in pharmacological activity and metabolic and kinetic behaviour, that is, the reduced affinity for the α₁-adrenoceptor and negligible noradrenaline reuptake of mirtazapine compared with mianserin.     

Effects of Stimulation Site on Diastolic Function in Cardiac Resynchronization Therapy

Background : Cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function and clinical status, and prolongs survival of patients suffering from heart failure. An optimal LV site selection is key with respect to improvements in systolic function, though whether a site-specific effect on diastolic function exists is unclear. This study compared the effects of CRT on changes in systolic and diastolic function from 2 LV stimulation sites.
Methods : We studied 21 patients in New York Heart Association functional classes ≥III, and a LV ejection fraction <0.30 and QRS duration > 130 ms. CRT leads were placed in the right ventricle, right atrium, and coronary sinus tributaries. LV stimulation was applied from the postero-lateral and antero-lateral wall. A LV conductance catheter was used to measure LV systolic and diastolic function. Systolic responders had >10% changes in dP/dt_max, and diastolic responders <10% changes in τ during CRT versus baseline. Response was highly dependent on LV lead position for both diastolic and systolic function. Diastolic responders decreased from 29% to 10% of patients, and systolic responders from 76% to 48%, in the best versus the worst lead position, respectively. Improvements in diastolic function were less pronounced than in systolic function (relative change −14% vs +28%, P < 0.05). Overall, 45% were both systolic and diastolic responders, 17% were both systolic and diastolic nonresponders, and 38% had opposite responses .
Conclusions : Changes in systolic and diastolic function were both highly dependent on the LV stimulation site. Diastolic function was less influenced by CRT and a high proportion of patients had discordant results.     

Efficacy and Safety of Rate Responsive Pacing in Patients with Coronary Artery Disease and Angina Pectoris

The present study included 17 patients with angina pectoris and coronary artery disease in whom a rate responsive ventricular pacemaker (Medtronic Activitrax) had been implanted. All patients had an exclusively paced rhythm. Single blinded, random, cross-over treadmill tests in the rate responsive pacing mode (VVIR) and in the fixed-rate demand mode (VVI) were performed, with an interval of 4-6 weeks. Mean exercise duration increased by 25% during VVIR pacing. Maximal heart rate increased significantly during VVIR compared to VVI pacing (VVI = 74 +/- 2 bpm, VVIR = 116 +/- 8 bpm, P less than 0.001) as did the rate-pressure product (VVI = 10.850 +/- 1,124, VVIR = 16.628 +/- 2,110, P less than 0.001). Despite improved performance, the number of anginal attacks per week and the nitroglycerin consumption did not show a significant difference between the two pacing modes. It is concluded that rate responsive pacing is beneficial and safe in patients with angina pectoris and coronary artery disease.     

Diagnosing the ''strange'' child

The diagnosis of children with a spectrum of autistic features, who do not qualify for the diagnosis of classical autism, has increased during the past decade. A case is reported of an 8-year-old child originally diagnosed as learning disabled with attention disorders and hyperactivity, who was later diagnosed as having an autistic spectrum disorder when abnormalities of social interaction and play activity became more obvious. The frequency of learning and attention problems in school-age children may obscure more significant psychiatric pathologies, such as autistic disorders. Improved awareness of disorders of social functioning and play activity in the school-age child and use of screening tools may lead to earlier detection, definitive diagnosis and treatment for these children. In addition, assessments from multiple sources, i.e. the school, the home and the clinic, are needed in the diagnostic process. Periodic re-evaluations of the school-age child with problem behaviour are necessary to insure that more significant pathologies, which were not clear on initial evaluation, are diagnosed at the earliest opportunity.     

TINEA CAPITIS IN NORTHWESTERN EUROPE 1963–1993: ETIOLOGIC AGENTS AND THEIR CHANGING PREVALENCE

Background. Although tinea capitis is endemic in many countries, its prevalence in Northwestern Europe (Belgium and the Netherlands) has not been established. Materials and Methods. Scales, pus, and hair were examined from 435 cases of tinea capitis for etiologic agents and their relative percentages calculated for 5-year periods between 1963 and 1992. Results. There was a change in organisms associated with tinea capitis in the Netherlands from Trichophyton schoenleinii to Trichophyton violaceum. Increased immigration from the Mediterranean is held partly responsible for the increased prevalence of T. violaceum infections. Infection with zoophilic dermatophytes, such as T. canis, has also become more frequent in the Netherlands. Conclusions. The zoophilic dermatophytes have supplanted the anthropophilic dermatophytes as the cause of tinea capitis in the Netherlands.     

Unusual Approach of a Pacemaker Electrode in a Patient with a Silent Superior Vena Cava Syndrome

A man with a history of bilateral pectoral pocket infection and subsequent pacemaker implantation with a screw-in epicardial lead was referred because of increasing lead impedance. Venography revealed bilateral total occlusion of the subclavian and innominate veins with extensive collateral formation in this asymptomatic patient. Both internal jugular veins were also totally occluded. Because repeated pacemaker implantation using epicardial leads resulted in increasing lead impedance of the ventricular lead within 1 year after implant, an alternative approach was found using the superior caval vein with minimal invasive thoracotomy for single lead VDD pacing.     

Usefulness of Echocardiography to Predict Inappropriate Atrial Sensing in Single-Lead VDD Pacing

Reliable atrial sensing is the prerequisite for restoration of atrioventricular synchrony in patients with single-lead VDD pacing systems. To determine echocardiographic variables associated with inappropriate atrial sensing, 21 consecutive patients with symptomatic second- or third-degree AV block and normal sinus node function were studied. Prior to implantation echocardiographic measurements of end-systolic and end-diastolic dimensions and volumes of the right atrium and right ventricle were performed. All patients underwent implantation of a Medtronic Thera VDD(d) pacemaker with a bipolar Medtronic Capsure electrode. A minimal amplitude of the unfiltered atrial electrocardiogram of > or =0.5 mV was required for permanent lead position and the atrial sensitivity was programmed below the lowest recorded value. Appropriate atrial sensing (atrial triggered ventricular paced complexes/total number of ventricular paced complexes) was assessed during 24-hour Holter monitoring and treadmill exercise testing 3 to 6 weeks after implantation. Inappropriate atrial sensing (<95% correct atrial synchronization during Holter registration and/or <97.5% during exercise testing) was present in nine patients. Right atrial volumes and the right ventricular end-diastolic volume was significantly higher, as compared to patients without inappropriate sensing (12 patients). The right atrial and diastolic volumes had the highest correlation with correct atrial sensing r = 0.83, P<0.0001). Using a postdefined cut-off value of > or =80 mL for the end-diastolic right atrial volume, sensitivity and specificity for inappropriate sensing was 100% and 92%, respectively. These findings show that preimplant echocardiography can identify patients with inappropriate sensing during VDD pacing, in whom DDD pacing should be considered.     

The Effect of Rate Responsive Pacing in Patients with Angina Pectoris on the Extent of Ischemia on 201-Thallium Exercise Scintigraphy

VAN CAMPEN, L.C.M.C., et al. : The Effect of Rate Responsive Pacing in Patients with Angina Pectoris on the Extent of Ischemia on 201-Thallium Exercise Scintigraphy. In patients with coronary artery disease (CAD), rate responsive pacing is considered to be contraindicated because an increase in heart rate may increase oxygen demand. Although previous studies have shown no subjective increase in ischemia during rate responsive pacing, data from objective assessment have not been documented. The goal of this study was to determine if there was an increase in ischemia on 201-Thallium (²⁰¹TI) exercise scintigraphy in this mode of pacing in patients with CAD and angina. Eighteen consecutive patients with chronic atrial fibrillation and symptomatic bradyarrhythmias with a pacemaker for more than 6 months participated in the study. In VVI and VVIR modes a symptom-limited exercise ²⁰¹TI scintigram was performed in a single blind randomized crossover fashion. Exercise duration, anginal attacks, use of nitroglycerine (NTG) tablets, blood pressure, and analysis of the scintigrams were assessed during each pacing mode. Fifteen men and three women were included (  age 65.9 ± 4.9 years, LVEF 0.44 ± 0.07  ). Four were in Class III angina pectoris, and 14 in class II. The mean exercise duration increased 28% in the VVIR group without an increase in anginal attacks per week or the use of NTG tablets. On scintigrams, no differences were seen between the two groups. One patient was withdrawn from the study because of an increase in angina pectoris (AP) attacks during VVIR pacing. Rate responsive pacing is safe and effective in patients with CAD without an increase in subjective and objective signs of ischemia.