CENTRAL CARDIOVASCULAR EFFECTS OF DIHYDROPYRIDINES IN SPONTANEOUSLY HYPERTENSIVE RATS

Summary— Intracerebroventricular (i.c.v.) injections of dihydropyridine derivatives calcium channel agonist (BAY K8644) and antagonists (nifedipine, nicardipine, PN 200–110) induced opposite long-lasting changes in blood pressure (BP) in pentobarbital anesthetized spontaneously hypertensive rats (SMR). I.c.v. nifedipine (NIF), nicardipine (NIC), and PN 200–110 decreased mean blood pressure dose-dependently and stereoselec-tively, (+) NIC and (+) PN being 8 and 3 times more potent than their (-) isomers, respectively. The decrease in BP was due to a withdrawal of the sympathetic tone, since NIF- and NIC-induced falls in BP were suppressed after either hexamethonium (HXM), 6 OHDA or bilateral adrenalectomy. I.c.v. BAY K8644 increased BP dose-dependently. The i.c.v. BAY K8644-induced hypertensive effect was inhibited: a), by NIF and (+) PN but not by (-) PN, therefore probably occurring at central DHP sites; b), by HXM and reserpine, thus probably mediated by an increase in sympathetic tone; c), by i.c.v. methylatropine (MA) while i.v. MA and i.c.v. HXM had no inhibitory effect, thus probably involving central muscarinic sites. In SHR, NIC did not after the K+-evoked ACh release but suppressed the BAY K8644-induced increase in ACh release. In anesthetized normotensive control rats (WKY), neither i.c.v. NIF, NIC or BAY K8644 changed BP, nor did the latter after ACh release. Moreover, in conscious WKY, i.c.v. nicardipine increased BP and HR while, in conscious SHR it decreased BP without any change in HR. These data suggest that central DHP sites may be involved in the cholinergic transmission and may participate in genetic hypertension via sympathetic tone.     

Dramatic improvement of severe dilated cardiomyopathy in an acromegalic patient after treatment with octreotide and trans-sphenoidal surgery

Severe congestive heart failure developed in an acromegalicpatient, and was successfully treated with octreotide followedby trans-sphenoidal surgery. Clinical, hormonal echocardiographicand haemodynamic findings as well as histological heart examinationbefore and after treatment revealed tliat over-production ofgrowth hormone may induce the myocardial cell degeneration responsiblefor mechanical heart dysfunction. In addition, this unique exampledemonstrates the reversibility of myocardial damage followingoctreotide and trans-sphenoidal surgery, leading to significantimprovement in cardiac function with minimal diastolic dysfunctionand moderate interstitial fibrosis.     

Lupus anticoagulant: a clinical and laboratory study of 100 cases

Summary The clinical and laboratory features of 100 patients with lupus anticoagulant (LA) are reviewed. Subjects were divided into three groups according to their age (1–5, 15–35, 45–89 years). Female prevalence was observed in each group and overall F/M ratio was 3/1. An underlying autoimmune disease (principally lupus erythematosus) was found in 47 cases (10% of the children, 80% of the 15–35-year-old patients and 37% of the elderly patients). Biological criteria for the LA diagnosis were prolonged activated partial thromboplastin time and diluted thromboplastin time (1.3 × control), not corrected after addition of control to patient's plasma. Thromboplastin time was normal in 77 patients. Other types of coagulation inhibitors were eliminated by specific factor assays (with a 10-fold increase of cephalin concentration when necessary). Twenty-three thrombotic episodes were observed. No significant difference was found in the incidence of thrombosis between the autoimmune and non-autoimmune disease group, but the age when first thrombosis occurred was clearly lower in the former. Fourteen obstetrical accidents were noted in eight women but 13 pregnancies terminated without accident. Four patients experienced haemorrhagic complications; they all presented with a severe thrombocytopenia associated with the LA. In our experience, LA is a frequent coagulation abnormality, associated in about half of the cases with a clearly defined autoimmune disease. Clinical presentation appears as notably different according to the patient's age; it is particularly noteworthy that in nine out of 10 children, LA disappeared spontaneously within 6 months.     

Obsessive Compulsive Disorder in a Patient with Twiddler's Syndrome

Twiddler's or twist syndrome is the twisting of pulse generators around themselves. It may result from mechanical manipulation that can induce the malfunction of the device. In this case, twiddler's syndrome resulted from compulsive checking of the device. The implantable cardioverter‐defibrillator (ICD) triggered the development of an obsessive compulsive disorder (OCD). Two invasive procedures were required to replace the ICD. Psychiatric intervention prevented the recurrence of twiddler's syndrome in this patient for more than 2 years. We believe that preimplant psychiatric assessment should be the rule.     

Determination of the ratios of the aromatic amino acid residues by first- or second-derivative UV spectrometry for a simple characterization of peptides

A method for the simultaneous determination of the ratios of the three aromatic amino-acid residues in peptides was set up in acidic conditions. Binary and ternary mixtures of these amino acids were prepared, and first- and second-derivative spectra then calculated from their 0.1 nm resolution spectra between 240 and 320 nm. Certain spectral bands were chosen to differentiate tyrosine from tryptophan on the first-derivative spectra, and phenylalanine from tyrosine and tryptophan on the second-derivative spectra. Variation of the amplitude of the chosen bands was shown to be a linear function of the ratio of the aromatic amino acids in the mixture. This technique was validated with peptides whose sequence was known. The difference between theoretical and experimentally determined ratios was lower than 10%. Since the results are obtained as ratios, neither the concentration nor the nature of the peptide has to be known. The feasibility of application using a photodiode array detector with high resolution in reversed-phase high-performance liquid chromatography is discussed. © Munksgaard 1995.     

Sudden Cardiac Arrest: ECG Repolarization After Resuscitation

Sudden Cardiac Arrest and ECG Repolarization. Introduction: Early repolarization (ERep) abnormalities on electrocardiogram (ECG) are common immediately following cardiac arrest. We characterized and correlated electrocardiographic repolarization abnormalities immediately after cardiac arrest with acute coronary angiography. Methods and Results: We studied 225 consecutive patients presenting with out‐of‐hospital cardiac arrest. All these patients had successful cardiopulmonary resuscitation and acute coronary angiography. The first ECG recorded after successful resuscitation was analyzed by two independent cardiologists. Patients were categorized according to their repolarization pattern.

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CHARACTERIZATION OF β-ADRENOCEPTORS IN MYOMETRIUM OF PREPARTURIENT RATS

The purpose of this study was to characterize the beta-adrenoceptor subtypes in pregnant rat myometrial membrane fractions and to determine the concentration of beta 2-adrenoceptors in uterus during late pregnancy. Two methods are compared. A non-subtype-selective antagonist radioligand [3H]dihydroalprenolol ([3H]DHA) was used to label all of the beta-adrenoceptors. [3H]DHA bound to both beta 1- and beta 2-adrenoceptors with indistinguishable affinity (KD = 1.31 nM, Bmax = 174 fmol/mg protein). Computer modelling of competition curves of unlabeled selective antagonists or agonists was then required in order to determine reliably beta 1- and beta 2-adrenoceptor affinities and proportions: the beta 1-adrenoceptors represent 35.5% and the beta 2-adrenoceptors 64.5% of the entire beta-adrenoceptor population in rat gravid myometrium at term. The second approach utilized the radioligand [3H]hydroxybenzylisoproterenol ([3H]HBI) which is a very high-affinity beta-adrenoceptor agonist. The characteristics of the [3H]HBI binding sites are essentially those expected of beta 2-adrenoceptors, but the [3H]HBI binding sites represent only 34% of [3H]DHA binding sites and may represent the fraction of beta 2-adrenoceptors that mediate adenylate cyclase stimulation and uterine relaxation. Between 21 d 09 h and 22 d 09 h of gestation, the number of beta 2-adrenoceptors was constant (mean = 225.6 +/- 20.2 fmol/mg protein). At term, the number of [3H]HBI binding sites dropped (-75%) during the last 7 h of pregnancy, suggesting a reduced ability to elicit relaxation through beta-adrenoceptor activation in parturient myometrium of rat.     

Combined immunophenotyping and in situ hybridization (FICTION): a rapid method to study cell lineage involvement in myelodysplastic syndromes

Summary. We present a study in which we used a recently described method combining fluorescence in situ hybridization (FISH) and immunophenotyping, i.e. FICTION, to assess the involvement of different cell lineages in myelodysplastic syndrome (MDS) with monosomy 7 (–7), trisomy 8 (+8) or loss of Y chromosome (–Y). Blood or marrow smears or cytocentrifuge preparations were stained both by antibodies to granulocytes (CD₁₅), monocytes (CD₁₄), T lymphocytes (CD₃), B lymphocytes (CD₂o) and by probes specific for chromosomes 7, 8 or Y. Of nine cases of MDS with –7, four with +8 and two with – Y studied, none showed lymphocytic involvement by the chromosome abnormality. In contrast, -7,-1-8 and – Y were found in granulocytes and monocytes in all patients studied, but they involved a variable proportion of those cells. The partial involvement by –7 and +8 seen in some cases suggests that myelopoi'esis was only partially clonal in those cases, or that the chromosome abnormality was a secondary event in the MDS process. FICTION therefore appears to be a simple and easily reproducible method that can be used for the assessment of lineage involvement in MDS and other haematological malignancies.     

Segmental analysis of stress thallium201 scintigraphy for the diagnosis and localization of coronary artery disease

Ninety-two patients (15 devoid of coronary artery disease, 24with atherosclerotic coronary lesions but without antecedentmyocardial infarction, 20 with prior anterior myocardial infarction,33 with prior inferior infarction) were submitted to a stresselectrocardiogram and thallium201 scan within the three monthspreceeding or the month following a coronary angiogram. Thisstudy first confirmed that by using a segmental analysis ofthe scans, the localization of the coronary lesion responsiblefor the appearance of zones of hypofixation can be determined.In general, however, defects appear only in the territory ofthe most stenosed vessels. For the detection of coronary diseasein the absence of antecedent myocardial infarction, the exerciseelectrocardiogram showed a sensitivity of 54% and a specificityof 67%. The sensitivity (92%) and specificity (93%) of stressmyocardial scintigraphy were clearly superior. Stress thallium201scintigraphy detected 60% of the patients with anterior infarctionand multiple vessel disease, but suggested the existence ofmultiple lesions in three out of five subjects with isolatedLAD disease. After inferior infarction, multiple vessel diseasewas detected by scintigraphy with a sensitivity of 45% and aspecificity of 82%. If an apical defect in the anterior viewwas considered to be the sign of LAD artery stenosis, the sensitivityof stress myocardial scintigraphy for the detection of multiplevessel disease in the presence of inferior myocardial infarctionreached 86% and the specificity 54%. Stress thallium²⁰¹ myocardialscintigraphy appears more sensitive and specific than exerciseelectrocardiography for the detection of coronary artery diseaseand residual ischaemia after myocardial infarction.