Fear and the startle reflex: Blink modulation and autonomic response patterns in animal and mutilation fearful subjects

The present study was designed to examine the pattern of startle reflex modulation and autonomic responses for individuals high in animal or blood-injury fear when viewing pictures of their feared objects. Sixteen individuals in each fear group and 16 low-fear control individuals viewed 32 color slides depicting fear-relevant, unpleasant but fear-unrelated, neutral, and pleasant scenes. Free viewing times were assessed in a second phase of the procedure as an index of avoidance behavior. Exposure to pictures of feared objects resulted in a consistent startle reflex potentiation and behavioral avoidance in both fear groups. This activation of the basic aversive system was independent of the autonomic pattern of the fear responses, which differed for the high-fear groups. These results suggest that the probe startle response indexes the organism's basic motivational disposition and add new information to the assessment of fear.     

Age-Dependent Prevalence of Cardioembolic Sources Detected by TEE: Diagnostic and Therapeutic Implications

To define the prevalence of cardioembolic sources found by transesophageal echocardiography (TEE) in different age groups of patients with and without cryptogenic systemic embolism, TEE risk factors for cardiogenic embolism were identified from 341 consecutive patients referred for TEE. One hundred and thirty-five had cryptogenic cerebral or systemic peripheral embolic events (CEE) and 206 other indications for TEE (CTR). Cardioembolic sources were found in 40% of CEE and in 29% of CTR (P < 0.02). Specifically, left atrial (LA) thrombi (P < 0.0001), atrial septal aneurysm with right-to-left shunt (P < 0.002), and atherosclerotic aortic plaques (P < 0.02) were more frequent. The prevalence of potential cardioembolic sources was significantly higher in patients ≥ 70-years old than in younger patients (P < 0.03), specifically LA thrombi (P < 0.004) and atherosclerotic aortic plaques (P < 0.0001). In patients ≥ 70-years old, potential cardioembolic sources were found in 63% and in 40% in CEE and CTR (P = 0.073), respectively. However, LA thrombi were more frequent in CEE (P < 0.003). Thus, potential cardioembolic sources observed by TEE are found more frequently in patients ≥ 70-years old than in younger patients. LA thrombi were more frequent in CEE than in CTR patients ≥ 70-years old. In patients ≥ 70-years old with CEE who are eligible for an anticoagulant regimen, a search for potential cardioembolic sources by TEE should be considered.     

The Effects of Allyl Isovalerate on the Hematopoietic and Immunologic Systems in Rodents

The Effects of Allyl Isovalerate on the Hempatopoietic and ImmunologicSystems in Rodents. HONG, H. L., HUFF, J. E., LUSTER, M. I.,MARONPOT, R. R., DIETER, M. P., HAVES, H. T., AND BOORMAN, G.A. (1988). Fundam. Appl. Toxicol. 10, 655–663. FemaleB6C3F1 mice plus male and female Fischer 344/N rats were gavagedwith allyl isovalerate (AIV) in corn oil at 0, 31,62, or 125(mice) and 0, 31. 62, 125, or 250 (rats) mg/kg body weight forfive daily exposures per week for a 2-week period. Hematologic,immunologic, and histopathologic studies were performed 48 to72 hr following the final treatment. AIV exposure had no effecton hematology or bone marrow cellularity in mice or rats. AIVexposure at 250 mg/kg was toxic to rats causing reduced weightgain and hepatotoxicity. In vivo and in vitro studies revealedthat pluripotent hematopoietic stem cells (CFU-S) and granulocyte-macrophageprogenitors (CFU-GM) in the bone marrow were decreased in thetreated mice. Hematopoietic suppression was correlated withthe reduction in the hexose monophosphate shunt metabolism ofbone marrow cells but the Embden-Meyerhof pathway and tncarboxylicacid pathway enzymes did not appear to be affected. Examinationof host resistance following Plasmodium and Listeria challengedid not demonstrate significant differences between treatedand control mice, nor were there other effects on the immunesystem. This suggests that the myelotoxic effects were minimaland of a degree that would not alter host resistance.     

Synthesis of thymosin α1 by fragment condensation using tert.-butyl side chain protection

A novel synthesis of thymosin α₁ by classical methods using seven tert. -butyl side chain protected fragments is described. Optimum conditions were found for the final DCC/HOBt coupling of the two key intermediates; decapeptide and octadecapeptide. Thymosin α₁ was purified by two stages of preparative HPLC (partial purification with C₈ and final purification with C₁₈ reverse phase silica gel) to give a 30% overall yield for the final four stages of synthesis (including catalytic hydrogenation of octadecapeptide, coupling, deprotection and purification). The product was shown to be homogeneous by thin-layer and paper high voltage electrophoresis, isoelectric focusing analysis, thin-layer chromatography and high performance liquid chromatography. Amino acid analysis, optical rotation, ¹ H-n.m.r. spectroscopy, FAB mass spectroscopy and peptide mapping after tryptic digestion confirmed the structure of thymosin α₁. Three minor stereoisomer contaminants were isolated by HPLC and characterized as [D-Lys¹⁴]-thymosin α₁, [D-Lys¹⁷]-thymosin α₁ and [D-Ala³]-thymosin α₁ resulting from racemization at Lys¹⁴, Lys¹⁷ and Ala³ during the coupling of the fragments. A final contaminant, isolated by HPLC, was characterized as N^α-isobutyloxycarbonyl-thymosin α₁ (15–28), which results from “wrong way opening” of an activated mixed anhydride.     

Comparison of a Unipolar Defibrillation System with a Dual Lead System Using an Enlarged Defibrillation Anode

The unipolar system for transvenous defibrillation, consisting of a single right ventricular lead as the cathode and the device shell as anode, has been shown to combine low de- fibrillation thresholds (DFTs) and simple implantation techniques. We compared the defibrillation efficacy of this system with the defibrillation efficacy of a dual lead system with a 12-cm long defibrillation anode placed in the left subclavian vein. The data of 38 consecutive patients were retrospectively analyzed. The implantation of an active can system was attempted in 20 patients (group 1), and of the dual lead system in 18 patients (group 2). Both groups had comparable demographic data, cardiac disease, ventricular function, or clinical arrhythmia. The criterion for successful implantation was a DFT of > 24 J. This criterion was met in all 18 patients of group 2, The active can system could not be inserted in 3 of the 20 group 1 patients because of a DFT > 24 J. In these patients, the implantation of one (n = 2) or two (n = 1) additional transvenous leads was necessary to achieve a DFT ≤ 24). The DFTs of the 17 successfully implanted group 1 patients were not significantly different from the 18 patients in group 2 (12.3 ± 5.7 f vs 10.8 ± 4.8 J). The defibrillation impedance was similar in both groups (50.1 ± 6.1 ± 48.9 ± 5.2 Ω). In group 1, both operation duration (66.8 ± 17 min vs 80.8 ± 11 min; P < 0.05) and fluoroscopy time (3.3 ± 2.1 min vs 5.7 ± 2.9 min; P < 0,05) were significantly shorter. Thus, the active can system allows reliable transvenous defibrillation and a marked reduction of operation duration and fluoroscopy time. The dual lead system, with an increased surface area defibrillation anode, seems to he a promising alternative for active can failures.     

Implantation of a Cardioverter/Defibrillator in the Subpectoral Region Combined with a Nonthoracotomy Lead System

An implantable cardioverter defibrillator was placed into a sub-pectoral pocket via the incision for cephalic venotomy during implantation of a nonthoracotomy lead system. The approach obviated another incision and subcutaneous tunneling of the leads. There were no perioperative complications and after 6 months of follow-up, the patient continues to tolerate the device satisfactorily.     

Cholecystokinin is a physiological regulator of gastric acid secretion in man

Abstract. CCK8 is a poor stimulant of gastric acid secretion in vivo , but is equipotent to gastrin-17 (G17) in in vitro systems. To further evaluate the role of cholecystokinin (CCK) in regulating acid output in humans, dose-response curves were constructed to CCK8 or G17 (6·4–800 pmol kg^-1 per h) with and without a specific CCK-A receptor antagonist (loxiglumide). During loxiglumide infusion, G17-stimulated acid output was unchanged, whereas CCK8-stimulated secretion increased significantly. Gastric somatostatin-14 release increased fivefold with CCK8 alone, but was blocked with loxiglumide administration. These data suggest that CCK8 directly stimulates acid secretion by binding to a CCK-B/gastrin receptor on parietal cells, but at the same time inhibits acid responses by stimulating gastric somatostatin release to a CCK-A receptor-mediated pathway. To test which action of CCK is relevant under physiological circumstances, the effect of loxiglumide on fasting and post-prandial acidity was measured through continuous pH-metry. After eating, gastrin levels increased fourfold compared to controls with concomitant increases in acid secretion. These results suggest that post cibum, CCK is an inhibitor of acid secretion by regulating gastrin through local somatostatin; they support the hypothesis that CCK acts as an enterogastrone.