Permanent Rapid Atrial Pacing to Control Supraventricular Tachycardia

A case is reported of a patient who had continuous supraventricular tachycardia with a ventricular rate of about 170. The arrhythmia was refractory to drugs and DC countershock, and did not convert with atrial pacing. Rapid atrial stimulation controlled the ventricular rate by simulating atrial fibrillation (pacing at 300-400/min), or by simulating a faster atrial tachycardia with 2:1 conduction (pacing at 205-210/min). This form of therapy was used on a permanent basis for more than five months.     

Analysis of Pacing/Defibrillator Lead Failure Using Device Diagnostics and Pacing Maneuvers

Patients with Medtronic Sprint Fidelis (Medtronic Inc., Minneapolis, MN, USA) lead failures present with oversensing, resulting in pacing inhibition and inappropriate shocks. We present a case of lead noise from the right ventricular (RV) ring conductor, resulting in multiple inappropriate shocks with subsequent pacing inhibition and syncope. RV pacing lead impedance at no point exceeded 1,000 ohms. We found that increased noise and oversensing was more likely to be induced when pacing at higher pulse widths. RV pacing outputs at lower pulse widths may decrease susceptibility to noise generation and prove an effective temporizing measure in pacing-dependent patients .     

Serine and d-serine position-1 substituted angiotensin II analogues Synthesis using new 2,3,5,6-tetrafluorophenyl active esters and biological activities

[Ser¹], ( 32 ), [d -Ser¹]- ( 29 ), [Ser¹, Leu⁸]- ( 31 ), and [d -Ser¹, Leu⁸] angiotensin II ( 30 ) were synthesized by a repetitive method in solution using new protected amino acid 2,3,5,6-tetrafluorophenyl active esters. 32 and 29 were agonists, and 31 and 30 were specific antagonists to angiotensin II (AII) receptors determined by the rabbit aortic strip (RAS) and rat blood pressure (RBP) assays. It was found that the hydroxymethyl side chains of serine and D-serine in position-l has an important influence on the agonistic activity of the analogues. The pressor activities of 32 and 29 were 129 and 314%, respectively, as potent as AII. On the other hand, 31 and 30 were effective in antagonizing the AII-induced contraction of RAS and rise in RBP.     

Halcinonide in the treatment of corticosteroid responsive dermatoses

Eighty-eight patients with bilateral lesions of atopic dermatitis, eczematous dermatitis, neurodcrmatitis or psoriasis were treated, without occlusion, with halcinonide and with betamethasone 17-valerate creams (0.1%) and evaluated in a double-blind, paired comparison study. In the forty-three psoriatic patients, halcinonidc was superior in twenty-three, betamethasone 17-valerate was superior in four, both drugs were equally effective in fourteen, and neither drug was effective in two. In the evaluation of all eighty-eight patients, halcinonide was superior in forty-two, betamethasone 17-valerate was superior in eight, both drugs were equally effective in twenty-nine, and neither drug was effective in nine. The overall superiority of halcinonide to betamethasone 17-valerate was highly significant (P <0.001). Halcinonide exhibited its superiority each week of the 3-week study. There were no side effects with either drug. The substitution of a chlorine atom for a hydroxyl group in the 21-position of the triamcinolone acctonide molecule, and the use of a specifically formulated cream vehicle containing propylene glycol and water, have yielded an extremely active topical anti-inflammatory drug.     

C5aR ligand peptide 3D QSAR study performed with an applied linear conformation

A 3D quantitative structure-activity relationship study (QSAR) of binding and activation of the human C5a receptor by peptide analogs of the C-terminal binding domain of C5a anaphylatoxin is reported. Using published C5a analog affinity and activity data, this paper seeks to elucidate the pharmacophore for the high affinity C-terminal binding domain of the C5a peptide with the molecular modeling technique of comparative molecular field analysis (CoMFA). In order to model peptides for which there was incomplete conformational data, an arbitrary linear conformation was imposed upon the highly flexible C5a analogs. The resulting models yield a crossvalidated q² of 0.889 and 0.787, for receptor-ligand affinity and EC₅₀ calcium release activity, respectively, suggesting these models have good predictive ability for other test peptides.     

Single-nucleotide polymorphism rs7754840 of CDKAL1 is associated with impaired insulin secretion in nondiabetic offspring of type 2 diabetic subjects and in a large sample of men with normal glucose tolerance

CONTEXT: CDKAL1 is a recently discovered susceptibility gene for type 2 diabetes. OBJECTIVE: Our objective was to investigate the impact of rs7754840 of CDKAL1 on insulin secretion, insulin sensitivity, and risk of type 2 diabetes. DESIGN AND SETTINGS: Study 1 (the EUGENE2 study) was a cross-sectional study including subjects from five white populations in Europe (Denmark, Finland, Germany, Italy, and Sweden). Study 2 is an ongoing prospective study of Finnish men. PARTICIPANTS: In study 1, 846 nondiabetic offspring of type 2 diabetic patients (age 40 +/- 10 yr; body mass index 26.7 +/- 5.0 kg/m(2)) participated. In study 2, subjects included 3900 middle-aged men (533 type 2 diabetic and 3367 nondiabetic subjects). Interventions: Interventions included iv glucose-tolerance test (IVGTT), oral glucose-tolerance test (OGTT), and euglycemic-hyperinsulinemic clamp in study 1 and OGTT in study 2. MAIN OUTCOME MEASURES: Parameters of insulin secretion, insulin resistance, and glucose tolerance status were assessed. RESULTS: In study 1, carriers of the GC and CC genotypes of rs7754840 had 11 and 24% lower first-phase insulin release in an IVGTT compared with that in carriers of the GG genotype (P = 0.002). The C allele was also associated with higher glucose area under the curve in an OGTT (P = 0.016). In study 2, rs7754840 was significantly associated with type 2 diabetes (P = 0.022) and markers of impaired insulin release [insulinogenic index (IGI), P = 0.012] in 2405 men with normal glucose tolerance. CONCLUSIONS: rs7754840 of CDKAL1 was associated with markers of impaired insulin secretion in two independent studies. Furthermore, rs7754840 was associated with type 2 diabetes in Finnish men (study 2). Therefore, CDKAL1 is likely to increase the risk of type 2 diabetes by impairing insulin secretion.