Characteristics of entrainment during autodecremental atrial and ventricular stimulation

The entrainment characteristics of orthodromic circus movement tachycardias occurring during autodecremental atrial and ventricular stimulation were studied in 9 patients with manifest Wolff-Parkinson-White syndrome. The phenomenon occurred in 34 of 38 episodes of tachycardia during autodecremental atrial stimulation. It was not seen in 4 episodes because the first impulse penetrating the circuit terminated the arrhythmia. Invariably, the HH and VV intervals were not equal to, but longer than, the stimulus-stimulus intervals, thus not fulfilling the definition of "classic" (constant cycle length) entrainment postulated by Okumura et al. Furthermore, the first 2 of the 3 diagnostic criteria were not demonstrated and the third only could be demonstrated in 7 episodes. Tachycardia termination was achieved in all 38 episodes. Entrainment occurred during autodecremental ventricular stimulation in 79 of 80 episodes, with the AA and H-H- intervals (when visible) being equal to the corresponding paced cycle lengths. Moreover, the intervals between the last paced ventricular beat and the first ventricular beat of the resumed tachycardia were invariably longer than the last stimulus-stimulus intervals. These characteristics were those which Okumura et al attributed to "concealed" entrainment. Tachycardia termination was achieved in 77 of 80 episodes. In summary: (1) autodecremental atrial pacing produced a specific form of entrainment that did not fulfill the "classic" definition of Okumura et al; (2) autodecremental ventricular pacing consistently produced "concealed" entrainment; and (3) autodecremental stimulation was very effective in terminating 115 of 118 (98%) of episodes of circus movement tachycardias.     

Association of the dopamine receptor D4 (DRD4) gene 7-repeat allele with children with attention-deficit/hyperactivity disorder (ADHD): an update.

Polymorphisms of the dopamine receptor D4 gene DRD4, 11p15.5, have previously been associated with attention-deficit/hyperactivity disorder (ADHD) [Bobb et al., 2005; Am J Med Genet B Neuropsychiatr Genet 132:109-125; Faraone et al., 2005; Biol Psychiatry 57:1313-1323; Thapar et al., 2005; Hum Mol Genet 14 Spec No. 2:R275-R282]. As a follow up to a pilot study [see Castellanos et al., 1998; Mol Psychiatry 3:431-434] consisting of 41 probands and 56 controls which found no significant association between the DRD4 7-repeat allele in exon 3 and ADHD, a greatly expanded study sample (cases n = 166 and controls n = 282) and long term follow-up (n = 107, baseline mean age n = 9, follow-up mean age of n = 15) prompted reexamination of this gene. The DRD4 7-repeat allele was significantly more frequent in ADHD cases than controls (OR = 1.2; P = 0.028). Further, within the ADHD group, the 7-repeat allele was associated with better cognitive performance (measured by the WISC-III) (P = 0.013-0.07) as well as a trend for association with better long-term outcome. This provides further evidence of the role of the DRD4 7-repeat allele in the etiology of ADHD and suggests that this allele may be associated with a more benign form of the disorder.     

Molecular and functional characterization of a mutant allele of the mitogen-activated protein-kinase geneSLT2(MPK1) rescued from yeast autolytic mutants

 We have further characterized the functionality of the Saccharomyces cerevisiae gene SLT2(MPK1), coding for a MAP-kinase homolog essential for cell integrity, which is involved in the Pkc1p signalling pathway. This gene was isolated on the basis of its capacity to complement the thermosensitive-autolytic, osmotic-remediable phenotype of lyt2 mutants. Both slt2Δ and lyt2 mutants displayed a caffeine-sensitive phenotype consisting of cell lysis that was not dependent on temperature. Caffeine concentrations affecting the growth of these mutant strains were dependent on the genetic background, the SSD1 allele being very significant in this regard. The SLT2 allele of several lyt2 strains was both rescued and amplified by PCR. The recovered allele was shown to be non-functional as it could not complement the lytic phenotype of both deletion (slt2Δ) and lyt2 strains. After nucleotide sequencing of the recovered allele, we found that the defect of lyt2 mutants consists in a substitution of an aspartic acid for a glycine at position 35 of the amino-acid sequence of Slt2p. Gly35 is the third glycine of a glycine cluster (Gly-X-Gly-X-X-Gly), a conserved region in protein kinases and other nucleotide-binding proteins. Received: 13 October/27 November 1995     

A pilot study of recombinant interferon beta (IFN-βser) in patients with recurrent glioma

Recombinant interferon beta (IFN-_ser) has been administered by intravenous bolus injection three times weekly at a dose of 90 × 10⁶ IU to 14, patients with recurrent malignant glioma in an ongoing study. The treatment period has ranged from 1 to 40 weeks. The most common adverse experiences were fever, chills, malaise, and headache. Fever, chills and headache were worse with the first two doses and were usually relieved with acetaminophen. All patients tolerated subsequent treatments without any difficulties. No neurologic or hematologic toxicities were observed. Of ten evaluable patients, five had progressive disease in 4 to 8 weeks; three had stable disease for 12 to 21 weeks; one has had a minor response for 13 weeks; and one has had a complete resolution of tumor for 150 + weeks. IFN-_ser appears to have activity in human glioma and is well tolerated at this dosage and schedule.     

Energy density but not fat content of foods affected energy intake in lean and obese women

BACKGROUND: Studies have shown that energy intake increases when both the fat content and energy density of the entire diet increases. When the fat content and energy density vary independently of one another, however, energy density, but not fat content, influences intake. OBJECTIVE: The present study examined whether energy intake in lean and obese women is affected when either the energy density or the fat content of a portion of the diet is manipulated and palatability is held constant. DESIGN: In a within-subjects design, 17 lean and 17 obese women consumed meals in the laboratory for four, 4-d test periods. In 3 of these test periods the energy density (4.4 and 6.7 kJ/g) or the fat content (16% and 36% of energy) of compulsory entrees representing 50% of each subject's usual energy intake was manipulated. Additional self-selected foods were consumed ad libitum at meals and as snacks. RESULTS: There were no systematic differences in palatability of the manipulated foods across conditions. Obese and lean participants responded similarly to the dietary manipulations. Intake of self-selected foods at meals was reduced significantly by 16% for both lean and obese subjects in the low- compared with the high-energy-density condition. The fat content of the compulsory foods had no significant effect on energy intake. Ratings of hunger did not differ between diets. CONCLUSION: These results indicate that when a portion of the diet was manipulated, the energy density, but not the fat content, of the foods affected total energy intake at meals in both lean and obese women.