Asystole with Syncope Secondary to Hyperventilation in Three Young Athletes

We describe three athletes who had syncope after (case 1) or during (cases 2, 3) hyperventilation. During the episode, ECG showed prolonged sinus arrest. Clinical data and noninvasive investigations were normal and the phenomenon was not reproducible. Electrophysiological study after autonomic blockade allowed a prolonged intrinsic heart rate in case 1, and abnormal corrected sinus node recovery time in cases 1 and 2. During follow-up, symptomatic sinus arrest provoked by deep inspiration occurred in case 3. These cases document prolonged asystole of unknown etiology, secondary to hyperventilation, and probably caused by different vagally-mediated mechanisms.     

The night-a dangerous time to be born?

Summary. An analysis of perinatal mortality by hour of birth among 10 059 births in Canton Ticino (Switzerland) during the years 1979–1982 showed that fewer births occurred at night than during the day. The variations in number of births by hour of birth were attributed to obstetric practices. The perinatal mortality rate for night-time births was more than twice as high as that for the daytime births (+127%, P<0·001) and the rates for night-time births exceeded those for daytime births for 13 of the 19 causes of death examined. A higher proportion of the low and very-low–birthweight babies (<2500g and <1500g) were born at night between 19·00 and 06·59 hours.     

Dehydro-dermorphins

Dehydrophenylalanine having the Z-configuration (ΔPhe) and D-Phe were incorporated in positions 3 and/or 5 into dermorphin-(1–5)-peptide amide (H-Tyr-D-Ala-Phe-Gly-Tyr-NH₂) in order to study the effect of structure or configurational changes. On GPI preparation, whereas the activity of [L-Phe⁵]-pentapeptide was fourfold higher than parent peptide and comparable to that of dermorphin, the substitution of Phe³ by its D-enantiomer was barely tolerated. The pentapeptides containing ΔPhe in positions 3 and/or 5 displayed even lower potency: particularly the unsaturation at position 3 alone or at position 3 and 5 was very detrimental to μ activity.     

Opioid peptides Synthesis and binding properties of dermorphin related heptapeptides

C-Terminal amino acid residues of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH₂) were replaced by N^α-methyl- or D-amino acids in order to examine the effect on opioid activity. In binding studies based on displacement of μ, Δ, and κ opioid receptor selective radiolabels from guinea pig brain membranes, the 13 new analogues showed, like dermorphin, a negligible affinity for the κ binding site. The introduction of N^α-methyl- or D-amino acid residues at position 5, 6, or 7 of dermorphin, when matched with C-terminal amide function modifications, generally produced analogues with reversed μ/δ specificity.     

Long-Term Survival in Patients Treated with Cardiac Resynchronization Therapy: A 3-Year Follow-Up Study from the InSync/InSync ICD Italian Registry

Background: Studies reporting the long-term survival of patients treated with cardiac resynchronization therapy (CRT) outside the realm of randomized controlled trials are still lacking. The aim of this study was to quantify the survival of patients treated with CRT in clinical practice and to investigate the long-term effects of CRT on clinical status and echocardiographic parameters.
Methods: The study population consisted of 317 consecutive patients with implanted CRT devices from eight Italian University/Teaching Hospitals. The patients were enrolled in a national observational registry and had a minimum follow-up of 2 years. A visit was performed in surviving patients and mortality data were obtained by hospital file review or direct telephone contact.
Results: During the study period, 83 (26%) patients died. The rate of all-cause mortality was significantly higher in ischemic than nonischemic patients (14% vs 8%, P = 0.002). Multivariate analysis showed that ischemic etiology (HR 1.72, CI 1.06–2.79; P = 0.028) and New York Heart Association (NYHA) class IV (HR 2.87, CI 1.24–6.64; P = 0.014) were the strongest predictors of all-cause mortality. The effects of CRT persisted at long-term follow-up (for at least 2 years) in terms of NYHA class improvement, increase of left ventricular ejection fraction, decrease of QRS duration (all P = 0.0001), and reduction of left ventricular end-diastolic and end-systolic diameters (P = 0.024 and P = 0.011, respectively).
Conclusions: During long-term (3 years) follow-up after CRT, total mortality rate was 10%/year. The outcome of ischemic patients was worse mainly due to a higher rate of death from progressive heart failure. Ischemic etiology along with NYHA class IV was identified as predictors of death. Benefits of CRT in terms of clinical function and echocardiographic parameters persisted at the time of long-term follow-up.     

Synthesis and biological activity of carboxyl terminally extended dermorphins

Dermorphinoyl(DMR)-glycine, DMR-sarcosine and DMR-glycyl-arginine have been prepared in order to examine the effect of C-terminal extension of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH₂) on opioid activity. On GPI preparation the addition of Gly, Sar, or Gly-Arg to the carboxyl terminus of dermorphinoic acid was detrimental to μ activity: dermorphinoyl-derivatives, in fact, retain only 5–20% of dermorphin potency. Following intracerebroventricular administration (tail-flick test), whereas the analgesic activities of compounds showed the trend dermorphin >DMR-Sar> DMR-Gly-Arg>DMR-Gly>morphine, the nonapeptide displayed highest activity after subcutaneous injection in mice: DMR-Gly-Arg was 2.5 and 10 times more potent than dermorphin and morphine, respectively.     

Solution conformational analysis of sodium complexed [Gly6]. - and [Gly9]. -antamanide analogs

To investigate the conformational flexibility of metal-complexed cyclodecapeptides, we synthesized and studied two antamanide analogs, in which the phenylalanine residue in position 6 or 9 of the sequence was substituted by Gly. Previous conformational studies on antamanide suggested that these backbone regions are affected by conformational variation. The NMR conformational study showed a high degree of flexibility for the two analogs. With sodium ions, on the other hand, [Gly⁹]. -antamanide was able to form a fairly stable equimolar complex, whereas [Gly⁶]. -antamanide showed a conformational heterogeneity, with one prevailing conformer. For the [Gly⁹]. -antamanide analog, the whole NMR data, combined with extensive theoretical calculations, were consistent with the presence of 1) two (β-turns of type I, centered on Gly⁹-Phe¹⁰ and Ala⁴-Phe⁵, respectively; 2) a central cavity with a six-carbonyl oxygen cage, optimal for a Na⁺ hexacoordination; 3) strongly H-bonded amide protons for residues 1 and 6, both involved in the formation of the two type I β-turns, which, however, exhibited some fluctuations during the molecular dynamics simulations. For the [Gly⁶]. -antamanide-Na⁺ complex the prevailing conformer was consistent with a more open structure, with the partial solvent exposure of all the amide protons; that is, the Gly residue in position 6 increases the flexibility of this critical site more than does the Gly in position 9. These data in some way parallel the results of the cytotoxicity tests on B16-F10 transformed cells for the two analogs: [Gly⁹]. -antamanide is cytotoxic after 48 h exposure, whereas [Gly⁶]. -antamanide is almost inactive. On the contrary, both analogs are practically inactive in vivo against phalloidin.     

Incidence of Atrial Fibrillation in Patients with Different Mode of Pacing. Long-term Follow-up

We evaluated the incidence of atrial fibrillation in 189 patients (92males, 97females, mean age 75 ± 12yrs, range 41–100yrs) with pacemaker, during a mean follow-up of 5.5yrs (range 1–24yrs). The indications for implant were: complete AV block (115pts), second degree Möbilz 2 AV block (51pts). bifascicular block (5pts). sick sinus syndrome (14pts), symptomatic bradycardia (4pts). The mode of stimulation considered were VVI (105pt), VVI rate responsive (21pts), single lead VDD (43pts), DDD (20pts). The occurrence of retrograde VA conduction in patients with VVI or VVI rate responsive pacing was also evaluated. Atrial fibrillation occurred in 40 pts (21%). The highest incidence was evidenced in patients with sick sinus syndrome (9pts, 64%), and in patients with VVI stimulation (28pts, 27%). On the contrary, the lowest incidence was found in single lead VDD stimulation (4pts, 9%). The patients with dual chamber pacing showed a relatively high incidence of the arrhythmia (5pts, 25%). Atrial fibrillation occurred in 9 out of 32 patients with retrograde VA conduction, and in 22 out of 94 patients without retrograde conduction (28% versus 23%, p=NS). In conclusion, it is confirmed that patients with sick sinus syndrome are at high risk for atrial fibrillation. Single lead VDD stimulation seems to be the better mode of pacing in preventing atrial fibrillation, while dual chamber pacing showed minor efficacy. The presence of retrograde VA conduction could not predict the occurrence of the arrhythmia.     

DENSITOMETRY OF PAUTRIER'S MICROABSCESS CELLS IN CUTANEOUS T CELL LYMPHOMA

Background. Epidermotropic lymphoid T cell infiltrates are part of a continuous spectrum of lesions ranging from “benign” parapsoriasis to frank cutaneous T cell lymphoma (CTCL, mycosis fungoides). Either the clinical or histologic differentiation between these entities prove often difficult and the prognosis may be difficult to assess. Patients and Methods. We studied 15 patients, men aged 50 to 81 years, mean ± SD 68 ± 12 years, with patch-plaque CTCL. Sections from punch biopsies from active lesions were stained with Feulgen reagent, coupled with a “twin” adjacent hematoxylin and eosin (H&E)-stained section and analyzed with a VIDAS Zeiss-Kontron Image Analyzer. At least 50 dermal infiltrating cells and 50 epidermotropic Pautrierian cells per specimen were counted and the biopsies were repeated periodically. Results. Nine patients with aneuploid Pautrierian cell DNA patterns did well after conventional phototherapy (dermal cell ploidy was irrelevant), whereas six patients with euploid Pautrierian cell DNA patterns had to be treated aggressively (IFN + retinoids, COP). Clinical and histopathologic aspects of the first group were comparable to those of the second group. Conclusions. The classical cytophotometric aphorism seems to be reversed in this sample: “The more abnormal the ploidy of epidermotropic Pautrierian cells, the better the prognosis.” Euploid epidermotropic cell prove more efficient in invading the skin and other areas and this efficiency may be reflected in more aggressive trends in the evolution of the lymphoma. Thus, DSM analysis of epidermotropic cells could prove very useful as an inexpensive tool for routine CTCL grading.     

Six-Month Feeding Study of Fenvalerate in Dogs

Six-Month Feeding Study of Fenvalerate in Dogs. Parker, C. M.,PICORILLO, V. J., KURTZ, S. L., GARNER, F. M., GARDINER, T.H., AND VAN GELDER, G. A. (1984) Fundam. Appl. Toxicol. 4, 577–586.Groups of six male and six female Beagle dogs were fed dietscontaining 0, 250, 500, or 1000 ppm fenvalerate for a periodof 6 months. Prominent in-life observations related to treatmentwere emesis, head shaking, biting of the extremities, ataxia,and tremors. One high-dose male dog was sacrificed in extremisduring the study period. Mean body weights of 1000-ppm femaledogs were significantly lower than those of controls. Red bloodcell counts and hematocrit and hemoglobin values in high-dosemale and female dogs were significantly lower than those ofcontrols at most sampling intervals. Serum cholesterol and alkalinephosphatase levels were also increased primarily in the high-dosegroup. Ophthalmic examination revealed changes in retinal vesseltortuosity in some mid- and high-dose dogs. Hepatic multifocalmicro-granulomata were observed in control and treated dogsmicroscopically. These changes increased in incidence and severitywith dose and were considered to be related to treatment Histiocyticcell infiltrate in mesenteric lymph nodes in some 500- and 1000-ppmfemale and 1000-ppm male dogs was the only other treatment-relatedmicroscopic effect.