Increased sharing of maternal HLA haplotypes among children exposed to diphenylhydantoin during pregnancy.

During investigation of HLA types among children exposed to diphenylhydantoin (DPH) in utero, we found no evidence of a distortion in haplotype sharing among affected sib pairs. Unexpectedly, however, we found a marked increase in the proportion of all sib pairs (not just affected ones) sharing maternal haplotypes. Among 14 two child families, 12 shared the maternal haplotype (expected would be seven); among families with more than two children the distortion was also pronounced. This finding, if verified in future studies, could indicate that something in the mothers, whether DPH use during pregnancy, or some genetic factor associated with seizures, or some effect of the seizures themselves, may be leading to non-random segregation of HLA haplotypes in their offspring.     

Organism resembling Neisseria gonorrhoeae and Neisseria meningitidis.

A problem isolate resembling Neisseria gonorrhoeae and Neisseria meningitidis is reported. Growth and biochemical characteristics indicated the organism to be N. meningitidis, whereas serological characteristics indicated it to be N. gonorrhoeae. This vaginal isolate may be a genetically transformed gonococcus with the ability to utilize maltose. Conversely, it may be a meningococcus which has acquired antigenic determinants of N. gonorrhoeae.     

Ataxia-Telangiectasia and Xeroderma Pigmentosum: No Evidence of Linkage to HLA

Nine HLA-typed multiplex nuclear families segregating ataxia-telangiectasia (A-T), an autosomal recessive disorder, were studied. Linkage analysis performed by lod scores and by a previously published sib pair method revealed no evidence for linkage between A-T and HLA. An alternative method of linkage detection, previously applied to xeroderma pigmentosum (XP) and HLA, was reexamined and found to contain an error. As a consequence, neither of these "DNA repair disorders" appears to be linked to HLA.     

Funicular location of ascending axons of lamina I cells in the cat spinal cord

The laminar distribution of spinal cord neurons projecting suprasegmentally through different funiculi was determined in the cat using horseradish peroxidase (HRP) injections combined with selective spinal cord lesions. The lesions were designed to limit the caudal transport of HRP to either the ventral funiculi or the dorsolateral funiculus. HRP injections in the ventromedial or ventrolateral funiculi resulted in labeling primarily within laminae IV–VIII and a virtual lack of labeling within lamina I. When the dorsolateral funiculus was injected, 20–25% of all labeled cells were located in lamina I, bilaterally. These results demonstrate that the ascending lamina I projections are through the dorsolateral funiculus.     

Pacing Mode and Long-Term Survival in Elderly Patients with Congestive Heart Failure: 1980-1985

Dual-chamber pacing may improve short-term hemodynamics and functional class in some patients with congestive heart failure, even in the absence of conventional indications for pacemaker implantation. However, the impact of different pacing modes on survival of patients with congestive heart failure is controversial. In this retrospective study we analyzed survival data from 546 elderly patients, aged 70 years and older, who underwent implantation of a permanent dual-chamber (DDD, n = 62, DVI, n = 102) or single-chamber (VVI) pacemaker (n = 382) between 1980 and 1985. Survival was further analyzed according to the presence or absence of congestive heart failure, and pacemaker mode (DDD vs. DVI vs. VVI). Overall, dual-chamber pacing (DDD and DVI) was associated with a more favorable long-term outcome when compared with single-chamber ventricular pacing, although differences were only significant for DDD pacing (P = 0.002). When patients with and without preexisting congestive heart failure were analyzed separately, survival following dual-chamber pacing (DDD and DVI) was significantly better than survival following single-chamber pacing in patients without congestive heart failure (P = 0.03), but not in patients with preexisting heart failure (P = 0.139). When patients were analyzed according to the electrophysiological indication for pacemaker implantation, overall survival of patients with AV block (P = 0.0025) but not sinus node dysfunction (P = 0.346) was improved with dual-chamber pacing. This survival advantage in patients with AV block following dual-chamber pacing was lost in the presence of heart failure P = 0.11). These findings suggest that dual-chamber pacing, in particular DDD pacing, improves the survival in elderly patients without preexisting congestive heart failure. In contrast to the short-term hemodynamic improvement observed in selected patients with congestive heart failure, dual-chamber pacing in elderly patients with congestive heart failure, paced for conventional indications, is not associated with improved survival when compared with single-chamber ventricular pacing.     

Differences in left ventricular ejection fraction and volumes measured at rest and poststress by gated sestamibi SPECT.

BACKGROUND: Some studies suggested that the poststress left ventricle ejection fraction (LV EF) is lower than rest LV EF in patients with stress-induced ischemia. METHODS AND RESULTS: By using a 2-day protocol and 30 mCi Tc-99m sestamibi, LV EF, end-systolic volume (ESV), and end-diastolic volume (EDV) were measured with gated SPECT. Of 99 eligible patients, 91 had technically adequate studies. Poststress LV EF minus rest LV EF was defined as DeltaLV EF. DeltaEDV and DeltaESV were similarly defined. Rest and poststress LV EF (r = 0.89), EDV (r = 0.78), and ESV (r = 0.93) were highly correlated (P <.001). Rest LV EF, EDV, and ESV were not significantly different between patients with and without stress-induced ischemia. DeltaLV EF was significantly lower in patients with stress-induced ischemia (-3.5% +/- 4.5% vs -1.1% +/- 4.7%, P = .02). Mean LV EF poststress in ischemic patients was 55.0% +/- 10.5% vs 61.2% +/- 10.0% in nonischemic patients (P = .008). However, only 1 patient (3%) with ischemia had DeltaLV EF that exceeded the 95% confidence limit of DeltaLV EF for normal patients. Ischemia was significantly associated with increased DeltaEDV and DeltaESV (P < .01). CONCLUSIONS: Stress-induced ischemia is associated with poststress reduction in LV EF and increased poststress EDV and ESV. However, the effect of ischemia on the difference between poststress and rest EF measurements is modest and rarely exceeds the confidence limits in normal patients undergoing 2-day protocols. In most patients, poststress LV EF is an accurate reflection of rest LV EF.     

Drawbacks of GENEHUNTER for larger pedigrees: application to panic disorder

Large pedigrees can pose a problem for GENEHUNTER linkage analysis software. Differences in two-point and multipoint lodscores were observed when comparing GENEHUNTER to other linkage software. Careful consideration must be given when selecting linkage analysis programs. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:781-783, 2000.     

A pilot investigation of mild hypothermia in neonates receiving extracorporeal membrane oxygenation (ECMO)

OBJECTIVE: To investigate the safety and feasibility of using mild hypothermia in neonates receiving extracorporeal membrane oxygenation (ECMO).Study design A prospective, nonrandomized pilot study of 25 neonates referred for ECMO. Whole body cooling was achieved by adjustment of the temperature of the extracorporeal circuit water bath. Five groups (N=5 per group) were each studied for the first 5 days of ECMO. The first group was maintained at 37 degrees C throughout the study period. Subsequent groups were cooled to 36 degrees C, to 35 degrees C, and, finally, to 34 degrees C, respectively, for 24 hours and the final group to 34 degrees C for 48 hours before being rewarmed to 37 degrees C. Patients were carefully assessed clinically and biologically. In addition to routine laboratory tests, cytokines (IL-6 and IL-8), complement (C3a), and molecular markers of coagulation (thrombin/antithrombin III [TAT], antithrombin III, and plasmin-alpha2plasminogen) were measured. RESULTS: No major clinical or circuit problems were noted during cooling or rewarming. In particular, there were no problems of bleeding or cardiac arrhythmia. No significant difference was found between groups in terms of molecular markers of coagulation, complement, cytokines, and platelet transfusions. CONCLUSIONS: Applying mild hypothermia (34 degrees C) for 24 or 48 hours to neonates receiving ECMO is both feasible and safe.     

High‐frequency ventilation with the Dräger Babylog 8000plus: measuring the delivered frequency

Background: Ventilator frequency is one of the determinants of tidal volume delivery during high‐frequency ventilation. Clinicians increasingly use data on ventilator displays to inform their decisions. Aim: To measure the frequencies delivered by the Dräger Babylog 8000plus ventilator when used in high‐frequency mode. Methods: Ventilator waveforms using a test lung were recorded at the full range of settings 5–20 Hz using Spectra software at 1000 Hz. The changes in frequency produced by a 1‐ Hz change in set frequency were calculated. Actual and displayed frequencies were compared. Results: For settings up to 12 Hz, median (range) difference between set and delivered frequencies was 0 (?0.4 to +0.1) Hz. Above 12 Hz, delivered frequency varied by ?0.3 (?1.9 to +0.3) Hz. For 1‐ Hz changes in frequency settings, in the range 5–12 Hz, 1‐ Hz changes produced a change in delivered frequency of 1.0 (0.6–1.4) Hz. Above 12 Hz, the corresponding changes were 0.7 (0–2.9) Hz. The ventilator displays the set frequency during operation rather than the delivered frequency. Conclusion: At 12 Hz and below, the differences between set and delivered frequencies were relatively small compared with those at 13 Hz and higher. Above 13 Hz, the difference between set and delivered frequencies was up to 2.9 Hz. Some frequency setting changes did not result in a change in delivered frequency.     

Addition of fexofenadine to inhaled corticosteroid therapy to reduce inflammatory biomarkers in atopic asthma.

BACKGROUND: We previously showed that H1-antihistamines may shift the PC20 (provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20%) threshold to adenosine monophosphate (AMP) challenge but may paradoxically prolong recovery. OBJECTIVES: To measure AMP recovery using a constant predetermined AMP PC20 and to evaluate whether fexofenadine use confers add-on effects to treatment with either fluticasone propionate alone or combined fluticasone propionate-salmeterol. METHODS: Fourteen atopic patients with mild-to-moderate asthma (forced expiratory volume in 1 second of 76%) completed a double-blind, randomized, crossover study consisting of 3-week treatment blocks of either fluticasone propionate-salmeterol, 250 microg twice daily, or fluticasone propionate alone, 250 microg twice daily, in conjunction with either fexofenadine, 180 mg once daily, or matched placebo. Recovery after a predetermined AMP PC20 challenge was measured (primary outcome), along with exhaled nitric oxide levels, plasma eosinophil cationic protein levels, peripheral eosinophil counts, pulmonary function, diary card outcomes, and quality of life (all secondary outcomes). RESULTS: There were no differences in any of the primary or secondary outcomes when fexofenadine was added to treatment with either fluticasone propionate-salmeterol or fluticasone propionate alone. The mean AMP recovery time was 25.0 vs 23.4 minutes for fexofenadine and placebo, respectively, as add-on to fluticasone-salmeterol and 22.5 vs 23.9 minutes, respectively, as add-on to fluticasone alone. CONCLUSION: Fexofenadine did not affect recovery to a fixed dose of AMP challenge or any other surrogate inflammatory markers when given as add-on therapy to corticosteroid-treatedatopic asthmatic patients.