Possible Involvement of Hypothyroidism as a Cause of Lithium-Induced Sinus Node Dysfunction

Although several reports have stated that even therapeutic levels of lithium can induce sinus node dysfunction, the mechanism has not been fully elucidated. We present here two patients with sinus node dysfunction after long-term lithium therapy. Following lithium discontinuation, sinus node function recovered completely. After resuming lithium, however, irreversible sinus node dysfunction recurred and a permanent pacemaker was implanted in one patient. The serum concentration of lithium was within therapeutic levels. Nevertheless, hypothyroidism was associated with the sinus node dysfunction in both patients. Thus, thyroid function may play an important role in sinus node dysfunction induced by lithium. (PACE 1999; 22[Pt. I]-.954-957) lithium, sinus node dysfunction, hypothyroidism, sick sinus syndrome     

Distribution of human herpesvirus 6 and varicella-zoster virus in organs of a fatal case with exanthem subitum and varicella

The distribution of human herpesvirus 6 (HHV-6) and varicella-zoster virus (VZV) was examined in autopsy samples from a fatal case with both virus infections. A 9-month-old boy developed convulsive seizures followed by macular skin rashes, rapidly progressed to brain death, and died 15 days after the onset, when signs of varicella were noted. An isolation of HHV-6 from blood and evaluation of antibody activities to various viral agents including HHV-6 were performed before his death. Postmortem examinations included: (i) isolation of HHV-6 and VZV from tissues or organs; (ii) detection of both virus antigens in tissues or organs by an indirect immunofluorescent assay using monoclonal antibodies to both viruses; (iii) amplification of both viruses and human herpesvirus 7 DNA sequences by a nested polymerase chain reaction assay; and (iv) endonuclease digestion of amplified products of HHV-6 DNA for differentation of variants A and B. Human herpesvirus 6 DNA was detected in peripheral blood mononuclear cells (PBMC) and plasma obtained at the eruptive stage but present only in PBMC 15 days after, indicating the primary infection with HHV-6, although the virus was not isolated from the same blood sample and a significant rise in the antibody titers to HHV-6 was not observed. Both virus antigens and DNA were detected in various tissues or organs obtained at autopsy, but only VZV was isolated from these samples, suggesting disseminated infection with both viruses in an infant. All the amplified products of HHV-6 DNA were variant B. Among the findings for the distribution of virus antigens, it was noteworthy that HHV-6 antigen was demonstrated in the endothelial cells of small vessels in the frontal lobe of the brain. There was no evidence of HHV-7 infection. These data indicate that the primary HHV-6 infection closely followed by the primary VZV infection had the potential hazard of an unexpected and apparently life-threatening event, in which disseminated infections with both viruses were noted in multiple tissues or organs including the brain.     

Guidelines for the treatment of Crohn''s disease in children

This paper shows guidelines for the treatment of Crohn's disease in children by the Working Group of the Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition (Chair: Yuichiro Yamashiro) and the Japanese Society for Pediatric Inflammatory Bowel Disease (Chair: Akio Kobayashi). The points in which these guidelines differ from those for adult patients are as follows. (i) Total enteral nutrition in the form of an elemental formula is indicated as primary therapy for children with Crohn's disease at onset as well as the active stage. Oral mesalazine is used together. (ii) Total parenteral nutrition (TPN) with oral mesalazine is required for children with serious illness. The use of a corticosteroid should be withheld for at least 1 week after TPN has been started. (iii) When TPN is not considered to be effective, additional corticosteroid is used. Full doses of corticosteroid should be used for at least 2 weeks after clinical improvement has been achieved, and then the dose of the corticosteroid should be tapered carefully. (iv) When surgery is indicated in pediatric patients with stricture or fistula formation and complicated by persistent growth failure despite medical therapy, the optimum time for surgery is thought to be before epiphyseal plates have been closed.     

Lingual cyst in infancy: Importance of palpation for diagnosis

Two infants, 5 and 12 weeks of age, with lingual cysts were presented. Histological findings were compatible with a salivary retention cyst in one and a thyroglossal duct cyst in the other. Both infants were admitted to our hospital because of severe stridor that had developed from one to two weeks of age. Their lingual cysts were easily recognizable by simple palpation and were confirmed by non-invasive imaging techniques, such as ultrasound sonography, computed tomography and magnetic resonance imaging. Lingual cyst in infancy may be large enough to cause stridor and dyspnea, and occasionally result in sudden infant death, although once diagnosis is made a radical operation can be easily performed. Therefore, it is important that palpation in the oral cavity should be performed with all infants with persistent stridor as a part of a physical examination.     

Decreased prostaglandin E2 synthesis by lung fibroblasts isolated from rats with bleomycin-induced lung fibrosis

In order to clarify the mechanism of pulmonary fibrosis, we examined the functional changes of lung fibroblasts in bleomycin (BLM)-induced pulmonary fibrosis. Lung fibroblastic cells were obtained from rat lungs after an intratracheal treatment of BLM or saline. The spontaneous proliferation of BLM-treated rat fibroblasts (BRF), which was estimated by 3H-TdR incorporation and direct cell counting, was significantly more rapid than that of normal saline-treated rat fibroblasts (NRF). Next, we investigated prostaglandin (PG) E2 synthesis by BRF and NRF, with or without stimulation by interleukin (IL)-1 alpha, and found that PGE2 production by BRF was significantly less than that by NRF. There was no significant difference in cyclooxygenase (COX) activity and COX-2 mRNA level between BRF and NRF, indicating that the change in PGE2 production was independent of COX, a rate-limiting enzyme for the production of PGE2. These results suggest that the proliferation of fibroblasts is down-regulated by PGE2 released from themselves in normal lungs in an autocrine fashion, thus the decreased PGE2 production observed in lung fibroblasts from rats with BLM-induced pulmonary fibrosis may result in the excessive fibroblast proliferation in this disorder. Overall, these findings throw some light on the mechanism of development of BLM-induced pulmonary fibrosis.     

Atrial Ectopy Originating from the Posteroinferior Atrium During Radiofrequency Catheter Ablation of Atrioventricular Nodal Reentrant Tachycardia

Atrial ectopy sometimes appears during RF ablation of the slow pathway in patients with atrioventricular nodal reentrant tachycardia (AVNRT). However, its origin, characteristics, and significance are still unclear. To examine these issues, we analyzed 67 consecutive patients with AVNRT (60 with slow-fast AVNRT and 7 with fast-slow AVNRT), which was successfully eliminated by RF ablation to the sites with a slow potential in 63 patients and with the earliest activations of retrograde slow pathway conduction in 4 patients. During successful RF ablation, junctional ectopy with the activation sequence showing H-A-V at the His-bundle region appeared in 52 patients (group A) and atrial ectopy with negative P waves in the inferior leads preceding the QRS and the activation sequence showing A-H-V at the His-bundle region appeared in 15 patients (group B). Atrial ectopy was associated with (10 patients) or without junctional ectopy (5 patients). Before RF ablation, retrograde slow pathway conduction induced during ventricular burst and/or extrastimulus pacing was more frequently demonstrated in group B than in group A (9/15 [60%] vs 1/52 [2%], P < 0.001). Successful ablation site in group A was distributed between the His-bundle region and coronary sinus ostium, while that in group B was confined mostly to the site anterior to the coronary sinus ostium. In group B, atrial ectopy also appeared in 21% of the unsuccessful RF ablations. In conclusion, atrial ectopy is relatively common during slow pathway ablation and observed in 8% of RF applications overall and 22% of RF applications that successfully eliminated inducible AVNRT. Atrial ectopy appears to be closely related to successful slow pathway ablation among patients with manifest retrograde slow pathway function.     

Albumin gene encoding free fatty acid and β-amyloid transporter is genetically associated with Alzheimer disease

Abstract  Alzheimer disease (AD), the major cause of dementia in the elderly, is characterized by β-amyloid deposition in senile plaques and hyperphosphorylated tau in neurofibrillary tangles. Since albumin, binding and transporting free fatty acids is also the major transporter of β-amyloid, we examined the association between the albumin ( ALB ) gene and the occurrence of late-onset AD (LOAD). We found that the allele distribution of the intron 4 microsatellite of the ALB gene showed a significant difference ( P  < 0.05) between LOAD ( n  = 285) and control group ( n  = 656). An allele with 11 CA repeat, termed (CA)₁₁ allele, was significantly predominant in the control group ( P  < 0.005), and the odds ratio carrying the (CA)₁₁ allele was 0.43 ( P  < 0.01, 95% CI = 0.24–0.79). Logistic regression indicated that this effect was independent of age and the ɛ4 dose of the apolipoprotein E gene ( P  < 0.01), while the ALB gene was supposed to be related to aging. Our results indicate that the ALB gene is genetically related with the occurrence of LOAD, supporting the link between fatty acid and β-amyloid transport in the development of LOAD.     

Varicella-zoster virus replication site in internal organs of an otherwise healthy child with varicella and sudden death

Pathological findings of an otherwise healthy 17 month old boy who was exposed to Varicella-zoster virus (VZV) in his family and unexpectedly died 3 days after onset of varicella are reported. They showed a disseminated VZV infection with involvement of skin, lung, liver, spleen, gastrointestinal tract and other organs where VZV antigen was detected by the enzyme-immunoassay with monoclonal antibodies to VZV. Since the subject was the full-term product of an uncomplicated pregnancy, who grew and developed normally, and had no symptoms or laboratory findings suggestive of immunodeficiency until his death, these findings suggest that many organs are involved as major internal sites of viral replication before or during infection of skin with VZV in the immunocompetent host.     

Demonstration of Entrainment and Presence of Slow Conduction During Ventricular Tachycardia in Arrhythmogenic Right Ventricular Dysplasia

During VT in two cases with arrhythmogenic right ventricular dysplasia, entrainment criteria, constant fusion beats except for the last entrainment beat, progressive fusion, and a localized conduction block associated with interruption of VT, were demon strated with rapid ventricular pacing performed during VT. Furthermore, a long conduction interval was present during entrainment from the pacing site to the earliest activation site during VT. indicating the presence of a slow conduction area. VT in these cases was, thus, due to reentry with an area of slow conduction within the circuit.     

Contribution of pulmonary surfactant with inhaled nitric oxide for treatment of pulmonary hypertension

BACKGROUND: Combined therapy of inhaled nitric oxide (iNO) with pulmonary surfactant replacement was reported to improve oxygenation in patients or animal models of persistent pulmonary hypertension of the newborn with pulmonary surfactant deficiency lung. To evaluate the potential of iNO for the treatment of persistent pulmonary hypertension of the newborn, pulmonary arterial pressure (PAP) was measured during iNO before and after pulmonary surfactant replacement in an animal model of pulmonary hypertension with surfactant deficiency. METHODS: Seven newborn piglets were injected with L-nitro-arginine-methylester to produce an animal model of pulmonary hypertension. After PAP increased, iNO (30 p.p.m.) was introduced. Then iNO was stopped, and animals were subjected to lung lavage with saline. After recording the effect of iNO, all animals then received exogenous pulmonary surfactant installation. After surfactant treatment, iNO was again introduced. RESULTS: Pulmonary arterial pressure and systemic arterial pressure were increased significantly by >30% after infusion of L-nitro-arginine-methylester. During iNO only PAP was reduced significantly. Respiratory system compliance decreased significantly after lung lavage, and increased significantly after pulmonary surfactant replacement with concomitant increase of PaO2. In contrast, significant reduction of PAP with iNO before and after pulmonary surfactant replacement were also observed. The reduction ratios of PAP under each condition were 75.2 +/- 7.4%, 81.3 +/- 3.1%, and 79.1 +/- 5.3%, respectively (not significant among conditions). CONCLUSION: These results suggest that iNO is still a potent pulmonary arterial vasodilator even under pulmonary surfactant deficiency in an animal model of pulmonary hypertension.