Successful use of sirolimus for refractory atrial ectopic tachycardia in a child with cardiac rhabdomyoma

Cardiac rhabdomyomas are common in tuberous sclerosis. We report a child who developed rhabdomyoma related arrhythmia refractory to antiarrhythmic drug therapy. Reversion of the atrial ectopic tachycardia was achieved with mammalian target of rapamycin pathway (mTOR) inhibitor sirolimus. As per our knowledge, this is the first time that sirolimus has been successfully used in this setting.     

IgG4 Related Cardiac Disease

IgG4-related systemic disease is an inflammatory disorder that can affect many organs. This case report describes a patient who in 2004 was found to have an inflammatory pseudotumor with IgG4 pathology. Over the next 3 years, visual symptoms responded well to recurrent courses of prednisone. In 2009, the patient developed chest pain and bradycardia with subsequent third-degree heart block, necessitating placement of a pacemaker. A subsequent PET scan showed extensive involvement of multiple organs as described in IgG4 disease as well as involvement of the myocardium and SA node. Pseudotumors involving the heart have been reported but have not been shown to be related to IgG4 disease. Although there was no pathology confirmation of heart involvement, the nature and extent of the organ involvement led us to conclude that it was due to IgG4-related disease. The use of the PET scan may help identify involvement of the myocardium.     

Inhibition of influenza A virus replication by short double-stranded oligodeoxynucleotides

Influenza A virus causes prevalent respiratory tract infections in humans. Small interfering RNA (siRNA) and antisense oligonucleotides (asODNs) have been used previously for silencing the RNA genome of influenza virus. Here, we explored the use of partially double-stranded oligodeoxynucleotides (dsODNs) to suppress the production of influenza A virus in cell cultures and animal models. We were able to inhibit influenza A virus replication in cultured human lung cells as well as in the lungs of infected C57BL/6 mice by treatment with dsODN 3-h post-infection. In about 20% of the cases (15/77) the titer was reduced by 10- to 100-fold and in 10% up to 1,000-fold. The antiviral effects of dsODNs were dose-dependent, sequence-dependent and comparable to those of its antisense and siRNA analogues. Thus, dsODNs may be developed as an additional class of nucleic acids for the inhibition of influenza virus replication.     

Partial Left Ventriculectomy and Limited Heart Transplantation Availability

BACKGROUND AND AIM: Partial left ventriculectomy, a novel cardiac volume reduction operation, is applied in countries without a developed heart transplantation program. We sought to determine its impact in our population of patients. METHODS: Partial left ventriculectomy was performed in 38 patients during the last 4 years. Basic inclusion criteria were nonischemic dilated cardiomyopathy and poor response to medical therapy for heart failure. Hemodynamic evaluation was carried out before and after operation. A modified surgical technique of mitral valve repair and ventricle suturing was applied. RESULTS: Thirty-day, 6-month, and 2-year survival rates were 82% +/- 7%, 65% +/- 8%, and 61% +/- 9%, respectively. Duration of heart failure symptoms was the only predictor of survival (p = 0.042). A high proportion of noncardiac causes of death was noted. Functional capacity in surviving patients improved at every successive measurement up to 1 year postoperatively. CONCLUSIONS: The introduction of partial left ventriculectomy in a country with limited heart transplantation availability had a great impact on the management of end-stage heart failure and may represent the only surgical option for some patients. The average cost per patient was substantially lower when compared to heart transplantation.     

Epilenticular intraocular lens implantation in traumatic cataract with a ruptured posterior capsule

PURPOSE: To present a case of rapidly progressing traumatic cataract caused by posterior capsule rupture after nonpenetrating ocular injury, as well as a surgical procedure to safely implant the intraocular lens in such a traumatized eye. METHODS: In a 23-year-old man with traumatic cataract and posterior lens capsule rupture, a one-piece polymethylmethacrylate IOL was implanted before cataract extraction into the ciliary sulcus in front of the cataractous lens. Subsequently, the cataract was removed by pars plana lensectomy. RESULTS: The surgery and postoperative course were uneventful. Postoperative visual acuity was 20/20. CONCLUSION: We present a method of intraocular lens implantation in cases of rapidly progressing traumatic cataract caused by posterior capsule rupture after a blunt ocular trauma.     

Successful surgical reconstruction of ruptured renal pelvis following blunt abdominal trauma

A 25-year-old man with occult ureteropelvic obstruction presented with abdominal pain 3 h following blunt abdominal trauma. Isolated rupture of the right renal pelvis was promptly diagnosed and the patient underwent immediate pyeloplasty according to the Anderson-Hynes procedure. The patient made an uneventful recovery. One year after surgery, renal function was satisfactory.     

Myotonic dystrophy and cardiac disorders

Myotonic dystrophy (MD) is a multisystem disease affecting numerous organs and systems. Cardiac involvement is frequent. Sudden death, due to fatal cardiac rhythm and conduction disturbances occurs in 30% of patients with MD. The aim of this study was to assess the possibilities and methods of early detection of myocardial and conduction system disturbances. ECG, 24-hr Holter monitoring, echocardiography and electrophysiologic studies of the conduction system (electrophysiologic study) were carried out in 45 patients. Analysis of late ventricular potentials was done in 36 patients. Genetic studies revealed multiplication of CTG triplets in all patients. Cardiological abnormalities were detected in 89% of our patients. Disturbances of intraventricular conduction with prolongation of HV interval were most frequent (72%). Electrophysiologic study was the most sensitive method for detecting heart involvement in MD (positive findings in 87% patients). Abnormal findings were also discovered by Holter monitoring (64%), ECG (58%), analysis of late ventricular potentials (55%) and by echocardiography in 46% patients. The results of this study indicate a high rate of cardiac involvement in MD.     

Retroviral gene transfer of dominant negative raf-1 mutants suppresses ha-ras-induced transformation and delays tumor formation

Activating mutants of ras are among the most frequently found genetic alterations in human cancers. Therefore, Ras appears to be an attractive target for therapeutic intervention using gene transfer. The protein kinase Raf-1 acts as a direct downstream effector of Ras and is involved in Ras-induced cellular transformation. Using the NIH3T3 fibroblast-derived tumor cell line PEJ, which expresses oncogenic Ha-rasG12V, we analyzed whether dominant negative mutants of Raf-1 can inhibit Ras-mediated transformation. Retroviral gene transfer was used to stably transduce PEJ cells with three different dominant negative mutants of Raf-1. This resulted in reversion of the transformed phenotype in vitro as evidenced by an increase in contact inhibition and reduced anchorage-independent growth. However, tumor formation in nude mice was significantly delayed only by one of these mutants. Therefore, dominant negative mutants of the oncoprotein Myc, which is known to synergize with Raf-1 in tumor formation, were transduced into PEJ cells expressing a dominant negative Raf mutant. This leads to killing of the cells. These results indicate that although interference with Ras-induced transformation using dominant negative mutants of Raf is feasible and effective in vitro using retroviral vectors, an additional block (e.g., that of Myc) is necessary to kill PEJ cells. These results also indicate that interference with Ras-dependent signaling is not sufficient for inhibition of tumor formation of PEJ cells in vivo.     

Induction of long-lasting cytokine effect by injection of IL-12 encoding plasmid DNA

We have recently demonstrated that DNA coding for both subunits of the murine IL-12 heterodimer exhibits a strong antimetastatic effect against B16-melanoma in C57BL/6 mice and after intratumoral injection tumor regression. Here we show that the antimetastatic effect can be detected when the DNA is injected intramuscularly 30 days before tumor cell challenge. A long-term IL-12 expression was measured for up to 50 days in the serum with a peak at day 20 amounting to about 10 ng/mL in C57BL/6 mice. CpG oligodeoxynucleotides also induce IL-12 expression, however, only for a few hours. IL-12 DNA administration induces long-lasting systemic IFN -gamma production, whereas IL-4 and TNF-alpha levels remained undetectable. NK cell-depleted mice showed a strong but reduced expression of murine IL-12. Expression of DNA encoding human instead of murine IL-12 resulted in a significantly lower and transient expression, indicating that not plasmid-derived IL-12 production alone but the immune system of the host contributes to the long- lasting antimetastatic effect. It may be attributable to an autocrine feedback mechanism maintaining murine IL- 12 expression, whereby several cell populations including NK cells are involved.