Perioperative conduction and rhythm disturbances after the Ross procedure in young patients

BACKGROUND: The Ross procedure is performed for a variety of left ventricular outflow tract diseases in children. The preoperative hemodynamic burden of pressure or volume overload and associated ventricular hypertrophy can predispose to ventricular arrhythmias. Additional procedures performed with the Ross procedure (eg, Konno) may damage the conduction system. METHODS: Between January 1995 and February 1997, the Ross procedure was performed in 42 patients, 31 (74%) of whom had 71 prior interventions. Concomitant procedures (n = 42 in 23 patients) included 17 annular-enlarging procedures. Screening was performed for perioperative conduction and rhythm abnormalities. RESULTS: There was one postoperative death. Perioperative ventricular tachycardia occurred in 12 patients (29%), with 2 receiving antiarrhythmic medication for ventricular tachycardia at discharge. Transient complete heart block occurred in 3 patients, all of whom had concomitant procedures performed in the subaortic area; all patients were discharged in sinus rhythm and no patient received a permanent pacemaker. CONCLUSIONS: The Ross procedure can be performed successfully in children with complex cardiac disease with low mortality and perioperative morbidity. The incidence of perioperative ventricular tachycardia is high (29%), suggesting the need for vigilant perioperative monitoring and long-term surveillance.     

The potential of subtype-selective neuronal nicotinic acetylcholine receptor agonists as therapeutic agents

Neuronal nicotinic acetylcholine receptors (NAChRs) are pentameric ligand-gated ion channel receptors which exist as different functional subunit combinations which apparently subserve different physiological functions as indicated by molecular biological and pharmacological techniques. It is possible to design and synthesize novel compounds that have greater selective affinities and efficacies than nicotine for different NAChRs, which should translate into different behavioral profiles and therapeutic potentials. Examples of NAChR agonists studied are nicotine, SIB-1508Y, SIB-1553A and epibatidine. These compounds have different degrees of selectivity for human recombinant NAChRs, different neurotransmitter release profiles in vitro and in vivo and differential behavioral profiles. Preclinical studies suggest that SIB-1508Y is a candidate for the treatment of the motor and cognitive deficits of Parkinson's disease, whereas SIB-1553A appears to have potential as a candidate for the treatment of Alzheimer's disease. Epibatidine has a strong analgesic profile, however the ratio between pharmacological activity and undesirable effects is so low that it is difficult to envisage the use of this compound therapeutically. Nicotine has a broad profile of pharmacological activity, for instance demonstrating activity in models for cognition and analgesia. As for epibatidine, the adverse effects of nicotine severely limits its therapeutic use in humans. The discovery of subtype-selective NAChR agonists such as SIB-1508Y and SIB-1553A provides a new class of neuropsychopharmacological agents with better therapeutic ratios than nonspecific agents such as nicotine.     

The self-reported handicapping effect of hearing disabilities

This study investigates the extent to which individuals see themselves as being handicapped by a hearing disability. Self-reports were obtained with the Amsterdam Inventory for Auditory Disability and Handicap which distinguishes five basic disabilities: intelligibility in noise, intelligibility in quiet, localization of sounds, distinction of sounds and detection of sounds. Responses of 239 hearing-impaired people with varying types of hearing loss have been examined. The occurrence of the five disabilities in the population as well as the self-reported limiting and annoying effect per disability has been examined. This study shows that the handicapping effects of the disabilities do not have equal weights. Handicap resulting from the inability to understand speech in noise is most strongly felt. This paper argues that the type of disability jointly determines the severity of a person's handicap.     

Oxygen transport through methacrylate-based hydrogels with potential biological capability

The permeability to oxygen of hydrogels prepared from copolymers of 2-hydroxymethyl methacrylate and p-methacryloxyl-oxyacetanilide have been studied by using an oxygen electrode in combination with a permeometer. The transmissibility Dk/L and the permeability Dk (where D, k and L are, respectively, the diffusion coefficient, the Henry constant and the thickness of the hydrogel) are measured by a combination of steady state and transitory state measurements. Both transport coefficients increase with the water content, which in turn depends on the copolymer composition. The values of these quantities tend toward a limiting value for water-saturated hydrogels. The ratio of the characteristic volume for diffusion of the oxygen molecule to the free volume of water per mole water is found to be in the vicinity of 0.10, and this value increases slightly as the fraction of the hydrophilic comonomer in the hydrogel increases. A detailed comparison of the biogels studied with six commercial contact lenses has also been performed.     

Specific selection of deoxycytidine kinase mutants with tritiated deoxyadenosine

We have shown previously that a low concentration of tritiated deoxyadenosine, i.e., 1 microCi/ml, selectively kills wild-type S49 murine lymphoma cells. Mutant cells resistant to [3H] deoxyadenosine lacked adenosine kinase completely but retained a significant level of deoxyadenosine phosphorylating activity. To study further the specificity of [3H] deoxyadenosine selection, lymphoma cell clones resistant to 15 microCi/ml [3H] deoxyadenosine have been derived. The resistant line, S49-dA15, is also resistant to high levels of nonradioactive deoxyadenosine and to deoxyguanosine but remains sensitive to thymidine. The thymidine inhibition of the growth of the mutant, in contrast to that of the wild-type cells, cannot be prevented by deoxycytidine. The mutant line lacks deoxycytidine kinase that also phosphorylates deoxyadenosine. In addition, the mutant cells excrete a large amount of deoxycytidine into culture medium, consistent with a failure of salvage of the nucleoside in the absence of an appropriate kinase, i.e., deoxycytidine kinase. In contrast, a deoxycytidine kinase-deficient cell line that was selected with arabinosylcytosine does not excrete deoxycytidine and contains high deoxycytidine deaminase activity. [3H] Deoxyadenosine can be used as a selective agent for specific selection of deoxycytidine kinase-negative mutants.     

Macrophages resistant to endogenously generated nitric oxide-mediated apoptosis are hypersensitive to exogenously added nitric oxide donors: dichotomous apoptotic response independent of caspase 3 and reversal by the mitogen-activated protein kinase kinase (MEK) inhibitor PD 098059

Nitric oxide (NO) induction through the inducible NO synthase has been demonstrated to cause cell death in macrophages. We demonstrate that, in macrophages that have been rendered resistant to apoptosis induced by inducible NO synthase (RES cells), exposure to exogenous NO donors results in a hypersensitive apoptosis reaction when compared with the parental RAW 264.7 cells. The apoptosis induced via exogenous NO donors was found to be caspase 3-independent. Although caspase 3 activity was stimulated in the apoptotic macrophages, inhibition of caspase 3 by the inhibitor DEVD-CHO (N-acetyl-Asp-Glu-Val-Asp-aldehyde) did not reverse the apoptosis induced by the NO donor S-nitrosoglutathione (GSNO). This suggests that although caspase 3 activity is stimulated during apoptosis in macrophages, this signal is not sufficient to induce apoptosis. Cleavage of the enzyme poly(ADP ribose) polymerase mirrors our results of the caspase activity. Interestingly, we show that exogenous NO donation results in an accumulation of cells at the G2/M-phase border. Here, we demonstrate that the mitogen activated protein kinase kinase (MEK) inhibitor PD 098059 can be used to reverse the G2/M-phase block and show that this treatment also inhibits the observed apoptosis in RES macrophages. Treatment with the MEK inhibitor also reversed both the caspase 3 activity and poly(ADP ribose) polymerase cleavage in cells treated with GSNO. This result indicates that the mitogen-activated protein kinase pathway may be involved in regulation of the caspase cascade. Alternatively, it may suggest an activity for the MEK inhibitor heretofore not observed, that of a cyclin kinase inhibitor. Our results suggest that selection of macrophages by resistance to endogenously generated NO may cause hypersensitivity to exogenous NO donors. These findings have relevant implications for the treatment of apoptotic-resistant cell populations that may occur in both cancer and atheroma.     

Nasopharyngeal Castleman's disease

A 19-year-old male was admitted to our clinic because of nasal obstruction and intermittent postnasal drip of 3 to 4 years' duration. Physical examination revealed a wide-based, smooth-surfaced nasopharyngeal tumor which was suspected to be a nasopharyngeal angiofibroma after examination of computed tomographic scans and an angiogram. However, after the tumor was removed by surgical excision via a transpalatal approach, the pathologic examination revealed Castleman's disease of the hyaline-vascular type. There was neither evidence of recurrence nor nasal problems at 4 years' follow-up. To our knowledge, Castleman's disease, or angiofollicular lymph node hyperplasia, may present as a local or generalized tumor-like condition, usually in the chest or abdomen, and may involve both the lymph nodes and non-nodal tissues. A review of previous articles reveals that there has not been any report of Castleman's disease found in the nasopharynx. This rare disorder is presented and discussed.