Improved Spatial Resolution for Cardiac Mapping Using Current Source Density-Based Electrode Arrays

The time of the minimum slope (i.e., the fastest negative deflection) in monopolar (MP) electrograms from normal hearts compares closely with time of phase 0 of the action potential in cells underlying the electrode, but poor rejection of far-field activity may limit the utility ofMP electrode technology in dense arrays used for the study of ventricular tachycardia and fibrillation. The purpose of this study is to evaluate more myopic discrete bipolar (BP) and nondirectional, two-dimensional current source density (CSD) based arrays for rejection of far-field potentials and precision of activation time determination. Simultaneous recordings of the CSD, MP, and multiple BP electrograms were performed on normal dog epicardium. The time of the minimum slope in MP electrograms was compared to activation times in CSD and BP derivations using: (1) peak; (2) steepest slope; (3) zero crossing of the steepest sloping segment in either direction; and (4) waveform morphology. In vivo, CSD amplitude was reduced significantly more than MP and BP amplitudes by insertion of inert media between the heart and the electrodes. The time of the steepest slope in CSD electrograms designated activation times closest to the time of the minimum slope in MP electrograms (0.9 ± 1.3 msec). We conclude that CSD provides a nondirectional electrode system that accurately defines the time of local activation and possesses better spatial specificity than MP electrode systems and BP electrode systems having the same interelectrode distances.     

The Epicardial Field Potential in Dog: Implications for Recording Site Density During Epicardial Mapping

Investigations into mechanisms and successful surgical therapy of ventricular tachycardia (VT) depend upon accurate endocardial/epicardial mapping. Deduction of local activation is based upon parameters derived from the field potentiai (FP) (monopolar recording) or its first spatial derivative (bipolar recording). Adequate electrode spacing is an assumption fundamental to the mapping process, but the electrode spacing required for accurate representation of the FP is unknown. The purpose of this work is to derive the electrode spacing necessary to accurately describe the FP on the epicardium. In 11 dogs, electrograms from vertical (V) (base to apex h) bands having 40 electrodes and horizontal (H) bands having 40 to 80 electrodes were sampled at I kHz. The spatial handwidths (BW) were computed according lo two criteria: (1) the frequency yielding 2% mean squared error (MSE) computed at the time of the greatest integrated magnitudes of the Fourier transform; and (2) the highest frequency bounding 95% power computed at each msec throughout the beat. Implied electrode spacings were defined according to the sampling theorem. The 5th percentiles of the implied electrode spacing distributions were used to define the widest interelectrode distance required to prevent spatial aliasing. H-5th percentile and V-5th percentile were, respectively; 2% MSE (3.5 mm, 2.3 mm); 95% power (3.6 mm, 2.3 mm). Thus, a typical 20-kg dog requires more than 250 recording sites for accurate epicardial mapping. Extrapolating to man, these results suggest inadequate electrode density may partially be responsible for incomplete and ambiguous reentry patterns often observed during intraoperutive mapping.     

Comparative Sensitivity of Eight- and 24-hour Bile Acid Breath Tests and Schilling Test in Ileopathies

The conventional eight-hour bile acid breath test ("acute measurements"), was compared with a modified, extended, 24-hour breath test ("ratio measurements") and the Schilling test to assess relative sensitivity in detecting ileal dysfunction. Sixty-four patients with ileopathies were studied. The presence or absence of bile acid malabsorption was documented by fecal excretion studies of bile acid labels. The sensitivity of the "acute measurements" in the breath test was not significantly different from that of the "ratio measurements" in the ileopathies, regardless of whether or not bile acid malabsorption was present. The "acute measurements" were positive in 49 (77%), the "ratio measurements" in 54 (84%) and the Schilling test in 49 (77%) of the patients. In about 30%, bile acid breath test and Schilling test were not positive in the same patient. A combination of "acute measurements" (breath test) and Schilling test increased the percentage of cases with at least one positive test to 91%. The results of the study show: 1. The sensitivity of the bile acid breath test does not increase if ¹⁴CO₂ measurements are carried out beyond eight hours. 2. Although the breath test and Schilling test are of similar sensitivity in ileopathies, they are frequently not positive in the same patient. Therefore, it would be clinically useful to combine both tests in order to increase the likelihood of diagnosing ileal dysfunction.     

Treatment Strategies for Long and Calcified Lesions

This study discusses the treatment strategies used to approach long lesions, lesions in small vessels, and calcified lesions. Traditional treatment strategies for these lesion subtypes have yielded high acute complication rates and poor long-term outcome. A prospective analysis of 160 lesions was performed using intravascular ultrasound (IVUS) guided PTCA for the treatment of long lesions and lesions in small vessels, while a retrospective analysis of 106 calcified lesions was performed that were treated with the combination of rotablation and stenting. Acute and short-term results of TVUS guided PTCA with spot stenting show a 30-day major adverse cardiac event rate (MACE) of 5% with a high procedural success rate (96%), while the long-term outcome resulted in an agiographic restenosis rate of 17.4% and a target lesion revascularization rate of 13%. The combination of rotablation and stenting also rendered results in calcified lesions of a 93% angiographic success rate and a long-term outcome of restenosis of 22.5%. Optimal coronary stenting after rotational atherectomy in calcified lesions can be performed with a high success rate, an acceptable rate of procedural complications, and a low rate of stent thrombosis. This approach was associated with a low incidence of angiographic restenosis compared with results obtained with other interventional approaches. IVUS guided PTCA with spot stenting allows safe treatment of long lesions and lesions in small vessels. Short-term and long-term outcomes including 6-month MACE and angiographic restenosis appear to be better than results achieved in historical controls that utilize balloon angioplasty alone or stents in a manner where the lesion is covered from the proximal normal segment to the distal normal segment.     

A novel homozygous mutation at the GAA gene in Mexicans with early-onset Pompe disease

Glycogen-storage disease type II, also named Pompe disease, is caused by the deficiency of the enzyme acid alpha-glucosidase, which originates lysosomal glycogen accumulation leading to progressive neuromuscular damage. Early-onset Pompe disease shows a debilitating and frequently fulminating course. To date, more than 300 mutations have been described; the majority of them are unique to each affected individual. Most early-onset phenotypes are associated with frameshift mutations leading to a truncated alpha-glucosidase protein with loss of function. Founder effects are responsible from many cases from few highprevalence world regions. Herein we described two apparently unrelated cases affected with classical early-onset Pompe disease, both pertaining to a small region from Central Mexico (the State of San Luis Potosí), the same novel homozygous frameshift mutation at gene GAA (c.1987delC) was demonstrated in both cases. This GAA gene deletion implies a change of glutamine to serine at codon 663, and a new reading frame that ends after 33 base pairs, which leads to the translation of a truncated protein. This report contributes to widen the knowledge on the effect of pathogenic mutations in Pompe disease. Here we postulate the existence of a founder effect.Key words: Early-onset Pompe disease, Acid maltase deficiency, Founder effectGlycogen storage disease type II (Online Mendelian Inheritance in Man, OMIM, accession number 232300), also called Pompe disease, was described by Johannes C. Pompe in 1932. The disorder is caused by a deficiency of the enzyme acid alpha-glucosidase (acid maltase, EC 3.2.1.20, Swiss) which originates lysosomal glycogen accumulation leading to lysosomal swelling, cellular damage and dysfunction (1-3). Affected individuals develop progressive neuromuscular damage, showing a debilitating and frequently fulminating course on the classical, early-onset type of the disease. Other main findings are hypertrophic cardiomyopathy, hypotonia, hepatomegaly, macroglossia, feeding problems and breath difficulty. Currently it is recognized that the late form of Pompe disease has a very variable phenotype that can be confused with a wide range of neuromuscular, pulmonary and cardiovascular diseases with mild, moderate or severe symptoms that present either alone or combined (4-6).Pompe disease has an autosomal recessive inheritance and it is caused by more than 300 mutations that occur all over the gene coding for acid alpha-glucosidase (GAA) located at locus 17q25.2q25.3. The molecular phenomenon responsible of the different types of clinical expression occur by the presence of two either homozygous or compound heterozygous pathogenic mutations in early-onset Pompe cases, whereas late-onset Pompe have one variant and one pathogenic mutation (7). The majority of disease-causing mutations are unique; nonetheless, relatively frequent mutations have been described in certain populations with a possible founder effect traced from the original mutated carrier to the newly occurring cases. Affected cases have been described worldwide with a few high-prevalence regions like South-Africa, Taiwan and Holland (1, 8-10).Herein, we described two unrelated cases affected with classical early-onset Pompe disease, both pertaining to the same small Mexican region, with the same novel homozygous frameshift mutation at gene GAA (c.1987delC), identified by complete gene sequencing.     

Political violence in the Third World: a public health issue

The impact of political violence on health and health servicesis substantial in many parts of the world. A variety of typesof political violence are discernible and may be broadly categorizedas structural, repressive, reactive and combative. These differenttypes of violence are described. Particular emphasis is givento a discussion of state repressive violence, including itsaetiology and magnitude. An agenda for research, policy and action is described arguingthat health personnel have a role to play in documenting theform and impact of political violence, providing treatment andcare for its victims, developing training and education packagesfor health workers who may deal with situations of violenceand advocacy work aimed at prevention.     

Individual Housing From Rearing Modifies the Performance of Young Rats on the Elevated Plus-Maze Apparatus

Previous studies from our laboratory have demonstrated that male and female rats exhibit a differential pattern of behavior in the elevated plus-maze as a function of age. In the present study, the influence of individual housing conditions on young animals treated with one of two classical anxioselective drugs, diazepam or pentylenetetrazole, was investigated in the elevated plus-maze. In Experiment 1, males and females were housed for 30 days after weaning either individually or in groups, and tested in the elevated plus-maze at 60 days of age. In Experiment 2, the effects of diazepam (0.75 or 1.0 mg/kg) or of pentylenetetrazole (20 or 30 mg/kg) on the behavior of isolated or grouped rats were studied at 60 days of age in the elevated plus-maze. The results show that isolated housed animals tested with diazepam at 60 days of age exhibited increased frequency and time spent on the open arms of the apparatus compared to control rats. The effect of diazepam was not observed in grouped animals tested at 60 days of age. Pentylenetetrazole produced a decrease in the frequency and time spent on the open arms. This effect was more prominent in grouped animals. The results suggest that 60-day-old rats deprived of playfighting experience present high basal anxiety levels and also that rearing conditions (isolated or grouped) are able to interact with both anxiolytic and anxiogenic effects of experimental drugs.