The Architecture of the Atrial Musculature Between the Orifice of the Inferior Caval Vein and the Tricuspid Valve: The Anatomy of the Isthmus

Anatomy of Electrophysiologic Isthmus. Introduction : Electrophysiologists recognize a so-called "isthmus" in the right atrium through which passes the reentrant circuit of common atrial flutter. Ablative lesions placed in this narrow channel have proved effective in breaking the circuit. To the best of our knowledge, however, no study has been performed to establish the arrangement and orientation of the atrial myocardial fibers in this crucial area.
Methods and Results : We examined 28 normal heart specimens, identifying a quadrilateral area composed of three morphologic sectors between the inferior caval vein and the tricuspid valve confluent superiorly with the triangle of Koch. Within this quadrilateral, there are constant recesses, or sinuses, inferior and lateral to the orifice of the coronary sinus. The inferior isthmus measured an average of 31 ± 4 mm (range 19 to 40). Gross examination identified marked differences in the atrial wall forming the quadrilateral. A smooth anterior component forming the vestibule of the tricuspid valve was found in all the hearts, but variations in the remaining sectors were seen in ten specimens. The usually membranous posterior sector was noticeably muscular in three specimens, while the middle, trabecular sector was more membranous in five specimens. We demonstrated the orientation of the subendocardial atrial fibers by dissection in 14 specimens, revealing a relatively constant overall pattern in eight specimens and variations in fiber orientation in the remaining specimens.
Conclusion : There are considerable anatomic variations in the atrial wall that comprises the so-called isthmus. The presence of recesses and membranous areas in some hearts and the variations in arrangement of the subendocardial fibers are relevant in improving understanding of conduction in this area.     

Non-pharmacologic treatment strategies in gastroesophageal reflux disease

Abstract   In the West, gastroesophageal reflux disease (GERD) is a common and well-recognized disease. Lately, it has been described as an emerging problem in the East as well. While it is not a rapidly fatal illness, it causes a myriad of disturbing symptoms that remarkably reduce the patients' quality of life (QOL). The economic impact that results from multiple consultations, diagnostic investigations, and administration of a variety of treatment regimens, including surgery, is enormous.
The operative management for GERD is fundoplication, for example Toupet (270 degree wrap of the distal esophagus) and Nissen (360 degree wrap of the distal esophagus). These surgical procedures are aimed at permanently controlling acid reflux by reconstructing the gastroesophageal junction. Currently, the ease, aesthetic advantages, and the comparable outcomes achieved by minimally invasive laparoscopic fundoplication have rekindled interest in the operative alternatives of GERD management. Fundoplication controls or diminishes considerably the severity of the symptoms associated with GERD. However, appearance of new symptoms i.e. dysphagia, 'gas–bloat syndrome', etc. as postoperative events have been reported.
Recently, several innovative endoluminal treatment modalities have been introduced, namely; endoscopic plicator/suturing devices, bulking injections, and radiofrequency treatment. They are focused on enhancing the performance of a malfunctioning lower esophageal sphincter. While results of several case series reflect substantial improvements in GERD-HRQL scores, lack of long-term durability data is a major concern when recommending these novel, relatively simple, peroral techniques to a long suffering patient. It is clear that these therapies are still evolving and long-term outcomes of properly designed comparative efficacy trials are awaited.     

Renal handling of indomethacin and its relationship with the secretory pathway of prostaglandins

The uptake of prostaglandin E₂, one of the main renal prostaglandins and of p-aminohippurate, an indicator of the anion organic transport, by slices of kidney cortex from adult female rats was studied in the presence and in the absence of indomethacin. The drug's inhibitory effect on the uptake of prostaglandin E₂ was observed both after in vivo administration as well as when it was present in the bathing media. The effect was more pronounced when the drug was given in vivo and in addition, was present in the bath. [¹⁴C]PAH uptake was inhibited by indomethacin in a dose-related pattern and the kinetic analysis of this effect is indicative of a competitive inhibition. As expected, uptake of PAH by medullary slices was not affected by the presence of either indomethacin of PGE₂. Indomethacin was more potent in inhibiting PGE₂ uptake than PAH uptake.     

Reproductive Toxicology of Aluminum in Male Mice

The reproductive toxicology of aluminum was studied in mice.Adult male mice were treated intraperitoneally with aluminumnitrate at doses of 0, 50, 100, and 200 mg/kg/day for 4 weeksbefore mating with untreated females. Decreased body weightwas seen in all aluminum-treated groups. Decreased pregnancyrate was observed in the females mated with males previouslytreated with 100 or 200 mg/kg/day of aluminum nitrate. High-dosemale mice showed significantly decreased testicular and epididymalweights, as well as significant decreases in testicular andspermatid counts and epididymal sperm counts. Spermatid countswere also reduced at 100 mg/kg/day. However, the sperm motilitywas unaffected, and the percentages of morphological normalspermatozoa in all mice exposed to aluminum were comparableto the values in control mice. Histological changes, includingnecrosis of spermatocytes/spermatids, were observed in the testesof male mice treated with 100 and 200 mg/kg/day of aluminumnitrate, whereas the tubu lar diameters were unaffected by aluminumadministration. The current study demonstrates adverse effectsof parenteral aluminum exposure on the mouse male reproductivesystem. The "no observable adverse effect level" (NOAEL) was50 mg/kg/day.     

A type‐specific study of human papillomavirus prevalence in cervicovaginal samples in three different Spanish regions

Human papillomavirus (HPV) is the most frequent sexually transmitted viral infection. It is necessary to know HPV genotype distribution to identify how many women will be protected by HPV vaccines. During a period of 18 months, we have analyzed 2362 HPV positive reporting data from a secondary demand screening program in three regions in Spain (Cantabria, Leon and Burgos). The study has been conducted using polymerase chain reaction and tube array hybridization covering the 35 HPV genotypes described as affecting anogenital mucosa. There were no significant differences between the three regions according to genotype distribution. The most frequent were HPV16 (19.18%), HPV53 (11.26%) and HPV58 (7.66%). HPV18 was the source of 4.02% of infections. High‐risk HPVs were found in 1863/2362 cases. HPV16 was present in 24.3% of high‐risk infections and HPV18 was found in 5.1%. Uncommon genotypes (<5% of the total prevalence each) were found in 17,9% of the total high‐risk infections (334/1863). Multiple infections were diagnosed in 22% of the cases. The HPV genotype distribution is different from previously published data when multiple types are included in the screening. Both HPV16/18 account for 30% of high‐risk infections in a clinical setting in Spain. The presence of multiple genotypes is very common among the population.     

The effect of maternal work on fetal growth and duration of pregnancy: a prospective study

Summary. The effect on birth outcome of work requiring different degrees of physical exertion was examined among 15 786 pregnant women who were followed through the Guatemalan Social Security Institute's hospital. Work inside and outside the home was ascertained through a questionnaire administered to each woman before delivery. Odds ratios were adjusted for household income, maternal height and age, and birthweight of previous infant. Women with three or more children and no household help were at increased risk for small-for-gestational-age (SGA) births compared with women with family (odds ratio (OR) 1.79; 95% confidence interval (CI) 1.31, 2.47) or hired help (OR 2.0; 95% CI 1-16 to 3-33). Compared with office work, manual work increased the risk for an SGA (OR 1.32 95% CI 1.12 to 1.56) and SGA/preterm birth (OR 2.56; 95% CI 1.10 to 5.96). Work in a standing compared with sitting position significantly increased the risk for a preterm birth (OR l.56; 95% CI l.04 to 2.60). There was a significant positive trend in frequency of SGA and SGA/preterm birth with an increase in the physical demands at work, as measured by an activity score. These data suggest that interventions to reduce physical exertion among pregnant women could improve birth outcome.     

THE EFFICACY OF INTRAVESICAL BACILLUS CALMETTE-GUERIN IN THE TREATMENT OF INTERSTITIAL CYSTITIS: LONG-TERM FOLLOWUP

Purpose

Interstitial cystitis is a severe debilitating bladder disease characterized by unrelenting pelvic pain and urinary frequency. A prospective, double-blind, placebo controlled study of the use of intravesical bacillus Calmette-Guerin (BCG) in the treatment of interstitial cystitis was recently completed with a mean followup of 8 months. Results demonstrated a 60% BCG response rate, compared to a 27% placebo response rate. We now report the long-term followup results of those patients who received intravesical BCG.

Materials and Methods

Subjects randomized to receive BCG were followed at routine intervals with questionnaires and voiding diaries identical to those in the blinded study. Adverse events were closely monitored in the treatment and followup phases of the study. Subject baseline values were compared to followup data.

Results

Of the BCG responders mean followup was 27 months (range 24 to 33), and 8 of 9 (89%) continue to have an excellent response in all parameters measured. The global interstitial cystitis survey improved 70%, daily voids decreased 31%, nocturia improved 54%, mean voided volume increased 61%, pelvic pain decreased 81%, vaginal pain decreased 71%, urgency decreased 71% and dysuria decreased 82%. Overall well-being improved 54% and the Rand-36 quality of life survey overall improved 64%. In 86% of the patients (6 of 7) dyspareunia resolved. Of the initial BCG nonresponders there was no significant difference in interstitial cystitis symptomatology from baseline to last followup, suggesting that BCG does not worsen interstitial cystitis symptoms. No long-term adverse events from BCG were noted.

Conclusions

Intravesical Tice^* BCG is safe, effective and durable in the treatment of interstitial cystitis. Of those patients who received only 6 weekly treatments and responded favorably 89% continue to have an excellent response with followup ranging from 24 to 33 months.     

INFLUENCE OF REGULAR ALCOHOL CONSUMPTION ON URICAEMIA IN UNSELECTED HEALTHY INDIVIDUALS

We analysed serum uric acid concentrations in a group of healthymale and female volunteers in Córdoba (Spain) possessingvarying nutritional habits, in order to correlate them withtheir usual alcohol intake as measured according to a protocolized,blind dietary questionnaire. There was no significant correlationbetween the serum uric acid and the amount of alcohol regularlydrunk by either male or female individuals. These results suggestthat a moderate alcohol intake has no effect on uricaemia inhealthy individuals.     

INVERSE EXPRESSION OF mdr 1 AND c-myc GENES IN A RHABDOMYOSARCOMA CELL LINE RESISTANT TO ACTINOMYCIN D

Cytotoxic agents used in cancer therapy may induce differentiation in tumour cells with no proliferative potential. However, chemotherapy can also induce multidrug resistance, a formidable obstacle to the successful treatment of tumours. Both events were recently shown to occur in a rhabdomyosarcoma cell line (RD-DAC) resistant to actinomycin D, a drug of choice in the treatment of these tumours. To analyse this connection, cell line RD cultures were investigated with progressive concentrations of actinomycin D and it was shown that a minimum dose (1·2×10⁻⁶ mm) of the drug was necessary to increase mdr 1 mRNA in RD-DAC. The mechanism of mdr 1 overexpression was an increase in the number of copies of the mdr 1 gene, although the mRNA levels were not correlated with mdr 1 amplification. Drug resistance mediated by mdr 1 overexpression coincided with the development of myogenic differentiation in RD-DAC and with a decrease in c- myc mRNA levels, whereas levels of N- myc mRNA showed no modulation. These findings suggest that factors implicated in cell proliferation and differentiation, such as c- myc , may be responsible for the control of genes related to the development of multidrug resistance in rhabdomyosarcomas. Modulation of these factors may determine the sensitivity of rhabdomyosarcoma cells to drugs and may play an important role in triggering the differentiation programme found in these resistant rhabdomyosarcoma cells.