Antagonistic properties of the suramin analogue NF023 at heterologously expressed P2X receptors

The suramin analogue 8,8'-(carbonylbis(imino-3,1-phenylene carbonylimino)bis(1,3,5-naphthalenetrisulfonic acid) (NF023) antagonizes in a competitive fashion P2X receptor-mediated responses in certain vascular and visceral smooth muscles. In the present study, the effect of NF023 on voltage-clamped Xenopus oocytes heterologously expressing homomultimeric P2X1-P2X4 as well as heteromultimeric P2X2/P2X3 receptors has been characterized. P2X1 receptors were most sensitive to inhibition by NF023 with IC50 values of 0.24 and 0.21 microM for the rat and human homologue, respectively. P2X3 receptors have an intermediate sensitivity with IC50 values of 8.5 and 28.9 microM for rat and human subtypes, respectively and P2X2 was the least sensitive subtype (IC50 > 50 microM). P2X4 receptors were insensitive to NF023 at concentrations up to 100 microM. Coexpression of rat P2X3 with rat P2X2 resulted in receptors whose sensitivity to NF023 was identical to that obtained for homomultimeric rat P2X3 receptors (alphabeta meATP as agonist; IC50 = 1.4 and 1.6 microM, respectively). NF023 inhibited P2X1 receptors in a voltage-insensitive manner. In addition, NF023 (5 and 30 microM) caused a shift of the concentration-response curve to the right without affecting the maximal response to ATP (K(B) = 1.1 +/- 0.2 microM). Our results indicate that NF023 is a subtype-selective and surmountable antagonist at P2X1 receptors heterologously expressed in Xenopus oocytes.     

How often is extracorporeal membrane oxygenation needed in cases of congenital diaphragmatic hernia?

Some newborns with congenital diaphragmatic hernia (CDH) and severe pulmonary hypertension cannot be saved by conventional treatment and may obtain some benefit from extracorporeal membrane oxygenation (ECMO) as a bridging measure until adequate hematosis is possible. Early prediction of the insufficiency of optimal assistance is still unclear; we reviewed our recent experience with CDH patients in an attempt to evaluate the real need for ECMO in our institution. Between 1987 and 1994, 47 newborns with CDH manifested in the first 24 h were treated with maximal ventilatory assistance (including high-frequency ventilation in 12 cases) and vasoactive drugs prior to surgical repair. In order to summarize the ventilatory and blood-gas parameters, we determined oxygenation index (OI) and ventilatory index (VI) and compared the results in survivors and nonsurvivors. Overall survival was 60% (2 cases of Fryns' syndrome were excluded from analysis). OI was 10.3±5.7 (mean ± SD) for survivors and 46.2 ± 37.8 for nonsurvivors (P < 0.01). VI was 460.9±303 and 1,532±500.6, respectively (P <0.01). Bayesian analysis and receiver operating characteristic curves enabled us to select a threshold value of OI of 20 as the best means of predicting survival in our current conditions (sensitivity: 0.7, specificity: 0.83). The generally accepted figure of 40 had a sensitivity of 1 but a specificity of only 0.44. For VI, the best threshold value was 1,100 (sensitivity: 0.93, specificity: 0.94), whereas the generally used figure of 1,000 had 0.89 and 1, respectively. According to our results, with our current management conditions, approximately 50% of our CDH patients might have obtained some benefit from ECMO.     

The evolution of breast cancer mortality and morbidity in Spain (1977–1988)

A study of breast cancer mortality and cancer morbidity has been carried out in Spain recently for the period 1977–1988, covering the population of the 17 Autonomous Communities and 50 provinces of the country. Data was obtained from INE, Instituto Nacional de Estadistica (National Institute of Statistics), with age standardization using the indirect method. The different Autonomous Communities and provinces were compared in order to establish possible significant differences. The crude mean mortality rate was 21 cases per 100,000 inhabitants/year; Las Palmas, Gerona, Barcelona, the Balearic Islands, Navarra and Zaragoza have the highest mortality rates, with a proportional increment of 54% in that period. The crude national mean morbidity rate for the considered period was 64.0 cases per 100,000 inhabitants, and the proportional increment 180%. According to provincial figures, Alava had the highest fitted mean morbidity rate, 135 cases per 100,000 inhabitants, whilst the highest fitted mean rate was Las Palmas (28 cases/100,000 inhabitants), and the highest proportional increment was the rate for the province of Huesca (169%). When using the ANOVA test on the mean rate of the period, for mortality as well as morbidity, we observed significant differences among provinces and among Autonomous Communities (p 0.05).     

Dynamic assessment of pelvic floor function in women using the intravaginal device test

The aim of the study was to assess pelvic floor function and dysfunction using intravaginal devices (IVD test). One hundred and eighty-five patients were evaluated, 65 (35.1%) in the control group without genital prolapse and 120 (64.9%) in the study group, with prolapse. Anatomic changes were evaluated on a scale described by Halban, and functional classification based on palpation of the muscles of the pelvic floor during contraction. Additionally, weighted vaginal devices were used to assess pelvic floor function. Statistic analysis was performed with the Spearman-Pearson correlation coefficient, the ² test and the response/ operator characteristic curve. There was an acceptable correlation between the IVD test and the functional classification of 0.75. Using this classification, the IVD test showed 86.58% sensitivity, 75.72% specificity, and had a positive predictive value 73.95% and a negative predictive value of 87.64%. Significant differences between pelvic floor muscle activity in those patients with and without genital prolapse were observed (X²=58.28, P=<0.005). It was concluded that pelvic floor assessment can be done through the evaluation of active muscle strength or pelvic floor integrity using the functional classification and the IVD test.EDITORIAL COMMENT: In 1988, Peattie and Plevnick introduced the use of weighted vaginal cones to exercise the pelvic floor muscles and treat stress urinary incontinence [1]. Contreras-Ortiz and Nuñez build on this earlier work, using a similar technique to assess pelvic floor muscle function and integrity. Specifically, pelvic floor function is assessed by a combination of digital palpation of the pubococcygeus muscle at rest and during contraction; pelvic floor integrity is assessed by the patient's ability to retain a weighted cone vaginally for 1 minute. Scoring of these two parameters can then be objectively followed for therapeutic response to treatment for urinary incontinence or pelvic relaxation. Many of us forget to palpate the pubococcygeus muscle at rest and during an elicited contraction during baseline or follow-up examination. As this study indicates, simple assessment of pelvic floor function and integrity is possible, and should be used both clinically and in research.     

Tissue-level biomarkers and biological effect of mercury on sentinel slugs, Arion ater

The present investigation was to determine the extent to which mercury (Hg) provokes measurable effects on the structure of the digestive gland of slugs as well as to relate the extent of these effects to the cell and tissue distribution of Hg. For this purpose, slugs (Arion ater) received various dietary concentrations of Hg (from 0 to 1,000 g Hg/g food) as chloride for 30 days and were histologically examined every third day. Autometallography was used to demonstrate Hg as black silver deposits (BSD) in paraffin sections. The lysosomes and residual bodies of digestive cells resulted to be the major accumulation sites. In addition, Hg was also evidenced in lipofuscine granules of vacuoles in excretory cells but, however, it was rarely observed within calcium cells. Generally, the extent of BSD increased with dietary Hg concentration and exposure time but, however, it became significant lowered after exposure to 1,000 g Hg/g food for 30 when the digestive epithelium appeared almost devoid of digestive cells. On the other hand, significant changes were recorded in the quantitative structure of digestive tubules. Mean Epithelial Thickness (MET), Mean Luminal Radius (MLR) and Mean Diverticular Radius (MDR) were recorded as measures of the sublethal biological effect of Hg. MET, MLR/MET and MET/MDR were affected by Hg concentration (C), exposure time (T) and CxT interaction, changes in MET, MLR, MLR/MET and MET/MDR being explained by regression models after logarithmic transformation of the data. In order to explain the nature of the changes in the quantitative structure of the digestive tubules this investigation was complemented with qualitative histological observations. According to them, the excretory activity in digestive cells was initially enhanced. Afterwards, the relative numbers of digestive cells declined until the extreme cases of exposure to 1,000 g Hg/g for 27 to 30 days in which the digestive epithelium was mostly comprised of calcium and excretory cells. Concomitantly, some changes took place in blood vessels where Leydig cells became disrupted and the connective tissue layers thickened. Finally, it is suggested to use slugs in soil quality assessment as sentinel organisms (Slug Watch) in which biomarkers of exposure to metallic pollutants and of biological effect are recorded.     

The septal arteries in the differential diagnosis of constrictive pericarditis

Angiographic study of the motion of the septal and left marginal arteries was performed in patients with restriction in ventricular diastolic filling in order to separate patients with constrictive pericarditis from those with restrictive cardiomyopathy. Twelve patients with constrictive pericarditis (group I) and 10 patients with restrictive cardiomyopathy (group II) were evaluated and compared with 21 patients with normal coronary angiograms (group III). The displacement of the septal arteries (23 +/- 2.04 mm) was abnormally exaggerated in group I and normal (9 +/- 0.81 mm) in groups II and III. The displacement of the left marginal arteries as seen by the "corrugating index" was similar in all groups. We conclude that study of the displacement of the septal arteries is a useful angiographic sign that helps to separate constrictive pericarditis from restrictive cardiomyopathy and normals.     

Chagasic heart disease in Mexico. 1st case diagnosed by positive xenodiagnosis

We describe the first case of chronic Chagas heart disease in México, in whom the illness was corroborated by means of the "xenodiagnosis". The patient had changing bundle branch block and also A-V block that required insertion of a pacemaker. This disease is seldom seen in Mexico.     

Computerized axial tomography for the diagnosis of cerebral cysticercosis

Summary Computerized Axial Tomography (CAT) has proved extremely useful for the diagnosis of cerebral cysticercosis. The calcified small, multiple, and scattered cysts provide a typical image on CAT.The collection of non-calcified cysts in the subarachnoid spaces (racemose form) or in the ventricles may produce areas of low density similar to that of the cerebrospinal fluid. The dilatation of the ventricular system, extreme degrees of hydrocephalus, areas of cerebral atrophy, and other related changes induced by the cysts in the subarachnoid spaces are also clearly shown in the CAT. Four personal cases are reported.     

Physiological responses to high radiant heat exposure

The physiological responses to four levels of radiant heat (R) in combination with two work loads and three ambient humidity levels were studied on seven clothed young men. The globe temperature (t_g) ranged from 40 to 74°C; metabolic work load (M) was either 20 or 50% of maximal aerobic capacity (V?₀₂ max); ambient vapor pressure was either 13 or 23 mm Hg; and dry-bulb temperature (t_db) was 38 or 49°C. The criteria for heat strain were the changes in rectal temperature (T_re), mean skin temperature (T_sk), heart rate (HR), and sweating (Sw). Stress was defined by the calculated heat load requiring dissipation (M + R + C = E_req), the ambient evaporative capacity (E_max), and the skin wettedness (w), defined as the ratio of E_req/E_max. The progressive increase in R resulted in a concomitant rise of T_re and HR reflecting the physiological strain. Similarly the increase in either M or in the humidity resulted in higher T_re and HR. The changes in R or E_max were best defined by the w, thus w and the physiological responses were highly correlated. For practical application a multiple regression of the increments of HR(ΔHR) on t_db above neutral (25°C) and on t_g above t_db was derived as follows:

$\text{△HR}{}_{\mathrm{<mtext>bpm</mtext>}}\text{= 0.96(t}{}_{\mathrm{<mtext>db</mtext>}}\text{? 25°}\text{C}\text{) + 0.81(t}{}_{\mathrm{g}}\text{? t}{}_{\mathrm{db}}\text{) ? 1}$

It was concluded that the calculated skin wettedness is most suitable in the evaluation of heat stress.     

Preoperative prediction from cineangiograms of postrepair right ventricular pressure in tetralogy of Fallot.

To aid preoperative decision-making, we have related the ratio of postrepair peak pressure in the right and left ventricles (PRV/LV) to preoperative cineangiographic measurements in a retrospective study of 135 patients undergoing complete repair of tetralogy of Fallot or tetralogy of Fallot with pulmonary atresia. Postrepair PRV/LV was related to the preoperative diameter of right (DRPA) and left (DLPA) pulmonary arteries normalized to the descending thoracic aorta (DescThAo) in patients undergoing repair with transannular patching or a valved external conduit by the dquation: PRV/LV = 0.4840/(DRPA/DescThAO + DLPA/DesThAo) + 0.2007. Stenosis of the right pulmonary artery orifice and pulmonary artery arborization abnormalities incrementally increased postrepair PRV/LV. When a transannular patch was not used in classical tetralogy of Fallot, an increment of postrepair PRV/LV usually resulted, depending upon the size of the "anulus" measured intraoperatively: Incremental PRV/LV = 0.09437 . exp(-0.6344 . Z) where Z is a normalized expression in circumference terms of the diameter of the pulmonary arterial outflow tract (DPAOT) measured intraoperatively after infundibular dissection and valvotomy. DPAOT is itself related to the cineangiographically measured pulmonary valve anulus diameter (DPVA): DPAOT = 3.357 . DPVA0.5789 . BSA0.1551. In toto, these relations allow postrepair PRV/LV without transannular patching to be estimated from preoperative cineangiographic measurements. This allows preoperative predictiom in classical tetralogy of Fallot of the need for transannular patching, and in infants this can determine the choice between primary one-stage repair and two-stage repair. Prediction of postrepair PRV/LV when transannular patching or an external conduit is planned allows identification of patients in whom right and left pulmonary arteries are too small for safe complete repair, and in them an initial palliative operation should be done to enlarge the arteries.