Correlation between mortality trends of ischaemic cardiopathy and some nutritional factors in Spain 1968–1986

After describing the evolution of mortality from ischaemic cardiopathy (IC) in Spain from 1951 to 1986, which is tending to stabilize in some age groups, and from cerebrovascular accidents (CVA), which is clearly declining, an attempt is made to relate these developments to the prevalence of the main risk factors (hypertension, cholesterol, tobacco) associated with IC and CVA. Certain advances, though of a limited number, have been made in recent years in the control of arterial hypertension in Spain, although campaigns on a national scale as in other countries have not been carried out. Regarding alimentary factors, there is an obvious increase in the consumption of food rich in proteins and animal fats, abandoning to a great extent the traditional Mediterranean diet, with health care action being limited to the improvement of nutrition education of the public. Furthermore, the consumption of tobacco has been increasing in Spain during the study period in spite of health legislation in force in recent years.It is therefore deduced that there is no obvious relationship between mortality due to IC and CVA and the prevalence of the main risk factors associated with these diseases, especially when taking into account that preventive actions on a public health level have been very limited.Corresponding author.     

Influence of incubation time/temperature on acrosome reaction/sperm penetration assay.

The acrosomal status of human spermatozoa was studied in relation to the score of the sperm penetration assay (SPA) at low-temperature (4 degrees C) incubation for induction and synchronization of the acrosome reaction (AR) and the incubation time of spermatozoa in conventional SPA. Spermatozoa were collected from 18 patients, selected by the "swim-up" method and treated in three different ways: (1) short-term incubation group (SIG): 3 h incubation at 37 degrees C, and (2) long-term incubation group (LIG): 20 h incubation at 37 degrees C, and (3) low temperature group (LTG): 24 h incubation at 4 degrees C followed by additional incubation at 37 degrees C for 3 h. The conventional methods of incubation, i.e. SIG (3 h) and LIG (20 h) did not show any significant differences as evaluated by the sperm penetration rate and the number of decondensing sperm heads per oocyte. In contrast, in the LTG all parameters were significantly increased, especially those of penetration rate (p less than 0.0005) and decondensing sperm heads per oocyte (p less than 0.0005). The percentage of AR significantly increased (p less than 0.0005) in the LTG (14.7%) compared with SIG (6.1%) and LIG (10.6%). A significant correlation was demonstrated between AR and the parameters used for evaluation of the SPA. The penetration rate (Spearman test, r = 0.462, n = 54, p less than 0.003) was the most significant parameter correlated with AR. It would appear that only human spermatozoa having completed AR are capable of fusing with the zona-free hamster ova.(ABSTRACT TRUNCATED AT 250 WORDS)     

A new method for evaluation of the acrosome reaction in viable human spermatozoa

The acrosome reaction of human spermatozoa was induced by changes of temperature. Spermatozoa were collected from fertile donors and a patient group, and selected by the "swim-up" method. The spermatozoa were treated in two different ways: Protocol I: 24 hours at room temperature followed by additional incubation at 37 degrees C for 3 hours (control), and protocol II: 24 hours at 4 degrees C followed by additional incubation at 37 degrees C for 3 hours. The acrosome reaction of the viable spermatozoa was evaluated by a new method utilizing indirect immunofluorescence with anti-outer acrosomal membrane antibodies and exposure to a hypo-osmotic medium. In fertile donors as well as in the patient group, significant induction of the acrosome reaction (20%) was evident after exposure to low temperature (4 degrees C). The spontaneous rate of acrosome reaction in the control group was below 7%.     

8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT,a potent and selective simplified ergot congener with central 5-HT-receptor stimulating activity

Summary It was demonstrated that the simplified ergot congener 8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT, is able to elicit pronounced biochemical and behavioural alterations indicative of central serotoninomimetic activity. Since these effects are resistant to prior monoamine depletion and/or synthesis inhibition by means of reserpine and-propyldopacetamide (H22/54), respectively, they are most likely to be attributable to direct serotonin-receptor agonism by 8-OH-DPAT. With regard to central 5-HT neurotransmission the effects of 8-OH-DPAT-increased 5-HT levels, decreased 5-HIAA levels, 5-HT-synthesis rate and 5-HT utilization and inhibited 5-HT neuronal firing-are virtually identical, and comparable in potency, to those reported to result from the administration of lisuride or LSD. In contrast, however, to lisuride and LSD (included for comparative purposes in this study) as well as to several differently N-substituted, 5,6-dihydroxy, 6,7-dihydroxy and 5-, 6- and 7-monohydroxy 2-aminotetralins, 8-OH-DPAT lacks appreciable effects on central catecholamine receptors. The compound may thus be regarded the most potent, selective centrally acting 5-HT agonist described to date. accordance with this it was shown that the full-blown 5-HT-like behaviour syndrome induced by 8-OH-DPAT cannot be antagonized by reserpin phenoxybenzamine, propranolol and haloperidol. In addition, of the truputative 5-HT-receptor blockers cyproheptadine, methergoline and methrothepin only the latter was able to counteract the 8-OH-DPAT-induce syndrome. The results are discussed in relation to the recent subclassification of central 5-HT receptor sites.A comparison between the chemical structures and biological activities for different fragments of the ergot nucleus was also made. The data suggest, in that while the role of the A ring in the ergot structure for dopaminer activity at present is unclear, this ring may be important for the 5-HT-receptor activity like in e.g. lisuride and LSD.Moreover, based on the present results and literature reports, it is speculated that a selective 5-HT-receptor agonist such as 8-OH-DPAT would be liable to induce hallucinations in man.Presented in part at the 19th ACNP meeting, San Juan, December 15–19,1980. [Psychoph. Bull.17, 180–183 (1981).]     

Executive function and verbal working memory in adolescents with closed head injury (CHI)

The relationship between executive function (EF) and working memory (WM) was studied in eight adolescents with closed head injury (CHI) and eight controls, matched for age, gender and socioeconomic status (SES). A cognitive-linguistic test (Scales of Cognitive Ability for Traumatic Brain Injury, SCATBI) was used to group CHI participants by severity. EF was tested with a measure of daily functioning (Pro-Ex) and WM was tested with a recognition memory task (RMT). When all subject test data were grouped, a positive linear correlation was found for the Pro-Ex and the RMT. A strongto-moderate positive correlation was found for components of the EF measure and the RMT. Severity of injury influenced test performance for both the EF and WM measures, with a significance between group effects found on the RMT task. Results indicate a relationship between executive function and working memory, severity of injury and test performance and the need to assess EF of CHI adolescents with a measure of daily functioning.     

Resolution of isoforms of mutalysin II, the metalloproteinase from bushmaster snake venom

Mutalysin II, a zinc endopeptidase possessing direct-acting fibrinolytic activity has been previously purified from bushmaster (Lachesis muta muta) snake venom. We now report a method to isolate two isoforms of natural mutalysin II (mut IIa and mut IIb) using chromatographies on Sephacryl S-200, CM Sepharose CL 6B and Sephadex G-50. The two proteins are monomeric non-glycosylated proteinases with similar molecular masses of 23 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Tryptic peptide mapping of the two native enzymes suggested a large degree of structural similarity. Both isoforms showed high similarity in all enzymatic properties using fibrinogen, fibrin and dimethylcasein as substrates. Thus, the specific fibrinolytic activity was estimated as 12±1.04 and 11.5±1.02 U/μg for mut IIa and mut IIb, respectively. The antigenic cross-reactivity of both isoforms was examined using rabbit hyperimmune serum or immunoglobulin G anti-mut IIa assays on immunodiffusion microscope slides, indirect enzyme-linked immunoabsorbent assay and western blots. From these experiments it was concluded that the two metalloproteinases mut IIa and mut IIb share identical antigenic structures. Since the stability of mutalysin II is dependent upon the presence of zinc, we examined the EDTA sensitivity of the isoforms of mutalysin II. Thus, the IC₅₀ values (concentration of EDTA to produce 50% inhibition of dimethylcasein hydrolysis) for mut IIa is 180 μM and 165 μM for mut IIb.     

The composite solubility versus pH profile and its role in intestinal absorption prediction

The purpose of this study was to examine absorption of basic drugs as a function of the composite solubility curve and intestinally relevant pH by using a gastrointestinal tract (GIT) absorption simulation based on the advanced compartmental absorption and transit model. Absorption simulations were carried out for virtual monobasic drugs having a range of pKa, log D, and dose values as a function of presumed solubility and permeability. Results were normally expressed as the combination that resulted in 25% absorption. Absorption of basic drugs was found to be a function of the whole solubility/pH relationship rather than a single solubility value at pH 7. In addition, the parameter spaces of greatest sensitivity were identified. We compared 3 theoretical scenarios: the GIT pH range overlapping (1) only the salt solubility curve, (2) the salt and base solubility curves, or (3) only the base curve. Experimental solubilities of 32 compounds were determined at pHs of 2.2 and 7.4, and they nearly all fitted into 2 of the postulated scenarios. Typically, base solubilities can be simulated in silico, but salt solubilities at low pH can only be measured. We concluded that quality absorption simulations of candidate drugs in most cases require experimental solubility determination at 2 pHs, to permit calculation of the whole solubility/pH profile.     

Postoperative mortality a university Department of General Surgery: incidence of cardiac-related deaths

OBJECTIVES: To evaluate the incidence of cardiac deaths following noncardiac nonvascular surgery. STUDY DESIGN: Retrospective survey. PATIENTS: All patients undergoing mainly endocrinous and digestive surgery in a University department of general surgery between 1991 and 1996. METHODS: Analysis of all deaths occurring intra- and postoperatively, until discharge of the patients. Demographic and medical data, including patent myocardial ischaemia and risk factors for coronary artery disease, were recorded and compared with a control group including all patients undergoing surgery from January to September 1996. RESULTS: In the 8,700 patients who underwent mainly endocrine neck surgery (66%), or intra-abdominal surgery (31%), the mortality rate (n = 96) was 1.1% (95% confidence interval [95% CI] = 0.9-1.3%). Patent myocardial ischaemia or high risk factors for coronary artery disease were existing in 24% of patients with neck surgery, 31% of those with intra-abdominal surgery, and in 60% of the deceased patients (P < 0.01 vs control group). Those who died were older, were in a higher ASA physical class, and had undergone an emergency procedure more often than patients of the control group (P < 0.002 for each parameter). Two cardiac deaths, in patients with a patent cardiopathy, were recorded (cardiac mortality: 0.02%; 95% CI = 0.003-0.08%). The main cause of death was infection (n = 46), followed by haemorrhage (n = 12). Seven deaths remained unexplained. CONCLUSION: This study suggests that cardiac morbidity is a rare cause of death after noncardiac nonvascular surgery.     

Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small-cell lung cancer: a Spanish Lung Cancer Group phase III randomized trial.

PURPOSE: To compare the survival benefit obtained with cisplatin plus gemcitabine, a cisplatin-based triplet, and nonplatinum sequential doublets in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Stage IIIB to IV NSCLC patients were randomly assigned to receive cisplatin 100 mg/m2 day 1 plus gemcitabine 1,250 mg/m2 days 1 and 8, every 3 weeks for six cycles (CG); cisplatin 100 mg/m2 day 1 plus gemcitabine 1,000 mg/m2 and vinorelbine 25 mg/m2 days 1 and 8, every 3 weeks for six cycles (CGV); or gemcitabine 1,000 mg/m2 plus vinorelbine 30 mg/m2 days 1 and 8, every 3 weeks for three cycles, followed by vinorelbine 30 mg/m2 days 1 and 8 plus ifosfamide 3 g/m2 day 1, every 3 weeks for three cycles (GV-VI). RESULTS: Five hundred fifty-seven patients were assigned to treatment (182 CG, 188 CGV, 187 GV-VI). Response rates were significantly inferior for the nonplatinum sequential doublet (CG, 42%; CGV, 41%; GV-VI, 27%; CG v GV-VI, P =.003). No differences in median survival or time to progression were observed. Toxicity was higher for the triplet: grade 3 to 4 neutropenia (GC, 32%; CGV, 57%; GV-VI, 27%; P <.05); neutropenic fever (CG, 4%; CGV, 19%; GV-VI, 5%; P <.0001); grade 3 to 4 thrombocytopenia (CG, 19%; CGV, 23%; GV-VI, 3%; P =.0001); and grade 3 to 4 emesis (GC, 22%; GCV, 32%; GV-VI, 6%; P <.0001). CONCLUSION: On the basis of these results, CG remains a standard regimen for first-line treatment of advanced NSCLC.