[Case control studies in investigation of food-borne infection outbreaks. Study of their utilization in France].

Among the 251 foodborne outbreaks investigated by public health officers in France in 1989, 62 (25%) used a case-control study to identify the responsible food. This survey aims to analyse the results of these 62 investigations. Thirty eight (61%) investigations found the responsible food(s); 10 investigations (16%) lacked power because of the small size of the population studied, but allowed to suspect the food with the highest odds ratio; 13 investigations (21%) gave results inconsistent with bacteriological studies or with hypothesis generated by the descriptive study: in 5 of it, food origin is questionable and in 8 investigations, methodological errors are likely. We could not conclude for one study. Among the surveys with case-control studies, 74% identified the food responsible with bacteriological or epidemiological confirmation, as opposed to 17% of other surveys which had only bacteriological confirmation. This study allowed us to give recommendations on the management of investigation and the interpretation of results to improve the efficiency of this practice.


[Trends in mortality characteristics in Aids in France 1983-1990].

From 1983 to 1990, the number of AIDS deaths in France (8119 deaths overall), increased substnatially but the annual rate of progression has fallen since 1987 (+35% in 1990). The socio-demographic characteristics of the deaths remained quite steady with the exception of the proportion of subjects living in Paris which decreased. The proportion of AIDS deaths out of all deaths is still low for the entire population (5 deaths out of 1000 in 1990) but appears important in some sub-groups. In 1990, AIDS represents for the 25-34 years old group, 12 deaths out of 100 for males and 7 deaths out of 100 for females and for the 25-44 years old group, 15 deaths out of 100 for nonmarried males and 4 deaths out of 10 for males working in an information or artistic profession. Furthermore, it accounts, in 1989, for the third of the deaths of males between 25 and 44 years living in Paris. The analyse tends to show that there is not an important under-declaration of AIDS deaths in France.


[Estimate of seroprevalence of HIV infection in Belgium using the back calculation method].

An estimation of HIV seroprevalence in Belgium in June 1990 was made by the "back calculation method". The theoretical calculation of the number of virus carriers gave a range of values from 5,750 to 16,800 carriers. The upper part of this range seems to be more consistent with data from epidemiologic monitoring (range of values from 8,900 to 16,800 carriers). HIV prevalence rate in Belgium in June 1990 would is estimated between 0.9/1000 and 1.7/1000. The detection rate of the infection among HIV positives individuals should be at least 34%.


A randomised 2 x 2 factorial design to evaluate different smoking cessation methods.

A study with a 2 x 2 factorial design was performed to evaluate the effectiveness of acupuncture, of nicotine gum and the effect of the association on smoking cessation. After a one-year follow-up period, the success rates were in the same order of magnitude for nicotine gum (active treatment: 10%, placebo: 8%) group and for acupuncture (active treatment: 8%, placebo: 10%) group.


[French-language adaptation of an evaluation test of knowledge meant for insulin-dependent children: methodology and value for research in clinical practice].

A measure of knowledge level of diabetic patients is useful in evaluating their educational needs as well as the impact of the educational programs specifically designed for them. The lack of such scales in French, led us to translate and validate an existing knowledge scale for diabetic children, the Test of Diabetes Knowledge (TDK) (Johnson et al.). After several translations and back translations, the 33 item scale was submitted to the staff members of a pediatric diabetology unit, to establish its content validity. An assessment the questionnaire was performed in a group of 49 children, aged 7.9 to 12.8 years. The mean duration of diabetes was 4.6 +/- 2.9 years and their scholastic level varied from 1st to 6th grades. Time spent in filling out the questionnaires was 12 to 25 minutes. Few missing values were noted. The reliability of the scale was excellent as shown by Cronbach's alpha coefficient: 0.83 for the overall scale, 0.72 for the general knowledge subscale (20 items) and 0.70 for the problem solving subscale (13 items). The level of correct responses was correlated with age and scholastic level (p < 0.0001), but not with sex, duration of diabetes, or HbA1c levels. This study shows that the French version of the TDK is a valid and reliable tool for measuring the level of knowledge in children and adolescents with diabetes. This scale provides the researcher and clinician with a tool that facilitates the performance of an educational diagnosis and the evaluation of educational programs based on the transmission knowledge.


Mass sociogenic illness in a youth center.

In July, 1989, 63 (42%) of 150 children ages 4-14 years attending an outreach program at a youth center in Florida, but no employees, developed acute and rapidly resolving upper gastrointestinal symptoms 2 to 40 minutes after a prepackaged lunch. All ill children were sent to 3 local hospital emergency departments for evaluation. However, clinical evaluation was normal for all. Of 102 children who ate any prepackaged foods, 48 (47%) became ill compared to 1/19 (5%) for children who did not eat (rate ratio [RR] = 8.9; 95% confidence interval [CI]: 1.3-60.9). No employees ate any of the food items served. Consumption of sandwiches was associated with a moderate increased risk of illness (RR = 1.7, 95% CI: 1.0-2.9). The attack rate did not differ by age, but was greater for girls (39/56, 70%) than for boys (9/46, 20%; [RR = 3.6, 95% CI: 1.9-6.6]). Over 3,000 similar prepackaged meals from the same caterer were served in the same area of Florida that day. An inquiry in the area documented absence of similar symptoms elsewhere. Unopened meal samples tested negative for pesticide residues, heavy metals, staphylococcal toxin, or Bacillus cereus. We diagnosed the outbreak as mass sociogenic illness. Complaints of a bad tasting sandwich by the index case and possible staff anxiety about food poisoning may have contributed to the development of the outbreak.


[Jackknife and bootstrap].

The jackknife and the bootstrap are two non parametric methods which provide estimates- of the bias and the variance of an estimator, without any assumption about its statistical distribution. The jackknife is based on the observation of the estimator for subsamples, generally of size n-1, obtained from the original sample. The bootstrap is based on the observation of the estimator on size n samples drawn from the original sample. The two methods are presented, their principle is illustrated through their application to simple examples and to more complex epidemiological problems.


[Prevalence of coronary disease in patients with aortic stenosis].

We analyzed a consecutive series of 188 patients, older than 44 years, with significant aortic stenosis, who underwent coronary arteriography (73 women and 115 men). There were 38 patients (20.2%) with coronary artery disease ( or = 50% reduction in the luminal diameter). Sixty-eight patients had typical angina pectoris, 52 atypical angina, and 68 did not have chest pain. We found to have coronary disease in 29.4%, 23.1% and 8.8% respectively. Sensitivity of typical angina to detect coronary disease was 52.6%, with an specificity of 68%, and a negative predictive value of 85%. Inclusion of atypical angina improved the sensitivity to 84.2%, and the negative predictive value to 91.2%, but lessened the specificity to 41.4%. Six patients among the 38 with coronary disease (15.7%), did not have chest pain, and 3 of them were younger than 60 years. We conclude that absence of angina is not enough to exclude coronary artery disease in patients 50 years old with aortic stenosis being considered for aortic valve replacement.


[Captopril + hydrochlorothiazide versus captopril + nifedipine in the treatment of arterial hypertension in diabetes mellitus type II].

Captopril is a suitable drug to treat high blood pressure in diabetic patients. This Angiotensin-Converting Enzyme Inhibitor (ACEI) is a vasodilator without tachycardia and saline retention. Furthermore, captopril is one of antihypertensive drugs with less adverse effects. It does not induce metabolic changes, improves glucose tolerance and brake the evolution of renal insufficiency. About 50-60% of patients are under control (DBP < 90 mmHg) with captopril monotherapy. In the present paper, were included 64 women and 16 men with diabetes mellitus and mild-moderate hypertension, I-II phase WHO. The average age (mean +/- S.D.) was 66.6 +/- 9.2 years. All patients were treated with 25 mg/12 h of captopril, for one month. If blood pressure was not under control, captopril treatment enhanced to 50 mg/12 h during second month. After this period of two months, patients under control were got out of this study. 37 patients (46.25%) needed a second drug. In randomized form, 20 patients associated 25 mg HCTZ one time a day (CAP + HCTZ); and 17 patients associated 20 mg/12 h of nifedipine retard (CAP + NIF). The study continued for 4 months more. Both treatments reduced blood pressure in significant form without changes statistical significant in the heart rate, weight, glycemia, cholesterol, triglycerides, c-HDL, uric acid, creatinine, Na+ and K+ blood levels. CAP + HCTZ controlled (DBP < 90 mHg) 85% and CAP + NIF 81.25% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)


[Determining factors of acceleration in sustained monomorphic ventricular tachycardias in response to bursts of stimuli].

To analyse the determinants of acceleration of sustained monomorphic ventricular tachycardias in response to bursts of rapid ventricular pacing, we studied 46 consecutive patients with 90 distinct ventricular tachycardias during which one or more burst of rapid pacing were delivered. Tachycardia acceleration was observed in 11 tachycardias in 8 patients. The highest incidence of acceleration was observed in patients with left ventricular dysfunction of non coronary origin. There was a non significant trend towards lower values of left ventricular ejection fraction in patients with acceleration. There were no significant differences between ventricular tachycardias with of without acceleration in respect to: clinical presentation, QRS morphology, tachycardia cycle length and treatment with antiarrhythmic drugs. The shortest cycle of bursts of rapid pacing, was lower in tachycardias with acceleration than in those without it (229 +/- 57 ms vs 283 +/- 67 ms; p = 0.006) and tachycardias with acceleration showed a lower relation between burst cycle length and tachycardia cycle length (69 +/- 9% vs 84 +/- 8%; p < 0.001). The negative predictive value of acceleration was 75% for bursts of rapid pacing with a cycle length > or = 250 ms, and 96% for values of the relation between the burst cycle length and the tachycardia cycle length > or = 70%. This parameter show a very high discriminating value with of without antiarrhythmic drugs effect. Acceleration of sustained monomorphic ventricular tachycardias in response to bursts of rapid pacing depends on, the pacing rate and the relation between pacing rate and tachycardia rate.(ABSTRACT TRUNCATED AT 250 WORDS)


[Isosorbide 5-mononitrate (delayed release) in stable effort angina].

This work has been carried out to evaluate over a short and medium space of time (100 days) the efficacy, tolerance and haemodynamic repercussion of 50 mg of sustained release Isosorbide 5-Mononitrate administered once day to patients with stable effort angina in a random and prospective study, which was double blind crossover and placebo-controlled. In this study we included 10 patients who showed positive exercise test using clinical (angina) and electrocardiographic (ischemic drop of the ST greater than 1 mm) criteria. The assessment was done with cycloergometry starting with 30W and increasing by 20W every 2 minutes until angina appeared accompanied by an ischemic drop of the ST. The effort tests were done basally and at intervals of 4, 12 and 24 hours after the dose. The parameters studied were obtained on the 1st, 25th and 100th days of the study and were compared with those of the placebo. The time taken for the ST to 1 mm to fall (seconds) increased when evaluated after 4 and 12 hours on the 1st, 25th and 100th days in comparison with placebo (p < 0.05). The time taken for angina (seconds) to appear lengthened considerably when evaluated 4 and 12 hours after the dose not only on the 1st day but also on the 25th and 100th days in comparison with placebo (p < 0.05). The duration of the effort (seconds) was significantly greater after 4 and 12 hours on the 1st, 25th and 100th days when compared to that of the placebo (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


[Transesophageal echocardiography study of the left atrium and the mitral valve plane after heart transplantation].

To assess the anatomy of the left atrium and mitral plane after heart transplantation, we performed a transesophageal echocardiographic study to 37 consecutive transplant patients. After heart transplantation no patient was under anticoagulant treatment and no case of atrial fibrillation was documented. The transesophageal approach allowed us to measure the left atrial free wall suture which was: less than 15 mm in 14 patients, between 15 and 25 mm in 16 patients, and more than 25 mm in 7 patients. In those patients with a left atrial free wall suture greater than 15 mm, blood flow turbulences within the "niche" underneath the protruding suture as well as blood flow acceleration at the rim of that suture were noted. In 4 patients a "pseudoaneurysm" of the interatrial septum was observed. Two patients had mitral valve prolapse. Mitral regurgitation was noted in 17 patients (46%) by color Doppler transesophageal echocardiography and graded as mild in 15 patients and moderate in 2 cases. In 16 patients (43%) spontaneous echo contrast within the left atrium was detected by transesophageal echocardiography. Both major and minor axis as well as left atrial area in patients with and without dynamic echoes were, respectively: 72.5 +/- 12.2 mm vs 56.9 +/- 5.9 mm (p < 0.001), 48.3 +/- 7.1 mm vs 39 +/- 7.9 mm (p < 0.001), and 35.4 +/- 7.1 cm2 vs 24.4 +/- 5.2 cm2 (p < 0.001). Atrial thrombi were not detected. After a mean follow-up of 15 +/- 10.7 months there was no arterial thromboembolism in patients with spontaneous contrast.(ABSTRACT TRUNCATED AT 250 WORDS)


[Effect of the inhalation ++ anesthetic isoflurane on heart electrophysiology].

In two groups, A and B, both composed of 10 mongrel dogs, we studied the cardiac electrophysiologic effects of 1 and 1.5 MAC isoflurane administered by liquid injection in a closed circuit. In group B the study was done under pharmacological autonomic blockade (AB). With electrode catheters for programmed pacing and endocavitary potential recordings, we determined during the anesthesia with 1 and 1.5 MAC isoflurane: RR, spontaneous and paced AH, and HV intervals, corrected sinus recovery time (CSRT), Wenckebach point (WP), functional and effective refractory periods of atria (AFRP, AERP) and AV node (AVNFRP, AVNERP), and ventricular effective refractory period (VERP), these were compared to the ones obtained with a previous thiopental control. In group A, 1 MAC isoflurane increased over control: AERP and AH interval (p < 0.05), AFRP (p < 0.005), RR and AH paced intervals, WP, AVNFRP and VERP (p < 0.001), adding to these CSRT (p < 0.01) in 1.5 CAM. This level did not show differences with 1 MAC. In group B, 1 MAC isoflurane increased over control: AH (p < 0.05), RR, paced AH intervals, WP and AVNFRP (p < 0.001), adding to these AFRP and AERP (p < 0.05) in 1.5 MAC. This level increased with regard to 1 MAC: AFRP, AERP, AH paced interval and AVNERP (p < 0.05), and AVNFRP (p < 0.005). Isoflurane alone or with AB increased parameters of sinusal automaticity, atrial refractoriness, AV nodal conduction and refractoriness, increasing only without AB ventricular refractoriness and CSRT. With AB atrial and AV nodal refractoriness increased in an anesthetic depth dependent way.


Relationship between erythropoietic rate and iron donating capacity of the Fe/transferrin complex in mouse.

The transfer of iron from the Fe/transferrin complex to the erythroid cells was studied in in vitro system in mice in which a drastic and opposite change in their erythropoietic activity was produced by bleeding or actinomycin D administration. A reduction of iron donation in the serum of bled animals was found, whereas the aplastic condition induce in the donors of the serum by actinomycin D did not produce any change in the transfer process. It was also found that in spite of the normalization of the saturation in the serum of bled animals, the diminished donation remained unchanged. The possibility that conditions other than quantitative could produce this behavior is discussed.


[Lipomatous hypertrophy of the interauricular septum: diagnosis with transesophageal echocardiography and computerized tomography].

Transesophageal echocardiographic and computed tomographic imaging in a patient with lipomatous hypertrophy of the interatrial septum and advanced left bundle branch block are presented. Transesophageal echocardiography demonstrated a thickening of the atrial septum sparing the fossa ovalis region. Computed tomographic scan at the level of the interatrial septum showed a mass of fat density, and the HIS bundle electrogram showed an advanced infra-his block after intravenous ajmaline. We stress the utility of transesophageal echocardiography in this disorder, and the possible relationship between lipomatous hypertrophy of the interatrial septum and conduction disturbances.


Effects of methylpalmoxirate on isolated rat atria.

The aim of the investigation was to assess whether endogenous triacylglycerol contributes to the maintenance of the contractile and pacemaker activities of the isolated atria from fed and fasted rats. To attain this information, the atria were treated with methylpalmoxirate which is a potent inhibitor of carnitine palmitoyltransferase I. In the presence of glucose, methylpalmoxirate abolished the lipolysis without affecting peak developed tension or the atrial rate. When exposed to a substrate-free medium containing 2-deoxyglucose, the atria displayed a progressive fall of the pacemaker frequency, a pronounced decay of contractile strength and the appearance of contracture. These derangements appeared faster in the atria from fed rats coinciding with a smaller triacylglycerol mobilization. Methylpalmoxirate suppressed triacylglycerol breakdown, increased the contracture strength, accelerated the fall of the atrial rate and in a significant number of fasted atria it led to a complete cessation of the spontaneous contractions. The decline of the peak tension was not altered by the inhibitor, probably because the contractile strength was too weak in the glucose-free medium, so that additional negative inotropic effects were not detectable. These data suggest that exogenous glucose in addition to that derived from glycogen meet the atrial energy requirements when the fatty acid oxidation is hindered. The deleterious effects exerted by methylpalmoxirate after the glucose metabolism was eliminated indicate that endogenous triacylglycerol supports, at least partly, the atrial functions.


[Listeria monocytogenes endocarditis in a patient with mitral prosthesis, left auricular thrombus and adenocarcinoma of the colon].

A case of Listeria monocytogenes endocarditis in a patient with mitral prosthetic valve, left atrial thrombus and colonic adenocarcinoma is reported. Vegetations were not demonstrated by transesophageal echocardiography and the clinical course was benign and without complications. Cure was achieved with antibiotic therapy, and surgery was not required. These features suggest that atrial thrombus could be the source of infection.


[Effect of brain serotonin on the arterial pressure and plasma renin in normal and hypertensive rats].

The effects of changes in brain serotonin content after injections of p-chlorophenylalanine (p-CPA), L-5-hydroxytryptophan (L-5HTP) and 5-6-dihydroxytryptamine (5-6DHT) on the mean arterial pressure (MAP), plasma renin activity (PRA) and peripheral levels of atrial natriuretic peptide (ANP) have been studied in normal and hypertensive (2K:1C model) male Wistar rats. The p-CPA (250 mg/kg) and L-5HTP (200 mg/kg) were injected i.p., while 5-6 DHT (15 micrograms/animal in 10 mu/animal vehicle) was injected into lateral brain ventricles. The effects were studied 24 h after the p-CPA injection, 2 h after L-5HTP and 10 or 20 days after 5-6DHT administration. The fall in brain serotonin produced by p-CPA and 5-6DHT did not modify the MAP values in the normal and hypertensive rat model, whereas the increase induced after L-5HTP injection only caused a slight decrease in arterial pressure in normotensive animals. The ARP experimented remarkable rises in the normal and hypertensive rats, these values increasing after L-5HTP and falling after p-CPA and 5-6 DHT injections. Similar changes are detected in the normal group after administration of these substances related to serotoninergic brain activity. The ANP levels rose after renal artery constriction, and they are not affected by the above mentioned substances. Only p-CPA and 5-6DHT reduced a low decrease in the ANP levels 10 days after their administration.(ABSTRACT TRUNCATED AT 250 WORDS)


Muscle cell growth in protein deficient rats following administration of sheep red blood cells.

In order to observe the effects of sheep red blood cells (SRBC) administration on the muscle cell growth in malnourished states, adult male Wistar rats (135 +/- 10 g 10 animals per group) subjected during 30 days to 1% and 10% protein diets, were injected (i.v.) either 15.5 x 10(8) sheep red blood cells or 0.5 ml saline/100 g b.w. after 20 days of experiment. On the 10th day after injection the animals were sacrificed and the gastrocnemius muscle was removed, weighed and homogenized. The supernatant fluids were used to evaluate muscle protein, DNA and RNA rates and acid DNase activity. All parameters were depleted in malnourished rats, indicating a muscle cellular atrophy as well as a decrease in muscle protein synthesis per DNA-unit. Muscle hyperplasia and hypertrophy were found in antigenically stimulated rats fed 10% protein against non-stimulated control. In contrast, muscle growth in protein-deficient rats SRBC-treated was unmodified when compared to non-stimulated malnourished muscle, although RNA functionality seems to be enhanced (RNA/DNA). These data suggest that a redistribution of essential nutrients occurred for muscle growth adaptation rather than for defensive mechanism.


[Bullet embolism of the right ventricle following gunshot wound].

Bullet embolism to the right ventricle after a gunshot wound is exceptional. We describe a patient in whom the bullet after entering through the superior vena cava migrated for the venous system with further embolism to the right ventricle. Clinical history, diagnosis and treatment are discussed.


[Ultrasonic decalcification of the aortic valve. Initial experience].

We report our initial experience in 2 patients with degenerative calcific aortic stenosis who underwent ultrasonic debridement of the aortic valve. Compared with preoperative studies, doppler echocardiographic and hemodynamic evaluation before hospital discharge revealed a reduction in the mean aortic valve pressure gradient (80 and 65 mmHg to less than 10 mmHg). There was no change in aortic regurgitation grade. Follow-up doppler echocardiographic evaluation at four and six months showed no changes in gradient or regurgitation in the comparison to the postoperative data. Long-term results will show the convenience to attempt or not ultrasonic salvage of the native aortic valve in severe calcific stenosis.


Role of -SH groups in rat sugar intestinal transport in vivo.

The effect of p-chloromercuribenzoic acid (pCMB), either alone or in the presence of 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), on the 1 mM galactose absorption by in vivo perfused rat intestine has been studied. At 0.25 mM concentration, pCMB inhibits galactose absorption in about 32% but it does not modify the absorption of this sugar when the transport is blocked by 0.5 mM phlorizin, or that of the non-transportable monosaccharide derivative 2-deoxy-D-glucose. This shows that only the active transport component of galactose absorption is inhibited. A 2 min preexposure period is required for the inhibition to appear. The inhibition was not reversed by washing with saline solution even when it contained 0.5 mM dithioerythritol, 10 mM cysteine or 5 and 10 mM EDTA. The simultaneous exposure to 0.25 pCMB and 0.25 mM DTNB inhibits the total galactose entry in about 50%, an effect higher than the one exerted by each reagent separately and close to the one obtained with 0.5 mM phlorizin. Our results, in vivo, confirm the importance of the thiol groups in the cotransport of Na+ and sugar. As DTNB is an SH-reagent of lesser liposolubility than pCMB, the existence of two populations of sulfhydryl groups related to sugar transport which differ in their location within the brushborder membrane and in accessibility from the intestinal lumen, is suggested.


Chloroplast polypeptides synthesized by leaf segments and isolated chloroplasts during senescence in barley.

Starting from senescent barley (Hordeum vulgare L. cv Hassan) leaf segments receiving light and hormone treatments affecting senescence, the plastid polypeptides synthesized by isolated chloroplasts and by leaf segments were analyzed by radiolabelling followed SDS-PAGE and fluorography. Among 20 to 30 polypeptides detected, a few were specifically synthesized (by chloroplasts and/or leaf segments) after each senescence treatment. Apparently, the polypeptides labelled in assays with isolated chloroplasts are truly synthesized in vivo, because most of them were also labelled in assays with leaf segments. The comparison of polypeptide profiles, for every senescence treatment, after labelling with isolated chloroplasts or leaf segments, suggests that most plastid polypeptides synthesized during senescence are coded in plastid DNA.


[Effect of the corpora allata on the development of the male accessory sex glands in Blatta orientalis].

The volumetric changes of the corpora allata (CA) during the first 15 days of imaginal life of Blatta orientalis L. (Dictyoptera, Blattidae) are studied in connection with the growth of the accessory reproductive glands (GSAM). Both, the CA and the GSAM, grow in parallel during the first 3-4 days of imaginal life, which suggests a possible functional link between both organs. If the CA are explained on freshly ecdysed adults, then GSAM protein accumulation is reduced (by 35%) when checked on day 5, and administration of juvenile hormone (JH) restores normal development. However, when the effects of allatectomy are studied on day 12, no significant differences with respect to the controls are observed. These results suggest that JH is not strictly necessary for protein synthesis in the GSAM of B. orientalis although it has a stimulatory effect on this synthesis.


[Comparison of homologous and heterologous standard curves using TR-FIA for the determination of total T4 in the rat].

A homologous standard curve for rat T4 measurement has been compared to heterologous standard curves, by a time resolved fluoroimmunoassay (TR-FIA). Homologous standard curves have been carried out starting from rat serum in the absence of thyroid hormone by using Samuel's technique. The security criteria (sensitivity, inter and intraassay precision, and accuracy), were measured and compared between the homologous and heterologous test. Analysis of variance and slopes between homologous and heterologous standard curves showed homogeneous variances, the differences in the slopes being not significant.


Acute alcoholic intoxication and naloxone. Effects on visual evoked potential.

Experimental assays analyzing visual evoked potential (VEP) changes during an acute alcoholic intoxication were carried out in two groups of cats: One with continuous ethanol (0.06 g/kg.min) i.v. perfusion. Another one with a naloxone (400 micrograms/kg) i.v. injection 10 min before ethylic perfusion. Naloxone potentiates alcohol effects on VEP parameters, and on the appearance of isoelectric postpotential and flat VEP.


Normal puberty onset in female rats treated with antiprogesterone RU486 during juvenile period.

The significance of the increased progesterone plasma levels after day 21 on the onset of puberty in female rats is unclear. To analyze this question, female rats were injected from day 21 to 32 with the potent antiprogestagen RU486 (1 mg/day) or vehicle. Treatment with RU486 did not modify either the age at which vaginal opening or first estrus occurs. Vaginal cycles were regular. Animals sacrificed on day 40 or 50 showed reduced uterus weight, whereas body, pituitary, adrenal and ovaries were not affected. These results evidence that antagonization of progesterone action during the juvenile phase did not affect the onset of puberty.


Glucose tolerance tests during gestation in the unanesthetized rat.

To establish the temporal stages at which changes in insulin/glucose interactions may appear during gestation in the rat, unanesthetized animals were subjected to oral glucose tolerance tests (2 g glucose/kg) at days 15 and 21 of gestation and were compared to virgin female controls. On day 15 glucose tolerance is enhanced in the pregnant rat whereas plasma insulin levels are like those in control animals. On day 21 glucose tolerance does not differ between the two groups although insulin is higher in the pregnant animals. Results show 2 differentiated stages of insulin/glucose relationships throughout gestation in the rat with enhanced insulin sensitivity on day 15 and enhanced insulin resistance during late gestation. It is suggested that these changes contribute to the anabolic tendencies of the mother during mid gestation and her catabolic condition during late gestation.


[Loop diuretics and the treatment of asthma].

Current data in the literature show a protective effect of loop diuretics in relation to certain types of experimental bronchospasm. This action has sometimes been observed after the administration of diuretics as aerosols in less severe cases of asthma. The initial observations on bronchospasm induced by physical stimuli (exercise, distilled water and hyperventilation), have been extended to bronchospasm provoked by allergens or certain chemical stimuli (metabisulphide, adenosine 5'-monophosphate, and salicylic acid). On the other hand provocation tests using histamine or acetylcholine are modified, either a little or not at all by diuretics. The proposed mechanisms of action are multiple, but are still very hypothetical: an action on ionic fluxes in the epithelial cells, in mastocytes, in nerve cells and in muscle cells inducing the secretion of prostaglandin. Diuretics certainly have opened some interesting patho-physiological approaches, but current data concerning their efficacy in asthmatics are still fragmentary and do not, at the current time, allow them to take a significant place in the therapeutic arsenal of asthma drugs.


[Mortality related to asthma. Trends in France from 1970 to 1987].

An increase in mortality related to asthma has been observed in a great number of countries during the last decade. The purpose of this work is to study this evolution in France from 1970 to 1987. Numbers of deaths were obtained from INSERM, by sex and age groups and the corresponding populations from INSEE. Data were interpreted from crude rates and with the computation of age adjusted and age specific rates. In men, we observed a decrease in mortality from 1972 to 1979, then an increase from 1980 to 1987. In women, the decrease stopped as early as 1974 and we observed an increase from 1975 to 1987. On the other hand their crude and age-adjusted rates become higher than men's rates as early as 1977.


[The influence of a new beta agonist: formoterol on mucociliary function].

The muco-ciliary apparatus has an essential role in the cleansing of the tracheo-bronchial tree of particulate matter. Disturbances linked to muco-ciliary function are well known in respiratory pathology and in cases of chronic bronchitis and asthma and lead to a reduced capacity for cleansing. In addition there are numerous pharmacological agents including sympathomimetics which are capable of altering the ciliary activity and the rheological properties of mucous. The role of Formoterol, administered as an aerosol has been assessed in vivo in 10 bronchitic patients who were in a stable state. After 6 days of treatment using the Formoterol aerosol the muco-ciliary clearance had significantly increased to 46% and was a real gain when compared to the muco-ciliary clearance measured on placebo. This gain was linked to a better function of the muco-ciliary carpet and not due to the bronchodilatation which was induced by Formoterol, because the penetration index did not change. At the same time the airway resistance was slightly reduced in a none significant fashion.


[Bronchogenic cysts in the carina].

Between 1977 and 1990, 11 children with carinal bronchogenic cysts were operated in our institution: 8 girls and 3 boys, ranging in age from 1 month to 5 years. All were symptomatic (acute respiratory distress and recurrent bronchiolitis). Chest X-ray showed an unilateral over distension in 10/11 cases. Barium oesophagogram showed a compression in 6/10 cases. Bronchoscopy noticed an extrinsic compression in 10/11 cases and a tracheal and/or bronchial diskinesia in 5/11 cases. The computed tomography showed a low density mass in 4/4 cases. 9 cysts were left-sided and 2 right-sided. Both children underwent a second surgery for a second cyst. 2 pneumonectomies for complete parenchyma destruction were realised. 1 left pulmonary hypoplasia was noticed. A tracheal and/or bronchial diskinesia in post-operative was noticed in 5/6 cases. The clinical and functional respiratory following was good in 10/11 cases. An early surgery treatment is necessary before definitive sequelae.


[Evolution of bronchial hyperreactivity during post-exercise asthma].

The occurrence of a late reaction following exercise induced asthma is questionable and its relationship with the non specific bronchial hyperreactivity is poorly known. In this study, nine patients (age 15-21 years) underwent an exercise challenge in order to (a) determine the incidence of immediate and late phase reaction and (b) analyse the modifications of non specific bronchial hyperreactivity. Study design was a follow; day-3: determination of bronchial responsiveness to metacholine; day 0: control day with FEV1 measurements every hour for 11 hours; day 1: exercise challenge followed by a careful observation of change in FEV1; day 2: new determination of bronchial responsiveness to metacholine. An immediate exercise induced bronchial obstruction was observed in 5 patients. A late phase reaction (6th hour) with a fall of FEV1 equal to or more than 20% has been demonstrated in two patients. For the former, the change in FEV1 did not differ from the value of the control day. For the second, the FEV1 changed spontaneously during the control day so that decreases of FEV1 during control and challenge days were parallel. Thus, no late phase reaction were observed (F = 0.46; ns). There was no modification of bronchial responsiveness to metacholine (pre-exercise: 1,784 +/- 1,970 [SD]; post-exercise 1,827 +/- 2,231 micrograms [SD]). The lack of true late phase reaction when the post-exercise change in FEV1 is compared to the one of a control day and the absence of modification of non specific bronchial hyperreactivity weaken the hypothesis of an inflammatory mechanism of exercise induced asthma.


[Bronchial cancers invading the chest wall].

One hundred and twenty five patients, considered as having a bronchial carcinoma invading the chest wall, suffered from a thoracic pain in 40 cases. They were operated on by pneumonectomy (23), bilobectomy (5), lobectomy (83) and atypical resection (1). Resection was impossible in 13 cases (10.4%), for anatomical (10) or functional reasons (3). Considering the chest wall, an extra-pleural resection was performed in 49 cases, a muscular resection in 25 cases and a skeletal resection in 38 cases. Parietal invasion was microscopically confirmed for 78 tumours out of 112 resections specimens and for 10 tumours out of 13 which were not resected: 65 T3 N0, 8 T3 N1, 15 T3 N2. Operative mortality was 12.5%. Global survival was 62.8% at 1 year, 14.2% at 3 years, 11.1% at 5 years. Median survivals were 393 days after resections dating back to more than 5 years and 158 days when the tumours were not resected. Thoracic pain is a symptom of chest wall invasion in 87.5% of cases, but the invasion is symptomless in 24% of cases. Sensitiveness, specificity and predicting values of imaging modalities are discussed: on the whole the negative predictive values are feeble (0.23 to 0.42). The operative estimation is also uncertain, especially considering invasion limited to the extra-pleural space. Practically, a fixed tumour with broad and firm adhesion to the chest wall is an indication for chest wall resection which gives better results, although this advantage is not statistically significant. Surgical prognosis of T3 cancers is, in this series, much worse than the prognosis of T2 tumours. Mortality is analyzed according to its causes.(ABSTRACT TRUNCATED AT 250 WORDS)


[High school students and tobacco. A survey of 630 students in Poitiers].

A survey of high school pupils and their attitudes to tobacco was carried out by an anonymous auto questionnaire by 630 pupils at the Alienor Aquitaine Lycee in Poitiers in April 1991. The population study had the following characteristics: 30% were boys, 70% were girls. The mean age was 18 +/- 1.31 years. The proportion of regular smokers (at least one cigarette per day, every day) was 33.9% in boys and 34.9% in girls. The boys had smoked on average 10.7 cigarettes per day for 3.5 years and the girls 9.1 cigarettes per day for 2.9 years. The smoker above all, used light colour tobacco (with filters 98%) but 29% only bought mild cigarettes. On the other hand 55% of the subjects wished to stop smoking. There was no statistically significant relationship between the smoking habits of the pupils and that of their parents on the one hand or on the regular participation in a sport, on the other. However, boarders smoked a lot more than the other pupils. The knowledge of the dangers of smoking were imperfectly understood, in particular, for chronic bronchitis, myocardial infarction, small birth weight of the newborn and cancer of the bladder. The changers of passive smoking were known by 91.6% of the pupils. Finally this study explored the opinion of the lycee pupils as regards to the six measures in the propaganda against smoking and on seven methods of information relating to the dangers of tobacco.


[Expiratory capnography in asthma. Perspectives in the use and monitoring in children].

The shape of the capnogram, which is related to uneven ventilation, is modified in obstructive diseases and especially during crisis of asthma. The most significant change is a rise in the slope of the "alveolar plateau". In this study, we measured the end-tidal slope (ETS) of the capnogram, calculated on 0.36 s before the end of expiration, and we compared this indice to usual spirometric measurements (FEV 1) in 21 control subjects and in 24 asthmatic subjects. The mean ETS in control subject was 0.08 +/- 0.06%/s, it was 0.3 +/- 0.23% in asthmatic subjects (p < 0.001). In the latter, we found a very significant correlation between ETS and FEV 1 (r = 0.83, p < 0.001). Thirteen asthmatic subjects were tested for a second time, immediately after inhalation of a beta 2-mimetic drug. They exhibit a very strong correlation between the rise of FEV 1 and the loss of ETS (r = 0.96, p < 0.001). These results show that the analysis of the capnogram's shape is a quantitative method for evaluating the severity of the bronchospasm. This ability, added to specific advantages (non-invasiveness, effort-independence) opens new fields of application to capnography: measurement of the bronchospasm in children, computerized monitoring of asthma.


[Idiopathic subacute pulmonary eosinophilia].

We report a case of pneumonia with hypoxaemia and a swinging fever which was resistant to antibiotics, but was associated with a hypereosinophilia (44%) noted in the bronchoalveolar lavage. Investigations as to the cause of the eosinophilic pneumonia were negative; a lung biopsy confirmed the eosinophilic infiltration and the absence of any angiitis. There was a rapid and favourable clinical outcome following steroid therapy, which was maintained for three months. No relapse has been noted in the ten months of follow up since ceasing the cortico-steroids. The diagnosis appears to be that of a sub-acute, idiopathic eosinophilic pneumonia. The similarities and differences between this case and the chronic idiopathic eosinophilic pneumonia of Carrington were discussed.


[A rare and curable cause of acute respiratory insufficiency after a pneumonectomy. The platypnea-orthodeoxia syndrome by the reopening of the foramen ovale].

We describe a case of a 54 year old patient who had developed a right to left shunt due to a patent foramen ovale as a late consequence of a pneumonectomy; this was responsible for acute respiratory insufficiency and respiratory failure. This is a rare complication, but its clinical presentation as platypnea-orthodeoxia should lead to the correct diagnosis. The diagnosis can be rapidly confirmed by a non-invasive examination, namely contrast echocardiography, coupled with color doppler. The treatment is surgical with excellent results. The pathophysiological mechanism is also discussed.


[Generalized histoplasmosis due to Histoplasma duboisii with mediastino-pulmonary infection. Cure after 15 months of treatment with ketoconazole].

We report a case of a young burkinabian, who presented with the disseminated african form of histoplasmosis, Histoplasma duboisii. There was pulmonary mediastinal disease with superficial lymphadenopathy and also hepatic involvement. The diagnosis was achieved by a histological examination of the peripheral glands and micrological examination of the expectorate. A clinical cure (despite the radiological persistence of enlarged but stable left hilar glands) with the follow up 10 months was achieved after 15 months of treatment with ketoconazole in a dose which was increased to 10 mg/kg/day.


[A unilateral hyperlucent lung...].

The occurrence in a young patient of a chronic cough with dyspnoea and restrictive ventilatory failure as shown by respiratory function tests suggested the possibility of a Mac Leod syndrome. However, other aetiologies could be considered such as vascular malformations, bronchial malformations and also tumours. If the chest X-ray sometimes enables an aetiological slant, bronchoscopy remains a first line investigation.


[Late diagnosis of mucoviscidosis based on the association of bronchiectasis and sterility].

We report a case of a man aged 36, in whom a diagnosis of mucoviscidosis was diagnosed based on the association of diffuse bronchiectasis and obstructive azoospermia. We discussed some clinical and biological aspects leading to the diagnosis of mucoviscidosis in the adult.


[Purulent pleurisy revealing an esophageal diverticulum].

We report a very rare case of a purulent pleurisy which was revealed to be caused by an oesophageal diverticulum. The pleuro-pulmonary infection probably followed the inhalation of septic material which refluxed from an oesophageal diverticulum into the trachea. This was suggested by a barium swallow which showed the transit of the barium into the trachea during swallowing movements.


[Wilson's disease].

Wilson's disease, also called hepatolenticular degeneration, is a serious inherited disorder of copper metabolism. The disease needs a particular attention because it is estimated that about half of the patients are never diagnosed. Beside, once the diagnosis is made, Wilson's disease can be effectively treated. After the epidemiological, pathogenetical and clinical data, authors present the diagnostical aspects of the disease, and the various approaches to the treatment of the symptomatic or presymptomatic patients and of the pregnant patients. Also reported are two cases of Wilson's disease.


[Insulin-like growth factors in human pathology].

IGFs-I and -II are single chain polypeptides (70 ad 67 aa respectively) structurally similar to proinsulin, synthesized ubiquitously and circulating carried by specific binding proteins. The IGFs act through two types of specific membrane receptors: the so called "type 1" or IGF-I receptor, and the "type 2" or IGF-II receptor. In physiological conditions IGF-I is correlated with GH secretion. However it is also influenced by other hormonal and non-hormonal factors. Little is known about the physiological significance of IGF-II, whose concentration, at variance with IGF-I, is not increased in acromegalic subjects. It has been recently postulated that IGF-II has a critical role in prenatal growth, while IGF-I exerts its action after birth. IGF-I is important in the clinical evaluation of growth defects and of acromegalic patients. As to growth defects an overlapping of values is reported between normal and hypopituitary subjects under 5-6 years of life. However, although it is possible that a normal subject presents with a reduced IGF-I concentration, it never happens to find a hypopituitary subject with normal values. It is, therefore, possible to establish a cut-off value (100 micrograms/l in our experience) over which the occurrence of hypopituitarism is excluded. On the contrary IGF-I concentration is extremely useful in the evaluation of acromegaly, in particular to evidence the disease activity status. Moreover the IGF-I concentration seems to be useful to evaluate the nutritional status, particularly in association with serum transferrin, in subclinical conditions and in the monitoring of the nutritional therapy.


[A 24-hour blood pressure and heart rate pattern in healthy persons over 70 years of age. A Campodimele study].

The present report is aimed at studying the 24-h pattern of blood pressure in elderly subjects (45 men and 47 women, aged from 76 to 102 years), recruited in Campodimele, a small city where the population of ultra septuagenaries is very dense. The investigation has been performed by mean of ambulatory non-invasive monitoring combined with chronobiometric estimates. The computation has been performed on raw data, rhythmic series and integral profiles. The analysis has been stratified according to sex. The tabulated estimates constitute an index of reference for blood pressure 24-h pattern in aged people.


[Prosopagnosia. Description and discussion of a clinical case].

Prosopagnosia was due to a right occipito-temporal infarct, but clinical and computed tomographic features emphasized a previous symmetrical damage in the left side. The case reported, and especially elaboration of literature data relative to this peculiar type of visual agnosia, suggest that bilaterality of cerebral lesions in the determining factor of prosopagnosia.


[Pheochromocytoma and homolateral stenosis of the renal artery. A rare association?].

A case of association between pheochromocytoma and homolateral stenosis of renal artery is discussed. Until now, this is the first notification of such an association. The authors examine the possibility of a link between the two pathologies on the basis of congenital or physical factors. This association could have been so rarely just only due to the difficulty to prove it.


[Diagnosis of cardiocirculatory autonomic failure by the tilting method].

The variation of SBP, DBP and HR is evaluated on tilting in a group of 34 patients affected by orthostatic hypotension versus a group of 54 healthy subjects, age and sex cross-matched. The patients affected by cardiovascular autonomic failure showed: 1) a fall of SBP greater than -19 mmHg in the 1st min; 2) a fall of the SBP average value (for 10 minutes) greater than -22 mmHg. Contrarily, the healthy subjects showed: 1) no variations of SBP values during the 1st minute and 2) a growing of SBP between the 2nd and the 10th minute; 3) a SBP average value (for 10 minutes) with a positive trend. The DBP and HR showed not differences between the groups. We suggest that the measure of SBP on standing may be considered an easy and fast method to perform a diagnosis of autonomic cardiovascular failure.


False positivity of tumor markers in pleural fluid of traumatic hemothorax.

Various biochemical parameters of pleural fluid have been employed to identify malignant effusions. However, many of them are also elevated in patients with nonmalignant conditions. We report on a patient with traumatic hemothorax, showing high pleural fluid concentrations of ferritin, tissue polypeptide antigen, and cancer antigen 125. This patient's pleural fluid also contained high levels of bilirubin and many macrophages containing phagocytized red blood cells, suggesting a local metabolism of hemoglobin. Our case confirms that some tumoral markers can give false positive results and suggests that their significance must be evaluated differently in bloody pleural effusions as compared with non-bloody pleural effusions.


[Factors influencing the effect of ursodeoxycholic acid therapy in chronic hypertransaminasemia].

The aim of this work was to detect, in patients with chronic hypertransaminasemia (CH), the factors associated with the changes of ALT serum levels after one year of 10 mg/Kg/die ursodeoxycholic acid (UDCA). One hundred and twenty two consecutive patients with ALT values more than twice the normal upper limit for at least six months were admitted to the study. At the liver biopsy 82 patients were affected by liver cirrhosis (LC), 7 by chronic persistent hepatitis (CPH), and 14 by chronic active hepatitis (CAH). Nineteen patients were classified as unspecified chronic liver disease (UCLD) due to biopsy refusal. Five patients (4 LC and 1 UCLD) did not finish the study. Before and after the beginning of the treatment ALT and the other routine tests of liver function were determined in serum by routine laboratory methods. In all the diagnosis a decrease of ALT was observed after one year UDCA therapy. Particularly, in cirrhotic patients a reduction of 40% in the ALT serum levels was detected (baseline m +/- ds 98 +/- 55 UI, one year transaminase decrease -39 UI with 95% C.I. -27 UI to -52 UI). Furthermore in liver cirrhosis there was an increase of serum albumin (baseline m +/- ds 3.5 +/- 0.6, one year albumin increase +0.2 gr with 95% I.C. +0.1 gr to +0.3 gr). The decrease of ALT showed an inverse association (p < 0.05) with the presence of antibodies to hepatitis C virus and with diagnosis of CAH, and a direct one with the basal values of ALT.(ABSTRACT TRUNCATED AT 250 WORDS)


[Controlled trial of thymostimulin treatment of patients with primary carcinoma of the larynx resected surgically. Immunological and clinical evaluation and therapeutic prospects].

The study aim was that of evaluate the effect of thymostimulin (Tp-1, Serono), either in vitro or in vivo, in patients with primary laryngeal carcinoma, treated only with surgery without any other complementary therapy. Nineteen patients have been studied: nine (mean age 62.5 years, range 48-70) have been treated with Tp-1 and ten patients (mean age 63.4 years, range 56-75) served as "controls". Tp-1 has been administered as follows: 60 mg/m2/daily i.m. days 1-15; 60 mg/m2 twice weekly i.m. days 16-30; 60 mg/m2 once weekly i.m. days 31-60. The treatment was stopped days 61-90. The same cycle was repeated until day 180. The treatment was stopped days 181-365. The following parameters have been assessed: clinical (at the protocol entry and after one year): Performance Status (PF, Karnofsky), local status, presence of relapses, incidence of chronic infections of the upper respiratory tract; immunological in vitro: 1) response to polyclonal mitogens, PHA, Con A and PWM, response to human recombinant Interleukin 2 (rIL 2) of PHA-prestimulated and non prestimulated peripheral blood lymphocytes. The immunological parameters also have been assessed at the protocol entry and after one year. Our results have shown that, in the group of patients treated with Tp-1, 5/9 patients (55.56%) exhibited a significant increase of the PHA response at the end of treatment as compared to pretreatment values, 3/9 (33.34%) showed a decrease and 1/9 (11.10%) an almost unchanged response. In the group of controls, 5/10 (50%) have shown a significant decrease of the response after one year, 3/10 (30%) an increase, 1/10 (10%) were unchanged and 1/10 (10%) exhibited a non univocal response.(ABSTRACT TRUNCATED AT 250 WORDS)


[Prevalence and risk factors of carotid and femoral atherosclerosis in a sample of the city of Turin].

Presence and severity of carotid and femoral atherosclerosis, in relation to the principal cardiovascular risk factors, have been non invasively evaluated using echodoppler in a sample of 457 subjects (average age 55.4 +/- 18.7 years) of the metropolitan area of Turin. Data of prevalence have been standardized for age and gender in order to obtain an estimate of prevalence representative of the city. In both districts, prevalence of lesions, echo structural characteristics of the plaques and related degree of stenosis have been considered. Results indicate a high prevalence of carotid and femoral atherosclerosis (38.5% and 39.4% respectively), and, particularly, of concomitant involvement of both districts (30%). Prevalence of the lesions and degree of stenosis rise with advancing age; nevertheless stenosis > 75% were not found among the oldest patients. Bifurcations were the most frequent site of lesion and the "hard" echo structure was the most commonly represented, especially in subjects over 45 years. After multiple logistic regression model both carotid and femoral atherosclerosis were strongly and independently associated with age, male sex, smoke of cigarette and plasma cholesterol concentration.


[Chronic alcoholism and arterial hypertension. Contribution to the comprehension of the phenomenon and practical implications].

Alcohol abuse is a frequent contributor to elevated blood pressure. 710 chronic alcoholics, aged 26-60 years, admitted for detoxification were studied. We compared hypertension prevalence in alcoholics with that in a similar group of non-alcoholics matched for age, sex, and miscellaneous diseases. The prevalence of hypertension was higher in heavy drinkers (11.4%) than in non drinker subjects (3.4%). Abstinence from alcohol during hospitalization was followed by normalization of hypertensive status in a high percentage of patients (70%). The majority of hypertensive alcoholics (75%) developed target organ damage ranging from retinopathy to hypertensive cardiomyopathy and renal lesion. In a 4.6 +/- 2.8 years follow-up study of 42 hypertensive alcoholic subjects, we observed that hypertension was 26% in those who abstained alcohol ingestion versus 84% in those who remained actively alcoholics. Four patients died of liver failure and two of stroke.


Inappropriate antidiuretic hormone secretion in a patient with systemic sarcoidosis.

A 59 year old man presenting fever, serum hyponatremia and hypoosmolality in association with hyperosmotic urine was hospitalized in our unit in February 1988. We demonstrated evidence of systemic sarcoidosis and inappropriate secretion of antidiuretic hormone (ADH). The patient was treated with corticosteroid therapy for a period of about 1 year, with regression of signs of the inappropriate vasopressin secretion as well as the symptomatology related to systemic sarcoidosis. This study identified systemic sarcoidosis as a definite cause of "syndrome of inappropriate ADH secretion".


[Clinical methodology employed to solve a case of probable sarcoidosis].

A case of interstitial lung disease with fever and arthralgia is described. Sarcoidosis was very probable, but the patient refused the invasive investigations that were needed in order to obtain a histological diagnosis of certainty. We discuss the clinical methodology employed to solve the case.


[Sublingual captopril in hypertensive crises].

Captopril is widely used in severe hypertension. Oral administration takes one-two hours to achieve a maximum effect and is not useful in hypertensive crisis. Few reports describe a more rapid effect on blood pressure following sublingual administration. We evaluated the effect of sublingual captopril 50 mg, in 26 patients with hypertensive crisis. Blood pressure levels started to decrease within 10 minutes and the maximum effect was observed 30 minutes after administration of the tablet. In all patients mean (CI 95%) systolic blood pressure dropped from 202.5 (199-206) mmHg to 160.6 (156-165) mmHg and diastolic blood pressure from 105.6 (102-109) mmHg to 86.9 (83-7-90.1) mmHg. This effect was maintained over two hours. There were no side effects. Sublingual captopril is highly effective in hypertensive crisis and its gradual hypotensive action avoid dangerous abrupt fall in blood pressure.


[Evaluation of the thyroid function in healthy aged patients residing in 2 geriatric institutions].

Thyroid function assessment in elderly inpatients. It is not well known whether normal ageing might lead to an impairment of thyroid function. We evaluated 297 elderly inmates in two geriatric institutions. After having excluded from the study those who were affected by chronic hepatic or renal disease, were under pharmacologic treatment or had suffered from acute ailments during the previous two months, we assessed thyroid function by determining circulating T4, T3, rT3, FT4, FT3 and TSH in 130 apparently healthy subjects. They could be divided into three groups composed of patients mentally competent, affected by either vascular or senile dementia, or affected by chronic psychosis. Results were also assessed with reference to three different age ranges (65-74, 75-84 and over 85 years). Two patients had subnormal thyroid hormone levels with elevated basal thyrotropin, while other two demonstrated only elevated thyrotropin levels, qualifying respectively for a diagnosis of primary hypothyroidism and subclinical hypothyroidism. In the remaining 126 patients thyroid function was normal, and no differences in thyroid hormone levels could be noticed among the various groups of patients, divided for sex, age range and mental condition. The results of our study confirm the presence of a high percentage of subclinical thyroid dysfunction in old age. They also suggest that in healthy aged subjects thyroid function parameters are not significantly different in reference to sex, age range and mental condition.


[Hypertension: when to consider it a risk factor?].

The results of a good deal of large epidemiological studies carried out in the last 3 decades clearly showed that moderate and severe arterial hypertension is a mayor risk factor for cardiovascular disease. At variance, mild hypertension was generally regarded as a more benign condition, if not associated with other risk factors. Recently, the attention of several investigators was focussed to identifying possible additional risk factors, which are related to high blood pressure, and might increase substantially the risk of mild blood pressure elevation. Left ventricular hypertrophy, activation of the renin-angiotensin system and a generalized increase in the Na+/Li+ countertransport are some of the factors that are implicated in hypertensive cardiovascular disease. Since not all available antihypertensive agents positively influence these factors, these observations could have not only pathophysiological and clinical, but also therapeutic consequences.


[Recent biological and therapeutic advances in multiple myeloma].

Multiple myeloma still remains a fatal disease. However, in the last months new biological and clinical informations have been provided about this disease. In particular, the immunophenotype of myeloma cells seems indicate, in some patients, a clonal involvement of a stem cell in the pathogenesis of mieloma. Moreover, new biological insights concerning the cytokine network, have revealed a probable effect of some cytokines, such as IL6, IL3, IL4. Finally, new insights in the biology of multiple myeloma have been provided by studies of molecular biology and flow cytometry. As for therapy, the best conventional induction treatment still remains to be defined. In the last years, the increased use of alpha Interferon and new therapeutic modalities, such as transplantation procedures in multiple myeloma, open new hopes toward a cure of this disease. Therefore, in the future a better knowledge of the multiple myeloma biology, associated with a wider use of new effective therapeutic approaches will certainly improve the natural course of this disease.


Immunotherapeutic approaches with monoclonal antibodies to immunological diseases.

The molecular events triggered by the interaction of the immune system with an antigen and leading to an immune response have been characterized in recent years. This information has provided the background to develop immunotherapeutic approaches to allograft rejection and to autoimmune diseases utilizing monoclonal antibodies to molecules which play a role in the immune response. The clinical trials performed thus far are described. The significance of the results obtained in these trials and the future potential developments are discussed.


DDA as an immunological adjuvant.

As compared to other adjuvants, DDA is a moderate or strong adjuvant for humoral responses and a strong adjuvant for CMI, especially DTH responses, against different types of antigens and in both laboratory animals and larger animals. DDA can collaborate with other immunomodulating compounds resulting in further enhanced responses. Mechanisms include interactions with both antigen and components of the host immune system and possibly, multiple beneficial effects contribute to the relatively strong adjuvanticity of DDA. Toxicity of DDA is not known but severe detrimental side effects were not seen. This adjuvant can be applied in experimental vaccines and in commercial vaccines for veterinary purposes, especially if cell-mediated immunity is considered to be important. In immunology, DDA can be of use to study T helper cells responsible for DTH responses (T helper cells type 1) and to characterize T helper cell epitopes on antigens (Snijder et al., 1992).


Synthetic lipopeptides as novel adjuvants.

Lipopeptides constitute potent novel immunoadjuvants in mice, rabbits and other species, enhancing markedly the immune response when given in mixture with antigens. Lipopeptides are non-toxic, non-pyrogenic and do not induce tissue damage when injected. They are thus well suited to replace Freund's adjuvant avoiding its side effects; the antibody titres obtained using lipopeptide analogues are in most cases comparable to the titres obtained by administering Freund's adjuvant. Lipopeptides also improve the efficiency of vaccines, which is important in decreasing the amount of vaccine required. Lipopeptides covalently coupled to low molecular weight haptens, e.g. peptides or toxins, are able to elicit high antigen-specific antibody titres in mice and rabbits. Conjugates containing B or T helper cell epitopes constitute novel synthetic vaccines which protect against viral infections by inducing virus-specific antibodies. When coupled to CTL epitopes, the conjugates are able to induce cytotoxic T lymphocytes in vivo which eliminate virus-infected cells. Thus, due to their efficacy and their lack of side effects, these novel lipopeptide adjuvants provide a substitute for many conventional adjuvants.


Mouse T-lymphocyte activation by Urtica dioica agglutinin. I.--Delineation of two lymphocyte subsets.

Urtica dioica agglutinin (UDA) is a mouse T-lymphocyte-specific mitogen endowed with proliferative characteristics different from ConA, the prototypic T-lymphocyte mitogen. In particular, UDA induces 2-3-fold-reduced thymidine incorporation as compared to ConA. In an attempt to define the basis of this reduced proliferation, we analysed whether UDA binds to a unique subset of T lymphocytes or whether it activates only a T-cell subset. Cytofluorimetric analysis showed that this lectin binds uniformly to all T lymphocytes and does not, on this criterion, distinguish a particular T-cell subset. We next analysed whether UDA provokes the activation of all T lymphocytes. This was carried out by measuring the increase in cell size and the induction of the p55 chain of the IL2 receptor. The analysis showed that, throughout the kinetics of cell activation, only one subset of T lymphocytes increased in size and expressed the p55 chain of the IL2 receptor, suggesting that UDA activates only a subpopulation of T cells. This conclusion was strengthened by the analysis of 5-bromo-2-deoxyuridine (BrdU) incorporation into the DNA of UDA-activated cells. Two populations were easily identifiable: a BrdU-negative subset consisting of all the small p55-negative lymphocytes, and a BrdU-labelled subset including all the large p55-positive cells. BrdU was incorporated in both CD4+ and CD8+ cells, indicating that UDA did not distinguish helper from cytotoxic T lymphocytes. In addition to the p55 chain of the IL2R, all cycling cells expressed the Pgp-1 activation marker. The T lymphocytes, which bound UDA but did not proliferate, remained fully susceptible to subsequent stimulation by ConA. In conclusion, the capacity to proliferate upon UDA binding differentiates a UDA-sensitive from a UDA-refractory subset among splenic mouse T lymphocytes.


Mouse T-lymphocyte activation by Urtica dioica agglutinin. II.--Original pattern of cell activation and cytokine production induced by UDA.

Urtica dioica agglutinin (UDA) is a T-lymphocyte-specific polyclonal activator that differs from ConA, the classical mouse T-cell mitogen, by inducing a late and limited proliferation of a distinct T-cell subset recruited among both CD4+ and CD8+ lymphocytes. We investigated the possibility that the particular kinetics may originate from UDA-specific activation processes in which the known early mandatory signals were completed only after an extended delay. We report that the time of contact required between lectin and the cell membrane to acquire the capacity to proceed into cell cycle was much longer (36-40 h) for UDA than for ConA (8-10 h). Addition of phorbol ester, which artificially induces PKC translocation, or ionomycin, which provokes Ca2+ mobilization, did not accelerate the proliferative kinetics, suggesting that these early mandatory signals are not the limiting factors in the delayed proliferation. The induction of c-myc was retarded in the UDA group, and there was a good correlation between the kinetics of c-myc induction and the kinetics of cell proliferation. The comparison of the level of transcription of the genes encoding different cytokines revealed additional differences between the two mitogens: the whole wave of cytokine gene expression was delayed with UDA. In particular, IL2, IL3 and IFN gamma gene expression was retarded compared to the ConA-induced single wave. An even later transcriptional wave took place at around 72 h for IL4 and IL5. Finally, this particular kinetics corresponded to an unusually high level of IL3 and IFN gamma and a low level of IL4 and IL5 gene transcripts.(ABSTRACT TRUNCATED AT 250 WORDS)


Analysis of heavy and light chain use of lupus-associated anti-La/SS-B and anti-Sm autoantibodies reveals two distinct underlying immunoregulatory mechanisms.

The immunoregulatory mechanisms involved in autoimmune diseases are still unclear. One approach to elucidating these mechanisms involves evaluation of the clonality of the lymphocytes involved in autoimmunity. Molecular analysis of the rearrangement patterns of antigen receptor genes in T cells and B cells has produced ambiguous results. The present study focuses on the analysis of the autoantibodies themselves, being the end products of autoimmune reactivity. Heavy and light chain use of autoantibodies and of total IgG was determined in sera containing anti-La/SS-B and/or anti-Sm antibodies, two autoantibody specificities associated with rheumatic diseases such as systemic lupus erythematosus and Sjögren's syndrome. From our experiments, the anti-La/SS-B response emerges as an oligoclonal, IgG1-restricted B-cell response associated with sharply elevated levels of total serum IgG1-kappa. These characteristics are in sharp contrast to the polyclonal, IgG-subclass-unrestricted anti-Sm response which is accompanied by normal or slightly elevated total serum IgG levels. These findings suggest that anti-La/SS-B autoantibodies, in contrast to anti-Sm autoantibodies, are the product of a restricted oligoclonal B-cell response and thus may be the consequence of a (virally triggered) benign B-cell lymphoma.


Effects of IL6 on B cells in mucosal immune response and inflammation.

Freshly isolated surface IgA+ (sIgA+) B cells from human gut-associated lymphoreticular tissues (GALT), e.g. the appendix, express high levels of IL6 receptor (IL6R) and respond to IL6 with significant increases in the number of IgA-secreting cells. On the other hand, neither sIgM+ nor sIgG+ B cells from appendix express IL6R. When the effect of IL6 on IgA subclass antibody synthesis was examined, the numbers of both IgA1- and IgA2-producing cells were increased upon incubation of GALT B cells with IL6; however, 60-70% of IgA-secreting cells were IgA2 subclass. Aberrant local production of IL6 can contribute to increased B-cell responses that occur in mucosal inflammation such as gingiva of patients with adult periodontitis (AP). When gingival mononuclear cells (GMC) isolated from AP patients were cultured without any stimulus, GMC spontaneously produced biologically active IL6 which induced peripheral blood mononuclear cells (PBMC) from the same patients to become IgG- and IgA-producing cells. Further, mRNA extracted from GMC possessed high message for IL6. When the expression of IL6R was compared between GMC and PBMC isolated from AP patients, IL6R-bearing cells were only seen in the former population. Thus, a high production of IL6, which have the ability to regulate later stages of IL6R+ B-cell development and to induce them to become Ig-secreting plasma cells and to support plasmacytoma growth, are important immunopathological elements for the induction of the increased B-cell response region in inflamed mucosal tissues.


Parental and peer influences on leisure-time physical activity in young adolescents.

Influence from parents and friends on adolescents' self-reported level of leisure-time physical activity was examined through measures of (a) perceived leisure-time physical activity of parents and best friend, (b) perceived direct support for physical activity from parents and friends, (c) direct help from parents in exercising vigorously, and (d) perceived value of physical activity of parents and friends. The present analysis included 904 students in western Norway (M age 13.3 years, SD 0.3) who took part in a health behavior survey, which included questions regarding physical activity. Students completed a confidential questionnaire at school. All four measures of influence were positively related to students' activity levels. None of the examined measures was clearly stronger than the other. Parental and peer physical activity level and parental and peer support for physical activity seem to influence the reported physical activity level of the respondents. The findings indicate that, by serving as models and supporters, significant others have an important impact in promoting physical activity in young adolescents.


Children's one-hand catching as a function of age, gender, and ball location.

A sizable body of literature exists on the product characteristics and developmental sequence for two-hand catching, but to date there is no description of the developmental characteristics of simple one-hand catching in young children. This study investigated the influence of age, gender, and ball location on children's one-hand catching. Boys and girls (N = 240) ranging in age from 5 to 12 years attempted to catch a total of 24 tennis balls, tossed from a 9-ft distance. Tosses were directed to four locations: (a) Waist, (b) Shoulder, (c) Above-the-Head, and (d) Out-to-the-Side. Descriptive data consisted of the percentage of successful catches at each ball location, and the hand-arm orientation selected by the child as a function of ball location. Results revealed that catching performance improved with age, boys caught more balls than girls, ball location influenced catching success, and, in general, the location of the toss constrained the child's selection of an appropriate hand-arm orientation. With the possible exception of the Shoulder location for girls, even very young children are sensitive to the perceptual aspects of the toss and respond with an appropriate orientation.


Effects of violating local independence on IRT parameter estimation for the Binomial Trials Model.

The appropriateness of the Binomial Trials Model for test data that consist of multiple attempts of the same item needs to be determined because the presence of learning or fatigue effects may violate the model's assumption of local independence. The purpose of this study was to determine what effect the severity of the violation of local independence (VLI), coupled with different sample size (SS), test length (TL), and test difficulty (TD) had on the estimation of the model difficulty parameter, b, using computer simulation techniques. Each of the following conditions was replicated 100 times under a completely crossed design: SS (100, 200, 500, 2,000); TL (5, 10, 20, 25 attempts); TD (-1.2, 0.0, 1.2); and VLI (from no violation to complete violation). Examinee ability or latent trait was pseudorandomly drawn from a standard normal distribution, and the b-parameter was estimated using a maximum likelihood procedure on generated test scores. Regardless of SS, TL, and TD, the b-parameter tended to be overestimated for situations in which the VLI condition simulated fatigue and underestimated when the VLI condition simulated late-test learning or practice effect. The findings suggest that violations of local independence, at least as simulated in this study, could seriously bias the difficulty parameter estimates if all examinees tested exhibited the dependency.


The reliability and validity of the 20-meter shuttle test in American students 12 to 15 years old.

The purpose of this study was threefold: to determine (a) the test-retest reliability of the 20-m shuttle test (20 MST) (number of laps), (b) the concurrent validity of the 20 MST (number of laps), and (c) the validity of the prediction equation for VO2max developed by Léger, Mercier, Gadoury, and Lambert (1988) on Canadian children for use with American children 12-15 years old. An intraclass coefficient of .93 was obtained on 20 students (12 males; R = .91 and 8 females; R = .87) who completed the test twice, 1 week apart (MT1 = 47.80 +/- 20.29 vs. MT2 = 50.55 +/- 22.39 laps; p > or = .13). VO2peak was obtained by a treadmill test to volitional fatigue on 48 subjects. The number of laps run correlated significantly with VO2peak in males (n = 22; r = .65; F [1, 20] = 14.30 p < or = .001), females (n = 26; r = .51; F [1, 24] = 8.34; p < or = .01), and males and females = (r = .69; F [1, 46] = 42.54, p < or = .001). When the measured VO2peak (M = 49.97 +/- 7.59 ml.kg-1.min-1) was compared with the estimated VO2max (M = 48.72 +/- 5.72 ml.kg-1.min-1) predicted from age and maximal speed of the 20 MST (Léger et al., 1988) no significant difference was found, t (47) = -1.631; p > or = .11, between the means; the r was .72 and SEE was 5.26 ml.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)


Age-related differences in the control of spatial aiming movements.

The experiment was designed to (a) examine age-related differences in the control of aiming movements, and (b) determine the locus of slowing in movement execution of older adults. Fitts's (1954) index of difficulty (ID) was used to manipulate movement execution demands, and kinematics were used to examine the response characteristics. Twelve young and 12 older adults performed simple aiming movements 10 cm or 20 cm in amplitude to targets of 0.5 cm, 1.0 cm, or 2.0 cm in width, resulting in IDs ranging from 3.32 to 6.32. The results for both young and older subjects support the prediction that movement time (MT) increases as a function of ID and that older adults are significantly slower and more affected by increases in ID than the young adults. Velocity and acceleration profiles of the older adults' movements displayed very different response characteristics than those of the young adults. The results suggest that older adults emphasize accuracy of response and are concerned with the latter phase of the movement in order to contact a target accurately.


A comparison of modeling modalities in the observational learning of an externally paced skill.

This study contrasted prepractice modeling with either the perceptual component (perceptual modeling) or the motor component (movement pattern) of a coincident-timing task to determine whether experiencing the modalities singly or in combination enhanced timing performance on initiation of active practice. The motor component was a 60-cm right-to-left arm movement coincident with the illumination of lights on a Bassin timer runway to displace a barrier as the final runway light was illuminated. Four groups were compared (n = 12 per group). A perceptual modeling group passively viewed stimulus runway lights prior to attempting the task. A motoric modeling group viewed a videotape prior to practice of a model performing the motor component of the skill with zero timing error. A perceptual modeling plus motoric modeling group experienced both modeling modalities prior to performance. Finally, a no modeling group simply initiated practice on the task without modeling. Results indicated that the groups experiencing perceptual modeling initiated practice with significantly less average timing error and variability. Thus, perceptual modeling appeared to be at least as important as motoric modeling as a source of prepractice information to make available to a learner to optimize coincident-timing skill acquisition.


What undergraduate physical education majors learn during a field experience.

Early field experiences and student teaching have a significant impact on the development of prospective teachers' perceptions of teaching and themselves as teachers (Dodds, 1989). The purpose of this study was to describe what happened to physical education majors during a secondary physical education methodology course that included two field experiences in which the undergraduates taught at least one lesson a day. The four research questions that guided the study were (a) What issues did the majors attend to as significant incidents from their teaching, and did these issues change during their field experiences? (b) What were the characteristics of field experience lessons they perceived as successful? (c) What were the characteristics of field experience lessons they perceived as unsuccessful? and (d) What were the physical education majors' conceptions of teaching? Participants in the study were 39 junior-year physical education teacher education majors. Data were collected using the critical incident technique (Flanagan, 1954) and an open-ended, written questionnaire that was designed to encourage the majors to reflect on various aspects of their teaching experience. The questionnaire and critical incidents were analyzed using an inductive analytical procedure and a series of categories developed from several readings of students' writings. The teacher preparation program affected how these trainees defined and evaluated their teaching experiences. In contrast to some of the earlier work in physical education, the results indicated pupil learning, quality lesson planning to ensure pupil learning, and efficient lesson management were major characteristics of successful lessons for these trainees. The trainees presented "theories of knowledge" that emphasized technical concepts of teaching with little attention to the social or ethical dimensions of their work or the content knowledge of their field. Additional research is needed to examine appropriate programmatic efforts to help preservice teachers reflect not only on teaching, learning, and schooling as a technical enterprise but also as a moral and ethical enterprise.


Cardiac structure and function in women basketball athletes: seasonal variation and comparisons with nonathletic controls.

To characterize hypertrophy and quantify seasonal changes in cardiac structure and function of women collegiate basketball (BB) athletes (n = 15), echocardiographic (echo) measurements were made in the fall (FALL1), winter (WIN), and spring (SPR), then again during the subsequent fall (FALL2; n = 10). Comparisons were made to age-matched nonathletes (NA) measured during FALL1 (n = 22) and SPR (n = 5). Left ventricular (LV) internal dimension-diastole (LVIDd), LV end-diastolic volume (LVEDV), stroke volume (SV), LV mass (LVM), septal thickness (IVS), LV posterior wall thickness (LVPW), right ventricular (RV) internal dimension-diastole (RVIDd), and aortic root diameter (AOD) were significantly larger (12-70%) in the athletes; RVIDd-, LVEDV-, SV-, and LVM-index were also significantly greater (8-46%). From FALL1 to SPR measurement periods, LVIDd, RVIDd, LVEDV, SV, IVS, and LVM-index increased significantly (7-18%) in the athletes. Over the same period of time, LVIDd, LAD, AOD, LVEDV, and SV measured in the five NA subjects increased significantly. In the athletes, LVIDs, RVIDd, IVS, LVPW, and LVM decreased significantly (5-30%) from the SPR to FALL2 measurement period. These data characterize the general nature of the cardiac hypertrophy noted in women BB athletes compared to NA controls and show that distinct changes in heart structure corresponding to different periods of the competitive season can occur in these athletes.


Relationship of optical density and skinfold measurements: effects of age and level of body fatness.

We examined relationships between skinfold (SKF) and optical density (delta OD) measurements across age and levels of body fatness (%BF) for 151 women, 20 to 72 years. There were significant (p < .05) relationships between delta ODs and SKFs at all sites, except the thigh. The interaction (SKF x Age) was significant (p < .05) for pectoral and biceps delta ODs. Slope comparisons indicated the relationships for younger (29 years) and older (59 years) women differed significantly from zero and each other (p < .05). Analysis of SKF x %BF interactions revealed that relationships between SKFs and delta ODs at the pectoral and biceps sites for leaner (22% BF) women differed significantly from zero (p < .05) and were larger than those for obese (39% BF) women (p < or = .05). Thus, the relationship between SKFs and delta ODs is stronger for younger and leaner women compared to older and fatter women. These findings may reflect differences in fat layering due to age or body fatness and provide insight as to why the manufacturer's near-infrared (NIR) equation significantly underestimates the %BF of obese women.


Coping by individuals with physical disabilities with perceived challenge in physical activity: are people consistent?

This study examined coping and affective experience to perceived challenge in physical activity settings in 30 individuals with physical disabilities in three separate situations over 6 months. On every occasion, each individual was asked to report the most challenging physical activity of the preceding week and indicate how he or she coped with the challenge and what affective states were experienced. Coping was measured using a modification of Carver, Scheier, and Weintraub's (1989) COPE inventory. Self-reported mood was assessed using the Positive Affect Negative Affect Schedule (Watson, Clark, & Tellegen, 1988). The data indicated that perceived challenge was characterized by high levels of positive affect. Generalizability theory, used to determine the relative stability of coping strategies, indicated that individuals with physical disabilities did not consistently use the same coping skill strategies across settings.


The role of sports as a social status determinant for children.

This study was designed to examine children's attitudes toward the role of sports in determining social status, as well as the activities in which children prefer to participate. A total of 227 boys and 251 girls in Grades 4, 5, and 6 completed a questionnaire to determine which criteria were most important in determining personal, female, and male popularity. Personal popularity was answered by the girls and boys according to "what would make you well liked by your classmates." Female and male popularity was determined by asking both girls and boys to decide "what would make (girls, for female subjects, and boys, for male subjects) well liked by your classmates." A comparison of results from the Buchanan, Blankenbaker, and Cotten (1976) investigation and the present study indicated that, in the last 15 years, appearance has become more important and academic achievement less important in determining personal popularity for girls. For boys, the comparison revealed that sports have become more important and academic achievement less important in determining personal popularity. Boys reported sports to be the most important determinant of personal and male popularity and appearance as the most important determinant of female popularity. Sports and appearance became more important for boys with each higher grade level. Girls reported appearance to be the most important determinant of personal, male, and female popularity. For girls, appearance became more important with each higher grade level. A comparison of results from the Buchanan et al. (1976) and the present study indicated that the activities in which girls and boys preferred to participate have changed.(ABSTRACT TRUNCATED AT 250 WORDS)


Correlates of change in walking for exercise: an exploratory analysis.

This study was designed to identify correlates of change in walking for exercise. Respondents to a random sample mailed exercise survey were asked to complete a follow-up questionnaire 24 months after the first. Responses were obtained from 1,739 adults, reflecting an 86.6% return rate. Nonrespondents did not differ from respondents for baseline level of walking for exercise. Respondents overrepresented Caucasian and middle to high education (or income) adults. Residualized measures of change in walking for exercise served as the dependent variable, adjusted for baseline walking. Similarly, key independent variables, subject to change over time, were included after residualization. At both baseline and 24 months follow-up, adults walked for exercise an average of just under 1 hour per week, and 23.5% of the initially active adults ceased walking for exercise at 2 years. Multiple regression analyses explained more variance in walking for exercise among women than men. Change in dynamic variables such as friend's support and vigorous physical activity accounted for most of the explained variance. Results suggest that dynamic variables may need to be sustained to maintain walking for exercise. The limited explained variance suggests that more precise measures and additional determinants of walking for exercise need to be identified.


Formation of multicellular spheroids composed of rat hepatocytes.

A novel method for the preparation of spheroids containing two types of cells (hetero-spheroid) has been successfully developed by using a collagen-conjugated thermo-responsive polymer, poly-N-isopropyl acrylamide, as a cell substratum. The hetero-spheroid was prepared by detaching the confluent monolayer composed of parenchymal and non-parenchymal rat liver cells at a temperature below lower critical solution temperature and culturing it on the non-adhesive substratum. The hetero-spheroid had activity in albumin secretion and PNPA hydrolase activity over a period of 60 days in dishes. These findings suggest that this spheroid formation system is a useful model of an alternative to animal tests of hepatotoxicity.


Elevation of the level of lipid peroxidation associated with hepatic injury in LEC mutant rat.

Long-Evans Cinnamon (LEC) mutant rat, which spontaneously develops a chronically necrotizing hepatic injury at 4-5 months of age, exhibits an excess hepatic copper accumulation. The hepatic injury was completely correlated to the excess hepatic copper accumulation in backcross progenies, supporting the previous hypothesis that the copper cytotoxicity causes the hepatic injury in LEC rat liver. The levels of the lipid peroxidation in symptomatic LEC rats at 4 months of age were significantly higher than those of age-matched asymptomatic LEC and normal rats. These results suggest that excessively accumulated copper provokes hepatic injury through initiating the lipid peroxidation.


Metabolic effects of diltiazem in the perfused rat liver.

The effects of diltiazem on oxygen uptake, glucose release, lactate production and pyruvate production in the perfused liver from fed rats were investigated. Diltiazem inhibits oxygen uptake and glycolysis. Glucose release from endogenous glycogen is increased after cessation of diltiazem infusion. The reversion of the inhibitory effects of diltiazem after cessation of infusion takes place very slowly. The compound also abolishes glucose release activation by norepinephrine, methotrexate and atractyloside. These effects seem to be the consequence of a more general effect of the drug on metabolism. It can be concluded that 0.5 mM diltiazem is highly toxic to the liver and that it should not be considered a specific agent against Ca(2+)-dependent hormones.


pNiXa, a Ni(2+)-binding protein in Xenopus oocytes and embryos, shows identity to Ep45, an estrogen-regulated hepatic serpin.

A Ni(2+)-binding protein (pNiXa, 45 kD, pI 8.5) discovered in Xenopus embryos, was isolated from oocytes. Based on amino acid sequences, pNiXa belongs to the serpin superfamily and shows identity to the cDNA sequence of Ep45, an estrogen-regulated hepatic serpin that contains an (HX)n-motif found in eukaryotic transcription factors. Nondenatured pNiXa, purified by Ni-affinity chromatography, inhibited bovine alpha-chymotrypsin. The presence of pNiXa in embryos when they are susceptible to Ni2+, the high avidity of pNiXa for Ni2+, and the (HX)n-motif point to pNiXa as a molecular target of Ni(2+)-teratogenesis.


Formation of reductive metabolite, 2-sulfamoylacetylphenol, from zonisamide in rat liver microsomes.

Zonisamide (1,2-benzisoxazole-3-methanesulfonamide) was metabolized to its reductive product, 2-sulfamoylacetylphenol, in rat liver microsomes under anaerobic conditions. The rate of NADPH-dependent reaction was much more rapid than that of NADH-dependent reaction. Furthermore, synergistic effect of NADH on NADPH-dependent reaction was not observed. The optimal formation of 2-sulfamoylacetylphenol from zonisamide in the presence of NADPH was observed around pH 7.0. Cimetidine showed an inhibitory effect on the formation of 2-sulfamoylacetylphenol in a dose-dependent manner. The reductive metabolism of zonisamide was almost completely inhibited by carbon monoxide, and was increased by pretreatment of rats with phenobarbital and pregnenolone 16 alpha-carbonitrile but not by pretreatment with ethanol, 3-methylcholanthrene and imidazole. These results suggest that phenobarbital- and pregnenolone 16 alpha-carbonitrile-inducible form(s) of cytochrome P-450 is responsible for the reductive metabolism of zonisamide to 2-sulfamoylacetylphenol in rat liver microsomes.


Serum amino acid levels and hepatic protein synthesis during liver regeneration after partial hepatectomy in rats.

The time courses of changes in serum concentrations of free amino acids and in hepatic protein synthesis during liver regeneration after partial hepatectomy were studied in rats. Hepatic protein synthesis was significantly higher 3, 5 and 7 days after partial hepatectomy than it was in sham-operated control rats, but there was no such difference 14 days after surgery. Serum total amino acid level was significantly higher in partially-hepatectomized rats than in control rats 3 days after surgery, and thereafter decreased slowly. By 7 days after surgery there was no significant difference between the two groups. Serum concentrations of threonine, serine, proline, histidine, tyrosine, methionine, ornithine and citrulline were significantly higher than in the control group 3 days after partial hepatectomy, and the concentrations of proline, histidine, tyrosine, methionine and ornithine were still high 5 days after surgery. In contrast, concentrations of branched-chain amino acids did not change.


Relationship among cardiac sympathetic nerve activity, blood pressure and heart rate during infusion of carperitide in rats.

The effect of the infusion of carperitide (alpha-human atrial natriuretic peptide; alpha-hANP) on cardiac sympathetic nerve activity, blood pressure and heart rate was studied in anesthetized rats. Intravenous infusion of carperitide (0.1 and 1.0 micrograms/kg/min) produced mild and dose-related decreases in mean arterial pressure without significant changes in cardiac sympathetic nerve activity or heart rate. In debuffered rats, carperitide (1.0 micrograms/kg/min) also produced a mild decrease in mean arterial pressure. No significant changes in cardiac sympathetic nerve activity or heart rate were observed. A significant correlation between changes in heart rate and cardiac sympathetic nerve activity was noted during infusion of carperitide and deafferentation did not alter this relationship. In contrast, no significant correlation was observed between changes in cardiac sympathetic nerve activity and blood pressure during infusion of carperitide in either buffer nerve intact or debuffered rats. These results suggest that the reduction of blood pressure induced by intravenous infusion of carperitide may not trigger the baroreceptor-mediated cardiac sympathoexcitation and this inhibition of baroreflex may be responsible for the anti-tachycardic effect of carperitide.


The anti-asthmatic agent KC 404 inhibits sodium absorption by canine tracheal epithelium.

To elucidate the effect of KC 404, an anti-asthmatic agent, on electrolyte transport across airway mucosa, we studied electrical properties of canine tracheal epithelium under isometric conditions in vitro. Addition of KC 404 decreased short-circuit current, transepithelial potential difference and cell conductance, accompanied by the decrease in 22Na flux from submucosa to mucosa. The KC 404-induced decrease in short-circuit current was inhibited by amiloride but not by diphenylamine-2-carboxylate. These results suggest that KC 404 selectively inhibits Na absorption by airway epithelium, thereby leading to the increase in water content in the respiratory lumen.


An evaluation of 2-benzyl-1-naphthol (DuP 654) analogs as systemic anti-inflammatory agents.

DuP 654 (2-benzyl-1-naphthol) is a topically active anti-inflammatory agent that was evaluated in phase II clinical trials as an anti-psoriatic agent. The compound is a potent 5-lipoxygenase inhibitor and exhibits inhibitory activity against lipopolysaccharide-stimulated release of interleukin-1 from human monocytes. DuP 654 cannot be used as a systemic anti-inflammatory compound due to its rapid and extensive metabolism. Fifteen analogs were synthesized in an attempt to block the systemic route(s) of metabolism. The compounds were evaluated (IP and PO) in the rat carrageenan paw edema inflammation model with plasma samples taken at 1, 2, 3, and 4 hours post-dose. Substitutions at the 4- and/or 8-positions on the naphthol, and/or on the benzyl group of the DuP 654 molecule were unsuccessful in achieving an analog which displayed both oral activity in the inflammatory model and high plasma levels without manifesting toxicity. The low plasma levels of some analogs may indicate poor absorption, high volume of distribution, or that the substitution did not inhibit the high hepatic "first-pass" metabolism observed with DuP 654. Other compounds not studied but similar in structure to DuP 654 may exhibit rapid and extensive metabolism.


Concurrent ingestion of lactate and aluminum can result in developmental toxicity in mice.

The influence of lactate on the potential developmental toxicity of high doses of aluminum (57.5 mg/kg/day) was evaluated. Three groups of pregnant Swiss mice were given by gavage daily doses of Al(OH)3 (166 mg/kg), aluminum lactate (627 mg/kg), or Al(OH)3 (166 mg/kg) concurrent with lactic acid (570 mg/kg) on gestational days 6-15. An additional group of pregnant mice received lactic acid (570 mg/kg) during the same period. Cesarean sections were performed on gestation day 18, and live fetuses were sexed, weighed and examined for morphological defects. Maternal toxicity was observed in the groups treated with aluminum lactate, and Al(OH)3 concurrent with lactic acid. The reproductive data did not show embryotoxic effects in any group, whereas fetal body weight was significantly reduced in the aluminum lactate group. In this group, morphological changes included cleft palate and an increased incidence of parietals with delayed ossification. Although not statistically significant, the incidence of skeletal variations was also increased in the group given Al(OH)3 concurrent with lactic acid. Taken together the present data, as well as the results of previous studies strongly suggest that the consumption of high doses of aluminum-containing compounds should be avoided during pregnancy.