Capillary blood lactate concentrations during intermittent all-out exercise.

The average maximal peak torques of the knee extensor and knee flexor muscles were measured during one, two or three series of 20 maximal contractions at an angular velocity of pi rad s(-1). Each series lasted about 20 s. After the first series, a 10 min rest was allowed before the second series of contractions. In one case only was a third series of contractions performed. Various sequences of contractions of the dominant and contralateral limbs were tested. Capillary blood lactate concentration ([LA]cap) was determined in the blood samples taken from an earlobe during each recovery. The difference between peak capillary blood lactate concentration and the concentration that would have occurred without any previous contraction (delta[LA]cap) was taken as the index of metabolic comparison between the exercise bouts. The mechanical power output during the first series of contractions was similar to that in the second and third series, but the lactate elevation was significantly higher in the first series. The discrepancy between the constancy of the power output and the decrease in lactate elevation was even more evident if delta[LA]cap was calculated as the difference between peak capillary blood lactate concentration and the value measured immediately before the second or third series. The decrease in lactate elevation was not affected by the change of the contracting limb from the first to the second series. In conclusion, the capillary blood lactate concentration profile during intermittent maximal exercise cannot be considered a suitable technique for evaluating lactate production.

Therapy with HMG CoA reductase inhibitors: characteristics of the long-term permanence of hypocholesterolemic activity.

Treatment with hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors has gained considerable success in the management of hypercholesterolemia. A large number of studies have shown the efficacy of these drugs in lowering plasma total and low density lipoprotein (LDL) cholesterol levels, but there have been less studies evaluating their effectiveness in standard clinical practice, particularly relating to the maintenance of hypocholesterolemic activity. In the present study, the long-term effectiveness of HMG CoA reductase inhibitors has been tested in 177 patients with familial hypercholesterolemia (FH) who had been on statin therapy (simvastatin or pravastatin) for at least 12 months and up to 5 years or longer. The mean 'dose normalized' LDL cholesterol reduction in the whole group was around 20%. However, in spite of a generally good efficacy of both statins in lowering total and LDL cholesterol, a wide variety of responses, either after short- or long-term treatment, was noted. Individual responses were calculated and patients classified into three different groups: (a) responders, (b) non-responders, and (c) response losers. Of the 177 patients, 4% did not respond to treatment and a further 10% showed an initial unsatisfactory response (LDL cholesterol reduction < or = 10%). Another 10% experienced a progressive loss of response over time. There appeared to be little difference between the two treatments in the long-term efficacy and no predictive index could be established. Treatment with HMG CoA reductase inhibitors is generally effective and well tolerated, but a non-negligible number of patients may show a primary non-response or a progressive loss of response.

Isokinetic torques and kicking maximal ball velocity in young soccer players.

The purpose of this study is to assess if there is any correlation between isokinetic testing and field performance of young soccer players. The isokinetic peak torques of the knee extensor muscles in sitting position (TKE), and those of the hip flexor muscles in standing position (THF) were measured in 24 junior soccer players. Four angular velocities (omega = 1.05, 3.14, 4.19, 5.23 rad.s-1 or 60, 180, 240, 300 deg.s-1) were used for the knee extensors and three (1.05, 3.14, 4.19 rad.s-1) for the hip flexors. On the field the subjects were asked to kick a stationary soccer ball as fast as possible against a barrier and the mean linear velocity over a 10 m path (v) was measured. TKE of the non dominant limb were higher than those of the opposite one at the three highest omega (p < 0.05). On the contrary the THF of the dominant limbs were higher than those of the controlateral, at the two highest omega. When the ball was kicked by the dominant or non dominant limbs, the mean values and standard deviations (+/- SD) of v were 23.6 (+/- 2.5) and 21.4 (+/- 2.6) m.s-1. Torques and v were always positively correlated to each other; however, only in few cases was this relationship statistically significant. In conclusion the isokinetic torques do not seem to be good predictors of v, one of the several factors which determine the global performances of the soccer players.

Pravastatin effectively lowers LDL cholesterol in familial combined hyperlipidemia without changing LDL subclass pattern.

Familial combined hyperlipidemia (FCHL) is the most common genetic lipid disorder among young survivors of myocardial infarction. Elevations of plasma total and low-density lipoprotein (LDL) cholesterol and the prevalence of small, dense LDL particles are both involved in the high coronary risk of FCHL patients. We investigated the ability of pravastatin to favorably correct plasma lipid and lipoprotein levels and LDL structure in FCHL patients. Twelve patients with FCHL, documented by studies of first-degree relatives, received pravastatin (40 mg/d) for 12 weeks. Pravastatin significantly lowered plasma total and LDL cholesterol levels by 21% and 32%, respectively. Triglyceride levels did not change, and apolipoprotein B (apoB) concentrations decreased by 9% (P = NS). High-density lipoprotein (HDL) cholesterol increased by 6% because of a significant 73% rise of HDL2 cholesterol. LDL were smaller (diameter, 24.5 +/- 0.5 nm), less buoyant, and apoB-rich (cholesteryl ester-apoB ratio, 1.64 +/- 0.46) in the selected patients compared with patients with familial hypercholesterolemia or healthy control subjects. LDL became even smaller (23.8 +/- 0.6 nm) and richer in apoB (cholesteryl ester-apoB ratio, 1.27 +/- 0.52) after pravastatin treatment. Although pravastatin favorably altered plasma lipid and lipoprotein levels in FCHL patients, the abnormal LDL particle distribution and composition were not affected. Because of the apparent resistance of the small, dense LDL to drug-induced modifications, a maximal lipid-lowering effect is needed to reduce coronary risk in FCHL patients.

Functionally abnormal monocytes in hypercholesterolemia.

We investigated some functions of monocytes from 20 type IIa hypercholesterolemic (HC) and five homozygous familial hypercholesterolemic (FH) patients. Monocytes from the HC patients contained as much cholesterol and formed as much thromboxane B2 in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP) or calcium ionophore A23187 as those from normal individuals. In contrast, the generation of prostaglandin E2 and 6-ketoprostaglandin F1 alpha in response to these agonists was 1.5-3 times normal, and that of leukotriene B4 was 40-60% of the normal value (p < 0.05 for all). Studies in which the combination of fMLP or A23187 with sodium arachidonate were employed suggested that these abnormalities were independent of the availability of the endogenous substrate for the lipoxygenase or cyclooxygenase enzymes. Quantitatively and qualitatively comparable abnormalities were found in monocytes from the five FH patients, and these were little affected when the patients' plasma cholesterol levels were almost normalized by low density lipoprotein apheresis. In keeping with the abnormalities in the eicosanoid metabolism, monocytes from HC patients exhibited a defective ability (p < 0.05) to generate O2-, the extent of which was correlated with the impaired formation of leukotriene B4. On the other hand, adhesion studies indicated that patients' cells exhibited an abnormally high ability to adhere to glass (p < 0.01). These data indicate the presence of functionally abnormal monocytes in hypercholesterolemia and suggest a direction to be followed to understand the importance of such cells in the premature atherosclerosis that occurs in these patients.

Hypertriglyceridemia and regulation of fibrinolytic activity.

A relation between elevated triglyceride (TG) levels and alterations of the fibrinolytic system has been recognized in studies of patients with coronary heart disease. In this investigation, the total fibrinolytic activity and the levels of specific components of the fibrinolytic system were evaluated in plasma samples from a highly selected group of patients with type IV hyperlipoproteinemia before and after a dietary treatment aimed at reducing TG levels. The fibrinolytic response of type IV patients was comparable to that of normolipidemic subjects, whereas tissue-type plasminogen activator antigen levels before and after venous occlusion (p less than 0.01) and resting plasminogen activator inhibitor-1 (PAI-1) antigen (p less than 0.01) and activity (p less than 0.01) were significantly higher in hypertriglyceridemic subjects compared with controls. After dietary treatment, a 22% reduction in TG levels was attained in type IV patients, with no appreciable modification of fibrinolytic parameters. The analysis of the single-patient data revealed a tendency toward normalization of PAI-1 levels only in those patients who showed a TG reduction greater than or equal to 20%. Very low density lipoproteins (VLDLs) from both normal and type IV patients concentration-dependently stimulated PAI-1 release by endothelial cells and HepG2 cells, with the effect of VLDL from type IV patients being more pronounced on HepG2 cells. The release of PAI-1 induced by VLDL in competent cells may thus account for the elevated levels of this antifibrinolytic protein that occur in hypertriglyceridemic patients.

Prenatal management of twin gestation. Experience with a new protocol.

We carried out a prospective cohort study to evaluate the usefulness of a specific protocol of prenatal management of twin pregnancy to decrease the incidence of prematurity in the population. The protocol particularly stressed the importance of early recognition of uterine contractile activity and early work leave (from 28 weeks' gestation). The outcome of 39 consecutive twin pregnancies that used the protocol over a five-year period was compared with the outcome of 76 twin pregnancies followed by private practitioners and delivered at our department. The two groups were comparable with respect to maternal age, parity, gestational age at diagnosis, socioeconomic level and educational level. The incidence of preterm delivery was significantly lower in the study group than in the control group. Even more significant was the difference in the incidence of severe prematurity (less than 34 weeks' gestation) between the two groups. The use of a protocol like ours, which does not include prolonged hospitalization, home bed rest or tocolytic treatment, is recommended.

Efficacy of cholestyramine does not vary when taken before or during meals.

Compliance to cholestyramine treatment, often unsatisfactory, may become further problematic because of the common indication that the resin should not be taken with meals. Since there is no convincing data on the validity of this therapeutic schedule, 10 type IIA hyperlipoproteinemic patients received cholestyramine either before or during the 3 major meals, according to a cross-over protocol. Plasma lipid levels were monitored after 4 and 6 weeks of each treatment schedule. The efficacy of the resin, in terms of total cholesterol (-16.5% together with food vs. -17.2% before food) and of low density lipoprotein cholesterol reduction (-22.8% with food vs. -23.1% before food) did not differ. The side effect profile was also not different between the two treatment protocols. These findings suggest that there are no significant interactions between food and the anion exchange resin and that the hypocholesterolemic effect does not depend upon a specific timing, supposedly close to the gallbladder contraction. They are particularly significant in view of the future availability of new resins in liquid form, suitable for intake during meals.

Results of a preventive program for congenital toxoplasmosis.

All pregnant women followed during the period 1982-87 were screened for toxoplasmosis, and 35 patients had documented seroconversion or doubtful toxoplasmosis titers. One patient opted for pregnancy termination. The remaining were followed with a protocol that included serial ultrasound examinations and prophylactic antibiotic treatment of the mother and neonate. No fetal abnormalities related to congenital toxoplasmosis were found. All the infants had negative toxoplasmosis test titers at birth; at follow-up only one was found to have developed a subclinical infection, at 2 months of age. Our data suggest that antiparasitic treatment during pregnancy for those at risk for Toxoplasma infection may reduce the transmission rate.

Hepatosplenomegaly as the only prenatal finding in a fetus with pyruvate kinase deficiency anemia.

A case of congenital pyruvate kinase deficiency manifested at antenatal ultrasound as isolated hepatosplenomegaly is reported and the differential diagnosis is discussed. An aggressive obstetric management and appropriate neonatal care permitted a favorable neonatal outcome.

The effect of range of motion and isometric pre-activation on isokinetic torques.

The effect of an increased angle of excursion and isometric pre-activation on isokinetic torques of knee extensors was investigated in five male subjects, mean age 35.0 years, SD 9.6. Peak torque and isoangular torque at 0.52 rad from full knee extension (FKE) were measured when contractions were carried out at 3.14, 4.19 and 5.24 rad.s-1 starting: 1) from a standard knee angle (SA) of 1.57 rad from FKE, 2) from the same starting angle as SA, plus an isometric preload (P) equivalent to 25% of isometric maximal voluntary contraction and 3) from an increased angle of knee flexion (IA), 2.09 rad from FKE plus P. Surface integrated electromyograms (iEMG) of the vastus lateralis muscle in SA and IA + P were also recorded. The IA + P had the effect of increasing peak torque, as compared to SA, on average by 12.0%, SD 7.5% (P less than 0.001) at 3.14 rad.s-1, 19.5%, SD 5.5% (P less than 0.001) at 4.19 rad.s-1, 21.6%, SD 10.7% (P less than 0.001) at 5.24 rad.s-1 and of increasing mean iEMG by 15.7%, SD 7.0% (P less than 0.001) at 5.24 rad.s-1. The IA + P also had the effect of increasing the angle from FKE at which peak torque occurred: from means of 0.80 rad, SD 0.11 to 1.00 rad, SD 0.07 at 3.14 rad.s-1, from 0.65 rad, SD 0.11 to 0.92 rad, SD 0.09 at 4.19 rad.s-1 and from 0.60 rad, SD 0.11 to 0.88 rad, SD 0.11 at 5.24 rad.s-1 (P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of serum triglycerides on the HDL pattern in normal subjects and patients with coronary artery disease.

The distribution and structure of high density lipoprotein (HDL) subfractions were examined by rate zonal ultracentrifugation in 200 consecutive subjects, 86 of whom showed a stable hypertriglyceridemia, 22 with coronary artery disease. Among the remaining 114 normotriglyceridemic subjects, 75 were healthy and 39 had coronary disease. The serum levels of the HDL2 subfraction were reduced by 22% in the 39 normotriglyceridemic coronary patients, and by 21% in the whole group of hypertriglyceridemic subjects. No difference in the HDL3 levels was found in any of the studied group. There was a clear negative correlation between HDL2 levels and triglyceridemia in the case of healthy people, not in coronary patients. By contrast, triglyceridemia was negatively correlated with the HDL3 flotation rate, both in healthy subjects and coronary patients at all triglyceride levels. Compositional data indicate that in hypertriglyceridemic subjects, HDL2 levels are reduced because of an enhanced transfer-exchanged process between the enlarged VLDL pool and HDL; in contrast, in coronary patients, a defective maturation of the HDL3 particle is the most likely underlying mechanism. Both in hypertriglyceridemic individuals, as well as in coronary patients, the HDL subfraction distribution is rather similar and drastically different from that of normotriglyceridemic healthy subjects. The mechanisms of the two conditions are probably different and, whereas a low concentration of HDL2 is definitely a major risk factor for normotriglyceridemic individuals, in the case of hypertriglyceridemics other factors may come into play in the final determination of the coronary risk.

Ureteropelvic junction obstruction in utero and ex utero.

Seventy cases of ureteropelvic junction obstruction, bilateral or unilateral, were followed prospectively throughout gestation and postnatally for an average of 2.3 years. Cases of ureteropelvic junction obstruction with a renal pelvis dilated less than 1 cm uniformly did well; those with a pyelectasis more than 2 cm, both bilateral and unilateral, had a favorable outcome in approximately three-quarters. Surprisingly, pelvis dilatation between 1-2 cm had a better outcome if bilateral than if unilateral.

Physiological responses during prolonged exercise at the power output corresponding to the blood lactate threshold.

Heart rate (HR) and oxygen uptake (VO2) at the mechanical power (W) corresponding to the capillary blood lactate ([la]cap) of 4 mmol.l-1 (Wlt) were measured in 34 healthy male subjects during incremental exercise (Winc). On the basis of these measurements, the subjects were asked to cycle at Wlt for 60 min (steady-state exercise, Wss). Twenty subjects could not reach the target time (mean exhaustion time, te, 38.2 min, SD 5.3), while 6 of the 14 remaining subjects declared themselves exhausted at the end of exercise. The final [la]cap if the two groups of exhausted subjects were 5.3 mmol.l-1, SD 2.3 and 4.3 mmol.l-1, SD 1.1, respectively. At the end of Wss, [la]cap and HR were significantly lower in the 8 unexhausted subjects than in the other subjects. This group also had a lower HR at Wlt during Winc. The HR and VO2 appeared to be higher during Wss than during Winc. When all subjects were ranked according to their te during Wss, Wlt (expressed per kilogram of body mass) was found to be negatively related to te. In conclusion, during Winc, measurements of physiological variables at fixed [la]cap give a poor prediction of their trends during Wss and of the relative te; at the same work load [la]cap can be quite different in the two experimental conditions. Furthermore, resistance to exercise fatigue at Wlt seems lower in the fitter subjects.

Is there an association between colonization with group B Streptococcus and prematurity?

The purpose of this study was to determine whether there is a relationship between colonization of the genitourinary tract with group B Streptococcus (GBS) and prematurity. A search of the literature was conducted to identify articles addressing this issue. Ten studies provided enough data for a critical review; seven studies focused on genital colonization and three on asymptomatic bacteriuria. An association between cervicovaginal colonization with GBS and prematurity could not be demonstrated in six of the seven studies. However, women with asymptomatic bacteriuria caused by GBS had a higher rate of prematurity than did women without asymptomatic bacteriuria. We conclude that the weight of the available evidence does not support an association between prematurity and GBS colonization of the genital tract in the absence of asymptomatic bacteriuria.

Plasma lipoprotein changes after treatment with pravastatin and gemfibrozil in patients with familial hypercholesterolemia.

The ability of pravastatin, a new hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, to lower plasma lipid levels and modify lipoprotein patterns was compared with that of gemfibrozil in 18 patients with familial hypercholesterolemia who participated in a 16-week, double-blind, parallel trial. Pravastatin proved better than gemfibrozil in lowering total and low-density lipoprotein (LDL) cholesterolemia: -23.6% and -28.2% versus -18.1% and -21.4%, respectively. A significant positive correlation was found between the starting level of serum cholesterol (both total and LDL) and the gemfibrozil-induced reduction (r = 0.72 and 0.69), whereas the hypocholesterolemic effect of pravastatin was apparently independent from pretreatment levels (r = 0.32 and 0.10). Apolipoprotein B concentrations were lowered by 25.4% (pravastatin) and 22.0% (gemfibrozil). Pravastatin and gemfibrozil reduced triglyceride levels by 13.9% and 49.4%, respectively. Both drugs increased the level of high density lipoprotein (HDL) cholesterol, but this change was significant only with gemfibrozil (p less than 0.05). The HDL subfraction structure and distribution were not modified by pravastatin treatment. Gemfibrozil, in contrast, increased HDL3 cholesterol level by 9% because of an enrichment of HDL3 particles in both free cholesterol and cholesteryl esters and lowered the flotation rate of HDL3 (p less than 0.05). LDL particles became smaller after gemfibrozil treatment (diameter: 25.4 +/- 0.3 nm vs 26.1 +/- 0.4 nm, p less than 0.01) and were not modified by pravastatin. This comparison shows a more pronounced efficacy of the HMG CoA reductase inhibitor on total and LDL cholesterol levels, also indicating that pravastatin acts by a single major mechanism, reducing the number of circulating LDL particles. Gemfibrozil may exert additional activities, possibly consequent to the stimulation of very low density lipoprotein catabolism.

Infection and labor. V. Prevalence, microbiology, and clinical significance of intraamniotic infection in women with preterm labor and intact membranes.

Amniotic fluid was retrieved by amniocentesis from 264 patients with preterm labor and intact membranes admitted to Yale-New Haven Hospital from Jan. 1, 1985, to July 31, 1988. The prevalence of a positive amniotic fluid culture was 9.1% (24/264). A total of 111 patients (42%) delivered preterm neonates, and 24 (21.6%) of those had positive amniotic fluid cultures. The diagnostic indexes of the Gram stain of amniotic fluid in the prediction of a positive amniotic fluid culture were as follows: sensitivity, 79.1%; specificity, 99.6%; positive predictive value, 95%; and negative predictive value, 98%. Endotoxin was detected with the limulus amebocyte lysate assay in 4.9% (13/264) of patients with preterm labor. All patients with endotoxin in the amniotic fluid delivered preterm neonates. The three most frequently isolated organisms were Ureaplasma urealyticum (n = 6), Fusobacterium species (n = 5), and Mycoplasma hominis (n = 4). Clinical chorioamnionitis was present in only 12.5% of the patients with positive amniotic fluid cultures. Women with positive amniotic fluid cultures had lower gestational ages and more advanced cervical dilatation on admission than women with negative cultures. Preterm infants born to mothers with positive amniotic fluid cultures had a higher incidence of respiratory distress syndrome and infectious complications than preterm neonates born after negative amniotic fluid cultures. These data underscore the frequency and importance of intraamniotic infections in women with preterm labor.

Mechanisms of HDL reduction after probucol. Changes in HDL subfractions and increased reverse cholesteryl ester transfer.

Treatment with probucol, a widely used lipid-lowering agent, is associated with a significant reduction of high density lipoprotein (HDL) cholesterol levels, but with an apparently improved removal of cholesteryl esters from tissues (e.g., from tendon xanthomas). The effects of probucol (500 mg twice daily) on HDL subfraction distribution and cholesteryl ester transfer activity were tested in 12 patients with stable type II hyperlipidemia [low density lipoprotein (LDL) cholesterol greater than 180 mg/dl] after a placebo-controlled cross-over trial. Probucol significantly lowered total cholesterol (-13.8%), LDL cholesterol (-9.1%), and HDL cholesterol (-30%). By rate zonal ultracentrifugation, a marked reduction of HDL2 cholesterol (-68%) was shown, whereas changes in HDL3 were less significant (-21%). These findings were confirmed by polyacrylamide gradient gel electrophoresis, typically showing a reduction or disappearance of HDL2b particles and the prevalence of particles in the HDL3a range. Cholesteryl ester transfer from HDL to lower density lipoproteins was significantly increased (30%) in all patients. These findings suggest that, in addition to the well-documented in vitro changes (prevention of LDL peroxidation and macrophage uptake), probucol characteristically modifies HDL particle distribution in vivo, and is associated with a significant increase of cholesteryl ester transfer activity.

First trimester diagnosis of a partial mole with the combined use of ultrasound and chorionic villous sampling.

A patient with vaginal bleeding in the first trimester of pregnancy had a serum human chorionic gonadotropin (hCG) titer of 495,132 mlU/ml and an abdominal ultrasound examination revealed an intrauterine gestational sac without a fetal pole. Two and a half weeks later the hCG titer was 385,000 mlU/ml and a fetal pole was visualized. Transabdominal villous sampling was performed because of the suspicion of a partial mole. Histopathologic examination showed hydropic villi and chromosomal studies were consistent with triploidy. The diagnosis of partial mole in the first trimester of pregnancy was made and the pregnancy terminated.

Accuracy of ultrasound in the prenatal diagnosis of spinal anomalies.

This study was undertaken to determine the accuracy of sonographic examination in the prenatal diagnosis of neural tube defects. The study population consisted of 237 patients divided into three groups according to the indication for the sonographic examination. The overall sensitivity of sonography in the diagnosis of neural tube defects was 94.7%, and the specificity was 98.3%. A false positive diagnosis of spina bifida occurred in a fetus affected with ventriculomegaly, omphalocele, severe kyphosis and scoliosis. There were three false negative diagnoses of spina bifida.