Sequence of fibrinogen proteolysis and platelet release after intrauterine infusion of hypertonic saline.

Plasma fibrinopeptide B (Bbeta1-14 or FPB) immunoreactivity was studied by radioimmunoassay in patients who received intrauterine infusion of hypertonic saline to terminate pregnancy. FPB immunoreactivity increased with thrombin treatment (TIFPB) suggesting the presence of a larger FPB-containing peptide, since purified FPB is not altered by thrombin, whereas thrombin increases the immunoreactivity of Bbeta1-42 (which includes FPB) 10-fold. TIFPB immunoreactivity in plasma, drawn 4 h after hypertonic saline infusion eluted from Sephadex G-50 similarly to isolated Bbeta1-42. Streptokinase, incubated with normal plasma progressively generated TIFPB immunoreactivity, which showed a major component which eluted from Sephadex G-50 similarly to Bbeta1-42. Streptokinase generated TIFPB much more rapidly in reptilase-treated plasma that contains fibrin I, (which still includes FPB), indicating that fibrin I is preferred over fibrinogen as a substrate for plasmin cleavage of arginine (Bbeta42)-alanine (Bbeta43). Serial studies were then made in 10 patients receiving intrauterine hypertonic saline. Fibrinopeptide A (FPA) levels rose immediately, reached a peak between 1 and 2 h, were declining at 4 h, and were normal at 24 and 48 h. TIFPB levels rose slightly in the 1st h, reached a peak at 4 h, and had returned to base-line values at 24 h. Serum fibrinogen degradation product levels were unchanged at 1 h, reached their highest level at 4 h, and were still markedly elevated at 24 and 48 h. Fibrinogen levels dropped slightly being lowest at 4 and 24 h. Platelet counts declined in parallel with the fibrinogen levels over the first 4 h, but continued to decrease through 48 h. Beta thromboglobulin (betaTG) levels generally paralleled FPA levels whereas platelet factor 4 (PF4) levels showed only slight changes. The data indicate that immediately after intrauterine hypertonic saline infusion thrombin is formed that cleaves FPA from fibrinogen to produce fibrin I and releases betaTG and PF4 from platelets. Later plasmin cleaves Bbeta1-42 from fibrin I to produce fragment X, which is further degraded to form serum fibrinogen degradation products. This sequence of proteolysis indicates that plasmin action on fibrin I serves as a mechanism that regulates fibrin II formation by removing the Bbeta chain cleavage site, which is required for thrombin action in converting fibrin I to fibrin II.

Activation of heat-shock factor by stretch-activated channels in rat hearts.

BACKGROUND: Previously, we have observed that the isolated, erythrocyte-perfused rabbit heart has increased levels of heat-shock protein (HSP) 72 after a mild mechanical stress. We hypothesized that stretch-activated ion channels (SACs) mediated this increase. Methods and Results-- To test this hypothesis, we subjected isolated, perfused rat hearts to mechanical stretch. Gel mobility shift assay showed that heat-shock factor (HSF) was activated in hearts with mechanical stretch, but not in controls. Supershift experiments demonstrated that HSF1 was the transcription factor. Northern blots revealed the concomitant increase in HSP72 mRNA in stretched rat hearts. In a separate set of experiments, gadolinium, an inhibitor of SACs, was added to the perfusate. Gadolinium inhibited the activation of HSF and decreased HSP72 mRNA level. Because gadolinium can inhibit both SACs and L-type calcium channels, we perfused a group of hearts with diltiazem, a specific L-type calcium channel blocker, to eliminate the involvement of L-type calcium channels. Diltiazem failed to inhibit the activation of HSF. CONCLUSIONS: Stretch in the rat heart results in activation of HSF1 and an increase in HSP72 mRNA through SACs. This represents a novel mechanism of HSF activation and may be an important cardiac signaling pathway for hemodynamic stress.

[Assessment and treatment of coexisting mental illness or dual diagnosis]. / Prise en charge des patients "double diagnostic": comment sortir du carrousel institutionnel?

Substance abuse touches around a quarter of psychiatric patients, which brings up various therapeutic problems. Literature shows us that between the "parallel", "series" and "integrated" approaches, it is the integrated approach which proves to be the most effective in terms of reducing symptoms, hospitalisations and criminality. An improvement in the patients' quality of life can also be observed. The integrated approach is developed by a team of in-patient and out-patient workers, whose job is to identify and evaluate clinically the motivation and the psychological and social functioning of the patients, and to propose suitable treatments according to the pathology and context of each case. A designated "case manager" guarantees the long term therapeutic project for each patient.

Simultaneous optical and nuclear magnetic resonance spectroscopy for monitoring cardiac energetics in vivo.

There are a number of applications in which it is useful to simultaneously collect data from what are traditionally separate instrumentation modalities. In particular, in vivo physiological investigations in which data from parallel experiments must be correlated would benefit from simultaneous data collection through 1) elimination of subject variability, 2) elimination of treatment variability, and 3) a reduction in the number of animal preparations required. Here we describe the simultaneous collection of fluo-3 optical fluorescence and 31P nuclear magnetic resonance (NMR) spectra to measure intracellular calcium levels and high-energy phosphate metabolism, respectively, in vivo. This work is part of ongoing research into the profound anoxia tolerance exhibited by the hearts of certain turtle species. An NMR compatible optical fluorescence spectrometer was constructed and tested. In the 31-cm bore of a 2 T superconducting magnet, NMR and optical spectra were collected every 10-15 min from the in situ, in vivo hearts of anesthetized turtle subjects prior to and during one to three hours of anoxia. It was found that while PCr stores became significantly depleted during anoxia, beta-adenosine triphosphate (ATP) levels remained within 20% of control values, and intracellular diastolic calcium levels did not vary by more than 10%. The ability to make simultaneous phosphorus and calcium measurements on a single subject is important to understanding the exact relationship between phosphorus energy state and maintenance of calcium homeostasis.

Anoxia and ischemia tolerance in turtle hearts.

It has been known since ancient times that turtle hearts exhibit extraordinary tolerance to anoxia or ischemia. The mechanisms by which they accomplish this remain obscure. The most important adaptation in anoxic turtles is a rapid and dramatic decrease in metabolic rate. Nuclear magnetic resonance measurements indicate that painted turtle (Chrysemys picta) hearts respond to anoxia with a rapid decrease in phosphocreatine (PCr; to 50% of control) after which PCr remains constant for at least 4 h. ATP is defended and does not decrease while intracellular pH (pHi) decreases by 0.2 pH units early in anoxia and is then maintained constant. Softshelled turtles (Trionyx spinifer) have been demonstrated to be far more sensitive than painted turtles to anoxia in vivo. However, isolated hearts from softshelled turtles appear to be as anoxia tolerant as those of Chrysemys. During ischemia there is also little difference in cardic performance, high energy phosphates, or pHi between these two species. A peculiar feature of turtle hearts is an extremely high concentration of phosphodiesters (PDE). The role of cytosolic PDEs remains controversial but they may function as lysophospholipase inhibitors and thereby limit phospholipid turnover (Burt CT and Ribolow H, Comparative Biochemistry and Physiology, 108B: 11-20, 1994). Whether PDEs promote anoxia/ischemia tolerance is unknown but these stresses can result in membrane lipid dysfunction in mammals. Metabolic control, acid-base, and phospholipid homeostasis all play a role in anoxia and ischemia tolerance in turtle hearts. These physiologic processes are interdependent, and how they interact in these animals is unknown, but they are experimentally accessible by modern analytical methods.

Walk-through surveys for child labor.

Child labor is increasing in both developing and developed countries. Walk-through surveys were used to identify children, aged 8-15 years, working in six sites in Tel Aviv and Jerusalem, the largest cities in Israel. Of the 45 children who were interviewed, 20 were Jewish Israeli born, 19 were recent Jewish immigrants from the former Soviet Union, and six were Arabs from Judea, Samaria, and Gaza. The majority of children were either too young for employment, according to the Israeli Child Labor Laws, and/or receiving less than the legal minimum wage. Many were performing physical labor that might be expected to interfere with normal growth and development. Many of the children had visible signs of impaired physical health. Some were subjected to physical and/or verbal abuse. Walk-through surveys are recommended as a tool for routine use for surveillance of hazardous working conditions, case-finding, and evaluating the efficacy of preventive measures. The World Health Organization recommendations are emphasized to eliminate hazardous working conditions and to provide on-the-job health and social services to working children.

Effects of anoxia and graded acidosis on the levels of circulating catecholamines in turtles.

We measured circulating levels of catecholamines in painted turtles subjected to anoxia with different degrees of concomitant acidosis at 20 degrees C and in turtles subjected to long-term submergence at 3 and 10 degrees C. Blood levels of both epinephrine (E) and norepinephrine (NE) increased during N2-breathing, N2/CO2 breathing and submergence, with NE generally being present in higher concentrations than E. During submergence at 20 degrees C, anoxic turtles experienced an extreme acidosis and NE levels exceeded 18,000 pg/ml. The greater the degree of acidosis in anoxic turtles the higher were the levels of plasma NE (log [NE; pg/ml] = 1.640 x pHa + 15.776, r = -0.826). Elevation of plasma E under anoxic conditions was more modest and the correlation between plasma E and pHa was less pronounced (log [E; pg/ml] = -0.329 x pHa + 6.069, r = -0.285). Submergence at lower temperatures also resulted in increases in plasma levels of NE, but while plasma E generally increased during anoxia, this elevation was less dramatic than that observed for NE. Exposure of turtles to either mild (6.5% CO2) or severe (14.5% CO2) normoxic hypercapnia resulted in no increase in E and only modest increases in NE. Upon resumption of air-breathing in all of the 20 degrees C protocols, turtles rapidly restored E and NE to control levels. The function of elevated plasma catecholamines during anoxia and acidemia in turtles is unknown but may be important in stimulating respiratory and cardiovascular recovery once air-breathing is resumed. Catecholamines may also play a role in mediating the rise in blood glucose we observed in this study, which may be an important factor in maintaining tissue viability during anoxic stress.

Acid-base balance and the control of respiration during anoxic and anoxic-hypercapnic gas breathing in turtles.

We studied the ventilatory and blood acid-base response of turtles to 6 h of breathing either 100% N2 (anoxic) or 95% N2-5% CO2 (anoxic-hypercapnic). In both groups, minute ventilation (VE) increased promptly with anoxia, with peak ventilation occurring between 1 and 3 h. VE then decreased but was still significantly above control at 6 h. The increase in VE resulted from increases in both respiratory frequency (f) and tidal volume (VT) but after ventilation peaked, f declined to control while VT remained elevated. We observed no significant differences in VE between the two groups in spite of significantly lower arterial pH and higher arterial PCO2 in the anoxic-hypercapnic turtles. During normoxic recovery, VE quickly increased to the peak anoxic values due primarily to a greatly increased f. In both groups, plasma [lactate-] increased during anoxia. Plasma cation concentrations also increased, partially compensating for the elevated blood lactate. We conclude that the anoxic hyperventilation did not depend on arterial pH and central chemoreceptor control but rather on peripheral hypoxic chemoreceptor control. We believe that the decline in VE during prolonged anoxic breathing results from a metabolic arrest response and/or a depression in central nervous function.

Biomedical device design discovery team approach to teaching physiology to undergraduate bioengineering students.

Teaching effectiveness is enhanced by generating student enthusiasm, by using active learning techniques, and by convincing students of the value of acquiring knowledge in the area of study. We have employed a technique to teach physiology to bioengineering students that couples students' enthusiasm for their chosen field, bioengineering, with an active learning process in which students are asked to design a biomedical device to enhance, replace, or create a new cellular or organ system function. Each assignment is designed with specific constraints that serve to direct students' attention to specific areas of study and that require students to create original designs. Preventing students from using existing designs spurred student invention and enthusiasm for the projects. Students were divided into groups or "design discovery teams" as might be done in a biomedical device industry setting. Students then researched the physiological issues that would need to be addressed to produce an acceptable design. Groups met with faculty to brainstorm and to obtain approval for their general design concepts before proceeding. Students then presented their designs to the instructors in a structured, written outline form and to the class as a 10-minute oral presentation. Grades were based on the outline, oral presentation, and peer evaluations (group members anonymously rated contributions of other members of their team). We believe that this approach succeeded in generating enthusiasm for learning physiology by allowing the students to think creatively in their chosen field of study and that it has resulted in students developing a more thorough understanding of difficult physiological concepts than would have been achieved with a traditional didactic lecture approach.

Effects of anoxia on intracellular free Ca2+ in isolated cardiomyocytes from turtles.

One of the most important negative consequences of hypoxic stress in the mammalian myocardium is a breakdown in intracellular calcium homeostasis. This study examines the effects of anoxic stress on intracellular calcium regulation in isolated ventricular myocytes from a hypoxia tolerant vertebrate, the western painted turtle (Chrysemys picta bellii). Isolated calcium tolerant cardiomyocytes from turtle hearts were mounted on a glass cover slip that formed the bottom of a sealed, Plexiglas perfusion chamber. Free [Ca2+]i (determined by FURA2 fluorescence) in isolated turtle cardiomyocytes averaged 31.7 +/- 3.2 nM after 30 min of normoxic perfusion (20 degrees C, pHc = 7.77). This value is on the low end of the published range for mammalian cardiomyocytes. Perfusion with anoxic Ringer equilibrated with 3% CO2, resulted in a significant increase in free [Ca2+]i to 941 +/- 494.6 nM after 60 min. Increasing the CO2 in the perfusion solution to 5% or 6% blunted this rise (peak levels after 60 min of anoxia were 420.5 +/- 176.0 nM and 393.8 +/- 132.8 nM, respectively). A further increase to 8% CO2 increased the maximal value for free [Ca2+]i to 610.9 +/- 297.5 nM. In eight cells from the 5% CO2 protocol in which [Ca2+]i was monitored during recovery, reperfusion with normoxic Ringer rapidly lowered intracellular calcium to 92.8 +/- 9.7 nM within 15 min. Anoxia at relatively high extracellular (and hence intracellular) pH results in an increase in free [Ca2+]i comparable in magnitude and time course to that seen in some mammalian cardiomyocyte preparations. Perfusion of anoxic myocytes with Ringer equilibrated with either 5% or 6% CO2 blunted this increase in intracellular calcium, possibly an example of the pH paradox effect. A more severe combination of respiratory acidosis and anoxia (8% CO2) removed this protective effect.

Extracellular and intracellular acid-base effects of submergence anoxia and nitrogen breathing in turtles.

We compared extracellular and intracellular acid-base state in turtles (Chrysemys picta bellii) subjected to anoxic submergence to turtles made anoxic by N2-breathing. Measurements made on control animals and on animals after 1, 2, 4, or 6 h of anoxia included blood pH, PO2, PCO2, and lactate as well as liver, heart, skeletal muscle, and brain pHi (using DMO equilibration), lactate, and glycogen concentrations. We hypothesized that the anaerobic metabolic rate of submerged turtles would be depressed by the more severe extra- and intracellular acidosis, and that this would be indicated by reduced lactate accumulation and glycogen depletion. Submerged turtles became extremely acidemic due to a combined metabolic and respiratory acidosis and had significantly lower arterial pH than N2-breathing animals (6.98 and 7.34, respectively, after 6 h). In spite of this disparity in pHa, 6 h pHi values for liver, heart, and brain were similar. Likewise, our data on glycogen depletion and lactate accumulation at h 6 in these tissues suggest no dramatic differences in anaerobic metabolic rate. While skeletal muscle pHi was somewhat lower at h 6 in the submerged group (6.73 vs 6.91 for N2-breathers), we observed no differences in either glycogen depletion or lactate accumulation in this tissue between our two treatments. Thus, at h 6, in spite of a 0.37 pH unit difference in pHa and a nearly 70 mm Hg difference in arterial and presumably cytosolic PCO2, pHi and tissue lactate and glycogen concentrations were similar. These results can be explained if the in vivo intracellular buffer values (beta) of turtle tissues are very high. We conclude that extracellular acid-base state is not necessarily reflected intracellularly in vivo in turtles and care must be taken in extrapolating from one compartment to another when attempting to make inferences about metabolic depression or acid-base regulation in this species.

Effect of induced hypercapnia on anaerobic metabolic rate of anoxic musk turtles.

To evaluate the possible effect of induced hypercapnia on anaerobic metabolic rate during anoxia, musk turtles (Sternotherus odoratus) were submerged in N2-equilibrated water at 10 degrees C for 3 days either with (anoxic hypercapnic) or without (anoxic normocapnic) elevated aquatic PCO2 (30-40 Torr). Control animals had access to air at 10 degrees C. Plasma [lactate] was significantly higher (P less than 0.01) in the normocapnic [59.4 +/- 7.4 (SD) mM; n = 22] than in the hypercapnic (47.4 +/- 8.5 mM; n = 19) anoxic turtles, although the hypercapnic turtles had lower blood pH (P less than 0.05). Plasma ion concentrations (Na, K, Cl, Ca, and Mg), however, were no different in the two groups, although all values other than Na were different from control. In some of the animals, [lactate] and [glycogen] (per g wet wt) of skeletal muscle, heart, and liver were measured in addition to blood acid-base values and lactate. Tissue lactates, although significantly elevated from control, and glycogens, although (with the exception of skeletal muscle) significantly reduced from control, were no different in the two anoxic groups. We suggest that these tissue data are more valid indicators of anaerobic metabolic rate than is plasma lactate and therefore conclude that induced hypercapnia does not significantly depress anaerobiosis in musk turtles at 10 degrees C.

Expression of heat shock proteins in turtle and mammal hearts: relationship to anoxia tolerance.

Heat shock proteins (HSPs) may play a cardioprotective role during hypoxia or ischemia. We hypothesized that cardiac tissue from hypoxia-tolerant animals might have high levels of specific HSPs. We measured myocardial HSP60 and HSP72/73 in painted and softshell turtles during normoxia and anoxia (12 h) and after recovery (12 or 24 h). We also measured myocardial HSPs in normoxic rats and rabbits. During normoxia, hearts from the most highly anoxia-tolerant species, the painted turtle, expressed the highest levels of HSP60 (22.6+/-2.0 mg/g total protein) followed by softshells (11.5+/-0.8 mg/g), rabbits (6.8+/-0.9 mg/g), and rats (4.5+/-0.5 mg/g). HSP72/73 levels, however, were not significantly different. HSP60 levels in hearts from both painted and softshell turtles did not deviate significantly from control values after either 12 h of anoxia or 12 or 24 h of recovery. The pattern of changes observed in HSP72/73 was quite different in the two turtle species. In painted turtles anoxia induced a significant increase in myocardial HSP72/73 (from 2.8+/-0.1 mg/g normoxic to 3.9+/-0.2 mg/g anoxic, P<0.05). By 12 h of recovery, HSP72/73 had returned to control levels (2.7+/-0.1 mg/g) and remained there through 24 h (2.6+/-0.2 mg/g). In softshell turtles, HSP72/73 decreased significantly after 12 h of anoxia (from 2.4+/-0.4 mg/g normoxic to 1.3+/-0.2 mg/g anoxic, P<0.05). HSP72/73 levels were still slightly below control after 12 h of recovery (2.1+/-0.1 mg/g) and then rose to significantly above control after 24 h of recovery (4.1+/-0.7 mg/g, P<0.05). We also conclude that anoxia-tolerant and anoxia-sensitive turtles exhibit different patterns of myocardial HSP changes during anoxia and recovery. Whether these changes correlate with their relative degrees of anoxia tolerance remains to be determined.

In vitro tolerance to anoxia and ischemia in isolated hearts from hypoxia sensitive and hypoxia tolerant turtles.

Although freshwater turtles as a group are highly anoxia tolerant, dramatic interspecific differences in the degree of anoxia tolerance have been demonstrated in vivo. Painted turtles (Chrysemys picta bellii) appear to be the most hypoxia-tolerant species thus far studied, while softshelled turtles (Trionyx spinifer) are the most hypoxia-sensitive. We have assumed that this dichotomy persists in vitro but have not, until now, directly tested this assumption. We therefore, directly compared the responses of isolated, perfused, working hearts from these two species to either 240 min of anoxia, 90 min of global ischemia, or 240 min of global ischemia followed by reoxygenation/reperfusion. Isolated hearts were perfused at 20 degrees C and monitored continuously for phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi), and intracellular pH (pHi) by 31P-nuclear magnetic resonance spectroscopy as well as for ventricular developed pressure and heart rate. Contrary to our expectations, we observed few significant differences in any of these parameters between painted and softshelled turtle hearts. Hearts from both species tolerated 240 min of anoxia equally well and both restored PCr, pHi, and Pi contents to control levels during reoxygenation. We did observe some significant interspecific differences in the 90 min (pHi and Pi) and 240 min (PCr) ischemia protocols although these seemed to suggest that Trionyx hearts might be more tolerant to these stresses than Chrysemys hearts. We conclude that: (a) the observed in vivo differences in anoxia tolerance between painted and softshelled turtles must either be due to differences in organ metabolism in organs other than the heart (e.g., brain) or to some integrative physiologic differences between the species; and (b) isolated hearts from a species known to be relatively anoxia sensitive in vivo can exhibit an apparent high degree of anoxia and ischemia tolerance in vitro.

Cardiovascular and metabolic responses during anoxic submergence in the bullfrog with and without maintained extracellular pH.

We studied metabolic, cardiovascular, and electrolyte responses of paralyzed bullfrogs to 6 hours of submerged anoxia at 15 degrees C, either with or without maintenance of extracellular pH at preanoxic values by NaHCO3 infusion. There were no differences in arterial PCO2 between acidemic and nonacidemic groups. Lactate appearance in arterial blood, as an indicator of anaerobic metabolic rate, was not significantly different between the anoxic groups, although both were significantly elevated over control. Heart rate in both anoxic groups was similar and significantly lower than in control. During anoxia, both systolic and diastolic pressures fell, and the group with maintained pH fell further. Plasma calcium concentration decreased in both anoxic groups, but the fall was more severe in the group in which pH was controlled. Survival was lower in this group, with a rapid decline in survival after 4 hours of anoxia. We conclude that the fall in extracellular pH seen during anoxia has a protective effect on cardiovascular function that may be partially due to maintenance of relatively high extracellular calcium levels.

Brain high energy phosphate responses to alcohol exposure in neonatal rats: an in vivo 31P-NMR study.

BACKGROUND: The mechanisms that mediate fetal brain injury which results from maternal alcohol consumption are not well understood. Although fetal hypoxia is a popularly proposed mechanism, it has been difficult to assess brain oxygenation in vivo. We measured intracellular high energy phosphate concentrations and estimated intracellular pH (pHi) in brains of unanesthetized neonatal rat pups by using in vivo 31P-NMR spectroscopy. We reasoned that decreases in brain oxygenation sufficient to result in brain injury would also reduce high energy phosphates and pHi. METHODS: On postnatal day 4, before alcohol administration, pups were placed into a 20 mm diameter NMR probe, their heads were positioned carefully in the center of the 31P detection coil, and spectra were collected over 20 min. Animals were then fed diet with or without 4.5 g/kg of ethanol in two (in succession) of 12 daily feedings via artificial rearing methods. A second spectrum was collected at 90 min after the beginning of the second alcohol feeding, at the time that coincided with the peak blood alcohol concentration (BAC). Identical feedings were performed daily until day 9, when pre- and postfeeding spectra were again obtained. Positive control groups were fed control diet and were studied in atmospheres of 5% oxygen, 95% nitrogen or 0% oxygen, 100% nitrogen. RESULTS: Phosphocreatine (PCr), beta-adenosine triphosphate (ATP), and pHi decreased and inorganic phosphate (Pi) increased in day 4 animals subjected to 0% oxygen (20 min) compared with pretreatment and all other treatment groups. Day 9 animals did not tolerate these conditions. There were no significant changes in response to 5% oxygen on day 4, but Pi increased and beta-ATP decreased compared with pretreatment values and compared with alcohol and control groups on day 9. There were no changes in PCr, beta-ATP, or pHi in response to alcohol treatment at either age. PCr was significantly increased in the alcohol and 5% oxygen groups and apparently increased in the control group on day 9 compared with day 4, most likely due to increases in cranial muscle mass within the NMR coil. CONCLUSIONS: We conclude that acute alcohol exposure that results in peak BACs of 315 mg/dl does not alter brain high energy phosphate concentrations or pHi in neonatal rat pups, although these BACs are known to result in significant brain injury. These findings do not support hypoxia as a mechanism of alcohol-mediated brain injury during the third trimester equivalent in the rat pup model.

Activation of the heat shock response: relationship to energy metabolites. A (31)P NMR study in rat hearts.

Heat shock factor (HSF), the transcription factor for the heat shock proteins, is activated by cardiac ischemia, but the mechanism of activation is unknown. Ischemia is accompanied by changes in the energy state and acid-base conditions. We hypothesized that decreased ATP and/or intracellular pH (pH(i)) might activate HSF. To test this hypothesis, we perfused rat hearts within an NMR spectrometer. NMR data showed that after 6.5, 13, and 20 min of ischemia, ATP dropped to 62.7, 23.1, and 6.9% of the control level, and pH(i) was 6.16, 5.94, and 5.79, respectively. Reperfusion after ischemia partially restored ATP levels, and this was associated with greater activation of HSF1. HSF1 was also activated after 6.5 min of ischemia. Activation of HSF1 was less after 13 min of ischemia and barely detectable after 20 min of ischemia. In conclusion, 1) a moderate decrease in intracellular ATP correlates with activation of HSF1 in the heart; and 2) a severe depletion in ATP correlates with an attenuation in HSF1 activation, and the restoration of ATP leads to greater activation of HSF1, suggesting that a critical ATP level is required for activation of HSF1.

Effect of religious observance on infants' sleep position in the Jewish population.

OBJECTIVES: To describe the effect of the level of religiousness on infants' sleep position in the Jewish population. METHODS: A longitudinal telephone survey of randomly selected 608 2-month-old Jewish infants repeated at 4 and 6 months. Results were analyzed versus the four levels of Jewish religion observance. RESULTS: A significant correlation was found between the level of religious practice and sleep position (P < or = 0.002). 56.8% (50/88) of ultra-orthodox parents put their babies to sleep in the non-prone position, compared with 79% (411/520) in the other three groups (P < 0.001). Non-prone sleeping decreased when infants grew. Higher parity correlated with the level of religiousness and with prone sleeping in religious families (OR = 1.15, 95% CI 1.00-1.33, P < 0.001). CONCLUSIONS: Jews and especially the ultra-orthodox families comply significantly less with recommendations to avoid prone sleeping. Specific measures may be required in this population that rely more on personal experience and belief than on health care provider advice.