Discriminant analysis of the Ullrich-Turner syndrome neurocognitive profile

OBJECTIVES: To evaluate the effect of fetal behavioral states on the relationship between fetal heart rate (FHR) and middle cerebral artery resistance index (MCA RI) in normal fetuses. METHODS: The FHR and MCA RI of 10 normal cases from 37 to 40 weeks of gestation were recorded consecutively over a 45-min period. Correlations between the MCA RI and FHR during resting and active phases, classified by an actocardiotocogram, were analyzed by simple regression analysis. RESULTS: The mean FHR and MCA RI were significantly higher during the active phase (140.3 +/- 6.6 bpm, 0.79 +/- 0.06) than those during the resting phase (137.4 +/- 6.8 bpm, 0.75 +/- 0.07, P < 0.01, two sample t-test). There was a significant negative correlation (r = - 0.22, n = 2642, P < 0.01) between RI and FHR during the active phase and a significant positive correlation (r = 0.28, n = 2066, P < 0.001) during the resting phase. CONCLUSIONS: The relationship between FHR and the MCA RI during the resting phase is different from during the active phase.     

Doppler velocimetry of the uterine arteries after hysteroscopic rollerball endometrial ablation

The aim of this study was to document the Doppler indices [pulsatility index (PI) and resistance index (RI)] of the uterine arteries in 30 patients who underwent hysteroscopic rollerball endometrial ablation for dysfunctional uterine bleeding by transvaginal pulsed Doppler sonography, and to reveal whether treatment failures (persistent menometrorrhagia) can be predicted by the blood flow characteristics of the uterine arteries in advance. On the basis of the outcome of patients at the end of the first postoperative year, the Doppler indices of the uterine arteries were meaningful 1 year after the operation when PI (1.32 +/- 0.11; mean +/- SD) and RI (0.71 +/- 0.04) in six menometrorrhagic patients were statistically different from PI (2.19 +/- 0.28; 1.95 +/- 0.36 and 1.82 +/- 0.37) and RI (0.87 +/- 0.06; 0.82 +/- 0.06 and 0.81 +/- 0.04) in normally menstruating, amenorrhoeic and hypomenorrhoeic patients respectively (P < 0.05). On the other hand, the patients who would be menometrorrhagic one year after the operation had a thicker endometrium in the first post-operative month. These findings suggest that the angiogenetic role of the persistent endometrial islands after endometrial ablation needs at some time to be reflected as changes in the Doppler parameters of the uterine arteries.     

Intravenous cocaine induces platelet activation in the conscious dog

BACKGROUND: Cocaine consumption has been associated with thrombosis of coronary and peripheral arteries. Since cocaine has been found to induce platelet activation in vitro, we sought to establish whether cocaine induced platelet activation in vivo. METHODS AND RESULTS: Chronically instrumented, conscious dogs were infused with cocaine (1 mg/kg), norepinephrine (0.2 to 0.4 mg/kg), or saline intravenously over 1 minute. Activated canine platelets were identified in whole blood collected from an indwelling aortic catheter by flow cytometric detection of the binding of a monoclonal antibody directed against the activation-dependent antigen P-selectin. Infusion of cocaine resulted in an elevation of mean arterial pressure (91 +/- 3 to 128 +/- 7 mm Hg [P < .01]) and heart rate (87 +/- 9 to 125 +/- 11 beats per minute [P < .01]). A similar change (P = NS) in mean arterial pressure followed norepinephrine infusion (100 +/- 5 to 137 +/- 13 mm Hg [P < .04]), whereas saline infusion had no effect. Cocaine resulted in a substantial but delayed increase in platelet P-selectin expression (14 +/- 7% [P < .08], 31 +/- 12% [P < .04], and 55 +/- 22% [P < .04] at 17, 22, and 27 minutes after drug infusion, respectively). The magnitude of this increase was similar to that found in blood treated ex vivo with the agonists ADP or PAF (23 +/- 7% and 53 +/- 15%, respectively). No significant increase in P-selectin expression was detected in the blood of animals that received norepinephrine or saline. Serum cocaine concentrations were highest immediately after infusion (538 +/- 55 ng/mL at 2 minutes) but declined rapidly (185 +/- 22 and 110 +/- 25 ng/mL at 17 and 32 minutes after infusion); in contrast, the increase in benzoylecgonine concentrations was delayed (from < 25 ng/mL in all but one animal [34 ng/mL] at 2 minutes to 46 +/- 4 and 71 +/- 11 ng/mL at 17 and 32 minutes, respectively, after infusion). CONCLUSIONS: Intravenous cocaine induces activation of individual circulating platelets; this effect is not reproduced by infusion of norepinephrine at doses sufficient to exert similar hemodynamic effects. The delay in detection of activated platelets after treatment with cocaine may result from the adhesion and subsequent detachment of activated platelets; alternatively, cocaine metabolites, rather than the drug itself, may induce platelet activation.     

Effect of dehydroepiandrosterone sulfate on uterine artery flow velocity waveforms in term pregnancy

OBJECTIVE: To investigate the interrelation between estrogen synthesis by the fetoplacental unit and uteroplacental hemodynamics in term pregnancy. METHODS: Transvaginal color Doppler flow imaging and pulsed Doppler ultrasonographic assessments were made on ten normal full-term pregnant women before and 3, 5, 10, 30, and 60 minutes after the administration of a 200-mg intravenous dose of dehydroepiandrosterone sulfate (DHAS) in 20 mL of 5% dextrose. Ten normal full-term pregnant women received 20 mL of 5% dextrose as controls. The pulsatility index (PI) values for the uterine artery, heart rate, and mean arterial pressure were recorded. Plasma estradiol (E2) was measured before and 10 minutes after the infusion. RESULTS: In the DHAS group, uterine artery PI decreased from baseline by 26% (P < .05) after 5 minutes, and the mean reduction was 36% (P < .05) after 10 minutes and 15% (P < .05) after 30 minutes. The PI returned to the baseline value 60 minutes later. In the control group, there was no change in uterine artery PI. No change was found in heart rate or mean arterial blood pressure in the control or DHAS groups. The mean plasma E2 increased from 22.3 +/- 6.6 to 56.2 +/- 24.1 ng/mL (P < .05) 10 minutes after the infusion in DHAS subjects, whereas there was no significant change in plasma E2 in the controls. CONCLUSION: Dehydroepiandrosterone sulfate induces a significant decrease in the uterine artery PI, which suggests a possible decrease in uterine vascular impedance in term pregnancy.     

Subchronic dietary toxicity of strychnine: bobwhite quail are less sensitive than mallard ducks

PURPOSE: This study was undertaken to evaluate in vivo the effect of recombinant hirudin (r-hirudin [HBW 023]), a potent thrombin inhibitor, on the process of microvascular thrombus formation and recanalization. METHODS: Thrombosis was induced photochemically in distinct arterioles (n = 25) and venules (n = 30) of the ear of 16 hairless hr/hr mice (8 to 10 weeks old, 25 to 30 g of body weight). r-Hirudin (1 mg/kg of body weight) was administered intravenously directly before thrombus induction; saline-treated animals served as controls. Thrombus formation (i.e., first platelet deposition at the endothelial lining [FPD]; inner luminal diameter reduction to 50% [D/2]; complete vessel occlusion [CVO]), vessel recanalization, microcirculatory parameters, and leukocyte-endothelial cell interaction were analyzed by means of intravital fluorescence microscopy. RESULTS: Hirudin significantly delayed the process of thrombus formation compared with saline-treated controls in both arterioles (FPD: 381 +/- 80 vs 137 +/- 25 seconds, P < 0.05; D/2: 627 +/- 49 vs 501 +/- 71 seconds; CVO: 925 +/- 78 vs 854 +/- 60 seconds) and venules (FPD: 173 +/- 11 vs 59 +/- 4 seconds; D/2: 342 +/- 54 vs 228 +/- 27 seconds; CVO: 541 +/- 85 vs 344 +/- 43 seconds; P < 0.05). In addition, r-hirudin-treated animals showed an increased rate of vessel recanalization at 24 hours after thrombus induction (arterioles: 54% [7 of 13] vs 0% [0 of 12], P < 0.05; venules: 77% [10 of 13] vs 53% [9 of 17]), whereas microcirculatory parameters and leukocyte-endothelial cell interaction were not affected. CONCLUSION: Our data indicate that r-hirudin not only counteracts the process of thrombus formation but also promotes vessel recanalization, thus supporting its use in clinical microvascular surgery.     

Prenatal cocaine, alcohol, and undernutrition differentially alter mineral and protein content in fetal rats

Alcohol exposure and undernutrition during pregnancy have been associated with altered fetal body composition. Recent observations suggest that cocaine exposure during pregnancy may impair delivery of nutrients to the fetus and could thereby alter body growth and composition. Such effects are important because they can adversely influence physical and neural development. Consequently, we investigated the dose-dependent effects of cocaine on fetal body composition in an animal (rat) model and compared such effects with those caused by prenatal alcohol exposure and undernutrition. Pregnant Sprague-Dawley rats received either 20, 30, 40, or 50 mg/kg cocaine HCl (SC) twice daily from gestation days 7 through 19. Pair-fed (undernutrition) and untreated control groups and a group receiving 3.0 g/kg alcohol (PO) twice daily served as comparison groups (n = 11 to 14/group). Females were sacrificed on gestation day 20. One male and one female fetus was removed from each dam. The fetuses were minced, dehydrated, defatted, and analyzed for content of protein and the minerals Zn, Ca, Fe, Mg, K, and Na. In terms of concentration per unit of fat-free dry solids, male fetuses in the cocaine groups showed significant decreases in protein compared to untreated controls (15+/-3 to 20+/-2 mg/g vs. 24+/-4 mg/g, p = 0.01). There was a significant treatment effect for Ca (p < 0.05), reflecting a trend for decreased Ca concentrations in the fetuses of the cocaine and undernutrition groups. Male fetuses in the alcohol group had significantly elevated Mg levels compared to male fetuses in the other groups (3.0+/-0.8 vs. 1.0+/-0.2 to 2.3+/-0.7 mg/g, p < 0.05). There were some sex differences, with female fetuses having significantly lower concentrations of Mg, Fe, K, and higher protein concentrations than male fetuses. Although the effects were few and modest, these results suggest that prenatal cocaine, alcohol, and undernutrition can differentially alter fetal body weight and composition and, therefore, adversely influence fetal development.     

The hemodynamic effects of maternal hypo- and hyperoxygenation in healthy term pregnancies

OBJECTIVE: To evaluate the hemodynamic effects of maternal hypo- and hyperoxygenation in normal term pregnancy. METHODS: Ten healthy women between 35-41 weeks' gestation were exposed to 10% oxygen in inspired air for 10 minutes and, after a 5-minute recovery period, to a stepwise increase in oxygenation with 50 and 100% oxygen for 10 minutes. Maternal ventilation, hemodynamics, and oxygenation were assessed noninvasively, and maternal and fetal vascular responses were assessed with pulsed-wave color Doppler velocimetry. Computerized cardiotocography was used for fetal heart rate (FHR) analysis. RESULTS: Substantial maternal hypoxia was achieved and accompanied by a statistically significant rise in the maternal heart rate (from 89 +/- 11 to 104 +/- 16 beats per minute) and systolic blood pressure (from 123 +/- 13 to 131 +/- 13 mmHg). Doppler measurements demonstrated a statistically significant decline in the pulsatility index (PI) of the maternal internal carotid artery (from 1.8 +/- 0.3 to 1.5 +/- 0.4) and an increase in the uterine artery PI (from 0.60 +/- 0.12 to 0.72 +/- 0.13). Baseline FHR, heart rate variability, and Doppler velocimetry in the umbilical artery and the middle cerebral artery showed no statistically significant changes. Hyperoxia did not cause changes in the maternal circulation, but the FHR decreased significantly (from 142 +/- 12 to 133 +/- 11 beats per minute). CONCLUSION: Acute short-term hypoxia modifies the maternal circulation, suggesting redistribution of maternal blood flow, but exerts no detectable effects on the healthy fetus. Maternal hyperoxygenation induces no apparent adverse effects.     

Alterations of pH in response to increased dietary protein in cattle are unique to the uterus

This study was undertaken with two objectives: 1) to determine whether the effect of excess dietary protein on intrauterine pH in cattle is specific to the uterus or manifested in other bodily fluids and 2) to determine whether the effect of excess ruminally degradable protein on uterine pH can be ameliorated by substitution with a less-degradable protein source. Thirty-six Holstein cows in early lactation were fed isoenergetic total mixed rations that either 1) met undegradable intake protein (UIP) and degradable intake protein (DIP) requirements (Balanced), 2) met DIP requirements and exceeded UIP requirements by 25% (High UIP), or 3) met UIP requirements and exceeded DIP requirements by 25% (High DIP). After diets had been fed > or = 2 wk, uterine, blood, salivary, and urinary pH and plasma urea nitrogen were determined at estrus (d 0) and d 7. Plasma urea nitrogen (mg/dL) was not different between estrus and d 7 but was significantly affected by diet (Balanced, 16.1 +/- 2.3; High UIP, 19.2 +/- 1.6; High DIP, 22.3 +/- 2.6; P < .05). There was no effect of treatment on the pH of any fluid measured at estrus: intrauterine, blood, salivary, and urinary pH averaged 6.84 +/- .05, 7.39 +/- .01, 8.30 +/- .05, and 8.15 +/- .05, respectively. In contrast, on d 7, uterine pH was significantly lower in both high-protein groups, regardless of protein degradability (Balanced, 7.13 +/- .05; UIP, 6.95 +/- .04; DIP, 6.85 +/- .05; P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of hepatocyte enlargement on the hemodynamic characteristics of the isolated perfused rat liver preparation

The influence of hepatocyte enlargement on intrahepatic hemodynamics was assessed in the isolated perfused rat liver preparation (IPRL) using two experimental models: hypotonic liver cell swelling and phenobarbitone-induced hepatocyte hypertrophy. The analysis of pressure-flow data obtained from the portal vascular bed over a flow range of 0 to 70 mL/min in the presence of a maximally-effective concentration of the vasodilator agent papaverine hydrochloride (6 x 10(-4) mol/L) enabled the calculation of P0, an estimate of the pressure required to passively distend the intrahepatic vasculature, and Gmax, the maximal portal vascular conductance. By comparison with an isotonic perfusion medium (Krebs-Henseleit buffer [KH] containing 2.5% bovine serum albumin [BSA]), perfusion with a hypotonic medium induced a significant increase in mean hepatocyte cross-sectional area (H(A)) (590 +/- 21 vs. 324 +/- 23 microm(-2), p < .05), a fall in Gmax (0.39 +/- 0.08 vs. 2.02 +/- 0.18 mL/min/g/mm hg, P < .001), and an increase in P0 (2.96 +/- 0.38 vs. 1.58 +/- 0.07 mm hg, P < .001). Phenobarbitone administered in drinking water (0.5 g/L) over a period of 60 days also induced a significant degree of hepatocyte enlargement (HA, 510 +/- 29 microm2, P < .05). On day 7, portal pressure measured in vivo in this group was significantly elevated compared with untreated controls (10.5 +/- 0.3 vs. 8.4 +/- 0.2 mm hg, P < .001), while in the IPRL Gmax was reduced (0.48 +/- 0.01 mL/min/g/mm hg, P < .001), and P0 was increased (2.23 +/- 0.17 mm hg, P < .05). However, with continued phenobarbitone treatment portal pressure, Gmax and P0 returned toward control values. The results confirm that hepatocyte enlargement is associated with a significant disturbance of intrahepatic hemodynamics but also that some adaptation occurs if hepatocyte enlargement is sustained over a prolonged period of time.     

Pharyngo-UES contractile reflex in patients with posterior laryngitis

BACKGROUND: Earlier studies have shown that stimulation of the human pharynx by injection of minute amounts of water stimulates the pharyngo-UES contractile reflex. It has been suggested that this reflex may be activated during pharyngeal reflux of gastric and/or esophageal content, thus increasing the UES pressure and possibly preventing further entry of the refluxate into the pharynx. However, the integrity of this reflex in patients with posterior laryngitis has not been studied. AIM: Evaluate the pharyngo-UES contractile reflex in a group of patients with objective findings of posterior laryngitis. METHODS: Fourteen consecutive patients with posterior laryngitis (mean age, 48+/-6 y) and 13 healthy volunteers (mean age, 53+/-6 y) were studied by concurrent pharyngeal water stimulation and UES manometry. RESULTS: The threshold volume required to evoke the pharyngo-UES contractile reflex in the laryngitis group (0.4+/-0.05 mL) was significantly higher than that of the control (0.2+/-0.04 mL) (P < .05). Following stimulation of the pharyngo-UES contractile reflex, the maximum postinjection pressure in patients (75+/-6 mm Hg) was similar to that of the controls (78+/-6 mm Hg). The percent increase in UES pressure following stimulation of the reflex in the laryngitis group (99%+/-15%) was significantly higher than that of controls (55%+/-11%) (P < .05). CONCLUSIONS: Compared with normal controls, a significantly larger volume of liquid is required to trigger this reflex in patients with posterior laryngitis. When triggered, the maximum UES pressure induced by the pharyngo-UES contractile reflex is similar between the two groups. These findings suggest an altered afferent sensory limb of this reflex in patients with posterior laryngitis.     

Isoflurane- and halothane-mediated dilation of distal bronchi in the rat depends on the epithelium

BACKGROUND: Respiratory epithelium releases substance(s) that can modulate bronchoconstriction in response to constrictive agonists and enhance bronchodilation in response to certain bronchodilators. The hypothesis that the bronchodilatory effect of isoflurane and halothane depends on the epithelium was tested in rat distal bronchial segments. METHODS: Wistar rat bronchial segments of the fourth order (diameter approximately 100 microns) were dissected. After preconstriction with 5-hydroxytryptamine, each bronchial segment was exposed to increasing concentrations of 0% to 3% isoflurane or 0% to 3% halothane under four conditions: after epithelial rubbing, after pretreatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine, after pretreatment with the cyclooxygenase inhibitor indomethacin, or with no preintervention (control). Changes in bronchial diameter were monitored using an in vitro video detection system. RESULTS: Both isoflurane and halothane produced concentration-dependent bronchodilation (P < 0.001 for either anesthetic; 40% +/- 11% [mean +/- SD] dilation for 3% isoflurane and 57% +/- 10% dilation for 3% halothane). For both anesthetics, bronchodilation was significantly but incompletely attenuated by epithelial rubbing (12% +/- 7% dilation for 3% isoflurane [P < 0.01] and 31% +/- 10% dilation for 3% halothane [P < 0.01]), by pretreatment with indomethacin (20% +/- 8% dilation for 3% isoflurane [P < 0.02] and 21% +/- 9% dilation for 3% halothane [P < 0.001]), or by L-NNA (9% +/- 7% dilation for 3% isoflurane [P < 0.005] and 39% +/- 12% dilation for 3% halothane [P < 0.05]). Epithelial rubbing did not impair nitroprusside-associated bronchodilation. CONCLUSIONS: Isoflurane- and halothane-mediated bronchodilation depends at least partially on the epithelium and may involve both a prostanoid and nitric oxide in distal rat bronchi.     

Does the onset of neonatal seizures correlate with the timing of fetal neurologic injury?

The onset of seizures after birth has been considered evidence of an intrapartum asphyxial event. The present study was undertaken to determine whether the timing of neonatal seizures after birth correlated with the timing of a fetal asphyxial event. Thus, singleton term infants diagnosed with hypoxic ischemic encephalopathy and permanent brain injury had a mean birth to seizure onset interval of 9.8 +/- 17.7 (range 1-90) hours. When these infants were categorized according to their fetal heart rate (FHR) patterns, the acute group (normal FHR followed by a sudden prolonged FHR deceleration that continued until delivery) tended to have earlier seizures than infants did within the tachycardia group (normal FHR followed by tachycardia, repetitive decelerations, and diminished variability) and the preadmission group (persistent nonreactive FHR pattern intrapartum). These seizure intervals were as follows: acute, 6.6 +/- 18.0 (range 1-90) hours; tachycardia, 11.1 +/- 17.1 (range 1-61) hours; and preadmission, 11.8 +/- 17.9 (range 1-79) hours (p < 0.05). But the range varied widely and no group was categorically distinct. In conclusion, the onset of neonatal seizures after birth does not, in and of itself, appear to be a reliable indicator of the timing of fetal neurologic injury.     

Newborn acid-base status and umbilical cord morphology

OBJECTIVE: To assess the relation between umbilical cord morphology and intrapartum fetal status and umbilical cord blood gases at birth. METHODS: In a prospective study of 134 consecutive newborns and their umbilical cords, relations were investigated between umbilical cord morphologic characteristics (umbilical cord length, number of vascular coils, coiling index, and vessel length index) and intrapartum fetal heart rate (FHR) decelerations, color of amniotic fluid, operative delivery for suspected fetal acidosis, umbilical vessel blood gases, and acid-base status. RESULTS: Statistically significant linear correlations were found between umbilical venous pH and the umbilical cord length (r = 0.30; 95% confidence interval [CI] 0.13, 0.46; P < .001), number of vascular coils (r = 0.27; 95% CI 0.10, 0.43; P = .001), coiling index (r = 0.15; 95% CI 0, 0.33; P = .05), and vessel length index (r = 0.30; 95% CI 0.13, 0.46; P < .001). Statistically significant negative linear correlations were found between the umbilical venous partial pressure of carbon dioxide (PCO2) and cord length (r = -0.34, 95% CI -0.49, -0.17; P < .001), number of vascular coils (r = -0.30, 95% CI -0.46, -0.13; P < .001), coiling index (r = -0.17, 95% CI -0.34, 0; P = .03), and vessel length index (r = -0.34, 95% CI -0.49, -0.17; P < .001). The umbilical artery pH was related to vessel length index and to the number of umbilical vascular coils (r = 0.17, 95% CI 0.03, 0.36; P = .04 and r = 0.17, 95% CI 0.02, 0.35; P = .047, respectively). No relation was found between umbilical cord indices and intrapartum FHR decelerations, meconium staining of the amniotic fluid, or mode of delivery. Placental weight also correlated with umbilical cord length and vessel length index (95% CI 0.15, 0.46; P < .001 and 95% CI 0.05, 0.38; P = .01, respectively), but not with the number of umbilical cord coils or the coiling index. CONCLUSION: Umbilical venous pH and PCO2 and umbilical artery pH are related to umbilical cord morphology. Associated variations in placental morphology or placental blood flow affecting maternal-fetal gas exchange may explain these findings.     

Pleural effusions in the medical ICU: prevalence, causes, and clinical implications

OBJECTIVE: To determine the prevalence and causes of pleural effusions in patients admitted to a medical ICU (MICU). DESIGN: Prospective. SETTING: MICU in a tertiary care hospital. PATIENTS: One hundred consecutive patients admitted to the MICU at the Medical University of South Carolina whose length of stay exceeded 24 h had chest radiographs reviewed daily and chest sonograms performed within 10 h of their latest chest radiograph. RESULTS: The prevalence of pleural effusions in 100 consecutive MICU patients was 62%, with 41% of effusions detected at admission. Fifty-seven of 62 (92%) pleural effusions were small. Causes of pleural effusions were as follows: heart failure, 22 of 62 (35%); atelectasis, 14 of 62 (23%); uncomplicated parapneumonic effusions, seven of 62 (11%); hepatic hydrothorax, five of 62 (8%); hypoalbuminemia, five of 62 (8%); malignancy, two of 62 (3%); and unknown, three of 62 (5%). Pancreatitis, extravascular catheter migration, uremic pleurisy, and empyema caused an effusion in one instance each. Heart failure was the most frequent cause of bilateral effusions (13/34 [38%]). When compared with patients who never had effusions during their MICU stay, patients with pleural effusions were older (54+/-2 years, mean+/-SEM, vs 47+/-2 years [p=0.04]), had lower serum albumin concentration (2.4+/-0.1 vs 3.0+/-0.01 g/dL [p=0.002]), higher acute physiology and chronic health evaluation II scores during the initial 24 h of MICU stay (17.2+/-1.1 vs 12+/-1.2 [p=0.010]), longer MICU stays (9.8+/-1.0 vs 4.6+/-0.7 days [p=0.0002]), and longer mechanical ventilation (7.0+/-1.3 vs 1.9+/-0.7 days [p=0.004]). No patient died as a direct result of his or her pleural effusion. Chest radiograph readings had good correlation with chest sonograms (p<0.0001). CONCLUSION: Pleural effusions in MICU patients are common, and most are detected by careful review of chest radiographs taken with the patient in erect or semierect position. When clinical suspicion for infection is low, observation of these effusions is warranted initially, because most are caused by noninfectious processes that should improve with treatment of the underlying disease.     

Serum insulin but not leptin is associated with spontaneous and growth hormone (GH)-releasing hormone-stimulated GH secretion in normal volunteers with and without weight loss

Weight loss in humans is associated with elevated hypothalamic-pituitary growth hormone (GH) secretion. This study evaluates the effects of weight loss on the hypothalamic-pituitary (GH-releasing hormone [GHRH]-GH) axis in 14 normal-weight (body mass index [BMI], 25+/-1 Kg/m2) subjects, of whom half had undergone a diet-induced weight loss of 14%+/-2% (mean+/-SEM). Insulin-like growth factor-1 (IGF-1), insulin, oral glucose tolerance, leptin, and GH pulse patterns were determined in both groups after weight maintenance for 1 week. Of note, we tested the effects of recent weight loss (3 months) and not a recent dietary intake, since both groups ingested a normal calorie diet for 2 days in the Clinical Research Center (CRC) prestudy. Serum insulin (3.8+/-0.7 v 9.0+/-0.9 microU/mL, P < .01) and C-peptide (0.44+/-0.06 v 0.59+/-0.04 ng/mL, P < .05) were significantly lower in the weight loss group. Serum leptin was not different. Endogenous GH pulse height (11.9+/-4.8 v 1.3+/-0.1 microg/L, P < .05), area per GH pulse ([AUC] 57+/-28 v 6+/-1 microg/L, P < .05), and mean GH (3.91+/-0.76 v 0.85+/-0.16 microg/L, P < .01) were increased in the weight loss group. The serum insulin level was inversely associated with the mean GH concentration (r=-.678, P < .01) and GH pulse height (r=-.733, P < .01). In addition to spontaneous GH secretion, the GHRH-stimulated GH pulse height (41.8+/-18.1 v7.1+/-1.6 microg/L, P < .05) and AUC (161+/-35 v46+/-13 microg/L/min, P < .05) were also increased in the weight loss group. The insulin concentration was also inversely correlated with the GHRH-stimulated GH pulse height (r=-.718, P < .01). The leptin concentration was correlated with the BMI (r=.554, P < .05) and body fat (r=.744, P < .01), but not with GH secretion. In summary, even though these patients were on a normal calorie diet, a history of recent weight loss in young men and women of normal weight and health can be associated with a significant increase in spontaneous GH pulse height and GHRH-stimulated pulse height. Weight loss was also associated with a reduced serum insulin level. The observed increase in GH secretion may be secondary to the reduction in insulin or alterations of other factors acting at the site of the pituitary.     

Proton MR spectroscopy after acute central nervous system injury: outcome prediction in neonates, infants, and children

PURPOSE: To evaluate the usefulness of proton magnetic resonance (MR) spectroscopy in predicting 6-12-month neurologic outcome in children after central nervous system injuries. MATERIALS AND METHODS: Localized single-voxel, 20-msec-echo-time MR spectra (including N-acetylaspartate [NAA], choline [Ch], creatine and phosphocreatine [Cr]) were obtained in the occipital gray matter in 82 patients and 24 control patients. Patient age groups were defined as neonates (< or = 1 month [n = 23]), infants (1-18 months [n = 31]), and children (> or = 18 months [n = 28]). Metabolite ratios and the presence of lactate were determined. Linear discriminant analysis-with admission clinical data, proton MR spectroscopy findings, and MR imaging score (three-point scale based on severity of structural neuroimaging changes)-was performed to help predict outcome in each patient. Findings were then compared with the actual 6-12-month outcome assigned by a pediatric neurologist. RESULTS: Outcome on the basis of proton MR spectroscopy findings combined with clinical data and MR imaging score was predicted correctly in 91% of neonates and in 100% of infants and children. Outcome on the basis of clinical data and MR imaging score alone was 83% in neonates, 84% in infants, and 93% in children. The presence of lactate was significantly higher in patients with poor outcome than in patients with good-moderate outcomes in all three age groups (neonates, 38% vs 5%; infants, 87% vs 5%; children, 64% vs 10% [chi 2 test, P < .02]). In children with poor outcomes, NAA/Cr ratios were significantly lower in infants (P = .006) and children (P < .001), and NAA/Ch ratios were significantly lower in infants (P = .001) and neonates (P = .05). CONCLUSION: Findings at proton MR spectroscopy helped predict long-term neurologic outcomes in children after central nervous system injury.     

Cerebral blood flow is increased throughout 12 h of hypoxaemia in the mid-gestation ovine fetus

The changes in regional cerebral blood flow (CBF) in response to prolonged hypoxaemia were measured using coloured microspheres in the 0.6-gestation ovine fetus (n = 5). Fetal hypoxaemia was induced for 12 h by reducing maternal uterine blood flow with an adjustable clamp. CBF (mL min-1 100 g-1) was increased (P < 0.05) from control values (38.7 +/- 3.5) to 105.6 +/- 5.6 at 6 h of hypoxaemia, and to 121.9 +/- 23.1 at 12 h of hypoxaemia. One hour after fetal hypoxaemia had ceased, CBF (54.0 +/- 3.3) had decreased (P < 0.05) towards control values indicating incomplete cardiovascular recovery. Cerebral vascular resistance at 6 h and 12 h of hypoxaemia was lower (P < 0.05) than control values, and returned to control values 1 h after fetal hypoxaemia had ceased. Cerebral oxygen delivery at 6 h and 12 h of hypoxaemia was not significantly different from control values, but was higher (P < 0.05) 1 h after hypoxaemia had ceased. It is concluded that CBF is sufficiently increased during prolonged hypoxaemia in the mid-gestation fetus to maintain cerebral oxygen delivery.     

Doppler study of the fetal cardiac function in prolonged pregnancies

OBJECTIVE: To evaluate the association between fetal cardiac function and amniotic fluid index (AFI) in postterm fetuses, and to determine if changes in fetal cardiac function precede the occurrence of nonreassuring intrapartum fetal heart rate (FHR) patterns. METHODS: Forty-five otherwise low-risk pregnant women between 41 and 43 weeks' gestation were studied longitudinally. Gestational age was confirmed in all patients by ultrasound before 20 weeks' gestation. Each subject had two or three tests performed every 3-4 days, including a non-stress test, a biophysical profile, and Doppler studies of the aortic and pulmonic outflow tracts. Aortic and pulmonic artery flow velocity waveforms were recorded slightly distal to the valves. Peak velocity, velocity time integral, and heart rate were calculated from the flow velocity waveforms we obtained. The change in AFI and aortic and pulmonic peak velocity and [velocity time integral] x [heart rate] were calculated for each fetus. RESULTS: Labor was induced at 42 weeks' gestation in 20 patients, and 17 entered labor spontaneously. Changes in AFI, observed during the follow-up period, correlated significantly with changes in aortic peak velocity (r = 0.54, P < .01) and with aortic outflow [velocity time integral] x [heart rate] (r = 0.60, P < .001) but not with pulmonic peak velocity and [velocity time integral] x [heart rate]. The decrease in aortic peak velocity and aortic and pulmonic [velocity time integral] x [heart rate] was significantly higher (P < .01) in eight fetuses that developed a nonreassuring intrapartum FHR (reduced FHR variability, late decelerations, and severe variable decelerations) than in those who had an uneventful labor. CONCLUSION: In prolonged pregnancies, cardiac function deteriorates in fetuses that develop a nonreassuring intrapartum FHR, and the changes in the left cardiac function correlate with changes in AFI.     

Growth hormone bioactivity, insulin-like growth factors (IGFs), and IGF binding proteins in obese children

In obese children, both spontaneous and stimulated growth hormone (GH) secretion are impaired but a normal or increased height velocity is usually observed. This study was undertaken to explain the discrepancy between impaired GH secretion and normal height velocity. We evaluated the GH bioactivity (GH-BIO), GH serum level by immunofluorimetric assay (GH-IFMA), insulin-like growth factor-I (IGF-I), IGF-II, and IGF binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 in 21 prepubertal obese children (13 boys and eight girls) aged 5.7 to 9.4 years affected by simple obesity and in 32 (22 boys and 10 girls) age- and sex-matched normal-weight controls. The results were as follows (obese versus [v] controls): GH-IFMA, 4.84 +/- 3.54 v 23.7 +/- 2.04 microg/L (P < .001); GH-BIO, 0.60 +/- 0.45 v 1.84 +/- 0.15 U/mL (P < .001); IGF-I, 173.8 +/- 57.2 v 188.6 +/- 132.6 ng/mL (nonsignificant); IGF-II, 596.1 +/- 139.7 v 439.3 +/- 127.4 ng/mL (P < .001); IGFBP-1, 23.25 +/- 14.25 v 107 +/- 165.7 ng/mL (P < .05); IGFBP-2, 44.37 +/- 62.18 v 385.93 +/- 227.81 ng/mL (P < .001); IGFBP-3, 3.31 +/- 0.82 v 2.6 +/- 0.94 microg/mL (P < .05); and IGFs/IGFBPs, 1.32 +/- 0.32 v 1.07 +/- 0.34 (P < .05). In conclusion, in prepubertal obese children, not only immunoreactive but also bioactive GH concentrations were low. In these subjects, therefore, nutritional factors and insulin may contribute to sustain normal growth also by modulating several components of the IGF-IGFBP system.     

Ovine fetal-placental cocaine pharmacokinetics during continuous cocaine infusion

OBJECTIVE: To investigate fetal-placental cocaine clearance, and to determine the fetal catecholamine and cardiovascular responses to continuous intravenous cocaine infusion in fetal sheep. METHODS: Eleven pregnant ewes and their fetuses (127 +/- 2 days' gestation; term 150 days) were chronically instrumented. Fetuses received intravenous cocaine at 0.05, 0.1, or 0.2 mg/kg/minute. Fetal cardiovascular and hematologic measurements were made before and serially for 90 minutes after initiation of the cocaine infusion. RESULTS: Steady-state fetal plasma cocaine concentrations were observed by 15 minutes of infusion and averaged 136 +/- 11, 318 +/- 65, and 610 +/- 36 ng/mL, respectively, at each dose. Fetal-placental cocaine clearance rate was independent of dose (337 +/- 39 mL/kg/minute), indicating that it is a first-order pharmacokinetic process. Fetal plasma concentration of benzoylecgonine, a principle cocaine metabolite, increased throughout the study to approximately 25% above cocaine levels by 90 minutes. There were significant increases in fetal heart rate (from 169 +/- 11 to 242 +/- 36 beats per minute), mean blood pressure (from 53 +/- 4 to 63 +/- 5 mmHg), and systolic blood pressure (from 68 +/- 2 to 80 +/- 5 mmHg), with a corresponding increase in catecholamine levels seen in the fetuses infused with 0.2 mg/kg/minute. These changes were not seen in the fetuses given lower doses of cocaine. CONCLUSION: Fetal-placental clearance of cocaine is a rapid, first-order pharmacokinetic process. During prolonged cocaine exposure, plasma benzoylecgonine concentrations accumulate significantly. Significant catecholamine and cardiovascular changes are seen in fetal sheep with a continuous infusion of cocaine at 0.2 mg/kg/minute or greater.