In vitro evaluation of three-dimensional ultrasonography based on magnetic scanhead tracking

The objective of this study was to evaluate the accuracy and precision of a magnetic position sensor system for acquisition of three-dimensional (3D) ultrasound images in volume estimation of phantoms in vitro. Installation of either 0.9% solution of saline at 37 degrees C or distilled water at 20 degrees C to a condom was performed. Scanning was performed either by a continuous or stepwise acquisition. This 3D ultrasound system demonstrated good correlation (r = 0.99-1.0, n = 8) between estimated (EV) and true volumes (TV). The errors were in the range 1.3%+/-0.3% (SEM) to 1.9%+/-0.6%, independent of sound velocity. Scanning through a porcine abdominal wall positioned at the fluid surface yielded a systematic underestimation of the volume: mean (EV - TV) = -7.2+/-0.8 ml. Eight repeated scans of the same volume yielded a coefficient of variation of 1.1%. Interobserver error of the tracing procedure was 2.6%+/-0.9%. This 3D ultrasound system gave high accuracy and precision in volume estimation in vitro, and yielded low interobserver error. A change in ultrasound velocity of approximately 60 m/s did not influence the accuracy significantly. Scanning through an abdominal wall underestimated volumes slightly.     

Articular cartilage volume in the knee: semiautomated determination from three-dimensional reformations of MR images

PURPOSE: To determine the accuracy of semiautomated quantification of articular cartilage volume from three-dimensional (3D) reformations of magnetic resonance (MR) images. MATERIALS AND METHODS: Sagittal, fat-suppressed, 3D, spoiled gradient-recalled-echo MR imaging of two bovine and two human cadaver knees was performed. Articular cartilage volume was calculated from 3D reformations of the MR images by using a semiautomated program written at the authors' institution. Calculated volumes were compared with directly measured volumes of the surgically removed articular cartilage. RESULTS: The percentage of error of the MR imaging-determined volumes was 6.53% +/- 4.75 (mean +/- standard deviation). A strong correlation between the two sets of observations was shown (r=.997). Linear regression showed the calculated volumes to be highly accurate (slope=1.002, P>.25). Repeated reformations yielded volumes that were reproducible (mean absolute error, 0.013 mL +/- 0.019) and not significantly different from the measured volume (P>.10). CONCLUSION: Semiautomated quantification of knee articular cartilage from MR images yields highly accurate cartilage volumes.     

Evaluation of an extracorporeal membrane oxygenation system using a nonporous membrane oxygenator and a new method for heparin coating

A new heparin binding method was applied to a miniature extracorporeal membrane oxygenation (ECMO) system with a nonporous membrane oxygenator (the priming volume, 45 mL; the membrane surface area, 0.4 m2; maximal flow rate, 2 L/min) that is resistant to plasma leakage. The authors evaluated the stability of the immobilized heparin in vitro and the feasibility of this system in animals. Samples of hollow fibers and tubing were rinsed at 40 degrees C for 4 days in normal saline, Ringer's lactate, and 1 mol/L NaCl solution. Heparin activities on hollow fibers after rinsing were 99 +/- 2.3% (mean +/- SD), 96 +/- 3.9%, and 93 +/- 2.0% of the control in each solution, while those of the tubing were 87 +/- 4.1%, 86 +/- 3.1%, and 76 +/- 8.6%, respectively. Veno-arterial ECMO using this heparin-coated system was performed on five beagles (8 to 12 kg) for 10 hours. Neither major thrombus formation nor plasma leakage was detected during the procedure in spite of a low flow rate (300 mL/min) and a reduced activated clotting time (mean, 128 seconds). Platelets decreased to 52% of the control (P < .01) at 1 hour, but no progressive decrease was seen thereafter. Antithrombin-III decreased (P < .01) and thrombin/antithrombin III complex increased (P < .05 at 4 hours and P < .01 at 6, 8, and 10 hours) during bypass, but the changes of fibrinogen and fibrinopeptide A were not significant. Fibrinogen/fibrin degeneration products, fibrinopeptide B beta 15-42, and plasma-free hemoglobin levels did not rise significantly. O2 transfer of the oxygenators at a flow rate of 300 mL/min were 12.3 +/- 0.4 mL/min at 30 minutes, 14.3 +/- 1.2 mL/min at 5 hours, and 14.7 +/- 1.7 mL/min at 10 hours (no statistical difference). Histological examination of the brains and the kidneys showed no evidence of thromboembolic sequela in any of the animals. These results suggest that this new system is a promising device for long-term ECMO in which the amount of systemic heparinization can be reduced with the minimal possibility of plasma leakage.     

Uncontrolled hemorrhage from parenchymal injury: is resuscitation helpful?

Fluid resuscitation increases blood pressure and may increase hemorrhage. We tested this hypothesis in a model of liver injury. After standardized injury, rats were randomized into four groups: no resuscitation (NR, n = 30), small volume lactated Ringer's solution (SVLR, 4 mL/kg, n = 30), large volume lactated Ringer's solution (LVLR, 24 mL/kg, n = 30), and hypertonic saline (HS, 4 mL/kg, n = 30). Terminal circulating volume was estimated using controlled hemorrhage experiments. Survival times and mortality rates were significantly lower in HS animals (10%) than in NR (50%) or SVLR (47%) animals. Blood pressure was significantly higher after HS, and this difference was sustained. Intraperitoneal blood volume was significantly higher with HS (26.0 +/- 0.7 mL/kg) and LVLR (26.9 +/- 0.6 mL/kg) compared with NR (21.5 +/- 0.7 mL/kg) and SVLR (22.5 +/- 0.7 mL/kg). Estimated terminal blood volume was significantly decreased in LVLR (29.3 +/- 0.6 mL/kg) compared with NR (33.3 +/- 0.7 mL/kg), SVLR (33.7 +/- 0.8 mL/kg), and HS (31.7 +/- 0.7 mL/kg). CONCLUSION: Vigorous resuscitation increases bleeding from solid viscus injury. Small volume HS improves blood pressure and survival compared with no resuscitation. Results of large vessel hemorrhage models may not apply to parenchymal viscus injury.     

Collagen in the fetal membranes of sheep: changes throughout gestation and effects of dexamethasone at 60 days

The tensile strength of fetal membranes is largely due to their collagen content. In this study we have examined the changes in collagen in the amniotic and allantoic membranes of the sheep over a wide gestational range (27-142 days of gestation; term, 145-150 days). The results have been correlated with volume changes in normal development, and in particular, the changes in allantois have been studied after a rapid and extensive increase in allantoic volume, as a result of maternal dexamethasone treatment (0.76 mg h-1 for 48 h) from Day 60 of gestation. Electron microscopy and immunohistochemistry were used to delineate collagen distribution, and gel electrophoresis was used to assess the relative proportions of each type. In the amnion, collagen content increased from 37 +/- 4% to 50 +/- 1% dry weight of the tissue from 41-102 days and declined slightly thereafter. In the allantois, collagen content increased from 20 +/- 1% at Day 27 to 50 +/- 6% at Day 142, significantly correlated with a volume increase from 25 +/- 3 mL to 813 +/- 274 mL. Collagen types I (>85%), III (10%) and small amounts of types IV and V (<5%) were identified in both membranes at all ages. When allantoic fluid volume was increased rapidly by maternal dexamethasone infusion, there was a significant decrease in collagen content from 38 +/- 6% to 25 +/- 2% (P < 0.05). By immunohistochemistry it was observed that both epithelial cells and fibroblasts were synthesizing collagen.     

Right atrial and right ventricular transmural pressures in dogs and humans. Effects of the pericardium

BACKGROUND: To determine the transmural pressure-dimension relations of the right atrium (RA) and right ventricle (RV) before and after pericardiectomy, six open-chest dogs were instrumented with pericardial balloons placed over the RA and RV free walls. METHODS AND RESULTS: PA appendage dimensions and RV free-wall segment lengths were measured using sonomicrometry. Intact-pericardium RA and RV transmural pressures were calculated by subtracting the pericardial pressures (measured using balloons) from the cavitary pressures. Pooled data from six animals with pericardium intact indicate that at RA and RV cavitary pressures of 5, 10, and 15 mm Hg, RV pericardial pressure was 4.3 +/- 0.3, 8.6 +/- 1.0, and 13.3 +/- 1.5 mm Hg, respectively, and RA pericardial pressure was 4.8 +/- 0.3, 9.6 +/- 0.6, and 14.6 +/- 0.6 mm Hg, respectively (mean +/- SD). With calculated unstressed dimensions, the cavity dimension data were normalized to strain (in percent). We determined that in the dog, RV strain would increase by 14% and RA by 68% to maintain cavitary pressure at 10 mm Hg on pericardiectomy. To compare these results with clinical data, RV (n = 7) and RA (n = 6) transmural pressures were measured using balloons in patients (age, 19 to 76 years) undergoing cardiac surgery. RA transmural pressure of six patients was 1.0 +/- 1.5 mm Hg when central venous pressures (CVPs) ranged from 3 to 16 mm Hg. RV transmural pressure equaled 1.2 +/- 1.9, 2.3 +/- 1.9, and 3.4 +/- 2.0 mm Hg when CVP was 5, 10, and 15 mm Hg, respectively. CONCLUSIONS: Pericardial constraint (as evaluated by the ratio of pericardial to intracavitary pressures when CVP is 10 mm Hg) accounted for 96% of RA cavitary pressure in the dog and 89% in humans and at least 86% of RV cavitary pressure in the dog and 77% in humans.     

Giovanni Di Chiro (1926-1997)

OBJECTIVE: To test the value of venous-arterial PCO2 gradient (deltaPCO2) measurements to reflect the adequacy of cardiac index (CI) to oxygen demand in patients submitted to rapid changes of CI and oxygen demand. DESIGN: Prospective, comparative study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Ten patients with congestive heart failure exhibiting low baseline CI (< or =2.5 L/min/m2) but no evidence of global tissue hypoxia, as attested by the absence of clinical signs of shock and by normal blood lactate concentrations. INTERVENTIONS: Infusion of incremental doses of dobutamine: 0 (D0), 5 (D5), 10 (D10), and 15 (D15) microg/kg/min. MEASUREMENTS AND MAIN RESULTS: The CI increased by a linear fashion from D0 (1.6+/-0.1 L/min/m2) to D15 (2.4+/-0.2 L/min/m2) (p< .05). The mixed venous oxygen saturation (SVO2) increased from D0 (49+/-2%) to D10 (61+/-2%) (p < .05) and remained unchanged from D10 to D15 (60+/-2%). The oxygen extraction ratio (O2 ER) and the deltaPCO2 decreased from D0 (48+/-2% and 9+/-1 torr [1.2+/-0.3 kPa], respectively) to D10 (36+/-2% and 5+/-1 torr [0.7+/-0.1 kPa], respectively) (p < .05 for both comparisons) and remained unchanged from D10 to D15 (36+/-2% and 6+/-1 torr [0.8+/-0.1 kPa], respectively). The biphasic courses of SVO2, O2 ER, and deltaPCO2 were related to the course of oxygen consumption that remained constant from D0 (113+/-9 mL/min/m2) to D10 (112+/-8 mL/min/m2) and significantly increased from D10 to D15 (127+/-10 mL/min/m2) (p <.05). CONCLUSIONS: deltaPCO2 can be reliably used at the bedside for informing on the adequacy of CI with respect to a given metabolic condition, and particularly for detecting changes in oxygen demand (e.g., the changes accompanying drug-induced changes in CI). In this regard, deltaPCO2, together with O2 ER and SVO2, can help to assess the adequacy of CI to global oxygen demand.     

Hyaluronic acid inhibits fetal platelet function: implications in scarless healing

Platelets are important for the initiation of inflammation in adults, but the role of fetal platelets in fetal wound healing is unclear because fetal dermal wounds heal with a minimal inflammatory response and lack of excessive scarring. Because fetal tissue is abundant in glycosaminoglycans (GAGs), predominantly hyaluronic acid (HA), this study was designed to test the hypothesis that HA inhibits the reactivity of platelets and thus contributes to the minimal scarring characteristic of fetal tissue repair. Platelets were isolated from 10 fetal pigs at day 80 of gestation (term, 115 days) and exposed to 0.5 mg/mL of arachidonic acid, an agent shown in prior studies to evoke maximal aggregation and degranulation of fetal platelets. The ability of HA at 0.1 and 0.5 mg/mL to inhibit this response was determined. The presence of HA resulted in a dose-dependent reduction in platelet aggregation at 180 seconds (control, 99.7 +/- 0.3%; HA [0.1 mg/mL] 91.7 +/- 3.8%; and HA [0.5 mg/mL] 48.5 +/- 9.0%; P < .005 v control). The onset of aggregation was also significantly delayed by 0.5 mg/mL of HA (13.5 +/- 2.5 seconds) compared to control (2.9 +/- 0.7 seconds), P < .05. No significant diminution of platelet aggregation could be achieved by the addition of other GAGs at similar concentrations. HA also significantly impaired the release of platelet-derived growth factor (PDGF)-AB from fetal platelets. The authors conclude that HA, the predominant GAG in fetal dermal matrix, inhibits platelet aggregation and cytokine release. This inhibition of platelet aggregation and resultant inflammatory response may explain, in part, the minimal inflammation and scarless healing characteristic of fetal dermal repair.     

Public health developments in colonial Malaya: colonialism and the politics of prevention

-Previous studies have shown that whereas the nonclipped kidney in two-kidney, one clip (2K1C) rats undergoes marked depletion of renin content and renin mRNA, intrarenal angiotensin II (Ang II) levels are not suppressed; however, the distribution and functional consequences of intrarenal Ang II remain unclear. The present study was performed to assess the plasma, kidney, and proximal tubular fluid levels of Ang II and the renal responses to intrarenal Ang II blockade in the nonclipped kidneys of rats clipped for 3 weeks. The Ang II concentrations in proximal tubular fluid averaged 9.19+/-1.06 pmol/mL, whereas plasma Ang II levels averaged 483+/-55 fmol/mL and kidney Ang II content averaged 650+/-66 fmol/g. Thus, as found in kidneys from normal rats with normal renin levels, proximal tubular fluid concentrations of Ang II are in the nanomolar range. To avoid the confounding effects of decreases in mean arterial pressure (MAP), we administered the nonsurmountable AT1 receptor antagonist candesartan directly into the renal artery of nonclipped kidneys (n=10). The dose of candesartan (0.5 microg) did not significantly decrease MAP in 2K1C rats (152+/-3 versus 148+/-3 mm Hg), but effectively prevented the renal vasoconstriction elicited by an intra-arterial bolus of Ang II (2 ng). Candesartan elicited significant increases in glomerular filtration rate (GFR) (0.65+/-0. 06 to 0.83+/-0.11 mL. min-1. g-1) and renal blood flow (6.3+/-0.7 to 7.3+/-0.9 mL. min-1. g-1), and proportionately greater increases in absolute sodium excretion (0.23+/-0.07 to 1.13+/-0.34 micromol. min-1. g-1) and fractional sodium excretion (0.38+/-0.1% to 1.22+/-0. 35%) in 2K1C hypertensive rats. These results show that proximal tubular fluid concentrations of Ang II are in the nanomolar range and are much higher than can be explained on the basis of plasma levels. Further, the data show that the intratubular levels of Ang II in the nonclipped kidneys of 2K1C rats remain at levels found in kidneys with normal renin content and could be exerting effects to suppress renal hemodynamic and glomerular function and to enhance tubular reabsorption rate.     

Estrogen-mediated neuroprotection after experimental stroke in male rats

BACKGROUND AND PURPOSE: We have previously shown that 17beta-estradiol reduces infarction volume in female rats. The present study determined whether single injection or chronic implantation of estrogen confers neuroprotection in male animals with middle cerebral artery occlusion (MCAO) and whether there is an interaction with endogenous testosterone. METHODS: Male Wistar rats were treated with 2 hours of reversible MCAO. In protocol 1, acute versus chronic estrogen administration was examined in groups receiving the following: Premarin (USP) 1 mg/kg IV, immediately before MCAO (Acute, n=13, plasma estradiol=171+/-51 pg/mL); 7 days of 25 microg (E25, n=10, 10+/-3 pg/mL) or 100 microg 17beta-estradiol (E100, n=12, 69+/-20 pg/mL) by subcutaneous implant; or saline (SAL, n=21, 3+/-1 pg/mL). Laser-Doppler flowmetry was used to monitor the ipsilateral parietal cortex throughout the ischemic period and early reperfusion. At 22 hours of reperfusion, infarction volume was determined by 0 2,3,5-triphenyltetrazolium chloride staining and image analysis. In protocol 2, rats were castrated to deplete endogenous testosterone and then treated with estradiol implants: castration only (CAST, n= 13, estradiol=5+/-2 pg/mL), sham-operated (SHAM, n= 10, 4+/-2 pg/mL), estradiol implant 25 microg (CAST+E25, n=16, 7+/-2 pg/mL) or 100 microg (CAST+E100, n=14, 77+/-14 pg/mL). RESULTS: Cortical infarct volumes were reduced in all estrogen-treated groups: Acute (21+/-4% of ipsilateral cortex), E25 (12+/-5%), and E100 (12+/-3%) relative to SAL (38+/-5%). Caudate infarction was similarly decreased: Acute (39+/-7% of ipsilateral striatum), E25 (25+/-7%), and E100 (34+/-6%) relative to SAL (63+/-4%). Castration did not alter ischemic outcome; cortical and caudate infarction (percentage of respective ipsilateral regions) were 37+/-5% and 59+/-5% in CAST and 39+/-7% and 57+/-5% in SHAM, respectively. Estrogen replacement reduced infarction volume in castrated animals in cortex (19+/-4% in CAST+E25 and 12+/-4% in CAST+E100) and in caudate (42+/-6% in CAST+25 and 20+/-7% in CAST + 100). Laser-Doppler flowmetry results during ischemia and reperfusion was not different among groups. CONCLUSIONS: Both acute and chronic 17beta-estradiol treatments protect male brain in experimental stroke. Testosterone availability does not alter estradiol-mediated tissue salvage after MCAO.     

An anthropomorphic phantom study on the effect of midvertebral slice placement and region-of-interest positioning on the reproducibility of single-energy quantitative CT (QCT) of the spine

PURPOSE: The purpose of our study was to develop an anthropomorphic phantom with a 3D external reference system capable of geometrically describing the region of interest (ROI) of single-energy quantitative CT (QCT) scans and to study the reproducibility of ROI placement (volume) and bone mineral density (BMD) after operator-defined and algorithm-supported midvertebral slice (MVS) placement. METHOD: In three vertebrae (L1-3) of 10 human cadaveric spines placed in a water phantom, MVSs were defined by an operator and an algorithm-supported technique on lateral digital CT radiographs, and QCT scans were performed accordingly. The measurements were repeated once after repositioning the phantom on the CT table. ROIs of the trabecular bone were determined with a standard technique. The percentage of bone volume was calculated for one ROI not covered by the repetition (volume mismatch percent). RESULTS: Reproducibility with algorithm-supported MVS placement was superior to that of operator-defined positioning with regard to volume mismatch (mean +/- SD): 10.6+/-8.4 vs. 7.9+/-5.3%; and mean of paired BMDs (mean of three vertebral bodies): 2.7 vs. 1.5% (p < 0.05). CONCLUSION: The ROI volume mismatch of repeated QCT scans, which is approximately 10% of ROI volume, can be quantified with an external reference system. Automated placement is superior to the manual technique and should be used in clinical practice.     

Femoral cortical remodeling after uncemented total hip arthroplasty. A prospective radiologic study of 26 hips followed for 2 to 4 years

Aging and disease may make the elderly patient with cardiac disease particularly susceptible to hypotension during spinal anesthesia. We studied 15 men, 59-80 y old, with histories of prior myocardial infarction (n = 9), congestive heart failure (n = 2), and/or stable myocardial ischemia (n = 11) given spinal anesthesia with 50 mg lidocaine in dextrose. Technetium-99m-labeled red blood cell imaging estimated left ventricular ejection fraction (EF) and changes in blood volume in the abdominal organs and legs. Arterial and pulmonary artery catheters provided hemodynamic measurements. Sensory block averaged T4 (range T1-10). Mean arterial pressure decreased 33% +/- 15% (SD) (P < 0.001), secondary to decreases in vascular resistance (SVR), -26% +/- 13% (P < 0.001) and cardiac output, -10% +/- 16% (P = 0.03). EF increased from 53% +/- 11% to 58% +/- 14% (P < 0.001) while left ventricular end-diastolic volume (LVEDV) decreased (-19% +/- 9%, P < 0.001). Blood volume increased in the legs (6% +/- 6%, P = 0.006), kidneys (10% +/- 9%, P < 0.001), and mesentery (7% +/- 5%, P 0.001) but not in the liver or spleen. Cardiac function was well maintained. We concluded that the primary mechanism of hypotension was a decrease in SVR, not cardiac output, despite the decrease in LVEDV.     

When should expanded criteria donor kidneys be used for single versus dual kidney transplants?

BACKGROUND: To increase the utilization of cadaveric donor kidneys, we have recently expanded our acceptable criteria to include aged donors (frequently with a history of hypertension), by selectively using both donor kidneys (dual transplant) into a single recipient. METHODS: To define when these expanded criteria donor (ECD) kidneys should be used as a single versus a dual kidney transplant, we retrospectively reviewed 52 recipients of ECD kidneys that had been turned down by all other local centers between 1/1/95 and 11/15/96. Fifteen patients received dual transplants, whereas the remaining 37 received single kidneys. Of the dual kidney recipients, 14 of 15 ECD were > or = 59 years of age, 10 of 15 were hypertensive, and 9 of 15 were both. Of the single recipients, 11 of 37 ECD were > or = 59 years of age, 11 of 37 were hypertensive, and 7 of 37 were both. All patients received cyclosporine-based triple-drug therapy. We compared seven donor (D) and sixteen recipient outcome variables in single versus dual kidney transplants as subgrouped by: (1) donor admission creatinine clearance (D-AdC(Cr)) < 90 ml/min; (2) D-age > or = 59 years; and (3) cold storage (Cld Stg) < or > 24 hr. RESULTS: In the group with D-AdC(Cr) < 90, there was a significantly higher incidence of delayed graft function (DGF) in single versus dual recipients (9 of 20 [45%] vs. 1 of 11 [9%]; P=0.04) and worse early graft function based upon mean serum creatinine at 1 and 4 weeks (5.3+/-3.3 and 2.8+/-2.0 vs. 1.7+/-0.6 and 1.4+/-0.5 mg] dl; P<0.05). In the group with D-age > or = 59, recipients of single kidneys had significantly higher mean serum creatinine at 1, 4, and 12 weeks versus recipients of dual kidneys (5.1+/-3.3, 3.4+/-2.1, 2.8+/-1.5 versus 2.8+/-2.5, 1.5+/-0.6, 1.6+/-0.5 mg/dl; P<0.05). Cld Stg time also had an impact on DGF and early outcome. Recipients of dual kidneys stored less than 24 hr had a significantly lower incidence of DGF versus single kidneys stored more than 24 hr (10% vs. 46%; P<0.05) and better early graft function based on mean serum creatinine at 1, 4, and 12 weeks (1.9+/-0.8, 1.3+/-0.4, 1.5+/-0.2 vs. 6.6+/-3.4, 3.0+/-1.6, 2.9+/-1.9 mg/dl; P<0.05). The overall 1-year patient and graft survivals were 96% and 81% vs. 93% and 87% (P=NS) in recipients of single ECD versus dual ECD kidneys. CONCLUSIONS: In conclusion, we believe that kidneys from ECD with D-AdC(Cr) < 90 ml/min and D-age > or = 59 should be used as dual kidney transplants, keeping the Cld Stg time at < 24 hr to minimize the effect of Cld Stg on early graft function.     

Maternal plasma hypo-osmolality: effects on spontaneous and stimulated ovine fetal swallowing

Fetal swallowing is a major route of amniotic fluid resorption, and thus swallowing activity may alter amniotic fluid volume. Near-term ovine fetal swallowing increases in response to plasma and/or cerebrospinal fluid hypertonicity. As maternal hydration status alters amniotic fluid volume, we hypothesized that maternal plasma hypotonicity may alter fetal swallowing activity. Pregnant ewes (130 +/- 1 d; n = 6) were chronically prepared with maternal and fetal vascular catheters, a fetal esophageal flow probe, and fetal thyrohyoid and nuchal and thoracic esophagus electromyogram electrodes. Spontaneous fetal swallowing and hypertonic saline thresholds for stimulated swallowing were determined prior to and following maternal hypotonicity induced with water loading and intravenous DDAVP (arginine vasopressin V2 agonist). Fetal swallowing thresholds were determined with intracarotid injections (0.15 ml/kg) of increasing sodium chloride concentrations (0.15-1.2 M) at 2-min intervals. Maternal DDAVP infusion significantly decreased mean (+/-SEM) maternal and fetal plasma osmolalities (298 +/- 2-284 +/- 3; 295 +/- 2-278 +/- 3 mOsm/kg, respectively) and sodium concentrations (147.3 +/- 0.4-137.5 +/- 0.9; 142.7 +/- 0.8-133.5 +/- 1.0 mEq/l, respectively), suppressed spontaneous swallowing activity and volume (1.1 +/- 0.2-0.6 +/- 0.1 swallows/min; 0.7 +/- 0.2-0.5 +/- 0.1 ml/min, respectively) and significantly increased the osmotic threshold for swallowing stimulation (0.77 +/- 0.08-1.03 +/- 0.09 M NaCl). We conclude that: (1) maternal, and thus fetal, plasma hypotonicity results in suppression of spontaneous fetal swallowing activity and a decrease in volume swallowed, suggesting that spontaneous fetal ingestive behavior results, in part, from tonic dipsogenic stimulation, and (2) under hypotonic conditions, the intracarotid NaCl injection concentration for swallowing stimulation increases. These results suggest that the reset (lower) maternal plasma osmolality during human pregnancy may serve to minimize fetal ingestive and perhaps arginine vasopressin-mediated antidiuretic responses to acute maternal hypertonicity.     

In vivo measurement of chloride and water secretion in the jejunum of cystic fibrosis patients

In the present study, we have investigated the possible consequences of the chloride channel defect in the intestine of cystic fibrosis (CF) patients for electrolyte and water transport in the jejunum in vivo, using a multilumen, double occluding balloon catheter, and an Ag/AgCl intraluminal electrode. During a chloride-free perfusion, to optimize the sensitivity of our measurements, the transmural potential difference (PD) (lumen with reference to serosal side) was found to be significantly higher in the jejunum of CF patients (+8.0 +/- 2.1 mV; n = 5) than in healthy control subjects (-2.2 +/- 2.0 mV; n = 9). The chloride concentration measured in chloride-free jejunal perfusates of CF patients was significantly lower than in controls (10.9 +/- 2.3 and 41.4 +/- 8.2 mM, respectively). Possible differences in net chloride and water secretion did not reach statistical significance (chloride secretion controls: -2.1 +/- 0.9 mmol/10 cm/h; CF: -0.8 +/- 0.2 mmol/10 cm/h; water secretion controls: -0.8 +/- 2.5 mL/10 cm/h; CF: -11.7 +/- 8.9 mL/10 cm/h). In control subjects, intraluminally applied theophylline stimulated the secretion of water (delta 23.4 +/- 4.6 mL/10 cm/h) and chloride (delta 4.1 +/- 1.1 mmol/10 cm/h), but not in CF patients (respectively delta 3.6 +/- 3.3 mL/10 cm/h and delta 1.1 +/- 1.1 mmol/10 cm/h). In controls, theophylline caused a significant increase in lumen negativity (PD -10.2 +/- 2.6 mV), but no change could be seen in CF patient transmural PD. These observations provide in vivo evidence for a decreased chloride permeability in the jejunum in CF, resulting in a significant reduction in net electrolyte and water secretion in the presence, but not in the absence, of an intestinal secretagogue.     

Physical fitness influences water turnover and body water changes during trekking

PURPOSE: This study was performed to assess water turnover and changes of body water during a trekking tour at moderate altitude. METHODS: Fifteen healthy normally trained adults participated in a 7-d backpack trek tour in the Swiss Alps (total walking distance: 120.5 km; cumulated altitude difference: 6990 m (uphill) and 7550 m downhill; lowest point: 1285 m; highest point: 3317 m). Total body water and water turnover were measured using deuterium dilution and elimination (oral load of 0.33 g 99.8% D2O per kg body weight, overnight equilibration period, pre- and postdose saliva samples immediately before and after sleep, analysis of D2O concentrations in saliva using Fourier-transform infrared spectroscopy, CV < 1%). Physical training state was assessed after the tour using the lactate-exercise intensity relationship obtained by performing 50-W increments every 3 min on a cycle ergometer. RESULTS: Body water decreased from the evening of day 0 to the evening of day 4 (from 45.3 +/- 7.3 L to 43.4 +/- 7.6 L, P < 0.05), and did not significantly decrease (43.5 +/- 7.9 L) until the evening of day 5 (maximum of trekking exercise intensity). Mean daily water turnover was 5.7 +/- 1.8 L x d(-1) corresponding to 78.7 +/- 17.5 mL x kg(-1) x d(-1). Body water changes and water turnover were significantly related to the exercise intensity obtained at the lactate threshold as well as at the level of 4 mM lactate. CONCLUSIONS: This correlation may be in part explained by differing glycogen content of muscle tissue.     

Multiplane transesophageal echocardiographic doppler imaging accurately determines cardiac output measurements in critically ill patients

OBJECTIVES: To compare cardiac output and stroke volume measured by multiplane transesophageal Doppler echocardiography with that measured by the thermodilution technique. DESIGN: Prospective direct comparison of paired measurements by both techniques in each patient. SETTING: Cardiac surgery and myocardial infarction intensive care units. PATIENTS: Twenty-nine patients, mean age (+/- SD) 67 +/- 8 years. Nineteen had undergone open heart surgery and 10 had suffered acute myocardial infarction. METHODS: Cardiac output and stroke volume were measured simultaneously by the thermodilution technique and multiplane transesophageal Doppler echocardiography via the transgastric view (119 +/- 8 degrees) with the sample volume positioned at the level of the left ventricular outflow tract. RESULTS: Stroke volume and cardiac output measurements were obtained in 29 of 33 patients (88%). Mean values were 50 +/- 13 mL and 4.8 +/- 1.3 L/min by Doppler and 51 +/- 14 mL and 4.9 +/- 1.4 L/min by thermodilution (r = 0.90, r = 0.91, p < 0.001). The mean differences in values obtained with the two techniques were 1 +/- 6 mL (2 +/- 12%) and 0.1 +/- 0.7 L/min (2 +/- 12%). CONCLUSIONS: Multiplane transesophageal echocardiography enhances the ability to estimate accurately cardiac output and stroke volume by providing new access to left ventricular outflow tract in critically ill patients.     

Role of the kidneys in the metabolism of furosemide: its inhibition by probenecid

The site where furosemide is metabolized and the location where probenecid reduces furosemide metabolism remain poorly defined. The liver appears to play a minor role, and there is indirect evidence suggesting that the kidneys could be responsible for the metabolism of furosemide. To assess the role of the kidneys in the metabolism of furosemide, its intravenous kinetics have been studied in control and anephric rabbits, after the ligation of the renal pedicles. Two additional groups of rabbits, control and anephric, have received probenecid before the administration of furosemide. In the control group, the total clearance of furosemide was 18.65 +/- 1.01 mL/ min per kg; urinary and metabolic clearances of furosemide were 7.95 +/- 0.65 and 10.70 +/- 1.11 mL/min per kg, respectively. In anephric rabbits, total clearance was reduced by 85% to 2.69 +/- 0.26 mL/min per kg (P < 0.001), secondary to the abolition of furosemide renal excretion and to the reduction in metabolic clearance from 10.70 +/- 1.11 to 2.69 +/- 0.26 mL/min per kg (P < 0.001). The pretreatment with probenecid reduced the total clearance of furosemide by 80%, to 3.62 +/- 0.24 mL/min per kg (P < 0.001), because of a reduction of 90 and 75% in urinary and metabolic clearances, respectively. The administration of probenecid to anephric rabbits did not reduce further the metabolic clearance. It is concluded that the kidneys are responsible for 85% of furosemide total clearance, either via excretion (43%) or biotransformation (42%), and that probenecid inhibits both processes.     

Real-time three-dimensional echocardiography for determining right ventricular stroke volume in an animal model of chronic right ventricular volume overload

BACKGROUND: The lack of a suitable noninvasive method for assessing right ventricular (RV) volume and function has been a major deficiency of two-dimensional (2D) echocardiography. The aim of our animal study was to test a new real-time three-dimensional (3D) echo imaging system for evaluating RV stroke volumes. METHODS AND RESULTS: Three to 6 months before hemodynamic and 3D ultrasonic study, the pulmonary valve was excised from 6 sheep (31 to 59 kg) to induce RV volume overload. At the subsequent session, a total of 14 different steady-state hemodynamic conditions were studied. Electromagnetic (EM) flow probes were used for obtaining aortic and pulmonic flows. A unique phased-array volumetric 3D imaging system developed at the Duke University Center for Emerging Cardiovascular Technology was used for ultrasonic imaging. Real-time volumetric images of the RV were digitally stored, and RV stroke volumes were determined by use of parallel slices of the 3D RV data set and subtraction of end-systolic cavity volumes from end-diastolic cavity volumes. Multiple regression analyses showed a good correlation and agreement between the EM-obtained RV stroke volumes (range, 16 to 42 mL/beat) and those obtained by the new real-time 3D method (r=0.80; mean difference, -2.7+/-6.4 mL/beat). CONCLUSIONS: The real-time 3D system provided good estimation of strictly quantified reference RV stroke volumes, suggesting an important application of this new 3D method.     

Influence of sex steroids on development of cultured fetal rat metatarsal bones

The effects of 17 beta-estradiol (E), dihydrotestosterone (D, a non aromatisable androgen), and progesterone (P) on osteogenesis were studied on fetal rat cartilaginous anlagues cultivated in vitro. The three medial metatarsal rudiments were harvested at day 19 of gestation and grown in 1% BSA MEM medium (MO 643, Sigma) without serum nor antibiotics. After a 18h preincubation period, hormones were added for 8 days. Paired controls were incubated in the same volume of medium. The length, the metacarpal thickness and the size of the mineralized zone were measured every day, using a calibrated eyepiece (magnification X 40). DNA and protein synthesis, cartilage metabolism and mineralization were evaluated by monitoring the incorporation of 3H-Thymidine, 3H-Proline, 35S and 45Ca into anlagues for the last three hours of incubation, respectively. The dose/response effect of each steroid was studied at the concentrations of 10(-4) M, 10(-6) M, 10(-7) M and 10(-9) M. No difference was observed between male and female fetuses. A significant positive effect on total length (% of length measured at harvesting day) was observed with the 10(-7) M dose of E (163% +/- 2 vs 148% +/- 4 in controls) or D (158% +/- 3). Endochondral growth was not modified by P treatment. The effect of the three steroids (given at a dose of 10(-7) M) alone or as combinations (E, D, P, EP, ED, PD, EPD) confirmed the positive effect of E on endochondral growth and, to a lesser extend, of D and the association ED. Nevertheless, D had a better effect than E on endomembranous growth. On the contrary, P did not affect growth neither administrated alone nor in combination with E or D, while a positive effect of P on mineralization was demonstrated. The treatment associating the three steroids slowed down all the parameters concerning growth but strongly stimulated calcification.