Effects of hypothermia in hypercapnia and hypercapnic hypoxemia

Anesthetized, paralyzed and mechanically ventilated pigs were hypoventilated to extreme hypercapnia (PaCO2 approximately 20 kPa) at FiO2 0.5, and allotted to a hypothermic group (31.5 +/- 0.1 degrees C, n = 6) or a control group (39.6 +/- 0.2 degrees C, n = 6). Compared with the controls, the hypothermic animals had higher PaO2 (19.2 vs 15.6 kPa, P < 0.05), SaO2 (97.2 vs 89.3%), SvO2 (78.7 vs 68.2%), end-tidal O2 (34.5 vs 24.8 kPa) and arterial pH (7.01 vs 6.91), (P < 0.01), but lower PvO2 (7.0 vs 10.2 kPa) and PaCO2 (13.2 vs 23.5 kPa), (P < 0.01). Hypothermia reduced O2 delivery (DO2), O2 consumption (VO2) and CO2 production by 40-45% (P < 0.05), but O2 extraction ratio, i.e. VO2.DO(2)-1 x 100(%), did not differ between groups. Hypothermic animals had lower heart rate (127 vs 223 beats.min-1, P < 0.05) and cardiac output (2.5 vs 3.9 l.min-1, P < 0.01). Subsequently, the inspired oxygen fraction (FiO2) was decreased stepwise (0.3, 0.25, 0.21, 0.15, 0.10) at 30-min intervals. At FiO2 0.3, the hypothermic group had higher PaO2 (10.0 vs 5.7 kPa), SaO2 (91.3 vs 28.5%), PvO2 (5.8 vs 3.4 kPa), SvO2 (70.7 vs 10.3%), end-tidal O2 (16.7 vs 8.5 kPa), O2 delivery (344 vs 155 ml.min-1), arterial pH (7.02 vs 6.94) and systemic vascular resistance (3850 vs 1652 dyn.s.cm-5 (38,500 vs 16,520 microN.s.cm-5)) compared with the controls (P < 0.01), while PaCO2 was lower (12.4 vs 22.7 kPa), as well as O2 extraction ratio (23 vs 63%) and O2 half saturation tension (4.3 vs 8.0 kPa) (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Transduction of cultured oligodendrocytes from normal and twitcher mice by a retroviral vector containing human galactocerebrosidase (GALC) cDNA

We examined in mice the effect of chronic diazepam treatment on the sensitivity to isoflurane, and that of repeated isoflurane exposure on the sensitivity to diazepam. Mice were divided into four groups: group 1, treated with diazepam, 10 mg/kg i.p. twice daily; group 2, vehicle-treated controls; group 3, exposed to 3% isoflurane for 25 min twice daily; and group 4, untreated controls. After 14 days the effect of the treatment was assessed. Twenty-four hours after the last 10 mg/kg diazepam treatment, groups 1 and 2 received diazepam, 5 mg/kg i.p., and were subjected to the horizontal wire test (HWT). All control mice but only 10% of the diazepam-treated mice failed the HWT. Groups 1 and 2 were then exposed to increasing concentrations of isoflurane. Diazepam-treated mice (group 1) lost the HWT at 0.7+/-0.7%, compared with 0.6+/-0.1% in controls (group 2) (P<0.001); the ED50 was 0.75% vs. 0.65%. Group 1 mice lost the righting reflex at 0.94+/-0.07% isoflurane vs. 0.87+/-0.06% in group 2 (P<0.01); the ED50 was 0.93% vs. 0.82%. Recovery time was 175+/-161 s in group 1 vs. 343+/-275 s in group 2 (P<0.02). Twenty-four hours after the last of the repeated exposures to isoflurane, we examined the responses of groups 3 and 4 to increasing concentrations of isoflurane. Mice in group 3 lost the righting reflex at 1.0+/-0.06% isoflurane vs. 0.9+/-0.04% in controls (group 4) (P<0.001); the ED50 was 0.96% vs. 0.85%. Recovery time was 113+/-124 s vs. 208+/-126 s in groups 3 and 4 (P<0.09). Diazepam, 3 mg/kg i.p. administered to groups 3 and 4, caused loss of the HWT reflex in 33% of group 3 mice and in 82% of controls (group 4) (P<0.001). It appears that prolonged exposure to both diazepam and isoflurane caused reduced sensitivity to each drug separately, as well as to the other drug. This finding may strengthen the theory that inhalational anesthetics may act via the same mechanism as the benzodiazepines.     

Neonatal diagnosis of familial hypercholesterolemia in newborns born to a parent with a molecularly defined heterozygous familial hypercholesterolemia

This study was designed to compare blood lipid levels in newborn individuals with molecularly defined heterozygous familial hypercholesterolemia [FH] to those in non-affected babies and to clarify the value of lipid determinations in assessment of diagnosis of FH at birth and 1 year of age. Twenty-five babies were born to 21 parents with DNA-documented heterozygous FH. Analysis of their cord blood samples revealed 11 newborns with the FH-North Karelia [FH-NK] mutation, 3 newborns with the FH-Helsinki [FH-HKI] mutation, and 11 nonaffected newborns. Cord serum total [TC] and LDL cholesterol [LDL-C] levels (mean +/- SD) in affected newborns (2.60 +/- 0.70 and 1.77 +/- 0.56, respectively) were significantly (P < .001) higher than those in nonaffected ones (1.54 +/- 0.23 and 0.78 +/- 0.15, respectively) and another cohort of 30 randomly selected control samples from apparently healthy newborns (1.84 +/- 0.46 and 1.03 +/- 0.30, respectively). However, there was overlapping of individual lipid levels in these three groups precluding the use of TC or LDL-C determinations in neonatal diagnosis of FH. In contrast, 1 year follow-up samples from 10 affected and 7 nonaffected individuals, as well as additional samples collected from another group of 8 affected and 9 nonaffected individuals, indicated that serum cholesterol levels showed much greater increment in children with FH. Thus, at the age of 1 year the mean serum TC and LDL-C levels in the affected infants (8.38 +/- 1.18 and 7.02 +/- 1.07, respectively) were much higher (P < .001) than the corresponding levels (4.40 +/- 0.66 and 2.89 +/- 0.68, respectively) in the nonaffected infants, and the individual ranges of TC and LDL-C levels were nonoverlapping in these two groups. Serum HDL cholesterol [HDL-C] levels in 1-year-old children with FH (0.95 +/- 0.14) were approximately 20% lower than those of their similar at birth. In conclusion, phenotypic expression of heterozygous FH, as defined by molecular analysis of genomic DNA, is evident in serum LDL-C (but not HDL-C) levels already at birth, but for diagnostic purposes blood lipid determinations carried out at the age of 1 year are highly superior to those performed at birth.     

An intrinsically stable antibody scFv fragment can tolerate the loss of both disulfide bonds and fold correctly

Several observations indicate that a low lipoprotein lipase (LPL)/hepatic lipase (HL) ratio clusters with clinical and laboratory features of atherosclerosis. Antihypertensive treatment can unfavourably interfere with lipid metabolism, counteracting the beneficial effects of lowering blood pressure. We have evaluated the effects of the Ca2+ channel antagonist nitrendipine on tissue LPL and HL in the normal rat. At the dose of 40 mg/day administered intragastrically, a 5-day nitrendipine treatment induced a significant decrease in HL activity in the liver, in comparison to control animals: 656 +/-82 mU/g tissue vs. 814+/-38 mU/g 3 h after the last administration; 640+/-70 mU/g vs. 893+/-101 mU/g 8 h after administration. LPL activity in heart was increased by active treatment: 2542+/-298 vs. 2115+/-244 mU/g in controls 3 h after administration, P < 0.05. At variance, LPL mass, measured 8 h after administration, was decreased in heart of treated rats: 2.38+/-0.4 microg/g tissue vs. 3.88+/-0.3 microg/g in controls. The ratio between heparin-releasable and residual LPL in heart was unaffected by the drug. No changes were observed in LPL activity and mass in soleus muscle or in periepididymal adipose tissue. Our results indicate that nitrendipine, at the dose used, induces changes in lipolytic enzymes of rat tissues that could be beneficial in relation to atherosclerosis. These data encourage further investigations in humans, at the usual therapeutical doses.     

High expression of leptin by human bone marrow adipocytes in primary culture

Inhaled nitric oxide (iNO) has been shown to improve oxygenation in severe persistent pulmonary hypertension of the newborn (PPHN). However, PPHN is often associated with various lung diseases. Thus, response to iNO may depend upon the aetiology of neonatal acute respiratory failure. A total of 150 (29 preterm and 121 term) newborns with PPHN were prospectively enrolled on the basis of oxygenation index (OI) higher than 30 and 40, respectively. NO dosage was stepwise increased (10-80 ppm) during conventional mechanical or high-frequency oscillatory ventilation while monitoring the oxygenation. Effective dosages ranged from 5 to 20 ppm in the responders, whereas iNO levels were unsuccessfully increased up to 80 ppm in the nonresponders. Within 30 min of iNO therapy, OI was significantly reduced in either preterm neonates (51+/-21 vs 23+/-17, P < .0001) or term infants with idiopathic or acute respiratory distress syndrome (45+/-20 vs 20+/-17, P < .0001), 'idiopathic' PPHN (39+/-14 vs 14+/-9, P < .0001), and sepsis (55+/-25 vs 26+/-20, P < .0001) provided there was no associated refractory shock. Improvement in oxygenation was less significant and sustained (OI=41+/-16 vs 28+/-18, P < .001) in term neonates with meconium aspiration syndrome and much less (OI=58+/-25 vs 46+/-32, P < .01) in those with congenital diaphragmatic hernia. Only 21 of the 129 term newborns (16%) required extracorporeal membrane oxygenation (57% survival). Survival was significantly associated with the magnitude in the reduction in OI at 30 min of iNO therapy, a gestational age > or =34 weeks, and associated diagnosis other than congenital diaphragmatic hernia. Conclusion, iNO improves the oxygenation in most newborns with severe hypoxaemic respiratory failure including preterm neonates. However, response to iNO is disease-specific. Furthermore, iNO when combined with adequate alveolar recruitment and limited barotrauma using exogenous surfactant and HFOV may obviate the need for extracorporeal membrane oxygenation in many term infants.     

The effect of cisapride on dysmotility-like functional dyspepsia: reduction of the fasting and postprandial area, but not of the postprandial antral expansion

OBJECTIVE: To test the effect of cisapride on symptom score and on fasting and postprandial antral area in patients with dysmotility-like functional dyspepsia compared with controls. METHODS: Nineteen consecutive patients with dysmotility-like functional dyspepsia (13 females, six males, aged 18-79 y) and 12 control subjects (six females, six males, aged 19-68 y) were investigated. A symptom score including six upper digestive symptoms rated from 0 to 3 was applied. The patients received in a randomized order cisapride 10 mg t.i.d. (n = 10), or placebo (n = 9) for 3 days. The controls also received cisapride (n = 6) or placebo (n = 6) in the same way. The antral area in fasting condition and immediately after a semiliquid test meal (250 ml, 342 kcal) was assessed by real-time ultrasonography in front of the aorta and mesenteric vein. The measurements were carried out before starting and after finishing the trials with cisapride and placebo. RESULTS: The symptom score (mean +/- SD) was 7.1 +/- 2.4 in dysmotility-like functional dyspepsia vs 0.5 +/- 0.2 in controls (P < 0.0001). The fasting antral area was 4.5 +/- 0.9 cm2 in dysmotility-like functional dyspepsia vs 2.2 +/- 0.2 cm2 in controls (P < 0.0001). Postprandial antral area was also larger in dysmotility-like dyspepsia than in controls (6.2 +/- 1.0 vs 3.0 +/- 0.3 cm2, Pb= 0.0001). Symptom score correlated with fasting antral area in dysmotility-like functional dyspepsia (rb= 0.38, Pb= 0.05). Cisapride decreased the symptom score to 4.5 +/- 2.5 (P = 0.0009) and placebo to 5.3 +/- 2.4 (P = 0.02). Cisapride significantly reduced the fasting antral area and the postprandial antral area in the dyspeptic group, but not in the control group. Postprandial antral expansion was not influenced by cisapride. Placebo did not change the sonographic parameters in both groups. CONCLUSIONS: In dysmotility-like functional dyspepsia, fasting and postprandial antral areas are wider than in controls. Despite a good placebo response, cisapride is effective in improving the symptoms in dysmotility-like functional dyspepsia, associated with the reduction of fasting and postprandial antral areas.     

Cell-mediated immunity imbalance in pregnancy-induced hypertension

Pregnancy is associated with modifications in the maternal immune system that may be involved in the absence of rejection of the fetoplacental graft characterized by the presence of paternal antigens. This active and specific tolerance towards the fetoplacental unit seems to be compromised in pregnancy-induced hypertension (PIH). To evaluate whether the immunological state in patients with PIH is altered with respect to normal pregnant women we studied 15 patients with PIH, 15 uncomplicated pregnant and 10 healthy nonpregnant women using monoclonal antibodies directed to specific lymphocyte antigen determinants, cytokines (TNF) and soluble molecules (sIL-2R, sCD8). The percentage of CD4 lymphocytes and of natural killer (NK) cells was significantly higher in PIH patients compared to controls (CD4: 42.9 +/- 10.5 vs. 32.7 +/- 12.5%; p < 0.05; NK: 14.7 +/- 6.3 vs. 8.3 +/- 3.4%; p < 0.01). However, these values did not differ when compared to normotensive nonpregnant controls (CD4: 53.1 +/- 5.9%; NK: 17.2 +/- 7.1%). In addition, the soluble IL-2 receptor (sIL-2R) was higher in PIH patients when compared to control patients (725.5 +/- 194.2 vs. 482.5 +/- 187.2 U/ml; p < 0.01). The immune response observed in normal pregnancies responsible for the tolerance towards the fetoplacental unit seems to be altered in PIH patients as suggested by higher levels of CD4 and NK cells, and sIL-2R. This may lead to a chronic rejection syndrome and be involved in the pathophysiology of PIH.     

Efficacy of dead-space washout in mechanically ventilated premature newborns

The prosthetic dead space makes a significant contribution to the total dead space in low-birth-weight premature newborns receiving artificial ventilation in response to respiratory distress. Use of an endotracheal tube with capillaries molded into the tube wall enables washout of the dead space without insertion of a tracheal catheter. In 10 premature newborns (mean gestational age, 27.5 +/- 2.2 wk; mean weight, 890 +/- 260 g) receiving continuous positive-pressure ventilation (Paw = 12.7 +/- 1.8 cm H2O; FIO2 = 39 +/- 17%), tracheal gas insufflation (TGI) for CO2 washout was conducted using this technique. The flow of tracheal insufflation (0.5 L/min) was derived from the inspiratory line of the ventilator circuit and blown into the trachea. Intratracheal pressures showed little or no TGI-related modification ( < 1 cm H2O). A control system enabled TGI discontinuation in the event of a pressure rise. At constant ventilation pressure, PaCO2 decreased by 12.1 +/- 5.9 mm Hg (delta PaCO2 = -26 +/- 12%) under TGI, whereas PaO2 remained unchanged. While maintaining PaCO2 constant, peak inspiratory pressure (PIP) was decreased by 5.4 +/- 1.7 cm H2O (delta PIP = -22.0 +/- 8.3%). TGI showed immediate efficacy (PCO2 reduction of at least 5 mm Hg) in nine of the 10 newborns who then received chronic TGI (14 to 138 h). TGI appears to be an effective method, suitable for long-term clinical application, enabling a reduction in the aggressive nature of conventional ventilation.     

Multicenter comparison of first- and second-generation IMx tacrolimus microparticle enzyme immunoassays in liver and kidney transplantation

Foetuses born to mothers with gestational diabetes are at increased risk of developing respiratory distress, foetal macrosomia, foetal anomalies and platelet hyperaggregability. High blood glucose level induces oxidative stress and decreases antioxidant defences. The present study discusses the possibility of lipid peroxidation and protein oxidation in both maternal and foetal erythrocytes as an indicator of oxygen radical activity. The level of lipid peroxidation and protein oxidation in erythrocytes was estimated in 20 mothers with gestational diabetes and their newborns. The maternal age varied between 19 and 42 y and foetal age ranged between 34 and 39 weeks. The proteolytic activities in the erythrocyte lysates obtained from mothers with gestational diabetes and their newborns were significantly greater [(mean +/- SD) 24.41 +/- 9.05 and 16.70 +/- 3.36 microM of amino groups/g haemoglobin, n = 20, respectively] than those from control group (10.18 +/- 4.84 and 14.64 +/- 6.21 microM amino groups/g haemoglobin, n = 15, respectively; p < 0.05 in both cases). Similarly erythrocyte malondialdehyde levels were significantly elevated in babies born to mothers with gestational diabetes (10.11 +/- 2.21 nM/g haemoglobin) when compared to controls (6.8 +/- 3.75 nM/g haemoglobin) (p < 0.05). In the erythrocytes of mothers with gestational diabetes, malondialdehyde levels correlated significantly with glycated haemoglobin levels (p < 0.01). The results of this study indicate that the oxidative stress induced by gestational diabetes manifests as increased lipid peroxidation and protein oxidative damage in the erythrocytes of both mothers with gestational diabetes and their newborn infants.     

The human photoreceptor rim protein gene (ABCR): genomic structure and primer set information for mutation analysis

In order to evaluate the effect of thyroid replacement therapy on bone metabolism in congenital hypothyroid children, we studied 23 (10 girls and 13 boys) consecutive patients. Their age ranged from 3 to 8 weeks. One of these patients had familiar dyshormonogenesis, 21 had ectopic glands and one hemiagenesis. As a control group, we studied 46 sex- and age-matched healthy newborns. Before the beginning of therapy, the hypothyroid patients showed higher values of calcium (2.78 +/- 0.04 vs 2.65 +/- 0.07 mmol/l; p < 0.05) and of 1,25-dihydroxy-vitamin D (159.7 +/- 31.6 vs 90.5 +/- 33.1 ng/l; p < 0.01), while they showed lower values of osteocalcin (1.9 +/- 0.8 vs 2.9 +/- 0.9 ng/ml; p < 0.01) than controls. After 3 months of therapy, we found a complete normalization of all these parameters and a progressive increase of osteocalcin. Our data show that in congenital hypothyroid children there are abnormalities in calcium metabolism which seem to be transient and reversible after L-thyroxine replacement therapy.     

The action profile of lispro is not blunted by mixing in the syringe with NPH insulin

OBJECTIVE: To assess the effect of mixing the insulin analog lispro (Humalog) with NPH (Humulin I) before injection on lispro's fast, short action profile. RESEARCH DESIGN AND METHODS: A total of 12 healthy volunteers received subcutaneous abdominal injections of 0.1 U/kg regular insulin and 0.2 U/kg NPH insulin as follows: lispro and NPH injected separately (treatment group A), lispro and NPH mixed in the syringe up to 2 min before single injection (treatment group B), and human regular insulin and NPH mixed and injected as in group B (treatment group C), on separate occasions, in random order. Plasma glucose was maintained for 12 h by intravenous 20% glucose. Pharmacokinetic and pharmacodynamic parameters were compared by analysis of variance for repeated measures. RESULTS: Peak plasma insulin levels (2.6 +/- 0.8 vs. 2.2 +/- 0.6 vs. 1.9 +/- 0.6 ng/ml, P = 0.075), total glucose infused (121.5 +/- 32.8 vs. 135.0 +/- 49.0 vs. 117.3 +/- 39.9 mg.kg-1.min-1, P = 0.53), and maximum glucose infusion rate (GIRmax) (8.3 +/- 0.9 vs. 8.0 +/- 1.7 vs. 7.1 +/- 2.4 mg.kg-1.min-1, P = 0.65) were not significantly different between treatments. The times until peak insulin concentrations were similar in treatment groups A and B, but significantly shorter than in treatment group C (0.9 +/- 0.3 and 1.2 +/- 0.2 vs. 2.0 +/- 0.4 h, respectively, P = 0.042). The times until GIRmax were also not different (113.9 +/- 41 and 122.0 +/- 45 vs. 209.0 +/- 51.3 min, respectively, P = 0.002). The glucose infusion rate (GIR) then fell to 50% GIRmax more quickly in treatment groups A and B than in treatment group C (239.9 +/- 40.5 vs. 292.4 +/- 133.3 vs. 399.5 +/- 78.3, respectively, P = 0.005). CONCLUSIONS: The action profile of lispro is not attenuated by mixing lispro with NPH in the syringe immediately before injection. The advantages are available to those individuals who need to combine types of insulin before injection to achieve optimal diabetes control.     

Use of a novel electronic data collection system in multicenter studies of irritable bowel syndrome

To evaluate whether atherosclerosis may be associated with altered leucocyte rheology, we assessed leucocyte count (by Coulter counter), aggregation (by means of the leukergy test) and expression of adhesion molecules integrin LFA-1 and CD 44 (by means of immunofluorescence staining and flow cytometry) in 9 patients with carotid plus lower limb artery atherosclerosis (group A), 14 patients with carotid atherosclerosis only (group B) and 23 controls without atherosclerosis (group C). The level of LFA-1 (calculated as mean fluorescence channels-MFCs) on neutrophils, lymphocytes and monocytes was significantly higher (p < 0.05) in group A and B patients than in controls (group A-mean +/- SE: 383.77 +/- 9.42 vs 295.45 +/- 5.76; 474.22 +/- 8.86 vs 388.35 +/- 7.84; 457.66 +/- 12.03 vs 396.25 +/- 4.37. Group B: 322.42 +/- 6.36 vs 295.45 +/- 5.76; 421.42 +/- 7.21 vs 388.35 +/- 7.84; 415.71 +/- 7.73 vs 396.25 +/- 4.37, respectively); furthermore, the MFC of LFA-1 on neutrophils was significantly different (p < 0.05) between group A and B patients. The percentage of aggregated leucocytes was significantly higher (p < 0.05) in group A patients (4.46 +/- 1.07) than those in groups B (1.75 +/- 0.38) and C (1.43 +/- 0.25), whereas no significant difference was detected between groups B and C. Leucocyte number and expression of CD44 were not significantly different among the 3 groups. In conclusion, changes in leucocyte rheology are present in patients with atherosclerosis and may contribute to chronic ischaemia.     

Prognostic value of Doppler transmitral flow velocity patterns in acute myocardial infarction

Doppler transmitral flow patterns are partially dependent on age. We investigated the correlations between the age-adjusted transmitral flow patterns, hemodynamic indexes, and the coronary and clinical outcome in 206 patients with acute myocardial infarction (AMI) and 102 normal control subjects. The peak flow velocity at atrial contraction was significantly lower in 50 of the 206 patients (24%) (low-A group) than in the 102 normal controls. Pulmonary capillary wedge pressure was significantly higher in the low-A group than in the remaining 156 patients with AMI (20 +/- 7 vs 11 +/- 5 mm Hg, p <0.001), and the cardiac index and left ventricular ejection fraction were significantly lower (2.2 +/- 0.6 vs 2.9 +/- 0.7 L/min/m2, p <0.001; 38 +/- 15% vs 52 +/- 13%, p <0.001). The incidence of cardiogenic shock was significantly higher in the low-A group than in the other patients with AMI (42% vs 19%, p <0.001). Regression analysis demonstrated a significant association between decreased atrial filling velocity and increased in-hospital mortality as well as the incidence of heart failure in AMI (p <0.001). The 5-year mortality rate was also significantly higher in the low-A group (p <0.001). The age-adjusted transmitral flow pattern in AMI can identify patients with left ventricular dysfunction, which can lead to a poor prognosis.     

Granulocytic Ehrlichia infection in ixodid ticks and mammals in woodlands and uplands of the U.K

BACKGROUND: The number of patients waiting lung transplantation greatly exceeds the supply of donors. This study was conducted to determine the effect of high-dose steroid administration on oxygenation and donor lung recovery after brain death. METHODS: A retrospective analysis was conducted on 118 consecutive organ donors from January 1 through December 31, 1995. Eighty donors received high-dose steroids (methylprednisolone, mean 14.5+/-0.06 mg/kg) after organ procurement organization management began; a second group was composed of 38 patients who received no steroids. PaO2/FiO2 ratios were used to evaluate oxygenation. The number of single and double lungs transplanted served as the endpoint. RESULTS: No differences were noted in hemodynamics, most clinical or demographic variables and initial values of PaO2/FiO2 between groups. However, nonsteroid-treated donors showed an overall decrease in oxygenation (mean decrease in PaO2/FiO2 -34.2+/-14), whereas steroid-treated donors had a significant and progressive increase in oxygenation (mean increase in PaO2/FiO2: 16+/-14) before aortic cross-clamping (p = 0.01). Time before cross-clamping was longer in the steroid-treated patients (p = 0.003). The number of procured lungs was markedly greater in steroid-treated than nonsteroid-treated donors (25/80 patients vs 3/38; p < 0.01). CONCLUSIONS: High-dose methylprednisolone given during donor management results in improved oxygenation at organ recovery. This treatment resulted in a significant increase in the number of lungs transplanted and may have enabled donors to be treated longer.     

Effect of surfactant on respiratory failure associated with thoracic aneurysm surgery

OBJECTIVE: To study the effects of surfactant administration on the left lung after surgical repair of descending aortic aneurysms on postoperative respiratory failure. DESIGN: Randomized, prospective, controlled study. SETTING: Clinical investigation. PATIENTS: Eleven patients with respiratory failure associated with thoracic aneurysm surgery. INTERVENTION: Eleven adult patients with acute respiratory failure (PaO2/FIO2 <300 torr [<40 kPa]) after surgical repair of descending aortic aneurysms. The artificial surfactant (30 mg/kg) was given to the operated side of the lung by intrabronchial instillation in six patients (surfactant group), whereas nothing was instilled in the other five patients (control group). MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters, blood gas, and peak inspiratory pressure were measured at the end of surgery, before surfactant instillation, and at 2, 6, 12, 24, and 48 hrs after surfactant instillation. At the end of surgery, the mean +/- SEM values of the PaO2/FIO2 ratio were 204 +/- 25 torr (27.2 +/- 3.3 kPa) in the surfactant group and 240 +/- 26 torr (32.0 +/- 3.5 kPa) in the control group. After 2, 6, 12, and 48 hrs, improvements in the PaO2/FIO2 ratios were observed in the surfactant group, whereas the control group showed no improvement. Two hours after surfactant instillation, the mean value in the PaO2/FIO2 ratio was significantly higher in the surfactant group (318 +/- 24 torr [42.4 +/- 3.2 kPa]) (p < .05) compared with the control group values (240 +/- 34 torr [32 +/- 4.5 kPa]). CONCLUSION: Surfactant administration immediately after surgery restored gas exchange in postoperative respiratory failure associated with thoracic aneurysm surgery.     

Insulin-like growth factor I is an independent coregulatory modulator of natural killer (NK) cell activity

We aimed to investigate the natural killer (NK) cell activity in hGH-deficient adults and to analyze the effect of insulin-like growth factor (IGF)-I in vivo and in vitro on NK cell activity. NK cell activity was measured in a 4-h nonisotopic assay with europium-labeled and cryopreserved K-562 cells. NK-cell numbers were measured after incubation with murine monoclonal CD3 and CD16 antibodies by flow cytometry analysis. In a cross-sectional study, the basal and interferon-beta (IFN-beta) stimulated (1000 IU/ml) NK cell activity of 15 hGH-deficient patients and 15 age- and sex-matched controls was measured. The percentages and absolute numbers of CD3-/16+ NK-cells were not significantly different in the patient vs. control group. The basal and IFN-beta stimulated NK cell activity however was significantly decreased in the patient vs. control group at all effector/target (E/T) cell ratios from 12.5-100 (e.g. 17 +/- 3 vs. 28 +/- 3% lysis without IFN-beta, P < 0.05, and 42 +/- 4 vs. 57 +/- 4% lysis with IFN-beta, P < 0.05; both at E/T 50). IGF-I levels of patients and controls showed a significant positive correlation with NK cell activity (r = 0.37; P < 0.05). In an IGF-I in vitro study (IGF-I in vitro 250-1250 microg/L), the basal and IFN-beta stimulated NK cell activity of 13 hGH-deficient patients and of 18 normal subjects was significantly enhanced by IGF-I in vitro (e.g. GH-deficient patients: 9 +/- 2 vs. 10 +/- 2% lysis without IFN-beta, P < 0.05 and 25 +/- 4 vs. 30 +/- 4% lysis with IFN-beta, P < 0.005; and normal subjects: 15 +/- 3 vs. 23 +/- 3% lysis without IFN-beta, P < 0.001 and 35 +/- 4 vs. 44 +/- 5% lysis with IFN-beta, P < 0.001; both at IGF-I 500 microg/L). In summary, in our cross-sectional study, adult GH-deficient patients showed a significantly lower basal and IFN-beta stimulated NK cell activity than matched controls, despite equal NK cell numbers. IGF-I levels of patients and controls showed a weak positive correlation with NK cell activity. In an in vitro study, IGF-I significantly enhanced basal and IFN-beta stimulated NK cell activity of hGH-deficient patients and also of normal subjects. The decreased NK cell activity in GH-deficient patients may be caused at least in part by low serum IGF-I levels. IGF-I appears to be an independent coregulatory modulator of NK cell activity.     

Protein-dependent reduction of the pyrene excimer formation in membranes

The study aimed at the evaluation of the gastric emptying (GE) kinetics in hypothyroid patients before and after a substitutive treatment with L-thyroxin. Twelve female hypothyroid (aged 45.3 +/- 8.7 years, mean +/- SD) and a control group of 12 healthy women (aged 34.5 +/- 8.1 years) were examined. The GE of a 99mTc-labelled solid meal was measured with the use of a gamma camera in every patient before the treatment, and in 10 of them a repeat GE examination was performed after the restoration of euthyroid; the median duration of the treatment was 5.5 mo (range 2.5 to 12 mo). The mean gastric transit time (MTT90) and the fraction of the test meal retained in the stomach after 90 min (F90) were statistically significantly greater in untreated hypothyroid than in healthy controls (MTT90: 42.01 +/- 1.86 min patients vs 40.06 +/- 1.00 min controls, p = 0.0043; F90: 64.3 +/- 15.4% patients vs 50.8 +/- 8.2% controls, p = 0.0173). In ten patients in whom a second GE measurement was taken after the achievement of euthyroid, a slight increase of the GE was observed (MTT90:41.46 +/- 1.49 min before vs 41.04 +/- 1.81 min after the treatment, NS) which was then no longer statistically significantly different from that of the healthy controls. No relationship was found between the GE and the severity of clinical symptoms of hypothyroidism. GE remained, however, slowed in some patients despite the restoration of euthyreosis. We conclude that: (I) long-lasting hypothyreosis is accompanied by a slightly slowed GE of solids, and (II) restoration of euthyreosis does not imply a parallel improvement of the hypothyroidism-associated delay in GE.     

Doppler analysis of pulmonary venous flow profiles in orthotopic heart transplant recipients: a comparison with mitral flow profiles and atrial function

Previous Doppler studies of transmitral flow profiles in heart transplant recipients suggested left ventricular (LV) diastolic dysfunction. The influence of left atrial filling and emptying on mitral Doppler profiles in heart transplant recipients has not been studied systematically. In the present study, pulmonary venous flow profiles, mitral flow profiles, left atrial area change and mitral annulus motion were analyzed in 20 orthotopic heart transplant recipient and 20 control subjects by transthoracic and transesophageal echocardiography and Doppler. Mitral flow profiles revealed a "restrictive" pattern with a high early-to-late diastolic flow velocity ratio in transplant patients (2.16 +/- 0.52 vs. 1.30 +/- 0.25, p < 0.0001), which was mainly due to a reduced late diastolic maximum mitral flow velocity (32.6 +/- 8.3 vs. 51.6 +/- 12.4 cm/s, p < 0.0001). Left atrial area change (35.9 +/- 13.9 vs. 58.1 +/- 17.0%, p < 0.0006) and mitral annulus motion (9.2 +/- 3.3 vs. 12.2 +/- 2.0%, p < 0.05) were reduced in transplant recipients, compared to controls. Pulmonary venous flow parameters in transplant recipients were markedly altered during systole, when pulmonary venous flow parameters are influenced primarily by atrial function rather than by diastolic LV properties: peak systolic flow velocity (45.5 +/- 8.2 vs. 62.3 +/- 14.0 cm/s, p < 0.001), maximum flow velocity ratio (0.87 +/- 0.19 vs. 1.45 +/- 0.33), time velocity integral of pulmonary venous flow during systole (9.3 +/- 2.3 vs. 17.1 +/- 4.0 cm, p < 0.001) and the systolic fraction of the time velocity integral (52.6 +/- 10.8 vs. 68.5 +/- 6.8%, p < 0.001) were lower in heart transplant recipients than in controls. These findings are compatible with atrial dysfunction and reduced mitral annulus motion. The results of this study indicate that LV diastolic dysfunction is not the only possible cause of altered transmitral Doppler profiles in heart transplant recipients. Atrial abnormalities represent a major contributing factor to altered mitral and pulmonary venous flow patterns. Analysis of transmitral Doppler profiles alone are therefore not adequate for analysis of diastolic LV function in heart transplant recipients.     

Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis

Patients with bacterial overgrowth of the small intestine developed spontaneous bacterial peritonitis (SBP) more frequently than patients without bacterial overgrowth of the small intestine. The objective of this study was to determine whether the incidences of small intestine dysmotility and bacterial overgrowth are higher in cirrhotic patients with a history of SBP than in cirrhotic patients without SBP. Forty cirrhotic patients were enrolled in this study. There were 20 patients with a history of SBP and 20 patients without a history of SBP. Small intestine bacterial overgrowth was diagnosed by breath hydrogen test. Small intestine motility was recorded, by a 3-channel solid-state manometric catheter, for 24 hours. There were no statistical differences in age or sex between the two groups. The Child-Pugh scores in the SBP group were higher than in the non-SBP group (10.5 +/- 2.1 vs. 8.1 +/- 1.9, P < .01). The incidence of bacterial overgrowth of the small intestine was higher in the SBP group than in the non-SBP group (70% vs. 20%, P < .01). The amplitude and duration of migrating motor complex (MMC) activity fronts, as well as the number of clusters per hour, were similar in both groups. However, the frequency of MMC activity fronts was higher in the non-SBP group than in the SBP group (4.8 +/- 2.3/24 hours vs. 3.5 +/- 1.2/24 hours, P < .05). In addition, the MMC velocity was significantly higher in the non-SBP group (8.3 +/- 2.6 vs. 5.3 +/- 2.1 cm/min, P < .01). The incidence of bacterial overgrowth of the small intestine was higher in cirrhotic patients with history of SBP than in those without SBP. Small intestine motility dysfunction was more severe in cirrhotic patients with history of SBP. Impaired motility of the small intestine, causing bacterial overgrowth of the small intestine, may be one of the explanations for recurrent SBP in cirrhotic patients.