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1.
Neo red cells (NRCs) are a blood substitute representing stroma free hemolysate (SFHL) encapsulated in liposomes and containing NAD, glucose, adenine, and inosine, etc. as substrates or coenzymes of the Embden-Meyerhof pathway in RBCs and inositol hexaphosphate (IHP) as an allosteric effector. The oxygen transport efficiency (OTE) of NRCs was increased to > 45% when the oxygen partial pressure in arterial blood increased. We carried out exchange transfusion with NRCs in rats, monitored their functioning as a blood substitute in vivo, and demonstrated that NRCs worked sufficiently. First, we confirmed that the OTE of NRCs was augmented by increasing the oxygen supply to the rats by using oxygen masks. Second, we carried out 70% blood exchange with NRCs (with hemoglobin concentrations of 4, 5, 6, or 7 g/dl), and compared these experimental groups with control groups (RBC and saline). Each sample was contained bovine albumin (final volume of 5% (w/v)). As a result, the NRC groups with hemoglobin concentrations of 5, 6, and 7 g/dl showed stability after the exchange transfusion. On the other hand, the NRC group with hemoglobin concentration of 4 g/dl and the saline group showed respiratory acidosis and a drop of blood pressure and heart rate, and thus did not maintain an adequate oxygen supply. We concluded that a hemoglobin concentration of > 5 g/dl was sufficient in the NRC solution, and demonstrated in an experiment on animals that the OTE of NRCs was increased by using oxygen masks.  相似文献   

2.
We describe a method for perfusion of a working isolated rat heart with washed erythrocytes suspended in a Krebs-Henseleit bicarbonate buffer containing bovine albumin (fraction V). With washed pig red cells, as hematocrit was varied between 0 and 40%, coronary flow (CF), aortic flow (AF), external work (W), and myocardial oxygen consumption (MVO2) were measured. Hemodynamic data at a hematocrit of 30% (CF = 5.4 +/- 0.7 ml/min per g, AF = 75 +/- 8 ml/min per g) were identical with those reported for the intact animal. Coronary sinus PO2 was highest with a red cell-free perfusate suggesting that coronary flow is partially shunted. Human red cells obtained from banked blood, were tried also with success. With careful filtration, the preparation is stable for 2 h and well suited for study of the dynamics of myocardial oxygen delivery.  相似文献   

3.
Information was collected retrospectively on three comparable groups, 25 patients in each, who had been operated on for thoracic scoliosis. Group 1 received homologous transfusions only. Group 2 and group 3 were transfused postoperatively with drained whole blood (Solcotrans orthopaedics). Group 3 received in addition peroperatively washed packed red blood cells (Haemolite 2 Cell Saver) recirculated. The need for homologous transfusions was reduced from 119 units to 23 patients in group 1, to 36 units to 14 patients in group 2 and 34 units to 13 patients in group 3. Three of the first 15 patients in group 2 experienced chills and fever reactions in connection with the autologous transfusion. No reactions were seen after infusion when we scrapped the last 50 to 100 ml of drained blood.  相似文献   

4.
OBJECTIVES: The purpose of this study is to compare normal saline with Isolyte S as the wash solutions during high-volume cell saver autologous blood transfusion. Normal saline, the standard wash solution in cell saver autologous blood transfusion, is associated with acid-base and electrolyte derangements. Isolyte S is a physiologic, balanced multielectrolyte crystalloid solution that approximates the electrolyte content of plasma. DESIGN: Open-label, prospective, randomized study. SETTING: Research laboratory in a Department of Veterans Affairs medical center. SUBJECTS: Fourteen mongrel dogs, weighing 22 to 23 kg each. INTERVENTIONS: Fourteen mongrel dogs were prospectively randomized to receive normal saline (n = 7) or Isolyte S (n = 7). Animals were anesthetized, received heparin for anticoagulation, and underwent 18 cycles of cell saver autotransfusion. In each cycle, 125 mL of blood was arterially withdrawn, and washed with either normal saline (mEq/L) (sodium 154, chloride 154) or Isolyte S (mEq/L) (sodium 141, potassium 5, magnesium 3, chloride 98, phosphate 1, acetate 28, and gluconate 23). The washed blood was retransfused. MEASUREMENTS AND MAIN RESULTS: Acid-base and electrolyte analyses were performed throughout the study on the systemic blood of each group and compared. By the end of the study, the Isolyte S group had a normal pH and an increased bicarbonate concentration (mEq/L: normal values 24 to 32; normal saline 9.0 +/- 1.9 vs. Isolyte S 13.2 +/- 3.0 [p < .01]) and an increased magnesium concentration (mg/dL: normal values 1.6 to 2.4; normal saline 1.6 +/- 0.2 vs. Isolyte S 2.2 +/- 0.2 [p < .0001]). Additionally, the Isolyte S group had a lower chloride concentration (mEq/L: normal values 95 to 110; normal saline 130 +/- 9 vs. Isolyte S 117 +/- 7 [p < .02]) and a lower potassium concentration (mEq/L: normal values 3.5 to 5.0; normal saline 4.4 +/- 0.5 vs. Isolyte S 3.7 +/- 0.3 [p < .01]). There were no significant differences between normal saline or Isolyte S in the values of PCO2, lactic acid, sodium, total and ionized calcium, inorganic phosphorus, total protein, albumin, hemoglobin, and hematocrit. CONCLUSIONS: Fewer systemic acid-base and electrolyte derangements were observed when blood was washed with Isolyte S. Differences between the normal saline and Isolyte S groups are ascribed primarily to the constituents of the wash solution. We conclude that Isolyte S, a physiologic, balanced, multielectrolyte solution, should be considered as the wash solution in high-volume autologous cell saver blood processing and transfusion.  相似文献   

5.
The hemoglobin vesicle (HbV) is a red cell substitute encapsulating purified concentrated Hb in a phospholipid vesicle. In order to improve the oxygen carrying capability of HbV, the pH value of the Hb solution should be adjusted to 7.0 in the HbV preparation, and then the pH value should be adjusted to 7.4 where HbV functions as an oxygen carrier, because the maximum value of [Hb]/[Lipid] was obtained in which the pH of the Hb solution was 7.0, and the metHb formation rate was suppressed in the pH 7.4. Generally, the pH control of the inner aqueous phase of HbV is difficult by changing the pH in the outer phase. We could control the pH of the Hb solution from 7.4 to 7.0 by dissolving CO2 into the Hb solution, and after the preparation of HbV, the pH of HbV is changed to 7.4 by reducing the pressure. The resulting pH-controlled HbV by CO2 gas showed a high [Hb]/[Lipid] value of 1.7 with a low rate of metHb formation.  相似文献   

6.
The oxygen-releasing behavior of hemoglobin vesicles (HbV) was measured in order to study the difference in oxygen dynamics inside and outside the cellular Hb using a conventional stopped flow method and a newly developed stopped flow flash photolysis method. The partial pressure of oxygen in the solution outside the HbV was monitored with the lifetime of the triplet state of meso-tetraphenylporphinatozinc(II) bound to human serum albumin excited by the laser flash. The change in the partial pressure of oxygen outside the HbV showed a biphasic profile and was slower than that inside the HbV. The first phase shows the oxygen-releasing process from Hb near the phospholipid bilayer membrane, and the second phase is considered the process in which oxygen diffuses to the bulk aqueous region and reaches the equilibrium value.  相似文献   

7.
BACKGROUND: The efficacy of intraoperative salvage and washing of wound blood and the predictors of allogeneic red cell transfusions in prosthetic hip surgery are insufficiently known. METHODS: In 96 patients, undergoing primary or revision surgery, salvaged and washed red cells and, if necessary, allogeneic blood were used to keep haematocrit not lower than 33%. The bleeding of red cells during hospital stay was calculated from the red cell balance. The preoperative red cell reserve (mililitres of red cells in excess of a haematocrit of 33%) was estimated and the difference between this volume and the total bleeding of red cells was retrospectively used to classify patients with regard to the need for red cells. Stepwise regression analysis was used to define patient-related variables associated with allogeneic blood transfusion. RESULTS: Preoperative knowledge of the type of operation (primary, revision), the preoperative red cell reserve, and the body mass could predict roughly half of the need for banked blood (r2 = 0.45). Only one-third of the total bleeding of red cells was retransfused. For complete avoidance of allogeneic blood, autotransfusion was most effective in patients with a moderate need (0-4 u). However, 32% of such patients required allogeneic blood. CONCLUSIONS: Autotransfusion has a limited efficacy to decrease the need for allogeneic blood, and other blood-saving methods should be added for this purpose. It is difficult to predict the need for allogeneic blood preoperatively.  相似文献   

8.
BACKGROUND: Hemoglobin (Hb) Bryn Mawr is an unstable Hb variant resulting in congenital hemolytic anemia. This variant Hb also has an increased affinity for oxygen. The perioperative transfusion management of this disorder is described, and the first genomic analysis of this Hb variant is given. CASE REPORT: An 11-year-old boy, heterozygous for Hb Bryn Mawr, was referred for cholecystectomy. Sequence analysis of genomic DNA confirmed that the patients was heterozygous for a T-->C transition in the codon for amino acid 85, causing a substitution of serine for phenylalanine in the beta-globin chain. On the basis of whole-blood O2 dissociation studies, projected tissue O2 delivery would have been suboptimal during general anesthesia; therefore, a partial red cell exchange transfusion was performed to lower variant Hb and prevent tissue hypoxia during surgery. The red cell mass to be exchanged (50%) was determined from the calculated increase in O2 delivery capacity required to maintain an O2 extraction of 4 to 5 mL of O2 per dL of whole blood. The p50 of whole blood from the patients immediately after the exchange transfusion was 16.0 torr. At the time of surgery, the p50 was normal (25.9 torr). The patient's whole blood 2,3 DPG levels were 4.70 mmol per mL of red cells (before transfusion) (normal range = 4.8 +/- 0.3 mmol/mL red cells), 4.07 mmol per mL of red cells (immediately after transfusion), and 4.55 mmol per mL of red cells (48 hours after transfusion). CONCLUSION: This patient with Hb Bryn Mawr was prepared for surgery with a partial exchange transfusion to prevent tissue hypoxia during anesthesia. Decreased 2,3 DPG levels immediately after transfusion resulted in increased O2 affinity of whole blood; however, 48 hours after exchange transfusion, a normal p50 (due to both removal of variant Hb and regeneration of 2,3, DPG) was observed. Partial exchange transfusion is useful in the preoperative management of patients with Hb variants characterized by increased O2 affinity.  相似文献   

9.
CPD-adenine blood (adenine in a final concentration of 0.25 mmol/1) was used in exchange transfusions in four newborn infants. The amount of adenine in one exchange transfusion ranged from 27 to 29 mumol per kg bodyweight. The maximum P-adenine concentration during the exchange transfusions ranged from 4 to 8 mumol/1 but decreased to pretransfusion levels 20 minutes after the exchange transfusions. During a 24-hour period following the exchange transfusions, the total urine excretion of adenine and 2,8-dihydroxyadenine corresponded to 0.5 to 1.3 per cent of the given adenine dose calculated on a molar basis. Accumulated data indicate that CPD-adenine blood can be used even in repeated exchange transfusions in newborn infants.  相似文献   

10.
Compound A is a degradation product of sevoflurane. Knowledge of the solubility of Compound A, CH2F-O-C(=CF2)(CF3), in blood and other solvents would aid in the definition of its kinetics. Accordingly, we determined solvent/gas partition coefficients of Compound A for saline (0.166 +/- 0.002 [mean +/- SD; n = 4]) and olive oil (20.1 +/- 1.1 [n = 4]). Measurement of solubility in blood was confounded by degradation of Compound A in blood and blood components. If a mixture of 99.3% saline and 0.7% oil provides the solubility equivalent to that possessed by blood (as it does for the parent compound, sevoflurane), then blood solubility and solubility in plasma, albumin, red blood cells, or pure hemoglobin is approximately 0.31. The order of Compound A degradation was human plasma = rat blood > whole human blood >5% human serum albumin = washed human red blood cells (hematocrit 50%) = 5% pure hemoglobin. Presuming a solvent/gas partition coefficient of 0.31, respective approximate times for 50% degradation equaled 2.7, 2.8, 4.6, 9.9, 11.0, and 12 min. The accuracy of these approximations was limited by the need to estimate, rather than determine, the solubility of Compound A in such solvents. Pasteurization (heating to 60 degrees C for 12 h) or pretreatment with N-ethylmaleimide (a compound that reversibly binds to sulfhydryl groups) decreased the degradation rate in plasma. These results suggest that degradation arises, at least in part, from reaction of Compound A with proteins in blood, possibly from covalent reaction of Compound A with protein and/or from an enzymatically mediated reaction. The products of degradation, the binding sites, and the clinical implications of such binding and degradation remain to be determined.  相似文献   

11.
The ability of stroma-free haemoglobin solutions to transport oxygen was investigated by determining the oxygen consumption by the liver using Warburg's microrespirator. 50 ml of blood were removed from the rabbit under general anaesthesia and replaced by an identical volume of a non-oxygenated or oxygenated haemoglobin solution. The control rabbits received no transfusions. It was found that arterial hypotension produced by blood-letting caused a significant rise in oxygen consumption by the hepatic tissue. The rise was increased even more when the rabbits received no transfusions. Transfusion of non-oxygenated haemoglobin solutions caused likewise a rise in oxygen consumption immediately after transfusion. This rise was, however, not so significant as in the control group. On the other hand, transfusion of oxygenated haemoglobin solutions produced no rise in the oxygen consumption by the liver as compared to its value after blood-letting.  相似文献   

12.
Acute normovolemic hemodilution has been reported to result in blood savings varying from 18% to 90%. Very few of these are randomized prospective studies. This study attempts to determine the blood transfusion savings if acute normovolemic hemodilution is used in combination with autologous predonated blood and cell saver. Thirty-three patients undergoing total hip arthroplasty were assigned randomly to one of two groups (control, n = 16; hemodilution, n = 17). Patients in both groups entered an autologous predonation program if cleared medically and were placed on Cell Saver intraoperatively and in the postanesthesia care unit. In addition, the hemodilution group underwent acute normovolemic hemodilution preoperatively. Only 41% of the patients in the hemodilution group required any autologous blood transfusion as compared with 75% of the control group. In addition, the hemodilution group required a mean lower quantity of autologous blood transfusion (41% of the estimated blood loss) as compared with the control group (71%). The net anesthesia time increased by an average of 11.4 minutes in the hemodilution group. Acute normovolemic hemodilution is a safe procedure even in an older patient population. Hemodilution resulted in fewer patients needing autologous predonated blood transfusions. The major benefit of hemodilution was seen when predonation was not possible.  相似文献   

13.
Titanium surfaces were coated with bovine serum albumin using carbodiimide, a crosslinking agent. The durability of the coated surfaces and the inhibitory effect of the albumin coating on bacterial adherence were tested in vitro for 20 consecutive days at 37 degrees C in phosphate buffered saline, with intermittent agitation. The results showed that only 10% of the coated bovine serum albumin decayed off the surface during the 20-day incubation period. The inhibition rate of the albumin coating on bacterial adherence remained high (greater than 8.5%) throughout the experiment. The results suggested potential use of this crosslinked albumin coating to reduce bacterial adherence and thus the subsequent possibility of prosthetic or implant infection in vivo.  相似文献   

14.
BACKGROUND: Allogeneic blood transfusions cause immunosuppression. The aim of this study was to determine whether complement anaphylatoxins, cytokines, or both are released in the recipient, after blood transfusions in general, and after autologous blood transfusions in particular. METHODS: Thirty-one patients having total hip joint replacement surgery were randomized to receive either allogeneic red blood cells (n = 15) or predeposited autologous whole blood transfusion (n = 16). Plasma concentrations of the anaphylatoxins C3a and C5a, the terminal C5b-9 complement complex, and cytokines IL-6 and IL-8 in the recipients were repeatedly analyzed before, during, and after surgery. RESULTS: Significantly increased concentrations of IL-6 and IL-8 appeared in both groups, with a significantly greater increase in the autologous blood group. Patients in both groups developed a moderate but significant increase of C3a without a significant difference between them. C5a and terminal C5b-9 complement complex were not greatly changed. CONCLUSIONS: The study showed a greater increase in cytokine concentration after autologous blood transfusion than after allogeneic blood transfusion. The lower response in the latter may result from transfusion-induced suppression of cellular immunity.  相似文献   

15.
OBJECTIVE: To evaluate the effect of recombinant human erythropoietin (EPO) and iron supplementation on transfusion requirements in pediatric patients with sarcoma who were receiving chemotherapy, we performed a double-blind, placebo-controlled, randomized trial. METHODS: Twenty-four pediatric patients with malignant solid tumors were randomly assigned to receive either placebo (saline solution) or EPO for a 16-week study period. The starting dose was 150 IU/kg per dose three times a week and was escalated by 50 IU/kg per dose increments monthly until packed red blood cell (PRBC) transfusion independence was achieved or a dosage of 300 IU/kg per dose was reached. Iron supplementation was prescribed at a dose of 6 mg of elemental iron per kilogram daily. The primary study end point was the comparison of PRBC transfusion requirements in the two groups. RESULTS: Of 24 patients, 20 were evaluable for response. The median PRBC transfusion requirement during the 16-week period was 23 ml/kg in EPO-treated patients versus 80 ml/kg in placebo patients (p = 0.02). The median number of single-donor platelet units transfused was zero in the EPO-treated patients compared with four in the placebo group (p = 0.005). No statistical difference in the intensity of bone marrow suppression was seen, as measured by the median number of complete blood cell counts with an absolute neutrophil count of < 1000 cells/microliter. CONCLUSIONS: Treatment with EPO and iron significantly reduces PRBC transfusions in pediatric patients receiving concomitant chemotherapy for malignant sarcomas. A decrease in the number of platelet transfusions was also seen and deserves further study.  相似文献   

16.
OBJECTIVES: a) To determine whether isovolemic exchange transfusion with cell-free, bovine fumaryl beta beta-crosslinked hemoglobin results in a different pattern of regional blood flow distribution than transfusion with a poor oxygen-carrying, colloidal solution. b) Because of potential nitric oxide scavenging by plasma-based hemoglobin, to determine whether blood flow differences are reduced after nitric oxide synthase inhibition. DESIGN: A prospective, randomized design with repeated blood flow measurements within groups. SETTING: Experimental physiology laboratory in a university medical center. SUBJECTS: Pentobarbital-anesthetized female cats. INTERVENTIONS: Three groups of eight cats were studied: a) a control group with no transfusion (hematocrit of 32%); b) an anemia group in which exchange transfusion with an albumin-containing solution reduced hematocrit to 18% over a 40- to 50-min period; and c) a group in which cell-free hemoglobin was exchanged transfused to reduce hematocrit to 18%, without a proportional reduction in oxygen-carrying capacity. Bovine hemoglobin was covalently crosslinked intramolecularly between the 81-lysine residues on the beta-subunits to stabilize the tetramer. Regional blood flow was measured by the radiolabeled microsphere technique before transfusion and at 10, 100, and 180 mins from the start of transfusion. At 190 mins, N omega-nitro-L-arginine methyl ester (L-NAME; 10mg/kg) was infused to inhibit nitric oxide synthase and blood flow was measured 30 mins later. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure was unchanged in the control and albumin-transfused groups. However, mean arterial pressure increased rapidly in the hemoglobin-transfused group. With hemoglobin transfusion, there were marked reductions in blood flow to the intestines, kidneys and adrenal glands. Administration of L-NAME after hemoglobin transfusion failed to increase arterial pressure or cause further reductions in intestinal, renal, or adrenal blood flow. Administration of L-NAME to the control and albumin-transfused groups increased arterial pressure and reduced intestinal, renal, and adrenal blood flows to values attained with hemoglobin transfusion. In contrast, in skeletal muscle and left ventricle, blood flow rates increased in the albumin-transfused group and were greater than those values found in the control group and hemoglobin-transfused group. The greater flow in the albumin-transfused group persisted after L-NAME administration. There was no difference in renal sodium, potassium, or osmolar excretion, or in urine flow between groups. CONCLUSIONS: Transfusion with cell-free, bovine crosslinked hemoglobin in cats can selective reductions in blood flow in the intestines, kidneys, and adrenal glands without evidence of renal dysfunction by a mechanism consistent with nitric oxide scavenging. In skeletal and cardiac muscle, the increase in blood flow persisted after nitric oxide inhibition in the albumin group relative to the hemoglobin-transfused group at equivalent hematocrit values. This finding is consistent with compensatory vasoconstriction with hemoglobin transfusion due to improved oxygenation by this oxygen carrier.  相似文献   

17.
Surgical resection remains the mainstay of treatment for patients with hepatic tumors, despite the associated morbidity including the need for blood transfusion. Acute isovolemic hemodilution (AIH) has been shown to decrease the transfusion requirement for cardiac, urologic, and orthopedic procedures. However, the reported experience with AIH during hepatic resections is limited. Seven patients underwent major hepatic resection from July 1992 to June 1994 with standard AIH. Their clinical parameters were compared with those of nine matched control patients during the same time period. AIH and control patients had similar preoperative laboratory values (hematocrit, bilirubin, and coagulation studies), extent of liver resection, and pathologic diagnoses. Mean tumor diameters were larger in the AIH group (9.3 cm vs. 5.8 cm). Most important, patients managed with AIH required homologous blood transfusions significantly less often than the control group (14% vs. 67%; P=0.05). Furthermore, if they did receive transfusions, AIH patients needed fewer units of red cells (0.1+/-0.1 units vs. 1.7+/-0.6 units). There was no morbidity associated with AIH. AIH can be safely performed in patients undergoing major hepatic resection for malignancy. AIH appears to reduce the number of patients requiring homologous blood transfusion as well as the number of units transfused per patient. This technique warrants further study in a larger prospective, randomized trial.  相似文献   

18.
OBJECTIVE: The study investigates the effect of continuous blood exchange with ultrapurified, polymerized bovine haemoglobin (UPBH) in comparison to hetastarch on haemodynamics, oxygen transport and skeletal muscle oxygen tension in a canine model. DESIGN: Sixteen anaesthetized beagle dogs underwent haemodilution with lactated Ringer's to a starting haematocrit of 20% followed by progressive blood exchange with 6% hetastarch 200,000/0.5 (HES, group 1) or UPBH (haemoglobin 13 +/- 1 g.dl-1, molecular weight (MW) 32-500,000, group 2) to haematocrit target levels of 15%, 10% and 5% or less. MEASUREMENTS AND RESULTS: Besides haemodynamics, skeletal muscle tissue oxygen tension (tPO2) was measured using a polarographic needle probe. In HES-treated animals, heart rate, cardiac output and blood flow were higher while systemic vascular resistance, systemic and regional arterio-venous oxygen difference (avDO2) and oxygen extraction ratios were lower when compared to the UPBH group. In spite of a higher final haematocrit of 5% in group 1, in comparison to group 2 with 2%, final muscular oxygen uptake (4.7 +/- 4 vs 10.1 +/- 2 ml.min-1) and mean tPO2 (11.8 +/- 2.3 vs 51.1 +/- 2.9 mm Hg) were lower in group 1 than in group 2. While tPO2 histograms were continuously shifted to lower oxygen tensions during progressive haemodilution with HES, UPBH-exchanged animals showed tPO2 histograms shifted to higher values than baseline. CONCLUSION: In spite of vasoconstriction, UPBH provided more haemodynamic stability and enhanced skeletal muscle tPO2 during progressive blood exchange when compared to HES.  相似文献   

19.
20.
BACKGROUND: All maternal red cell antibodies found during pregnancy in a 12 year period have been compiled. The efficacy of the current antenatal screening and management programme has been ascertained by reviewing the outcome of all newborns to these immunized mothers. METHOD: Patient selection was carried out by computerised searching for all known records of registered antibodies during the study period. Each mother's obstetric record and her baby's hospital file was studied and relevant clinical treatment and laboratory data on both mother and child was recorded and analysed. RESULTS: Eight hundred and twenty-one alloantibodies were detected in 629 immunized pregnant women with 753 fetuses. An overall antibody incidence of 0.57% was observed which included 373 clinically significant antibodies found in 261 mothers (0.24%). Multiple antibodies were present in 8.2% of all samples. Anti-D, by itself or in combination with other Rh-antibodies, caused more severe forms of hemolytic disease of the newborn (HDN) with 46% of all Rh-positive babies having phototherapy and 29% having exchange transfusion. Three of 18 Fya-positive infants required phototherapy and one required exchange transfusion and in the 16 Kell-positive babies, three required phototherapy and one required exchange transfusions. CONCLUSIONS: Few antibodies to blood group antigens other than those in the Rhesus system were found to cause severe HDN. Antibodies that are generally considered non-significant did not cause HDN in this study. All antibodies that induced HDN were detected in time so that adequate measures could be taken to reduce the effects in the newborn. The antenatal screening and management programme currently in use is considered to be reliable.  相似文献   

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