Bovine haemoglobin is more potent than autologous red blood cells in restoring muscular tissue oxygenation after profound isovolaemic haemodilution in dogs

PURPOSE: This study compares the effects of stored red cells, freshly donated blood and ultrapurified polymerized bovine haemoglobin (HBOC) on haemodynamic variables, oxygen transport capacity and muscular tissue oxygenation after acute and almost complete isovolaemic haemodilution in a canine model. METHODS: Following randomization to one of three groups, 24 anaesthetized Foxhounds underwent isovolaemic haemodilution with 6% hetastarch to haematocrit levels of 20%, 15% and 10% before they received isovolaemic stepwise augmentation of 1 g.dl-1 haemoglobin. In Group 1, animals were given autologous stored red cells which they had donated three weeks before. In Group 2, animals received freshly donated blood harvested during haemodilution. In Group 3, animals were infused with HBOC. Skeletal muscle tissue oxygen tension was measured with a polarographic 12 mu needle probe. RESULTS: In all groups, heart rate and cardiac index were increased with decreasing vascular resistance during haemodilution (P < 0.05). Haemodynamic variables showed a reversed trend during transfusion when compared to haemodilution but remained below baseline (P < 0.05). Arterial and venous oxygen content were changed in parallel to changes of haematocrit and haemoglobin concentrations but were lower in Group 3 than in Groups 1 and 2 (P < 0.05) during transfusion. In contrast, the oxygen extraction ratio was higher in Group 3 (59 +/- 8%, P < 0.01) at the end of transfusion than in Group 1 (37 +/- 13%) and 2 (32 +/- 5%). In Group 3, mean tissue oxygen tension increased from 16 +/- 5 mmHg after haemodilution to 56 +/- 11 mmHg after transfusion (P < 0.01) and was higher than in Group 1 (41 +/- 9, P < 0.01) and Group 2 (29 +/- 11, P < 0.01). While in Group 3 an augmentation of 0.7 g.dl-1 haemoglobin resulted in restoring baseline tissue oxygenation, higher doses of 2.7 g.dl-1 and 2.1 g.dl-1 were needed in Groups 1 and 2 to reach this level (P < 0.01). CONCLUSION: The results show a higher oxygenation potential of HBOC than with autologous stored red cells because of a more pronounced oxygen extraction.     

Allogeneic matched T-cell-depleted bone marrow transplantation for acute leukemia patients

It has been shown that high doses of human recombinant erythropoietin (r epo) increase haemoglobin levels by augmentation of F-cells, and Hb-F production in animal models and in human trials. In this study, r epo was used in patients with beta thalassemia intermedia. Our purpose was to improve haemoglobin levels by at least 2 g and maintain an average level between 10 and 12 g/dl. Ten patients aged 6-29 years (mean 14 +/- 7.6 years) with thalassemia intermedia were treated with r epo. It was given subcutaneously in rising doses from 500 to 1000 U/kg three times weekly for 3 months. During r epo therapy eight cases (80 per cent) showed an increase in haemoglobin, haematocrit, and reticulocyte levels, and an increase of at least 2 g of haemoglobin was obtained. Blood transfusion was not needed during the study except in one case. Five cases (50 per cent) improved life quality with therapy. Hb levels of all patients returned to baseline values over 1 or 2 months after r epo was discontinued. There was no significant change in absolute Hb-F, F-cells, and ferritin levels during treatment. Generally, the drug was well tolerated. No patient had hypertension. Recombinant erythropoietin seems to be an effective treatment for anaemia of beta-thalassemia intermedia, but longer term randomized trials are needed especially in patients with beta thalassemia major.     

Early histopathologic and ultrastructural changes in the heart of Sprague-Dawley rats following administration of soman

Anaemia of prematurity, a postnatal fall in haemoglobin concentration and haematocrit, is particularly common in those born at less than 32 weeks of gestation. Experimental and clinical data implicate inadequate erythropoietin production as an important reason. In this study recombinant human erythropoietin (r-HuEpo) was used in an attempt to treat or prevent this anaemia and thereby provide an alternative to erythrocyte transfusions. Premature infants (birth weight < or = 1250 g and gestational age < or = 32 weeks), who were likely to need transfusions, were randomly assigned to receive 4 weeks of treatment with either subcutaneously administered r-HuEpo (200 U; n = 12) or placebo (n = 12), three times weekly. All patients had oral supplements of elemental iron at a dose of 3 mg/kg/day. Treatment was started in the third week of life. Reticulocyte counts were significantly raised (P < 0.05) in the group treated with r-HuEpo at the end of treatment. The neonates in the group treated with r-HuEpo needed fewer erythrocyte transfusions than those in the placebo group during treatment. There were no toxic effects attributable to r-HuEpo. The results indicate that treatment of infants with very low birth weights with r-HuEpo will reduce their need for erythrocyte transfusions.     

Pregnancy in a Jehovah's witness with cervical cancer and anemia

A 34-year-old Jehovah's Witness presented with vaginal bleeding and anemia at 23 weeks gestation. She was diagnosed with a FIGO Stage IB2 squamous cell carcinoma of the cervix. The patient refused transfusion of blood products and strongly desired to continue the pregnancy. She was hospitalized and at 33 weeks gestation underwent a Cesarean-radical hysterectomy with measures that minimized blood loss.     

Erythropoietin in very preterm infants

Three neonates (a male and two females of gestational ages 27, 27 and 29 weeks with birthweight 985, 660 and 1130 g), born to parents who are Jehovah's Witnesses, were admitted to our neonatal intensive care unit over a 2 month period in 1992. Human recombinant erythropoietin (rHuEpo, 200 u/kg sc. on alternate days for 6-8 weeks) was started early in conjunction with strict control of blood sampling in an attempt to avoid the need for blood transfusion. The lowest haemoglobin recorded was 95 g/L at 35 days of age in the first infant. The amount of blood withdrawn for sampling was 21.4 mL, 20.7 mL and 5.5 mL, respectively. All were discharged near their expected birthdate, never having received a blood transfusion in the Nursery. It is possible to manage sick, very preterm, very low birthweight neonates in a neonatal intensive care setting without the use of blood transfusions by the early use of rHuEpo in conjunction with strict control of blood sampling.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Nine pregnant women with homozygous beta-thalassaemia major followed a strict transfusion regimen to maintain their haemoglobin level > 10 g/dl. One pregnancy was terminated because of concern about desferrioxamine teratogenicity and another ended in miscarriage at 11 weeks. All other women were delivered by elective caesarean section between 37 and 38 weeks. There were no obstetric complications or perinatal deaths.     

A retrospective audit of blood loss in total hip joint replacement surgery at Middlemore Hospital

AIMS: To quantify the level of inappropriate red cell transfusion in primary and complex hip replacement surgery. METHODS: Data extraction was by retrospective review of patients records. Calculation of total red cell volume loss was by use of pre and postoperative (day 7) haematocrit levels, patient weight and number of units transfused. Transfusion was accepted as justified only if instituted for a 30% red cell volume loss or loss sufficient to drop the haematocrit below 0.28. RESULTS: Of 104 patients having primary hip joint replacement, 58 were transfused with a total of 157 units of red cells; 37 (24%) of these units were given inappropriately. Of 38 patients having complex hip replacement operations, 32 were transfused with a total of 139 units of red cells; 12 (9%) of these were given inappropriately. CONCLUSIONS: Inappropriate transfusion occurs in hip replacement surgery. A concurrent audit of red cell usage is required to better define the magnitude of the problem. Two unit transfusion is commonly given when one unit would have been sufficient.     

The Guinea worm eradication effort: lessons for the future

It is a well known fact that the haemoglobin concentration and haematocrit vary in proportion to one another in most clinical situations. Therefore routine, simultaneous measurement should not be necessary. In 400 consecutive patients' blood samples, a strong correlation between the two variables is demonstrated. Routine, simultaneous measurement of the haemoglobin concentration and haematocrit increases the workload and should be avoided.     

Treatment with a gonadotrophin releasing hormone agonist before hysterectomy for leiomyomas: results of a multicentre, randomised controlled trial

OBJECTIVES: To ascertain whether uterine shrinkage induced by a gonadotrophin releasing hormone agonist before hysterectomy for fibroids increases the possibility of a vaginal procedure. DESIGN: A multicentre, prospective, randomised, controlled study. PARTICIPANTS: One hundred and twenty-seven premenopausal women with a uterine volume of 12 to 16 gestational weeks. INTERVENTIONS: Twelve weeks of triptorelin depot treatment before hysterectomy or immediate surgery. MAIN OUTCOME MEASURES: Number of vaginal and abdominal hysterectomies, operating time, blood loss, degree of difficulty of the procedure, perioperative serum haemoglobin and haematocrit levels, hospital stay, and patients' overall satisfaction with treatment. RESULTS: After randomisation, four women withdrew from the study, leaving 60 women in the triptorelin arm and 63 in the immediate surgery arm. At baseline evaluation a vaginal hysterectomy was indicated in seven women allocated to pre-operative medical therapy (12%), and in 10 of those allocated to immediate surgery (16%). Clinical assessment after the 12-week GnRH agonist course showed that abdominal hysterectomy was no longer indicated in 25/53 women (47%) as a vaginal procedure appeared appropriate. Thus the overall rate of indication for a vaginal procedure in the pre-operative medical treatment arm was 32/60 cases (53%), with a between-group difference of 37% (95% CI, 26% to 51%; chi2(1) = 19.18, P < 0.0001; OR 6.06; 95% CI, 2.60 to 14.10). Pre- and post-operative serum haemoglobin and haematocrit levels were significantly higher in the GnRH agonist than in the immediate surgery arm. No appreciable difference was observed between the groups in the other intra- and post-operative variables, including patients' satisfaction. CONCLUSIONS: Pre-operative GnRH agonist therapy increased the rate of vaginal hysterectomy in selected women with fibroids and uterine volume of 12 to 16 gestational weeks.     

Low-dose subcutaneous recombinant erythropoietin in children with chronic renal failure. Australian and New Zealand Paediatric Nephrology Association

In a multicentre trial, low-dose subcutaneous recombinant human erythropoietin (r-Hu EPO) was evaluated in 22 children aged 4 months to 16 years with anaemia of chronic renal failure over a 12-month period. A starting dosage of 50 U/kg twice weekly was given until a target haemoglobin of 9-11 g/dl was achieved. The dosage was increased by 50 U/kg per week, each 4 weeks, if the haemoglobin did not increase by 1 g/dl per month. When the target haemoglobin was achieved, the same weekly dosage was given as a single injection. After 10 weeks, the mean haemoglobin increased from 6.7 +/- 0.7 to 9.6 +/- 1.9 g/dl (P < 0.001) and the haematocrit from 19.8% +/- 2.4% to 29.3% +/- 6.3% (P < 0.001). By 4 months the target haemoglobin was achieved in 19 patients on 50 U/kg twice weekly and 1 patient on 75 U/kg twice weekly. Two children with severe renal osteodystrophy failed to respond to 95 U/kg and 150 U/kg twice weekly. The maintenance weekly dose of r-Hu EPO in 9 children over 4-12 months ranged between 45 and 125 U/kg. The Wechsler intelligence score increased in 11 children from 92 +/- 16 to 97 +/- 17 over the 12-month period (P = 0.007). No adverse effects were recorded. A starting dose of r-Hu EPO of 50 U/kg subcutaneously twice weekly is recommended as effective and safe for the majority of children with anaemia of chronic renal failure.     

The long-term course of mastalgia

A pregnancy after Mustard repair for transposition of the great arteries and ventricular septal defect with pulmonary stenosis is reported. The 23-year-old gravida 1 was treated with ACE inhibitors up to 26 weeks of gestation until cardiac medication was changed to dihydralazine. At 28 weeks of gestation the patient developed cardiac decompensation leading to caesarean section for maternal indication at 29 weeks of gestation. The neonate did not show any congenital malformation nor anuria. The patient was moved to a normal ward six days after delivery. A cardiac follow-up examination showed no difference to the condition before pregnancy.     

In utero fetal cardiac resuscitation: a case report

A patient presented at 21 weeks gestation with nonimmune hydrops of her singleton fetus. A cordocentesis confirmed fetal anemia. During the course of the procedure, fetal cardiac arrest occurred. The fetus was resuscitated with intracardiac epinephrine and fetal transfusion was performed. The resuscitation was initially successful, however the fetus died 12 h later.     

Successful pregnancy outcome following Tompkins metroplasty done early in pregnancy

A hysterosalpingogram revealed a septate uterus in a 29 year old nulliparous woman with a history of recurrent pregnancy loss. The patient underwent Tompkins metroplasty in the proliferative phase of the menstrual cycle. One month after the operation she presented with a delay in her menses and a positive pregnancy test. Ultrasound revealed a viable fetus commensurate with 10 weeks gestation, making the gestation period 5 weeks at the time of surgery. After reviewing the patient's menstrual history it was found that the period the patient had before surgery was on time but with unusually minimal bleeding. A repeat ultrasound scan for anomaly done 7 weeks later was commensurate with 17 weeks gestation. The patient carried her pregnancy for the first time until approximately 37 weeks when she delivered by Caesarean section a healthy female baby weighing 3700 g.     

Randomised trial of elective continuous positive airway pressure (CPAP) compared with rescue CPAP after extubation

AIM: To determine if a weaning regimen on flow driver continuous positive airway pressure (CPAP) would decrease the number of ventilator days but increase the number of CPAP days when compared with a rescue regimen. METHODS: Fifty eight babies of 24-32 weeks gestation with respiratory distress syndrome (RDS) were studied prospectively. After extubation they were randomly allocated to receive CPAP for 72 hours (n = 29) according to a weaning regimen, or were placed in headbox oxygen and received CPAP only if present "start CPAP" criteria were met (n = 29, rescue group). RESULTS: There was no difference in successful extubation at 72 hours, 1 and 2 weeks, between the groups in terms of the number of reventilation episodes, reventilation days, or in total days of CPAP. Birthweight, gestational age, race, day of first extubation, antenatal or postnatal steroids, patent ductus arteriosus status and maximal mean airway pressure used were of no value in predicting success or failure at 72 hours, 1, or 2 weeks. CONCLUSION: The weaning regimen did not decrease the number of ventilator days or days on CPAP compared with the rescue regimen. The rescue regimen on flow driver CPAP seems to be a safe and effective method of managing a baby of 24-32 weeks gestation who has been ventilated for RDS or immature lung disease.     

Haematological variables in prostatic carcinoma patients

Routine laboratory tests of the red, white and platelet blood cell systems were performed in 49 patients with benign prostatic hyperplasia (BPH), in 24 hormonally treated patients with metastatic prostatic carcinoma, in 17 patients with untreated prostatic carcinoma without metastases and in 14 patients with untreated metastatic prostatic carcinoma. Significantly lower erythrocyte counts, haemoglobin levels and haematocrit values were found in the hormonally treated cancer group compared to all three other groups. The untreated metastatic cancer group had significantly lower haemoglobin levels and haematocrit values compared to the untreated non-metastatic cancer group. These results indicate that patients with metastases were developing anaemia and that this development was not influenced by palliative hormonal therapy. The results of this study showed that abnormal platelet counts in patients with prostatic carcinoma were rare and that the white blood cell system did not seem to be affected in patients with prostatic carcinoma.     

Modulation of human epidermal cell response to 2,3,7,8-tetrachlorodibenzo-p-dioxin by epidermal growth factor

OBJECTIVE: To investigate cranial ultrasonographic findings in survivors of monochorionic pregnancies complicated by fetofetal transfusion syndrome. STUDY DESIGN: Case details of all monochorionic twin pregnancies complicated by fetofetal transfusion syndrome were obtained from the Centre for Fetal Care database for a 3-year period. Fetofetal transfusion syndrome was diagnosed according to ultrasonographic criteria. Eligible for entry were twin pregnancies resulting in live-born preterm infants and complicated by fetofetal transfusion syndrome severe enough to require amnioreduction. Cranial ultrasonographic scans performed within 48 hours of birth were reviewed for evidence of abnormality. RESULTS: Seventeen pregnancies were eligible for inclusion in the study. Median gestational age was 25 weeks (between 17 and 29 weeks) at diagnosis and 30 weeks (between 25 and 35 weeks) at delivery. Three infants died before ultrasonography could be performed. The remaining 31 twin infants received an early cranial ultrasonographic scan. One of the 31 had a major cerebral infarct; 10 others had evidence of other, more minor, antenatally acquired lesions. CONCLUSIONS: Both donor and recipient survivors from pregnancies complicated by fetofetal transfusion syndrome are at significant risk for antenatally acquired cerebral lesions. Long-term neurologic follow-up studies are indicated to determine the clinical significance of these lesions.     

Functional abilities at age 4 years of children born before 29 weeks of gestation

OBJECTIVES: To assess the rate of impairment and disability among babies born very preterm and to investigate the association between such impairment and gestational age at birth. DESIGN: Cohort study of a geographically defined population of babies. SETTING: Oxford Regional Health Authority. SUBJECTS: All babies born alive before 29 weeks of gestation to mothers resident in the region during 1984-6. MAIN OUTCOME MEASURES: Survival rates and rates of impairment and disability among survivors at the age of 4 years. RESULTS: Of the 342 babies, half (170) survived to be discharged home. Of the 164 survivors to age 4 years, 153 (93%) were assessed. A total of 35 (23%; 95% confidence interval 16% to 30%) were severely disabled and only 54 (35%; 28% to 43%) were unimpaired. The risk of impairment and disability increased with decreasing gestational age at birth (p < 0.003). CONCLUSIONS: With the increasing survival rate among babies born before 29 weeks of gestation, we need urgently to establish reliable ways of monitoring the proportion of survivors who have a disability.     

Liveborn twin with intrauterine death of one twin: report of two cases

Twin pregnancies carry a greater mortality and morbidity rate than singleton pregnancies. In case of an intrauterine fetal death (IUFD), the risk of mortality and morbidity of the surviving twin is increased. The pathogenesis is usually due to twin to twin transfusion. The donor twin is hypovolemic, anemic and often shows a growth retardation or even severe enough to cause an IUFD. The recipient twin is hypervolemic, polycythemic and weighs more than its co-twin. In this paper we reported two cases of liveborn twin complicated by an IUFD of its co-twin. Both cases were monochorionic twins. The first case was born at 29 weeks and 6 days of gestation, a male infant weighed 1054 g. His co-twin was stillborn and weighed 722 g. At birth the surviving infant showed respiratory distress syndrome (RDS), anemia and bilateral periventricular echogenicity (PVE). The second case was a female infant with a gestational age of 26 weeks and 2 days and weighed 850 g. Her stillborn co-twin weighed 804 g. Both twins showed signs of hydrops, and the liveborn infant had RDS, marked anemia (Hb 6 g/dl) and hypoalbuminemia. We will discuss the possible pathogenesis in our cases and also review some literature.     

False-positive WBC imaging secondary to a distended bladder and fecal retention

We present the sonographic findings of a fetus with a vesicoallantoic cyst. The cyst was first identified at 17 weeks of gestation; it was associated with an omphalocele, and disappeared spontaneously at 29 weeks. The fetal urinary bladder was not visualized thereafter. An omphalocele and exstrophia of the urachus were found at birth and repaired. Non-visualization of the fetal urinary bladder suggested rupture of the covering membrane of the omphalocele and allantois during fetal life. A defect in the wall of the omphalocele supported our hypothesis.     

Isolation of a novel mouse gene MA-3 that is induced upon programmed cell death

Haematopoietic progenitor cells were isolated from human fetal liver, obtained between 6 and 15 weeks gestation. After preparation of a single cell suspension, the cells were stored using a stepwise freezing protocol; taking the cells from room temperature through -70 degrees C to liquid nitrogen. Viability (trypan blue exclusion), morphology (Leishman stain), identification of cell type (flow cytometry) and growth characteristics in semi-solid culture medium were assessed using the fresh cell suspension. We were able to confirm that the predominant cells in human fetal liver up to about 15 weeks gestation are those of the erythroid lineage. It was established that viability in excess of 75% was required to ensure adequate growth in culture after frozen storage and it was deemed important to ensure morphological integrity of the cell preparations. The colonies formed in culture were observed to be producing haemoglobin between 7 and 9 days after initial seeding. We have determined that cells can be stored in liquid nitrogen for up to 2 years without loss of (1) viability, (2) morphological features and (3) ability to form colonies and produce haemoglobin in culture. These findings offer encouragement for the implementation of a cell bank to support an in utero transplantation programme.