Reappraisal of endometrial thickness for the detection of endometrial cancer in postmenopausal bleeding: a retrospective cohort study.

OBJECTIVE: To estimate the accuracy of transvaginal ultrasound (TVS) measurement of endometrial thickness (ET) in diagnosing endometrial cancer in postmenopausal women with vaginal bleeding (PMB). DESIGN: Retrospective cohort study. SETTING: One-stop PMB clinic in a Hong Kong teaching hospital. POPULATION: A cohort of 4383 women with PMB. METHODS: Transvaginal ultrasonic measurement of ET and endometrial biopsies were obtained in women presenting with PMB between 2002 and 2013. Endometrial histology was used as the reference standard to calculate accuracy estimates. MAIN OUTCOME MEASURES: Accuracy data for TVS ET presented as sensitivity, specificity, and area under the receiver operator characteristic (ROC) curve. RESULTS: Endometrial cancer was diagnosed in 3.8% of women. The median ET in those with endometrial cancer was significantly higher than those with benign conditions (15.7 versus 3.2 mm, P < 0.001). The area under the ROC curve was 0.92 (95% CI 0.89-0.94). The sensitivity for the detection of endometrial cancer at 3-, 4-, and 5-mm cut-offs were 97.0% (95% CI 94.5-99.6%), 94.1% (95% CI 90.5-97.6%), and 93.5% (95% CI 89.7-97.2%), respectively. The corresponding estimates of specificity at these thresholds were 45.3% (95% CI 43.8-46.8%), 66.8% (65.4-68.2%), and 74.0% (72.7-75.4%). CONCLUSIONS: Transvaginal ultrasound using a 3-mm cut-off has high sensitivity for detecting endometrial cancer and can identify women with PMB who are highly unlikely to have endometrial cancer, thereby avoiding more invasive endometrial biopsy.

Menstrual problems and health-seeking behaviour in Hong Kong Chinese girls.

OBJECTIVE: To ascertain the prevalence of menstrual problems in adolescent girls and their health-seeking behaviour. DESIGN: Questionnaire survey on menstruation, menstrual problems, medical consultation, and factors influencing girls seeking medical care. SETTING: Secondary schools in the catchment area of a tertiary teaching hospital in Hong Kong. PARTICIPANTS: A total of 5609 girls from 10 secondary schools. MAIN OUTCOME MEASURES: Prevalence of menstrual problems and health-seeking behaviour of adolescent girls. RESULTS: The mean age of the girls and their mean age at menarche were 15.1 (standard deviation, 2.0) years and 12.3 (1.1) years, respectively. The prevalence of menorrhagia, dysmenorrhoea, and menstrual symptoms were 17.9% (95% confidence interval, 16.9-19.1%), 68.7% (67.7-70.3%), and 37.7% (36.7-39.3%), respectively. The prevalence of menstrual symptoms (P<0.001) and dysmenorrhoea (P<0.001) increased with gynaecological age (calendar age minus age at menarche), whilst the proportion having short or long cycles decreased (P=0.002 and P=0.009). One in eight girls reported having been absent from school, whilst only 6.4% had sought medical care because of menses. Multivariate analysis indicated that seeking medical care for menorrhagia was dependent on the opinion of a family member (P=0.005), and for dysmenorrhoea on its severity (P=0.046) and anxiety about embarrassing questions (P=0.039). CONCLUSIONS: The prevalence of menstrual problems in Hong Kong Chinese girls is high and causes significant disruption to their school and daily activities. However, only a minority seek medical advice.

A randomised controlled trial of prophylactic levonorgestrel intrauterine system in tamoxifen-treated women.

OBJECTIVE: To study the prophylactic use of levonorgestrel intrauterine system (LNG-IUS) in the prevention of endometrial pathology in women having breast cancer treated with tamoxifen. DESIGN: Randomised controlled trial. SETTING: A tertiary teaching hospital. POPULATION: One hundred and thirteen women (66 premenopausal/47 postmenopausal) who required adjuvant tamoxifen for breast cancer after the completion of postoperative radiotherapy and chemotherapy. METHODS: Women were randomised to treatment group (prophylactic LNG-IUS insertion before the commencement of tamoxifen) or control group. Uterine cavity was examined by outpatient hysteroscopy and endometrial biopsy before and at 12 months after commencement of tamoxifen. MAIN OUTCOME MEASURES: De novo endometrial pathology at 1 year of tamoxifen. RESULTS: Women in the treatment group had a much lower incidence of endometrial polyp (1.8 versus 15.5%, P= 0.017) (relative risk: 0.12; 95% CI: 0.02-0.91) at 12 months. There was no significant difference in the incidence of submucosal fibroid between the two groups (1.8 versus 3.4%, P= 1.0). LNG-IUS was retained in 95% women in the treatment group at 1 year. CONCLUSION: LNG-IUS reduces the occurrence of de novo endometrial polyp in women treated with tamoxifen for breast cancer.

An audit on hysterectomy for benign diseases in public hospitals in Hong Kong.

OBJECTIVE: To assess the standard of hysterectomy in public hospitals in Hong Kong, so as to improve the quality of patient care and outcome. DESIGN: Clinical audit. SETTING: Twelve Hong Kong Hospital Authority public hospitals. PATIENTS: All patients undergoing hysterectomy for benign gynaecological conditions during the period from 1 July 2002 to 31 December 2002 inclusive. RESULTS: A total of 1330 patients were included for analysis: 934 (70.2%) having abdominal hysterectomies, 184 (13.8%) having laparoscopic hysterectomies, and 212 (15.9%) undergoing vaginal hysterectomies. Uterine fibroids constituted the commonest indication for abdominal (73.7%) and laparoscopic (61.4%) hysterectomies, while genital prolapse was the most common indication (96.2%) for vaginal hysterectomy. The majority of patients undergoing laparoscopic and vaginal hysterectomy (86.3% and 84.8% respectively) were given prophylactic antibiotics, in contrast to only 45.8% of those undergoing abdominal hysterectomy. In all, 85.8% of the abdominal and vaginal hysterectomies performed by trainees were supervised, while for trainees performing laparoscopic hysterectomy, all had specialists as their first assistant. The overall incidence of complications for vaginal hysterectomy was lower than that for both abdominal hysterectomy (P<0.001) and laparoscopic hysterectomy (P<0.05). Infectious morbidity was significantly higher in patients undergoing abdominal hysterectomy without prophylactic antibiotics. CONCLUSION: The overall incidence of complications was lower for vaginal hysterectomies, as compared to both abdominal and laparoscopic hysterectomies, whereas the risk of urinary tract injury was significantly higher for laparoscopic hysterectomy. According to our audit, the level of supervision for the trainees was high. However, routine antibiotic prophylaxis should be more consistently used in the territory.

Avoiding manual removal of placenta: evaluation of intra-umbilical injection of uterotonics using the Pipingas technique for management of adherent placenta.

BACKGROUND: Manual removal of placenta is performed in 1-3% of cases, and whilst a well established and relatively safe procedure, it is not without complications, which include infection, hemorrhage, uterine rupture, and occasional maternal death. METHODS: A three-arm randomized controlled trial of 50 IU Syntocinon (in 30 ml N saline) versus 800 mcg misoprostol (in 30 ml N saline) versus 30 ml N saline alone (control), injected into the placental bed via the umbilical vein using the Pipingas method. A group sequential research model (triangular test: PEST4) was adopted to minimize the sample size, as retained placenta is a relatively uncommon condition. RESULTS: No significant difference in the rate of manual removal was observed between the control and Syntocinon groups. On triggering the automatic stopping rule for this arm of the trial all subsequent cases recruited were allocated to receive either Syntocinon or misoprostol. After a total of 54 cases a significant reduction in manual removal of placenta was observed in the misoprostol group, triggering the automatic stopping rule and terminating the trial. CONCLUSION: Misoprostol (800 mcg) dissolved in 30 ml N saline and administered by intraumbilical injection using the Pipingas technique significantly reduces the need for manual removal for retained adherent placenta, whereas Syntocinon has similar effectiveness to injection of N saline alone.

A double-blind randomized controlled trial of oral misoprostol and intramuscular syntometrine in the management of the third stage of labor.

BACKGROUND: The aim of this study was to compare the efficacy and safety of oral misoprostol 400 mug with intramuscular syntometrine in the management of the third stage of labor. MATERIAL AND METHODS: This was a double-blind randomized controlled trial conducted in a tertiary care hospital. Three hundred and fifty-five women randomized to receive either oral misoprostol 400 mug or intramuscular syntometrine in the third stage of labor were studied. The change in hemoglobin level from before to 48 h after delivery, use of additional oxytocics and treatment related side effects were the main outcome measures. RESULTS: There were no significant differences between the two groups in terms of the change in hemoglobin level and mean blood loss. The incidence of shivering was significantly higher in the misoprostol group whilst that of vomiting was significantly higher in the syntometrine group. There were no differences in the incidence of nausea, headache, diarrhea and pyrexia between the two groups. CONCLUSION: Orally administered misoprostol at a dose of 400 mug is an acceptable alternative in preventing post-partum blood loss, as measured by the peri-partum change in hemoglobin level and was not associated with an increased incidence of side effects.

Bone mineral density in children with thalassaemia major: determining factors and effects of bone marrow transplantation.

Osteoporosis and osteopenia affect up to half of patients with thalassaemia major (TM). We investigate the effects of acquired factors and BMT on bone mineral density (BMD) in these patients. In all, 53 patients on regular transfusion (BT group) and 33 patients at 5.7+/-1.9 years post transplant (BMT group) were recruited. BMD was measured by dual energy X-ray absorptiometry. Serum concentrations of osteocalcin, bone-specific alkaline phosphatase (ALP), beta-crossLap and urinary cross-linking deoxypyridinoline (DPD) were measured by chemiluminescence and enzyme immunoassay, respectively. Severe BMD deficit (Z-score <-2.5) at spine and hip were noted in 62 and 35% of BT group. Serum osteocalcin (beta=-0.463; P=0.006) was predictive of spine BMD, whereas age (beta=-0.843; P=0.007) and urine DPD (beta=-0.439; P=0.037) were associated with hip BMD in BT group. Among BMT patients, post transplant duration (beta=0.450; P=0.009) and serum bone-specific ALP (beta=-0.495; P=0.013) were associated with spine BMD. Severe BMD deficit was less common among BMT than BT patients (6 vs 35%; P=0.036). The mean (s.d.) osteocalcin levels in BMT and BT groups were 96.4 (72.7) microg and 68.9 (40.3) microg/l, respectively (P=0.037). In conclusion, severe BMD deficit is common in Chinese TM patients and BMT may reverse BMD deficit in these patients.

Multipotent neural precursors express neural and hematopoietic factors, and enhance ex vivo expansion of cord blood CD34+ cells, colony forming units and NOD/SCID-repopulating cells in contact and noncontact cultures.

In view of the possible crosstalks between hematopoiesis and neuropoiesis, we evaluated two microenvironments, murine neonatal neural cell line C17.2 and primary embryonic aorta-gonad-mesonephros (AGM) stromal cells, on the ex vivo expansion of CD34+ cells from human cord blood. In a contact culture system, C17.2 or AGM cells significantly enhanced the expansion of CD34+ cells to a panel of early and committed hematopoietic progenitor cells. In a noncontact transwell system, pre-established C17.2 cells significantly increased the expansion of total nucleated cells, CD34+ cells and multilineage colony forming cells (P<0.01). Expanded cells were infused into nonobese diabetic/severe-combined immunodeficient mice. The engraftment of human (hu)CD45+ cells in the bone marrow of these mice was consistently higher in all the 10 experiments conducted with the support of C17.2 cells when compared with those in respective control groups (11.9 vs 2.43%, P=0.03). Using RT-PCR and Southern blot analysis, we showed that AGM and C17.2 cells expressed a panel of hematopoietic, bone morphogenetic and neurotrophic factors. Our data provided the first evidence on the promoting effects of a neural progenitor cell line on hematopoiesis at a noncontact condition. The mechanism could be mediated by the expression of multilineage regulatory factors.

Outcome in laparoscopic management of persistent adnexal mass during the second trimester of pregnancy.

BACKGROUND: This study evaluated the safety of laparoscopic management for persistent adnexal mass in the second trimester of pregnancy. METHODS: Between April 1994 and March 2003, 67 consecutive women underwent laparoscopic removal of adnexal masses that had persisted into the second trimester of pregnancy in an academic tertiary referral center. Operative complications, pregnancy, and labor outcomes were evaluated. RESULTS: The median gestation was 10.5 weeks (range, 5-25 weeks) at diagnosis and 16 weeks (range, 12-25 weeks) at the time of operation. Only two women required for conversion to laparotomy. Cystectomy was performed for 55 women, oophorectomy for 9 women and fenestration in 3 women. There were no intraoperative complications or major postoperative complications. No women were given tocolytic therapy, and none experienced uterine contractions. There was one spontaneous abortion 6 weeks after the operation, and one patent was lost to follow up. Of the remaining 65 women, the median gestation at delivery was 39 weeks (range, 33-42 weeks), and the median birthweight was 3,160 g (range, 2,220-4,200 g). CONCLUSIONS: Laparosocpic surgery for persistent adnexal masses in the second trimester of pregnancy is safe when performed by experienced surgeons.

Torsion of a paraovarian myoma in a teenage woman.

Myomas are uncommon in adolescence and very rarely occur outside the uterus. Torsion of a paraovarian myoma in an 18-year-old woman was managed laparoscopically. Awareness of the condition and high index of suspicion are keys to early diagnosis and prompt intervention.

Unrelated umbilical cord blood transplantation in children: experience of the Hong Kong Red Cross Blood Transfusion Service.

OBJECTIVE: To review the outcome of unrelated umbilical cord blood transplantation in children using cord blood from the Hong Kong Red Cross Blood Transfusion Service. DESIGN: Retrospective study. PATIENTS: Records of eight patients who received unrelated umbilical cord blood transplants between 1999 and 2003 were reviewed. MAIN OUTCOME MEASURES: Engraftment of haematopoietic cells and graft-versus-host disease after transplantation. RESULTS: The median age of the patients was 4.9 years (range, 1.0-9.4 years). Five patients had acute leukaemia, one had non-Hodgkin's lymphoma, one had X-linked adrenoleukodystrophy, and one had mucolipidosis. The infused umbilical cord blood units contained a median of 6.7 x 10(7) /kg nucleated cells and 4.0 x 10(5) /kg CD34-positive cells. Neutrophil engraftment was achieved at a median of 13 days (range, 11-19 days) and, for seven patients, platelet engraftment was achieved at a median of 39 days (range, 24-98 days). Acute graft-versus-host disease occurred in all patients (grades I to III). One of the patients died because of encephalitis; of the other seven, five developed chronic graft-versus-host disease of the skin. At a median follow-up of 2 years, the four patients with leukaemia and the one with non-Hodgkin's lymphoma remained in continuous complete remission; the patient with adrenoleukodystrophy showed stabilisation of neurological condition. CONCLUSION: The Hong Kong Red Cross Blood Transfusion Service Cord Blood Bank stored cord blood units of good quality for transplantation, the outcome of which was comparable to that of bone marrow transplantation.

Oseltamivir prophylaxis during the influenza season in a paediatric cancer centre: prospective observational study.

OBJECTIVE: To determine the role of oseltamivir prophylaxis for immunocompromised patients. DESIGN: Prospective, non-blinded, non-controlled observational study. SETTING: A paediatric cancer centre, Hong Kong. PARTICIPANTS: Thirty-two patients, immunocompromised by chemotherapy or bone marrow transplantation during an influenza season in 2001. INTERVENTION: Oral oseltamivir prophylaxis 75 mg/d for 8 weeks. MAIN OUTCOME MEASURES: Laboratory-confirmed influenza infection, symptoms of influenza, drug compliance, and any side-effects from oseltamivir treatment. Laboratory monitoring included virological surveillance for influenza A and B, blood counts, and renal and liver function tests. RESULTS: Patients' median age was 14.3 years (range, 6.3-23.4 years). Underlying conditions included malignancy (n=29) and other haematological diseases (n=3). No documented influenza infection according to serological tests was present throughout the study period. Five patients with symptoms of upper respiratory tract infection did not have any influenza infection detected by rapid virological assay and viral culture. For 16% of patients, the main side-effect in the study was gastro-intestinal upset. CONCLUSIONS: Oral oseltamivir 75 mg once daily for 8 weeks may be useful in the prevention of influenza infection in patients immunocompromised by chemoradiotherapy; side-effects are few and acceptable.

Is vaginal dermoid cyst a rare occurrence or a misnomer? A case report and review of the literature.

Vaginal dermoid cyst is a rare finding. Preoperative diagnosis of this lesion is difficult as the sonographic features are similar to those of an epidermal inclusion cyst. We report a case of vaginal dermoid cyst and present its sonographic characteristics.

Implication of maternal-cell contamination in the clinical banking of umbilical cord blood.

BACKGROUND: The increasing utilization of human UC blood (UCB) in transplantation has drawn attention to the need for rationalization of selection, collection, processing, testing, banking and release of UCB. However, the issue of maternal blood contamination has not been well addressed. There are concerns that maternal T cells might elicit GvHD post-UCB transplant. METHODS: Maternal T cells in 58 male UCB allografts were enumerated using fluorescent in situ hybridization and flow cytometry. Obstetric factors, preceding labor, multi-parity and gestational age, were also analyzed. RESULTS: Levels of maternal cells of 0.75-5.25% were found in 15.5% (9/58) UCB. There was no association of maternal-cell contamination with preceding labor [25% (2/8) with previous delivery versus 35.4% (17/48) first born, P = 0.702], nor any correlation with multi-parity [37.5% (3/8) para > or = 3 versus 16.7% (8/48) para < 3, P = 0.181]. Gestation age of newborns also exhibited no association with maternal-cell contamination (39.47 weeks in newborn UCB with maternal cells, versus 39.58 weeks without: P = 0.674). The extrapolated maternal T cells/kg in nine UCB transplants were 1.05 x 10(5) +/- 1.12 x 10(5) (3.40 x 10(4) - 3.18 x 10(5)). DISCUSSION: In relation to the arbitrary threshold of 1 x 10(5) T cells/kg in HLA-mismatched transplants utilizing T-cell depleted BM, 22.2% (2/9) of UCB transplants having maternal-cell contamination might be at risk of GvHD. Data support the need for testing for maternal blood in UCB, and evaluating the clinical relevance of GvHD in patients post-UCB transplant. The establishment of guidelines and standards for release of such UCB collections would be advisable in evidence-based UCB transplantation.

Cobblestone area-forming cells, long-term culture-initiating cells and NOD/SCID repopulating cells in human neonatal blood: a comparison with umbilical cord blood.

Our prior study demonstrated that neonatal blood (NB) contained hematopoietic stem and progenitor cells that declined rapidly after birth. To validate that NB is a source of functional stem cells, we characterized this population in terms of cobblestone area-forming cells (CAFC), long-term culture-initiating cells (LTC-IC) and NOD/SCID mouse repopulating cells (SRC) in NB and umbilical cord blood (CB). Our data demonstrated that the frequencies of CAFC (30.2 vs 37.1, P = 0.14) and LTC-IC (28.6 vs 31.0, P = 0.49) in 1 x 10(5) mononuclear cells (MNC) of NB and CB were similar, suggesting that these cells were preserved in the circulation of the neonates shortly after birth. Sublethally irradiated NOD/SCID mice were transplanted with CD34(+) cells enriched from thawed NB and CB. At 6 weeks post transplant, human (hu)CD45(+) cells were detected in the bone marrow (BM), spleen and peripheral blood (PB) of the mice as demonstrated by flow cytometric and DNA analysis. Levels of huCD45(+)cells and colony forming units (CFU) appeared to be dependent on the infusion cell dose and were higher in animals receiving CB cells when compared with those of the NB group. The transplanted cells were capable of differentiation into multi-lineage progenitor cells (CD34(+) cells and differential CFU), as well as mature myeloid (CD14(+), CD33(+)), B lymphoid (CD19(+)) and megakaryocytic (CD61(+)) cells in the recipients. NB cells, subjected to ex vivo culture in an optimized preclinical condition, were significantly expanded to early and committed progenitor cells. Expanded NB contained SRC at a reduced quantity but with high proportions of CD14(+) cells and CD33(+) cells. Our study confirms that NB contains pluripotent hematopoietic stem and progenitor cells capable of homing and engrafting the NOD/SCID mice.

Morbidity and mortality patterns of thalassaemia major patients in Hong Kong: retrospective study.

OBJECTIVES: To study the morbidity and mortality patterns of transfusion-dependent thalassaemia major patients in Hong Kong, and compare the outcomes of these patients according to different periods of birth. DESIGN: Retrospective study. SETTING: Paediatric departments of three regional hospitals, Hong Kong. SUBJECTS AND METHODS: Medical records of thalassaemia major patients were reviewed. Data gathered included demographic and survival data, complications of iron overload, repeated transfusion, and bone marrow transplantation; the probability of survival of three cohorts was also estimated. RESULTS: Two hundred and thirty-two patients were studied at a median age of 15.5 years (range, 1.4-30.3 years). There were 60 patients born before 1980 (cohort 1), 117 patients born between 1980 and 1989 (cohort 2), and 55 patients born after 1989 (cohort 3). The median age of starting desferrioxamine was 8 years, 4 years, and 3 years for cohorts 1, 2, and 3, respectively. Cardiomyopathy, diabetes mellitus, and hypothyroidism occurred in 15.1%, 8.6%, and 6.9% of patients with thalassaemia major, respectively. The above complications developed in 5% to 12% of cohort 2 patients. Delayed puberty was present in 38.4% and hormonal replacement for gonadal failure was required in 29.7% of evaluable patients. Short stature was common and the median height standard deviation score was -1.63. Twenty patients had died, and cardiomyopathy was the leading cause of death, followed by complications of bone marrow transplantation. The probability of survival beyond the age of 20 years was 87.6%. CONCLUSION: Despite the use of iron chelation in the past two decades, severe complications of iron overload still occurred even in those who started chelation therapy early. Cardiomyopathy was the leading cause of death, while endocrinopathies and short stature were common complications especially in teenagers and adults.

A prospective randomized trial comparing patient-controlled sedation using propofol and alfentanil and physician-administered sedation using diazepam and pethidine during transvaginal ultrasound-guided oocyte retrieval.

BACKGROUND: This open label study compared the effectiveness of patient-controlled sedation (PCS), with physician-administered sedation (PAS) during transvaginal ultrasound-guided oocyte retrieval (TUGOR). METHODS: A total of 106 patients was randomized using a computer model to receive either PCS (n = 51) or PAS (n = 55). Intra-operative sedation and co-operation were measured on a 5-point scale while severity of pain, and doctor and patient satisfaction were assessed using a 100 mm visual analogue scale. Number of oocytes retrieved and fertilization, cleavage and clinical pregnancy rates were also recorded. RESULTS: Levels of sedation and co-operation were similar between groups. The pain score was higher in the PCS group during (mean +/- SD, 53 +/- 23 versus 35 +/- 24; P < 0.01) and 2 h after the procedure (29 +/- 27 versus 17 +/- 22; P < 0.05). Doctors were less satisfied with PCS than PAS (62 +/- 25 versus 71 +/- 26; P < 0.05) while patients were highly satisfied with both methods (76 +/- 23 versus 74 +/- 21; not significant). There were no oversedation or peri-operative complications. Fertility outcomes were similar. Patients tended to prefer PCS when given the choice of sedation method. CONCLUSION: Although PCS provides less analgesia then PAS during TUGOR, it is safe, satisfactory and accepted by patients.

Human herpesvirus-6 encephalitis after unrelated umbilical cord blood transplant in children.

Three children developed human herpesvirus-6 (HHV-6), variant B encephalitis after unrelated umbilical cord blood transplant, in a single center. They developed clinical manifestations of encephalitis around day 17 post transplant. Impairment of consciousness, incoherent speech, episodic focal pruritus, motor weakness, convulsions and severe hyponatremia were features at presentation. Radiological investigation of brain ranged from unremarkable to extensive white matter and meningeal lesions. Diagnosis was established by the presence of HHV-6 DNA in cerebrospinal fluid (CSF). Retrospective analyses of plasma revealed the presence of viral DNAemia prior to the onset of disease in two subjects. Treatment with ganciclovir or foscarnet was given. Two subjects did not achieve engraftment and died of other transplant-related complications on day 38 and 56 post-transplant, respectively. One subject achieved disease-free survival for more than 1 year with a satisfactory neurological outcome. In conclusion, HHV-6 encephalitis is not uncommon among patients undergoing umbilical cord blood transplantation. It is worth conducting further studies on early diagnosis and optimal management of this potentially fatal disease.

Liver disease in transfusion dependent thalassaemia major.

AIMS: To study the prevalence and severity of liver diseases of transfusion dependent thalassaemia major patients, and correlate the histological and biochemical changes of iron overload in liver with the peripheral blood markers. METHOD: Liver biopsy was performed to assess the histological changes and liver iron content (LIC). RESULTS: One hundred patients were evaluated (median age 11.7 years, range 1.5-27). A total of 81 liver biopsies were performed in 73 patients; 43 samples were analysed for LIC. Grade 3-4 haemosiderosis and hepatic fibrosis was found in 44% and 30% of patients respectively; both were significantly associated with higher serum ferritin, liver enzymes, and LIC. Very high LIC (>15 mg/g dry weight) was present in 16.3% of patients. CONCLUSION: Severe haemosiderosis and hepatic fibrosis were common in patients with thalassaemia major despite the use of chelation therapy. Liver biopsy provided information on fibrosis and LIC which could not be accurately predicted from peripheral blood markers.

A randomised controlled trial of intramuscular syntometrine and intravenous oxytocin in the management of the third stage of labour.

OBJECTIVE: To compare the efficacy and safety of intravenous oxytocin with intramuscular syntometrine in the management of the third stage of labour. DESIGN: A prospective randomised trial. SETTING: A university teaching hospital. METHODS: A total of 991 women having a singleton pregnancy and vaginal delivery were randomised by a computer-generated number to receive either 1 ml syntometrine intramuscularly or 10 units of intravenous Syntocinon after delivery of the anterior shoulder of the fetus. MAIN OUTCOME MEASURES: Blood loss during delivery, rate of postpartum haemorrhage, need for repeated oxytocics, haemoglobin level before and 24 hours after delivery, duration of third stage, need for manual removal of placenta and sides effects including hypertension, nausea, vomiting, headache and chest pain. RESULTS: The use of intravenous oxytocin was associated with a reduction in postpartum blood loss (P < 0.001) but there was no difference in the risk of postpartum haemorrhage in the need for repeated oxytocic injections and the drop in peripartum haemoglobin level between the two groups. There was also no difference in the risk of prolonged third stage, or in the need for manual removal of placenta. The use of syntometrine was associated with a higher risk of hypertension (RR 2.39, 95% CI 1.00-5.70). Other side effects were mild in nature with no differences between the two groups. CONCLUSIONS: There are no important clinical differences in the effectiveness of intramuscular syntometrine and intravenous oxytocin for the prevention of postpartum blood loss. Intravenous oxytocin is less likely to cause hypertension.