A synopsis of current haemophilia care in Hong Kong.

OBJECTIVE: To provide a synopsis of current haemophilia care in Hong Kong. DESIGN: Retrospective survey. SETTING: All haematology units of the Hospital Authority in Hong Kong. PATIENTS: All patients with haemophilia A and haemophilia B. RESULTS: To date, there were 222 mild-to-severe haemophilia patients (192 type A, 30 type B) under regular public care in Hong Kong (43% were considered severe, 33% moderate, and 24% mild), which gave a crude prevalence of 6.8/100 000 male inhabitants. A total of 12.8 million units of Factor VIII and 3 million units of Factor IX were prescribed annually. This amounts to 1.83 units of FVIII per capita of the population, which is comparable to that of other developed countries. Leading causes of mortality were human immunodeficiency virus-related complications (10 cases) and cerebral bleeding (2 cases). The life expectancy of patients with severe haemophilia in Hong Kong is improving; currently the oldest patient is 60 years old. Such improved survival may be due to enhanced factor availability, prompt treatment of bleeding episodes at home, safer factor products, and better antiviral treatment. Primary prophylaxis is the accepted standard of care for severe and moderate cases, and "Factor First" has become hospital policy. However, 12 patients continue to present treatment challenges, due to the documented presence of factor inhibitors. In all, 28, 100, and 14 cases respectively were positive for human immunodeficiency virus, hepatitis C virus, and hepatitis B virus; the youngest patients with the corresponding infections being 28, 13, and 22 years old. Comprehensive care with dedicated physiotherapy, surgical support, and radionucleotide synovectomy may reduce morbidity further. CONCLUSION: A multidisciplinary approach can further improve the future care for haemophilia patients in Hong Kong.

Initial presentation and management of osteosarcoma, and its impact on disease outcome.

OBJECTIVE: To evaluate the initial presenting symptoms and management of osteosarcoma in Hong Kong Chinese children, in relation to any possible impact on disease outcomes. DESIGN: Retrospective study. SETTING: A tertiary referral centre of bone cancer in a university teaching hospital in Hong Kong. PATIENTS: All children aged younger than 18 years with a diagnosis of osteosarcoma who received treatment from March 1994 to October 2005. RESULTS: A total of 51 children were studied. The median age of onset was 13 (range, 3-20) years; 61% were males. The tumours were located in the distal femur and proximal tibia, which accounted for 45% and 22% of the cases, respectively; 24% of patients had metastatic disease at presentation. Swelling (76%) and pain (90%) were the most common presenting complaints. Approximately one third of the patients had a preceding history of trauma. The median duration of initial symptoms to first medical consultation of any sort was 30 (range, 0-360) days. The median time from the first consultation to a definitive diagnosis was 21 (range, 0-350) days; 25% were diagnosed more than 52 days after presentation. Bonesetters were initially consulted by 37% of these patients. From presentation to diagnosis, the median duration was 61 (range, 4-361) days. Analysis of the duration of pre-diagnosis symptoms did not correlate significantly with the development of metastatic disease, response to chemotherapy, feasibility of limb salvage surgery, relapse rates, or survival rates. CONCLUSIONS: In Hong Kong, initial consultation to bonesetters was common. A relatively long delay in between symptom onset and diagnosis of osteosarcoma was encountered. The public and medical practitioners should be made aware of this disease, especially in adolescents.

Haematopoietic stem cell transplantation for thalassaemia in Chinese patients.

Beta thalassaemia major is a common hereditary haematological disease in southern Chinese. Advances in transfusion and iron chelation improve survival but haematopoietic stem cell transplantation (HSCT) is still the only curative treatment. Due to repeated blood transfusion and iron overload, thalassaemia patients undergoing HSCT are at a higher risk of graft rejection and transplant-related mortality. The prognostic factors identified to be affecting transplant outcome include hepatomegaly, hepatic fibrosis, and compliance to chelation therapy. Patients can be classified into three classes and conditioning regimens are modified according to the risk. Early stage patients have 85 to 90% chance of disease-free survival, whereas advance stage only has 60% disease-free survival. Mixed chimerism is common after HSCT but majority have satisfactory erythropoiesis without need for further transfusion. Sibling cord blood and bone marrow transplantation has similar outcome. Recently alternative donor transplant has been performed in patients without human leukocyte antigen (HLA)-identical siblings. The result of unrelated-donor bone marrow transplantation is in general inferior but extended HLA matching may improve outcome. The use of unrelated cord blood transplant from a single-centre study showed promising result. The survivors require iron depletion to remove excessive iron store and some may require hormonal replacement therapy. Most of the patients have good quality of life after successful HSCT.

Biofeedback exercise improved the EMG activity ratio of the medial and lateral vasti muscles in subjects with patellofemoral pain syndrome.

Patellofemoral pain syndrome (PFPS) is usually due to weakness of vastus medialis obliquus (VMO) resulting in abnormal patellar tracking. One of the objectives of rehabilitation is to strengthen the VMO so as to counterbalance the vastus lateralis (VL) action during normal activities. This study compared the effects of an 8-week exercise program with and without EMG biofeedback on the relative activations of VMO and VL. Twenty-six subjects with PFPS were randomly allocated into an "exercise" group (Group 1) and a "biofeedback+exercise" group (Group 2). Both groups performed the same exercise program but subjects in Group 2 received real time EMG biofeedback information on the relative activations of VMO and VL during the exercises. After 8 weeks of training, Group 1 had insignificant changes in their VMO/VL EMG ratio (p=0.355), whereas Group 2 had significantly greater VMO/VL EMG ratio (p=0.017) when performing normal activities throughout a 6-h assessment period. The present result reveals that the incorporation of an EMG biofeedback into a physiotherapy exercise program could facilitate the activation of VMO muscle such that the muscle could be preferentially recruited during daily activities.

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.

Bone marrow transplantation for beta-thalassaemia major by an HLA-mismatched parent.

A six-year-old boy was diagnosed with beta-thalassaemia major during infancy. Since then, he required monthly blood transfusion and irregular iron chelation therapy. He had hepatosplenomegaly and elevated liver enzymes; the serum ferritin was up to 3800 ng/mL. An echocardiogram showed left-ventricular enlargement. His one-antigen-mismatched mother was chosen as a bone marrow donor. He was pretreated with intensive red blood cell transfusion and hydroxyurea for 6 weeks prior to conditioning. The conditioning included total body irradiation (300 cGy), busulfan (14 mg/kg), cyclophosphamide (160 mg/kg) and anti-thymocyte globulin (rabbit; 90 mg/kg). Marrow cell dose was 5.4 x 108/kg. Graft versus host disease (GVHD) prophylaxis included cyclosporine A (CSA) and methylprednisolone. Neutrophil engraftment occurred on day 23. Grade II acute GVHD occurred on day 45. The patient developed complications including septicaemia, haemorrhagic cystitis, intracranial haemorrhage and heart failure. He subsequently recovered from the complications without sequelae. The patient remained transfusion-independent at a follow-up examination after 18 months. This case suggested that a mismatched family member may be considered as a bone marrow donor for beta-thalassaemia major. In places where conventional treatment is not feasible, for example, in China, this approach may be an alternative option. A more intensive immunosuppressive regimen and a higher marrow cell dose may be important for successful engraftment. High-dose anti-thymocyte globulin may also prevent severe GVHD.

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.

Deferoxamine-induced dysplasia of the knee: sonographic features and diagnostic performance compared with magnetic resonance imaging.

OBJECTIVE: To evaluate the features and diagnostic performance of sonography in the assessment of deferoxamine-induced dysplasia of the knee. METHODS: The left knees of 32 patients with thalassemia who were receiving regular blood transfusions and chelation therapy were studied with sonography for signs of deferoxamine-induced bone dysplasia. Abnormal physeal and metaphyseal changes detected on sonography included notching at the metaphyseal corner, a blurred or irregular peripheral juxtaphyseal metaphyseal contour, and widening of the peripheral juxtaphyseal metaphyseal echogenic interface. The accuracy of sonography in diagnosing dysplasia was evaluated by using magnetic resonance imaging as the standard of reference. RESULTS: There were 14 true-positive findings, 10 true-negative findings, 7 false-negative findings, and 1 false-positive sonographic diagnosis of dysplasia, giving 67% sensitivity, 91% specificity, a 93% positive predictive value, and a 59% negative predictive value. CONCLUSION: Sonography was specific but only moderately sensitive in the diagnosis of deferoxamine-induced dysplasia at the knee when compared with magnetic resonance imaging.

Desferrioxamine-induced long bone changes in thalassaemic patients - radiographic features, prevalence and relations with growth.

AIM: To study the radiographic findings of desferrioxamine-induced bone dysplasia, its prevalence and relation to growth in thalassaemic patients. MATERIALS AND METHODS: A cross-sectional study was performed in 35 thalassaemic patients on a hypertransfusion scheme and chelation therapy at a dose not exceeding 50 mg/kg/day. Radiographs of the left hand taken for bone age assessment in consecutive patients over the past 12 months were evaluated for signs of desferrioxamine-induced bone dysplasia. The findings were correlated with data on growth, chelation and body iron content. RESULTS: Twelve of 35 patients had evidence of desferrioxamine-induced long bone dysplasia. There was no significant difference in the groups with and without radiographic evidence of bone dysplasia with respect to the height percentile at time of initiation of therapy, height percentile at time of radiography, skeletal age delay, age at starting chelation, chelation dose and duration, units of blood transfused, average chelation dose, and serum ferritin levels at time of radiography. Both groups showed a reduced percentile growth with a significantly greater reduction (P = 0.03) in the patients with dysplastic change. CONCLUSION: Desferrioxamine-induced bone dysplasia is associated with height reduction and can be seen in patients receiving desferrioxamine chelation therapy at doses of less than 50 mg/kg/day. Awareness of the diagnosis is of importance as reduction of the desferrioxamine dose may improve bone growth.

Incidence, risk factors and outcome of varicella-zoster virus infection in children after haematopoietic stem cell transplantation.

We report a retrospective analysis of VZV infection after haematopoietic stem cell transplantation (HSCT) in children. Thirty-three (30%) of the total 109 children who were transplanted during a 7 year period developed post-transplant VZV infection. Twenty-four of these 33 (73%) children had VZV infection within 1 year following HSCT. The cumulative incidences of post-transplant VZV infection at 1 and 5 years were 26% and 45%, respectively. The positive and negative predictive values of pretransplant VZV serology in recipients on the development of HZ following HSCT were 39% and 88%, respectively. Pretransplant VZV seropositivity in recipients was the only risk factor for post-transplant herpes zoster (HZ) infection on multivariate analysis. All patients responded to acyclovir. The median duration of VZV infection was 5 days. Three (11%) and one (3%) children with HZ developed visceral dissemination and post-herpetic neuralgia, respectively. No mortality was directly attributed to VZV infection. VZV infection remains a major cause of morbidity in children after HSCT. Further studies are warranted to evaluate the potential use of VZV vaccine in these children. Bone Marrow Transplantation (2000) 25, 167-172.

Routine analysis of plasma busulfan by gas chromatography-mass fragmentography.

Busulfan (BU) is a widely used alkylating agent for antineoplastic therapy and marrow ablation in preparation for bone marrow transplantation (BMT). High-dose BU often leads to successful preparation and low relapse but is associated with veno-occlusive disease of liver. We established a protocol to determine postdosage plasma BU concentrations by gas chromatography-mass fragmentography in an attempt to relate clinical outcome to plasma BU concentrations. We used nonisotopic pusulfan as the internal standard. After extraction into ethyl acetate, BU and pusulfan were iodinated into 1, 4-diiodobutane and 1,5-diiodopentane, respectively. Gas chromatography-mass spectrometry (GC-MS) analysis was carried out on an Hewlett-Packard (HP) 5890II gas chromatograph with a 30-m 100% methyl silicon narrow bore, fused-silica capillary column interfaced with an HP 5970A mass spectrometer. Helium was the carrier gas. The sample molecules were identified by total ion monitoring and quantified by selective ion monitoring of m/z 183 and 197. The calibration curve was linear to 4 mg/L. The limit of quantification was 0.04 mg/L, and the analytical recovery was approximately 97%. The within-day and between-day imprecision (CV) was <6% and 9%, respectively. In a preliminary study of 12 children, the BU areas under the BU-time curve were 616-949 micromol. min/L after the first dose and 793-1143 micromol. min/L after the fifth dose. We conclude that the GC-MS procedure is suitable for routine analysis of plasma BU.

Magnetic resonance imaging evaluation of the pituitary gland and hypothalamus in thalassaemic children with elevated serum ferritin levels.

OBJECTIVE: Despite modern treatment with hypertransfusion and chelation therapy, growth retardation continues to be observed in a significant proportion of thalassaemic children. The underlying reason remains unclear, but hypothalamic-pituitary axis disorder has been implicated. We aimed to assess iron overloading in the hypothalamus and pituitary gland in thalassaemic children with elevated serum ferritin, with and without growth retardation. METHODOLOGY: Twelve thalassaemic children on hypertransfusion and chelation therapy with high serum ferritin were investigated with magnetic resonance imaging (MRI). Five children, all over 10 years of age, had growth retardation. Gradient recalled echo sequence was used to highlight any susceptibility effect that could be due to iron in the hypothalamus or pituitary gland. RESULT: There was no evidence of abnormal hypointense signal in the hypothalamus or pituitary gland in the patients studied, regardless of the presence of growth retardation. CONCLUSION: There was no apparent characteristic MRI appearances of iron deposition in the hypothalamus or pituitary gland in thalassaemic children with high serum ferritin.

[Qualitative analysis of Chinese drug xiakucao (Prunella)].

A high performance gas chromatographic procedure has been developed for the quantitation of ursolic acid and oleanolic acid in different parts of Xiakucao collected in different periods. The study provides a scientific foundation for increased availability and rational collecting periods of Xiakucao.

[Immunological change in pigmentary degeneration of retina and its relation to traditional Chinese medicine differentiation of syndromes].

Using monoclonal antibody technique, T lymphocyte cell subgroups, immunoglobins, complements, and circulating immune complexes (CIC) were measured in 60 patients with pigmentary degeneration of retina (RP) and 40 normal subjects. The results indicated that T1, T4, T8, C3 and C4 of the patients were lower than those of the controls; T4/T8, IgM and CIC of the patients were more than those of the controls. The differences between the patients and the controls were remarkably significant. Similarly, by investigating the objective quota of TCM differentiation of syndromes, the authors divided the RP patients into Liver-Kidney deficiency of Yin and Spleen-Kidney deficiency of Yang groups, and compared them with normal subjects. The results indicated that the two groups underwent similar change of immunology. But they had their own characteristics. The Yin-deficiency group showed remarkable increase of T4/T8 and normal T4; the Yang-deficiency group showed remarkable reduction of T1 and reduction of T4.

[Acupuncture to alleviate pain during colonoscopy]. / Akupunktur zur Schmerzlinderung bei Koloskopie.

36 patients (18 males and 18 females, mean age 51 [21-76] years) were prepared for colonoscopy with acupuncture (points: Hegu, Neiguan, Zusanli and Gongsun bilaterally), without acupuncture or pretend acupuncture at points not expected to bring about pain relief. In the 12 acupuncture patients mean pain sensitivity, estimated during the examination by means of a visual analog scale, was significantly (P = 0.003) lower (1.4 +/- 0.4) than in the groups without acupuncture (n = 12; 2.7 +/- 0.3) or pretend acupuncture (n = 12; 3.0 +/- 0.3). In addition, analgesics and sedatives needed to be given significantly less to those with acupuncture (one patient each; P = 0.005) than those without (analgesics to five, sedatives to eight patients) or with pretend acupuncture (analgesics to four, sedatives to five patients). These data demonstrate that pain connected with colonoscopy can be reduced by preceding acupuncture.

Increased sarcolemmal membrane permeability of cardiac muscle cells in rats fed grains cultivated in a Keshan disease endemic area: a study with horseradish peroxidase as a tracer.

The alteration of sarcolemmal membrane permeability of cardiac muscle cells in rats fed grain from a Keshan disease (KD) endemic area was studied with horseradish peroxidase (HRP) as a tracer. Weanling male rats were divided at random into three groups and fed the following three diets, respectively, for 3 months: a diet with grain from a KD endemic area (Group A), a diet with grain from a KD nonendemic area (Group B), and standard laboratory chow (Group C). At the end of the experiment, HRP was injected intravenously and localized in the ventricular myocardium by light microscopy. The experimental results showed that the percentage of cardiac muscle cells containing HRP reaction product in rats fed grain from the KD endemic area was significantly greater than that in rats fed grain from nonendemic area and standard laboratory chow. This suggests that the sarcolemmal membrane permeability of cardiac muscle cells in rats of Group A was markedly increased. The distribution of cardiac muscle cells with increased sarcolemmal membrane permeability was similar to that seen in the myocardium of KD patients. The present study suggests that the abnormal membrane permeability of cardiac muscle cells may play an important role in the pathogenesis of myocardial necrosis in KD.