Clinical characteristic and management of haemophilia patients in Malaysia: A single centre experience.

INTRODUCTION: Haemophilia is one of the commonest inherited bleeding disorders which may lead to long term disabilities if not treated properly. Our aim of study is to understand the clinical characteristic, treatment and complications of adult haemophilia patients in our centre. MATERIALS AND METHODS: A retrospective cross-sectional review of all adult haemophilia A (HA) or haemophilia B (HB) patients who received treatment in Hospital Pulau Pinang from January 2021 to December 2022 was conducted. Data was retrieved from patients' medical records. RESULTS: A total of 75 haemophilia patients (64 HA and 11 HB) were included in this study with median age of 37 years (range 19 70). 42 of them had severe haemophilia (50% of HA, 91% of HB). All HB and 93.8% of severe HA patients were on prophylaxis. Six severe and one mild HA patients developed inhibitor with four of them currently on non-factor prophylaxis. 24 patients (32%) had prior hepatitis C infection and all of them have been successfully treated. The mean annual bleeding rate for severe haemophilia patients were 1.77 (SD ±3.6). Target joints were observed in 9.3% of patients with ankle joint (71.4%) being the most affected joint. More than one quarter (26.7%) of our patients have comorbidities with majority of them having hypertension (17/20), followed by diabetes mellitus (5/20) and ischemic heart disease (5/20). CONCLUSION: Our study showed that a significant number of adult patients with haemophilia have comorbidities. Apart from optimising factor replacement therapy, future planning should include improvement in screening, risk modification and prevention of cardiovascular disease.

High prevalence of central hypothyroidism among patients with transfusion dependent thalassemia in Hospital Pulau Pinang: A cross sectional study.

INTRODUCTION: Thalassemia is the most common heritable haematological disorder in Malaysia. Hypothyroidism is one of the complications of the transfusion dependent thalassemia (TDT) patients as a result of iron overload. MATERIALS AND METHODS: All registered TDT patients attending Haematology day care, Hospital Pulau Pinang from January 2019 to January 2020 were included in the study. Hypothyroidism was defined according to TSH and FT4, or based on the history of treatment for diagnosed hypothyroidism. RESULTS: There were 51 TDT patients, with 24 (47%) males and 27 (53%) females. Most of the patients were Malays (27, 53%) followed with Chinese (23, 45%) and Indonesian (1, 2%). Beta thalassemia major and HbE beta thalassaemia accounted for 35 (68.8%) and 14 (27.5%) TDT patients respectively, while two (3.9%) were HbH Constant Spring. Eleven (21.6%) had hypothyroidism; of which seven (63.6%) had central hypothyroidism, three (27.3%) had subclinical hypothyroidism, the remaining one (9.1%) had primary hypothyroidism. Three (27.3%) had concomitant hypogonadism, one (9.1%) had hypocortisolism and another (9.1%) had both diabetes mellitus and hypogonadism. There was no statistical relationship between the prevalence of hypothyroidism and age, serum ferritin, splenectomy history and iron chelation therapy. CONCLUSION: High prevalence of central hypothyroidism is reported. Measurement of both TSH and FT4 is recommended as initial screening for thyroid dysfunction among patient with TDT.

Prevalence of endocrine complications in transfusion dependent thalassemia in Hospital Pulau Pinang: A pilot study.

INTRODUCTION: Frequent blood transfusions results in iron overload and lead to multiple endocrine complications. In spite of improvements in iron chelation therapy, a significant number of transfusion dependent thalassaemia (TDT) patients still develop endocrine complications. The aim of this study is to evaluate the prevalence of various endocrine complications in our adult TDT patients and to study the correlation with serum ferritin and liver iron concentration (LIC). METHODS: A retrospective review of all TDT patients treated in Haematology Unit, Hospital Pulau Pinang (HPP) was conducted. RESULTS: Of the 45 adult TDT patients, 22 were males and 23 were females with mean age of 28.8±6.9 years old. Majority of TDT in HPP were beta thalassemia major (71.1%), followed by E-Beta thalassemia (24.4%) and HbH-Constant Spring (4.4%). Frequency of transfusion was 3-4 weekly. 40.0% of adult TDT suffered from at least one endocrine complication. Among the adult TDT patients with endocrine complication, 50% have one endocrinopathy, 38.9% with two types of endocrinopathies and 11.1% of them have three or more types of endocrinopathies. Hypogonadism (22.2%) was the commonest endocrine complication, followed by osteoporosis (20%), hypothyroidism (13.3%), diabetes mellitus (6.7%) and hypocortisolism (4.4%). Patients with endocrine complications were significantly older. Mean serum ferritin level and LIC was higher among patients with endocrine complications but both were not statistically significant. CONCLUSION: Endocrinopathy is still prevalent in 40% of adult TDT patients. This leads to higher health-care resource utilization, cost and significant morbidities among patients with TDT. Therefore, regular monitoring and early detection with intensification of chelation therapy is essential.

Adjuvant hepatic intra-arterial iodine-131-lipiodol following curative resection of hepatocellular carcinoma: a prospective randomized trial.

BACKGROUND: The purpose of the present study was to determine whether intrahepatic injection of (131)I-lipiodol (Lipiodol) is effective against recurrence of surgically resected hepatocellular carcinoma (HCC). METHODS: From June 2001 through March 2007, this nationwide multi-center prospective randomized controlled trial enrolled 103 patients 4-6 weeks after curative resection of HCC with complete recovery (52: Lipiodol, 51: Control). Follow-up was every 3 months for 1 year, then every 6 months. Primary and secondary endpoints were recurrence-free survival (RFS) and overall survival (OS), respectively, both of which were evaluated by the Kaplan-Meier technique and summarized by the hazard ratio (HR). The design was based on information obtained from a similar trial that had been conducted in Hong Kong. RESULTS: The Lipiodol group showed a small, and nonsignificant, improvement over control in RFS (HR = 0.75; 95 % confidence interval [95 % CI] 0.46-1.23; p = 0.25) and OS (HR = 0.88; 95 % CI 0.51-1.51; p = 0.64). Only two serious adverse events were reported, both with hypothyroidism caused by (131)I-lipiodol and hepatic artery dissection during angiography. CONCLUSIONS: The randomized trial provides insufficient evidence to recommend the routine use of (131)I-lipiodol in these patients.

Endocrine complications in transfusion dependent thalassaemia in Penang Hospital.

Frequent blood transfusions can lead to iron overload which may result in several endocrine complications especially in the absence of adequate chelation therapy. The objectives of this study are to determine the prevalence of endocrine complications in transfusion dependent thalassaemia patients and the correlation of endocrine complications with the degree of iron chelation. This retrospective study looked at cases of adult patients with transfusion dependent thalassaemia treated in the Haematology Unit, Penang Hospital. Of the 25 transfusion dependent thalassaemia patients, there were 10 male and 15 female patients respectively with almost equal number of Malay and Chinese patients (13 and 12 patients respectively). Short stature was seen in 36.0% of our patients. In our cohort, 12 patients had delayed puberty (male 70.0% and female 33.3%). Prevalence of osteoporosis was 36.0%. Hypogonadism was noted in 40.0% of males and 46.7% of females. 53.4% of the female population had menstrual abnormalities with prevalence of primary and secondary amenorrhoea at 26.7% each. The prevalence of other endocrinopathies was much lower: 8.0% had diabetes mellitus and only one patient had hypocortisolism. Iron chelation appeared insufficient in our study population. The high frequency of endocrine complications noted in our study supports the rationale for regular follow-up of transfusion dependent thalassaemic patients to ensure early detection and timely treatment of associated complications.

Upper airway dilating forces during wakefulness and sleep in dogs.

We measured the pressure within an isolated segment of the upper airway in three dogs during wakefulness (W), slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Measurements were taken from a segment of the upper airway between the nares and midtrachea while the dog breathed through a tracheostoma. These pressure changes represented the sum of respiratory-related forces generated by all muscles of the upper airway. The mean base-line level of upper airway pressure (Pua) was -0.5 +/- 0.03 cmH2O during W, increased by a mean of 2.1 +/- 0.2 cmH2O during SWS, and was variable during REM sleep. The mean inspiratory-related phasic change in Pua was -1.2 +/- 0.1 cmH2O during wakefulness. During SWS, this phasic change in Pua decreased significantly to a mean of -0.9 +/- 0.1 cmH2O (P less than 0.05). During REM sleep, the phasic activity was extremely variable with periods in which there were no fluctuations in Pua and others with high swings in Pua. These data indicate that in dogs the sum of forces which dilate the upper airway during W decreases during SWS and REM sleep. The consistent coupling between inspiratory drive and upper airway dilatation during wakefulness persists in SWS, but is frequently uncoupled during REM sleep.

99Tcm-(tin) colloid scans in the evaluation of renal transplant rejection.

Technetium-99m-(tin) colloid uptake in renal transplants was quantified to evaluate rejection. A dynamic acquisition following i.v. injection of 110 MBq of this radiopharmaceutical enabled quantification of 15 to 20 min transplant uptake (PU), in terms of percentage of an injected dose after allowing for attenuation in the patient. An uptake ratio (UR) i.e. the ratio of 15 to 20 min uptake over the 0 to 5 min uptake was also derived. Normal values were obtained in 20 stable functioning transplants (normal PU less than or equal to 1%, normal UR less than or equal to 0.7). In 66 patients, PU and UR were compared with clinical, biochemical, histological and radiological, evidence of rejection. A sensitivity of 70% and specificity of 85% was obtained for this 99Tcm-(tin) colloid study in the diagnosis of renal transplant rejection.

99Tcm-polyclonal IgG and 99Tcm nanocolloid scans in orthopaedics: a comparison with conventional bone scan.

The bone scan is sensitive in detection of active bone/joint lesions. A normal bone scan virtually excludes the presence of an inflammatory process with high precision, but the poor specificity of bone scans is well known. In recent years, various new agents including 99Tcm-hexamethylpropylene amine oxime (HMPAO)-labelled white blood cells, nanocolloid, polyclonal IgG, anti-granulocyte antibody, 111In-labelled IgG, leucocytes, chemotactic peptides etc. have been widely evaluated in inflammatory imaging, especially in the orthopaedic context. This study was undertaken to compare the usefulness of 99Tcm-nanocolloid and 99Tcm-polyclonal IgG in the detection of focal bone/joint inflammation. Twenty-seven patients with a common presentation of bone/joint pain resulting from various pathologies were included in the study. A total of 47 lesions were imaged. The overall sensitivity and specificity of both nanocolloid scan and IgG scan were identical with 95% sensitivity and 100% specificity, in detecting inflammatory foci. However, specificity dropped to 18% with nanocolloid scans and 16% with IgG scans when an attempt was made to distinguish noninfective from infective inflammatory processes; thus neither type of scan permits differentiation between septic and nonseptic inflammatory processes with sufficient accuracy. As both nanocolloid and IgG scans are equally sensitive and specific in detecting inflammation, the choice of type of scan will depend on cost, imaging time and availability of the radiopharmaceutical.

Single institution's initial experience with sentinel lymph node biopsy in breast cancer patients.

BACKGROUND: The sentinel lymph node is the first draining node from a cancer-bearing area and is therefore the first to manifest metastasis. In breast cancer it has been shown to predict the axillary status. Axillary dissection provides information determining prognosis and need for adjuvant therapy but carries a certain morbidity. Our aim was to determine the feasibility of detecting the sentinel node in a teaching hospital and whether the sentinel node accurately predicts the axillary status. METHODS: All patients with stage I and II breast cancer and non-palpable axillary nodes were eligible, including those with previous excision biopsy. We excluded pregnant women, those with previous axillary surgery and women with advanced breast cancer with enlarged axillary nodes. The sentinel node was detected with technetium-99m-labelled tin colloid and vital blue dye and removed, and axillary clearance was performed. RESULTS: A total of 312 patients were examined from August 1996 to December 1998. The mean age was 53 years (range 28-83) and mean tumour size 2.6 cm (range 0.2-9.0). The detection rate of the sentinel node was 86%. The sentinel lymph node predicted the axillary status with a sensitivity of 83% and specificity of 100%. The false-negative rate was 16.7%. CONCLUSIONS: Detection of the sentinel lymph node is feasible and it can accurately predict the nodal status of the axilla. However, the high false-negative rate precludes as yet the use of sentinel lymph node biopsy in replacing axillary clearance as the standard of care for breast cancer.

Radionuclide imaging in primary hyperparathyroidism using 99mTc sestamibi--four case reports.

Radionuclide imaging using the 99mTc sestamibi either singly or as a subtraction technique with pertechnetate is a recent and reliable method in localising parathyroid adenomas prior to surgery. This is of use in pre-operative planning, as well as in failed first neck exploration. Four local patients with primary hyperparathyroidism whose parathyroid adenomas were localised by this scintigraphy are presented. The value and limitations of this imaging modality are discussed.

Intermediate probability lung scans (IPLS): retrospective review of 82 cases.

OBJECTIVE: In the light of a reported 30-40% prevalence of pulmonary embolism (PE) in intermediate probability lung scans (IPLS) based on results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study, we examined the frequency of documented PE in 82 patients with IPLS, the management strategy employed in these patients with regards to additional imaging (e.g. further evaluation with venous sonography or spiral computed tomographic angiography (CTA)), anticoagulation therapy, and subsequent follow-up outcomes. METHOD: Retrospective review of the medical records of 82 patients with intermediate probability ventilation-perfusion (V/Q) lung scans from January 1998 to July 1999. RESULTS: 14.1% of V/Q scans were reported as having an intermediate probability of PE. 72% of IPLS were subject to further evaluation with venous Doppler ultrasound and/or CTA, and 39% of these patients had evidence of thrombo-embolic disease. All patients with imaging evidence of thromboembolic disease were started on anticoagulation therapy. In addition, 19 patients were treated based on clinical judgement. Amongst the 35 patients who were not treated, 17 (49%) were based on clinical findings without further imaging. There was no mortality on follow-up of 28 cases of untreated IPLS. CONCLUSION: The majority of IPLS will have further imaging, out of which over one-third will have thrombo-embolic disease. Approximately half of IPLS cases will receive anticoagulation therapy. No mortality or PE was found on follow-up of patients who were not treated.

Case report of a parathyroid adenoma demonstrated by dual tracer (T1-201 and Tc-99m) subtraction scan.

It is generally agreed that the Technetium-Thallium Subtraction Scan is a reliable method for locating abnormal parathyroid glands in patients with clinical and biochemical evidence of parathyroid hyperactivity. This report illustrates the value of scintigraphy in diagnosis and in the subsequent surgical management of a patient with primary hyperparathyroidism.

Clinical positron emission tomography imaging--current applications.

Positron emission tomography (PET) is an established imaging technique based on the use of short-lived radiotracers. The unique value of PET lies in the ability of various radiochemical compounds to serve as tracers for measuring specific metabolic processes in the body. This enables detection of the early biochemical anomalies that precede the structural changes seen on other imaging techniques. For decades, PET had remained essentially a research tool in academic institutions. However, in recent years, it has emerged as a vital clinical tool, particularly for cancer diagnosis and management. In this era of evidence-based medicine, the clinical applications of PET imaging have been subjected to intense evaluation, and its roles in oncology, neurology and cardiology have dominated nuclear medicine research and scientific publications in the past 5 to 8 years. This review article summarises the present status of the major clinical indications for PET scanning. The field is rapidly evolving and, with the recent advent of hybrid PET-CT scanners, new data continue to emerge, refining these clinical applications. Another important area of ongoing research is the development of new radio-labelled compounds for PET imaging.

Radionuclide bone imaging in patients with low back pain presenting to the orthopaedic surgeon.

This study looks retrospectively at 113 patients with low back pain referred by orthopaedic surgeons for bone scanning. 79 scans (70%) were reported normal and 34 scans (30%) abnormal. 61 out of the 79 patients with normal scans were diagnosed and managed as "chronic back strain". Negative bone scans were also encountered in 3 patients with degenerative disease, 3 with prolapsed intervertebral disc and one with spondylolysis. In those patients with positive scans, a varied range of diagnoses was encountered, the main ones being bone metastases, previous trauma, osteomyelitis and degenerative disease. The scan was shown to be helpful in deciding on the presence or absence of pathology, and in identifying the sites of involvement, but not the nature of the disease. A higher likelihood of positivity is seen in the more elderly patients as well as those below 20 years of age. In interpreting the scan, the clinical context is important e.g. a history of trauma, previous surgery or of malignant disease. The bone scan may be normal in disc prolapse and in degenerative disease of the spine.

99mTechnetium(V) dimercaptosuccinic acid (99mTc(v) DMSA) as a tumour seeking agent in nasopharyngeal carcinoma.

We prepared 99mTechnetium(V) DMSA (pentavalent form) as an imaging agent for eighteen patients with proven nasopharyngeal carcinoma. The head, neck, chest and abdomen were scanned. The nasopharyngeal tumour showed tracer accumulation in only 5 out of the 18 patients (28%). The study indicates that 99mTechnetium(V) DMSA is not a useful radiopharmaceutical for visualising nasopharyngeal tumours although it may have other useful properties.

Role of technetium-99m sestamibi in localisation of thyroid cancer metastases.

Technetium-99m sestamibi (MIBI) is a routinely used myocardial perfusion imaging agent. We have studied groups of patients with differentiated thyroid carcinoma, in order to evaluate the usefulness of this agent in localising regional neck and nodal disease and metastases. There are three groups of patients. Group 1 consisted of patients with known nodal disease or metastases (22 patients) and with raised serum thyroglobulin levels (Tg). Group 2 comprised patients with normal I-131 scans and normal Tg levels (nine patients). Non-thyroid malignancies (six patients) comprised an additional group 3. In group 1, the MIBI scan showed 47 sites of metastases, while the I-131 scan revealed 49 sites. The MIBI scan was positive in two patients where the I-131 scan was negative, while in two other patients, the MIBI study was negative whereas the I-131 scan was positive. In group 2, 6/9 patients had no disease, 2/9 had thyroid remnants, and 1/9 had a fresh primary lung tumour, unrelated to the earlier thyroid cancer. All of them had normal MIBI scans. In group 3, two patients with lung cancer and two with breast cancer and metastases had normal MIBI scans. A further two patients with nasopharyngeal cancer (NPC) had mildly increased MIBI localisation in neck nodes and bone metastases. In summary, Tc-99m sestamibi appears to be as good as I-131 in search for thyroid carcinoma metastatic spread, especially nodal disease and this tracer does not localise well in the primary or metastases of other cancers.(ABSTRACT TRUNCATED AT 250 WORDS)

Nuclear cardiology in the detection of coronary artery disease--an overview of its role in the Singapore General Hospital.

Nuclear cardiology at the Singapore General Hospital (SGH) had a humble beginning in 1983 when it was carried out by the joint staff of the departments of cardiology and nuclear medicine. At the onset the bulk of the scans were blood pool studies. In 1984, qualitative tomographic myocardial perfusion studies replaced the less accurate planar scans and this was carried out on a routine basis. Its superiority to conventional exercise electrocardiography in the detection, management and prognostication of coronary artery disease (CAD) has since been validated locally. We have since progressed to the fields of research involving pharmacological stress testing with intravenous dipyridamole and use of technetium-based isonitrile as an alternative to the conventional myocardial perfusion agent, thallous chloride. Our results mirror those from other research centres. On this encouraging note we are looking into newer areas such as the role of diastolic function for early detection of cardiac disease. In under a decade we are in a position to provide scintigraphic service expected of an established nuclear cardiac laboratory. This article provides an overview of our work in the management of CAD.

Nuclear medicine--an overview.

A radioactive isotope behaves chemically and biologically like its non-radioactive counterpart. The application of this principle to medical diagnosis has evolved into a whole specialty called nuclear medicine. The development of the rectilinear scanner and gamma camera has extended the study of molecular pathways into an exciting imaging modality while developments in radiopharmaceuticals have made radionuclide imaging of many organ systems widely available. The most significant improvements have occurred in bone, hepatobiliary and cardiac imaging. Today, however, nuclear medicine is evolving into a more dynamic study of physiological processes in the body and how these processes may be affected by disease and medical treatment. Emission tomography with a new generation of both gamma and positron emitters will be integral part of nuclear medicine in the future. The challenge to develop radio-labelled antibodies for immunotherapy and immunodetection remains while many of the older techniques like radioimmunoassay, and even the simple colloid liver scan, will continue to contribute significantly to health care.

Hepatobiliary scintigraphy in the diagnosis of biliary atresia--a Singapore experience.

In recent years, 99mTechnetium IDA hepatobiliary scintigraphy has been widely accepted as a highly sensitive and fairly accurate test in the diagnosis of biliary atresia and evaluation of neonatal jaundice. Over a period of 4 years from 1982 to 1986, a total of 110 paediatric patients had undergone 99mTechnetium IDA hepatobiliary scans in our department for prolonged neonatal jaundice. Their scans were reviewed to evaluate the role of this nuclear imaging technique in the diagnosis of biliary atresia. There were 43 true positive and 49 true negative scans. No false negative scan was encountered in our study. Hence the sensitivity was 100%. However, out of the 110 scans, there was misdiagnosis of biliary atresia in 18 cases. This gave a specificity of 73% with an accuracy of 84%. From this study we concluded that 99mTechnetium IDA imaging is a highly sensitive test in the screening of biliary atresia. However, its specificity is possibly limited by the short half life of the radioisotope 99mtechnetium in delayed 24 hr imaging and we feel that this could be improved by using slightly higher doses than what we are presently using.

Radionuclide measurement of liquid and solid gastric emptying in normal subjects in Singapore.

Scintigraphic methods for liquid and solid gastric emptying were utilised to study normal patterns in 21 volunteers. Of these, 19 had solid emptying studies and 14 had liquid emptying studies. The liquid study lasted 1/2 hour, while the solid study was for 1 hour. The gastric emptying half-time (T 1/2), as well as percentage retention at 15 minutes (liquids), and at 60 minutes (for solids) were noted. The time-activity curves were also corrected for tissue attenuation. Results indicated normal average liquid emptying T 1/2 to be 14.2 minutes, while that for solids was 116 minutes.