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The integration of microarray technologies and machine learning methods has become popular in predicting the pathological condition of diseases and discovering risk genes. Traditional microarray analysis considers pathways as a simple gene set, treating all genes in the pathway identically while ignoring the pathway network's structure information. This study proposed an entropy-based directed random walk (e-DRW) method to infer pathway activities. Two enhancements from the conventional DRW were conducted, which are (1) to increase the coverage of human pathway information by constructing two inputting networks for pathway activity inference, and (2) to enhance the gene-weighting method in DRW by incorporating correlation coefficient values and t -test statistic scores. To test the objectives, gene expression datasets were used as input datasets while the pathway datasets were used as reference datasets to build two directed graphs. The within-dataset experiments indicated that e-DRW method demonstrated robust and superior performance in terms of classification accuracy and robustness of the predicted risk-active pathways compared to the other methods. In conclusion, the results revealed that e-DRW not only improved the prediction performance, but also effectively extracted topologically important pathways and genes that were specifically related to the corresponding cancer types.

Background: In Singapore, research teams seek informed patient consent on an ad hoc basis for specific clinical studies and there is typically a role separation between operational and research staff. With the enactment of the Human Biomedical Research Act, there is increased emphasis on compliance with consent-taking processes and research documentation. To optimize resource use and facilitate long-term research sustainability at our institution, this study aimed to design and pilot an institution level informed consent workflow (the "intervention") that is integrated with clinic operations., Methods: We used the Consolidated Framework for Implementation Research (CFIR) as the underpinning theoretical framework and conducted the study in three stages: Stage 1, CFIR constructs were used to systematically identify barriers and facilitators of intervention implementation, and a simple time-and-motion study of the patient journey was used to inform the design of the intervention; Stage 2, implementation strategies were selected and mapped to the Expert Recommendations for Implementing Change (ERIC) taxonomy; Stage 3, we piloted and adapted the implementation process at two outpatient clinics and evaluated implementation effectiveness through patient participation rates., Results: We identified 15 relevant CFIR constructs. Implementation strategies selected to address these constructs were targeted at three groups of stakeholders: institution leadership (develop relationships, involve executive boards, identify and prepare champions), clinic management team (develop relationships, identify and prepare champions, obtain support and commitment, educate stakeholders), and clinic operations staff (develop relationships, assess readiness, conduct training, cyclical tests of change, model and simulate change, capture and share local knowledge, obtain and use feedback). Time-and-motion study in clinics identified the pre-consultation timepoint as the most appropriate for the intervention. The implementation process was adapted according to clinic operations staff and service needs. At the conclusion of the pilot, 78.3% of eligible patients provided institution level informed consent via the integrated workflow implemented., Conclusions: Our findings support the feasibility of implementing an institution level informed consent workflow that integrates with service operations at the outpatient setting to optimize healthcare resources for research. The CFIR provided a useful framework to identify barriers and facilitators in the design of the intervention and its implementation process., (© 2023. The Author(s).)

Numerous cancer studies have combined different datasets for the prognosis of patients. This study incorporated four networks for significant directed random walk (sDRW) to predict cancerous genes and risk pathways. The study investigated the feasibility of cancer prediction via different networks. In this study, multiple micro array data were analysed and used in the experiment. Six gene expression datasets were applied in four networks to study the effectiveness of the networks in sDRW in terms of cancer prediction. The experimental results showed that one of the proposed networks is outstanding compared to other networks. The network is then proposed to be implemented in sDRW as a walker network. This study provides a foundation for further studies and research on other networks. We hope these finding will improve the prognostic methods of cancer patients.

Microarray technology has become one of the elementary tools for researchers to study the genome of organisms. As the complexity and heterogeneity of cancer is being increasingly appreciated through genomic analysis, cancerous classification is an emerging important trend. Significant directed random walk is proposed as one of the cancerous classification approach which have higher sensitivity of risk gene prediction and higher accuracy of cancer classification. In this paper, the methodology and material used for the experiment are presented. Tuning parameter selection method and weight as parameter are applied in proposed approach. Gene expression dataset is used as the input datasets while pathway dataset is used to build a directed graph, as reference datasets, to complete the bias process in random walk approach. In addition, we demonstrate that our approach can improve sensitive predictions with higher accuracy and biological meaningful classification result. Comparison result takes place between significant directed random walk and directed random walk to show the improvement in term of sensitivity of prediction and accuracy of cancer classification.

This is a retrospective review of the use of microvascular flaps in the salvage of severely injured lower limb. From January 1992 to December 1994, we treated 10 patients using 10 microvascular flaps; 8 patients with Type III compound tibial fractures and 2 patients with infected implants following internal fixation of comminuted tibial fractures. The size of soft tissue defect ranged from 6 x 3 cm to 20 x 10 cm. One patient had a 6 cm bony defect. Soft tissue cover was achieved in 9 patients using microvascular muscle flaps with meshed split skin grafts and 1 patient using a scapula osteocutaneous flap. They were performed within 5 to 27 days following injury or removal of implants (mean 18 days). All the microvascular flaps were successful (100%). One re-exploration was performed. The mean period of hospitalization following microsurgical flap cover was 16.8 days. Eight out of 10 patients were followed up for a mean period of 48 months. All the 8 lower limbs were successfully salvaged. Three out of 8 patients (37.5%) had chronic osteomyelitis which required sequestrectomy and bone grafting. No amputation was necessary. Two patients required adjunctive cancellous bone grafting to accelerate bony union. Six out of 8 patients (75%) achieved bony union and full weight bearing capacity. The use of microvascular flap in achieving soft tissue cover plays an important role in the salvage of severely traumatized lower limb. Microvascular muscle flap is preferred when only soft tissue defect is present. Successful soft tissue cover facilitates secondary bone grafting procedures. Although the timing of surgery per se does not adversely affect the success rate of microvascular flaps, delayed soft tissue cover is associated with a high chronic infection rate (37.5%). An adequate surgical debridement is crucial in reducing the complication of deep infection.

Verrucous haemangioma is an uncommon skin lesion which increases in size and also evolves in appearance with time. Early diagnosis is important so that surgical treatment can be instituted early for better cosmetic results. Its similarities and differences to angiokeratoma circumscriptum are also highlighted, and the importance of distinguishing the two in terms of management is discussed.

The use of patient-controlled analgesia with alfentanil (PCA-alfentanil) as a form of pain relief for dressing procedures in patients during the acute phase of their burn injuries was investigated. Five ASA 1 and 2 patients with 10-30 per cent total body surface area (TBSA) thermal burns, had PCA-alfentanil for their dressing procedures after standard fluid resuscitation. One patient who did not receive a loading dose and a background infusion of alfentanil had unsatisfactory pain relief. Four patients had good pain relief after a loading dose of IV alfentanil 1 mg followed by a continuous background infusion of 200-800 micrograms/h. Demand dose ranged from 200 to 400 micrograms and lockout time ranged from 1 to 3 min. The total dose of alfentanil delivered ranged from 0.8 to 4.48 mg and duration of the dressings ranged from 30 to 60 min. All patients were mildly sedated, calm, communicative and cooperative during dressing procedures. None of them experienced hypotension or respiratory depression. One patient experienced nausea but no vomiting, no other adverse effects of alfentanil were noted. From the pilot study, PCA-alfentanil may be an effective form of pain relief for dressing procedures in patients during their acute phase of burn injuries. The optimal PCA-alfentanil setting has yet to be determined.

Vancomycin-resistant Enterococcus (VRE) is becoming an important cause of nosocomial infections. An outbreak of VRE in a burns unit, if it ever occurs, will be a catastrophe as vancomycin-resistance can potentially be transferred to other organisms like methicillin-resistant Staphylococcus aureus. We report a case of VRE in our burns centre in which it was detected and the patient isolated from other patients early. Measures to control the occurrence of VRE include the restriction of the use of vancomycin and the practice of other established infection-control measures.

The fibula osteoseptocutaneous flap is a versatile method for reconstruction of composite-tissue defects of the mandible. The vascularized fibula can be osteotomized to permit contouring of any mandibular defect. The skin flap is reliable and can be used to resurface intraoral, extraoral, or both intraoral and extraoral defects. Twenty-seven fibula osteoseptocutaneous flaps were used for composite mandibular reconstructions in 25 patients. All the defects were reconstructed primarily following resection of oral cancers (23), excision of radiation-induced osteonecrotic lesions (2), excision of a chronic osteomyelitic lesion (1), or postinfective mandibular hypoplasia (1). The mandibular defects were between 6 and 14 cm in length. The number of fibular osteotomy sites ranged from one to three. All patients had associated soft-tissue losses. Six of the reconstructions had only oral lining defects, and 1 had only an external facial defect, while 18 had both lining and skin defects. Five patients used the skin portion of the fibula osteoseptocutaneous flaps for both oral lining and external facial reconstruction, while 13 patients required a second simultaneous free skin or musculocutaneous flap because of the size of the defects. Four of these flaps used the distal runoff of the peroneal pedicles as the recipient vessels. There was one total flap failure (96.3 percent success). There were no instances of isolated partial or complete skin necrosis. All osteotomy sites healed primarily. The contour of the mandibles was good to excellent.

With reconstructive microsurgical techniques, some previously hopelessly mutilated hands have become reconstructable. The functional and esthetic results of such hands can be improved to an acceptable degree with through prereconstruction evaluation and planning. This case report demonstrates the approach to reconstruction of a mutilated hand using the following: a pedicle groin flap for soft tissue reconstruction of the first web space and the amputation stump of the thumb; a combined second and third toe transfer for reconstruction of opposable fingers at the amputated index and middle finger stumps; a single second toe for reconstruction of the thumb, and an iliac osteocutaneous flap for reconstruction of the ulnar border of the palm.

The problem in extensive burns is the relative lack of available donor sites for skin grafting. Before the burnt areas can be covered, infection often sets in and the patients may then succumb. Skin grafts can be expanded in a limited way. Biological dressings or synthetic dressings can be used to buy time till donor sites become available. Cultured epithelium grown in the tissue culture laboratory permits massive expansion of skin and has been used with success as epithelial autografts in patients. Composite skin equivalents or skin substitutes have been developed and show promise.

One of the major problems in extensive burns is the relative lack of available donor sites for skin grafting. Keratinocyte cell culture in the laboratory was carried out successfully in Singapore General Hospital and shows promise as an alternative source for skin replacement. Our experience further proved that a fibroblast base is necessary for keratinocyte cell culture. It is observed that heterogenous cell source can grow concurrently and become confluent. The colony forming efficiency from trypsinized skin is about 1-4% in primary cultures and 35-40% in secondary cultures. The time taken to reach confluency are 20-21 days and 10-12 days respectively. The thickness of cultured skin is estimated as 0.5 mm (5-6 layers) under light microscope. The size of the harvested cultured skin is approximately one third of the cultured area due to contraction. The expansion ratio before shrinkage is estimated to be approximately 6000-fold based on our data.

We describe a patient with Ménétrier's disease in whom acute administration of ranitidine reduced gastric protein loss more effectively than cimetidine or propantheline. This patient went into remission following a course of ranitidine. We reviewed the literature on remissions in Ménétrier's disease occurring without surgery. More detailed studies of various anti-secretory agents on individual patients are required to determine whether or not they are truly efficacious.

Forty consecutive cases of liver abscess from the Department of Medicine III, Singapore General Hospital, from 1978 to July 1983 were reviewed. Nineteen (47.5%) were amoebic, 15 (37.5%) pyogenic and 6 (15%) of unknown aetiology. Of the first 20 cases from 1978 to 1980, amoebic abscesses (60%) predominated. An increased incidence of pyogenic abscess constituting 50% was seen in the next 20 cases. Though all racial groups were affected, a predilection among Indians was seen. Males outnumbered females (4:1), and peak incidence occurred in the 40 to 70 age group (62.5%). Fifty percent presented early (less than one week of symptoms) to hospital. Common physical signs were fever (97.5%) and hepatomegaly (92.5%). Investigations showed leucocytosis in excess of 10,000 WBCs/cmm (87.5%), an ESR of 80 mm/hr (80%) and an elevated alkaline phosphatase of at least twice normal (73.6%). Single abscesses (72.5%) located in the right lobe were more likely to be amoebic. Where abscesses were multiple, they were more likely to be pyogenic (63.6%). Two-thirds of the pyogenic abscesses were due to either Klebsiella species or E. coli. Medical treatment consisted of broad spectrum antibiotics, usually in combination with metronidazole. Aspiration or drainage (open or closed) was employed when indicated. These were carried out more often for pyogenic than amoebic abscesses. Amoebic abscesses responded faster to treatment compared to pyogenic abscesses. Mortality in the first 20 cases prior to 1981 was 30%, being mainly confined to pyogenic abscesses. However, after 1981, there has been no mortality in the ensuing 20 cases.

Fifty-five Chinese healthy asymptomatic Hepatitis Bs Antigen carriers, 49 males and 6 females, were studied over a six year period, 1978 to 1984. Seventeen patients (30.9%) had normal transaminases, and 38 patients (69.1%) had fluctuating levels of transaminases throughout the period of study. 83.6% of patients were below 40 years, and mean age was 29.5 years (range 18 to 49 years). Twenty three patients (41.8%) had liver biopsy, and a spectrum of chronic liver diseases was seen, with Chronic Lobular Hepatitis (CLH) and Chronic Persistent Hepatitis (CPH) being the commonest. Six patients (26.1%) had normal histology, seven patients (30.4%) had CLH, seven patients (30.4%) had CPH, two patients (8.7%) had Chronic Active Hepatitis (CAH), and one patient (4.4%) with Active Cirrhosis (AC). An attempt to correlate the severity of histological changes with the levels of transaminases at the time of biopsy failed to show any definite correlation. However, three patients with transaminases of more than four times normal had severe liver diseases (2 CAH and 1 AC).

This paper evaluates the haemodynamics of intravenous Acebutolol (SECTRAL) (0.5 mgm/Kgm) in the acute phase of myocardial infarction uncomplicated by hypertension, cardiac failure or conduction abnormalities. Nineteen observations were made on 15 consecutive patients. Haemodynamic parameters were recorded just before, and at 15 and 30 min after injections, using Swan-Ganz Catheter-Thermister and Edslab Cardiac Output Computer (9520) in the Intensive Care Unit. All patients survived; none had extension of infarction. The Heart Rate dropped by 9 +/- 1% (+/- SEM) (from 90.2 +/- 4.0 to 81.6 +/- 3.1 per min, P less than 0.001) but systolic and mean Blood Pressures were not significantly altered. Pulmonary Capillary Pressure was elevated by 2.5 +/- 6% (from 11.6 +/- 0.8 to 14.4 +/- 0.9 mmHg P less than 0.001) but cardiac failure hardly ever developed clinically. The mean Pulmonary Arterial Pressure rose by 10 +/- 2% (P less than 0.005) while the Right Atrial mean increased from 6.0 +/- 1.0 to 8.3 +/- 1.3 mm Hg (P less than 0.005). Although the Cardiac Index was depressed by 11 +/- 2% (from 3.0 +/- 0.1 to 2.7 +/- 0.1 L/min/M2; P less than 0.001), the Stroke Index remained virtually unaffected. Myocardial oxygen consumption per min as reflected by Heart Rate x BP product declined by 12 +/- 2% (P less than 0.001), while the Stroke Work Index was lowered by 9 +/- 3% (P less than 0.005). The haemodynamic profile indicates that intravenous Acebutolol in uncomplicated infarcts is well tolerated, and that it could be employed with advantage to manipulate determinants of myocardial oxygen consumption through reduction of Heart Rate Pressure product and Stroke Work Index.

Hepatocellular carcinoma afflicts mainly Chinese Singaporeans 75/77 (97.4%), of which 71/77 (92.2%) of the patients are males. It is rare below the 3rd decade of life (1.3%), with the peak incidence occurring in the 5th to 7th decade of life (68.5%). Common presenting features are hepatomegaly (85.7%), jaundice (63.6%), and right hypochondrial pain (51.9%). Liver function tests were abnormal in 98.7%. Alpha-foetoprotein were positive in 61/77 (79.2%) of patients. Hepatitis B surface Antigen were positive in 43.75 (57.3%) of patients. Radiology and ultrasound studies demonstrated that 70.1% had lesions involving both lobes at diagnosis. Only 4/77 (5.1%) had surgical resections of the tumour. 50/65 (76.9%) died within six months of diagnosis, 11/65 (16.9%) survived for one year, 1/65 (1.5%) for 1 1/2 years, 1.65 (1.5%) for 2 years and 2/65 (3.0%) for more than 2 1/2 years; the longest survivor is still alive, at 4 1/2 years after diagnosis.

The clinical features and hormonal abnormalities were surveyed in 117 men with cirrhosis of the liver. Compared with healthy men of similar ages, the patients had significantly lower metabolic clearance rates, plasma production rates and total and free levels of testosterone, reduced testosterone responses to human chorionic gonadotrophin stimulation, higher oestradiol, luteinizing hormone and follicle stimulating hormone levels and higher binding capacities of sex steroid binding globulin. The peripheral conversion of testosterone to oestradiol was also found to be significantly increased. However, the metabolic clearance and plasma production rates of oestradiol were not significantly different from those of healthy men. Patients who were severely ill with liver failure and one with haemochromatosis had low levels of luteinizing hormone and follicle stimulating hormone and sub-normal responses to clomiphene and luteinizing hormone-releasing hormone. Higher plasma oestradiol levels were found in patients with gynaecomastia and spider naevi than in those without these signs. However, the clinical features of androgen deficiency--that is, testicular atrophy, impotence and loss of secondary sex hair--were only poorly related to the low testosterone levels, and production rates and longtitudinal studies indicated that the hormonal levels, endocrine features and severity of the liver disease could change independently. It is concluded that the clearance of oestradiol from plasma is not limited by liver disease in all patients, and that reduced degradation of oestrogens is not the initial event in the sequence leading to the hormonal abnormalities of cirrhosis. While gonadotrophin deficiency occurs with liver failure and in some patients with haemochromatosis, the more usual findings are of elevated gonadotrophin levels and a poor Leydig cell response to chorionic gonadotrophin. These suggest that the hypogonadism is primary in most patients with cirrhosis. The causes of the high oestradiol levels were not discovered. Increased peripheral conversion of precursors to oestradiol or increased testicular secretion of oestradiol are possibilities. The high binding capacities of sex steroid binding globulin were not significantly correlated with either the low testosterone or high oestradiol level and the cause of this abnormality remains uncertain. The low metabolic clearance rates of testosterone appeared to result from the increased plasma protein binding of testosterone. The discrepancies in the expected relationships between the hormone and clinical changes suggest that factors other than those studied are also involved in the genesis of the endocrine features of hepatic cirrhosis.

Hypoglycemia can give rise to a variety of neurological signs and symptoms. This may occur in the absence of the well known signs of acute hypoglycemia taught to diabetics on insulin. In the past year, 6 patients with hypoglycemia were admitted with a diagnosis of cerebrovascular accident. They were all being treated with oral hypoglycemic drugs. The neurological signs all reversed immediately with the restoration of a normal blood glucose. Their circumstances of admission illustrate some of the difficulties in making the correct diagnosis in this group of patients.

Graduating in 1951 and up-to-date, I have been engaged in hospital practice. It is appropriate at this juncture, the year of the Silver Jubilee of the Academy of Medicine, to recollect and record the changes and progress of medicine in Singapore, during the last three decades, 1951 to 1980.

Sixty-one consecutive cases of ulcerative colitis from the Department of Medicine, Singapore General Hospital, over a 16-year period (1971 to 1986) were reviewed. Mean duration of follow-up was 35.9 months (range 2 months to 16 years). Fifty-one (83.6%) cases were diagnosed in the last 8 years. Sex ratio was almost equal (males 30, females 31) and mean age was 38.2 years. All racial groups were affected but a predilection among Indians (21.3%) was observed. At presentation, the disease was mild in 36 (59.0%), moderate in 14 (22.9%) and severe in 11 (18.1%) patients. Fifty-two (85.2%) patients had symptoms of at least one month's duration before presentation. The 3 commonest symptoms were haematochezia (95.1%), diarrhoea (95.1%) and mucoid stools (83.6%). Extraintestinal manifestations of disease such as backache (8.2%), peripheral arthritis (6.5%), iritis (6.5%) and liver disease (1.6%) were uncommon. Severe intestinal complications include toxic megacolon (1.6%), colonic perforation (1.6%) and massive gastrointestinal haemorrhage (1.6%). Haematological and biochemical indices at presentation generally reflected the activity and severity of disease. The disease was limited to the rectum and sigmoid colon in 12 (19.7%) patients, extended up to the splenic flexure in 16 (26.2%), up to the hepatic flexure in another 16 (26.2%) and involved the whole colon in 17 (27.9%). Pseudopolyposis was present in 13 (21.3%) patients. Of 49 patients: (a) 18 (36.7%) had remission and were relapse free subsequently (b) 14 (28.6%) had infrequent relapses (less than 3 x/year) (c) 3 (6.1%) had frequent relapses (greater than 3 x/year) (d) 10 (20.4%) had chronically active disease (e) 4 (8.2%) had a short fulminant course terminating in death.(ABSTRACT TRUNCATED AT 250 WORDS)

The treatment of 205 patients with primary hepatocellular carcinoma in Singapore from 1975 to 1980 is reviewed. Adriamycin given at a dose of 40 mg/m(2) intravenously every 4 weeks for irresectible tumours achieved a response rate of 32% alone and has significantly prolonged the median survival time to 4 1/2 months (135 days) in these individuals. Despite this response only 1/34 (3%) patient showed complete remission and is alive at 2 1/2 years. Use of other combinations with Adriamycin e.g. 5 Fluorouracil and Vincristine produced a significant response in the first 16 weeks (p < 0.005) but not thereafter, when completed with the historical group. To improve the response and to consolidate this response, split doses of total hepatic irradiation (to a maximum of 3,150 rads) and alternate day administration of intravenous Adriamycin 10 mg (to a maximum of 90 mg) were given. 12/23 patients (50%) responded. This was followed by a four weekly Adriamycin, 5 F.U. and Vincristine. Median survival time was 5 1/2 months (165 days). Relapse occurred in all patients. Similarly in 5 patients who had resections, early recurrences occurred in 3/5 (60%) within 3 months, inspite of postoperative chemotherapy with Adriamycin, 5 F.U., Vincristine and Cyclophosphamide given every four weeks. In view of the high recurrence rate following effective treatment, further studies on the biological behaviour of these abnormal livers is required.

A retrospective study of 22 patients with cancer of the pancreas seen in a medical department was carried out. The mean age was 61.7 years, although the youngest was only 32 years. Weight loss, pain and jaundice were the most frequent presenting symptoms. Hepatomegaly and jaundice were the most common physical findings. The gall bladder was palpable in 27.3%. Serum alkaline phosphatase, bilirubin and ESR were raised in most cases. Ultrasound examination was done in 72.7% of cases and was diagnostic in 62.5% with 12.5% falsely negative. Five patients had CT scan of the abdomen, of which 4 were diagnostic. Percutaneous transhepatic cholangiogram was positive in all the 8 patients where it was carried out. The cancer was of the pancreatic head in 72.7%. Gallstones were present in 22.7%. Secondary tumour involvement of the liver was present in 40.9%. Laparotomy was performed in 11 patients of which only 2 had a curative procedure (Whipple's operation). The overall prognosis was very poor: 54.5% died during the same admission.

Nine cases of Crohn's disease from the Department of Medicine, Singapore General Hospital were collected over a duration of 9 years (1978-1986). Male (5): Female (4) ratio was nearly equal. Predominantly young people (mean age 30.5 year, range 12-59 year) from all races in Singapore were affected. Presentation could be acute (1), subacute (2), or chronic (6). The commonest symptoms were abdominal pain (8) diarrhoea (6) and weight loss (6). Three patients had a palpable right iliac fossa mass, 3 had definite malabsorption from ileal disease and 1 had perianal involvement leading to an anal stricture. The only extraintestinal manifestations of disease were clubbing and sacroiliatis. Haematological (haemoglobin, total white count, erythrocyte sedimentation rate) and biochemical (albumin) parameters generally reflected the degree of activity and chronicity of disease prior to presentation. The diagnosis and assessment of disease sites were based on a combination of radiological, endoscopic, operative and histological criteria. Ileal disease (4) per se was commonest followed by ileocolic disease (3) and colonic disease (2). Medical treatment consisted of sulphasalazine +/- steroids in all patients. Azathioprine and metronidazole were used for steroid sparing and perianal disease respectively. Laparotomy was performed in 2 patients. Six patients were well with infrequent (less than or equal to 2 times/year) or no relapses during follow up. Of the remaining three, 2 had either chronically active disease or frequent relapses (greater than 2 times/year) and one severe recurrent disease despite repeated gut resection.

Arsenic poisoning, a disease of the past, was recently found in 74 patients in Singapore over a 15-month period. Most victims (70%) had a chronic form of poisoning and 64% of the cases were caused by a local anti-asthmatic herbal preparation containing 12,000 ppm of inorganic arsenic sulphide. The other patients were poisoned by six other brands of herbal preparations used for the treatment of asthma and a variety of other illnesses. Subsequent investigations revealed another 22 other brands of Chinese herbal preparations containing high concentrations of inorganic arsenic ranging from 25 to 107,000 ppm, of which most were imported. Nearly 40% of the patients had taken the medicine for less than six months, but the others had a longer history of exposure ranging from one to 15 years. Systemic involvement was confined mainly to the skin (91%), nervous system (51%), gastrointestinal system (23%) and blood (23%). Malignancy of the skin was present in six patients, and of the visceral samples, toxicological confirmation was found in half of the cases investigated. There was no correlation between the clinical status of the patients and their tissue arsenic content. The importance of arsenic poisoning by herbal preparations is discussed, as there are no known reports of their association.

Sixty-nine patients with chronic active hepatitis without cirrhosis were studied to define the prognostic implications of bridging necrosis of various types. There were 19 patients without bridging necrosis compared with 50 patients with bridging necrosis. The two groups did not differ significantly at presentation in age, sex, clinical or laboratory features. In the group without bridging necrosis, no patient died from the disease and none of 13 having a later biopsy developed cirrhosis. In the group with bridging necrosis, one patient died from hepatic failure and 7 of 36 developed cirrhosis (19%). When analyzed statistically, a significant (p less than 0.05) relationship is seen between increasing severity of initial lesion and the subsequent development of cirrhosis. It is concluded that patients with piecemeal necrosis without bridging should not be grouped together with patients with bridging necrosis or cirrhosis when considering management decisions.

The clinical features and investigations of 17 patients were analysed. Thirteen of them were Chinese and the rest Indians. Their ages at presentation ranged from 8 to 63 years (mean 18.35 years). Thirteen patients (76%) were symptomatic; 8 with predominantly hepatic manifestations and 5 with neurological features. Four were asymptomatic siblings. At diagnosis, however, 10(59%) had features of liver involvement singly, 3 (18%) had neurological involvement alone and 4 (27%) had mixed presentations. Family histories were available in 15 patients; 26.9% of siblings had Wilson's Disease. Serum ceruloplasmin was low in 82% of the patients. 24-hour urinary copper was measured in 16 patients and was raised in all of them. About half the patients (41%) had evidence of concomittant renal tubular dysfunction with hypouricaemia and aminoaciduria. Three patients (18%) had joint involvement at presentation. All 17 patients were treated with Penicillamine. Complications due to therapy included pemphigus in one and toxic epidermal necrolysis and later a lupus like syndrome in another. The features of clinical improvement included fading of K-F rings, improvement of neurological signs and the normalisation of serum transaminases. One patient developed primary hepatocellular carcinoma 5 years after presentation. Delay in diagnosis was encountered in half of the patients reviewed. Being a treatable condition, Wilson's Disease, although rare, should always be thought of in patients with haemolysis, liver diseases or extrapyramidal disorders.

Fifty consecutive patients (32 males and 18 females) with cholestatic jaundice were examined by grey-scale ultrasound from June 1981 to June 1983. All patients were studied without access to case notes. All patients had a diagnosis established by subsequent liver biopsy, clinical course, surgery or autopsy. Using the presence or absence of a dilated biliary system as the criterion, intrahepatic or extrahepatic cholestasis was correctly differentiated in 48 of the 50 patients, giving an overall accuracy of 96%. All 16 patients with intrahepatic cholestasis were correctly identified. Two of the 34 patients with extrahepatic cholestasis, each of whom had biliary stones, were misdiagnosed as intrahepatic cholestasis. In the 34 patients with extra-hepatic cholestasis, site of obstruction was defined in 55.9%, and specific aetiology diagnosed in 44.1%. Ultrasound proves to be an accurate method for the evaluation of cholestatic jaundice, and would have a definite value as a screening test before proceeding to invasive studies.

Recording of median and ulnar digital sensory nerve action potentials in normal subjects showed that the ratio of the median (index finger) to ulnar (little finger) potential amplitude was consistently greater than one. In 15 patients with the carpal tunnel syndrome (seven bilateral) this ratio was found to be less than one for all but two of the 22 clinically affected hands, including three of the four hands with a normal motor latency to threshold stimulation and four of the five hands with a normal sensory conduction. It is concluded that the estimation of the ratio of the median to ulnar sensory potential amplitude is a sensitive test in the diagnosis of the carpal tunnel syndrome and is particularly useful in those patients who show a normal motor latency and sensory conduction.