Late-onset post-transplant lymphoproliferative disease presenting as massive occult gastrointestinal haemorrhage.

Post-transplant lymphoproliferative disease (PTLD) is a widely-recognised complication of solid organ transplants with a myriad of clinical presentations. We report a 56-year-old Chinese woman who developed PTLD 17 years after a renal transplant. She initially presented with constitutional symptoms, and a diagnosis of diffuse large B-cell lymphoma was confirmed on liver biopsy. Staging computed tomography demonstrated widespread adenopathy. Initial treatment consisted of reduction of immunosuppression and Rituximab. Prior to institution of chemotherapy, she presented with life-threatening melaena. Laparotomy revealed a mid-jejunal ulcerating tumour which was resected. Histology confirmed necrotic diffuse large B-cell lymphoma and the cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy regime was subsequently commenced. The aim of this case report is to highlight the unique challenges in the management of PTLD in the context of an acute abdomen.

Calcium binding protein containing neurons in the gliotic mouse hippocampus with special reference to their afferents from the medial septum and the entorhinal cortex.

In CA1 area and the hilus of the dentate gyrus of the mouse hippocampus, drastic reduction of NeuN, calbindin, calretinin, or parvalbumin immunopositive neurons was shown at 3, 7 and 60 days after pilocarpine-induced status epilepticus. In gliotic CA1 area at 60 days, few dendritic branches of calcium binding protein immunopositive neurons could be found suggesting reorganization of the afferents of surviving calcium binding protein immunopositive neurons. Calbindin, calretinin, or parvalbumin and 5-bromo-2'-deoxyuridine (BrdU) double labeling showed that calcium binding protein immunopositive neurons in gliotic CA1 area at 60 days were surviving instead of newly generated neurons. Iontophoretic injection of Phaseolus vulgaris leucoagglutinin into the medial septum and the nucleus of the diagonal band of Broca or the lateral entorhinal cortex showed contacts between Phaseolus vulgaris leucoagglutinin immunopositive en passant and terminal boutons and surviving calcium binding protein immunopositive neurons in the hippocampus. The presence in the gliotic hippocampus of enlarged and/or aggregated bouton-like structures 60 days after pilocarpine-induced status epilepticus is indicative for the reorganization of connections between the hippocampal afferents and surviving hippocampal neurons. This reconstruction could be a factor in the ongoing epileptic activity in this model of mesial temporal lobe epilepsy.

Metabotropic glutamate receptor 2/3 in the hippocampus of patients with mesial temporal lobe epilepsy, and of rats and mice after pilocarpine-induced status epilepticus.

A comparative study of the expression of metabotropic glutamate receptor 2/3 (mGluR2/3) was done in the hippocampus of rats and mice after pilocarpine-induced status epilepticus (APISE), and of patients with mesial temporal lobe epilepsy. At 1 day APISE, there was a marked increase in mGluR2/3 immunoreactivity in the stratum lacunosum moleculare (SLM) of CA1 area and in the middle one-third of the molecular layer (MM) of the dentate gyrus. Immuno-electron microscopic study showed degenerating mGluR2/3 positive axons in the SLM of CA1 area at 1 day APISE. From 7 days, mGluR2/3 immunopositive product decreased, and by 31 days APISE, it almost disappeared in two-thirds of the SLM near CA2. In the mouse model at 2 months APISE, mGluR2/3 immunopositive product in two-thirds of the SLM near the stratum radiatum disappeared, and so did in the whole SLM of CA1 area in patients with mesial temporal lobe epilepsy. Neuropharmacological study by intravenous injection of mGluR2/3 agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate [(2R,4R)-APDC] at different doses at 1h during pilocarpine induced status epilepticus showed that (2R,4R)-APDC could not stop seizures and neuronal death in the hilus of the dentate gyrus. The present study, therefore, suggests that the reduction of mGluR2/3 immunopositive product in the SLM of CA1 is a consequence of neuronal loss in either the entorhinal cortex or CA1 area of the hippocampus, and at the dosage range from 12.5 to 600 mg/kg, (2R,4R)-APDC may not be effective in the prevention of seizures or neuronal death in the hilus of the dentate gyrus.

Expression of different isoforms of protein kinase C in the rat hippocampus after pilocarpine-induced status epilepticus with special reference to CA1 area and the dentate gyrus.

At 4 h during pilocarpine-induced status epilepticus (DPISE) in rat, protein kinase C (PKC)beta1, PKCbeta2, and PKCgamma were induced at the border between the stratum oriens and alveus (O/A border) of CA1 in the hippocampus. Induced PKCgamma was colocalized with metabotropic glutamate receptor alpha (mGluR alpha). By intracerebroventricular injection of mGluR1alpha antagonists, (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA), PKCbeta1, PKCbeta2, and PKCgamma immunoreactive products decreased dramatically; however, intracerebroventricular injection of saline did not change the expression of PKCbeta1, PKCbeta2, and PKCgamma, suggesting that these three PKC isoforms might be involved in mGluR1alpha-related excitoneurotoxicity. One day after pilocarpine-induced status epilepticus (APISE), PKCdelta was induced in microglial cells. At this time point, both PKCgamma and PKCepsilon immunopositive products decreased in the inner molecular layer of upper blade of the stratum granulosum. At 7-31 days APISE, induced PKCbeta1, PKCdelta, PKCeta, and PKCzeta positive astrocytes were demonstrated in all parts of hippocampus, suggesting that they may be involved in gliosis. By this time, both PKCgamma and PKCepsilon immunopositive products in the inner molecular layer had almost disappeared, suggesting that they may be involved in the inhibition of granule cells by controlling neurotransmitter release presynaptically in the dentate gyrus of normal rats.

Fragment of Japanese encephalitis virus envelope protein produced in Escherichia coli protects mice from virus challenge.

A fragment from the N-terminal part (E(A)) and a fragment from the C-terminal part (E(B)) of the envelope (E) protein of Japanese encephalitis virus (JEV) was synthesized in Escherichia coli. These two fragments were overlapping with each other by nine amino acids, however, they were not cross-reacting with each other at the antisera level. Both E(A)and E(B)are antigenic by themselves when injected into mice, but when tested against sera from mice, rabbit, swine and human that had been immunized or naturally infected with JEV, E(B)acted as a better antigen than E(A)by ELISA assays. E(B)also proved to be a better immunogen in protection against lethal JEV infection than E(A). The protection appears to be correlated with the neutralizing titres of the anti-JEV sera. The response elicited by E(B)is a Th1 response and the antibody produced contained higher neutralizing titre than E(A)fragment. The major difference between E(A)and E(B)fragments is the solubility during expression in E. coli, while E(B)fragment is soluble, E(A)was isolated from the insoluble inclusion bodies. Therefore the antigenicity and immunogenicity expressed by the E(B)fragment may probably be due to its proper folding to assume a correctly assembled form during expression in E. coli, a quality that is important for a protein to qualify as a good vaccine candidate.

Pyogenic liver abscess--a tropical centre's experience in management with review of current literature.

AIM OF STUDY: To perform a retrospective study, with the help of literature review, of the management of patients with pyogenic liver abscess in a general hospital. METHOD: A retrospective study of 73 consecutive patients treated atTanTock Seng Hospital between January 1994 and December 1997 was conducted to determine the demographic, clinical, laboratory, radiological and microbiological characteristics of these patients, as well as the management strategies employed. RESULTS: Liver abscess was more common in males, occurring more frequently in the right hepatic lobe. Most patients presented with non-specific clinical and biochemical features. A raised alkaline phosphatase level was the most common biochemical abnormality found in about two-thirds of patients. Ultrasonography was not as sensitive as computed tomographic scans in detecting abscesses. Klebsiella pneumoniae was the most common etiological agent detected in cultures of blood and abscess aspirates. All patients were treated with intravenous antibiotics. Twenty-two (30%) needed percutaneous catheter drainage and five (7%) required surgical management. There was no hospital mortality in our series. Prolonged hospitalisation was associated with advanced age, degree of loculation within the abscess, concomitant diabetes mellitus and Klebsiella septicaemia. CONCLUSION: Pyogenic liver abscesses require a high index of suspicion for early diagnosis. When appropriate therapy in the form of antibiotics in combination with percutaenous drainage or surgery is administered, mortality is very low. However, significant morbidity is still a problem, particularly in the elderly, diabetic patient.

Pruritus as a presenting symptom of chronic hepatitis C.

Pruritus is a common symptom in cholestatic liver disease but is rare in chronic hepatitis C. Eight patients with chronic hepatitis C and severe pruritus were compared with regard to biochemical, serological, and histological features to eight disease controls with primary biliary cirrhosis and seven with cirrhosis due to hepatitis C. Among those with severe pruritus associated with chronic hepatitis C, serum aminotransferases were raised in all, alkaline phosphatase in four, and gamma-glutamyl-transpeptidase levels in all except one. Serum cholylglycine levels were elevated in seven of eight patients. Liver biopsies showed moderate to severe fibrosis in all patients and cirrhosis in five. Compared to control subjects with cirrhosis due to hepatitis C but no pruritus, ductopenia, and cholestatic changes were prominent, although less so than in controls with primary biliary cirrhosis. Chronic hepatitis C with moderate to severe fibrosis may result in low-grade cholestasis with pruritus, possibly in association with bile duct disappearance.

An aflatoxin-associated mutational hotspot at codon 249 in the p53 tumor suppressor gene occurs in hepatocellular carcinomas from Mexico.

The p53 tumor suppressor gene is commonly mutated in human hepatocellular carcinoma (HCC). The most frequent mutation in HCC in populations exposed to a high dietary intake of aflatoxin B1 (AFB1) is an AGGarg-->AGTser missense mutation in codon 249 of the p53 gene. We analyzed HCCs from Monterrey, Mexico, for the codon 249ser hotspot mutation. We also analyzed the serum AFB1-albumin adduct levels of the donors and family members to measure the current AFB1 exposure in this population. Moreover, the presence of hepatitis B and/or C viral infection (HBV or HCV) was analyzed serologically in the patients. Tumor cells were microdissected from tissue sections and exon 7 p53 sequences were amplified by polymerase chain reaction from genomic DNA and sequenced directly. The serological tests for anti-p53 antibodies, HBV or HCV were done by ELISA. Immunohistochemical analysis of p53 protein was done using a polyclonal rabbit antiserum (CM-1). Eight of 21 cases were positive by p53 immunohistochemistry. Of the 16 cases sequenced for exon 7 of p53 three codon 249 AGGarg-->AGTser mutations were found. Serum antibodies recognizing p53 protein were found in one of 18 patients. Positive serology for HBV and/or HCV was found in 12 of 20 cases. The serum AFB1-albumin adduct levels in this population ranged from 0.54 to 4.64 pmol aflatoxin/mg albumin. These results indicate that dietary AFB1 and hepatitis viruses are etiological agents in the molecular pathogenesis of HCC in this geographic region of Mexico.

Endoscopic adrenaline injection in treatment of bleeding peptic ulcers.

This study aimed to compare the results of bleeding peptic ulcer treated by endoscopic adrenaline injection with controls treated conventionally. Between January 1991 and December 1993, 69 patients with actively bleeding peptic ulcers with visible vessel received endoscopic adrenaline injection. This group of patients was compared with 31 endoscopically similar patients treated conventionally, using H2 blockers with or without surgery, from October 1987 to December 1990 prior to the introduction of endoscopic injection therapy in this hospital. Both groups of patients were comparable in terms of age, haemoglobin level on admission and site of ulcer (gastric or duodenal). Permanent haemostasis was attained with endoscopic adrenaline injection in 97% of our patients. Rebleeding occurred in 9% in the injected group vs 39% in the historical control group (p < 0.005). Three percent of patients in the injected group had emergency surgery compared with 48% in the control group (p < 0.005). The median hospital stay and transfusion requirements in the injected group were 6 days and 2 units respectively vs 8 days and 3 units in the control group but the difference was not statistically significant. We conclude that endoscopic adrenaline injection is effective in the treatment of bleeding peptic ulcer leading to a reduction in rebleeding rate and emergency surgery.

Seroprevalence of antibodies against hepatitis A (anti-HAV) in Singapore: the NFDD experience.

At the 4th National Foundation for Digestive Disease (NFDD) Day in 1991 where public lectures on prevention of hepatitis and early detection of hepatocellular carcinoma were given, screening of sera obtained from 364 registrants for antibodies to Hepatitis A (IgG) was undertaken. The overall sero-prevalence rate was 50%, with 55% for males and 46% for females with antibodies for HAV. None of the subjects below 20 years old had antibodies to HAV. This rose to 16% for those 21-30 years old and 92% for those above 61 years. This study shows that in Singapore, prevalence of anti-HAV antibodies rise with age and is approaching the low endemicity pattern that is seen in developed countries.

Peptic ulcer disease in the elderly in Singapore.

Of 460 patients with peptic ulcer disease seen over a 30-month period, there were 174 elderly patients (defined as > or = 60 years old), constituting 38%. In this group of elderly, gastric ulcers (GU) were observed more frequently than duodenal ulcers (DU) with a ratio of 1.6:1 and the male to female ratio was 1.7:1. In patients < 60 years old, there were more DU than GU with a ratio of 2.7:1, and a higher male to female ratio of 3.7:1. Seventy-two per cent of the elderly had at least one other medical condition with 20% having three or more medical problems. Hypertension and ischaemic heart disease were the most frequently encountered illnesses. Half the elderly presented with upper abdominal pain and one-third had an atypical presentation. Analgesic ingestion in the preceding 4 weeks was present in 29% of the elderly. In the elderly, bleeding was the most frequent complication occurring in 50%; perforation occurred in 2%. In those with bleeding ulcers, 44% had history of analgesic usage. The mortality of bleeding peptic ulcer in the elderly, was 11% and this was largely due to concurrent medical conditions. Only two deaths occurred due to bleeding ulcer.

Clotest (rapid urease test) in the diagnosis of Helicobacter pylori infection.

Over a period of 3 months, 85 patients who underwent gastroscopy had antral biopsy taken for Clotest, histology and/or culture for Helicobacter pylori (HP). The sensitivity and specificity of Clotest were found to be 77% and 96% respectively with negative predictive value of 63% and positive predictive value of 98%. Ninety-two percent of the positive Clotests were positive within 20 minutes, thus giving rapid result. Therefore, Clotest is a rapid, sensitive and highly specific test for HP infection. A high correlation between HP infection and chronic gastritis was noted and the prevalence of HP infection in patients with duodenal ulcer (90%) was higher than that of gastric ulcer (64%) or non-ulcer group (65%).

Prevalence of antibody to hepatitis C in patients with liver disease.

We studied the seroprevalence of antibody to hepatitis C virus (HCV) in patients with liver disease using the Abbott HCV EIA. Twenty-four patients with acute sporadic nonA nonB hepatitis, 19 patients with chronic hepatitis, 28 patients with cirrhosis and 47 patients with hepatocellular carcinoma (HCC) were assayed. The seroprevalence was 8.3% (2/24) in acute hepatitis; 10.5% (2/19) in chronic hepatitis; 3.6% (1/28) in cirrhosis and 14.9% (7/47) in hepatocellular carcinoma. The seroprevalence rates were lower in all categories of liver disease compared to figures reported in developed countries. Possible reasons included a delayed or missed seroconversion in the acute hepatitis group. Other etiologies like hepatitis B and alcohol may play a more important role in chronic liver disease. On the other hand, the seroprevalence locally may actually be low. Sporadic, non-blood transfusion appears to be a common method of acquiring the infection.

Nizatidine versus cimetidine in the treatment of duodenal ulcers.

An open comparative trial of nizatidine in the treatment of duodenal ulcer (DU) was carried out with cimetidine as control. Forty-three patients with endoscopically proven DU were recruited into the study. Twenty-three patients were assigned to treatment with nizatidine 300 mg daily and 20 patients (controls) were on cimetidine 800 mg daily. Both groups were comparable in age and sex distribution - age range 21 to 74 years; mean 53.4 years and 43 years in the nizatidine and cimetidine groups respectively. Liver function tests, full blood counts, platelets, urea, electrolytes were done together with endoscopy at four, eight, twelve weeks. In the nizatidine group, 16 patients completed the study whilst 17 patients on cimetidine completed the study. Healing rates at four and eight weeks on nizatidine were 9/16 (56%) and 14/16 (87.5%) respectively. On cimetidine, healing rates at four and eight weeks were 14/17 (80%) and 16/17 (94%) respectively. There was no statistical difference in healing rates between the two groups at four and eight weeks (p = 0.1, p = 0.47). One patient on nizatidine developed urticaria rash which resolved on drug withdrawal. No other adverse clinical or biochemical effects were observed in the cohort after twelve weeks of treatment. Nizatidine is as effective as cimetidine in healing DU at four and eight weeks.

The changing trend in the surgical treatment of macular holes.

The Vitreo-Retinal Service in the past 2 years enjoyed a high level of success in managing retinal detachments arising from macular holes. There was only one recorded failure. Twelve eyes in 11 patients were subjected to various modalities of treatment. This ranged from single out-patient laser photocoagulation to conventional sling procedure and ultimately the complex vitrectomy with its adjust gas-fluid exchange. Numerous intraoperative complications and their remedies were also highlighted. Competency in the management of this rare and difficult condition is an indicator of the maturity of the Vitreo-Retinal Service.