Dengue Encephalitis associated with symptomatic hyponatremia due to Syndrome of Inappropriate Antidiuretic Hormone Secretion.

A previously well 21-year-old girl presented to Hospital Teluk Intan, Perak, Malaysia with a short history of fever, vomiting and altered sensorium. She was diagnosed with dengue encephalitis as her dengue NS-1 antigen was positive and her cerebrospinal fluid (CSF) dengue polymerase chain reaction (PCR) was positive with serotype DENV-2. She also had severe hyponatremia due to Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) which caused an episode of seizure. She recovered well with supportive management. SIADH and dengue encephalitis should be considered as one of the differential diagnosis in patients presenting with fever and altered sensorium especially in dengue endemic countries like Malaysia.

Risk factors and outcome of community onset Pseudomonas aeruginosa bacteraemia in two Malaysian district specialist hospitals.

INTRODUCTION: Despite the ever-growing number of community onset (CO) Pseudomonas aeruginosa (P. aeruginosa) bacteraemia, there is a dearth of district hospital-based research examining this significant infection, which is associated with high mortality. The objectives of this study were as following: (1) to determine the risk factors of CO P. aeruginosa bacteraemia, (2) to compare the 30-day mortality rate between P. aeruginosa and Escherichia coli bacteraemia and (3) to identify the predictors of 30-day mortality for CO gram negative bacteraemia. METHODS: This is a retrospective case control study in Hospital Seri Manjung and Hospital Teluk Intan, Perak, Malaysia. P. aeruginosa bacteraemia cases that occurred between 1st January 2015 to 31st December 2019 were included, whilst E. coli bacteraemia cases that occurred within the same period were recruited successively until 1:2 case control ratio was achieved. Subjects below 12-year-old and those with polymicrobial bacteraemia were excluded. Demographic, clinical and treatment data were collected using pre-tested data collection forms by trained investigators. RESULTS: A total of 61 patients with P. aeruginosa bacteraemia and 122 patients with E. coli bacteraemia were included. Recent admission in the earlier three months, regular haemodialysis, immunosuppressive therapy in the past 30 days, chronic wound/pressure sore at presentation and indwelling urinary catheter at presentation were identified as independent predictors of CO pseudomonal bacteraemia. Whilst older age was identified as a negative predictor of CO Pseudomonal bacteraemia (all p<0.05). The 30-day mortality rate was 34.4% in subjects with P. aeruginosa bacteraemia and 27.0% in those with E. coli bacteraemia (p=0.302). Predictors of 30-day mortality for community onset gram negative bacteraemia were as follow: older age, underlying solid tumours, neutropaenia at presentation, in-patient mechanical ventilation, and inpatient nasogastric tube insertion. Unexpectedly, receipt of inappropriate empirical antibiotics which was switched later (delayed and non-delayed switching) was identified as the negative predictors of mortality (all p<0.05). CONCLUSION: It is prudent to restrict the usage of empirical anti-pseudomonal antibiotics among individuals at risk as liberal usage of broad-spectrum antibiotics engenders emergence of drug resistant organism, particularly in district setting where community onset pseudomonal bacteraemia remains scarce. Subjects with elevated risk of mortality should receive early escalation of care as per sepsis management guidelines.

Radiofrequency ablation for 110 malignant liver tumours: preliminary results on percutaneous and surgical approaches.

BACKGROUND: Radiofrequency ablation (RFA) has been widely applied for the treatment of hepatocellular carcinoma and liver metastases. The reported mortality and morbidity rates are low. The aim of this study is to evaluate the safety and efficacy of RFA, and compare the results performed percutaneously versus surgically. PATIENTS AND METHODS: From 2003 to 2006, 79 patients with hepatic malignancies (59 hepatocellular carcinoma, 20 liver metastases) with a total of 110 lesions underwent RFA in our centre. Postablation assessment by CT scan was performed in all patients at 1-, 3- and 6-month intervals. Post-procedural complications, recurrence and survival were analysed. RESULTS: The patients' mean age was 60.0 years. In 46.8% of cases, we used a percutaneous approach; in 53.2% of cases, a surgical approach (8.9% laparoscopic; 44.3% open) was used if percutaneous approach was not feasible. The mean tumour size was 2.4 cm. Within the surgical group, 69% of patients received concomitant operative procedures such as cholecystectomy and hepatectomy. No treatment-related mortality was observed. Immediate complications occurred in five patients (6.3%), including gastric serosal burn (n = 1), ground pad superficial skin burn (n = 1), intra-abdominal bleeding (n = 2) and pleural effusion (n = 1). All patients except one attended subsequent follow-up, with a mean period of 16 months. Ablation was considered complete in 82.3% of patients (percutaneous approach 81.1%, surgical approach 83.3%, p = 0.72). Intrahepatic recurrence was observed in 52.3%, the majority of them located away from the RFA site. Extrahepatic recurrences were observed in 16.9% (percutaneous approach 16.7%, surgical approach 17.1%, p = 0.76). The overall one- and two-year survival rate was 93.7% and 74.4% respectively, and no statistically significant difference was observed between the two approaches. CONCLUSION: RFA is a safe and effective procedure for treating patients with malignant liver tumours. No difference in short term outcomes was observed between percutaneous and surgical approaches. A more prolonged follow-up study is required to assess longer-term outcomes.

Dimethyl sulfoxide as an inducer of differentiation in preosteoblast MC3T3-E1 cells.

Osteoblastic differentiation is an essential part of bone formation. Dimethyl sulfoxide (DMSO) is a water miscible solvent that is used extensively for receptor ligands in osteoblast studies. However, little is known about its effects on osteoblastogenic precursor cells. In this study, we have used a murine preosteoblast cell line MC3T3-E1 cells to demonstrate that DMSO effectively induces osteoblastic differentiation of MC3T3-E1 cells via the activation of Runx2 and osterix and is dependent upon the protein kinase C (PKC) pathways. We further demonstrated that prolonged activation of PKC pathways is sufficient to induce osteoblastic differentiation, possibly via the activation of PKD/PKCmu.

The role of the human placenta in embryonic nutrition. Impact of environmental and social factors.

The human placenta has been implicated in the poor growth and development of the embryo/fetus due to alterations in blood flow and reductions in the transfer of nutrients such as amino acids and carbohydrates. Deficiencies of such nutrients have been the principal of many research investigations. The role of micronutrients, however, may also be major factors in appropriate growth and development, and there may be a general reduction in the availability of such nutrients, for example, the role of folate supplementation during early pregnancy and the reduction in the incidence of neural tube defects. Vitamins are not all transported via a common mechanism. Therefore, the modulation of human placental transport can be different for different vitamins, for example, A and B12. It is apparent that the human placenta can oxidatively metabolize retinoids (isotretinoin and tretinoin) to more toxic or less toxic metabolites. These metabolites can then be transferred to the fetal circulation. Such metabolism/transfer is in contrast to how vitamin B12 is bound to transcobalamin proteins, which are produced by the placenta and directionally released into the maternal and fetal circulations.

Phase II study of mitoxantrone in unresectable primary hepatocellular carcinoma following hepatitis B infection.

A total of 20 patients with histologically proven primary hepatocellular carcinoma (PHC) received mitoxantrone IV at a dose of 10-16 mg/m2 every 3 weeks. All patients had previous hepatitis B infection. None underwent remission after treatment; 2 had stable disease and 18 progressive disease. The median overall survival was 13 weeks (range, 1-59 weeks). There was no evidence of significant antitumor activity for mitoxantrone in our patients with PHC. Hematotoxicity occurred in 100% of the patients with grades 2-4 leukopenia, 89% of those with grades 1-4 anemia, and 26% of those with grades 2-3 thrombocytopenia. Cardiotoxicity occurred in 20% of the patients after 14-30 mg/m2 mitoxantrone; these included complete heart block with fatal outcome in one case, decreased ventricular ejection fraction in one, and sinus tachycardia in two. Nausea, vomiting, fever, diarrhea, and alopecia were mild and occurred in 15%-45% of the patients Therefore, patients with PHC following hepatitis B infection may be less tolerant to mitoxantrone, resulting in the apparent increase in toxicities.

Pseudogastroparesis as a presentation of small-bowel malignancy.

Establishing the diagnosis of small-bowel malignancy is sometimes an extremely difficult challenge owing to its non-specific symptoms. The mainstay of treatment is early recognition, diagnosis and surgical resection. The prognosis depends primarily on the degree of spread and stage at presentation. We present two cases with initially obscure presentations of a small-bowel tumour. One was a jejunal adenocarcinoma, but an initial upper gastrointestinal and small-bowel series did not disclose the lesion; the other was a primary ileal lymphoma, first thought to be diabetes mellitus gastroparesis. Therefore, a negative small-bowel series or presentation of a systemic disease-associated intestinal pseudo-obstruction or gastroparesis does not exclude the possibility of a small-bowel malignancy, if the clinical symptoms are not alleviated after prokinetic medications. The clinicians should further pursue the possibility of an obstructing lesion.

The efficacy of the third pump inhibitor--pantoprazole--in the short-term treatment of Chinese patients with duodenal ulcer.

BACKGROUND/AIMS: To study the efficacy and tolerability of pantoprazole 40 mg once daily before breakfast compared with ranitidine 300 mg once daily at bedtime in Chinese patients with duodenal ulcer, and to evaluate the relationship between Helicobacter pylori (H. pylori) clearance and ulcer healing rate. METHODOLOGY: A total of 160 patients (80 in each group) with endoscopically diagnosed, active duodenal ulcers were studied in this randomized double-blind trial. Endoscopy was performed after 2 weeks of treatment. If unhealed, then the patients were re-endoscoped after an additional 2 weeks of similar treatment. RESULTS: The healing rates after 2 and 4 weeks were 61.3% and 97.3%, respectively in the pantoprazole group, and 50.7% and 76.9% in the ranitidine group. The difference between the two groups was significant at 4 weeks (p < 0.01, per protocol analysis). The rate of pain free ulcer was higher in the pantoprazole group than in the ranitidine group at 2 weeks (84.2% vs. 59.6%, p < 0.01). Higher clearance of H. pylori was also observed in the pantoprazole group compared with the ranitidine group at 4 weeks (20% vs. 0%, p = 0.05). The healing rate tended to be higher in patients who were H. pylori-cleared at 2 weeks (p = 0.07) in the pantoprazole group. Both medications were well tolerated without any serious adverse effects. CONCLUSIONS: Pantoprazole 40 mg daily is superior to ranitidine 300 mg daily in the short-term treatment of acute duodenal ulcer in Chinese patients, in terms of ulcer healing and pain relief, and appears to be well-tolerated.

Macromolecule transfer in the human trophoblast: transcobalamin II-vitamin B12 uptake.

The accumulation of the large and hydrophilic IgG, TC II-B12 and B12 molecules is demonstrated for the first time in a human placental system which has metabolic and physiological functions. A trypsin-sensitive component is present in the human term placental uptake of TC II-B12, for which a placental membrane receptor has been previously identified; this component is absent for the accumulation of free B12, which has no known receptor. Analyses of the cytosol and incubation media indicate degradation, binding and release of TC II-B12 and B12 as TC II-B12, free B12 and TC I-like complexes. It is suggested that the human placental tissue slice be used for studies involving the binding, uptake and processing of macromolecules as exemplified by TC II-B12.

Comparative in vitro antibacterial activity of ofloxacin and ciprofloxacin against some selected gram-positive and gram-negative isolates.

The in vitro activities of ofloxacin and ciprofloxacin were tested against five selected groups of clinical bacterial isolates. Both were active against: Staphylococcus aureus and Staphylococcus epidermidis, irrespective of their resistance to methicillin or gentamicin; Haemophilus influenzae and Neisseria gonorrhoeae, irrespective of their beta-lactamase production; members of the Enterobacteriaceae family which were resistant to most oral beta-lactams, and most intestinal bacterial pathogens including Campylobacter, Vibrio, Salmonella, Shigella and Yersinia. Ciprofloxacin was found more active than ofloxacin against Pseudomonas with most isolates of Pseudomonas aeruginosa and Pseudomonas fluorescens susceptible, while those of Pseudomonas cepacia were resistant.

In-vitro stability of beta-lactam antibiotics to hydrolysis by beta-lactamases of Neisseria gonorrhoeae from Southeast Asia.

Extracts of penicillinase-producing strains of Neisseria gonorrhoeae obtained from several localities in Southeast Asia exhibited similar patterns of relative rates of hydrolysis of benzylpenicillin, ampicillin, carbenicillin, and cephaloridine. Methicillin and oxacillin were not hydrolyzed. The isoelectric point of the beta-lactamase from these strains was 5.38 +/- 0.05, and the molecular weight was approximately 22.5. These properties, as well as the Km values determined for a range of substrates, were the same for the enzyme purified from one of the strains. These observations are consistent with those reported for other gonococcal beta-lactamases of the TEM-1 type. Cefamandole and to a lesser extent, cefoperazone, were also hydrolyzed by these extracts; however, the newer beta-lactam antibiotics piperacillin, cefuroxime, cefoxitin, ceftriaxone, ceftazidime, and moxalactam were stable. These stable compounds had little inhibitory effect on the activity of the enzyme toward benzylpenicillin or cephaloridine.

Colonic mucosal changes in patients with liver cirrhosis.

BACKGROUND: Portal colopathy has been reported in patients with cirrhosis of the liver. The aim of this study is to evaluate colonic mucosal changes and their clinical significance. METHOD: Seventy-five cirrhotic patients with anemia and hemoccult-positive stool and 75 control subjects underwent endoscopic examinations of lower gastrointestinal tract. RESULT: Colonic ectasiae were found to be significantly more common in the 75 cirrhotic patients (80% with hepatitis B or C infection) than control subjects (84% vs 0, p < 0.0001). The lesions in 63 cirrhotic patients were found throughout the entire colon. They included colonic telangiectasiae or angiodysplastic-like lesions in 56 (89%) patients, red spots in 14 (22%), features suggesting mild chronic colitis in 8 (13%), and midrectal colorectal varices in 10 (16%). Pathologic findings in patients with telangiectasiae or angiodysplastic-like lesions showed dilation of vessels (7 of 9 patients) and edema of mucosa (6 of 9 patients). There was no correlation between the severity of cirrhosis, grade of esophageal varices, and the presence of colonic ectasiae. CONCLUSIONS: Our observations demonstrate that colonic mucosal changes commonly occur in cirrhotic patients with viral hepatitis. The risk of intermittent hemorrhage from colonic ectasiae should be considered in cirrhotic patients with anemia but without evidence of upper gastrointestinal bleeding. These characteristic lesions may represent a spectrum of portal in hypertensive intestinal vasculopathy.

Antibiotic sensitivities of Neisseria gonorrhoeae in the Far East: comparison of plasmid species in isolates from six countries.

In vitro susceptibility testing of 36 strains of Neisseria gonorrhoeae isolated in the Far East in 1979 and 1980 demonstrated that 27 penicillinase-producing (PPNG) isolates and nine non-penicillinase-producing (non-PPNG) isolates were susceptible to chloramphenicol, thiamphenicol, spectinomycin, trimethoprim-sulfamethoxazole, cefoperazone, moxalactam, cefotaxime, and ceftriaxone. In comparison, 50% of the strains had MICs of tetracycline of greater than 2 micrograms/ml, and 75% had MICs, of streptomycin of greater than 128 micrograms/ml. Eighty-two per cent of PPNG and 100% of non-PPNG isolates examined had MICs of kanamycin of greater than 32 micrograms/ml. None of the nine non-PPNG strains had MICs of ampicillin and penicillin of greater than 1 microgram/ml. A 4.4-megadalton plasmid, previously associated with beta-lactamase production, was found in all 27 PPNG isolates examined; 93% of PPNG and 22% of non-PPNG isolates contained a 24-megadalton plasmid previously associated with transfer of the 4.4-megadalton plasmid.

Comparative in vitro antibacterial activities of two new oral cephalosporins, ceftetrame (Ro 19-5247) and cefetamet (Ro 15-8074).

The in vitro activities of two new oral cephalosporins, ceftetrame (Ro 19-5247) and cefetamet (Ro 15-8074), were tested against 990 clinical bacterial isolates in comparison with that of cephalexin. Both compounds were more active than cephalexin against gram-negative bacteria, inhibiting most isolates of the family Enterobacteriaceae at concentrations of less than or equal to 4 micrograms/ml, but were not active against Acinetobacter species, most Pseudomonas species, Campylobacter jejuni, and Flavobacterium meningosepticum. Ceftetrame was also more active than cephalexin against most streptococcal isolates and as active as cephalexin against methicillin-susceptible Staphylococcus aureus; against the latter cefetamet was ineffective.

In vitro activities of Ro 17-2301 and aztreonam compared with those of other new beta-lactam antibiotics against clinical isolates of Pseudomonas aeruginosa.

The in vitro activities of Ro 17-2301 and aztreonam against 191 Pseudomonas aeruginosa isolates were compared with those of five other beta-lactam antibiotics. Both compounds showed activities comparable to that of ceftazidime and were bactericidal. They were as effective against gentamicin-or carbenicillin-resistant isolates as against susceptible ones.

Effect of 5-hydroxytryptamine and its antagonists on colonic smooth muscle of the rabbit.

The effect of 5-hydroxytryptamine (5HT) was studied in circular and longitudinal muscle from the proximal and distal colon of New Zealand white rabbits. 5HT stimulated a dose-dependent isometric contraction of distal and proximal circular muscle that was greater than in distal longitudinal muscle (P less than 0.01). 5HT did not stimulate taenia coli longitudinal muscle. The EC50 for 5HT stimulation of distal circular muscle (-7.0 +/- 0.1), distal longitudinal muscle, and proximal circular muscle was similar. Methysergide dose-dependently inhibited the 5HT stimulation of both proximal and distal circular muscle. The IC50 for methysergide inhibition of 5HT (5 x 10(-7) M) stimulation was -5.5 +/- 0.2. Ketanserine and ICS 205-930 did not inhibit 5HT stimulation of colonic muscle. Tetrodotoxin (TTX) decreased the potency, but not the efficacy of 5HT stimulation of proximal and distal circular muscle. Atropine decreased the potency (EC50 = -6.6 +/- 0.1) (P less than 0.05) and the efficacy by 40%. Electrical field stimulation (EFS) caused an on-contraction and off-contraction of distal circular muscle and an on-contraction of proximal circular muscle. 5HT decreased the off-contraction of the distal circular muscle but did not affect the on-contraction of the other muscle strips. 5HT receptor antagonists did not affect EFS of the tissue. The studies suggest: (1) 5HT stimulates circular colonic muscle with greater efficacy than longitudinal muscle, (2) 5HT stimulates circular muscle through a 5HT1 receptor, (3) there is atropine-sensitive and atropine-insensitive 5HT stimulation of circular colonic muscle, (4) 5HT inhibits neurons responsible for the off-contraction in distal circular muscle without affecting the on-contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnesium citrate-bisacodyl regimen proves better than castor oil for colonoscopic preparation.

BACKGROUND: A clean colon preparation prior to endoscopy or X-ray examination is essential to obtain an accurate diagnosis. In order to determine which of two easily made preparations is better, this study compares colon cleansing efficacy, patient acceptance and side effects in patients given either a magnesium citrate-bisacodyl or a castor oil regimen prior to colonoscopy. METHODS: Seventy outpatients scheduled for colonoscopy were randomized to receive one of two bowel evacuation regimens on the day prior to the examination. Group 1 (n = 36) received a magnesium citrate solution (250 mL) and bisacodyl (10 mg, orally). Group 2 (n = 34) received castor oil (60 mL, orally). RESULTS: The cleansing effect of the magnesium citrate-bisacodyl regimen was significantly better than that of castor oil in the ascending colon and caecum (cleansing scores 5.2+/-1.2 vs 3.5+/-1.3, P< 0.0001), but similar to that of castor oil in the recto-sigmoid, descending and transverse colon. Abdominal pain (38 vs 11%, P< 0.01) and nausea (29 vs 8%, P<0.05) were significantly more common in patients receiving the castor oil preparation than in patients administered with the magnesium citrate-bisacodyl regimen. More patients complained of poor acceptance with the castor oil regimen than with the magnesium citrate-bisacodyl regimen (24 vs 8%, P=0.06). CONCLUSIONS: A combined oral magnesium citrate and bisacodyl regimen is effective and better than castor oil for colonoscopic preparation.

Clinical values of CA19-9, CA125 and CEA in malignant obstructive jaundice.

BACKGROUND: Serum CA19-9, CA125 and CEA are glycoproteic tumor markers and they have been used for detecting patients with pancreatobiliary diseases in whom obstructive jaundice is common. This study was designed to investigate whether cholestasis may interfere with the clinical application of these tumor markers or not. METHODS: Radioimmunoassay for serum CA19-9, CA125 and carcinoembryonic antigen (CEA) was obtained from 86 patients with hyperbilirubinemia, including 50 patients with malignant jaundice (pancreatic carcinoma 20, biliary tract carcinoma 30) and 36 patients with benign jaundice (choledocholithiasis 33, acute cholangitis 3). Clinical follow-up for the utility of these markers on the patients with obstructive jaundice was conducted. RESULTS: In patients with malignant jaundice, higher positive rates of CA19-9 (94% vs 56%, p < 0.01), CA125 (52% vs 17%, p < 0.01) and CEA (42% vs 6%, p < 0.01) than in those with benign jaundice were found. In diagnosis of malignant tumors, sensitivity was superior in CA19-9 (94%) than in CA125 (52%) and CEA (42%), but the latter two had higher specificities (83% and 95%). In malignant jaundice, elevated serum bilirubin levels were correlated with CA125 (r = 0.34, p < 0.05) but not with CA19-9 levels. In benign jaundice, serum bilirubin were correlated with CA19-9 (r = 0.58, p < 0.001) and CA125 (r = 0.45, p < 0.01) levels. The correlation between serum bilirubin and CEA levels was not significant in either group. After effective drainage, all markers decreased significantly in patients with benign jaundice but not in those with malignant diseases. CONCLUSIONS: Elevated serum CA19-9, CA125 and CEA levels were observed in both benign and malignant pancreatobiliary diseases with obstructive jaundice. Longitudinal follow-up of these markers and other complementary studies are essential for diagnosis of malignant tumors when cholestasis is present.

The prevalence and characterization of verotoxin-producing Escherichia coli isolated from cattle and pigs in an abattoir in Hong Kong.

The aim of the study was to define the prevalence of verotoxin-producing Escherichia coli (VTEC) in cattle and pigs in a Hong Kong abattoir. Faecal and carcass samples collected from 986 cattle and 487 pigs from an abattoir were tested for verotoxin (VT) by PCR and cytotoxicity assays. VTEC was isolated from 415 and 1-8% of cattle faecal and carcass samples and from 2.1 and 0.2% of porcine faecal and carcass samples, respectively. Amongst 409 VTEC isolates from cattle, 9 were serotype O157:H7 and eaeA+. The most prevalent vt genotype among bovine VTEC was vtl+vt2 (73.8%) and in porcine VTEC was vt2e+ (30%). None of the porcine VTEC isolates and 9.3% of the bovine VTEC isolates was eaeA+. The non-O157 serogroup VTEC isolates carrying eaeA and EHEC-hlyA belonged to serogroups O172, O15, O84, O91, O110 and O121. The local dietary preference for pork or chicken (rather than beef), the low VTEC carriage in pigs, the rarity of additional virulence factors (caeA) in VTEC isolated from cattle may explain the apparently low incidence of human diarrhoeal disease associated with VTEC in Hong Kong hitherto. However, the presence of non-O157 VTEC strains carrying the eacA virulence marker in cattle highlights the fact that sole reliance on sorbitol-MacConkey agar for screening human VTEC isolates may underestimate the human disease burden. The changing dietary habits of the population in Hong Kong reinforce the need for continued vigilance.