Outcome of adult critically ill patients mechanically ventilated on general medical wards.

OBJECTIVE. A significant number of critically ill mechanically ventilated patients are not admitted to the Intensive Care Unit but are cared for on general wards. This study looked at the outcome of these patients. DESIGN. Case series. SETTING. A 1100-bed tertiary hospital in Hong Kong. PATIENTS. All adult patients admitted in a 2.5-year period who received invasive mechanical ventilation on general medical wards without admission to Intensive Care Unit or other special care areas. INTERVENTIONS. Invasive mechanical ventilation. MAIN OUTCOME MEASURES. The observed number of deaths, the expected number of deaths as derived from the Mortality Probability Model II system admission model, and other morbidity measures. RESULTS. Among 755 patients studied, the observed number of deaths was 673, which amounts to a mortality of 89.1%. The expected number of deaths was 570. The risk-standardised mortality ratio was 1.18 (95% confidence interval, 1.09-1.28; P<0.0005). Patients with chronic obstructive pulmonary disease had the lowest mortality rate of 70.8% (P<0.005). The post-cardiac arrest subgroup had the highest mortality of 99.0%. CONCLUSIONS. There was a worse-than-predicted survival in the absence of Intensive Care Unit care for the critically ill patients who received mechanical ventilation on general wards. Patients with chronic obstructive pulmonary disease warranted more Intensive Care Unit admissions. Early discontinuation of invasive support should be seriously considered in the post-cardiac arrest patients.

The first nocturnal home haemodialysis patient in Hong Kong.

We report our experience of the first use of nocturnal home haemodialysis in Hong Kong. The patient, a 40-year-old man with end-stage renal failure, was recruited into the Nocturnal Home Haemodialysis Programme at Princess Margaret Hospital in 2006. He received haemodialysis at home on alternate nights (3.5 sessions per week) for 5.5 to 6 hours per session. After 1 year of nocturnal home haemodialysis, his recombinant human erythropoietin requirement had been reduced by more than 50%. His serum phosphate level decreased by 35% and calcium phosphate product by 34%. After nocturnal home haemodialysis, his blood pressure control has been excellent and he was able to cease taking anti-hypertensive medications soon after commencing nocturnal home haemodialysis. Regression of his left ventricular hypertrophy has also been noted, with a 39% decrease in his left ventricular mass index. The haemodialysis adequacy index, weekly single-pool Kt/V, increased by 59% after switching to nocturnal home haemodialysis and his quality-of-life indices also showed significant improvement. Nocturnal home haemodialysis holds promise as an alternative dialytic therapy for patients on chronic haemodialysis in Hong Kong.

Two isoforms of GABA(A) receptor beta2 subunit with different electrophysiological properties: Differential expression and genotypical correlations in schizophrenia.

Single nucleotide polymorphisms in type A gamma-aminobutyric acid (GABA(A)) receptor beta2 subunit gene (GABRB2) were found to be associated with schizophrenia in Chinese, German, Japanese and Portuguese. To explore potential functional consequences of these DNA sequence polymorphisms, this study examined the expression and electrophysiological properties of two alternatively spliced products of GABRB2 along with genotypical disease association analysis. Real-time quantitative polymerase chain reaction, performed with a cohort of 31 schizophrenics and 31 controls of US population, showed 21.7% reduction in the expression of the long isoform beta(2L), 13.4% in the short isoform beta(2S) and 15.8% in the sum of the two isoforms beta(2T) in postmortem schizophrenic brain. Furthermore, two independent mRNA quantitation methods showed that the relative expression of the long over the short isoforms was significantly decreased, suggesting the occurrence of altered splicing, in schizophrenia. In male schizophrenics, the heterozygous genotypes of rs1876071 (T/C) and rs1876072 (A/G) were correlated with reduced expression of beta(2L), beta(2S) and beta(2T), and the heterozygous of rs2546620 (A/G) and homozygous-minor of rs1876071 (C/C) and rs1876072 (G/G) were correlated with reduced expression of beta(2T). Significant correlations of expression levels with different alleles and haplotypes were also indicated by quantitative trait analysis. Recombinant GABA(A) receptors expressed in HEK293 human cells containing beta(2L) underwent a steeper current rundown upon repetitive GABA activation than receptors containing beta(2S). The results thus revealed genotype-dependent expression of the alternatively spliced isoforms of GABA(A) receptor beta2 subunit, giving rise to electrophysiological consequences that could play an important role in the pathogenesis mechanism of schizophrenia.

Minimal change disease following exposure to mercury-containing skin lightening cream.

A 34-year-old woman developed nephrotic syndrome after using a skin lightening cream that contained an extremely high level of mercury. Blood and urine mercury levels were elevated and a renal biopsy revealed minimal change disease. Membranous nephropathy was excluded using immunofluorescence and electron microscopy. Her proteinuria remitted 9 months after she stopped using the cosmetic cream. This is the first reported case in the English literature of proven minimal change disease secondary to mercury exposure. It is important that mercury poisoning due to cosmetic cream is considered in the differential diagnoses for any woman who presents with nephrotic syndrome.

Sodium ramping reduces hypotension and symptoms during haemodialysis.

OBJECTIVES: To evaluate the effectiveness of sodium ramping (profiling) in reducing hypotensive episodes and symptoms during haemodialysis. DESIGN: Prospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: Thirteen patients who experienced frequent episodes of hypotension and/or symptoms such as cramps, dizziness, chest pain, nausea, vomiting, and headache during haemodialysis in the preceding 4 weeks. INTERVENTIONS: Each patient was switched from standard haemodialysis with a constant dialysate sodium concentration of 135 to 140 mmol/L to a ramped sodium haemodialysis for a period of 4 weeks. During this time the dialysate sodium concentration was ramped linearly downwards from 150 mmol/L at the beginning of dialysis to 140 mmol/L at the end of dialysis. MAIN OUTCOME MEASURES: Intradialytic hypotensive episodes, intradialytic symptoms, nursing interventions, systolic and diastolic blood pressures, and interdialytic weight gain. RESULTS: A total of 248 haemodialysis sessions undertaken by 13 patients were analysed. Switching from constant sodium haemodialysis to ramped sodium haemodialysis resulted in a significant reduction in the number of intradialytic hypotensive episodes from 5.8 (standard deviation, 6.4) to 2.2 (3.3) [P<0.05], the total number of intradialytic symptoms from 7.1 (3.4) to 0.9 (1.3) [P<0.01], and nursing interventions from 11.3 (6.3) to 1.7 (3.9) [P<0.01]. Post-dialysis systolic and diastolic blood pressures were higher during ramped sodium haemodialysis compared with constant sodium haemodialysis (systolic blood pressure, 139 [standard deviation, 23] vs 133 [22] mm Hg, P<0.001; diastolic blood pressure, 77 [11] vs 74 [13] mm Hg, P<0.01), and there was a trend towards a smaller drop in blood pressure after dialysis. The interdialytic weight gain with sodium ramping haemodialysis was greater compared with constant sodium haemodialysis (3.1 [standard deviation, 1.0] vs 2.7 [1.1] kg, P<0.001). CONCLUSION: Sodium ramping during haemodialysis effectively reduces hypotensive episodes and intradialytic symptoms. Post-dialysis blood pressure is better maintained. A side-effect of sodium ramping is a greater interdialytic weight gain.

Renal tubular acidosis and severe hypophosphataemia due to toluene inhalation.

A 21-year-old woman developed severe muscle paralysis after sniffing toluene-containing thinner solution for 2 weeks. Her serum chemistries revealed severe hypokalaemia and a normal anion gap hyperchloraemic metabolic acidosis secondary to renal tubular acidosis. Her initial presentation mimicked hypokalaemic periodic paralysis, but toxicology screening of her blood and urine revealed the correct diagnosis of toluene poisoning. Her electrolyte and acid-base status returned to normal 4 days after cessation of toluene sniffing. On another occasion, apart from renal tubular acidosis, the patient also developed severe hypophosphataemia with the phosphate level decreasing to 0.15 mmol/L. Hypophosphataemia with such a low phosphate level after toluene poisoning has been rarely reported in the literature. Toluene inhalation can result in multiple electrolyte and acid-base abnormalities, and should be considered in the diagnosis of any young patient who presents with unexplained hypokalaemia and normal anion gap metabolic acidosis.

Primary immunosuppression with tacrolimus and low-dose mycophenolate mofetil in renal transplant recipients.

Both tacrolimus and mycophenolate mofetil (MMF) are potent immunosuppressive agents used in combination for prevention of acute rejection in renal transplantation. We studied the efficacy and safety of tacrolimus/MMF-based primary immunosuppression as well as their pharmacokinetics (PK) in Chinese renal transplant recipients. Oral tacrolimus was initiated at about 0.2 mg/kg/d, dose which was adjusted to achieve target trough levels of 10 to 20 ng/mL at 3 months and 5 to 10 ng/mL thereafter. The patients also received MMF (0.5 g bid) and prednisolone. PK profiles were studied at 1 week, and 1, 3, and 6 months posttransplant. Blood samples were taken at 0 (predose), 20, 40, 60, 75, and 90 minutes and 2, 4, 6, 8, 10, and 12 hours postdose for each profile. Plasma MPA and whole blood tacrolimus levels were determined by HPLC and EMIT methods respectively. Eight patients were studied with mean follow-up of 16.1 +/- 2.4 months. One patient (12.5%) experienced a borderline acute rejection episode. Both 1-year graft and patient survival rates were 100%. Posttransplant diabetes, diarrhea, and hand tremor occurred in 12.5%, 12.5%, and 37.5%, respectively. No patient had an opportunistic infection. Tacrolimus trough concentrations showed a fair correlation with AUC(0-12h) (R(2) = 0.587). Mean MPA AUC values at 1, 3, and 6 months were 40.5 +/- 9.4, 44.4 +/- 17.3, and 57.2 +/- 20.7 mug*h/mL, respectively (P = .0486, n = 7). In conclusion, primary immunosuppression with tacrolimus, low-dose MMF (0.5 g bid), and prednisolone is effective and safe with adequate systemic MPA exposure in renal transplant recipients.

Novel mutation in the GRHPR gene in a Chinese patient with primary hyperoxaluria type 2 requiring renal transplantation from a living related donor.

We identified a patient with primary hyperoxaluria type 2 (PH2) showing recurrent stone formation, nephrocalcinosis, end-stage renal failure, and rapid oxalate deposition after renal transplantation from a living related donor. Urinary organic acid analysis performed after renal transplantation confirmed the diagnosis of PH2. We analyzed the glyoxylate reductase/hydroxypyruvate reductase (GRHPR) gene of the patient. DNA sequencing of all nine exons and exon-intron boundaries showed a novel homozygous mutation deleting the last two nucleotides of exon 8, ie, 862delTG. This deletion results in a frameshift and introduction of a premature stop codon at codon 310, ie, Ala310Stop. One of the patient's sisters is heterozygous for this mutation, and the other sister, who is the donor, does not have this mutation. The rapid deposition of oxalate in the transplanted kidney indicates that the kidney is not a major site of oxalate production. The more favorable long-term prognosis of PH2 needs to be reevaluated now that the molecular basis of PH2 has been established. DNA-based diagnosis will facilitate carrier detection, prenatal diagnosis, genetic counseling, and selection of living related donors.

Isolated non-compaction of ventricular myocardium: a report of three cases.

INTRODUCTION: Isolated non-compaction of ventricular myocardium (INVM) is a rare disorder of myocardial morphogenesis in the absence of other cardiac anomalies. Both sporadic and sex-linked recessive forms have been described. It can be identified with two-dimensional echocardiography. CLINICAL PICTURE: We report a series of 3 cases of adult males with INVM in June 2000. Clinical manifestations were congestive cardiac failure with severely depressed left ventricle systolic function and stroke. One patient had biventricular INVM. CONCLUSION: Early diagnosis of INVM is important as it is associated with a high incidence of cardiac failure, ventricular arrhythmia and remobilisation. Anticoagulation and screening of first-degree relatives is advisable.

Leopard syndrome.

The Leopard syndrome is a complex of multisystemic congenital abnormalities characterised by lentiginosis, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth and deafness (sensorineural). Hypertrophic cardiomyopathy, though not included in the mnemonic, is often associated. Although the Leopard syndrome is rare, it is important to recognise it since it can be associated with serious cardiac disease. It is advisable to follow up patients with Leopard syndrome for new onset of cardiac abnormalities and to monitor the progression of existing cardiac disease. We present a case report and review of the literature of this syndrome.

Modular construction of the protoderm and peripheral root cap in the "open" root apical meristem of Trifolium repens cv. Ladino.

Roots with open apical organization are defined by not having specific tiers of initial cells in the root apical meristem; those with closed apical organization have specific initial tiers to which all cell files can be traced. An example of the clear organization of closed roots is the development protocol of the root cap and protoderm. The key event in differentiating these tissues is the T-division, a periclinal division of the root cap/protoderm (RCP) initial that establishes a module. Each module comprises two packets, the protoderm and peripheral root cap. Consecutive T-divisions of the same RCP initial produce up to five modules on average in a lineage of cells in white clover (Trifolium repens cv. Ladino), with all lineages around the circumference of the root dividing in "waves" to form one module prior to the next. On average, clover has approximately 32 axial protoderm and peripheral root cap cells in each module, and 32 RCP lineages. The occurrence of RCP T-divisions in white clover, a root with open apical organization, and the subsequent modular construction of the root cap and protoderm, provides a link between open and closed roots and suggests a common developmental feature that most roots of seed plants may share independent of their root meristem organization type. The open apical organization of the white clover root varies from roots with closed apical organization in that the RCP initials occur in staggered positions instead of connected to discrete tiers, and the peripheral root cap and columella daughter cells form additional layers of cells. White clover also forms root hairs on all protoderm cells irrespective of their position relative to the underlying cortical cells.

Relationship between adequacy of dialysis and nutritional status, and their impact on patient survival on CAPD in Hong Kong.

OBJECTIVE: Superior patient survival on continuous ambulatory peritoneal dialysis (CAPD) with 3 x 2-L exchanges has been reported from Hong Kong. This study examined the relationship between indices of dialysis adequacy and nutrition and patient survival on CAPD in Hong Kong. DESIGN: A cross-sectional study on prevalent CAPD patients. Patients were assessed for indices of dialysis adequacy and nutritional status with a composite nutritional index (CNI). Patients were then followed for 24 months. Survival data were analyzed according to adequacy indices and nutritional status. SETTING: All prevalent CAPD patients in nine dialysis centers in Hong Kong as of 1 April 1996. MAIN OUTCOME MEASURE: Mortality. RESULTS: 937 patients were assessed: 68.2% were using 3 x 2-L exchanges per day; mean age was 54.6 +/- 13 years. Mean total Kt/V was 1.83 +/- 0.42 and total creatinine clearance was 55.6 +/- 19.5 L/week/1.73 m2. 19% of patients were moderately to severely malnourished according to the CNI. There was no significant correlation between indices of adequacy and serum albumin or CNI. The 1- and 2-year patient survival from the time of assessment was 90.9% and 79.8%. There was a trend toward better survival in patients with Kt/V greater than 2.0, but it was not statistically significant. Peritoneal Kt/V did not impact survival in anuric patients. Malnourished patients had poorer survival than patients who were better nourished (p = 0.0259). After adjusting for age and diabetes, CNI was predictive of mortality but Kt/V and creatinine clearance were not. CONCLUSIONS: This study demonstrates the importance of nutritional status over adequacy indices in predicting patient survival. There was a lack of correlation between nutritional status and conventional indices of dialysis adequacy.

A case series of drug-induced long QT syndrome and Torsade de Pointes.

INTRODUCTION: Torsade de Pointes (Tdp) is a form of polymorphic ventricular tachycardia in the setting of prolonged QT interval. Any drug that prolongs repolarisation, and hence QT interval, may cause Tdp. Predisposing factors of drug-induced Tdp include female sex, bradyarrhythmia and hypokalaemia. METHODS: We retrospectively analysed the case notes of 13 patients with drug-induced LQTS from 1991 to 2000 from National Heart Centre and Changi General Hospital. RESULTS: Causative drugs in the series were amiodarone (seven patients, 54%), sotalol (two patients), quinidine (one patient), phenothiazine (two patients) and astemizole (one patient). There were eight females and all were Chinese. The mean age was 72 +/- nine years. The patients commonly present with syncope (38%) and cardiac arrest (38%). The mean corrected QTC interval was 545 ms. The most common precipitating factor was hypokalaemia (31%). Nine patients require cardiopulmonary resuscitation and two patients (15%) died. Nine patients (69%) had underlying structural heart disease such as ischaemic heart disease, valvular heart disease and hypertensive heart disease. The left ventricular ejection fraction was normal in six patients. The onset of Tdp ranged from Day 2 to Day 5 in the seven patient with amiodarone-induced LQTS. These were inpatients who were given intravenous loading doses of amiodarone. Both patients with sotalol-induced LQTS were females on sotalol 80 mg and 240 mg per day with Tdp occurring on Day 2 and 10 months respectively. CONCLUSION: Tdp is a potentially life-threatening arrhythmia. The list of torsadogenic drugs is ever expanding. Physicians need to know the drugs which can lead to Tdp. Careful assessment of risk-benefit ratio is important before prescribing such drugs. Amiodarone-induced Tdp is not uncommon in our local population. Initiation of a class III agent, especially amiodarone, should be done judiciously, with monitoring of the QT interval and avoidance of hypokalaemia.