Management of chronic kidney disease: a Hong Kong consensus recommendation.

Chronic kidney disease (CKD) imposes a significant burden on healthcare systems worldwide, and diabetes is a major risk factor for CKD. There is currently no consensus in Hong Kong regarding the prioritisation of early identification and intervention for CKD. A comprehensive and Hong Kong-specific diabetes and CKD treatment guideline is also lacking. A multidisciplinary group of experts discussed issues surrounding the current management of CKD and reviewed evidence in the context of local experience to support recommendations. The experts used a modified Delphi approach to finalise recommendations. Consensus was regarded as ≥75% acceptability among all expert panel members. The panel members finalised 14 CKD-focused consensus statements addressing disease definition, screening, disease monitoring, lifestyle management, and treatment strategies. The recommendations provided are relevant to the Hong Kong healthcare setting and can be used as a guide by physicians across various specialties to facilitate the appropriate management of CKD.

Cost-effectiveness of influenza immunization in adult cancer patients in Taiwan.

The aim of this study was to investigate the efficacy of the influenza vaccine among cancer patients in Taiwan. We determined the effect of immunization on the following outcomes of disease: hospitalizations, emergency department visits, hospital outpatient visits, physician office visits, and deaths. Cost-effectiveness was analysed from the perspectives of the healthcare system and society. A decision tree was used, with estimates of disease burden and costs based on data from published and unpublished sources. The model followed 34 112 cancer patients aged 20-64 years who were registered by the Taiwan National Cancer Registry in 2002. An influenza immunization programme for the cancer population would prevent 2555 cases of all types of influenza infection, 660 of which would be serious cases involving hospitalization, emergency department visits and death. From the perspective of the healthcare system, the programme would cost US$7.7 million, providing net savings of US$5.4 million. From a societal perspective, the programme would cost US$28.6 million, providing net savings of US$22.3 million. This corresponds to savings of US$2107 and US$6338 per case averted, from healthcare and societal perspectives, respectively, as well as 110 lives saved. Lesser disease burden, greater vaccine efficacy and lower cost of hospitalizations increased cost-effectiveness. Influenza immunization for cancer patients is cost-saving and cost-effective from a healthcare and societal perspective in Taiwan. We highly recommend annual influenza vaccinations for this patient group.

Videokeratography of keratoconus in monozygotic twins.

PURPOSE: To determine the corneal topographic appearance in a pair of monozygotic twins and family members of the twins because one of the twins had keratoconus and the other appeared normal by clinical examination. METHODS: Clinical examination and videokeratography (Topographic Modeling System, Tomey) of the patient, his monozygotic twin brother, an older brother, and his parents were performed. The I-S values (difference in the average dioptric powers of symmetrical points between the inferior and superior cornea) were calculated. RESULTS: The patient, a 28-year-old man, had clinical keratoconus confirmed with videokeratography. Clinical examination of family members including a twin brother, an older brother and both parents revealed no corneal abnormalities. Videokeratography of the clinically normal twin brother showed inferior steepening with progression over time. The I-S value of the clinically normal brother was 1.36 (right eye) (greater than 2.00 SD of normal controls), which progressed to 1.69 (right eye), 1.32 (left eye) 5 months later and to 1.87 (right eye), 1.43 diopters (D) (left eye) 14 months later. Minimal asymmetric inferior steepening was noted in an older brother who had an I-S value of 0.81 (right eye), 1.27 (left eye). The mother appeared topographically normal. CONCLUSIONS: This study lends support to the existence of subclinical keratoconus detectable by videokeratography only.

Imprinting of hepatic microsomal cytochrome P-450 enzyme activities and cytochrome P-450IIC11 by peripubertal administration of testosterone in female rats.

The influence of peripubertal exposure to physiological doses of testosterone on the adult androgen responsiveness of hepatic microsomal cytochrome P-450 was investigated. Male and female Sprague-Dawley rats were sham-operated or gonadectomized before puberty, at 25 days of age. They were injected subcutaneously with testosterone enanthate (5 mumol/kg/day) during the pubertal time period, on days 35-49. Responsiveness to this same dose of testosterone was tested by administering the compound during adulthood, on days 81-89. The females provided a model that had not been exposed to neonatal androgen imprinting, in contrast to the males. Testosterone 2 alpha-hydroxylase activity and cytochrome P-450IIC11, which are normally expressed only in adult males, were expressed in the gonadectomized females administered testosterone during puberty with no further exposure to the hormone for the next 40 days. The levels found were similar to those in the gonadectomized male group. When the combined pubertal and adult testosterone regimen was used, a synergistic effect was produced; the 2 alpha-hydroxylase activity reached control male levels in both gonadectomized and sham-operated females and, in addition, cytochrome P-450IIC11 attained control male levels in the gonadectomized females. Testosterone 6 beta-hydroxylase and erythromycin N-demethylase activities were used as indicators of the cytochrome P-450IIIA subfamily. These activities were significantly increased only in the females treated with testosterone during both the pubertal and adult periods, reaching control male levels of 6 beta-hydroxylation. A similar effect, but in the opposite direction, was found with testosterone 7 alpha-hydroxylase, an enzyme activity indicative of cytochrome P-450IIA1. A decrease in this enzyme was produced in the females administered testosterone during both time periods, resulting in levels equivalent to those found in control males. In general, a highly significant interaction was found between the pubertal and adult treatment periods for the females, indicating a chronic effect of the pubertal exposure. The experiments with castrated males did not result in synergistic interactions, although there was some evidence of an additive effect. The results of this study support the hypothesis that the peripubertal period is a time during which testosterone imprinting of both increased basal levels and adult androgen responsiveness of some hepatic cytochrome P-450 enzymes can occur in the female rat.

Plasma, cardiac tissue and brain morphine concentrations in acute and chronic morphine-treated rats.

1. The plasma, cardiac tissues and brain morphine concentrations in rats after acute or chronic morphine treatment were measured by high-performance liquid chromatography. 2. Morphine concentrations in plasma and cardiac tissues were found to be significantly higher than those in brain after acute morphine injection. However, after chronic oral administration, morphine concentrations in plasma, cardiac tissues and brain were similar. 3. Brain concentrations of morphine following chronic administration were higher than those obtained after acute administration although concentrations in plasma and cardiac tissues were lower.

Influence of acute myocardial ischaemia on ventricular cyclic AMP concentrations in naive and morphine-treated rats.

1. Ventricular cyclic AMP (cAMP) concentrations of naïve and morphine-treated rats subjected to acute myocardial ischaemia were examined. 2. In naïve rats, ventricular cAMP levels were increased at 3 min but decreased 5 and 10 min after left coronary artery ligation. Statistically significant changes were observed in the right ventricle after 3 min and in the left ventricle after 10 min. 3. Acute morphine treatment did not significantly alter ventricular cAMP content in rats subjected to either sham operation or acute left coronary artery ligation. 4. Ventricular cAMP concentrations were significantly lower in sham-operated rats after 5 weeks of chronic morphine treatment while after 3 weeks of chronic morphine treatment, this phenomenon was seen only after acute coronary ligation. The reductions were reversed by opiate withdrawal. 5. These observations support the theory that elevated cAMP levels may contribute to the production of early ventricular arrhythmias during acute myocardial ischaemia. It is suggested that the reduction in ventricular cAMP concentrations may partly account for the previously reported decreased occurrence of early ventricular arrhythmias in chronic morphine-treated rats subjected to acute left coronary artery ligation.

Ventricular histamine concentrations in naive and morphine-treated rats during acute myocardial ischaemia.

The ventricular histamine concentrations of naive and morphine-treated rats subjected to acute left coronary artery ligation were examined. In naive animals, there was a significant increase in the right ventricular histamine level at 5 min following ligation, but not at 3 or 10 min. Left ventricular histamine concentrations tended to decrease, but the changes were not statistically significant. In shamoperated rats, neither acute nor chronic morphine treatment significantly altered either right or left ventricular histamine levels. Acute morphine treatment also did not significantly affect the ventricular histamine content at 5 min following coronary artery ligation. However, both right and left ventricular histamine concentrations were found to be significantly lower in chronic morphine-treated rats than in the naive animals when they were subjected to acute myocardial ischaemia. If the hypothesis that histamine release may contribute to the genesis of early ventricular arrhythmias resulting from acute myocardial ischaemia is accepted, the present findings suggest that the previously reported decreased incidence and delayed onset of early ventricular arrhythmias induced by acute left coronary artery ligation in chronic morphine-treated rats may be attributed to the reduced ventricular histamine concentrations.

Ventricular noradrenaline concentrations in naïve and morphine-treated rats subjected to acute myocardial ischaemia.

1 Ventricular noradrenaline concentrations in morphine-treated rats subjected to acute left coronary artery ligation were measured by high performance liquid chromatography with electrochemical detection. 2 In naïve rats, acute left coronary artery ligation induced a significant increase in right ventricular noradrenaline concentration at 5 min and significant decreases in left ventricular noradrenaline concentration at 3 and 10 min. 3 Acute morphine treatment did not significantly alter ventricular noradrenaline concentrations in rats subjected to acute coronary artery ligation. 4 Chronic morphine treatment caused significant declines in ventricular noradrenaline concentrations in rats subjected to acute coronary artery ligation. The reductions increased with duration of opiate treatment, and were reversed by opiate withdrawal. 5 These findings indicate that there is an increase in sympathetic activity during acute myocardial ischaemia. It is suggested that chronic morphine treatment may be able to retard this response, and consequently to lessen the occurrence of early ventricular arrhythmias resulting from acute myocardial ischaemia.

Cardiovascular responses to acute myocardial ischaemia in morphine-dependent rats.

1. The cardiovascular responses to acute myocardial ischaemia were studied in opiate-dependent animals before and after 2 weeks morphine withdrawal. 2. Rats were treated with morphine sulphate in drinking water for 2, 3 or 5 weeks. The development of morphine tolerance and dependence was verified by the tail-immersion test for analgesia and the naloxone-precipitated withdrawal syndrome, respectively. 3. Acute left coronary artery ligation induced a decrease in blood pressure, a slight increase in heart rate and ventricular tachycardia or fibrillation in anaesthetized naive rats. 4. Chronic morphine treatment did not alter the haemodynamic responses to coronary artery ligation. However, a significantly lowered incidence, and prolonged time of onset, of ventricular arrhythmias was found in 3 and 5 week morphine-treated rats. This phenomenon did not occur in animals receiving morphine for 2 weeks and in a 3 week morphine-treated group which was subsequently withdrawn for 2 weeks. 5. It is suggested that the decreased occurrence of early ventricular arrhythmias resulting from acute myocardial ischaemia in chronic morphine-treated rats may be related to the degree of opiate tolerance and dependence.

Effects of morphine on cardiovascular responses to acute myocardial ischaemia in rats.

The effects of acute coronary artery ligation on cardiac rhythm and haemodynamics were studied in rats receiving either acute or chronic morphine-treatment. In chronic opiate-treated animals, increasing concentrations of morphine sulphate were administered in drinking water over a 3 week period, and the development of morphine tolerance and dependence was verified by decreased analgesic responses to morphine in the tail-immersion test and the occurrence of naloxone-precipitated withdrawal syndromes, respectively. Acute coronary artery ligation induced a decrease in blood pressure, a slight increase in heart rate, and ventricular tachycardia or fibrillation in anaesthetized rats. The changes in blood pressure and heart rate following acute coronary artery ligation were not significantly altered by acute or chronic morphine administration. The incidence and the time of onset of ventricular tachycardia or fibrillation were found to be significantly reduced and prolonged, respectively, in chronically morphine-treated rats, but were not significantly affected by acute morphine administration in naïve animals. These findings suggest that chronic morphine treatment lessens the occurrence of early ventricular arrhythmias caused by acute myocardial ischaemia in rats. The mechanism of this effect is unclear.

Binding of antigen in the absence of histocompatibility proteins by arsonate-reactive T-cell clones.

Inducer T-cell clones reactive to the p-azobenzenearsonate (arsonate) hapten possess binding sites for radioactive arsanylated proteins, which are not present on clones with other antigen specificities. Binding occurred in the absence of histocompatibility proteins. Binding was specific for the p-azobenzenearsonate hapten, since unconjugated proteins and proteins conjugated to the nonactivating o-azobenzenearsonate hapten neither bound to the clones nor competed binding of radioactive antigen. One of the clones was studied in more detail, using a panel of structural analogs of arsonate conjugated to the carrier protein ovalbumin. All conjugates that activated the clone in the presence of antigen-presenting cells also competed binding of radioactive antigen in the absence of antigen-presenting cells. Nonactivating conjugates did not compete binding. Based on evidence in this and the succeeding paper (Rao et al., accompanying paper), we suggest that these arsonate-binding sites may include the physiological antigen receptors of arsonate-reactive T-cell clones.