Renal hypophosphatemic rickets.
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Biomedical subjects
Publications and source records attributed to J C Chan.
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Edema develops in the neonate from diverse clinical conditions; sometimes it heralds serious underlying disorders. In this review, we discuss the diagnosis and treatment of edema in the neonate.
There are two types of edema: localized edema and generalized edema. The causes of generalized edema in childhood are diverse. Formation of generalized edema involves retention of sodium and water in the kidney. The treatment of generalized edema depends on the primary etiology. Supportive nutritional and medical therapies are needed to prevent further edema. These and related features of edema in childhood are discussed in this review.
A 22-year-old Chinese woman presented with typical features of diabetic ketoacidosis. There was a family history of diabetes but she was not obese. Plasma glucose and bicarbonate levels were 27.0 mmol/l and 5 mmol/l, respectively. Significant insulin resistance was noticed: she needed up to 15 units of insulin per hour. She required up to 120 units daily for her diabetic control even after her acidosis had subsided. She was then noticed to have the clinical features of acromegaly. The diagnosis was confirmed, and a cranial CT scan confirmed the presence of a pituitary macroadenoma. She underwent uneventful trans-sphenoidal resection of the tumour and her insulin requirement gradually lessened. Acromegaly should be considered in the differential diagnosis of unexplained insulin resistance.
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We have previously proposed that a cluster of surface-exposed hydrophobic amino acids, viz., F4, L5, and L8, present at the amino-terminus of the Ca(2+)-bound form of gamma-carboxyglutamic acid domain (GD) of human protein C (PC), contributes a substantial portion of the total functional binding energy of PC and its activated form, APC, to acidic phospholipid (PL) vesicles. A deeper understanding of the importance of the hydrophobic nature of sequence position 5, and the particular relevance of leucine at that location, was sought by examination of the properties of a series of mutant proteins containing A5, V5, I5, and W5 as replacements for L5 in recombinant (r)-PC and APC. The Ca(2+)- and PL-dependent plasma-based anticoagulant activities of [L5A]r-APC, [L5V]r-APC, [L5I]r-APC, and [L5W]r-APC were determined to be approximately 28%, 51%, 98%, and 105%, respectively, of that of wild-type r-APC. A similar trend in activities of the mutant enzymes was observed in in vitro factor V/Va and factor VIII/VIIIa inactivation assays. Apparently normal Ca(2+)-dependent conformations were adopted by each of the mutant proteins, but the Ca(2+)-bound form of [L5A]r-PC was relatively the most defective of the mutants in its binding to PL. These results confirm the importance of the hydrophobic character at sequence position 5 as critical to the functional binding of PC to PL.
In order to examine relationships between albuminuria, insulin resistance, and dyslipidaemia in non-insulin-dependent diabetes (NIDDM), we studied 164 Chinese patients (68 men, 96 women), treated with diet or oral hypoglycaemic agents, on three occasions during a 6-week period. Antihypertensive treatment, if previously prescribed, was withdrawn for at least 2 weeks before the study period. Insulin resistance was calculated from simultaneous fasting plasma glucose and insulin concentrations using the homeostasis model assessment (HOMA) method. Based on two of three 24 h urinary collections, 87 (53%) patients had normoalbuminuria, 46 (28%) microalbuminuria, and 31 (19%) macroalbuminuria. Despite similar glycaemic control, patients with abnormal albuminuria had higher mean arterial pressure, fasting plasma total cholesterol, triglyceride and serum apo B concentrations and were more insulin resistant than normoalbuminuric patients. Albuminuria correlated with mean arterial pressure (r = 0.31, p < 0.001), triglyceride (r = 0.36, p < 0.001), total cholesterol (r = 0.28, p = 0.001), apolipoprotein B (apo B) (r = 0.25, p = 0.003), and insulin resistance (r = 0.25, p < 0.002). These close associations may contribute to the increased cardiovascular risk in Chinese NIDDM patients with abnormal albuminuria.
The short insulin tolerance test (ITT) is both a simple and valid method of quantifying insulin sensitivity although arterialization of samples and the risk of hypoglycaemia remain as potential difficulties. We examined the safety and reproducibility of using venous sampling with insulin doses of 0.1 U kg-1 and 0.05 U kg-1 in healthy subjects. Whole blood glucose concentrations were measured contemporaneously and the rate of plasma glucose decline (mmol l-1 min-1) for each test was estimated from unlogged venous plasma glucose concentrations measured at 1 min intervals. The mean rates of plasma glucose decline for the 0.1 U kg-1 and 0.05 U kg-1 insulin doses were 0.26 mmol l-1 min-1 (n = 11, range = 0.17-0.41, intrasubject coefficient of variation (CV) = 9.4%) and 0.25 mmol l-1 min-1 (n = 6, range 0.19-0.46, intrasubject CV = 15.9%), respectively. Reversal of significant hypoglycaemia was necessary in one subject before 15 min post-insulin. We found that: (1) venous sampling provides a reproducible measure of glucose uptake after insulin, (2) contemporaneous bedside glucose sampling identifies those at risk of significant hypoglycaemia during the ITT, and (3) the 0.1 U kg-1 dose response is more reproducible and no less safe than the half dose response. We conclude that the current ITT protocol would be made safer and simpler with the above modifications although further studies comparing venous with arterialized sampling are needed.
To test whether the peripheral macrophage functions as early index of oxygen free radical release in association with the development of IgA nephropathy (IgAN), we studied female Lewis rats. IgAN was produced by treatment over 8 weeks with 0.1% bovine gamma globulin (BGG) in drinking water, followed by three daily intravenous injections of BGG, 1 mg/dose. Fifteen rats were divided randomly into three groups: control, IgAN, and IgAN fed vitamin E 100 IU/kg chow. At the end of the treatment period, rats were placed in individual metabolic cages for 24-h urine collections and then anesthetized with Inactin (100 mg/kg BW) for aspiration of peritoneal macrophages. The results (mean +/- SD) extended our previous data in male rats, confirming that the elevated proteinuria of IgAN (3.62 +/- 0.79 mg/day) was significantly reduced with vitamin E treatment (2.59 +/- 0.28 mg/day) in female rats (P < 0.002) More importantly, we indicated for the first time that oxygen free radicals production by peritoneal macrophages in IgAN was significantly reduced by vitamin E: 1.58 +/- 0.91 nmol/10(6) cells/15 min in the untreated group vs 3.28 +/- 0.54 nmol/10(6) cells/15 min in the vitamin E-treated group (P < 0.05).
Antibodies to glutamic acid decarboxylase (anti-GAD) and pancreatic beta cell secretory function were measured in 39 consecutive Chinese patients with a clinical diagnosis of insulin-dependent diabetes mellitus (IDDM) (19 males, mean +/- SD age. 37 +/- 15 years; body mass index (BMI), 22 +/- 4 kg/m2; mean duration of disease, 6.7 +/- 5.6 years). IDDM was defined on the basis of acute symptoms with heavy ketonuria (> 3+) or ketoacidosis at diagnosis, or requirement for continuous insulin treatment within one year of diagnosis. Insulin deficiency was defined as a post-glucagon stimulated plasma C-peptide concentration < or = 0.6 nmol/l. Overall, anti-GAD antibodies were positive (> 18 units) in 23% (n = 9) of these patients. Of the 39 patients, 29 (74%) were insulin deficient and 10 (26%) were non-insulin deficient. Anti-GAD antibodies were positive in 31% of the insulin-deficient patients but in none of the non-insulin-deficient group. Insulin deficiency and anti-GAD positivity were associated with younger age, earlier age of clinical onset and lower BMI. There were independent negative relationships between levels of anti-GAD antibodies and blood pressure and a positive relationship between insulin dosage and albuminuria. This study emphasises the difficulty in differentiating clinically between IDDM and NIDDM in Chinese patients. Despite the acute presentation, these patients had variable pancreatic beta cell secretory function. The varying duration of disease may partly explain the low prevalence of positive anti-GAD antibodies in these patients, but seems unlikely to explain fully the difference from Caucasian IDDM patients.
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The maximum surgical blood ordering schedule (MSBOS) was developed to permit efficient use of blood stocks and reduce blood wastage due to outdating. Success of the MSBOS required full cooperation between surgeons, anaesthetists, blood bankers and house officers. However, clinical staff sometimes disregarded the system or distrusted the ability of the laboratory to provide blood in an emergency. This led to frustration and wastage of laboratory staff effort. We developed a computer crossmatch system that could overcome the shortcomings of the MSBOS. The advantages of this system are reported.
BACKGROUND: A good blood bank must be able to provide compatible blood units promptly to operating room patients with minimal wastage. A "self-service" by nursing staff blood banking system that is safe, efficient, and well-accepted has been developed. STUDY DESIGN AND METHODS: Specific blood units are no longer assigned to surgical patients who have a negative pretransfusion antibody screen, irrespective of the type of surgery. A computer-generated list of the serial numbers of all group-identical blood units currently in the blood bank inventory is provided for each patient. The units themselves are not labeled with a patient's name. The group O list will be provided for group O patients, the group A list for group A patients, and so forth. Should the patient require transfusion during surgery, the operating room nurses go to the refrigerator, remove any group-identical unit, and check the serial number of the unit against the serial numbers on the patient's list. If the serial number is on that list, the blood bank will accept responsibility for compatibility. The system was implemented in 1995. RESULTS: Since implementation, a total of 2154 patients have undergone operations at this hospital. Thirty-two patients received more than 10 units of red cells each. There were no transfusion errors. The crossmatch-to-transfusion ratio was reduced from 1.67 to 1.12. Turnaround time for supplying additional or urgent units to patients in operating room was shortened from 33 to 2.5 minutes. There was no incidence of a blood unit's serial number not being on the list. Work by nurses and technical staff was reduced by nearly 50 percent. CONCLUSION: The "self-service" (by nursing staff) blood banking system described is safe and efficient. It saves staff time and can be easily set up.
OBJECTIVE: This study was designed to assess sequentially the nutrient intake in children with chronic renal insufficiency and its relationship to body size, the level of renal failure, and growth velocity. METHODS: The nutrient intake from 401 4-day food records obtained from 120 children with renal insufficiency over a 6-month observation period was analyzed. The height and weight were measured at the beginning and end of the observation period. The glomerular filtration rate was estimated from the height and serum creatinine. RESULTS: The mean caloric intake in these children was 80 +/- 23% (mean +/- SD) of the Recommended Dietary Allowance (RDA) for age. Fifty-six percent of the food records obtained from these children revealed a caloric intake that was less than 80% of the RDA. Caloric intake expressed as the %RDA for age decreased with increasing age. However, the mean caloric intake when factored by body weight was in the normal range. There was no correlation between caloric intake and height velocity. The mean protein intake in these children was 153 +/- 53% of the RDA. Further, 45% of the food records indicated a protein intake greater than 150% of the RDA. There was no relationship between the degree of renal insufficiency and caloric or protein intake. Calcium, vitamin, and zinc intakes were also low. CONCLUSIONS: Children with chronic renal failure consume less calories than their age matched peers, but the majority of these children appear to ingest adequate amounts for their body mass. This reduction in caloric intake occurs early in renal insufficiency. They also ingest inadequate amounts of calcium, zinc, vitamin B6, and folate.
1. Increased salt sensitivity has been reported in first-degree relatives of hypertensive patients. To determine if the enhanced effect of oral salt intake on blood pressure in such individuals is related to abnormal renal dopamine (DA) or sympathetic nervous system responses, we studied the effects of two different sodium intakes (20 mmol/day followed by 220 mmol/day each given for 5 days) on mean arterial pressure (MAP) and urinary excretion of sodium, free DA and noradrenaline (NA) in seven normotensive Chinese subjects with a family history of hypertension. We compared these results with those we have reported previously for normotensive subjects without a family history of hypertension. 2. There was a seven- to ten-fold increase in sodium excretion (P < 0.02). MAP increased from 80.1 +/- 2.5 to 83.1 +/- 2.1 mmHg (P < 0.05). A 23% increase in urine DA (P < 0.02) was seen on day 1. From day 2 to day 5, the increase in urine DA (12-15%) became attenuated and reached statistical significance only on days 2 and 5. There was no significant change in urinary NA output. 3. As in healthy Chinese subjects without a family history of hypertension, those with a family history showed an early but unsustained rise in urine DA during oral sodium loading. Such an increase was rather small compared to the increase in urine sodium, suggesting that renal DA only contributes partly to the natriuretic response. Unlike those with no family history, subjects with a family history showed an increase in blood pressure after oral salt loading, possibly because of inadequate suppression of sympathetic nervous system activity.
A temporary elevation of serum alkaline phosphatase has been described in young children who have no evidence of liver or bone disease. This phenomenon has been termed benign hyperphosphatasemia of infancy. Its occurrence is described in three children undergoing chemotherapy for acute lymphoblastic leukemia and lymphoma. All three children were in remission and in the consolidation or maintenance phase of their therapy when the hyperphosphatasemia occurred. All children were also receiving methotrexate (IM and IV), oral 6-mercaptopurine, and oral sulfamethoxazole/trimethoprim. Although these agents are associated with hepatotoxicity, other liver transaminases (ALT, AST) remained at normal concentrations, and there was an elevation only in the bone isoenzyme of alkaline phosphatase, thus making hepatic toxicity an unlikely etiology for the hyperphosphatasemia. No alteration in chemotherapy was necessary for resolution of the elevated alkaline phosphatase in these children.
OBJECTIVE: To investigate the usage patterns of antidiabetic and antihypertensive drugs and to identify any discordance between recommended management guidelines and clinical practice in two study locations. DESIGN: Prescription survey. SETTING: A government- operated general outpatient clinic (GOPC) and a medical/geriatric specialist clinic (SC) affiliated with a regional hospital in the same district. PATIENTS: Patients presenting with a prescription during the study period at the respective pharmacy were classified as having diabetes if at least one antidiabetic agent was prescribed and as having hypertension if a cardiovascular drug was prescribed in a hypotensive dosage. MAIN OUTCOME MEASURE: The pattern of use of antidiabetic and antihypertensive drugs. RESULTS: One thousand one hundred forty-four consecutive prescriptions were collected in the GOPC, and 1523 in the SC. Of 9.4% (n = 107) of patients were classified as having diabetes in the GOPC and 20.4% (n = 310) in the SC (p<0.001). Most patients with diabetes were taking oral hypoglycemic agents (98.1% in GOPC vs. 84.5% in SC). Glibenclamide was the sufonylurea used most often as monotherapy in both settings (50.5% in GOPC vs. 40.6% in SC). The combined use of a sulfonylurea with metformin was common in both settings (22.4% in GOPC vs. 28.4% in SC). Metformin monotherapy (1.9% in GOPC vs. 2.6% in SC) and combination treatment of insulin with an oral agent (0% in GOPC vs. 2.6% in SC) were rarely prescribed. In the GOPC, 24.5% (n = 280) of patients were prescribed an antihypertensive drug compared with 47.1% (n = 717) in the SC (p< 0.001). In the GOPC, the use of antihypertensive drugs was more prevalent in those with diabetes (53.5%) than in the remaining patients without diabetes (21.5%, p<0.001). In the SC, 51% of patients with diabetes were receiving antihypertensive drugs, but 40% of patients without diabetes were also receiving three treatments. In the GOPC, diuretics (indapamide 14.3% other 59%) and methyldopa (9.5%) were the most frequent choices of antihypertensive drugs when used as monotherapy in subjects without diabetes. In the SC, apart from diuretics (indapamide 12.9%, other 20.3%), beta-blockers (29%) also were prescribed frequently. If treated with only one antihypertensive drug, most patients with diabetes in the GOPC were prescribed indapamide (72.7%), and patients in the SC were treated mainly with angiotensin-converting enzyme inhibitors (35%) indapamide (22.5%), or calcium-channel blockers (13.8%). CONCLUSIONS: In this prescription-based survey, diabetes mellitus and hypertension were found to be common diseases in general practice and in a hospital SC. Oral hypoglycemic agents were the main from of antidiabetic therapy in both settings, with glibenclamide being the most commonly prescribed sulfonylurea. The types of antihypertensive drugs used were different in the two locations and varied according to the coexistence of type II diabetes mellitus. Despite some potential limitations, prescription-based surveys are an easy and economical method for surveying the occurrence of some common medical problems and the pattern of drug use in a fairly large number of patients in health institutions.
BACKGROUND: Many risk factors for cardiovascular disease (CVD) have been identified. Recently an association between low concentration of serum bilirubin and increased risk of CVD has been reported. However, information on this topic remains scarce. METHODS: We examined the relationships between serum bilirubin and CVD risk factors in 1508 Hong Kong Chinese. We divided the subjects into four quartiles based on serum bilirubin concentrations. Cardiovascular risk factors studied include age, sex, smoking, obesity glycaemic status and lipid indices. RESULTS: Decreasing serum bilirubin concentration was associated with older age, increased prevalence of smoking, higher body mass index and systolic blood pressure, increased glycated haemoglobin, fasting and 2 h insulin, triglyceride, very-low-density lipoprotein and apolipoprotein B concentrations, and lower high-density lipoprotein concentration. Women had lower bilirubin concentrations than men. After adjustment for age, sex, smoking and insulin levels as covariates, the associations between serum bilirubin concentration and glycated haemoglobin, triglyceride, high-density lipoprotein and very-low-density lipoprotein persisted. The prevalence rates of abnormal glucose tolerance (impaired glucose tolerance or diabetes) were similar amongst the four quartiles of bilirubin concentrations. However, the mean bilirubin concentration was significantly lower in subjects with abnormal glucose tolerance (9.3 +/- 3.5 mumol/l, n = 178) than in normal subjects (10.1 +/- 5.2 mumol/l, n = 1330, P = 0.039). When analysed as a continuous variable by age-adjusted partial correlation coefficients, serum bilirubin concentration was inversely correlated with fasting insulin, triglyceride, very-low-density lipoprotein and glycated haemoglobin level. CONCLUSIONS: There were close associations between low serum bilirubin concentration and increased CVD risk factors. Subjects with abnormal glucose tolerance also had lower serum bilirubin concentration than normal subjects. Some of these associations (body mass index, systolic blood pressure) could be explained by differences in insulin level. These relationships between bilirubin and CVD risk factors require further clarification, although abnormal intermediary metabolism and antioxidant deficiency may be possible linking factors.