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Biomedical subjects

J T Kwan

Publications and source records attributed to J T Kwan.

At least 37 records · Page 2Linked to original sources

Parathyroid sensing of the direction of change of calcium in uremia.

It could be advantageous for the parathyroids to be able to sense not only the absolute concentration of extracellular Ca2+, but also the rate and direction of change of Ca2+, thereby allowing the parathyroids to respond earlier to threats to Ca2+ homeostasis. By using high and low Ca2+ dialysis in a single session, we examined the parathyroid response to direction of change of Ca2+ during acute Ca2+ perturbation in nine hemodialysis patients. Separate PTH/ionized calcium (PTH/iCa) response curves were generated for rising Ca2+ and falling Ca2+. Significant directional hysteresis (higher PTH level during falling than during rising Ca2+) was found. During hypercalcemia, PTH levels were between 2.2 and 1.6 times higher at iCa concentrations of between 0 and +0.1 mM above the baseline iCa, when Ca2+ was falling than when it was rising. During the phase of induced hypocalcemia, parathyroid fatigue was seen in six of the nine patients. Fatigue patients tended to have higher basal PTH (1-84) levels than those not showing fatigue. The existence of fatigue provides an explanation for directional hysteresis during hypocalcemia, and therefore parathyroid sensing of the direction of change of Ca2+ could not be assessed during hypocalcemia. These studies demonstrate a capacity of the parathyroids to sense the direction of movement of Ca2+ during hypercalcemia.

Adult↗

Serum and urinary alpha-1 microglobulin levels in renal disease.

Serum and urinary levels of alpha 1-microglobulin (AM) were measured in healthy volunteers and patients with varying degrees of renal insufficiency (from mild impairment to functionally anephric patients). In all 33 healthy volunteers, 57 chronic renal disease and 22 functionally anephrics were studied. Serum creatinine (sCr) and 24-hour creatinine clearance (CCr) were used to assess renal function. Serum AM (SAM) increased with declining glomerular filtration and correlated well with CCr (r = -0.89, n = 90, P < 0.001) and sCr (r = 0.90, n = 112, P < 0.001). sAM increased faster than sCr as the filtration function diminished and may be a more sensitive indicator of impairment in renal glomerular filtration. Urinary AM (uAM) also increased as renal filtration decreased and the number of functional nephrons reduced. uAM correlated with sAM (r = 0.62, P < 0.001) and CCr (r = -0.50, P < 0.001). uAM had a higher percentage increase compared with sAM during the decline in renal function but was more poorly correlated with CCr or glomerular filtration function. It is concluded that AM is useful in assessing glomerular filtration function in addition to its well established relevance in tubular evaluation, and has potential in the longitudinal assessment of changes in renal function in renal disease and systemic diseases that affect the kidney.

Adult↗

Juvenile chronic arthritis and Wegener's granulomatosis.

We present a case of Wegener's granulomatosis in a teenage boy with systemic onset juvenile chronic arthritis. We discuss the implication of these two uncommon conditions coexisting in one patient. The recent characterization of the antineutrophil cytoplasmic antibody (ANCA) as a marker of small vessel vasculitis has helped in the differential diagnosis of pulmonary renal syndromes.

Adolescent↗

Carbamylated haemoglobin in normal, diabetic and uraemic patients.

Carbamylated haemoglobin arises from the non-enzymic modification of haemoglobin monomers by isocyanate derived from the spontaneous dissociation of urea. We measured carbamylated haemoglobin by high performance liquid chromatography in healthy subjects, non-uraemic hospital patients, diabetics, and different groups of uraemic patients. Carbamylated haemoglobin levels were found to be raised in uraemic subjects, but were independent of age, sex, glycaemic state and haemodialysis procedure. There was no significant difference in carbamylated haemoglobin levels between two groups of patients having different modes of dialysis treatment, probably indicating a similar degree of uraemic exposure in these patients.

Adult↗

'Pulse' oral calcitriol in uraemic patients: rapid modification of parathyroid response to calcium.

We performed dynamic parathyroid function tests, with generation of parathyroid hormone/ionized calcium (PTH/iCa) response curves, obtained during sequential hypercalcaemic and hypocalcaemic dialysis, on six haemodialysis patients before and after 4-weekly 'pulse' doses of oral calcitriol. There were no significant changes in the pretreatment, 2-week and 4-week values of blood ionized calcium, serum total calcium, phosphate, and alkaline phosphatase. PTH decreased significantly after 4 weeks of treatment with calcitriol (P less than 0.03), and the post-treatment PTH/iCa curves were all displaced leftwards and downwards, indicating a marked inhibitory effect of calcitriol on parathyroid responsiveness across and beyond the physiological range of calcaemia. The mean shift of the PTH/iCa relationship was equivalent to a reduction of iCa of 0.2 mM for any given concentration of PTH, and conversely to a 70% reduction of PTH for any given blood iCa. The results suggest that wide spacing of oral 'pulse' doses of calcitriol can achieve favourable modification of the PTH/iCa relationship, and that dosing interval and dose size, rather than route of administration, may be the major determinants of the previously reported superiority of intravenous over daily oral calcitriol regimens.

Administration, Oral↗

Changes in total body bone mineral content and regional bone mineral density in renal patients following renal transplantation.

We performed serial measurements of total body bone mineral content (BMC) and bone mineral density (BMD), and of regional BMD at the lumbar spine and femoral neck using dual energy X-ray absorptiometry. Twenty-six patients (15 females and 11 males) were studied at the time of transplantation, and 3 and 6 months post-transplant. At baseline, the total body BMC and regional BMD values of the patients did not differ significantly from age- and sex-matched controls. Total body BMC had fallen progressively at 3 months, followed by partial recovery at 6 months. Significant decreases of BMD were seen in the lumbar spine and femoral neck at 3 months with no evidence of recovery at 6 months. The changes in these indices correlated well with the duration of hospital stay in the first 3 post-transplant months. This preliminary study demonstrated rapid deterioration of skeletal integrity following renal transplantation and that this might be progressive. Preventative strategies to avoid this early bone loss may need to be investigated.

Absorptiometry, Photon↗

Mycobacterial infection is an important infective complication in British Asian dialysis patients.

To define the extent and nature of mycobacterial infection in patients on an adult dialysis unit whose catchment population contains a large proportion of non-Caucasian subjects, a retrospective survey of all new patients accepted onto our maintenance dialysis programme between January 1987 and December 1989 was carried out. Twenty-six Asian, 13 Afro-Caribbean, two Oriental and 170 Caucasian patients were accepted onto the dialysis programme in the three-year recruitment period. Eight of the 26 Asian patients, but none of the others, had developed mycobacterial infection by the end of December 1990. One patient had a cerebral tuberculoma with miliary mottling on chest X-ray, one pulmonary tuberculosis, one tuberculous adenitis and 5 tuberculous peritonitis (four due to Mycobacterium tuberculosis and one Mycobacterium kansasii). All the patients had been living in the UK for an average of 15 (range 6-24) years, with no known recent exposure to tuberculosis. Five patients are now alive and well, one developed malabsorption following M. kansasii peritonitis, but two with tuberculous peritonitis died before treatment could be instituted. Mycobacterial infections were associated with a high level of mortality and morbidity. No Asian patient developed mycobacterial infection during post-transplant immunosuppressive therapy in the study period, probably because of the routine anti-tuberculous chemoprophylaxis employed in this group of patients. The diagnosis of mycobacterial infection should be suspected when an Asian dialysis patient develops a pyrexia of unknown origin. It is likely, though not proven, that anti-tuberculous chemoprophylaxis might reduce this high incidence of tuberculous infection in Asian dialysis patients.

Adult↗

Carbamylated haemoglobin, urea kinetic modelling and adequacy of dialysis in haemodialysis patients.

Urea kinetic modelling (UKM) has increasingly been used for assessing adequacy of dialysis and protein nutritional status of dialysis patients. Using a precise HPLC method we developed, we measured carbamylated haemoglobin (CarHb) values in 20 stable twice-weekly dialysed patients and attempted to correlate their CarHb values with their UKM-derived indices. Based on these indices, 11 patients were found to have been adequately dialysed with sufficient protein intake, three patients were adequately dialysed but malnourished and six patients were under-dialysed. Estimated dietary protein intake correlated poorly with calculated daily protein catabolic rate in our patients. CarHb values were found to correlate strongly with the time-averaged urea concentrations, suggesting that CarHb might be a time-integrated urea-derived index. Those adequately dialysed patients have a mean (SD) CarHb value of 142 (29) micrograms CV/gHb against the underdialysed patients, 197 (30) micrograms CV/gHb (t-test, P = 0.002). We suggest that a CarHb value less than 175 micrograms CV/gHb may represent satisfactory uraemic exposure, whereas CarHb value greater than 175 micrograms CV/gHb is undesirable.

Adult↗

Crescentic transformation in primary membranous glomerulonephritis.

A 31 year old man first developed steroid-resistant idiopathic membranous glomerulonephritis in 1981. Stable normal renal function was maintained until August 1988 when he suffered a clinical relapse with heavy proteinuria and declining renal function. Immunosuppressive therapy with prednisolone and cyclophosphamide was instituted in an attempt to arrest this relapse. Despite this, he later developed acute renal failure with histological evidence of crescentic transformation of his nephritis. This unusual transformation was not associated with features of systemic vasculitis or positive anti-glomerular basement membrane and anti-neutrophil cytoplasmic antibodies.

Adult↗

Determination of carbamylated hemoglobin by high-performance liquid chromatography.

We have developed an HPLC method for measuring carbamylated hemoglobin (CarHb), based on the quantification of valine hydantoin formed from the released NH2-terminal carbamyl valine residue after acid hydrolysis of hemoglobin. In uremia, CarHb is produced by nonenzymatic post-translational modification of the terminal amino group of hemoglobin monomers by isocyanic acid, derived from the spontaneous dissociation of urea. We measured CarHb in 25 nonuremic control subjects, 24 nonuremic diabetic subjects, and 30 patients with stable chronic renal failure. There was no significant difference between the controls and diabetic patients, their mean (SD) CarHb values being 41 (11.5) and 38 (10.8) micrograms of carbamyl valine per gram of hemoglobin (microgram CV/gHb), respectively. Mean (SD) CarHb values in the uremic patients were much greater, 164 (87.7) microgram CV/gHb. There was significant correlation between the concentrations of CarHb and plasma urea in the uremic subjects. Thus CarHb provides a urea-derived index of chronic uremia.

Buffers↗

Isolation of organisms in CAPD peritonitis: use of nutrient broth cultures and Bactec blood culture media.

Cultures of the first cloudy dialysates from 51 consecutive episodes of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis were carried out using concentrated nutrient broth and Bactec blood culture media in addition to primary culture on solid media. Thirty-seven episodes (73%) were positive on solid media, and 42 episodes (82%) were positive by both nutrient broth and Bactec methods. The value of Gram-stained smears and WBC counts on dialysates is discussed.

Bacteria↗

Caecal perforation in a renal transplant patient with disseminated histoplasmosis.

A renal transplant patient developed a fatal caecal perforation after Histoplasma capsulatum infection acquired abroad. Disseminated histoplasmosis is an uncommon fungal infection, usually seen in patients with impaired immunity. The diagnosis should be considered in immunosuppressed patients who develop prolonged fever or whose health deteriorates unexpectedly after travelling overseas. The infection is endemic in parts of the United States of America but occurs all over the world. Rapid diagnosis is often possible by histological examination of infected tissues. Treatment if started early may lead to recovery, but if it is not treated it is usually fatal.

Cecal Diseases↗