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Biomedical subjects

K Lynn

Publications and source records attributed to K Lynn.

15 recordsLinked to original sources
PubMed2004

Differences in the metabolism and pharmacokinetics of two structurally similar PPAR agonists in dogs: involvement of taurine conjugation.

1. The metabolism and pharmacokinetics of two structurally similar PPAR agonists, MRL-I, (2R)-7-[3-[2-chloro-4-(4-fluorophenoxy)phenoxy]propoxy]-2-ethyl-3,4-dihydro-2H-benzopyran-2-carboxylic acid, and MRL-II, (2R)-7-[3-[2-chloro-4-(2,2,2,-trifluoroethoxy)phenoxy]propoxy]-3,4-dihydro-2-methyl-2H-benzopyran-2-carboxylic acid, in dogs were investigated. 2. MRL-I was absorbed rapidly in dogs and exhibited linear pharmacokinetics over the dose range examined, 1-25mgkg(-1). In contrast, the pharmacokinetics of MRL-II were non-linear following both intravenous and oral administration. 3. The acyl glucuronide (AG) conjugate was the only radioactive component detected in bile from dogs dosed with [14C]MRL-I, whereas bile from dogs dosed with [14C]MRL-II contained varying amounts of both the AG and taurine conjugates. The percentages of the acyl glucuronide and taurine conjugates of [14C]MRL-II in dog bile were dose dependent. A higher percentage of radioactivity was associated with the taurine conjugate (about 41%) following intravenous administration at 0.2mgkg(-1) than at 0.9mgkg(-1) (about 14%) or oral administration at 5 mgkg(-1) (about 6%). The decrease in the percentage of radioactivity associated with the taurine conjugate at 0.9 mgkg(-1) was accompanied by a concomitant increase in the amount of the acyl glucuronide. 4. MRL-I, but not MRL-II, was subject to significant enterohepatic recirculation in dogs. Continuous collection of bile resulted in an 11-fold decrease in the terminal half-life of MRL-I in plasma (1.5 versus 16.6 h), and a 2.4-fold increase in its plasma clearance (4.0 versus 1.7 ml min(-1) kg(-1)) after intravenous administration at 1 mg kg(-1). 5. Collectively, the data suggest that the presence and subsequent saturation of the taurine conjugation pathway might have contributed to the non-linear pharmacokinetics of MRL-II in the dog.

Administration, Oral↗
PubMed2000

Thirty years of universal home dialysis in Christchurch.

AIM: To review 30 years of universal home dialysis in a single dialysis unit. METHOD: Analysis for patients using home dialysis since 1969 of information from hospital visits, clinical case notes and demographic and survival data from the Australia and New Zealand Dialysis and Transplant Registry. RESULTS: Since 1969 treatment options at the Christchurch Nephrology Unit for patients with end-stage renal disease have been home haemodialysis (HD), renal transplantation and, since 1979, continuous ambulatory peritoneal dialysis (CAPD). No long-term, hospital-based treatment has been offered. During this time 493 patients, aged 3-82 years, began treatment. The mean training time for home HD was 79 days (range 23-268) and for home CAPD 7 days (range 1-35). The mean HD treatment time was 7 hours x 3 per week (range 10-36 hours/week). Between 1980 and 1995, less than 5% of patients took antihypertensive drugs and 73% of those aged 18-65 years were in full or part-time employment. The mean age of patients commencing treatment increased from 41.8 years in the 1970s to 50.1 years in the 1990s. The median patient survival from 1970-1997 was 7.75 years on home HD and 2.1 years on home CAPD. Median survival on dialysis fell in the 1990's as more diabetics and older patients with comorbidity started treatment. CONCLUSIONS: Home HD allows good rehabilitation, long treatment times and good blood pressure control which may all contribute to the superior survival of home versus hospital HD. CAPD survival in Christchurch was worse than HD, but this is probably due to patient selection. A policy of universal home dialysis is still workable provided there are sufficient resources for training and support of patients in the community.

Adolescent↗
PubMed2000

A controlled trial of the effect of folate supplements on homocysteine, lipids and hemorheology in end-stage renal disease.

Elevated plasma homocysteine (Hcy), dyslipidemia and hemorheological abnormalities all occur commonly in end-stage renal disease (ESRD) and are recognized risk factors for arteriosclerosis. To study the effect of folate supplementation on these factors we conducted a randomized controlled trial. Thirteen hemodialysis (HD) and 8 continuous ambulatory peritoneal dialysis (CAPD) patients received either 5 mg folic acid daily or placebo for 3 months. After 1 and 3 months, fasting blood samples were taken for Hcy, lipid profile, blood and plasma viscosity, red blood cell (RBC) osmotic fragility, plasma fibrinogen concentration and in vivo platelet aggregability. At baseline, the CAPD patients had a higher mean plasma fibrinogen concentration than the HD patients and they also tended to have higher mean plasma viscosity. Folate-treated patients showed marked increases in RBC folate and an average decrease in plasma Hcy concentration of 33%. Mean total cholesterol, LDL cholesterol and triglyceride concentrations decreased significantly in the CAPD patients who took folate. Folate had no significant effect on hemorheology. In conclusion, folate supplements in ESRD reduce plasma Hcy concentrations and may improve lipid profiles. In our patients, hemorheological abnormalities were more marked in patients on CAPD than in those on HD and were not improved by folate supplementation.

Adult↗
PubMed1999

Spectrum of disease in familial focal and segmental glomerulosclerosis.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is the underlying pathologic entity in 5% of adults and 20% of children with end-stage renal disease (ESRD). FSGS is generally considered to be sporadic in origin. METHODS: Recently, we identified 60 families involving 190 individuals with familial FSGS, providing evidence for a subset of families in which a genetic form is segregating. Each family had at least one member with renal biopsy-confirmed FSGS and at least one other member with either renal biopsy-confirmed FSGS or ESRD. RESULTS: Twenty-six families had individuals affected in more than one generation [multigeneration (MG)], and the remaining 34 families had only a single generation (SG) affected. There was equal representation of males and females among affected individuals. Ten percent of MG families were African American, and 52% of SG families were African American. The mean age of presentation was significantly higher in the MG families (32.5 +/- 14.6 years) compared with the SG families (20.1 +/- 12.1 years, P = 0.0001). SG cases had higher levels of proteinuria at presentation (7.0 +/- 5.6 g/24 hr, compared with 3.8 +/- 3.4 g/24 hr, for the MG families, P = 0.002). On renal biopsy, tubulointerstitial damage was more severe in patients in the SG families than in the MG families; however, the level of glomerular damage did not differ between these groups. Fifty percent of the patients had progressed to ESRD by the age of 30 years. Variables measured at presentation that were independently associated with poor renal survival were decreased age, increased serum creatinine, and increased urinary protein excretion. Forty-one patients underwent successful renal transplantation, with a 10-year graft survival rate of 62%. One patient developed clinical and biopsy evidence of recurrence of FSGS in the allograft. CONCLUSION: These data confirm the existence of a non-Alport's form of hereditary glomerulonephritis, which has a morphological pattern of FSGS.

Adult↗
PubMed1999

The PINHEAD/ZWILLE gene acts pleiotropically in Arabidopsis development and has overlapping functions with the ARGONAUTE1 gene.

Several lines of evidence indicate that the adaxial leaf domain possesses a unique competence to form shoot apical meristems. Factors required for this competence are expected to cause a defect in shoot apical meristem formation when inactivated and to be expressed or active preferentially in the adaxial leaf domain. PINHEAD, a member of a family of proteins that includes the translation factor eIF2C, is required for reliable formation of primary and axillary shoot apical meristems. In addition to high-level expression in the vasculature, we find that low-level PINHEAD expression defines a novel domain of positional identity in the plant. This domain consists of adaxial leaf primordia and the meristem. These findings suggest that the PINHEAD gene product may be a component of a hypothetical meristem forming competence factor. We also describe defects in floral organ number and shape, as well as aberrant embryo and ovule development associated with pinhead mutants, thus elaborating on the role of PINHEAD in Arabidopsis development. In addition, we find that embryos doubly mutant for PINHEAD and ARGONAUTE1, a related, ubiquitously expressed family member, fail to progress to bilateral symmetry and do not accumulate the SHOOT MERISTEMLESS protein. Therefore PINHEAD and ARGONAUTE1 together act to allow wild-type growth and gene expression patterns during embryogenesis.

Alleles↗
PubMed1999

Rapid resolution of tumoral calcinosis after renal transplantation.

Three patients with extensive, symptomatic tumoral calcinosis (TC) were studied after renal transplantation. Changes in TC-related symptoms, radiological appearances, calcium, phosphate and intact parathyroid hormone concentrations were recorded. All patients noted an immediate reduction in pain and in 2 patients the TC rapidly resolved. Their TC was not palpable by 6 months and radiographs showed near complete resolution at 12 months. Both developed hypercalcemia and in one patient this was associated with polyuria and renal impairment. Bisphosphonates reduced the hypercalcemia but increasing the corticosteroids had no effect. The third patient remained dialysis dependent due to technical problems and rejection but continued on immunosuppression to preserve residual graft function. His TC improved symptomatically but grew radiologically. These cases demonstrate that rapid resolution of TC may occur after successful renal transplantation and that bisphosphonates can ameliorate the associated hypercalcemia. Early symptomatic benefit may occur without graft function and is probably due to the anti-inflammatory action of corticosteroids.

Adult↗
PubMed1996

Impaired stem cell collection by consecutive courses of high-dose mobilizing chemotherapy using cyclophosphamide, etoposide, and G-CSF.

Tandem cycles of myeloablative chemotherapy can increase dose intensity and total dose of chemotherapy, but sufficient numbers of progenitor cells must be collected to ensure hematologic recovery after each treatment. This study was undertaken to determine if two courses of mobilizing chemotherapy given 4 weeks apart using cyclophosphamide 4000 mg/m2 and etoposide 400 mg/m2, combined with G-CSF 5-10 mg/kg on days 3-16 could each provide sufficient numbers of peripheral blood progenitor cells to support tandem cycles of myeloablative chemotherapy in 20 patients with stage IV breast cancer. Leukapheresis of blood with WBC > 1000/mm3 was performed daily for up to five collections (days 12-16), and mononuclear cells, CFU-GM, and CD34+ cells were compared between the first and second collections. The second course of mobilizing treatment resulted in similar numbers of mononuclear cells collected but far fewer CFU-GM and CD34+ progenitor cells. This prevented using the second collection of progenitor cells as the sole source for the second transplant. The data suggest that a second course of cyclophosphamide, etoposide, and G-CSF given 4 weeks after the first leads to progenitor cell depletion, and efforts to increase the yield of blood-derived progenitors should focus on the initial mobilizing procedure.

Adult↗
PubMed1989

Increased skin temperature after vibratory stimulation.

The skin temperature effect of vibratory stimulation was studied in 28 healthy subjects. Vibration (50 Hz or 100 Hz) was applied to the volar surface of the left forearm for 15 min. Skin temperature of the bilateral forearms was measured before and immediately after cessation of vibration and at 5 and 10 min postvibration. Vibration at 100 Hz for 15 min on all 28 subjects was associated with a temperature increase of 4.20 +/- 0.79 degrees F that was significantly (P less than 0.01) higher than that in the controls (0.38 +/- 0.33 degrees F). Skin temperature decreased to previbration levels by 50 min of postvibration. The 11 subjects who received 50-Hz vibration for 15 min showed a skin temperature increase (0.75 +/- 0.23 degrees F) in the vibrated forearm significantly (P less than 0.01) higher than that in the control forearm (0.11 +/- 0.17 degrees F). All measurements decreased to previbration skin temperatures by 10-min postvibration. Vibration at 100 Hz also produced skin erythema in all subjects, whereas 50-Hz vibration produced no erythema. The mechanism by which 100-Hz vibration relieves pain is largely unclear, but it could be associated with increased skin temperature and erythema.

Adult↗
PubMed1982

Nortriptyline metabolism in chronic renal failure: metabolite elimination.

Single oral dose kinetics of nortriptyline and of tis two major metabolites, conjugated and unconjugated 20-hydroxynortriptyline, were studied in eight healthy subjects and 15 patients with chronic renal failure, five of whom were being treated with hemodialysis. Nortriptyline kinetics were unaltered, but the elimination of the metabolites was reduced in both groups of patients. In chronic renal failure the excretion of nortriptyline metabolites appeared to be the rate-limiting step in nortriptyline elimination. Three depressed hemodialysis patients were treated with nortriptyline (75 mg at night) for 6 wk. The ratios of the steady-state plasma concentrations of unconjugated 10-hydroxynortriptyline to nortriptyline (0.74 to 2.30) were in the same range as those in a control group of depressed patients with adequate renal function (0.53 to 4.08) who were also receiving nortriptyline. Conjugated 10-hydroxynortriptyline in renal failure patients was slow to reach steady-state concentrations and these were 10 to 20 times as high as those of the control depressed patients. Conjugated 10-hydroxynortriptyline in dialysis fluid during treatment showed that a mean 43 +/- 7% (SD) of the dose was removed by a 10-hr dialysis. Dialysis clearance of conjugated 10-hydroxynortriptyline was 58 +/- 8 (SD) ml min-1, but nortriptyline and unconjugated 10-hydroxynortriptyline were not appreciably removed by dialysis. Hemodialysis is not likely to be of value in the management of acute nortriptyline poisoning.

Adolescent↗
PubMed1981

Comparison of the serum protein binding of maprotiline and phenytoin in uraemic patients on haemodialysis.

The serum protein binding of maprotiline and phenytoin has been compared in a group of 22 uraemic patients receiving haemodialysis. Determination of protein binding was carried out in vitro using equilibrium dialysis at 37 degrees C and 14C-labelled drug. The mean percentage unbound maprotiline found in patients (10.0%, SD 2.5) was not significantly different from that obtained in healthy volunteers (mean 10.5%, SD 1.0). However, there was a significantly increased variability in binding in patients compared with healthy subjects. The mean percentage unbound phenytoin in the same patients (22.2%, SD 3.3) was significantly greater than that obtained in healthy control subjects (12.5%, SD 0.6). Although there was no correlation between maprotiline and phenytoin binding and serum concentrations of alpha 1-acid glycoprotein, there was a significant correlation between percentage unbound maprotiline and serum albumin concentrations. The findings indicate that the binding of this tricyclic antidepressant is essentially normal in uraemia, although there may be increased interindividual variability in the free fraction of drug.

Adolescent↗
PubMed1981

The pharmacokinetics of nortriptyline in patients with chronic renal failure.

1 The pharmacokinetics of single oral doses of nortriptyline were studied in twenty patients with chronic renal failure, eight of whom were receiving treatment with haemodialysis. 2 The median nortriptyline half-life was 25.2 h (range 14.5-140.0 h) and the median nortriptyline clearance was 32.3 l/h (range 8.1-122.0 l/h). 3 No differences were observed between the dialysed and non-dialysed groups. 4 Comparisons of nortriptyline half-life and clearance between the patients and groups of physically healthy subjects revealed no significant differences. 5 There was no significant linear correlation between age and either of these measurements. In the twelve patients not receiving haemodialysis there was no correlation between nortriptyline clearance and glomerular filtration rate. 6 Chronic renal failure is not associated with a significant alteration in nortriptyline metabolism as measured by its half-life or clearance, but the drug should nonetheless be used with caution, and monitored whenever possible. However, the marked inter-individual differences observed in nortriptyline half-life and clearance in patients with chronic renal failure may not be solely responsible for their unpredictable response to tricyclic antidepressant therapy, and other possible contributory factors are discussed.

Adolescent↗