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Biomedical subjects

W J Sluiter

Publications and source records attributed to W J Sluiter.

13 recordsLinked to original sources
PubMed1992

Relationship of cellular glutathione to the cytotoxicity and resistance of seven platinum compounds.

The role of glutathione (GSH) in the effectiveness of and resistance to 7 platinum compounds [5 Pt(II) and 2 Pt(IV) drugs] was evaluated in a 8.6-fold cisplatin (CDDP)-resistant human small cell lung cancer cell line (GLC4/CDDP), the parent GLC4 line, a 3.7-fold CDDP-resistant human embryonal carcinoma cell line (Tera-CP), and the parent Tera line (NTera2/D1). Resistance factors for both CDDP-resistant cell lines were determined after continuous incubation (4 days) with CDDP. Continuous incubation with the other studied platinum drugs revealed complete cross-resistance for carboplatin (CBDCA) and zeniplatin but less for enloplatin (ENLO) and iproplatin in both models. Tetraplatin and lobaplatin showed, respectively, partial and complete cross-resistance in GLC4/CDDP but no cross-resistance in Tera-CP. GSH level, but not glutathione S-transferase activity, of the 4 cell lines correlated with platinum drug concentrations inhibiting cell survival by 50% after continuous incubation (r = 0.86, P < 0.05). GSH depletion by DL-buthionine-S,R-sulfoximine (BSO) increased sensitivity, as measured after a 4-h exposure to the drugs, of GLC4/CDDP for CDDP 2.0-fold, for CBDCA 1.7-fold, for zeniplatin 1.7-fold, and almost to the level of the sensitive GLC4 for ENLO, whereas no effect was observed for lobaplatin and the Pt(IV) compounds iproplatin and tetraplatin. BSO-modulating effect was higher in the sensitive GLC4 line for most compounds; therefore reduction of resistance could be achieved only for CDDP and ENLO. In contrast to GLC4, no modulation occurred in Tera. In Tera-CP BSO increased sensitivity for CDDP 1.5-fold, for CBDCA 1.9-fold, and for zeniplatin 1.2-fold; no effect was observed for ENLO, lobaplatin, and the Pt(IV) compounds. Reduction of CDDP resistance by BSO was known to occur with identical cellular platinum levels and higher Pt-DNA binding in GLC4/CDDP. However, pretreatment with BSO followed by 4 h ENLO incubation increased cellular platinum levels in both GLC4 and GLC4/CDDP while Pt-DNA binding remained unchanged. In conclusion, GSH reflected sensitivity to platinum-containing drugs. However, since the involvement of GSH differed between the models and the various platinum drugs, the effect of modulation with BSO was unpredictable.

Antineoplastic Agents↗
PubMed1992

Changes in rectal epithelial cell proliferation and intestinal bile acids after subtotal colectomy in familial adenomatous polyposis.

Subtotal colectomy and ileorectal anastomosis in familial adenomatous polyposis patients can induce temporary regression of adenomas in the rectum. The mechanism for this phenomenon is unclear. We evaluated the effect of colectomy on rectal mucosal proliferation, in relation to changes in bile acid metabolism. Four familial adenomatous polyposis patients were studied before and 3-6 months after surgery, and eight others 7-22 years postoperatively. Within 6 months after surgery, the size of the proliferative zone of the colonic crypts was found to be reduced (P less than 0.05). The proliferative activity of total colonic crypts was not affected within this period. More than 7 years postoperatively, increased cell proliferation of total crypts (P less than 0.02), as well as mid (P less than 0.05) and basal (P less than 0.05) crypt compartments, were observed compared to shortly after colectomy. In duodenal bile, deoxycholic acid was absent shortly after operation, whereas several years after operation only a small fraction (2%) was present. Fecal secondary bile acid excretion diminished after colectomy and did not change several years postoperatively. In postoperative stools only, small proportions of ursocholic and ursodeoxycholic acids (about 5% each) were consistently found. As subtotal colectomy causes a temporary decrease in the length of the proliferative zone of rectal crypts toward a normal pattern, this may explain regression of rectal polyps. This temporary effect may be mediated, at least in part, by decreased amounts of cytotoxic secondary bile acids in the rectal lumen.

Adenomatous Polyposis Coli↗
PubMed1992

Long-term effects of linoleic-acid-enriched diet on albuminuria and lipid levels in type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion.

We conducted a 2-year prospective randomised study to investigate the effects of a linoleic-acid-enriched diet on albuminuria and lipid levels in Type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion (overnight urinary albumin excretion rate between 10 and 200 micrograms/min). Thirty-eight patients were randomly assigned to increase dietary polyunsaturated:saturated fatty acids ratio to 1.0 by replacement of saturated fat with linoleic-acid-rich products (n = 18, two dropouts, analysis was performed in n = 16) or to continue their usual diet (n = 20). The total fat and protein content of the diet was unaltered. Clinical characteristics, albuminuria, blood pressure, glomerular filtration rate, metabolic control and dietary composition were similar in the two groups at baseline. In the high linoleic acid diet group, linoleic intake rose from 7 +/- 4 to 11 +/- 2 energy % and polyunsaturated:saturated fatty acids ratio rose from 0.60 +/- 0.28 to 0.96 +/- 0.16 (p less than 0.001 compared to usual diet group). The median increase albuminuria was 58% (95% confidence interval, 13 to 109) during the first year (p less than 0.02) and 55% (95% confidence interval, 11 to 127) (p less than 0.01) during the second year. Glomerular filtration rate remained unaltered and filtration fraction tended to rise (p less than 0.05 compared to usual diet group). In the usual diet group, albuminuria did not significantly increased by 16% (95% confidence interval, -17 to 38) and glomerular filtration rate declined during the second year. Blood pressure tended to rise similarly in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effect of a somatostatin analogue, octreotide, on renal haemodynamics and albuminuria in acromegalic patients.

Although insulin-like growth factor I increases renal function, the renal haemodynamic abnormality underlying the glomerular hyperfiltration in acromegaly is unknown. In normal subjects, amino acids and low doses of dopamine increase the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), presumably by a predominant vasodilation of the afferent and efferent glomerular arterioles, respectively. We studied baseline GFR and ERPF (determined with 125I-iothalamate and 131I-hippuran, respectively), the renal stimulatory effects of amino acid and dopamine infusion, and albuminuria before and after 3 months octreotide treatment in seven acromegalic patients with metabolically active disease. Octreotide reduced growth hormone concentrations from 14.7 +/- 3.0 to 5.5 +/- 1.0 micrograms l-1 (mean +/- SEM, n = 7; P less than 0.001) and insulin-like growth factor I levels from 4.12 +/- 1.31 to 2.44 +/- 0.68 kU l-1 (P less than 0.02). Glucagon concentrations did not change. Baseline GFR and ERPF declined from 132 +/- 5 to 117 +/- 6 and from 547 +/- 32 to 478 +/- 31 ml min-1 1.73 m-2, respectively (P less than 0.05 for both). Initially the response to amino acids was impaired (increment in GFR: 4.8 +/- 6.0%, NS; ERPF: -1.5 +/- 6.8%, NS), whereas the response to dopamine was normal (GFR: 10.6 +/- 1.1%, P less than 0.05: ERPF: 33.2 +/- 3.1%, P less than 0.01). After octreotide, amino acid infusion increased GFR by 15.0 +/- 6.8% (P less than 0.02) and ERPF by 11.3 +/- 5.6% (P less than 0.02), while the dopamine response was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1992

Renal reserve filtration capacity in growth hormone deficient subjects.

In normal subjects, the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) acutely increase in response to infusion of amino acids and to low doses of dopamine. It is uncertain whether circulatory growth hormone (GH) is a permissive factor for these stimulatory effects. GFR and ERPF (constant infusion technique using 125I-iothalamate and 131I-hippuran, respectively) were measured before and during the infusion of dopamine and amino acids in 8 GH deficient subjects. The clearance study was repeated during concomitant administration of octreotide to investigate whether this somatostatin analogue would modify the amino acid and dopamine-induced renal haemodynamic changes. Dopamine increased baseline GFR from 89 +/- 3 (mean +/- SEM, n = 8) to 102 +/- 4 ml min-1 1.73 m-2 and ERPF from 352 +/- 19 to 476 +/- 26 ml min-1 1.73 m-2, P less than 0.001 for both. During amino acid infusion GFR and ERPF increased to 108 +/- 3 and 415 +/- 23 ml min-1 1.73 m-2, respectively, P less than 0.001 for both. Octreotide did not significantly decrease baseline and dopamine-stimulated renal haemodynamics but lowered the amino acid-stimulated GFR (98 +/- 4 ml min-1 1.73 m-2, P less than 0.05) and ERPF (381 +/- 18 ml min-1 1.73 m-2, P less than 0.05). Basal plasma glucagon concentrations were not suppressed by octreotide, whereas the amino acid-induced increments in plasma glucagon were partially inhibited. It is concluded that GH is not a necessary factor for the stimulatory effects of amino acids and dopamine on renal haemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1992

The effects of dietary supplementation with fish oil on renal function and the course of early postoperative rejection episodes in cyclosporine-treated renal transplant recipients.

In a randomized prospective coconut oil (daily 6g[63% C8:0 and 36% C10:0] [EPA-] [n = 48])-controlled trial, we investigated the effect of a one-month dietary supplementation with daily 6 g fish oil (30% C20:5 omega-3 and 20% C22:6 omega-3 as their methyl esthers [EPA+] [n = 40]) on the incidence and course of early postoperative rejection in 88 first cadaveric, cyclosporine-treated renal transplant recipients. At one month there were no differences in renal function and incidence of rejection episodes. When analyzed separately for rejection (re+) or nonrejection (re-), the rejecting and fish oil-treated patients showed a significant better recovery of renal function after a histologically confirmed rejection episode, creatinine clearance being 43 ml/min/1.73m2 in the EPA+re+group versus 27 ml/min/1.73 m2 in the EPA-re+group (P less than 0.05), and serum creatinine being 183 and 283 mumol/l (P less than 0.05), respectively. The prerejection renal function and the decline of renal function during the rejection episode did not differ significantly between the EPA+re+ and the EPA-re+ groups. The nonrejecting fish oil-treated patients showed no better renal function than the nonrejecting coconut oil-treated patients. However, cyclosporine trough levels were significantly higher in the fish oil-treated group (EPA+re- 251 versus EPA-re- 200 ng/ml [P less than 0.05]). From these results we conclude that dietary supplements with fish oil favorably influence renal function in the recovery phase following a rejection episode in cyclosporine-treated renal transplant recipients. We further conclude that one month after grafting there is no difference in the incidence of rejection episodes between the fish- and coconut oil-treated patients. The same holds true for renal function in the absence of rejection, and for the decline in renal function during a rejection episode.

Creatinine↗
PubMed1979

A renal function study in 30 patients on long-term lithium therapy.

30 patients on long-term lithium therapy have been studied. The results are presented of the urinary concentrating ability after water deprivation and the intranasal administration of vasopressin, of the simultaneous determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), of the minimal urine pH after an oral dose of ammonium chloride, and of the urinary beta-2-microglobulin excretion. Mean urine concentration (+/- SEM) after 22 hr water deprivation (= Uosm) amounted to 854 +/- 22 mOsm/kg H2O, mean GFR was 101 +/- 4 ml/min, mean ERPF 360 +/- 18 ml/min, and mean minimal urine pH 4.95 +/- 0.06. In 8 out of 30 patients there was polyuria. In these 8 patients the values were 778 +/- 51 mOsm/kg H2O, 113 +/- 6 ml/min, 415 +/- 33 ml/min and 4.99 +/- 0.08, respectively. Serum levels of beta-2-microglobulin and lysozyme and the urinary excretion of beta-2-microglobulin were normal in all patients. No correlation was established between Uosm and the serum lithium concentration during the test (0.8 +/- 0.05 mmoles/l) nor between Uosm and the average serum lithium level during treatment (0.79 +/- 0.03). GFR was only correlated with age. It was found that administration of indomethacin during the concentration test increased Uosm in these patients. The results suggest that, given proper dosage and surveillance, long-term treatment with lithium is not likely to cause disturbances in renal function.

Acid-Base Equilibrium↗
PubMed1977

[Primary amenorrhoea, hypertension, and hypokalaemia in 17-hydroxylase deficiency, a not uncommon condition (author's transl)].

Five phenotypic female patients with primary amenorrhoea, mild hypertension, and hypokalaemia are described. The condition originates from 17-hydroxylase deficiency in both adrenals and gonads. Two cases had a XY chromosome pattern, two cases were familial. It is suggested to determine serum potassium in all cases with unexplained primary amenorrhoea.

Adolescent↗
PubMed1977

Differential response of serum LH in hypogonadotropic hypogonadism and delayed puberty to LH-RH stimulation before and after clomiphene citrate administration.

The differential diagnosis between hypogonadotropic hypogonadism and delayed puberty is facilitated by comparing the response of gonadotropins to LH-RH stimulation before and after administration of clomiphene citrate 200 mg daily during 7 days. Premedication of clomiphene citrate depresses peak values of LH and FSH on LH-RH in delayed puberty. In hypogonadotropic hypogonadism clomiphene citrate raises LH-RH induced peak LH while FSH does not change.

Adolescent↗
PubMed1976

Glucose tolerance and insulin release, a mathematical approach. II. Approximation of the peripheral insulin resistance after oral glucose loading.

A parameter of peripheral insulin activity (A = 10(4)/IpGp) can be obtained after oral glucose loading by simple calcuation using insulin and glucose levels at the glucose peak. In combination with a glucose-independent parameter of beta-cell function (CIR = 100. I/G(G-70) a parameter of glucose tolerance (GT = A-CIR) is defined. The parameters allow one to separate the contributions of beta-cell function and peripheral insulin resistance to the glucose tolerance observed after glucose loading. Examples, based on the literature and our own work, illustrate the increase of A and GT by cortisone acetate premedication as well as long-term oral contraceptive medication.

Body Weight↗