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Biomedical subjects

S Meijer

Publications and source records attributed to S Meijer.

At least 145 records · Page 8Linked to original sources
PubMed1994

Thymidylate synthase inhibition after administration of fluorouracil with or without leucovorin in colon cancer patients: implications for treatment with fluorouracil.

PURPOSE: To determine the time-dependence of fluorouracil (5FU)-induced thymidylate synthase (TS) inhibition in colon cancer patients, the effect of leucovorin (LV), and the relation to response. PATIENTS AND METHODS: A 5FU injection (500 mg/m2) was given to 47 patients with advanced colorectal cancer; tumor biopsy specimens were obtained 1 to 72 hours after laparotomy. Eleven patients received LV (2-hour infusion of 500 mg/m2) with 5FU midinfusion; biopsies were obtained after 45 hours. TS inhibition was evaluated by comparing the number of total and free 5-fluoro-2'-deoxy-uridine-5'- monophosphate (UMP) (FdUMP) binding sites and the total and residual catalytic activity of TS. RESULTS: The total catalytic TS activity varied from 0 to 621 pmol/h/mg protein and the total number of FdUMP binding sites varied from 0 to 976 fmol/mg protein. The residual catalytic TS activity after 2, 23, and 45 hours was 41%, 65%, and 74% of the total catalytic activity; the number of free FdUMP binding sites was 12%, 27%, and 49% of the total number, respectively. LV enhanced TS inhibition after 45 hours; the residual catalytic activity decreased from 74% to 49%, and the number of free FdUMP binding sites from 49% to 24%. Eleven of 19 patients treated with hepatic arterial infusion of 5FU had a partial response (PR). In the nonresponding patients, total TS activity was significantly higher (P < .05) than in responding patients. A high TS activity with a poor inhibition correlated with no response. CONCLUSION: Residual and total TS activity are predictive for response to 5FU. The findings may be applicable for treatment of patients with advanced disease and TS should be evaluated as a prognostic factor in adjuvant chemotherapy studies.

Adult↗
PubMed1994

Effects of cyclosporin A withdrawal on renal function and renal stimulation in liver transplant patients treated with triple-drug immunosuppression for over 2 years.

The influence of CsA withdrawal on the glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) was prospectively studied in nine stable liver transplant recipients. Before CsA withdrawal (test 1), and 6 months thereafter (test 2) the renal function was determined by measuring GFR and the ERPF with 125I-iothalamate and 131I-hippuran respectively. The renal function was also stimulated with dopamine, with an amino-acid infusion and a combination of both. After CsA withdrawal the GFR increased, median from 74 ml min-1 to 90 ml min-1, (P < 0.04). The ERPF also increased, median from 310 ml min-1 to 380 ml min-1, (P < 0.03). In test 1 as well as in test 2 the renal function could be stimulated, especially with dopamine. GFR and ERPF improved, even after more than 2 years of CsA treatment. These results suggest that long-term CsA treatment impairs the renal function, though in these liver transplant patients CsA treatment did not prevent afferent and efferent arteriolar vasodilatation after renal stimulation. This reversible intrarenal vasoconstriction during CsA treatment may predict renal improvement after CsA withdrawal.

Adult↗
PubMed1994

Unimpaired immune functions after laparoscopic cholecystectomy.

BACKGROUND: The advantages of laparoscopic cholecystectomy over the open procedure seem to be related to the lesser surgical trauma. Whether this is also reflected by reduced postoperative immune suppression is not known. METHODS: The perioperative cellular immunocompetence of patients undergoing either laparoscopic (n = 8) or open (n = 8) cholecystectomy was evaluated before operation and at 24 hours and 6 days after operation for inflammatory reactivity by white blood cell counting and serum interleukin-6 assessment. Immunocompetence was evaluated by skin testing with phytohemagglutinin and by phenotyping blood mononuclear cells. RESULTS: Although 24 hours after conventional cholecystectomy granulocyte and interleukin-6 levels were strongly increased, laparoscopic cholecystectomy did not affect these acute inflammation parameters. Patients who had undergone conventional cholecystectomy showed a strong reduction of phytohemagglutinin responsiveness, in contrast to laparoscopic patients (67% versus 0% reduction). Flow cytometric analysis of blood mononuclear cells revealed a distinct reduction of HLA-DR expression on monocytes in the open cholecystectomy group only. Both parameters returned to baseline levels within 6 days after operation. CONCLUSIONS: In contrast to open cholecystectomy, laparoscopic cholecystectomy does not significantly affect parameters reflecting immunocompetence. This lack of interference with cellular immune functions provides another argument favoring laparoscopic rather than open cholecystectomy.

Adult↗
PubMed1993

Laparoscopic ultrasonography for hepatobiliary and pancreatic malignancy.

Despite the advances made since the introduction of ultrasonography, computed tomography and magnetic resonance imaging, a wide discrepancy may occur between preoperative and peroperative staging of gastrointestinal malignancy with liver and peritoneal metastases. Diagnostic laparoscopy performed immediately before a planned laparotomy can provide valuable information for the accurate assessment and appropriate management of some forms of gastrointestinal malignancy, especially that of the liver and pancreas. For evaluation of small liver and retroperitoneal malignancies, intraoperative ultrasonography performed by laparotomy is of proven value. It is now technically possible to perform ultrasonography through a laparoscopic cannula using high-resolution ultrasonographic transducers. This combination of laparoscopy and ultrasonography was studied in 25 patients with established liver lesions, carcinoma of the gallbladder or pancreatic cancer. Additional information leading to a change in surgical approach was obtained in 20 patients. Laparoscopic ultrasonography, although still in a preliminary phase of development, is a simple and reliable technique that will contribute to more accurate staging of intra-abdominal malignancy.

Adult↗
PubMed1993

Colon carcinoma during pregnancy: a lethal coincidence.

Carcinoma of the colon during pregnancy is rare. A 38-year-old woman with an obstructive adenocarcinoma of the left colon diagnosed at 27 weeks of gestation is described. Three months and 21 months after hemicolectomy a right, subsequently left ovariectomy was performed because of metastatic disease. Three years after initial surgery, which was followed by chemotherapy, the patient died of metastatic disease. Until now 26 cases of colon cancer during pregnancy have been described; none of these patients have survived 5 years. Metastatic spread of colon cancer to the ovaries in pregnant patients is frequently observed (25%). The fetal risk is very small, because placental and fetal involvement in maternal malignancy is rarely observed, even in widespread metastatic disease.

Adenocarcinoma↗
PubMed1993

Zeniplatin in patients with advanced ovarian cancer, a phase II study with a third generation platinum complex.

25 patients with residual or recurrent ovarian cancer were treated with the new platinum complex zeniplatin (CL 286,558) and 23 patients were evaluable for response. Responses were achieved in 4 patients, 1 complete and 3 partial remissions (16%). 7 patients had stable disease and 12 patients had tumour progression. At a median follow-up of 12 months, the median progression-free survival in responding patients was 11 months and overall survival 81%. The median overall survival of progressive patients amounted to 9 months, indicating the advanced stage of disease in most patients. Renal function was monitored by isotope clearance studies. There was no significant change in effective renal plasma flow (ERPF) or glomerular filtration rate (GFR) in 10 patients who completed six cycles of treatment. 1 patient with a marginal creatinine clearance at baseline suffered from sudden and severe renal failure during the first cycle. Zeniplatin may be active in relapsing, platinum-pretreated patients, and has no direct effects on renal function as measured by isotope clearance. Despite these findings, occasional nephrotoxicity may occur in patients with compromised kidney function, even with prophylactic hydration, and thus limit the application of this new analogue.

Adult↗
PubMed1993

Macrophage populations in different stages of induced hepatic metastases in rats: an immunohistochemical analysis.

Macrophages play a role in the host defence against cancer. Little is known about changes in macrophage populations during early metastatic growth. To evaluate the distribution, number and phenotype of macrophages in the development of hepatic metastases in a rat model (Wag/Rij rats and syngeneic CC531 colon carcinoma cell line), an immunohistochemical study was performed with the monoclonal antibodies ED1 (monocytes, and all macrophages), ED2 (resident tissue macrophages, like Kupffer cells) and ED3 (a subpopulation of macrophages which may play a role in the recruitment of lymphocytes). OX19 and His14 were used to identify lymphocytes. In this study a new monoclonal antibody CC52 is described, which recognizes the CC531 tumour cell line. Liver metastases were induced by injection of CC531 colon carcinoma cells into a mesenteric vein. Rats were killed at various intervals. Results show three major macrophage populations during hepatic tumour growth: (1) on day 3, infiltrates are observed around the micrometastases, which contain mainly newly recruited macrophages (ED1+ and ED2-); (2) after 7 days, ED3-positive (ED3+) macrophages together with T lymphocytes are found in the infiltrates; (3) an increase in the number of ED2-positive (ED2+) Kupffer cells is observed in the liver parenchyma after 14 days. In conclusion, the present results suggest that various populations of macrophages, newly recruited (ED1+) as well as resident Kupffer cells (ED2+), are involved in the immune response against tumour cell deposits in the liver.

Adenocarcinoma↗
PubMed1993

Long-term effects of protein-restricted diet on albuminuria and renal function in IDDM patients without clinical nephropathy and hypertension.

OBJECTIVE: To determine the long-term effects of an LPD on albuminuria and renal hemodynamics in IDDM patients without nephropathy. RESEARCH DESIGN AND METHODS: We selected 31 patients with overnight albuminuria between 10 and 200 g/min and without hypertension from a referral-based diabetic clinic. One participant dropped out. A 2-yr randomized prospective study was conducted on 14 patients assigned to an LPD (0.6 g.kg-1.day-1) and 16 patients assigned to continue their UPD. Protein intake was assessed by using urinary urea excretion. Albuminuria (three overnight collections) was measured at baseline and on seven occasions thereafter. GFR and ERPF were measured annually using [125I]iothalamate and [131I]hippuran, respectively. RESULTS: In the LPD group, protein intake decreased from 1.05 +/- 0.32 to 0.79 +/- 0.16 g.kg-1.day-1 (P < 0.005), but only seven participants consumed < 0.8 g.kg-1.day-1. Protein intake was unaltered in the UPD group (P < 0.001 vs. LPD). Baseline albuminuria and renal hemodynamics were not different in the groups. In the LPD group albuminuria decreased from 36 (95% CI, 16-83) to 30 micrograms/min (95% CI, 14-67) (P < 0.05). After adjustment for MAP and diabetes duration, the decrease in albuminuria in the LPD group was 26% (95% CI, 13-36) (P < 0.001), which was significantly different from the 5% (95% CI, -10-22) change in the UPD group (P < 0.005 vs. LPD). Multiple regression analysis showed the actual decrease in protein intake lessened (P < 0.005), whereas prevailing MAP accelerated albuminuria (P < 0.001). Low-protein intake independently reduced ERPF (P = 0.009) and GFR (indirectly via ERPF, P < 0.001) after 1 yr. Only minor changes in renal hemodynamics occurred in the second yr. CONCLUSIONS: This study suggests that long-term dietary protein restriction beneficially reduces albuminuria and renal hemodynamics in IDDM patients with mildly elevated albuminuria. Systemic BP counteracts these effects even in the absence of hypertension. Suboptimal compliance limits diet efficacy.

Adult↗
PubMed1993

Contributory roles of circulatory glucagon and growth hormone to increased renal haemodynamics in type 1 (insulin-dependent) diabetes mellitus.

The stimulatory effects of growth hormone (GH) and glucagon on renal function are well known, but it is uncertain whether these hormones are involved in the increase in renal function, characteristic of type 1 (insulin-dependent) diabetes mellitus. Therefore, the circulatory levels of GH and glucagon were measured in 10 type 1 diabetic patients with an elevated glomerular filtration rate (GFR > 130 ml min-1 1.73 m-2) and in 20 age and sex matched normofiltering patients (GFR ranging from 90-130 ml min-1 1.73 m-2). In the patients, fasting glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined using 125I-iothalamate and 131I-hippuran, respectively, during near-normoglycaemia. On a separate day, the levels of glucagon and GH were determined in the fasting basal state and after exercise. Multiple regression analysis disclosed that GFR was positively correlated with HbA1 (r2 = 0.18, p < 0.01), glucagon (r2 = 0.14, p < 0.03) as well as exercise-stimulated GH (r2 = 0.10, p < 0.05). ERPF was independently associated with HbA1 (r2 = 0.24, p < 0.005) and glucagon (r2 = 0.18, p < 0.01), whereas renal vascular resistance (RVR) was negatively correlated with stimulated GH (r2 = 0.18, p < 0.02). Kidney volume was positively correlated with HbA1 (r2 = 0.26, p < 0.001) and inversely with RVR (r2 = 0.16, p < 0.01), but not with glucagon or stimulated GH. The present study suggests that circulatory GH and glucagon play a contributory role in the renal haemodynamic changes in type 1 diabetes mellitus.

Adult↗
PubMed1993

Laparoscopic rectopexy.

Laparoscopic rectopexy has been performed in four female patients with rectal prolapse. Four or five trocars were used in each case, with the same introduction places as for laparoscopic anterior resection. After dissecting the rectum free, a polypropylene mesh was introduced and fixed to the promontorium with an endoscopic stapler device, and then sutured to the rectum leaving a fourth of the anterior rectal wall free. The average operating time was three hours and the hospital stay six days. No constipation has been observed postoperatively in the patients with preoperative normal bowel habit. The introduction of laparoscopic rectopexy opens the possibility of performing different fixation techniques for various functional problems in the pelvis, offering a significant decrease in morbidity.

Aged↗
PubMed1992

Hepatic resections for colorectal metastases in The Netherlands. A multiinstitutional 10-year study.

BACKGROUND AND METHODS: The records of 118 patients who had hepatic resections for colorectal liver metastases were analyzed retrospectively. RESULTS: The patient group, from 15 institutions in The Netherlands, was found to have a 5-year actuarial survival rate of 21% and a 5-year actuarial disease-free survival rate of 19%. The postoperative mortality rate was 7.6%. In the remaining group, the morbidity rate was 34.7%. A number of factors were examined that were reported to be of prospective significance in other studies. In the multivariate proportional hazard model of Cox, the number of metastases (P = 0.001) and the amount of perioperative blood loss (P = 0.002) were related significantly to disease-free survival. A factor that may be considered a contraindication to resection is the presence of extrahepatic disease (whether nodal or visceral), even if resectable. CONCLUSIONS: Although the actual benefit of resection is limited, and it is associated with considerable morbidity, surgical therapy offers some patients a chance for cure. It is a valid expectation that improvement in techniques and a proper understanding of hepatic anatomy will improve the safety and efficacy of hepatic resections in the future. Future research should focus on defining better selection criteria and on study of the value of adjuvant treatment modalities.

Adult↗
PubMed1992

Kinetics and dosimetry of iodine-131-labelled antibody fragments after local administration in patients with rectal cancer.

In 11 patients with rectal cancer, a mixture of F(ab')2 fragments of anti-carcinoembryonic antigen and anti-CA 19.9 labelled with a diagnostic dose of iodine-131 (3-10 MBq) was administered submucosally around the tumour. In this study, the local kinetics in and the dose to the rectal wall, the whole body kinetics and the effective dose equivalent are presented. The early disappearance of the activity from the injection spot was characterized by a T1/2 of 21 h. Initially, about 50% of the plasma activity was due to free 131I. After 4 h, the plasma activity was almost completely protein bound (86%). Maximum plasma activity was observed after the 2nd day. From 72 h p.i., the plasma activity decreased with a T1/2 of 53 h. In the first 24 h, 14% of the injected dose was excreted in the urine and within 4 days about half of the administered activity. The absorbed radiation dose to the rectal wall was estimated to be 0.2 Gy/MBq, presuming a 20 cm3 distribution volume. The dose to the bone marrow was 0.2 mGy/MBq or 0.4 mGy/MBq, assuming a homogeneous tracer distribution or equal blood and bone marrow activity concentrations, respectively. The effective dose equivalent is 1.9 mSv/MBq, mainly determined by the dose to the rectal wall and to a lesser extent by the dose to the remaining body. Postulating comparable kinetics, 123I- or 111In- or 99mTc-labelled fragments would result in 4-25-fold lower effective dose equivalents.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
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

Anal sphincter imaging in fecal incontinence using endosonography.

Clinical anal examination, manometry (resting and squeeze pressures), and single-fiber electromyography were compared with endosonography of the anal sphincters in 14 patients with fecal incontinence. Technical aspects of the procedure and normal imaging of the puborectal muscle and both sphincters were defined. Defects in both sphincters were seen in nine patients. The defect is visualized as a clear discontinuity in the muscular ring. Compared with the conventional studies, anal endosonography gave significant information in six patients (four male patients after perianal surgery and two women), showing sphincter defects in five patients and integrity of the sphincters in another one. This information obtained by endosonography was important in understanding the type and extension of the lesion and deciding upon the surgical repair. Anal endosonography is an imaging technique of the sphincters that can assess their integrity in fecal incontinence.

Adult↗