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Biomedical subjects

S Meijer

Publications and source records attributed to S Meijer.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Intraluminal ultrasound of rectal tumours: a prerequisite in decision making.

The use of intraluminal ultrasound (IUS) as a staging technique was evaluated in 58 patients with a rectal tumour. Thirty-four patients had a rectal carcinoma, four had a local recurrence after a previous anterior resection and 20 other patients had a villous adenoma. IUS assessment of rectal wall invasion, infiltration into adjacent organs, and the presence of perirectal lymph node involvement was compared with the definitive histological findings. In 90% of all patients the pre-operative local tumour staging was predicted correctly. In 38 patients with a rectal carcinoma the overall accuracy for the T grade was 84%. The sensitivity for the detection of perirectal fat infiltration was 91%, with a specificity of 70% and a negative predictive value of 78%. The accuracy in predicting direct infiltration into adjacent organs was 100% (n = 5). In the four patients with a local recurrence, the diagnosis was suspected by means of IUS and confirmed by biopsies. Extraluminal tumour growth was predicted correctly in all cases, with extension into the coccygeal bone in one patient. IUS identified lymph nodes in 29 of 38 cases, with a sensitivity of 57% and a specificity of 76%. All 20 villous adenomas were correctly staged as non-infiltrative tumours. After transmural excision, three adenomas proved to contain a completely removed T1 carcinoma. IUS is the most accurate tool in predicting the depth of local tumour invasion and needs a place in the preoperative screening programme in patients with a rectal tumour, as well as in the postoperative follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Villous↗
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

Cryosurgery for locally recurrent rectal cancer.

Locally recurrent rectal cancer is, in most cases, unresectable and incurable. Palliative treatment is warranted in many cases because of the presence of severe distressing symptoms. In recurrent disease, intraluminal cryotherapy is an option for palliation. Twenty patients with local recurrence after anterior resection were treated palliatively with cryosurgery for their local symptoms. Six patients had previously had a colostomy before they were referred for palliative treatment. Thirteen patients had more than one symptom. Distant metastases were present in ten cases. The beneficial effect of cryosurgery was evident after two to three sessions. In nine patients cryotherapy achieved complete relief of local symptoms. In these patients the symptom free interval varied from 1 to 24 months (median 11 months); five patients died of disease without local symptoms. Three of these nine patients underwent a bowel diversion at a later stage because of complete stenosis. The number of treatment sessions in this group of patients varied from three to 14. The palliative index varied from 37 to 100% (mean 78%). In nine patients cryotherapy of the local recurrence gave no relief at all. Our results show that in almost half of the patients cryosurgery can palliate local complaints resulting from recurrent tumor growth after anterior resection.

Aged↗
PubMed1992

Time course of inhibition of thymidylate synthase in patients treated with fluorouracil and leucovorin.

The inhibition of thymidylate synthase (TS) by the fluorouracil (5-FU) metabolite 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) is considered to be one of the main mechanisms of action of 5-FU. The inhibition of TS is mediated by the formation of a ternary complex between TS, FdUMP, and the folate cofactor 5,10-methylene tetrahydrofolate. The activity of TS, its inhibition by FdUMP, and the binding of FdUMP to TS have been determined in biopsy specimens of colorectal tumors, liver metastases, normal colon mucosa, and liver obtained from patients who never had received chemotherapy, and patients treated with 5-FU or 5-FU with leucovorin (LV). In nontreated patients we observed a large variation in the activity of TS both at 1 microM and 10 microM dUMP (40- to 80-fold difference). In contrast, in normal colonic mucosa this variation was less than 10-fold. FdUMP binding in tumors also varied considerably but was not detectable in normal mucosa. The deviations from normal (ie, as found in mucosa) kinetic patterns of TS may represent a mutant TS form. Thirty-five patients with advanced colorectal cancer received 5-FU (500 mg/m2) at 1 to 48 hours prior to surgery. In biopsy specimens of tumor and normal tissues the residual catalytic activity of TS and the percentage of free-binding sites for FdUMP (TS-free) were determined. After dissociation of FdUMP, total catalytic activity of TS- and total FdUMP-binding sites (TS-tot) were determined. Total and residual catalytic TS activity in primary tumors and metastases showed a large variation. TS-tot and TS-free in tumors also varied considerably. At least eight patients with an undetectable TS-free showed response to subsequent intraarterial treatment with 5-FU. To several patients leucovorin (2-hour infusion of 500 mg/m2) was administered with a 5-FU bolus (500 mg/m2) in the middle of the infusion. Biopsy specimens were obtained about 48 hours after treatment. In these patients inhibition of TS was markedly enhanced compared with patients who did not receive LV. The large variation in TS may be related to the observed variation in clinical response to 5-FU treatment.

Adult↗
PubMed1991

The effects of alpha-adrenoceptor blockade on dopamine-induced renal vasodilation and natriuresis.

To establish the effects of alpha-adrenoceptor blockade on dopamine-induced changes in renal hemodynamics and sodium excretion, dopamine dose-response curves were performed without and with pretreatment with the selective postsynaptic alpha 1-adrenoceptor antagonist prazosin in normal volunteers and in patients with renal disease and moderately impaired renal function. Prazosin (1 mg p.o. every 4 h) in 7 volunteers did not significantly affect baseline values but impaired the response of effective renal plasma flow (ERPF) and filtration fraction (FF) to infusions of dopamine in doses ranging from 0.5 to 8 micrograms/kg per minute and completely abolished the dopamine-induced increase in sodium excretion. In 7 patients with renal disease and a glomerular filtration rate (GFR) ranging from 38-85 ml/min pretreatment with prazosin did not affect baseline ERPF, GFR or FF or their response to dopamine infusion, but sodium excretion and its response to dopamine infusion were reduced (fractional excretion of sodium at baseline 1.78 without and 0.89 with prazosin pretreatment). We conclude that alpha 1-adrenoceptor blockade with prazosin abolishes the effects of exogenous dopamine on sodium excretion in normal man. Prazosin also impairs the renal vasodilatory action of dopamine. However, the effect on sodium excretion is not directly related to inhibition of dopamine-induced renal vasodilation since in patients with renal disease prazosin also markedly reduces sodium excretion but does not influence the renal hemodynamic effects of dopamine.

Adult↗
PubMed1991

Qualitative and quantitative kinetics of submucosally administered antibody fragments in patients with rectal carcinoma: the detection of lymph node metastasis in relation to local tracer diffusion.

Immunoscintigraphy after submucosal administration of a mixture of 131I-anti-CEA and 131I-anti-CA-19-9 around the tumor in patients with rectal carcinoma may improve pre-operative staging and may contribute to the selection of patients eligible for local treatment. However, visual discrimination of local lymph node metastasis appears unreliable, partly because of scatter from the injection site and substantial diffusion of the radiotracer into the interstitium. Analysis of the diffusion profile, however, may improve the sensitivity and accuracy of this immunoscintigraphic approach.

Aged↗
PubMed1991

Renal and neurohumoral effects of ibopamine and metoclopramide in normal man.

The effects of 100 mg ibopamine, an orally active nonselective dopamine agonist on renal haemodynamics, sodium excretion, blood pressure (BP), heart rate (HR) and neurohumoral parameters were investigated in 10 healthy volunteers, with and without metoclopramide pretreatment. A small and temporary rise of glomerular filtration rate (GFR) was found after ibopamine without but not with metoclopramide pretreatment. No differences in effective renal plasma flow (ERPF) but a small rise in sodium excretion were observed comparing ibopamine with control. Metoclopramide induced a fall in sodium excretion which was not reversed by ibopamine. Ibopamine failed to affect BP and HR and no changes of PRA or plasma aldosterone concentration (PAC) were found. Metoclopramide induced a pronounced increase of PAC which was blunted by ibopamine. Plasma and urinary catecholamines were unchanged for all study days. We conclude that ibopamine induces natriuresis probably not by the observed small and temporary renal haemodynamic effects but by direct stimulation of DA1 dopamine receptors in the proximal tubule.

Adolescent↗
PubMed1991

Continuous infusion carboplatin on a 21-day schedule: a phase I and pharmacokinetic study.

A phase I study with continuous infusion carboplatin for 21 days every 6 weeks using a venous access port and portable pump was performed over a dose range of 12 to 32 mg/m2/d, with increments of 2 mg/m2/d. Forty-four patients received 107 courses (median, two; range, one to nine). World Health Organization (WHO) grade III/IV leukopenia and thrombocytopenia occurred in one of seven patients at 30 mg/m2/d, and in two of six and four of six patients at 32 mg/m2/d. Cumulative platelet depression was found at dose levels of 28 mg/m2/d or more. Median glomerular filtration rate (GFR) and effective renal plasma flow, monitored by radioisotope clearances at doses greater than or equal to 20 mg/m2/d, decreased 8.2% (P less than .05) and 10.9% (P less than .01) after two courses. There was a relationship (r = .50, P less than .0002) between the percentage of platelet depression and GFR. No other toxicity was observed. Of the 17 patients who were evaluable, one complete response and four partial responses were observed. In addition, six patients had stable disease. Pharmacokinetic analysis of total and ultrafiltrable platinum (UFPt) was performed by atomic absorption spectrophotometry. Steady-state plasma levels for UFPt were reached after 8 hours. These levels could be detected from the 20 mg/m2/d dose. During steady state, carboplatin dose and UFPt plasma levels were not correlated, but steady-state UFPt and GFR (r = -.27, P less than .05) were. Twenty-four percent of total platinum (Pt) was present as UFPt during steady state (x = 160 +/- 10 micrograms/L). Total body clearance of UFPt exceeded GFR 2.2 times. Mean area under the curve (AUC) for UFPt during continuous infusion was 4,921.8 +/- 301.72 mg.min/L. For total Pt, steady-state plasma levels were not reached; total Pt plasma levels increased between day 7 and day 21 (P less than .0001). There was a significant relation between total Pt serum levels day 7, 14, and 21 and the drug dose administered. Immunohistochemical analysis of DNA-bound Pt in leukocytes showed a linear increase from day 7 to day 14 to day 21 (r = .97) between DNA-bound Pt and duration of infusion in individual patients. The maximum-tolerable dose of carboplatin is 30 mg/m2/d for 21 days (total dose 630 mg/m2) and is recommended for phase II studies.

Adult↗
PubMed1991

Accessory soleus muscle mimicking a soft tissue tumor. A report of 2 patients.

An accessory soleus muscle is rare, and may present as a soft tissue tumor at the ankle. We report 2 patients in whom the diagnosis was not considered until after surgical exploration. Magnetic resonance imaging (MRI) after biopsy clearly identified muscle tissue, and electromyography showed normal motor unit activity.

Adult↗
PubMed1991

Retroperitoneal sarcomas: pre-operative assessment and surgical therapy.

The clinical and pathological records of 22 patients treated for retroperitoneal sarcomas were retrospectively studied. The initial symptoms were pain and swelling of the abdomen in 11 patients. All tumours had a diameter of more than 10 cm. The pathological diagnosis was in 16 cases liposarcoma or leiomyosarcoma. Fourteen tumours were graded as high and eight as low. Sixteen of the 22 operated patients had complete resection of the tumour. Eleven patients had recurrence after five to 42 months, nine of them local recurrence and two distant metastases. Eleven patients needed repeated radical or palliative resections. Additional therapy (pre- or post-operative radiation or chemotherapy) was given to 11 patients. Radical resection of primary and recurrent tumours seems to give the best results in patients with retroperitoneal sarcomas but debulking of the tumour improves the quality of life in selected patients.

Combined Modality Therapy↗