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Biomedical subjects

J W Nortier

Publications and source records attributed to J W Nortier.

At least 37 records · Page 2Linked to original sources
PubMed1993

Phase I study using desferrioxamine and iron sorbitol citrate in an attempt to modulate the iron status of tumor cells to enhance doxorubicin activity.

A novel approach to enhance the activity of doxorubicin is to increase the availability of cellular "chelatable" iron to participate in doxorubicin-mediated free-radical generation. To achieve this, we designed a regimen consisting of desferrioxamine (DFO, 50 mg/kg daily given as an i.v. infusion over 72 h) to increase cellular iron uptake. Thereafter, the combination of iron sorbitol citrate (ISC) and doxorubicin (as a single agent or as part of the CHOP regimen) was given. In a phase I study we investigated the toxicity of this regimen in nine patients with refractory malignant disease. Severe but reversible ocular toxicity (i.e., acute maculopathy) was observed in two patients. As these patients were the only ones who were pretreated with cisplatin, we caution against the use of DFO in cisplatin-pretreated patients. Severe phlebitis was encountered in five of nine patients. A partial remission was observed in two of four patients with refractory Non-Hodgkin's lymphoma who were treated with DFO, ISC, and doxorubicin as part of the CHOP regimen. We conclude that pretreatment with DFO and iron sorbitol citrate may be of benefit in the treatment of malignancies with doxorubicin-containing regimens, but ocular toxicity and severe phlebitis limits the use of DFO in this approach. The attachment of DFO to biocompatible polymers may be a method of overcoming the observed toxicity and warrants further study.

Adult↗
PubMed1992

[Villous adenoma of Vater's papilla; a therapeutic dilemma].

After a cholecystectomy in 1980, local excision of a villous adenoma of the ampulla of Vater was performed in 1983 in a 69-year-old female; this had to be repeated in 1990 because of recurrence. In case of a tumour of this kind, pancreaticoduodenectomy should be considered because of the relatively high risk of recurrence or malignant degeneration. After a radical local excision regular duodenal endoscopy and if possible endoscopic ultrasonography should be performed.

Adenocarcinoma↗
PubMed1992

A randomized trial of two doses of granisetron in the treatment of chemotherapy-induced emesis. Dutch results within a multinational study.

Granisetron is a new serotonin-receptor antagonist with considerable activity in preclinical models and early clinical studies against drug-induced nausea and vomiting. In a randomized, double-blind trial, two dose levels of granisetron were compared with regard to their efficacy and safety if given to patients receiving emetogenic chemotherapy with or without cisplatin. The present paper reports the Dutch experience with 125 patients included in this international trial. The two dose levels (40 and 160 micrograms/kg given once i.v. prior to chemotherapy) were equally effective in preventing acute emesis and nausea (within the first 24 h); in the group receiving cisplatin doses of 50 mg/m2 or more, 39% of patients had a complete response (no vomiting and mild nausea at most), with a complete response rate of 82% in the patients receiving moderately emetogenic chemotherapy. Sixty-three percent of patients receiving highly emetogenic chemotherapy with a complete response within 24 h lost this response during the next 6 days, as did 20% of the other patients. Headache was the most frequently reported adverse event (18%), followed by constipation (6%) and dizziness (4%). All adverse events were mild and occurred equally frequently at both dose levels. Granisetron at 40 micrograms/kg i.v. given once is effective in the prevention of acute chemotherapy-induced emesis and nausea, in particular in patients receiving moderately emetogenic therapy.

Adult↗
PubMed1990

Comparison of breast cancer mucin (BCM) and CA 15-3 in human breast cancer.

The Breast Cancer Mucin (BCM) enzyme immunoassay utilizes two monoclonal antibodies (Mab), M85/34 and F36/22, for the identification of a mucin-like glycoprotein in serum of breast cancer patients. We have compared BCM with CA 15-3, another member of the human mammary epithelial antigen family. Serum BCM was evaluated in 151 and CA 15-3 in 134 patients with breast cancer, in 30 normal controls, in 9 pregnant women, and in 13 cancer patients (non-breast). Neither the normal controls nor the pregnant women had BCM levels greater than 25 U/ml. In contrast, 87 of 115 patients (75%) with metastatic breast cancer had BCM levels greater than 25 U/ml. All control persons had CA 15-3 levels less than 25 U/ml, but 2 out of 9 pregnant women (22%) had levels greater than 25 U/ml. Seventy-four out of 97 patients (76%) with metastatic breast cancer had CA 15-3 levels greater than 25 U/ml. A statistically significant correlation was found between BCM and CA 15-3 in the breast cancer patient group (r = 0.883, p less than 0.001, n = 134) and in the normal control group (r = 0.743, p less than 0.001, n = 30). BCM and CA 15.3 both showed no correlation with CEA in breast cancer patients (r = 0.060, n = 81; and r = 0.146, n = 78, respectively). BCM had a range of sensitivity similar to that of the CA 15-3 RIA. Our results suggest that BCM may be a useful new marker for monitoring the clinical course of patients with breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗
PubMed1990

Once-daily dosing regimen for aminoglycoside plus beta-lactam combination therapy of serious bacterial infections: comparative trial with netilmicin plus ceftriaxone.

PURPOSE: Once-daily dosing of aminoglycosides has been suggested to improve their efficacy and reduce their toxicity. To test the clinical validity of this suggestion, we conducted a prospective, randomized trial comparing a conventional multiple-daily-dosing regimen of netilmicin with once-daily administration of the same total daily dose of this aminoglycoside. PATIENTS AND METHODS: We enrolled 141 predominantly elderly patients with severe bacterial infections. All patients received once-daily doses of 2 g ceftriaxone, in addition to netilmicin. RESULTS: Patients randomized to either of the two dosing strategies were comparable regarding age, APACHE II score, concomitant diseases, infection site, and rate of culture-proven bacteremia. Netilmicin treatment did not differ significantly in mean daily dose per kg body weight and days of therapy between the two treatment arms. Compared to patients receiving conventional doses, patients treated with a once-daily dose had higher serum peak netilmicin levels and lower trough levels. Outcome of infection and mortality were not influenced by dosing strategy. Although the overall incidence of nephrotoxicity was similar in both groups (16%), the occurrence of nephrotoxicity in patients treated with once-daily doses of netilmicin was significantly shifted to those given prolonged treatment, i.e., beyond 9 days. Auditory toxicity was documented in one patient treated with conventional doses and two patients treated with once-daily doses. CONCLUSION: Once-daily dosing of an aminoglycoside plus a long-acting cephalosporin in these patients constituted cost-effective and safe treatment for severe bacterial infections. Netilmicin-induced toxicity may be reduced by using once-daily dosing regimens and limiting the duration of treatment.

Adolescent↗
PubMed1989

Mitoxantrone, methotrexate, and 5-fluorouracil (MMF) in hormone-refractory advanced breast cancer.

Thirty-nine patients with metastatic breast cancer who had not received prior chemotherapy for metastatic disease were treated in a phase II trial with a combination of mitoxantrone (10 mg/m2), methotrexate (40 mg/m2) and 5-fluorouracil (600 mg/m2) i.v. every 3 weeks (MMF). Thirty-three patients could be evaluated with regard to response and toxicity. Objective response was observed in 33% (3/33 complete responses, 8/33 partial responses). Dominant sites of disease were bone (16 patients), liver (7 patients), skin/lymph node (7 patients), lung (1 patient) and breast (2 patients). Responses occurred in bone (4/16), liver (3/7) and skin/lymph node (4/7). Moderate to severe alopecia (grade 3-4 WHO criteria) occurred in 3/33 (10%) patients; moderate to severe nausea and vomiting in 2/33 (6%) patients. Haematological toxicity consisted of predominantly leukopenia. Leukopenia grade 3-4 (nadir below 2000 x 10(9)/litre) occurred in 22/33 (67%) patients; thrombocytopenia grade 3-4 (nadir below 50,000 X 10(9)/litre) occurred in 3 patients (9%). The MMF regimen appears to be effective. The non-haematological toxicity compares favourably with that of the more commonly used chemotherapy regimens, but the anti-tumour activity may be less.

Adult↗
PubMed1988

Transsphenoidal microsurgery as primary treatment in 25 acromegalic patients: results and follow-up.

Twenty-five patients with acromegaly were treated by transsphenoidal microsurgery. Fourteen patients (56%) were considered cured according to the following criteria: a. basal plasma GH less than 10 mU/l; b. glucose suppressed plasma GH less than or equal to 4 mU/l, and c. disappearance of TRH responsiveness if present preoperatively. Thirteen of the cured patients were re-evaluated after a mean follow-up period of 3.5 years (range 1.5 to 5.5 years). At that time, basal plasma GH was still less than 10 mU/l and glucose suppressed plasma GH was still less than or equal to 4 mU/l in all patients, indicating the practical value of our criteria. The remaining 11 patients (44%) received additional treatment by external pituitary irradiation and bromocriptine. Owing to surgery, 5 patients (20%) developed partial or panhypopituitarism.

Acromegaly↗
PubMed1986

Buprenorphine versus domperidone in chemotherapy-induced emesis: a pilot study.

A randomized double-blind cross-over study was performed to evaluate the possible anti-emetic effect of the partial opiate antagonist buprenorphine in comparison to domperidone in chemotherapy-induced nausea and vomiting. Emesis was of significantly shorter duration on domperidone treatment. Most patients preferred domperidone, mainly due to adverse side-effects of buprenorphine. Nevertheless, emesis in buprenorphine treatment was less disabling. Therefore, it might be useful to search for new alternatives in this group of drugs or to use them in a combination regimen of anti-emetic agents.

Adult↗
PubMed1986

Comparison of bioavailability in man of tamoxifen after oral and rectal administration.

The bioavailability of tamoxifen from 40 mg suppositories was tested in six male volunteers and compared with that of tamoxifen (Nolvadex) tablets. Plasma concentrations of tamoxifen and its major metabolites, 4-hydroxytamoxifen and N-desmethyltamoxifen, were measured by extraction from plasma obtained at different times after administration, separated by HPLC, converted on-line to fluorescent phenanthrene derivatives and quantified with a fluorescence detector. The mean relative bioavailability from the suppositories was 28%; the addition of a surfactive agent diminished the bioavailability to 13%. Simulation of repeated administration of 40 mg suppositories suggests a mean steady state plasma concentration for tamoxifen of approximately 70 ng ml-1, i.e. 30% of the steady state value after simulated oral administration. Rectal administration of tamoxifen leads to a lower bioavailability than that by oral administration and therefore cannot be recommended when used in equivalent doses.

Administration, Oral↗
PubMed1986

No effect of treatment with sodium valproate on plasma growth hormone in bromocriptine unresponsive acromegaly.

Administration of sodium valproate for 6 months at a dose of 300 mg three times daily to 7 bromocriptine unresponsive acromegalic patients who all but one had been treated with pituitary surgery and/or radiotherapy in the past did not result in a significant reduction of the plasma growth hormone (GH) level or in any clinical improvement. It is concluded that sodium valproate is not suitable for the treatment of acromegalic patients who do not show a favourable response to bromocriptine.

Acromegaly↗
PubMed1986

Bromocriptine treatment of prolactin secreting macroadenomas: a radiological, ophthalmological and endocrinological study.

Twelve patients, six women and six men, with macroprolactinomas characterized by extrasellar extension and basal plasma prolactin levels greater than 6 U/l were treated with 10-20 mg bromocriptine daily in four divided doses for a mean period of 2.4 years (range 0.5-3.5 years). The following observations were made: Plasma prolactin levels fell dramatically in all patients and values in the low normal range were obtained in 10 patients. Tumour size was reduced by more than 75% in 11 patients and by 50-75% in one patient. Tumour-reduction was associated with the development of a partial empty sella in eight cases. In four cases the pituitary became visible. Diminished visual acuity (three patients), bitemporal hemianopia (three patients), unilateral or bilateral central scotomas (three patients) and oculomotor palsy (two patients) restored to normal. Hypogonadism (all patients), hypothyroidism (six patients) and hypocorticism (three patients) improved or normalized in most cases. It is concluded that in the medical treatment of macroprolactinomas 10-20 mg bromocriptine in four divided doses effectively reduces both plasma prolactin level and tumour size.

Adenoma↗