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Biomedical subjects

H J Groen

Publications and source records attributed to H J Groen.

At least 73 records · Page 4Linked to original sources

Pharmacokinetics and scintigraphy of indium-111-DTPA-MOC-31 in small-cell lung carcinoma.

UNLABELLED: Radiolabeled MOC-31 retains its immunoreactivity and shows good in vivo immunolocalization to human SCLC xenografted in nude rats. METHODS: We evaluated the immunotargeting properties and safety of 111In-labeled monoclonal antibody (MAb) MOC-31 (125 MBq, 5 mg) in six patients with histologically proven small-cell lung cancer (SCLC). Scintigraphy and pharmacokinetics were performed up to 3 days after injection. RESULTS: No adverse reactions were found after injection of MAb MOC-31. Pharmacokinetics obtained from plasma radioactivity showed plasma disappearance described most properly by a monoexponential model with a mean half-life value of 17.0 +/- 1.4 hr. HPLC analysis documented the monomeric MOC-31 without evidence of immune complexes or radioactive lower molecular weight fractions. Mean 24-hr urinary excretion of radioactivity was 4.3% of the injected dose. Scintigraphy detected primary tumor or metastases in five of six patients. Localization of radioactivity in normal tissue was restricted, but additional experiments need to be performed to elucidate possible cross-reactivity of MOC-31 with normal tissue in vivo. CONCLUSION: Preliminary results justify further studies to reveal the possible usefullness of radiolabeled MOC-31 in the therapeutic and diagnostic management of SCLC.

Antibodies, Monoclonal↗

Effects of recombinant human interleukin-6 in cancer patients: a phase I-II study.

To define the toxicity profile of recombinant human interleukin-6 (rhIL-6) and to study its effect on hematopoiesis, biochemical parameters and other cytokines, rhIL-6 was administered in a phase I-II study to 20 patients with breast carcinoma or nonsmall cell lung cancer. RhIL-6 doses were 0.5, 1.0, 2.5, 5.0, 10, and 20 micrograms/kg/d, with at least three patients per dose level. RhIL-6 was administered 24 hours by continuous intravenous infusion followed by subcutaneous (SC) administration for 6 days, partly on an outpatient basis. RhIL-6-related side effects were fever, headache, myalgia, and local erythema. Starting at 2.5 micrograms/kg/d, these side effects were compounded by nausea, reversible increase in liver enzymes, and anemia. Flu-like symptoms were controllable up to and including 10 micrograms rhIL-6/kg/d with acetaminophen. RhIL-6 increased platelet counts with a decrease in mean platelet volume and increased leukocytes caused by neutrophil, monocyte, and lymphocyte increase, with an increase in T cells and natural killer cells at 1.0 and 2.5 micrograms rhIL-6/kg/d. The reversible anemia was characterized by a decrease in serum iron, and an increase in ferritin and erythropoietin without reticulocytosis. RhIL-6 reduced total cholesterol levels and a dose-related increase of C-reactive protein and serum amyloid A plasma levels was observed. Serum IL-6 levels were increased, especially at 10 and 20 micrograms/kg/d, whereas no change in IL-1 beta and tumor necrosis factor alpha levels was observed. RhIL-6 can be administered with controllable side effects in this setting, up to and including a SC dose of 10 micrograms/kg/d on an outpatient basis, and has a promising stimulating effect on leukopoiesis and thrombopoiesis.

Adult↗

Surgical resection for small cell carcinoma of the lung: a retrospective study.

BACKGROUND: A retrospective review was undertaken of the survival of 21 patients with histologically proven small cell carcinoma of the lung resected between 1977 and 1991. METHODS: Twenty one patients (20 men) of median age 60 (range 44-73) years underwent surgical resection. Patients were subjected to standard clinical staging procedures. Preoperative diagnosis was small cell carcinoma of the lung in 13, non-small cell lung cancer in one, and uncertain in seven patients. Clinical staging was stage I disease in 11 and stage II in 10 patients. RESULTS: Resection included pneumonectomy in 12 cases, lobectomy in eight, and one wedge resection. Resection was complete in 16 patients. Postoperative histopathological examination confirmed small cell carcinoma of the lung in 19 specimens and mixed small cell and non-small cell carcinoma of the lung in two. Pathological staging was stage I in 11, stage II in three, and stage III in seven patients. The final pathological diagnosis of the resected specimens (n = 18) was atypical carcinoid in one, pure small cell carcinoma of the lung in 15, and mixed small cell and non-small cell carcinoma of the lung in two patients. Fourteen patients also received chemotherapy and 10 received prophylactic cranial irradiation postoperatively. Excluding the patient with a final diagnosis of atypical carcinoid, the median survival (n = 20) was 29 months (range two to 133+). Median survival for patients with pathological stage I and II disease (n = 13) was 40 months (range nine to 133+) and for patients with pathological stage III disease (n = 7) 20 months (range two to 116+). The median disease free survival was 23 months. Eleven patients relapsed between two and 101 months. There was no advantage for those patients who received postoperative chemotherapy. CONCLUSION: Curative resection offers the best chance for long term survival in patients with small cell carcinoma of the lung with very limited stage disease.

Adult↗

Carboplatin as second line treatment for recurrent or progressive brain metastases from small cell lung cancer.

Patients with brain metastases from small cell lung cancer (SCLC) have a poor prognosis. Although most patients die from metastatic disease outside the central nervous system, this disabling metastatic site often needs treatment to mitigate the signs and symptoms of intracranial disease. The effect of carboplatin (400 mg/m2 every 4 weeks) as second line treatment for recurrent or progressive brain metastases was studied in 20 SCLC patients. 19 patients could be evaluated: 16 by contrast enhanced brain computer tomography (CT) scan (2 patients had complete response, 6 partial response, 4 stable disease and 4 progressive disease) and 3 patients clinically, who had progressive disease. The objective response rate in the brain was 40% (95% CI:22-61%). The median response duration was 8 weeks (range 2-29). The median survival was 15 weeks (range 1-44). Previous cranial irradiation appeared to be beneficial for survival. There was only mild haematological and gastrointestinal toxicity. Carboplatin has activity against brain metastases and gives palliation in responding patients.

Adult↗

Clinically undetected occlusal dentine caries: a radiographic comparison.

The occlusal bite-wing radiograph evaluations of 131 14-year-old and of 123 17- and 20-year-old Dutch persons were compared with the clinically collected observations. The clinical observations and the bite-wing radiographs were collected as part of a longitudinal epidemiological survey conducted in 1987 and 1990. Comparison of the evaluations of the first and second molar teeth showed significantly more radiolucencies in all three age groups than expected clinically. Of the clinically judged 'sound' surfaces, 26% in the 14-, 37.5% in the 17- and 50% in the 20-year-old group showed a radiolucency on the bite-wing radiograph. In the 14-, 17- and 20-year-old age group a radiolucency was noticed on the bite-wing radiograph in 32, 44 and 58% of the sealed teeth, respectively. The radiolucencies below the occlusal enamel of sealed teeth were most likely due to the problems in diagnosing occlusal dentine lesions correctly with the clinical diagnostic methods. Therefore not only approximal but also occlusal bite-wing radiograph judgement before sealant application seems to be advisable now. Because of the numbers of clinically undetected lesions it may be advisable to reconsider the criteria for occlusal diagnosis in epidemiological surveys and to judge not only the approximal but also the occlusal surfaces in epidemiological surveys when bite-wing radiographs are available.

Adolescent↗

Diffusion capacity in heart transplant recipients.

Preoperative diffusion capacity per liter alveolar volume (Kco) in cardiac transplant recipients with an intrinsic normal lung is within the normal range. In the first postoperative year, Kco showed a significant mean decrease of 12 percent (p less than 0.004). Lung function (TLC, VC, FEV1) tended to normalize after heart transplantation. Ventilation distribution remained stable before and after heart transplantation. Preoperatively, weak correlations were found between Kco and diastolic pulmonary arterial pressure (dPAP) and mean pulmonary capillary wedge pressure (PCWP). Postoperatively, correlation between Kco and PCWP was weak, and between Kco and dPAP it was not significant at all. These pressures determine the capillary blood volume before and after transplantation. Probably these weak correlations indicate that intrapulmonary factors, not cardiac factors, are of primary importance in the regulation of blood distribution. The percentage of decrease in Kco in the first postoperative year correlated with the change in dPAP and PCWP, but also with the cyclosporine level in the first posttransplant year. No correlation was found between cyclosporine level and pulmonary vascular resistance. It is suggested that higher levels of cyclosporine influence the alveolar capillary membrane, so that Kco decreases. The percentage of decrease in Kco was significantly more outspoken in patients who had rales on auscultation preoperatively. Using multiple regression analysis, we found that the factors most strongly related to the percentage of change in Kco in the first posttransplant year were the preoperative Kco, the cyclosporine level in the first postoperative year, and the change in dPAP in that year.

Adult↗

Approaches to lung cancer treatment using the CD3 x EGP-2-directed bispecific monoclonal antibody BIS-1.

The bispecific monoclonal antibody (bsAb) BIS-1 combines a monoclonal-antibody(mAb)-defined specificity for the CD3 complex, as present on all T lymphocytes, with a mAb-defined specificity for the pancarcinoma/epithelium associated glycoprotein EGP-2. In vitro studies indicate that BIS-1 can direct T lymphocytes to kill EGP-2-positive tumour target cells. T cell pre-activation is necessary for this activity and can be obtained either via incubation of isolated peripheral blood mononuclear cells with CD3 mAb, followed by short culturing in recombinant interleukin-2-containing medium, or via costimulation with CD5- and CD28-based bsAb. Clinical application of BIS-1 was started in a pilot study in which carcinoma patients suffering from malignant ascites or intrapleural effusion were treated. In this study, ex vivo activated autologous lymphocytes were applied locally, i.e. intraperitoneally or intrapleurally, in the presence of BIS-1. Local inflammation and antitumour activity were observed, whereas no or only minor systemic toxicity was seen in these patients. Intravenous administration of BIS-1 F(ab')2 in combination with subcutaneously given recombinant interleukin-2 (i.v. bsAb/rIL-2 treatment) induced transient but considerable toxicity including peripheral vasoconstriction, dyspnoea and fever with a maximal tolerated dose of 5-8 micrograms/kg. High plasma concentrations of the inflammatory cytokines tumor necrosis factor alpha and interferon gamma were observed at this dose. Whereas bsAb-dictated antitumour activity could be demonstrated to be present in blood samples of these patients in an in vitro assay, no clear clinical responses were observed. In a rat model it was found that i.v. bsAb/rIL-2 treatment of EGP-2-positive tumours was effective when a low systemic tumour burden was present, suggesting that systemic bsAb/rIL-2 treatment might be effective in situations of minimal residual disease.

Aged↗

Activity of single-agent gemcitabine as second-line treatment after previous chemotherapy or radiotherapy in advanced non-small-cell lung cancer.

The aim of the study was to evaluate activity, toxicity and health-related quality of life (HRQL) with gemcitabine as second-line treatment after previous chemo- or radiotherapy in non-small-cell lung cancer (NSCLC). Patients with previously treated NSCLC were treated with gemcitabine (1000 mg/m(2)) on days 1, 8 and 15 in a 28-day cycle. Eighty patients were included; median age was 57 years (range 38-77). Prior treatment consisted of platinum-containing chemotherapy in 29 patients and high-dose thoracic radiotherapy in 51 patients. Median number of cycles was three (range 1-6). Granulocytopenia CTC grade 3 and 4 occurred in 9% and thrombocytopenia CTC grade 3 and 4 in 9% of cycles. Non-haematological toxicity was mild. Tumour response was achieved in 13% of the patients (95% CI 7-20), median survival time was 26 weeks and 1-year survival was 22%. Tumour response to second-line gemcitabine could not be predicted from response to first-line therapy, first-line treatment modality or treatment interval. In a subset of 35 patients HRQL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-LC13 questionnaires and showed improvement or control of symptoms and functioning in approximately 30% of patients. We conclude that gemcitabine in second-line treatment has modest anti-tumour activity, is well tolerated, and may control tumour-related symptoms and improve HRQL in a significant minority of patients.

Adult↗

Dyract versus Tytin Class II restorations in primary molars: 36 months evaluation.

Due to the changed treatment approach of proximal caries and the amalgam controversy, clinicians are in search for new materials. The aim of the present study was to compare amalgam with an adhesive material in deciduous molars in a clinical, split-mouth design study. At baseline 30 polyacid modified composite (Dyract) and 30 amalgam (Tytin) restorations were placed in primary molars, of which 24 and 17 could be evaluated after 24 and 36 months, respectively. Modified USPHS criteria were used for clinical evaluation every 6 months. Annual bite-wing radiographs were taken for evaluation of recurrent caries and cervical gap formation. In the present study, for Dyract as well as for Tytin restorations, low rates of recurrent caries were found, while Dyract restorations showed a better marginal adaptation and surface texture compared to Tytin restorations. In the Dyract group more radiolucencies were found at baseline. In both groups no patient complaint or pain was reported related to the radiolucencies. After 3 years the colour of Dyract was not comparable to the original. For Dyract no excessive wear was noticed compared to enamel. During the study one Dyract (recurrent caries: 18 months) and two Tytin (pulpal aetiology: 6 months, recurrent caries: 36 months) restorations had to be replaced. Even though the restorations were placed in caries risk children, at the 36 months' evaluation of this clinical study, the results indicate that Dyract can be an alternative for Tytin in the primary dentition.

Child↗

Effects of dental treatment and single application of a 40% chlorhexidine varnish on mutans Streptococci in young children under intravenous anaesthesia.

Clinical studies suggest that application of a highly concentrated chlorhexidine varnish results in a decrease in the number of mutans streptococci and thereby a decrease in the caries risks. The aim of this study was to determine the effect of dental treatment on the levels of mutans streptococci (MS) and lactobacilli (LB) and the additional effect of a single application of 40% chlorhexidine varnish (EC40) on the level of MS. Twenty-three children under the age of 5 years scheduled for full dental treatment were selected. Of these 23 children (mean dmf-s 27.1, SD 19.3), 11 children had nursing bottle caries. The mean sugar exposure was 6.4. Subjects were randomly distributed into two groups of approximately equal size. One group received an EC40 application after dental treatment, while the other group received only full dental treatment, both with intravenous anaesthesia with propofol as a single drug. An unstimulated saliva sample and a plaque sample were taken prior to dental treatment. The saliva and plaque sampling of the subjects was repeated after 6 weeks. MS and LB were isolated and counted. The number of children harbouring more than 10(6) MS in a pooled plaque sample decreased significantly from 8 to 2 children 6 weeks after dental treatment. No additional effect of EC40 was found. The number of salivary MS did not change significantly between the groups or before and after treatment. The figures for LB remained at a high level of more than 10(4)/ml saliva before (21 children) and 6 weeks after treatment (17 children). The results of this study indicate that dental treatment results in a significant suppression of plaque MS, while a single application of EC40 showed no significant additional suppression after 6 weeks.

Anesthesia, Dental↗

A PCR-aided transcript titration assay (PATTY) to measure topoisomerase I gene expression in human tumor specimens.

UNLABELLED: Topoisomerase I (topo I) inhibitors are promising anticancer agents with demonstrated activity against a wide range of solid tumors. Quantitative information on topol mRNA levels in tumor biopsies may predict response to topo I inhibitors. MATERIALS AND METHODS: A polymerase chain reaction aided transcript titration assay (PATTY) was developed to allow quantitation of topol mRNA in small samples. Concentrations of topol mRNA in total RNA samples were estimated by RT-PCR analysis in a human small cell lung cancer (SCLC) cell line (GLC,) and its topotecan (GL2C/SK and F) and camptothecin (GL2C/Campt) resistant sublines, human non-small cell lung cancer (NSCLC) and ovarian carcinoma samples. RESULTS: Topol PATTY showed a decreased topo I mRNA level in GLC2/SK and F (4.5 pg/100 ng total RNA) and GLC,/Campt (2.2 pg/100 ng total RNA), respectively, compared to the parent cell line GLC2 (5.4 pg/100 ng total RNA). Topol protein levels as measured by Western blotting were compatible with topol mRNA levels. Median (range) topol mRNA levels were 3.23 (2.33-5.10) pg/100 ng total RNA in resected NSCLC specimen (n = 6), and 2.03 (0.54-0.95) pg/100 ng total RNA in resected ovarian cancer specimen (n = 6). CONCLUSION: We conclude that topol PATTY is a new assay that quantitates topol mRNA levels in cell lines and small tumor samples.

Blotting, Northern↗

99mTc-Sestamibi scanning with SDZ PSC 833 as a functional detection method for resistance modulation in patients with solid tumours.

BACKGROUND: Our aim was to determine the value of 99mTc-Sestamibi scanning as functional detection method of P-glycoprotein (Pgp) blockade by PSC 833 in solid tumour patients. PATIENTS AND METHODS: Day 1 and day 4 after 2,200 mg orally administered PSC 833 the tumour area was scanned after intravenous (i.v.) administration of 400 MBq 99mTc-Sestamibi. In tumours with net 99mTc-Sestamibi uptake and in the hepatic region K-efflux was determined. Whole blood was analyzed for 99mTc-Sestamibi, and PSC 833 levels. RESULTS: Fourteen patients were included. In the only Pgp-positive tumour with positive 99mTc-Sestamibi scanning K-efflux of 99mTc-Sestamibi decreased significantly after PSC 833 intake. A net inhibition of liver efflux of Sestamibi after PSC 833 intake was observed in all evaluable patients. PSC 833 blood levels were all above 2 mg/L during scanning; 99mTc-Sestamibi blood levels post versus pre PSC 833 were unchanged. CONCLUSIONS: PSC 833 induced modulation of K-efflux of 99mTc-Sestamibi in a Pgp positive tumour and in all patients in the liver.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Evaluation of the experiences of fearful children at a Special Dental Care Centre.

A representative sample of parents was interviewed one to two years after their children had been treated at a Dutch Special Dental Care Centre (SBT). Information was sought about the children's current behavior during visits to family dentists. Within one to two years after the experiences at SBT more than 90 percent of the children visited a family dentist, 60 percent of them required restorative treatment and 80 percent of this treatment was performed, using local anesthesia. Retrospectively, the parents report a decrease of their children's dental anxiety, when leaving the SBT. This level of anxiety is unchanged after one to two years visiting a family dentist. For the children there was a significant relationship between dental anxiety as reported by the parents and not visiting a family dentist. Results suggest that referring dentists arrange the initial treatment at the Special Dental Care Centre and that the children in this group referred for dental anxiety belong to a caries-risk group.

Adolescent↗

Ketac Molar Versus Dyract Class II restorations in primary molars: twelve month clinical results.

The aim of the present clinical study was an in vivo evaluation of an improved conventional glass ionomer cement Ketac Molar (ESPE), compared to a polyacid modified composite resin, Dyract (Dentsply/De Trey), used in primary molars. Fifty-three Ketac Molar and fifty-two Dyract restorations were placed in box-only preparations in primary molars. The application time for the chemically cured Ketac Molar, was longer compared to the light-cured Dyract. In comparing the materials, no differences were found, comparing both materials regarding secondary caries, marginal adaptation, wear and fracture toughness. One case of recurrent caries adjacent to a Ketac Molar restoration and two cases in the Dyract group were reported. Two Ketac Molar restorations and one Dyract showed bulk fracture at the time of evaluation. At the twelve-month evaluation, no difference between the investigated materials was registered, which indicates that Ketac Molar can be used as a proximal restoration in the primary dentition. It should be emphasized, however, that one-year data should not be extrapolated to indicate the long-term success of restorations.

Analysis of Variance↗

Prevalence of cheese molars in eleven-year-old Dutch children.

In the Netherlands, first permanent molars with idiopathic enamel disturbances (IED) are called cheese molars. Though concern is expressed about their prevalence, adequate figures on the subject are missing. The porous enamel of cheese molars can be very sensitive to cold air and can decay rapidly. The aim of the present study was to investigate the prevalence in eleven-year-old Dutch children of cheese molars (IED). During an epidemiological study performed in four cities in the Netherlands, the first permanent molars and central incisors of eleven-year-old children were examined for hypoplasia, opacities, posteruptive enamel loss, premature extraction, and atypical restorations. The observation of a hypoplasia excluded the possibility of cheese molar. A total of 497 children were examined. Six percent (n = 128) of the molars (n = 1988) showed signs of IED (cheese molars), 10 percent of the children had cheese molars of which 8 percent two or more. Incisors (4 percent) with opacities were found in 3 percent in combination with two or more cheese molars. Among the four cities, no significant differences in occurrence were found. The results of this study showed that in 10 percent of the Dutch children eleven years of age, cheese molars (IED) were found. The cause for the phenomenon called cheese molars appears to be child centered. Further studies on prevalence, causes and prevention are mandatory.

Chi-Square Distribution↗

Dental treatment of fearful children, using nitrous oxide. Part I: Treatment times.

This study investigated the influence of nitrous oxide on treatment time when it is used as an additional aid to behavior management. Different parts of the treatment of highly anxious child dental patients may vary during sequential dental visits, and separate consecutive parts of the treatment were considered in terms of their duration. Fifty-six children between the ages of six and eleven, each with a previous negative dental experience, were selected. They were randomly assigned into one of two matching groups: one with behavioral management only (control); the other also having nitrous oxide sedation (experimental). Interval 1, involved getting used to the procedures; interval 2 was sedation; interval 3, local anesthesia; and interval 4, preparation and filling. Most children required between four and six sessions. Results show that in terms of total treatment time (TTT), the use of nitrous oxide does not save time, although dental treatment did not require a greater number of sessions. For the dentist to erase the negative imprint of a previous dental experience, special skills are required. Further research is advised concerning the anxiety levels of this age-group.

Anesthesia, Local↗