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Biomedical subjects

J Hermans

Publications and source records attributed to J Hermans.

At least 523 records · Page 29Linked to original sources

Pharmacokinetic interactions of cyclophosphamide and 5-fluorouracil with methotrexate in an animal model.

In tumor-bearing WAG/Rij rats the interaction of cyclophosphamide and/or 5-fluorouracil (5-FU) with methotrexate as manifested at the pharmacokinetic level was studied. Four groups were formed of at least ten animals. The control group, which received single-agent methotrexate, was compared with groups that received methotrexate plus cyclophosphamide, methotrexate plus 5-FU, and methotrexate plus cyclophosphamide plus 5-FU. There appeared to be an increase of 40% in the clearance of methotrexate by the triple combination. Cyclophosphamide especially diminished the terminal part of the concentration-time curve of methotrexate.

Animals↗

[Detection of thyroid cancer : utopia or reality? Or the value of thallium 201 in thyroid pathology].

Faced with a diagnosis of cold thyroid nodule as evidenced by routine scintigraphy, the clinician has to determine whether this nodule is malignant or not. This is a serious problem since, according to literature, 7-20% of cold thyroid nodules are malignant. In 1982 some Japanese authors demonstrated the possibility of using 201 T1 in diagnosing thyroid tumors. This study refers to 120 patients who underwent an operation for thyroid disorders characterized by the presence of one or several cold nodules (as evaluated with conventional scintigraphy) and enables a comparison between a thorough evaluation of the thyroidal status and the 201 T1 scintigrams. These were obtained with a gamma-camera using a pinhole collimator. If a cold nodule is positive with 201 T1, surgery is incontestably indicated, as such a finding correlates with the existence of a thyroid tumor (benign follicular adenoma or carcinoma) in 89.5% of the observed cases. In the cancer group the sensibility of the Thallium test is of 85% and its specificity 80%. We may assert that there is a very low risk of Thallium negative (old) nodules being malignant. The pre-operative 201 T1 scintigraphy is easy to perform in any Nuclear Medicine department. Nowadays, the combination of aspiration cytology and 201 T1 scintigraphy should make it possible to make and accurate diagnosis in the vast majority of differentiated and undifferentiated thyroid cancers.

Adenoma↗

Parallel characterization of bovine von Willebrand protein (factor VIII-associated protein) by light scattering and SDS gel electrophoresis.

Highly purified bovine von Willebrand protein (vWP) has been studied with two complementary techniques. Light scattering measurements on different samples give weight average molecular weights in the range from 7 to 13 million, radius of gyration between 75 and 140 nm and diffusion coefficient near 4.15 X 10(-8) cm2/sec. Scans after electrophoresis in sodium dodecyl sulfate on 2% agarose gels, stained with Coomassie blue, allow calculation of a mass distribution over a series of oligomers with relative size in a range from 1 to 20. The ratio of the average mol. wt. from light scattering and the average size for the observed distribution, which is the mol. wt. increment for successive vWP oligomers, has been determined and found to be 1.0 million. This implies that the molecules of vWP are oligomers of subunits themselves consisting of 4 polypeptide chains each of mol. wt. circa 250,000.

Animals↗

The value of morphometry to classic prognosticators in breast cancer.

In 271 breast cancer patients with adequate follow-up for at least 5.5 and maximally 12 years, the value of morphometry to classic prognosticators of breast cancer (tumor size and axillary lymph node status) was assessed. Previous studies had indicated the value of this quantitative microscopic technique. Apart from quantitative microscopic features, subjective qualitative features such as nuclear and histologic grade were assessed as well. Univariate life-table analysis showed the significance (p less than 0.001) of several features such as lymph node status, tumor size, nuclear and histologic grade, and several morphometric variables (mitotic activity index, mean and standard deviation of nuclear area). Cellularity index was also significant (p = 0.02). Survival analysis with Cox's regression model, using a stepwise selection as well as backwards elimination, pointed to three features: mitotic activity index, tumor size, and lymph node status. Mitotic activity was the most important prognostic feature, but the combination of these three features in a multivariate prognostic index had even more prognostic significance. Kaplan-Meier curves showed that the 5-year survival of lymph node-negative patients (n = 146) is 85%, versus 93% in patients with a "good prognosis index" (n = 150). For lymph node-positive patients (n = 125), 5-year survival was 55%, compared with 47% in the "high index" (poor prognosis) patients (n = 121). Logistic discriminant analysis with 5.5-year follow-up as a fixed endpoint (191 survivors and 80 nonsurvivors) essentially gave the same results. Application of two instead of one decision threshold (e.g., numerical classification probability 0.60 and 0.40) decrease the number of false-negative and false-positive outcomes, however, with a number of patients falling in the class "uncertain." Thus, in agreement with other studies, morphometry significantly adds to the prognosis prediction of lymph node status and tumor size. Mitotic activity index is the best single predictor of the prognosis. An additional index advantage is that the multivariate model results in a continuous index variable that can be subdivided in many classes with an increasing risk of recurrence, so that more refined clinical therapeutic decision making is possible in individual patient care. The morphometric techniques are inexpensive and fairly simple and therefore can be applied in most pathology laboratories.

Actuarial Analysis↗

The value of complement and immune complex determinations in monitoring disease activity in patients with systemic lupus erythematosus.

Serial serum samples from 33 patients with systemic lupus erythematosus were tested for CH50, C3, C4, and circulating immune complexes. Circulating immune complexes were determined by 5 different assays. Disease activity was determined by a scoring system we devised. On an interpatient analysis, overall disease activity correlated significantly with levels of CH50, C3, and a positive result on C1q binding assay. However, with the exception of depressed C3 levels, the sensitivity, specificity, and predictive values of all the serologic tests were low. An intrapatient analysis revealed a patient-specific activity parameter in 11 of the 33 patients. We conclude that these serologic tests are not reliable in assessing disease activity in patients with systemic lupus erythematosus, although a small subgroup of patients will exhibit a patient-specific activity parameter.

Adolescent↗

HLA class II restriction repertoire of antigen-specific T cells. I. The main restriction determinants for antigen presentation are associated with HLA-D/DR and not with DP and DQ.

In order to study the HLA class II restriction repertoire in antigen presentation to T cells, T lymphoblasts (T-LB) of ten different HLA class II donors were generated by a simple and rapid technique; peripheral blood lymphocytes (PBL) were restimulated in vitro with purified protein derivative (PPD) or tetanus toxoid (TET), and then propagated in interleukin-2 containing conditioned medium (IL2-CM). These T-LB appeared to be antigen specific and devoid of alloreactivity. Antigen was presented to these T-LB by allogeneic irradiated PBL as antigen-presenting cells (APC) in 179 combinations. T-LB proliferative responses were restricted mainly by determinants associated with HLA-DR and not with -DP or -DQ; in 102 fully DR mismatched T-LB/APC combinations matching for DP or DQ determinants had no significant influence on T-LB responses. For PPD, preferential DR1 restriction was observed, and the results suggest a preferential DRw11 vs. DRw12 restriction for TET. Moreover, DRw13 may be associated with low anti-PPD T-LB responsiveness.

Antigen-Presenting Cells↗

Clinical evaluation of a technetium-99m bone imaging agent based on the vicinal diphosphonate 1,2-diphosphonoethyleneglycol (DPEG).

From a series of technetium-99m labelled agents based on a vicinal diphosphonic acid structure, the ligand 1,2-diphosphonoethyleneglycol (DPEG) was selected for clinical study on the basis of a biodistribution in rats which compared well with that of methylene disphonphonate (MDP). The 99Tcm-DPEG agent was assessed in ten patients in whom bone metastases had been demonstrated by 99Tcm-MDP imaging two to seven days previously. Visual comparison of the skeletal images obtained with the two agents revealed the same number of bone metastases at the same locations. Statistical analysis of the data revealed no significant differences between the two radiopharmaceuticals on the basis of lesion to soft tissue ratio and lesion to normal bone ratio, although a slightly higher lesion to soft tissue ratio was found for MDP than for DPEG (p less than 0.03). At least for the formulation tested, it is concluded that this new radiopharmaceutical based on the P-C-C-P structure does not possess diagnostic advantages over 99Tcm-MDP for the detection of bone metastases.

Aged↗

Carrier detection in factor VII congenital deficiency.

Thirty obligate and 28 possible carriers of factor VII congenital deficiency, belonging to 16 families, were studied in relation to the immunological variants to which the kindreds belonged, namely, VII+, VIIR and VII-. Factor VII activity and antigen determinations in these subjects formed two phenotypical patterns: a discrepant pattern characterized by a low ratio activity/antigen present in VII+ heterozygotes, and a non-discrepant pattern (normal ratio activity/antigen) which is present in the VII- and VIIR variants. In the first genetic variant the detection of carriers can be performed using the ratio VII:C/VII:Ag. In the other variant, which accounts for the vast majority of heterozygotes, the distribution of the carriers' factor VII is so widespread that a large overlap results between these subjects and the normals. The application of a probabilistic calculation performed by combining the actual values of factor VII:C and the genetic probability of carriership using Fisher's linear discriminant analysis, makes discrimination between carriers and normals easier.

Adolescent↗

The splenic red pulp; a histomorphometrical study in splenectomy specimens embedded in methylmethacrylate.

The anatomy and pathology of the splenic red pulp was studied in three-dimensional reconstructions of methylmethacrylate embedded blocks of tissue obtained after splenectomy, as well as by morphometrical analysis of a large number of specimens. The sinuses of the spleen form a plexus of anastomosing vessels with remarkable buds. Capillaries end as sheathed capillaries in the cord tissue, the 'filtering' area, but a large proportion of the red pulp cords appear to be 'non-filtering'. These might form part of the lymphatic compartment, which is separate from the white pulp and its extension along the capillaries. This area has not yet been described in man. The change in the volume and structure of the various components of the red pulp were studied in 60 controls and in cases of traumatic rupture, idiopathic thrombocytopenic purpura, aplastic anaemia, autoimmune haemolytic anaemia, congenital spherocytosis, splenic congestion, and Hodgkin's disease. Significant differences were found in the volume of filtering and non-filtering areas, the size of the sinus compartment, and the degree of vascularization; these differences were only partially expected, for instance in disorders with excessive erythrocyte sequestration. A decrease of the 'non-filtering' area in Hodgkin's disease might indicate an unknown aspect of this disease. In agreement with our previous paper on the amount of white pulp, spleens removed because of traumatic rupture and those incidentally removed during abdominal surgery may not be combined as a single control group, because of significant and probably functional differences in the composition also of the red pulp.

Adolescent↗

Variations in histopathological evaluation of non-neoplastic colonic mucosal abnormalities; assessment and clinical significance.

The variation between three pathologists examining histological features seen in non-neoplastic colonic mucosa from 40 biopsies was analysed. Several procedures to express observer variation were used and compared, with emphasis on kappa statistics. Only five features, the presence of ulceration, villous surface, epithelioid granulomas, severe mucus depletion and crypt abscesses were sufficiently reproducible by the three pairs of pathologists. These findings suggest that other criteria used for the classification of inflammatory bowel disease are potentially unsatisfactory. When results from different studies on biopsies are being compared, influence of observer variation should be identified. Comparison of statistical techniques showed overall variation to be less useful than other statistical procedures. There was little difference between results from kappa statistics and other measures of agreement (overall agreement excluded).

Biopsy↗

Colon polyps and carcinomas: prospective comparison of the single- and double-contrast examination in the same patients.

Single-contrast (SC) and double-contrast (DC) colon examinations were compared in 425 consecutive patients for detection of polyps and stricturing carcinomas. Each patient was examined with both SC and DC during the same session. In patients with carcinoma, there was no significant difference between the two modalities. DC was far superior to SC for detection of rectal or colonic polyps (p less than 0.05); however, the techniques appeared to be complementary in the sigmoid and cecum. The authors conclude that DC is superior to SC as a means of screening for polyps of the rectum and colon, with SC being useful as an adjunct in problem areas such as the sigmoid and cecum.

Adolescent↗

Pharmacokinetics of tobramycin in patients with cystic fibrosis. Implications for the dosing interval.

The pharmacokinetics of tobramycin were evaluated in 15 patients (8 to 22 years of age) with cystic fibrosis (CF). A dose of 3.0 to 3.3 mg/kg of body weight was given intravenously over 20 minutes, and concentrations in serum were followed up to eight hours after initiation of the infusion. In the calculation of pharmacokinetic parameters, a two-compartment open model was used. The elimination half-life of the drug was highly inversely correlated with age (p less than 0.0004), and body weight (p less than 0.00002). Total body clearance (TBC), and volume of distribution at steady state (VDSS) were directly correlated with age and body weight. However, when TBC and VDSS were corrected for BSA, no correlation could be demonstrated. The mean one-hour and eight-hour serum concentrations of tobramycin were 5.40 and 0.45 microgram X ml-1, respectively. Between patients, considerable differences were found in the time after administration at which the serum concentration decreased below 1 microgram X ml-1. This interpatient variation has clinical implications for tobramycin therapy in CF, in particular for the dosing interval.

Adolescent↗

Neuronal nuclear membrane indentation and astrocyte/neuron ratio in Huntington's disease. A quantitative electron microscopic study.

Ultrastructural study of the nucleus accumbens, caudate nucleus and frontal cortex of patients with Huntington's disease showed that neuronal nuclear membrane indentations were significantly more frequently present in the nucleus accumbens and caudate nucleus, than in a control group. The astrocyte/neuron ratios in the same areas were also found to be higher in the Huntington patients. In a search to find out whether this finding is unique in Huntington's disease the brains of patients with several other diseases of the central nervous system, characterized by involuntary movements and/or dementia (Pick's disease, Down's syndrome, Alzheimer's disease, Parkinson's disease, Creutzfeldt-Jakob disease, tardive dyskinesia and multi-infarct dementia) were investigated in the same way. Although some findings were similar in this group, the Huntingtonian brains could be almost completely separated, with the exception of one patient with Creutzfeldt-Jakob disease, by the use of a discriminant analysis, taking into account the percentage of neurons with nuclear membrane indentation and astrocyte/neuron ratio of three areas of grey matter.

Astrocytes↗

Short-term and long-term intra-individual variations and critical differences of clinical chemical laboratory parameters.

Twenty eight clinical chemical blood parameters were studied with respect to intra-individual variations. Both short term variations, within one day and during one week, and long term variations, during a six months period, were investigated in groups of 62, 16 and 274 individuals. Moreover, critical differences were calculated from the total variations, i.e. physiological (personal) and analytical variations. The influences of external factors (sex, smoking, and oral contraceptives) were being studied. It was concluded that the use of laboratory data in clinical diagnosis is considerably improved when intra-individual variations and critical differences are used.

Adolescent↗

Short-term and long-term intra-individual variations and critical differences of haematological laboratory parameters.

The complete blood cell count and the differential leukocyte count have been studied for their variations within-one-day and during one week (short-term variations) and during a period of six months (long-term variations) with an automatic haematology analyser (H-6000, Technicon), in which some new parameters (large unstained cells, high peroxidase cells, red cell distribution width, platelet distribution width, mean platelet volume, plateletcrit) are included. The influence of external factors such as sex-differences, smoking/non-smoking, use of oral contraceptives etc. have also been studied. It appears that the use of critical differences together with haematological data improves the value of these parameters in diagnosis and treatment of patients.

Adolescent↗

Short-term and long-term intra-individual variations and critical differences of coagulation parameters.

The intra-individual variations of 9 coagulation parameters were studied during short-term (within-one-day) and long-term (six months) periods. Two groups of healthy individuals (viz. 60 and 274 persons) were involved. Moreover, critical differences have been calculated from the total variations, comprising both biological and analytical variations. The influences of external factors such as sex, smoking and the use of oral contraceptives have also been studied. The variability and critical differences found in coagulation parameters in this study appeared to be of the same order as those observed in parameters usually determined in clinical chemistry and haematology. The application of critical differences in the evaluation and use of laboratory data, also in coagulation studies, enhances the objectivity of the judgement. Moreover, in the follow-up of patients the sensitivity of the parameters is increased.

Adolescent↗