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Biomedical subjects

J Hermans

Publications and source records attributed to J Hermans.

At least 577 records · Page 32Linked to original sources
PubMed1983

Comparative pharmacokinetics of brotizolam and triazolam in healthy subjects.

Pharmacokinetics of oral brotizolam (0.50 mg) and triazolam (0.50 mg) were studied in healthy young volunteers. The plasma concentration profile of brotizolam can be described as a one compartmental open model with first-order absorption. The absorption of triazolam was less regular and in half of the subjects was not consistent with first-order kinetics. Inter-individual variability in absorption rate (peak times) was larger for brotizolam. Mean peak times were 1.1 +/- 1.0 h for brotizolam and 1.2 +/- 0.5 h for triazolam. Mean peak concentrations were 7.3 +/- 3.1 ng/ml and 5.0 +/- 3.9 ng/ml respectively. The elimination half-life of brotizolam was twice that of triazolam with mean values of 5.0 +/- 1.1 h and 2.6 +/- 0.7 h respectively. There was no correlation between the half-lives of the two drugs. Protein unbound fraction was similar for triazolam and brotizolam with mean values of 9.9 +/- 1.5% and 8.4 +/- 0.7% respectively.

Administration, Oral↗
PubMed1983

The amount of white pulp in the spleen; a morphometrical study done in methacrylate-embedded splenectomy specimens.

This report deals with a morphometrical study on 92 surgically removed human spleens, to investigate the composition of spleens which are considered to be normal, i.e. spleens which had ruptured in traffic accidents or which had been incidentally removed during abdominal operations. A comparison was made with 16 spleens with hypersequestration of platelets and to 11 with hyper-sequestration of erythrocytes. Methyl-methacrylate embedding was used because of the superiority of this technique over conventional paraffin embedding. Significant differences were found between both 'normal' groups as to the absolute and relative amount of white pulp as well as the perifollicular red pulp zone. Based also on the few morphometrical reported studies in the literature, spleens removed during abdominal surgery form the best control group. Traumatic rupture of the spleen in traffic accidents might specifically occur in spleens which already contained a stimulated lymphatic compartment. A probably non-specific increase of white pulp was found in splenomegaly of varied aetiology. An expected influence of age on weight and composition of the spleen was not found in our study. The spleen changes in weight and composition only up to 5 years of age. Significant involution at older age was not found in ours nor in other reported larger series.

Adolescent↗
PubMed1983

Role of granulocytes and monocytes in experimental Staphylococcus epidermidis endocarditis.

The role of granulocytes and monocytes during the induction and course of Staphylococcus epidermidis endocarditis was investigated by the selective depletion of monocytes with the drug VP16-213 and of both granulocytes and monocytes with nitrogen mustard. The induction of endocarditis was influenced only by the depletion of monocytes: the 50% infective dose differed significantly, being 3.4 X 10(5) CFU in control rabbits and 3.4 X 10(4) CFU in the monocyte-depleted rabbits, whereas no significant differences were found between the latter and those depleted of both granulocytes and monocytes. Also, control rabbits injected with 10(6) or 10(7) CFU had a significantly higher incidence of sterile vegetations than did rabbits selectively depleted of granulocytes or monocytes. Compared with baseline values, mean monocyte numbers at the time of bacterial inoculation were significantly increased in control rabbits whose vegetations remained sterile, whereas this effect was not seen in rabbits whose vegetations became infected. The course of the endocarditis appeared to be significantly influenced by both granulocytes and monocytes. Comparison showed that a decrease of the same numbers of these cells per microliter of blood was accompanied for the monocytes by an approximately fourfold higher increase of the number of staphylococci in the vegetations. The correlation between the number of granulocytes and of monocytes on the one hand and the number of staphylococci in the vegetations on the other was not substantially influenced by the duration of the disease or the number of staphylococci injected to induce the endocarditis. The number injected proved to be significantly correlated with the number of staphylococci in the vegetations. In rabbits with numbers of CFU per gram of vegetation exceeding 10(7), blood cultures were usually positive. This finding applied rarely to control rabbits, but generally to drug-treated rabbits. In the latter animals a significant correlation between the number of staphylococci in the vegetations and in the circulation was found. We conclude that only monocytes have a measurable effect on the induction of Staphylococcus epidermidis endocarditis but during its course both granulocytes and monocytes keep the endocardial infection in check.

Animals↗
PubMed1983

Relative importance of C4 binding protein in the modulation of the classical pathway C3 convertase in patients with systemic lupus erythematosus.

Serum concentrations of C1q, C4, C4 binding protein (C4bp), C3 and C2 haemolytic activity have been measured in 110 samples from 20 patients with systemic lupus erythematosus (SLE). Significant reductions in comparison to normal levels were found in the mean serum concentrations of C4, C3 and C4bp as well as C2 haemolytic activities. For patients serum concentrations of C4 correlated with C2 haemolytic activities (r = 0.91) and C4bp (r = 0.79); the C2 haemolytic levels correlated with the concentration of C4b (r = 0.72). It is concluded that serum concentrations of the complement components C4 and C2, which are the constituents of the classical pathway C3 convertase, are regulated by C4bp in vivo. Further metabolic studies are required to determine the causes of decreased serum concentrations of C4bp in patients with SLE.

Carrier Proteins↗
PubMed1983

Clinical diagnosis of primary biliary cirrhosis: a classification based on major and minor criteria.

The presence of antimitochondrial antibodies (AMA) is a sensitive marker for the diagnosis of primary biliary cirrhosis (PBC). Since these antibodies are not specific for PBC, and differentiation of PBC from autoimmune chronic active hepatitis (CAH) has important therapeutic and prognostic implications, additional diagnostic criteria were investigated in 92 patients with AMA. Patients were classified as PBC, CAH, undefined chronic liver disease, or no liver disease by means of three objective methods, and these diagnoses were compared with those of the patients' own physicians. Using internationally accepted strict diagnostic criteria, it was possible to classify 42% of 92 AMA-positive patients. An unbiased computer cluster analysis with 17 variables yielded groups which varied in the severity of the disease, but did not separate clinically different nosological entities. With a diagnostic scheme which uses major and minor criteria for both PBC and CAH, the large majority of patients (86%) were classified as follows: definite PBC (n = 47), probable PBC (n = 20) and no liver disease (n = 12). Seven patients with definite PBC also showed some features of CAH, but there were no patients with only classical CAH. Patients who could not be classified, frequently had very mild liver disease not requiring treatment (6/12), or had not had liver biopsy (6/12). This new diagnostic scheme is promising as it seems to combine sensitivity with specificity for the diagnosis of PBC. If validated in another group of patients with liver disease, it may be helpful for studies on the natural history of the disease and for evaluation of treatments.

Adult↗
PubMed1983

[Clinical importance of the level of the free fraction of thyroid hormones].

The physiologic importance of the free fraction of thyroid hormones is well accepted for some time. The determination of free thyroid hormones plasma levels by column chromatography and radio-immunoassays has been tested in our laboratory since november 1980. Six hundred and ten patients have been submitted to a precise anamnesis, a clinical examination and a thyroid investigation by scintigraphy and echography. We have compared the following parameters: T4 and fT4, T3 and fT3, TSH, TBG in euthyroidism and in the pathologic status of hyperthyroidism, we have found an excellent correlation (r greater than 0,9) between the values of T4 and T3 and their free fraction. The determination of fT3 and fT4 seems to be specially interesting in comparison of the T4 and T3 because of the low incidence of false abnormal results in those patients regarding the other parameters. Hyperthyroidism is characterized by a lack of correlation between total and free hormones; the levels of the free fraction being widely increased. The determination of the free hormones levels improves the sensitivity and the accuracy of the diagnosis of hyperthyroidism. It permits an early diagnosis of the disease, an earlier detection of the recurrence and makes easier the follow-up of the treated patients. In hypothyroidism, there is a so light decrease in the value of fT3 and fT4 that the TSH estimation remains the method of choice to assure the diagnosis. Thus, we can conclude that the determination of fT3 and fT4 by column chromatography and radio-immunoassays is more discriminating in euthyroidism and hyperthyroidism. In hypothyroidism TSH and fT4 are the most sensitive parameters.

Chromatography↗
PubMed1982

Anticoagulant and calcium-binding properties of high molecular weight derivatives of human fibrinogen (plasmin fragments Y).

The present study was undertaken as a step to delineate further the localization of the calcium-binding sites in fibrinogen and to assess the anticlotting properties of fibrinogen degradation products. To this purpose, fragments Y were prepared by plasmin digestion of human fibrinogen in the presence of added Ca2+, and purified. We found that, on a molar basis, fragments Y exhibit twice as much anticlotting activity as fragments X. They possess two calcium-binding sites with Kd = 1.9 . 10(-5) M. Their predominant amino-terminal amino acids are alanine and tyrosine. It is known that one binding site in fragment Y is related to its D moiety. We conclude that the other calcium-binding site may be located in the central domain of the molecule.

Binding Sites↗
PubMed1982

A fibrinogen fragment D (D intermediate) with calcium binding but without anticlotting properties.

Plasmin digestion of fibrinogen in the presence of Ca2+ or of EGTA leads to the formation of two sets of fragments, designated Dcate and D EGTA, respectively. Fragments Dcate, in contrast to D EGTA, bind one calcium ion and are anticlotting. Both these properties of Dcate are related to a 13-kDa carboxyl-terminal stretch of its gamma-chain, which is missing in D EGTA. The molecular weights of the gamma-chains of Dcate and D EGTA are 38000 and 25000, respectively. Now we have prepared a D-fragment, Dint, which has a gamma-chain with a molecular weight of 29000. Dint binds one calcium ion per molecule but has no anticlotting properties. Thus the Ca2+-binding site of Dint (and Dcate) is directly dependent on the 4-kDa piece of the gamma-chain that is present in Dint but not in D EGTA. As a consequence, the anticlotting properties of Dcate reside in the gamma 9-kDa stretch that is absent in Dint.

Amino Acid Sequence↗
PubMed1982

Influence of water and salt solutions on UVB irradiation of normal skin and psoriasis.

The influence of tap-water (TW) and salt solutions on the minimal erythema dose (MED) was investigated for normal human skin and uninvolved skin of psoriasis patients. MED (UVB) determinations on the forearm revealed that: (1) the MED definitely decreases whenever the arm is immersed in TW or NaCl solutions with a low concentration (4%) prior to UVB exposure, whereas almost saturated NaCl solution (26%), as well as locum Dead Sea water (LDSW), do not produce a change in the MED, and (2) the decrease in MED obtained by wetting the skin with TW was no longer present when the skin was allowed to dry for 20 min. A decrease in water uptake by skin (in vivo) and by callus (in vitro) was found as the salt concentration of the external solution increased. It is proposed that water taken up by the skin plays an important role in the sensitivity of the skin to UVB exposure. Bathing in TW or 4% NaCl prior to UVB exposure offered a slight to moderate improvement in psoriasis over UVB irradiation alone. Finally, it was shown that there is no obvious difference in clearance of the psoriatic skin between a bath in TW, 4% NaCl, or LDSW prior to UVB exposure.

Adolescent↗
PubMed1982

Detection of lesions in thallium-201 myocardial perfusion scintigraphy.

Experimental studies have been made of the lesion detectability in myocardial perfusion studies using thallium-201. A series of images (AP-view) was generated using a convolution of a mathematical model of the left ventricular myocardium and an experimentally determined point spread function. Background was added. Images were simulated with 100 k, 200 k, and 300 k counts for the complete image. Each image contained a lesion with either 0% or 50% of the normal tracer concentration. All images were interpreted by five experienced observers, independently of each other. Their interpretations were analysed using the Kolmogorov-Smirnov two sample test. The true positive fraction (TPF) was hardly affected by changes in count density. The TPF decreased significantly if the lesion tracer concentration changed from 0% to 50% of the normal myocardial tracer concentration. The decrease was independent of the count density. The false positive fraction (FPF) decreased significantly if the count density increased; no difference in FPF was found for a change in lesion tracer concentration. In addition, plots were generated with the TPF versus lesion volume. The TPF was lowest for locations far from the camera; FPF was high for these segments. Increase of the count density mainly improved the FPF in these segments. Small lesion were more difficult to detect.

Heart Diseases↗
PubMed1982

Diagnostic value of fibrinopeptide A and beta-thromboglobulin in acute deep venous thrombosis and pulmonary embolism.

The purpose of this study was to assess the predictive values of the assays of fibrinopeptide A (FPA), beta-thromboglobulin (BTG) and their combination in patients suspected of having acute deep venous thrombosis (DVT) or pulmonary embolism (PE). In 80 controls the mean (+/- SD) plasma concentrations of FPA and BTG were 0.72 +/- 0.47 and 28.2 +/- 10.1 ng/ml, respectively. In 26 patients in whom DVT was confirmed by phlebography and Doppler ultrasound, clearly raised mean FPA (5.62 ng/ml) and BTG (70.6 ng/ml) concentrations were measured compared to those in 13 patients in whom this disorder was excluded (1.00 and 33.6 ng/ml, respectively). Also in 25 patients, in whom PE was established by perfusion lung scanning, clearly increased mean FPA (6.28 ng/ml) and BTG (82.4 ng/ml) concentrations were measured compared to those in 12 patients without this disease (1.03 and 32.5 ng/ml, respectively). Raised FPA and BTG concentrations were also found in 20 patients with inflammatory disorders and in 10 with various types of malignancy. The mean FPA and BTG concentrations did not differ between patients with renal failure or diabetes mellitus and patients without these diseases. From the predictive values of these assays and their combination it can be concluded that raised FPA and BTG concentrations are not specific for thrombosis. However, when normal FPA and BTG concentrations are present, acute DVT or PE can safely be excluded in symptomatic patients. In the group with confirmed DVT/PE, anticoagulant treatment (heparin and phenprocoumon) brought down the mean FPA concentration to levels within the normal range in less than 1 hour while the mean BTG concentration remained elevated throughout the 10-day study period.

Acute Disease↗
PubMed1982

Cutaneous T-cell lymphoma: clinicopathological relationships, therapy and survival in ninety-two patients.

Clinicopathological findings, methods of treatment and survival in ninety-two patients with cutaneous T-cell lymphoma (CTCL) (eighty-five mycosis fungoides and seven Sézary syndrome), seen in the Leiden University Hospital between 1974 and 1980, are reported. All patients were staged and treatment was given accordingly. Patients without signs of extracutaneous disease (74%) were treated with eigher total-skin electron-beam irradiation (E beam), topical mechlorethamine (HN2) or PUVA. Topical HN2 and E beam had an equal effect on survival. Electron-beam induced a higher number of initial complete remissions than HN2, but fewer patients relapsed while on maintenance treatment with HN2. In the patients with lymph node and/or visceral involvement, E beam followed by systemic chemotherapy--cyclophosphamide, vincristin (Oncovin) and prednisone (COP)--gave better results than topical therapy or COP alone. Survival was influenced most by the type of skin lesion, the presence or absence of lymph node and/or visceral involvement, and the ability to induce a complete remission initially.

Adult↗
PubMed1982

Morphometric characterization of diffuse large-cell (histiocytic) lymphomas.

From 28 large-cell lymphomas, defined by marker studies, enzyme histochemistry, and electron microscopy as large noncleaved follicle center cell tumors (lnc FCC), B-immunoblastic or true histiocytic lymphomas, morphometric cell parameters, including nuclear size and shape, cytoplasmic area, and cytoplasm-to-nucleus ratio, were measured. Moreover, size, number, and location of nucleoli in the nuclei of the characteristic cells of lnc FCC and B-immunoblastic lymphoma were determined. Statistical evaluation of the data showed the nuclear shape to be the most sensitive parameter in the differentiation of true histiocytic lymphoma from lnc FCC and B-immunoblastic lymphomas. With nucleolar parameters lnc FCC could be differentiated from B-immunoblastic lymphoma: lnc FCC had a higher mean number of nucleoli per cross-section of nucleus and more eccentrically located nucleoli. Moreover, the measurements show that the differences in number and location of nucleoli between large noncleaved follicle center cells and B-immunoblasts are smaller than generally described in the literature. Our results show that it is possible to differentiate by morphometry between lnc FCC, B-immunoblastic, and true histiocytic lymphomas.

Analysis of Variance↗
PubMed1982

The implications of subjective recognition of malignant cells in aspirations for the grading of prostatic cancer using cell image analysis.

A pilot study of selective morphometry was performed in smear preparations from fine needle aspirates of six cytologically graded prostatic carcinomas. Given the instruction to select carcinoma cells with large nuclei for measurement, cytotechnologists and a cytopathologist differed in the selection of cells from grade III tumors. The cytotechnologists had discarded large bare atypical nuclei because they assumed that these were degenerated cells. Transmission electron microscopy, using an open-face embedding technique, demonstrated, however, that these cells were not degenerated but were poorly differentiated carcinoma cells that had lost their cytoplasm during smear preparation. It is obviously of great importance for the morphometric discrimination of grade I and grade III carcinomas that such bare atypical nuclei be included in the selections of cells to be measured. Our data indicate that the measurement of 20 selected cells per smear preparation is sufficient for accurate morphometric grading and that such measurements are reproducible.

Biopsy, Needle↗
PubMed1982

Clinical staging system for hairy-cell leukemia.

To find a clinical staging system for patients with hairy cell leukemia, 391 patients contributed by 22 centers were analyzed using the proportional hazard survival model. Attention was paid to nonsplenectomized patients to find a staging system to predict the survival length at the time of diagnosis. On the basis of hemoglobin level and spleen size at the time of diagnosis, 3 stages could be distinguished with significantly different prognoses (stages I-III). In addition, we addressed the question of splenectomy to identify those patients who benefit from the operation. Using arbitrary, but clinically relevant, criteria to call the operation beneficial, splenectomy appears to be indicated for patients with large spleens (greater than or equal to 4 cm under costal margin) or with smaller, but palpable, spleens when anemia (Hb less than 12 g/dl) is present. The third question concerned the splenectomized patients. To indicate the patients who have a poor postsplenectomy survival, a staging system was developed on the basis of hemoglobin level and number of neutrophils at 2-3 mo after the operation (stages A-C). The validity of the two staging systems was supported by the results of an analysis of an independent test series of patients. These staging systems may be helpful for the choice of therapy and in the planning of clinical trials in patients with hairy-cell leukemia.

Actuarial Analysis↗
PubMed1981

Characterization of the inhibition of fibrin assembly by fibrinogen fragment D.

Fragment D (Mr 100 000) prepared from a terminal plasmin digest of fibrinogen was isolated and used to study its effect on fibrin formation. Increasing amounts of fragment D added to a solution of fibrinogen and thrombin decrease the rigidity of the resultant gel (10% of control at 2 mol of fragment D/mol of fibrinogen). Half-maximal inhibition is achieved at 1 mol of fragment D/mol of fibrinogen for non-cross-linked clots and at 1/2 mol of fragment D/mol of fibrinogen for cross-linked clots. "Clottability' decreases concomitantly with the rigidity. Only small amounts of fragment D (less than 10% for non-cross-linked gels) are incorporated into the gel. Light-scattering shows an increase in the final fibre thickness at fragment D concentrations up to 2 mol of fragment D/mol of fibrinogen, from 60 molecules/cross-section for the control to 120 molecules/cross-section. Higher fragment D concentrations lead to a decrease in the final fibre thickness. The limit fibre thickness is 8 nm, with a length of 80 nm, which is equivalent to a fibrin trimer. On the basis of results of synthetic-substrate and fibrinopeptide-release assays, it is clear that thrombin inactivation is not responsible for this effect. These data suggest that fragment D may inhibit fibrin formation by blocking the bimolecular polymerization of activated fibrin monomer molecules to form protofibrils, although additional effects on subsequent assembly steps may also be involved.

Blood Coagulation↗