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Biomedical subjects

J Poortman

Publications and source records attributed to J Poortman.

At least 19 recordsLinked to original sources

Distribution of inspired gas to each lung in the anaesthetised horse and influence of body shape.

The distribution of inspired gas to each lung, time constants of the lungs and parameters of gas exchange were studied in 2 groups of horses (mean bwt 606 kg), anaesthetised using thiopentone and chloral hydrate and breathing room air. One group (n = 4) had a downward curved abdominal contour (round-bellied) and the other group (n = 4) had an upward curved abdominal contour (flat-bellied). An equal distribution of inspired gas between the lungs existed in both groups in dorsal recumbency. Flat-bellied horses maintained this equal distribution in lateral recumbency whereas in round-bellied horses an uneven distribution of tidal volume (VT) developed. The percentage of (VT) distributed to the dependent lung was 23% and 38% for left and right lateral recumbency respectively. The distribution of VT agreed with the ratio of time constants of the lungs in flat-bellied horses but differed markedly from this ratio in round-bellied horses suggesting that, in the latter, factors other than compliance and resistance play a role in distribution of ventilation. Round-bellied horses had a lower PaO2 and a larger (A-a)PaO2 than flat-bellied horses in all body positions. The results are compatible with the known hypothesis that pressure exerted by abdominal contents on the dependent lung and diaphragm is an important factor in ventilation/perfusion mismatch of the anaesthetised horse.

Anesthesia

Differential artificial ventilation in anesthetized horses positioned in lateral recumbency.

Effects of differential ventilation on gas exchange were studied in 7 isoflurane-anesthetized, laterally recumbent horses, and were compared with effects of conventional ventilation, using similar minute volume. A tracheal tube-in-tube intubation technique allowed each lung to be connected separately to an anesthetic circle system with a ventilator. Two distribution patterns of tidal volume were investigated; half the tidal volume was distributed to each lung and two-thirds the tidal volume was distributed to the dependent lung. Effects of the combination of these patterns with positive end-expiratory pressure (PEEP) of 10 and 20 cm of H2O to the dependent lung were investigated. Differential ventilation maintained PaCO2, but significantly increased PaO2 from 180 to 270 mm of Hg (+44%) and decreased shunt perfusion from 22 to 19% (-15%), regardless of the distribution pattern used. Mean airway pressure was lower than the value detected during conventional ventilation. The combination of differential ventilation with selective PEEP was followed by a decrease in PaCO2 and further increase of PaO2 and decrease of shunt, which were similar for both distribution patterns. Effects of PEEP of 20 cm of H2O were more pronounced than those of PEEP of 10 cm of H2O. Owing to the combined effects of differential ventilation and selective PEEP, PaO2 increased to 399 mm of Hg and shunt decreased to 15%. This represents increase of 112% and decrease of 33% respectively, compared with values for conventional ventilation. Mean airway pressure increased maximally to 23 cm of H2O, which was 11 cm of H2O greater than the value for conventional ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General

Insect-sting challenge in 138 patients: relation between clinical severity of anaphylaxis and mast cell activation.

One hundred thirty-eight patients with a previous anaphylactic reaction to a yellow jacket or a honeybee sting, as well as eight volunteers, were subjected to an in-hospital sting challenge. Plasma levels of histamine, tryptase, and prostaglandin D2 (PGD2) during sting challenge were studied in relation to clinical symptoms. Prechallenge levels (mean +/- SD) of histamine, tryptase, and PGD2 were 2 +/- 1 nmol/L, 0.3 +/- 0.3 U/L, and 320 +/- 223 ng/L, respectively. In the volunteers and in none except for one of the nonreacting patients, these levels did not change significantly after challenge. In contrast, mean increases in the group of 18 patients with a mild reaction were significant for histamine and tryptase at one or more time points after the challenge. (Five patients demonstrated no increase in histamine; nine demonstrated no increase in tryptase.) Except for histamine levels in one patient, these increases were considerably more in all 17 patients with a severe reaction, starting from the first anaphylactic symptoms. Fifteen minutes later, peak values were reached of 1275 +/- 2994 nmol of histamine per liter (range, 3 to 12800 nmol/L; median, 11 nmol/L) and 406 +/- 1062 U of tryptase per liter (range, 1.8 to 4400 U/L; median, 17 U/L). This rise in levels inversely correlated with the mean arterial pressure. Plasma levels of PGD2 in severely reacting patients did not differ significantly from those in patients with a mild or no reaction. In conclusion, only 28% of patients with a history of Hymenoptera anaphylaxis developed an anaphylactic reaction after an in-hospital challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis

The effect of oral iron supplementation on erythropoiesis in autologous blood donors.

The effect of oral iron supplementation on erythropoiesis was studied prospectively in 34 autologous blood donors. The subjects, all of whom were to undergo total hip surgery, had normal iron status at the start of the study. During the preoperative period, in which 4 units of blood were collected, 17 patients received oral iron supplementation with 287 mg of ferrous sulfate (105 mg of elemental iron/day), while 17 patients did not use any iron supplementation. Oral iron supplementation during the 4-week preoperative period lessened the decrease in ferritin levels after two phlebotomies. Neither the decrease in hemoglobin nor the increase in erythropoietin levels was influenced by iron supplementation. In both iron-supplemented and control patients, serum erythropoietin levels returned to initial values within a few days after surgery. In autologous blood donors with a normal iron status, the use of supplemental iron does not affect erythropoiesis and is insufficient to maintain iron stores.

Administration, Oral

Nonisotopic binding assay for measuring vitamin B12 and folate in serum.

We evaluated a nonisotopic method (CEDIA; cloned enzyme donor immunoassay) for estimating vitamin B12 and folate in serum. The assays were performed with a Cobas-Mira analyzer. Intra-assay CVs were from 3.7% to 11.0% for vitamin B12 and from 1.2% to 10.7% for folate. Interassay CVs ranged from 9.5% to 11.9% for vitamin B12 and from 6.1% to 18.5% for folate. Linearity was satisfactory, with analytical recovery of 94% at 8.7 and 25.4 nmol/L for folate and 280 and 554 pmol/L for vitamin B12. The detection limit was 3.6 nmol/L for folate and 12.3 pmol/L for vitamin B12. Results of this assay correlated well with those of a conventional radioassay: r = 0.98 for vitamin B12 (n = 51) and r = 0.97 for folate (n = 57). The CEDIA was easy to perform but appeared to be unreliable for use with samples from myeloma patients.

Folic Acid

[Desmopressin in hemophilia A and Von Willebrand's disease].

The treatment with desmopressin prior to surgery of patients with mild haemophilia A (HA) and Von Willebrand's disease (VWD) was retrospectively evaluated in a general hospital, from 1978 until 1987. From a group of 87 treated patients, 40 patients are reported (21 VWD, 19 HA) of which plasma factor VIII (FVIII) and Von Willebrand factor (VWF) concentrations were determined before, and twice after desmopressin treatment. Desmopressin was administered intravenously at a dose of 0.4 micrograms/kg body weight. Tranexamic acid was used only when surgery in the mouth cavity was performed, at a dose of 1 gram three times a day. Side effects were seen only in 5 patients (3 VWD, 2 HA). No significant difference between both groups was seen in bleeding tendency, transfusion necessity and side effects (chi 2 test). In both groups, FVIII and VWF concentrations increased significantly after 20 and 60 minutes following DDAVP administration (paired t-test). After 360 minutes, the FVIII concentration increased significantly in both groups, however, only in the VWD patients did VWF increase significantly. In neither group did initial FVIII concentrations correlate with the increase in FVIII (linear regression analysis). One female patient reacted differently to DDAVP, with a decrease in FVIII and VWF values. Desmopressin is a safe and effective agent in the management and prophylaxis of bleeding tendency in patients with mild HA and mild VWD.

Deamino Arginine Vasopressin

New possibilities in erythrocyte survival studies with the application of a Well-type germanium semiconductor detector.

The application of a Well-type germanium semiconductor detector creates new possibilities in erythrocyte survival studies. Using 51Cr, the effective dose equivalent in a standard procedure can be reduced from approximately 780 to 2 microSv. The properties of the detector, namely, high efficiency and high energy resolution, also enable the application of two or even more radionuclides within one individual. This is demonstrated by some experiments utilizing a novel dual-label technique with 57Co tropolonate and 58Co tropolonate. Although this new dual-label technique needs further investigation, it underlines the potential possibilities of studying certain unanswered but clinically relevant questions in the field of transfusion medicine with the application of a Well-type germanium semiconductor detector.

Adult

A new dual-label technique for platelet survival studies with the use of 111indium and 114mindium tropolonate.

A dual-label technique to study the survival of two different populations of platelets within one individual was developed using 111indium and 114mindium. The validity of the technique was demonstrated in seven individuals with an expected equal survival time of two platelet populations and in two persons with an expected difference in platelet survival time. Since the energy spectra of the two indium isotopes are very close, a well-type germanium semiconductor detector was applied. By adaptation of the counting time the effective dose equivalent of the dual-label procedure could be restricted to 1.6 mSv. The dual-label technique provides an instrument for studying the survival of two different populations of platelets simultaneously within one individual.

Adult

Flow cytometric analysis of DNA ploidy in canine mammary tumors.

DNA ploidy has been determined using flow cytometry in 23 nonmalignant and 34 malignant (primary and metastatic) mammary tumors from 46 dogs. This parameter was compared with clinical stage, histology, and estrogen and progesterone receptor analysis. Twenty-one of 34 cancers (61.8%) from 32 dogs were DNA aneuploid. Aneuploidy was also found in 4 of 23 nonmalignant tumors (17.4%) from 20 dogs. Regional lymph nodes were involved in 6 of 10 diploid and 3 of 9 aneuploid cancers of dogs with operable disease. The aneuploidy incidence was higher in dogs that had distant metastasis at initial diagnosis (8 of 11) than in those presented with local or locoregional disease (9 of 19), although this difference was not statistically significant. DNA aneuploidy incidence was not found to be related to histological tumor type, histological malignancy grade, nuclear grade, or steroid receptor presence. Heterogeneity in DNA content was found in 4 of 32 cancers (30 dogs) in samples from primary or locally recurrent lesions. In 3 of 16 cancers that were analyzed both at the primary and at secondary sites of growth, a significant variation in DNA content was observed. The degree of aneuploidy in the dog cancers was much lower than seen for human breast carcinomas with a relatively high frequency of hypoploid stemlines (7 of 34 cancers, 20.6%). The frequency distribution of DNA indices in dog mammary cancers indicates that aneuploidy evolution probably differs from that of human breast cancer.

Animals

The endogenous concentration and subcellular distribution of androgens in normal human premenopausal endometrium, myometrium and vagina.

The endogenous concentrations of testosterone (Testo), androstenedione (Adion), 5-androstene-3 beta, 17 beta-diol (Adiol), dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) have been measured in endometrium, myometrium and vagina from 23 premenopausal women at different stages of the cycle. The tissue to plasma gradient was positive for all androgens except DHEAS; a significant correlation existed between plasma and tissue levels of Adiol and DHEAS. In all tissues significant correlations were calculated between Adiol and DHEA, Adion and Testo, and Adiol and DHEAS. Except for Testo, androgen concentrations were different in the tissues with a significant correlation between the tissues, each tissue seeming to be able to create its own specific intratissue androgen pattern. During the cycle Testo was highest in myometrium and vagina and Adion in myometrium and endometrium during the secretory phase. Except for DHEA, androgens were preferentially localized in the cytosol fraction of the cells. From this localization and the known inhibitory effects of androgens on the activity of estrogen metabolizing enzymes, it is postulated that androgens play a role in enzymatic rather than receptor-mediated processes in uterine cells.

Adult

The endogenous concentration of estradiol and estrone in pathological human postmenopausal endometrium.

The endogenous estrone (E1) and estradiol (E2) levels (in pg/g tissue) were measured in 7 postmenopausal patients with a hyperplastic endometrium, in 3 with an atypical adenomatous hyperplastic endometrium and in 13 with a carcinomatous endometrium. These tissue concentrations were compared with the E1 and E2 concentrations in plasma (pg/ml) and with data from a control group of postmenopausal women with atrophic endometria. The tissue levels of both steroids showed large variations and there were no significant correlations with their plasma levels. In the hyperplastic and the atypical adenomatous hyperplastic group the mean E2 tissue level was higher compared with the mean E1 tissue level, despite the excess of E1 over E2 in peripheral plasma. In the carcinomatous group the mean E1 tissue level was higher, although not significantly, than the mean E2 tissue level. There were no significant differences between the E1 and E2 tissue levels in the three different pathological groups as compared to the atrophic control group. We conclude that it is unlikely that estrogens alone play a crucial role in the development of a pathological endometrium.

Adenocarcinoma

Uptake and concentration of steroid hormones in mammary tissues.

In order to exert their biological effects, steroid hormones must enter the cells of target tissues and after binding to specific receptor molecules must remain for a prolonged period of time in the nucleus. Therefore the endogenous levels and the subcellular distribution of estradiol, estrone, DHEAS, DHEA ad 5-Adiol were measured in normal breast tissues and in malignant and nonmalignant breast tumors from pre- and postmenopausal women. For estradiol the highest tissue levels were found in the malignant samples. No differences were seen in these levels between pre- and postmenopausal women despite the largely different peripheral blood levels. For estrone no differences were found between the tissues studied. Although the estradiol concentration was higher in the estradiol-receptor-positive than in the receptor-negative tumors, no correlation was calculated between the estradiol and the receptor consent. Striking differences were seen between the breast and uterine tissues for the total tissue concentration of estradiol, the ratio between estradiol and estrone, and the subcellular distribution of both estrogens. At similar receptor concentrations in the tissues these differences cannot easily be explained. Regarding the androgens, the tissue/plasma gradient was higher for DHEA than for 5-Adiol, and for DHEAS there was very probably a much lower tissue gradient. The highly significant correlation between the androgens suggests an intracellular metabolism of DHEAS to DHEA and 5-Adiol. Lower concentrations of DHEAS and DHEA were observed in the malignant tissues compared with the normal ones and the benign lesions. For 5-Adiol no differences were found and therefore these data do not support our original hypothesis on the role of this androgen in the etiology of breast abnormalities. Hence the way in which adrenal androgens express their influence on the breast cells remains unclear.

Adult

A case-control study of endometrial cancer within a cohort.

In a population-based prospective study it was shown that weight, height, overweight, total body size, age at first birth, parity and age at menopause are risk factors for the development of endometrial cancer. The finding that the patients had had a higher oestrogen excretion level than the controls some time before diagnosis constitutes the biochemical background for the effect of some of the above variables.

Age Factors

Endogenous concentration and subcellular distribution of androgens in normal and malignant human breast tissue.

The endogenous concentrations and the subcellular distribution of dehydroepiandrosterone (DHEA) and 5-androstene-3 beta,17 beta-diol (ADIOL) were measured in malignant and nonmalignant human breast tissue from both pre- and postmenopausal women. DHEA 3-sulfate was measured only in the cytosol. A greater tissue-plasma gradient of DHEA was present with large variations. The highest concentration of DHEA and ADIOL occurred in the nuclear fraction (average, 2.9 and 1.6 times the concentration in cytosol). With respect to DHEA, this finding is remarkable because no specific binding protein in human breast tissue has been reported. The concentration of DHEA 3-sulfate was significantly higher in the cytosol of nonmalignant than in malignant breast tissues. No significant differences in tissue concentrations of DHEA and ADIOL were found in malignant and nonmalignant breast tissue. The concentration of estrogens was measured in the cytosol and the nuclear fraction of the same tissues, as reported in a previous paper. We found a significantly higher estradiol concentration in malignant tissue as compared to nonmalignant tissue. When the ratio of ADIOL to estradiol was calculated from the combined data, a significant difference was found only in the cytosol of premenopausal cancer patients versus normal women. No difference was seen in the postmenopausal women. No difference in the ADIOL:estradiol ratio was found between normal and malignant breast tissue of patients of the same menopausal status.

Adolescent

Endogenous concentration and subcellular distribution of estrogens in normal and malignant human breast tissue.

The endogenous concentrations and subcellular distribution of estrone and estradiol were measured in malignant and nonmalignant human breast tissue from pre- and postmenopausal women. The most striking finding was the significantly higher concentration of estradiol per g of tissue in the malignant tissues than in the nonmalignant tissues. The tissue concentrations of estradiol in pre- and postmenopausal women were similar despite the large differences in the peripheral plasma levels. No correlation was found between the estradiol receptor content and endogenous concentration and subcellular distribution of estradiol. No difference in the estrone tissue concentration was found between malignant and nonmalignant tissues. In comparison with human uterine tissues, which we have reported previously, human breast tissue "handles" estrogenic hormones differently from human uterine tissue. At equal concentrations of the estradiol receptor, concentrations and subcellular distribution of the estrogens are different in both tissues. It is concluded that the mechanism of action of estradiol via its receptor, a mechanism mainly based on studies in animal uterine tissue, applies only qualitatively to human breast cancer tissue.

Adolescent

Uptake and metabolism of oestriol in human target tissues.

The uptake, metabolism and subcellular distribution of oestradiol and oestriol in endometrial, myometrial and vaginal tissue of postmenopausal women under physiological conditions were studied by giving 3H-labelled oestradiol or oestriol in subphysiological doses by continuous infusion lasting 12 h before hysterectomy. The three tissues obtained from each woman were separated into three fractions: two cytosol fractions (free oestrogens and specifically bound) and one nuclear fraction. The results show an accumulation of both oestrogens in the target tissues, we found an approximately 33 times higher [3H]E2 concentration in endometrium (dpm per g) than in plasma (dpm/ml), 20 times in myometrium and 10 times in vaginal tissue. After the E3 infusions the tissue/plasma gradient was 37 for endometrium, 19 for myometrium and 11 for vagina. In plasma and tissues a metabolite of E3 could tentatively be identified as 16 alpha-hydroxyoestrone. The subcellular distribution showed that 60-80% of E2 and E3 is accumulated in the nuclear fraction of all tissues studied, no nuclear bound oestrone could be detected. From these results the conclusion was drawn that oestradiol still is the major tissue oestrogen in postmenopausal women and that it is mainly nuclear bound. Endometrium of postmenopausal women accumulates higher concentrations of E2 and E3 than vaginal tissue from the same individual, no preferential uptake of oestriol occurs under physiological conditions.

Endometrium

Effects of oestriol: preliminary results on receptor kinetics in target tissues of postmenopausal women.

This in vivo investigation was done to study the effects of intravaginal oestriol (E3) administration on endometrial, myometrial and vaginal tissue of normal postmenopausal women. All women received intravaginal E3- suppositoria (containing 0.5 mg E3) once a day for 3 weeks prior to hysterectomy. The medication was continued until the day of operation. At the time of operation both uterine and vaginal tissue was obtained. The receptor content in the cytosol was measured by a multiple point-dextran -coated-charcoal assay using [3H]E2 and [3H]ORG-2058 as ligands. The receptor content in the nucleus was measured by incubating purified whole nuclei in 10 nM [3H]E2 for 18 h at 0 degrees C. We have shown that under these conditions there is a total exchange of all occupied receptors. Preliminary data on 4 patients are available. Vaginal cytology clearly showed an increase of the maturation value. Oestrogen receptor concentrations in the cytosol of all three tissues studied were lower than those obtained in untreated women, suggesting nuclear transformation of the receptor as a consequence of treatment. The nuclear E2 receptor levels cannot be compared with normal women yet. Progesterone receptors in endometrial and myometrial cytosol seemed to be higher than those in untreated women, indicating effects of the treatment. In the human, vaginal progesterone receptor cannot be used as a marker for oestrogenic stimulation because only exceptionally could their presence be detected in either treated or untreated women.

Aged