Biomedical subjects

F van Mil

Publications and source records attributed to F van Mil.

6 recordsLinked to original sources

PubMed2001

Immune response in hormonally-induced prostatic hyperplasia in the dog.

We induced prostatic enlargement in castrated dogs using either androgen alone or androgen combined with estrogen. In addition to previously reported hyperplastic changes, marked infiltration with immune effector cells was observed. This mononuclear cell infiltrate was phenotypically characterized using CD3 as pan T-lymphocyte marker, CD79 for B-lymphocytes, MAC378 for macrophages, and antibodies against kappa- and lambda-immunoglobulin (Ig) light chains for plasma cells. The majority of inflammatory cells (>80%) in the mononuclear infiltrates were T-lymphocytes and the numbers correlated with the degree of inflammation. The B-lymphocytes were found particularly in areas with marked follicular formation and diffuse infiltration, whereas there were only a few positive cells (<10%) in areas with a moderate or slight inflammation. Macrophages were found primarily in areas with atrophic and cystic changes with and without inflammation. The expression of lambda-Ig-positive cells depended on the degree of inflammation (5-10%), whereas immunoreactivity of kappa-Ig did not correlate with the extent of inflammatory reaction. Our present findings together with the evaluation of longitudinal biopsies of hormonally-induced BPH indicate that hyperplasia preceded cell-mediated and humoral immune response.

Androstane-3,17-diol↗

PubMed2001

Improving the well-being of elderly patients via community pharmacy-based provision of pharmaceutical care: a multicentre study in seven European countries.

OBJECTIVE: This study aimed to measure the outcomes of a harmonised, structured pharmaceutical care programme provided to elderly patients (> or =65 years of age) by community pharmacists in a multicentre international study performed in 7 European countries. DESIGN AND SETTING: The study was a randomised, controlled, longitudinal, clinical trial with repeated measures performed over an 18-month period. A total of 104 intervention and 86 control pharmacy sites participated in the research and 1290 intervention patients and 1164 control patients were recruited into the study. MAIN OUTCOME MEASURES AND RESULTS: A general decline in health-related quality of life over time was observed in the pooled data; however, significant improvements were achieved in patients involved in the pharmaceutical care programme in some countries. Intervention patients reported better control of their medical conditions as a result of the study and cost savings associated with pharmaceutical care provision were observed in most countries. The new structured service was well accepted by intervention patients and patient satisfaction with the services improved during the study. The pharmacists involved in providing pharmaceutical care had a positive opinion on the new approach, as did the majority of general practitioners surveyed. The positive effects appear to have been achieved via social and psychosocial aspects of the intervention, such as the increased support provided by community pharmacists, rather than via biomedical mechanisms. CONCLUSIONS: This study is the first large-scale, multicentre study to investigate the effects of pharmaceutical care provision by community pharmacists to elderly patients. Future research methodology and implementation will be informed by the experience gained from this challenging trial.

Aged↗

PubMed2001

Submission bias.

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Data Interpretation, Statistical↗

PubMed2000

The mercapturic acid biotransformation pathway of hexachlorobenzene is not involved in the induction of splenomegaly, or skin and lung lesions in the Brown Norway rat.

Involvement of the mercapturic acid pathway in the induction of splenomegaly and skin and lung pathology by hexachlorobenzene (HCB) in the rat was investigated by seeking to determine whether pentachloronitrobenzene (PCNB) has the same inflammatory effects as HCB, since both compounds are directly conjugated to glutathione, and further processed into the same mercapturic acid metabolites which are excreted via the urine. Female Brown Norway (BN/SsNO1aHsd) rats at 3 to 4 weeks of age were orally exposed to diets with or without supplementation with 450 mg HCB or equimolar (467 mg) or higher (934 mg) amounts of PCNB per kilogram of diet over 4 weeks. Gross skin lesion development and body weight gains were assessed during exposure and spleen and liver weights as well as histopathologic changes in skin and lung were assessed after exposure. After 3 weeks of exposure, urinary metabolites of the mercapturic acid and oxidative biotransformation pathways were identified using high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). Oral exposure of the rats to 450 mg/kg HCB resulted in an increase in relative spleen and liver weights as well as in the development of skin and lung pathology in the absence of overall liver toxicity. Equimolar or higher concentrations of PCNB caused none of these effects. Urinary levels of the mercapturic acid N-acetyl-S-(pentachlorophenyl)-cysteine (PCP-NAC), were comparable in HCB- and PCNB-treated rats. Levels of closely related methylsulfide derivatives of PCP-NAC, also generated via the same mercapturic acid pathway, appeared to be significantly higher in PCNB- than in HCB-treated rats, whereas the reverse was true for the urinary levels of the oxidative metabolite pentachlorophenol (PCP). Thus, results indicate that metabolites of the mercapturic acid pathway are not involved in the induction of splenomegaly and skin and lung pathology caused by HCB exposure in BN rats and that the main urinary metabolite of HCB in these BN rats is PCP. Since PCP itself, as well as other cytochrome P450-derived metabolites from HCB, are not likely to be involved in the induction of splenomegaly and skin and lung pathology, it is suggested that either the parent compound HCB or as-yet-unidentified non-P450-generated metabolites are involved in these inflammatory effects of HCB.

Acetylcysteine↗

PubMed2000

Immunohistochemical analysis of estrogen receptors in feline mammary gland benign and malignant lesions: comparison with biochemical assay.

Estrogen receptors (ER) were determined by both the biochemical dextran-coated charcoal (DCC-ER) and the immunohistochemical Avidin biotin-peroxidase complex (IHC-ER) methods in proliferative mammary lesions collected from 37 cats: 20 malignant tumors without metastasis at first presentation, seven malignant tumors with lung and/or lymph node metastases and 10 benign tumors and dysplasias. Total number of samples analyzed by both methods was 44. The DCC-ER method was applied to frozen tissue samples and the IHC-ER method was applied to neutral buffered formalin-fixed, paraffin wax-embedded tissue samples by using the NCL-6F11 monoclonal antibody. Biochemically, 21 (47.7%) cases had equal or more than 5 fmol/mg of protein (standard positivity threshold). Immunohistochemically, 11 (25%) cases were scored positive, the percentage of positive nuclei being statistically linked to the intensity of immunostaining. Normal mammary gland tissue (13 cases) and/or dysplastic areas (5 cases) found in the surroundings of the main lesion were IHC-ER positive in 76.9% and 40% of the cases, respectively. Concordance between DCC-ER and IHC-DCC was 72.7% and the results of the DCC and the IHC-ER methods were significantly correlated (P < 0.05) by the chi2 test. Specificity (true negatives) and sensitivity (true positives) of the ICH-ER method were 95.6% and 47.6%, respectively. One out of eleven DCC-ER positive and IHC-ER negative discordant cases (9.09%) was a DCC-ER false positive, because the surrounding normal mammary gland tissue was IHC-ER positive. The remaining 10 cases had ER content values equal or lower than 23 fmol/mg of protein, a figure that could represent the sensitivity threshold of the immunohistochemical method employed.

Adenocarcinoma↗

PubMed1997

Hexachlorobenzene-induced immunomodulation and skin and lung lesions: a comparison between brown Norway, Lewis, and Wistar rats.

Strain dependence of the induction of skin and lung lesions by hexachlorobenzene (HCB) in the rat was studied to further the insight into the etiology of the lesions. To this end, 3- to 4-week-old female Brown Norway (BN), Lewis, and Wistar rats received diets supplemented with 150 mg (BN and Lewis), 450 mg (BN, Lewis, and Wistar) or 900 mg (BN and Wistar) HCB per kilogram diet for 4 weeks. Gross skin lesion development during exposure as well as pathologic changes in skin and lungs and various parameters of immunomodulation after exposure were assessed. General toxicity as judged by a slight increase in body weight gain and induction of liver cell hypertrophy was similar in BN and Lewis rats exposed to 450 mg/kg HCB and in Wistar rats exposed to 900 mg/kg HCB. Skin lesions ranged from redness to large exudating sores with crusts. With regard to dose, time of onset, incidence, and severity, skin lesions were very severe in BN, moderate in Lewis, and negligible in Wistar. Porphyrins could not be detected in the skin, whereas porphyrins in the liver were seen only in Lewis rats. Histology showed epidermal hyperplasia, deep dermal venules with activated endothelium, and deep dermal inflammatory infiltrates mainly consisting of eosinophilic granulocytes in BN and of mononuclear cells in Lewis and Wistar. Nonlesional skin of HCB-exposed rats showed very similar, though less prominent, changes. Lung pathology appeared negligibly strain-dependent; histology showed venules with an activated endothelium surrounded by a perivascular infiltrate as well as focal alveolar macrophage accumulations in all strains. Parameters of immunomodulation showed moderate strain dependence; relative spleen weights were dose-dependently increased in BN and Wistar and in the 450 mg/kg group in Lewis rats. BN rats showed a more marked splenomegaly than the other strains. Relative popliteal lymph node weights were increased significantly in BN and Lewis rats exposed to 450 mg/kg HCB. In all strains, HCB increased lymph node HEVs. Serum IgE and IgG levels were increased significantly in a dose-dependent way in BN rats only. Total serum IgM levels were elevated significantly in BN, Lewis, and Wistar rats that received 450 mg/kg and in Wistar rats that received 900 mg/kg HCB. Serum IgM levels against ssDNA were dose-dependently increased in all strains, being more marked in BN and Lewis than in Wistar rats. It is concluded that the HCB-induced inflammatory skin and lung pathologies have different etiology. Pronounced strain differences in the skin lesions suggest a specific involvement of the immune system. Skin lesions correlated significantly with all assessed parameters of immunomodulation in BN, with some in Lewis and with none in Wistar rats. No correlation was observed between the parameters of immunomodulation and lung lesions.

Animals↗