M H van der Hage

Universiteit Utrecht, Utrecht, Provincie Utrecht, Netherlands

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Publications (38)42.82 Total impact

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    ABSTRACT: Pituitary tumours are the cause of hyperadrenocorticism in a variety of species, but the role of the pituitary gland in hyperadrenocorticism in ferrets is not known. In this species, the disease is mediated by the action of excess gonadotrophins on the adrenal cortex and is characterized by an excessive secretion of sex steroids. In this study, the pituitary gland of four healthy control ferrets, intact or neutered, and 10 neutered ferrets with hyperadrenocorticism was examined histologically following immunohistochemical labelling for adrenocorticotrophic hormone, alpha-melanocyte-stimulating hormone, growth hormone, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and prolactin. Immunohistochemistry revealed that somatotrophs, thyrotrophs and lactotrophs were the most abundant cell types of the pars distalis of the pituitary gland in the healthy ferrets. The distribution of corticotrophs was similar to that in the dog and man. In ferrets, as in dogs, the melanotrophic cell was almost the only cell type of the pars intermedia. Gonadotrophs were found in the pars distalis of neutered, but not intact ferrets. All the ferrets with hyperadrenocorticism had unilateral or bilateral alterations of the adrenal gland. In addition, in the pituitary gland of two of these ferrets a tumour was detected. These tumours were not immunolabelled by antibodies against any of the pituitary hormones, and had characteristics of the clinically non-functional gonadotroph tumours seen in man. In some of the other ferrets low pituitary immunoreactivity for gonadotrophic hormones was detected, which may have been due to the feedback of autonomous steroid secretion by the neoplastic transformation of the adrenal cortex. It is concluded that initially high concentrations of gonadotrophins resulting from castration may initiate hyperactivity of the adrenal cortex. The low incidence of pituitary tumours and the low density of gonadotrophin-positive cells in non-affected pituitary tissue in this study suggest that persistent hyperadrenocorticism is not dependent on persistent gonadotrophic stimulation.
    Journal of Comparative Pathology 06/2004; 130(4):255-65. · 1.38 Impact Factor
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    J IJzer, G M Dorrestein, M H Van Der Hage
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    ABSTRACT: A 2-year-old male peach-faced lovebird (Agapornis roseicollis) with a subcutaneous sarcoma on the right carpus was treated by surgical amputation. Three months after surgery, lung metastases causing clinical signs of dyspnoea were diagnosed radiographically and subsequently the bird was euthanased. At necropsy, a tumour firmly attached to the right testis, kidney and lung was found, and several tumours were present in the lung parenchyma. Histopathology revealed a mesenchymal growth pattern in the carpal subcutis and lung neoplasms, and an infiltrating epithelial pattern in the abdominal one. Immunohistochemistry for muscle actin, keratin, neurone-specific enolase and chromogranin confirmed the different cell lineage of the neoplasms, thus leading to the diagnosis of a fibrosarcoma in the subcutis with pulmonary metastases, and a carcinoma of indeterminate origin in the cranial abdomen.
    Avian Pathology 03/2002; 31(1):101-4. · 1.73 Impact Factor
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    M M Zandvliet, G M Dorrestein, M Van Der Hage
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    ABSTRACT: In the Netherlands, a syndrome affecting several species of older Amazon parrots (Amazona sp.) has been described. This syndrome was characterized as a chronic respiratory disease resulting in exercise intolerance. Pathological examination revealed loss of functional lung tissue, pulmonary interstitial fibrosis, and right heart failure. Haematology revealed an elevated packed cell volume as a result of an increase in erythrocyte size and an increased haemoglobin mass per erythrocyte. In two patients, hypoxia and hypercapnia were demonstrated. The aetiology of this syndrome is currently not known. The microscopic lesions resemble those found in Diffuse Interstitial Fibrosis in humans.
    Avian Pathology 11/2001; 30(5):517-24. · 1.73 Impact Factor
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    ABSTRACT: Signs of oestrus, including vulvar swelling and alopecia are frequently seen in ovariectomized ferrets. Between 1997 and 1999, 25 ovariectomized ferrets presented with symptoms of vulvar swelling and symmetric alopecia at the University Clinic of Companion Animals. In 18 of these animals, ovarian remnants were found. To prevent failure to remove all ovarian tissue in the ferret, thorough identification of the ovaries, which are surrounded by large fat deposits, is necessary. The incision should be long enough to allow good visualization of the surgical field.
    Tijdschrift voor diergeneeskunde 09/2001; 126(16):526-8. · 0.13 Impact Factor
  • A P Koets, V P Rutten, D Bakker, M H van der Hage, W van Eden
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    ABSTRACT: Pathogenesis studies of Mycobacterium avium subsp. paratuberculosis infection in ruminants are hampered by the long incubation time of the disease. A laboratory animal model with a shorter incubation time would facilitate research in this field. Although small rodents are usually considered to be resistant to M.a. paratuberculosis infection, several susceptible murine strains have been found. To our knowledge, there are no detailed reports with regard to susceptibility in rats. The Lewis rat is a valuable model for inflammatory bowel disease studies as well as autoimmune diseases involving mycobacteria as inducing agents. In this study Lewis rats were used to investigate their potential as a small laboratory animal model for paratuberculosis. In total 28 female Lewis rats were orally inoculated with M.a. paratuberculosis. The rats were first inoculated at 3 weeks of age, and 12 more inoculations followed in increasing intervals during the 3 months to follow. Eight control rats received a sham inoculation. Over 9 months, two rats from each group were sacrificed at regular intervals and immunological and histopathological examinations were performed on the gastrointestinal tract, the liver and the spleen. None of the rats developed lesions which were indicative of mycobacterial infection as determined by histology with HE and Ziehl-Neelsen staining. The bacteria could not be recultured from samples taken from the gut, the liver or the spleen. The immunological tests however, showed that bacteria had entered via the intestinal tract. From this study it appears that Lewis rats are resistant to oral inoculation with M. a. paratuberculosis, and not suitable as a model to study the immunopathogenesis of paratuberculosis as it occurs in ruminants.
    Veterinary Microbiology 01/2001; 77(3-4):487-95. · 3.13 Impact Factor
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    ABSTRACT: T cell receptor (TCR) peptide immunizations have been demonstrated to protect against experimental autoimmune diseases. These findings have led to clinical trials employing TCR peptides in multiple sclerosis and rheumatoid arthritis patients. Previously, we identified a strongly immunogenic region of the TCR alpha chain of an arthritogenic T cell clone (AV11 66-80). In this report, we show that rats immunized with AV11 66-80 developed arthritis with clinical symptoms and histology similar to adjuvant arthritis (AA). Transfer of this disease into naive rats using AV11 66-80-specific T cells proved the T cell-mediated character of the disease. The AV11 66-80 arthritic rats developed resistance to Mycobacterium tuberculosis-induced AA, indicating that both forms of arthritis depended on similar regulatory mechanisms. This first demonstration of TCR peptide-induced arthritis, together with an earlier report on a polymorphism in this very same AV11 66-80 region involved in arthritis resistance in mice, suggests a central role of the public epitope AV11 66-80 in the control of autoimmune arthritis. Although TCR peptide immunizations can be exploited to prevent experimental autoimmunity, caution should be taken in the induction of TCR peptide-specific T cells for immunotherapy to avoid adverse effects as shown here.
    European Journal of Immunology 09/2000; 30(8):2164-71. · 4.97 Impact Factor
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    ABSTRACT: To investigate the long-term effects of total-body irradiation (TBI) on kidneys in non-human primates. The kidneys of Rhesus monkeys were histologically examined at 6-8 years after TBI with low single doses of 4.5-8.5Gy or two fractions of 5.4Gy. The kidneys of age-matched non-irradiated monkeys served as controls. Irradiation was performed on adult monkeys aged about 3 years; 6-8 years later animals were sacrificed and the kidneys removed and processed for histology. A semi-quantitative scoring system was used to evaluate overall histological damage. Glomerular changes were also morphometrically analysed according to previously published criteria. In selected dose groups (pro)thrombotic and inflammatory changes were investigated by immunostaining cryosections with antibodies against von Willebrand factor (vWF), leukocytes and macrophages. Histological changes were generally mild and only seen in kidneys irradiated with doses higher than 7 Gy. Glomerular changes were characterized by increased mesangial matrix and capillary dilatation. Tubulo-interstitial changes included hypercellularity, fibrosis and mild tubular atrophy. The mean glomerular area expressing vWF protein in the irradiated kidneys was not different from that in the age-matched controls. Numbers of infiltrating leukocytes were not significantly different between irradiated kidneys and controls. However, slightly increased numbers of macrophages were present in the renal cortex after irradiation. Renal damage after TBI of Rhesus monkeys with single doses of 4.5-8.5 Gy or two fractions of 5.4 Gy was mild, even after follow-up times of 6-8 years.
    International Journal of Radiation Biology 06/2000; 76(5):641-8. · 1.84 Impact Factor
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    ABSTRACT: High dose total body irradiation (TBI) in combination with chemotherapy, followed by rescue with bone marrow transplantation (BMT), is increasingly used for the treatment of haematological malignancies. With the increasing success of this treatment and its current introduction for treating refractory autoimmune diseases the risk of radiation carcinogenesis is of growing concern. Studies on tumour induction in non-human primates are of relevance in this context since the response of this species to radiation does not differ much from that in man. Since the early sixties, studies have been performed on acute effects in Rhesus monkeys and the protective action of bone marrow transplantation after irradiation with X-rays (average total body dose 6.8 Gy) and fission neutrons (average dose 3.4 Gy). Of those monkeys, which were irradiated and reconstituted with autologous bone marrow, 20 animals in the X-irradiated group and nine animals in the neutron group survived more than 3 years. A group of 21 non-irradiated Rhesus monkeys of a comparable age distribution served as controls. All animals were regularly screened for the occurrence of neoplasms. Complete necropsies were performed after natural death or euthanasia. At post-irradiation intervals of 4-21 years an appreciable number of tumours was observed. In the neutron irradiated group eight out of nine animals died with one or more malignant tumours. In the X-irradiated group this fraction was 10 out of 20. The tumours in the control group, in seven out of the 21 animals, appeared at much older age compared with those in the irradiated cohorts. The histogenesis of the tumours was diverse with a preponderance of renal carcinoma, sarcomas among which osteosarcomas, and malignant glomus tumours in the irradiated groups. When corrected for competing risks, the carcinogenic risk of TBI in the Rhesus monkeys is similar to that derived from the studies of the Japanese atomic bomb survivors. The increase of the risk by a factor of 8, observed in the monkeys, indicates that patients are likely to develop malignancies more frequently and much earlier in life after TBI than non-exposed individuals. This finding underlines the necessity of regular screening of long-term surviving patients subjected to TBI and BMT.
    Radiotherapy and Oncology 04/2000; 54(3):247-53. · 4.52 Impact Factor
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    ABSTRACT: This paper describes the signs, clinical pathology, and postmortem findings in 14 young African grey parrots (Psittacus erithacus erithacus) that were naturally infected with psittacine beak and feather disease (PBFD) virus (psittacine circovirus). All but two of the parrots had severe leukopenia at clinical presentation. Two other parrots also had severe anemia. All birds died within 3 wk after presentation. Postmortem examination documented liver necrosis in 11 of 14 birds and secondary bacterial or fungal infections in 9 of 14 birds. Tests for Chlamydia psittaci, polyomavirus, and Salmonella sp. were negative. PBFD viral infection could be demonstrated in all birds by polymerase chain reaction. Supporting evidence of PBFD viral infection was gathered by histologic examination of the bursa of Fabricius, electron microscopy, and DNA in situ hybridization. Electron microscopic examination of both the bursa of Fabricius and liver revealed virus particles resembling circovirus. DNA in situ hybridization of six liver tissue samples confirmed the presence of PBFD virus and excluded the presence of avian polyomavirus. Our findings suggest that a specific presentation of peracute PBFD viral infection, characterized by severe leukopenia, anemia, or pancytopenia and liver necrosis in the absence of feather and beak abnormalities, may occur in young African grey parrots.
    Avian Diseases 04/2000; 44(2):470-8. · 1.73 Impact Factor
  • M J Kik, M H van der Hage
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    ABSTRACT: A llama (Lama glama) died after 1 wk of obstipation, lethargy, and rolling. Necropsy showed that the stomach and small intestine were distended with gas and fluid. The cecum was impacted with dry contents and the colon was empty. No gross lesions were found in the wall of the gastrointestinal tract or other organs. Histologic changes consisted of chromatolysis of neurons of autonomic ganglia, enteric plexi, and the accessory cuneate nucleus, consistent with lesions associated with dysautonomia in other domestic animals.
    Journal of Zoo and Wildlife Medicine 10/1999; 30(3):435-8. · 0.43 Impact Factor
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    ABSTRACT: To investigate the effect of total-body irradiation (TBI) on growth, thyroid and pituitary gland in primates. Thirty-seven rhesus monkeys (mean age 3.1+/-0.6 years) received either a low-dose (4-6 Gy) TBI (n = 26) or high-dose (7-12 Gy) TBI (n = 11) and were sacrificed together with 8 age-matched controls after a post-irradiation interval of 5.9+/-1.5 years. Anthropometric data were collected: thyroid and pituitary glands were examined; serum levels of thyroid stimulating hormone (TSH), free thyroxin (FT4), insulin-like growth factor-I (IGF-I) and its binding protein-3 (IGFBP-3) were measured. Decrease in final height due to irradiation could not be demonstrated. There was a dose-dependent decrease in body weight, ponderal index, skinfold thickness and thyroid weight. The latter was not accompanied by elevation of TSH or decrease in FT4. Structural changes in the thyroid gland were found in 50% of the irradiated animals. Levels of IGF-I and IGFBP-3 did not differ between the dose groups, but the high-dose group had a lower IGF-1/IGFBP-3 ratio. Total body irradiation had a negative effect on body fat. There was no evidence of (compensated) hypothyroidism, but dose-dependent decrease in thyroid weight and changes in follicular structure suggest some effect of TBI on the thyroid gland. The decreased IGF-I/IGFBP-3 ratio in the high-dose group can indicate that the somatotrophic axis was mildly affected by TBI. These results show that TBI can have an effect on the physical build and thyroid gland of primates even in the absence of cytostatic agents or immunosuppressive drugs.
    Radiotherapy and Oncology 06/1999; 51(2):187-92. · 4.52 Impact Factor
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    ABSTRACT: To investigate the long-term effects of X-irradiation on different aspects of gastrointestinal function in the non-human primate (Macaca mulatta). Animals were exposed to X-radiation (5 or 6 Gy) or not (sham) and gastrointestinal function was investigated 4-6 years after exposure. Basal and agonist-stimulated short circuit current (Isc) responses were measured in isolated jejunum. Intestinal tissue was taken for histological analysis as well as for determination of mucosal marker enzyme activities and gastrointestinal regulatory peptide levels. Vasoactive intestinal peptide receptor characteristics were determined as well as VIP-stimulated Isc responses. GI peptides were also measured in plasma. Few differences were seen in basal electrical parameters or tissue morphology but there was a tendency for reduced basolateral membrane enzyme activity. VIP-stimulated Isc responses were reduced in irradiated animals as were VIP-stimulated adenylate cyclase responses. Plasma and tissue (ileal and colonic muscle layers) gastrin releasing peptide levels were increased in irradiated animals. In contrast circulating gastrin levels were lower. Late effects of total-body irradiation on GI function in monkeys showed altered circulating and tissue levels of some GI peptides. In addition the biological effects of vasoactive intestinal peptide were modified.
    International Journal of Radiation Biology 03/1999; 75(2):183-91. · 1.84 Impact Factor
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    ABSTRACT: A fishing cat (Felis viverrina) died overnight, within 12 hr of peracute onset of depression, slight tremors, pallor, and icterus. Necropsy showed widespread hemorrhage and hematomata in the heart, stomach, and kidneys. The lungs were hyperemic and edematous. The liver was swollen and yellowish green. The spleen was very large and hyperemic. Histologic changes consisted of pneumonia, hepatic necrosis, and renal hemorrhage with glomerular fibrin clots. Chlamydia antigen was detected in liver and kidney using a direct immunofluorescence assay, and Chlamydia were cultured.
    Journal of Zoo and Wildlife Medicine 07/1997; 28(2):212-4. · 0.43 Impact Factor
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    ABSTRACT: Quill mite (Dermoglyphus passerinus) infestation of canaries (Serinus canaria): diagnosis and treatment. Quill mites are described in many species of birds. Most reports state that the infestation is difficult or impossible to treat. In this case report the diagnosis, identification and successful treatment of the quill mite in canaries is described.
    Avian Pathology 04/1997; 26(1):195-9. · 1.73 Impact Factor
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    ABSTRACT: A review is given of current knowledge of taxonomy, clinical symptoms, pathogenesis and pathology, diagnosis, epizootiology and prevention of Viral Haemorrhagic Disease (VHD). We also report our own experiences with the (histo)pathology, laboratory diagnosis, and epizootiology of this disease. The frequency of other diagnoses in an eighteen months period.
    Tijdschrift voor diergeneeskunde 05/1996; 121(7):184-8. · 0.13 Impact Factor
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    ABSTRACT: A 13-year-old sulphur-crested cockatoo (Cacatua galerita) was presented with a mass surrounding the right elbow joint. Radiographs showed a soft tissue mass. The right wing was amputated. Histological examination of the mass revealed an incompletely lobulated tumour composed of strands of spindle-shaped cells and of epithelial cells resembling acini. On morphological grounds the tumour was classified to be a synovial cell sarcoma. After 6 months the bird was returned for examination because of lameness in the right leg. Radiographs showed osteolysis in the right tibiotarsal bone. Cytological investigation of a bone marrow biopsy revealed neoplasia. The bird was euthanized. Necropsy revealed metastases in many organs. This is believed to be the first reported case of synovial cell sarcoma in a bird.
    Avian Pathology 03/1996; 25(1):179-86. · 1.73 Impact Factor
  • M H van der Hage
    Tijdschrift voor diergeneeskunde 09/1993; 118(16):526-7. · 0.13 Impact Factor
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    ABSTRACT: The clinical manifestation of mange in a guinea-pig population in Utrecht is discussed. The etiology and the treatment with two subcutaneous injections of ivermectin 0.2 mg/kg with a ten-day interval, is described. A total of 37 guinea-pigs with symptoms and 36 guinea-pig without signs of mange were treated. On the 21st day all previously infested guinea-pigs were free of symptoms. During this study side-effects occurred in 11 of the 73 animals. The most prominent side-effects were a (sub-)dermal necrosis in the younger animals and an inflammation of the cutis in the older animals. The side-effects were probably caused by propylene glycol which was used as a diluent.
    Tijdschrift voor diergeneeskunde 02/1993; 118(2):42-6. · 0.13 Impact Factor
  • M H van der Hage, G M Dorrestein, A G Burger
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    ABSTRACT: Several potential causes of disease were detected in young as well as in full-fledged parakeets of several species in an outbreak of disease on a parakeet-breeding farm. Both papovavirus and Absidia sp. were isolated; the drinking water contained a toxic level of nitrates. The pathological findings are presented and the possible role of the various findings in the pathogenesis of the disease complex is discussed.
    Tijdschrift voor diergeneeskunde 11/1990; 115(20):928-34. · 0.13 Impact Factor
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    ABSTRACT: The literature concerning the effects of plant lectins on the small intestinal epithelium is reviewed. It appears that after oral intake, intact plant lectins can reach the small intestinal lumen. Their binding to the mucosal surface evokes an increased synthesis of glycoproteins and a degeneration of the intestinal epithelium. The epithelial alterations may result in hyperregenerative villus atrophy and endogenous nitrogen loss. These changes ultimately can lead to less efficient feed conversion, diminished growth, scouring, wasting and death. The possible significance of plant lectins in digestive disturbances in farm animals is suggested.
    The Veterinary quarterly 05/1989; 11(2):108-15. · 0.85 Impact Factor