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Biomedical subjects

A M Huisman

Publications and source records attributed to A M Huisman.

At least 19 recordsLinked to original sources

[New developments in glucocorticoid therapy: selective glucocorticoid receptor agonists, nitrosteroids and liposomal glucocorticoids].

Two mechanisms of the genomic action ofglucocorticoids (GCs) can be distinguished: transrepression, yielding mainly an anti-inflammatory effect, and transactivation, resulting mainly in metabolic-endocrine side effects. Selective glucocorticoid receptor agonists (SEGRAs) cause selective transrepression, yielding the same anti-inflammatory effect as GCs, but with fewer side effects. NO is bound to several drugs to increase their effect; in nitrosteroids, NO is coupled to GC, resulting in a synergistic anti-inflammatory effect. Drug targeting can be achieved with GCs by incorporation of GC into polyethyleneglycol(PEG)-liposomes, resulting in very high concentrations ofGCs at the site of inflammation. Well-designed studies are needed to determine the place of SEGRAs, nitrosteroids and liposomal GCs in clinical practice.

Anti-Inflammatory Agents↗

[Arthritis as a consequence of diabetes mellitus or haemochromatosis].

Four patients with arthritis appeared to have this as a consequence of an internal disorder: a 60-year-old woman and a 20-year-old man with diabetes mellitus and arthritis of an ankle had Charcot arthropathy, whilst a 53-year-old woman and a 60-year-old man with polyarthritis had previously undiagnosed haemochromatosis. Patients were then adequately treated. Charcot arthropathy and haemochromatosis are not uncommon. Early diagnosis is important with respect to preventive and therapeutic measures. In patients with Charcot arthropathy immobilisation allows healing of the fractures. Bisphosphonates may be given in order to decrease bone resorption. In patients with haemochromatosis therapeutic bleeding may limit further damage to the joints and to the internal organs.

Adult↗

Prevalence of vertebral deformities and symptomatic vertebral fractures in corticosteroid treated patients with rheumatoid arthritis.

OBJECTIVE: This study was designed to determine whether the prevalence of vertebral deformities in patients with rheumatoid arthritis (RA) treated with corticosteroids (Cs) is higher than in RA patients not receiving Cs therapy. PATIENTS AND METHODS: This multicentre cross-sectional study included 205 patients with RA who were receiving Cs orally on a daily basis and 205 patients with RA who did not receive Cs, matched for sex and age. Vertebral deformities were scored according to the Kleerekoper method. RESULTS: Vertebral deformities were found in 52 (25%) patients on Cs and in 26 (13%) patients not on Cs. Sixteen (8%) patients in the group on Cs had experienced clinical manifestations of an acute vertebral fracture in the past vs only three patients (1.5%) among those not on Cs. The use of Cs tended to increase the risk of developing a vertebral deformity [adjusted odds ratio (OR) 1.56, 95% confidence interval (CI) 0.81-2.99] and symptomatic vertebral fracture (adjusted OR 1.42, 95% CI 0.24-8.32). Each 1-mg increase in the current daily Cs dose increased the risk of a vertebral deformity (adjusted OR 1.05, 95% CI 0.98-1.13) and of a symptomatic vertebral fracture (adjusted OR 1.05, 95% CI 0.89-1.24). CONCLUSION: There is a higher prevalence of vertebral deformities and clinical manifestations of vertebral fractures in patients on Cs than in those not on Cs. Our data indicate that the use of Cs and each 1-mg increase in the current daily Cs dose may increase the risk of development of a vertebral deformity and symptomatic vertebral fracture in patients with RA.

Aged↗

Vitamin D levels in women with systemic lupus erythematosus and fibromyalgia.

OBJECTIVE: Many patients with systemic lupus erythematosus (SLE) and fibromyalgia (FM) may spend less time exposed to the sun than healthy individuals and thus might have low vitamin D levels. It is known that hydroxychloroquine (HCQ) inhibits conversion of 25(OH)- to 1,25(OH)2-vitamin D both in vitro and in patients with sarcoidosis. We assessed winter serum 25(OH)- and 1,25(OH)2-vitamin D levels in patients with SLE and FM. METHODS: We recruited 25 consecutive female SLE and 25 female FM patients in London, Ontario, between January and March 2000. Subjects completed a brief questionnaire. Serum levels of 25(OH)-, 1,25(OH)2-vitamin D, and parathyroid hormone (PTH) were measured. RESULTS: In SLE patients mean 25(OH)-vitamin D was 46.5 nmol/l and mean 1,25(OH)2-vitamin D was 74.4 pmol/l. In FM patients these means were 51.5 nmol/l and 90.1 pmol/l, respectively. Serum 25(OH)-vitamin D levels did not significantly differ between SLE and FM patients, nor after adjusting for age and vitamin D, milk consumption, and sun block use. In 14 of the SLE patients and 12 of the FM patients 25(OH)-vitamin D levels < 50 nmol/l were found. SLE patients not using vitamin D supplements had lower 25(OH)-vitamin D levels than those who did. 1,25(OH)2-vitamin D tended to be lower in the SLE compared to the FM patients. This difference could be attributed to HCQ use: HCQ users (n = 17) had lower 1,25(OH)2-vitamin D levels than nonusers (n = 33); the mean adjusted difference was 24.4 pmol/l (95% CI 2.8-49.9). CONCLUSION: Half the SLE and FM patients had 25(OH)-vitamin D levels < 50 nmol/l, a level at which PTH stimulation occurs. Our data suggest that in SLE patients HCQ might inhibit conversion of 25(OH)-vitamin D to 1,25(OH)2-vitamin D.

Adolescent↗

[Paget's disease of the bones: diagnosis and treatment].

Paget's disease of bone affects one or more bones and is characterized by increased bone turnover (remodelling) with hypertrophy and abnormal bone structure with diminished strength leading to deformity and fracture. The cause of the disease is not known, possibly is a slow virus infection. For diagnosis and follow-up the conventional bone markers, serum alkaline phosphatase and urine hydroxyproline, are still useful. Paget's disease cannot be cured, but it may be suppressed. Specific drug treatment aims at reducing the increased bone remodelling. New and potent biphosphonates enable early and more effective treatment of Paget's disease than in the past and better prevention of late complications of the disease.

Adult↗

Disturbed liver function in heart transplantation candidates: two case reports.

Heart transplantation candidates frequently have a disturbed liver function. Two cases with jaundice are described in whom the cause and prognosis of the associated liver disease were analysed. In the 4-yr period during which heart transplantation patients with a disturbed liver function were investigated, "cirrose cardiaque" was not encountered; liver tests usually normalized after a successful heart transplant.

Adult↗

Intermittent bleeding from anorectal varices.

A patient with anorectal varices is reported. Anorectal varices are a rare cause of rectal bleeding and are often erroneously diagnosed as bleeding hemorrhoids. However, the subcutaneous extension of the varices should alert the clinician. Although local treatment such as ligation of the varices has been advocated, in the presence of portal hypertension a more radical operation is recommended. A portosystemic shunt, preferably between the inferior mesenteric vein and the vena cava or renal vein, is then the treatment of choice.

Aged↗

Retrograde double labeling of neurons: the combined use of horseradish peroxidase and diamidino yellow dihydrochloride (DY X 2HCl) compared with true blue and DY X 2HCl in rat descending brainstem pathways.

Three series of double-labeling experiments were carried out in a study of the collateralization of brainstem nuclei which project to the spinal cord in the rat. The fluorescent tracer Diamidino Yellow Dihydrochloride (DY X 2HCl) was injected in one half of the spinal gray and white matter at T7-T8 or T13-L1. Subsequently, either True Blue (TB), wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) or free HRP were injected ipsilaterally in the gray matter at C5-C8. The distributions of single and double retrogradely labeled neurons were studied in the following cell groups: red nucleus, interstitial nucleus of Cajal, ventrolateral pontine tegmentum, nuclei coeruleus and subcoeruleus and nuclei raphe magnus and raphe pallidus including the adjoining ventral reticular formation. The numbers of TB- or HRP-labeled neurons present in those nuclei were counted and the percentages of double-labeled neurons were calculated when TB or HRP had been used in combination with DY X 2HCl. The results indicate: The HRP-TMB reaction product and the DY X 2HCl fluorescence can be visualized simultaneously in retrogradely single- or double-labeled neurons. The distributions of single- and double-labeled neurons in the various brainstem nuclei were entirely comparable when using TB with DY X 2HCl or HRP with DY X 2HCl. The percentages of double-labeled neurons obtained with HRP and DY X 2HCl were consistent over a series of cases, and were comparable to those obtained with TB and DY X 2HCl in several structures. However, in the red nucleus slightly lower percentages of double-labeled neurons were obtained using HRP and DY X 2HCl as compared with the percentages obtained using TB and DY X 2HCl.

Amidines↗

Collateralization of brainstem pathways in the spinal ventral horn in rat as demonstrated with the retrograde fluorescent double-labeling technique.

The collateralization of brainstem pathways to the spinal ventral horn was studied in rat by means of injections of True Blue (TB) and Diamidino Yellow Dihydrochloride (DY .2HCl) at different levels in the spinal cord. TB (or DY .2HCl) was injected in the cervical gray and DY .2HCl (or TB) was injected ipsilaterally either at mid-thoracic or at lumbar levels. The retrogradely single- and double-labeled neurons were studied in the interstitial nucleus of Cajal, the lateral vestibular nucleus of Deiters, the nucleus (sub) coeruleus and the nucleus raphe pallidus, including the adjoining ventral medullary reticular formation. In all those brainstem nuclei many double-labeled neurons were present after both mid-thoracic and lumbar injections. This indicates that these brainstem spinal pathways to the ventral horn probably give off many collaterals along their trajectory in the spinal cord.

Animals↗

Retrograde neuronal labeling of cells of origin of descending brainstem pathways in rat using SITS as a retrograde tracer.

Recently, the retrograde tracer SITS has been introduced, a cytoplasmic label, which seems to be taken up by terminals only. In order to test the transport of SITS from terminals of brainstem pathways to he spinal cord SITS was injected in different rats at different spinal levels. It could be concluded that SITS is taken up primarily from axon terminals.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

Collaterals of rubrospinal neurons to the cerebellum in rat. A retrograde fluorescent double labeling study.

In a previous study the collateralization of the rubrospinal tract in the spinal cord of rat, cat and monkey was studied by means of the fluorescent retrograde double labeling technique. In the present study the existence of rubrospinal collaterals to the cerebellar interpositus nucleus (NI) has been studied using the same technique. In rat 'True Blue' (TB) was injected in the cerebellar NI and 'Nuclear Yellow' (NY) was injected ipsilaterally in white and gray matter of C5-C8 spinal segments. In some cases a new fluorescent retrograde tracer was used instead of NY, i.e. 'Diamidino Yellow' (DY), which produces retrograde labeling similar to NY but which migrates only very slowly out of the retrogradely labeled neurons. In these experiments only very few single TB-labeled rubrocerebellar neurons occurred, but many (+/- 90%) of the TB-fluorescent rubrocerebellar neurons were TB-NY or TB-DY double-labeled from the spinal cord. At least 37% of the NY and DY-fluorescent rubrospinal neurons were NY-TB and DY-TB double-labeled from the cerebellum. These findings indicate that, in rat, almost all rubrocerebellar fibers represent collaterals of rubrospinal neurons, and that at least 37% of the rubrospinal neurons give rise to such cerebellar collaterals.

Amidines↗

Diamidino yellow dihydrochloride (DY . 2HCl); a new fluorescent retrograde neuronal tracer, which migrates only very slowly out of the cell.

Earlier studies showed that Nuclear Yellow (NY), True Blue (TB) and Fast Blue (FB) are transported retrogradely through axons to their parent cell bodies. NY produces a yellow fluorescent labeling of the neuronal nucleus at 360 nm excitation wavelength, while TB and FB produce a blue fluorescence of the cytoplasm at this same wavelength. Therefore, NY may be combined with TB or FB in double-labeling experiments demonstrating the existence of axon collaterals. However, retrograde neuronal labeling with TB or FB requires a relatively long survival time, while NY requires a short survival time since NY migrates rapidly out of the retrogradely labeled neurons. This complicates double-labeling experiments since TB and FB must be injected first and NY later, a short time before the animal is sacrificed. We report a new yellow fluorescent tracer which labels mainly the nucleus and migrates much more slowly out of the retrogradely labeled neurons than NY. This new tracer can be used instead of NY in combination with TB or FB in double-labeling experiments and unlike NY can be injected at the same time as TB or FB. The new tracer is a diamidino compound (no. 28826) which is commercially available. It will be referred to as Diamidino Yellow Dihydrochloride (DY . 2HCl). According to the present study DY . 2HCl is transported over long distances in rat and cat, and produces a yellow fluorescence of the neuronal nucleus at 360 nm excitation wavelength, resembling that obtained with NY. When combined with TB or FB, DY . 2HCl is as effective as NY in double labeling of neurons by way of divergent axon collaterals.

Afferent Pathways↗