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Biomedical subjects

J A Geelen

Publications and source records attributed to J A Geelen.

At least 19 recordsLinked to original sources

Intracerebral haemorrhage in neurofibromatosis type I.

Neurofibromatosis type I patients usually present themselves with multiple neurofibromas and cafe-au-lait spots. We report a case with an intracerebral haemorrhage as an uncommon feature of the disease. The clinical, radiological, neurosurgical and histological features of this case are discussed and a review of the literature on the broad spectrum of neurofibromatosis is presented. The etiological factors and clinical consequences of this and other cerebrovascular features are briefly discussed.

Adult↗

Tuberculous meningitis: pitfalls in diagnosis.

OBJECTIVES: The diagnosis of tuberculous meningitis is easily missed because the variety of symptoms give rise to problems with the differential diagnosis. MATERIAL: Five cases of difficult to diagnose tuberculous meningitis are presented. RESULTS: Several reasons for the diagnostic delay are highlighted. The fact that tuberculous meningitis is rather rare in developed countries contributes to this problem. Recommendations for a quick diagnosis are given. CONCLUSION: The diagnosis of tuberculous meningitis in developed countries is often made after a substantial delay. In case of suspicion on the diagnosis additional examination should be performed and treatment should be started immediately.

Adult↗

[Tingling in the hands].

Four patients whose most prominent complaint was tingling in the hands are presented. In the first patient, a 33-year-old man, the cause appeared to be a traumatic cervical myelomalacia caused by a rear end collision three years before. The second patient, a 34-year-old woman, initially only had tingling in the hands but eventually developed paresis of the right arm and leg. MRI followed by surgery revealed a centrally located ependymoma. The third patient had a cervical disc protrusion to the left at CVI-CVII. This 49-year-old man recovered after rest and physical therapy. The last patient, a 23-year-old woman, had tingling in the ulnar area of the left hand. This appeared to be caused by an avulsion of the medial epicondyle of the humerus, the result of a trauma 10 years before. After extirpation of the epicondyle the complaints disappeared. In patients with paraesthesias it is very important to take the history meticulously and to perform thorough neurological examination. A simple neuroanatomical scheme may be used to interpret the somatosensory findings.

Adult↗

Successful conservative treatment of rheumatoid subaxial subluxation resulting in improvement of myelopathy, reduction of subluxation, and stabilisation of the cervical spine. A report of two cases.

OBJECTIVE: To report the efficacy of conservative treatment with cervical traction and immobilisation with a Halo vest, in two consecutive rheumatoid arthritis patients with progressive cervical myelopathy caused by subaxial subluxation. METHODS: Description of neurological symptoms and signs and findings in plain radiography (PR) and magnetic resonance imaging (MRI) of the cervical spine before and after treatment of the subaxial subluxation by traction and immobilisation with a Halo vest during four months. RESULTS: During four months of traction and immobilisation neurological examination showed a considerable improvement of the signs and symptoms of cervical myelopathy. Afterwards PR and MRI of the cervical spine showed reduction of the subaxial subluxation. Eventually firm stabilisation was obtained in both patients without surgery of the cervical spine. CONCLUSION: Cervical traction and immobilisation with a Halo vest can be considered as an independent conservative treatment in rheumatoid arthritis patients with cervical myelopathy caused by subaxial subluxation.

Aged↗

A study of multiple sclerosis patients with magnetic resonance spectroscopic imaging.

Eleven patients with clinically definite MS and three healthy controls were investigated by magnetic resonance spectroscopic imaging. The data sets were analysed for all voxels containing white matter only. We classify these voxels in healthy controls as normal white matter (NWM), and in MS patients as normal-appearing white matter unaffected by MS lesions (NAWM) or white matter affected by MS lesions. The spectra belonging to the voxels were analysed for content of cholines, creatines and N-acetylaspartate (NAA), and compared as a group. It was found that lesions differ from white matter in chemical composition and, moreover, that normal-appearing white matter differs from healthy white matter. Specifically, levels of NAA are lower in patients. There seems to be a linear relation between the composition of white matter and the expanded disability status scale value for the patient. The presence of lactate could not be established, and no unambiguous differences were found between patients with relapsing-remitting and relapsing-progressive disease.

Adult↗

SPECT, CT and MRI in a Turkish family with Huntington's disease.

A Turkish family with Huntington's disease documented on CT, MRI and SPECT is reported. Whereas in clinically definite cases CT and MRI are of limited value and SPECT does not add anything of value, in one asymptomatic subject SPECT showed moderate caudate nucleus hypoperfusion, underlining the hypothesis that SPECT may have a role in predicting Huntington's disease.

Adult↗

Release kinetics of 3-keto-desogestrel from contraceptive implants (Implanon) in dogs: comparison with in vitro data.

Ethylene-vinyl acetate (EVA) polymeric contraceptive implants (Implanon) containing 3-keto-desogestrel have been prepared aiming at an in vitro initial release rate of 60 micrograms 3-keto-desogestrel/day. These implants are designed to have an intended life-time of 2 years. During a 3-year period, the release of these implants was studied in 4 dogs after subdermal insertion, using plasma clearance of 3-keto-desogestrel assessed after intravenous administration of 3-keto-desogestrel and steady state plasma levels of 3-keto-desogestrel. The mean plasma level of 3-keto-desogestrel decreased gradually during the first year of the study, viz. from 1.64 nmol/1 at 7 days after implantation to 0.69 nmol/l after one year. At the end of the second year, the level had decreased further to 0.45 nmol/l while after 3 years, the mean 3-keto-desogestrel plasma level was 0.42 nmol/l. The calculated mean daily release of 3-keto-desogestrel decreased during the first year from 70 micrograms/day to 30 micrograms/day. During the second and third year, the decrease in release rate was much less, viz. going from 30 micrograms/day to 28 micrograms/day and from 28 micrograms/day to 25 micrograms/day, respectively. This indicates a much more constant release during the second and third year of the study. The calculated cumulative amount of 3-keto-desogestrel released from the implant during the dog study was 34.0 mg. Based on the initial amount of 3-keto-desogestrel in the implant of 68.3 mg, the remaining amount in the implants at termination of the study should be approximately 34.3 mg. Actually, the mean remaining amount of 3-keto-desogestrel was 33.8 mg, which is in very close agreement with the calculated value. Implants from the same batch as used in the in vivo study were also analyzed for the in vitro release at regular times during the 3-year study period. After one year, the in vitro release rate was about 43 micrograms/day whereas this release rate was 33 and 27 micrograms/day after 2 and 3 years, respectively. Although the in vitro set-up constantly gave a somewhat higher release in comparison with the in vivo release, it is apparent that the in vitro procedure is valuable for prediction of the in vivo release characteristics of the implant. There were no indications for 3-keto-desogestrel accumulation at the implantation site. No local irritations were seen and the animals had no discomfort at all.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Org 33201: a new highly selective orally active aromatase inhibitor.

Org 33201 has been selected as a very potent aromatase inhibitor. The compound is an enantiomer of a SC2H5 substituted imidazoylethylphenalene. Org 33201 inhibited human aromatase activity for 50% at a concentration of 2.2 x 10(9) mol/l. More than 200-fold higher concentrations were needed for the inhibition of other cytochrome P-450 enzymes. In vivo the compound was active in rats (ED50 = 0.035 mg/kg) and dogs (1 mg/kg gave 70% inhibition) after oral administration. It can be concluded that Org 33201 is a potent and highly selective orally active aromatase inhibitor.

Administration, Oral↗

Selection of 19-(ethyldithio)-androst-4-ene-3,17-dione (ORG 30958): a potent aromatase inhibitor in vivo.

UNLABELLED: 19-Mercaptoandrost-4-ene-3,17-dione (ORG 30365) has been reported to be both a competitive and irreversible inhibitor of aromatase. In comparison to the known aromatase inhibitors 4-hydroxy-androst-4-ene-3,17-dione (4OH-AD) and 1-methyl-1,4-androstadiene-3,17-dione (SH 489), ORG 30365 was found to be, respectively, about 16 and 8 times more active in vitro using human placental microsomes. Although the activity profile of ORG 30365 is very attractive, this compound was not selected for further development because it has limited pharmaceutical stability, which is probably due to its free--SH group and therefore a number of more stable dithio-derivatives of ORG 30365 have been synthesized. These derivatives are considered to be converted to ORG 30365 before they become active. The in vivo aromatase inhibiting activity of these derivatives was determined in hypophysectomized rats treated with the estrogen precursor dehydroepiandrosterone sulphate (DHEAS) using inhibition of cornification of vaginal epithelium as parameter. The 19-(ethyldithio)-derivative (ORG 30958) appeared to be the most active inhibitor in this series being twice as active as ORG 30365 and about 8 times as active as inhibitors like 4OH-AD and SH 489. Besides inhibition of cornification of vaginal epithelium ORG 30958 decreased ovarian aromatase and plasma E2 levels in DHEAS-treated hypophysectomized rats. Plasma estradiol levels were also lowered by ORG 30958 in dogs which were treated with pregnant mare serum gonadotrophin in order to induce pro-estrus. ORG 30958 displayed much less than 1/400th of the androgenic activity of testosterone propionate in immature castrated rats and appeared to be devoid of estrogenic and anti-estrogenic activity in ovariectomized mature rats. A twice daily dose of 1.5 mg ORG 30958/kg postponed ovulation in mature female rats. IN CONCLUSION: ORG 30958 is a potent aromatase inhibitor in vivo. It probably becomes active after cleavage of the -S-S- bond yielding ORG 30365 a potent irreversible aromatase inhibitor. ORG 30958 does not display other hormonal activities making it an attractive candidate for the treatment of estrogen-dependent diseases.

Androstenedione↗

The early effects of methylmercury on the developing rat brain.

The effects of organic mercury compounds on the development of the brain are well known since the exposure of people at a large scale to methylmercury in the Minamata Bay area and in Iraq. The neuropathological examination of the brains of children prenatally exposed revealed dysplasia of the cerebral and cerebellar cortex, neuronal ectopia and several other developmental disturbances. In this experimental study we examined developmental mechanisms involved in methylmercury-induced cerebral anomalies. By examining the fetuses soon after treatment we concentrated in the initial effects of the treatment. The pregnant rats were given 10 mg/kg methylmercury chloride i.p. on day 18. Already at 2 h after administration mitochondrial degeneration occurred in the endothelium of the cerebral capillaries. Subsequently hemorrhages developed interfering with the cellular arrangement in the ventricular zone, with neuronal migration in the intermediate zone and with the development of the cortical cytoarchitecture. Macrophages and cavities appeared in the hemorrhagic areas. It is suggested that the abnormalities seen in the experiments can be considered as the initial methylmercury-induced effects which, in combination with various other toxic effects, ultimately result in the anomalies that have been observed in the brains of children prenatally exposed to methylmercury.

Animals↗

Thoracic outlet syndrome after corrective surgery for pectus excavatum.

Two patients are described who developed a thoracic outlet syndrome (TOS) after undergoing Ravitch's operation for the correction of pectus excavatum. In one case the syndrome developed a few days after surgery, whereas in the second patient it manifested more gradually. A third patient presented with latent TOS and pectus excavatum. It is recommended that prior to the correction of pectus excavatum, the patient should be examined to detect signs of neurovascular compression due to latent thoracic outlet syndrome. After surgery the possibility of this complication should be kept in mind to avoid permanent lesions of the cervicobrachial plexus.

Adolescent↗

Sciatic nerve compression by an aneurysm of the internal iliac artery.

A 73-year-old female with severe sciatica suffered from an aneurysm of the left internal iliac artery. At first minimal caudographic abnormalities suggested intervertebral disc herniation and lumbar root compression but at exploratory surgery the diagnosis had to be rejected. Once the correct diagnosis was established by echography, CT-scanning and angiography surgical treatment of the aneurysm resulted in complete recovery. Because sciatic nerve lesions due to aneurysms in the pelvic region very seldom occur and may be the cause of diagnostic confusion, symptoms and treatment of these aneurysms are discussed.

Aged↗

Metabolism and receptor binding of nandrolone and testosterone under in vitro and in vivo conditions.

The metabolism and receptor binding of nandrolone (N) and testosterone (T) were studied under in vitro and in vivo conditions. The results of both in vitro incubation studes with 3H-N and 3H-T in tissue homogenates from rats and in vivo infusion studies with 3H-N and 3H-T in conscious rats show the importance of the enzymes 5 alpha-reductase and 3 alpha/beta-hydroxysteroid-oxidoreductases in the prostate and the importance of the enzyme 17 beta-hydroxysteroid dehydrogenase in the kidney for the effects of N and T on these tissues. Following infusion of a combined dose of 3H-N and 3H-T there is a preferential retention at the receptor of 5 alpha-dihydrotestosterone (DHT) over 5 alpha-dihydronandrolone (DHN), N and T (DHT much greater than DHN greater than N greater than T) in the prostate because T is a better substrate than N for 5 alpha-reductase and because DHT binds more strongly to the androgen receptor than DHN, N and T. In the kidney 5 alpha-reductase is not important; there is a preferential retention of N in T (DHN and DHT were only present in small amounts) because N is less susceptible than T for metabolic inactivation by the enzyme 17 beta-hydroxysteroid dehydrogenase and N binds strongly to the androgen receptor. Both in vitro and in vivo studies show that N and T were relatively stable in spleen, thymus and muscular tissue (only shown in vivo) and, as a result, the same amount of N and T was bound to the receptor in these tissues in the in vivo infusion experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Progressive infantile poliodystrophy (Alpers' disease) with a defect in citric acid cycle activity in liver and fibroblasts.

We present the case history of a boy, who died at the age of 3 1/2 years after a rapidly progressive neurologic disorder, characterized by psychomotor retardation, hypotonia, hemiparesis, seizures and myoclonic contractions. Histopathologic studies showed slight lipid storage in liver. Autopsy showed the characteristic features of progressive infantile poliodystrophy (Alpers' disease); ultrastructural examination showed an increased density of mitochondria in cerebral gray matter. Biochemical studies in leukocytes, cultured fibroblasts and liver indicated a deficiency in the citric acid cycle between succinate and fumarate; this deficiency was not present in muscle tissue. This study supports the view that progressive infantile poliodystrophy is associated with abnormalities in pyruvate metabolism and/or in cell mitochondria.

Brain↗

Cysts in rabbit foetal brains. Malformation or artefacts?

Reports have appeared in the literature on brain cysts in rabbit foetuses. This paper reports on investigations carried out to assess whether "cystic dilatation" is a malformation or an artefact. The results show that "cystic dilatation" arises by splitting of the pia-arachnoid membrane leading to a space between the skull and the neural tissue which is lined by the pial layer on its interior aspect and the arachnoid on its exterior aspect. The evidence presented indicates that "cystic dilatation" is a fixation-induced artefact. In addition, the presence of several artificial tissue clefts and spaces in preserved rabbit foetal brains is reported.

Animals↗

Connatal Pelizaeus-Merzbacher disease with congenital stridor in two maternal cousins.

Two maternal cousins are described with the connatal form of Pelizaeus-Merzbacher Disease (PMD) and congenital stridor. Study of brain biopsy material confirms the diagnosis of PMD. The neuropathological findings are suggestive for the transitional form of this disease. Quantitative morphology gives support to the hypothesis that PMD is a disturbance in maturation of neurons and in myelin formation rather than an active degenerative process. The hereditary transmission is most consistent with a sex-linked recessive pattern. Different X-linked signs seem combined in the presented cases.

Biopsy↗