Biomedical subjects
Publications and source records attributed to J Bondeson.
We present a case of histologically proven giant cell arteritis presenting as an acute unilateral oculomotor nerve palsy without pupillary dilatation. The etiology and mechanisms involved in this uncommon phenomenon are discussed. It is emphasized that a giant cell arteritis with cranial nerve involvement is a medical emergency, and that swift diagnosis and treatment is necessary to avoid permanent disability.
Tenidap is a novel antirheumatic drug that combines cyclooxygenase inhibition with cytokine modulating qualities. We demonstrate here that tenidap inhibits the zymosan-induced expression of both interleukin 1 and tumor necrosis factor alpha in macrophages, at the mRNA and protein levels. The concentration-dependence of the tenidap-induced inhibition of the expression of mRNA for these proinflammatory cytokines agrees with that of its inhibitory effects on zymosan-induced arachidonate mobilization and changes in phosphoprotein pattern. The effects of tenidap on the lipopolysaccharide-induced expression of these cytokines are more complex. Tenidap inhibits the induction of interleukin 1 by lipopolysaccharide or bacteria, but less potently than the interleukin 1-response induced by zymosan. In contrast, the drug markedly potentiates the lipopolysaccharide-induced expression of tumor necrosis factor alpha at both the mRNA and protein levels. The latter effect is demonstrated to be due to cyclooxygenase inhibition and is reversed by prostaglandin E2.
Tenidap is a novel, once-daily antirheumatic drug which has shown promising results against rheumatoid arthritis in extensive clinical trials. It combines NSAID-like cyclooxygenase inhibition with suppression of the acute phase response. In macrophages, tenidap inhibits the lipopolysaccharide-induced synthesis of interleukins-1 and -6, but it tends to potentiate the lipopolysaccharide-induced synthesis of tumor necrosis factor alpha, due to its cyclooxygenase inhibition. In macrophages, tenidap is a potent inhibitor of zymosan-induced responses, not only the induction of proinflammatory cytokines, but also arachidonate mobilization, protein phosphorylation, and inositol phosphate formation, possibly through interference with the receptor-mediated upregulation of phospholipase C. Tenidap also acts as an intracellular acidifier in many cell types, which may explain at least some of its other effects. Recent studies have indicated that, in addition to modulation of prostanoid and cytokine formation, tenidap has many other effects beneficial in rheumatic disease. It has been shown to inhibit bone resorption, neutrophil adhesion and degranulation, the interleukin-1-induced suppression of glycosaminoglycan synthesis, as well as the production of active metalloproteinases from chondrocytes.
A lithopaedion, or stone-child, is a dead fetus, usually the result of a primary or secondary abdominal pregnancy, that has been retained by the mother and subsequently calcified. This paper describes the earliest known case of this phenomenon. It was discovered in 1582, at the autopsy of a 68-year-old woman in the French city of Sens, and described in a thesis by the physician Jean d'Ailleboust. The woman had carried her lithopaedion for 28 years. In this historical vignette, the lithopaedion of Sens is compared to later instances of this phenomenon. The ultimate fate of the lithopaedion specimen, which was widely traded throughout Europe in the 1600s before finally ending up in Copenhagen, is traced.
A Burmese family with congenital hypertrichosis lanuginosa had an eventful history in the nineteenth century. The earlier members of this family were employed at the court of Ava, but the later ones spent their lives in show business, being widely exhibited for money in the 1880s. Their extraordinary hairiness attracted much curiosity, and they were photographed several times. The hairy Burmese are the only example of a four-generation pedigree of congenital hypertrichosis lanuginosa, which is consistent with an autosomal dominant mode of inheritance. There is good evidence that, when the members of this family were hairy, their dentition was also deficient.
According to an obscure medieval legend, the Countess Margaret of Henneberg, a notable Dutch noblewoman, gave birth to 365 children in the year 1276. The haughty Countess had insulted a poor beggar woman carrying twins, since she believed that a pair of twins must have different fathers, and that their mother must be an adultress. She was punished by God, and gave birth to 365 minute children on Good Friday, 1276. The Countess died shortly after, together with her offspring, in the village of Loosduinen near The Hague. The Countess and her numerous brood were frequently described in historical and obstetrical works. To this day, a memorial tablet and two basins, representing those in which the 365 children were baptized, are to be seen in the church of Loosduinen.
Gold compounds are widely used in the treatment of rheumatoid arthritis, but their mechanisms of action remain unclear. We demonstrate here that auranofin (AF) (0.1-3 microM), but neither the hydrophilic gold compounds aurothiomalate (ATM) and aurothioglucose nor methotrexate or D-penicillamine, inhibits the induction of interleukin 1 beta and tumor necrosis factor (TNF) alpha mRNA and protein by either zymosan, lipopolysaccharide (LPS), or various bacteria in mouse macrophages. The auranofin-mediated inhibition of the induction of TNF-alpha mRNA was stronger than that of interleukin (IL) 1 beta mRNA. AF, but not the other drugs, also inhibited zymosan-induced mobilization of arachidonate. The fact that AF inhibited the induction of mRNA for both these proinflammatory cytokines, irrespective of which stimulus was used, may indicate that it affects some common signal transduction step vital to their induction.
Tenidap is a novel antirheumatic drug which combines non-steroidal antiinflammatory drug-like cyclooxygenase inhibition with cytokine modulating qualities in rheumatoid arthritis. We show herein that tenidap (5-20 microM) inhibited protein kinase C-mediated signalling leading to release of arachidonate in mouse macrophages by interfering with the up-regulation of the 85 kDa arachidonate-mobilizing phospholipase A2, although it did not inhibit this enzyme directly. The Ca(2+)-mediated activation of arachidonate mobilization was inhibited only at higher concentrations (20-40 microM). Studies of protein phosphorylation indicated that tenidap in itself was capable of inducing the phosphorylation of several protein bands through interaction with intracellular protein kinases and/or phosphatases. Importantly, tenidap inhibited both arachidonate release and the increase in intracellular protein phosphorylation when the cells were stimulated with zymosan. We propose that the main inhibitory influence of tenidap on the macrophage signalling investigated here is exerted at some level between protein kinase C and the 85 kDa phospholipase A2 and quite possibly also at the receptor-linked activation of phospholipase C.
Julia Pastrana (1834-1860) has gained immortality as one of the most extreme cases of generalized hypertrichosis upon record. When she was exhibited for money in the United States and Europe during the years 1855-1860, people thronged to see her, and she was several times described in the medical press of the day. After Julia Pastrana's death in childbirth, her corpse was embalmed in a very life-like manner, and exhibited all over Europe for several decades. Later, the mummy was believed to be lost, but in 1990 it was discovered at the Oslo Forensic Institute. Some writers have included Julia Pastrana among the cases of congenital hypertrichosis languinosa. However, a microscopic examination of hair samples from the mummy shows that her hairy growth is unmistakably terminal in character, and we propose that she instead was an example of congenital, generalized hypertrichosis terminalis with associated gingival hyperplasia. While many earlier writers have asserted that Julia Pastrana's dentition was abnormal, a radiographic examination of the mummy has shown that she had a complete permanent dentition.
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The effects of antirheumatic gold compounds and D-penicillamine on protein kinase C- and Ca(2+)-mediated activation of arachidonate mobilization and the formation of eicosanoids in mouse macrophages have been investigated. Auranofin (0.2-2 microM) enhanced the response to phorbol ester two- to three-fold, and similar enhancement was caused by aurothiomalate, aurothioglucose, and penicillamine, but only after pretreatment for 1-4 h. The enhanced mobilization of arachidonate was accompanied by increased formation and release of prostaglandin E2 and 6-keto prostaglandin F1 alpha, but not of lipoxygenase metabolites. No such enhancement occurred when the arachidonate-mobilizing phospholipase A2 was activated directly (calcium ionophore A23187). Instead, auranofin caused selective inhibition of calcium ionophore-induced formation of leukotriene C4. Treatment of macrophages with 4 beta-phorbol 12-myristate 13-acetate causes a rapid increase in the phosphorylation and a 1.4-1.8-fold increase in the activity of the 85-kd arachidonate-mobilizing phospholipase A2 as determined in an in vitro assay. The increase in activity was further enhanced by both the gold compounds and penicillamine. These findings indicate that the target for the enhancing effect of the antirheumatic drugs is located between protein kinase C and phospholipase A2 in the signal chain leading to activation of the latter enzyme.
Pachyonychia congenita is an uncommon type of ectodermal dysplasia, characterized by thickened, dystrophic nails and hyperkeratotic skin lesions. In the literature, it has been widely accepted that the first cases of this syndrome were published in the first years of the 20th century. However, a search of the older literature reveals several older cases of definite pachyonychia congenita, some of them from the 17th and 18th centuries. In 1716, the Danish physician Musaeus described a case of the pachyonychia congenita syndrome in some detail, with an excellent plate showing all the major symptoms.
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One of the most remarkable cases of extreme dwarfism on record is Caroline Crachami, the Sicilian Fairy. She was born in 1815, and was taken to London to be exhibited for money in 1824. Due to her proportional dwarfism, severe intrauterine growth retardation, and typical "bird-headed" profile, Caroline Crachami has by some been diagnosed as a case of the autosomal recessive Seckel syndrome. In this historical vignette, the Sicilian Fairy's life and death are presented in some detail using new material, and the problem of her correct diagnosis is discussed.
A case of tongue necrosis in a patient with temporal arteritis who was taking ergotamine is described, and the role of ergotamine tartrate in provoking the tongue necrosis is considered. The literature on this unusual complication is critically reviewed, and the value of a carotid angiography in assessing the tongue ischaemia is exemplified.
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A case of diclofenac-induced thrombocytopenic purpura in a 59-year-old woman is described. Unlike the majority of earlier cases, ours was associated with renal insufficiency and jaundice. Despite the dramatic clinical picture, with severe thrombocytopenia and marked renal insufficiency, the prognosis appears to be excellent, as is shown in our case and in similar ones reported in the literature. A high dose of steroids is the treatment of choice.