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Biomedical subjects

J Willems

Publications and source records attributed to J Willems.

At least 19 recordsLinked to original sources

"In vitro" effect of interleukin-1 beta on human glioma cell lines: regulation of cell proliferation and IL-6 production.

The human glioma cell lines U251 and HP591 were chosen as "in vitro" models for functional astrocytes. When cultured in the presence of IL-1 beta these cell lines demonstrated a marked increase in interleukin-6 production and in [3H]-thymidine uptake. The addition of dbcAMP could mimic the first effect of IL-1 beta but at the same time suppressed cell proliferation. These results suggest that IL-1 beta possibly exerts one of its biological effects (IL-6 synthesis) by means of the cyclic AMP pathway.

Bucladesine

Posttreatment itraconazole levels in the nail. New implications for treatment in onychomycosis.

BACKGROUND: A problem in the treatment of onychomycosis is the lengthy duration of therapy. The pharmacokinetics of itraconazole suggest a potential for briefer treatment. OBJECTIVE: This study was designed to investigate itraconazole nail kinetics in 39 patients with onychomycosis in relation to their therapeutic outcome. METHODS: All patients received itraconazole for 3 months at a dose of 100 or 200 mg daily. Itraconazole levels of distal nail clippings were determined during a 6-month posttherapy period. RESULTS: Therapeutic itraconazole concentrations were found in the nail plates of fingernails and toenails for up to 6 months after treatment. Cure of the toenails was observed in 79% of the patients treated with the 200 mg dosage and in 26% of those treated with 100 mg at 6 months after therapy. CONCLUSION: The data suggest that the drug reaches the nail via incorporation into the matrix and by diffusion from the nail bed and is eliminated with regrowth of the nail after discontinuation of treatment.

Antifungal Agents

Isolated single coronary artery: a review of 50,000 consecutive coronary angiographies.

Single coronary artery is a rare congenital anomaly of the coronary arteries where only one coronary artery arises from the aortic trunk by a single coronary ostium, supplying the entire heart. A database consisting of the angiographic reports of 50,000 consecutive coronary angiographies performed in adult patients in the University Hospital of Leuven between March 1973 and August 1991 was searched for the diagnosis of single coronary artery. All films concerned were reviewed and classified according to their anatomical type. Thirty-three cases of single coronary artery were retrieved, yielding an incidence of 0.066%. Patient characteristics and clinical data are described, with a discussion on the pathological importance of this finding.

Adult

Intermediate syndrome due to prolonged parathion poisoning.

A parathion-poisoned patient with prolonged cholinesterase inhibition due to impaired hepatic metabolism and urinary excretion is reported. An intermediate syndrome characterized by respiratory paresis, weakness in the territory of several motor cranial nerves and of proximal limb and neck flexor muscles, persisted for 3 weeks. During this whole period, cholinesterase remained markedly reduced. Serial EMGs with repetitive nerve stimulation pointed to a combined pre- and postsynaptic disorder of neuromuscular transmission. Electron microscopy of an intercostal muscle biopsy showed focal degeneration at the poorly branched postsynaptic folds, and was considered to be nonspecific.

Acetylcholinesterase

The intermediate syndrome in organophosphate poisoning: presentation of a case and review of the literature.

A dimethoate-poisoned woman gradually developed a moderately severe cholinergic crisis that was readily treated by atropine. After being symptom-free for nearly two days, she suffered from sudden life-threatening respiratory paresis and weakness of the facial, extraocular, neck flexor and proximal limb muscles. Muscarinic symptoms were absent. Cholinesterase inhibition was severe, and EMG revealed marked decrements at low rates of repetitive nerve stimulation, and increments at a high rate. The clinical course was compatible with the Intermediate Syndrome. This syndrome seems due to persistent cholinesterase inhibition presumably leading to combined pre- and postsynaptic impairment of neuromuscular transmission. Inadequate pralidoxime therapy is proposed but not established as contributory. Prolonged monitoring of respiratory function in patients poisoned by particular organophosphate agents is mandatory.

Adult

Prolonged toxicity with intermediate syndrome after combined parathion and methyl parathion poisoning.

A prolonged type of organophosphate toxicity, previously characterized as the Intermediate Syndrome, has been recognized in 6 out of 7 prospectively studied patients poisoned by insecticide containing parathion and methyl parathion in equal proportions. The clinical characteristics included respiratory paresis, weakness in the territories of several motor cranial nerves, neck flexors and proximal limb muscles, and depressed tendon reflexes, all lasting for several days or weeks. Electromyography in the early stages disclosed diverse types of impaired neuromuscular transmission. EMG normalization preceded clinical recovery. Severe plasma butyrylcholinesterase and erythrocyte acetylcholinesterase inhibition persisted along with the occurrence of Intermediate Syndrome-related symptoms. We conclude that combined parathion and methyl parathion poisoning is more likely to induce Intermediate Syndrome than parathion poisoning alone. The mechanisms underlying this difference remain obscure. The Intermediate Syndrome shows clinical and electromyographic hallmarks of combined postsynaptic impairment of neuromuscular transmission.

Adult

Hyperparathyroidism associated with treatment of manic-depressive disorders by lithium.

OBJECTIVE: To clarify the association between treatment of affective psychiatric disorders with lithium, and the development of secondary hyperparathyroidism. DESIGN: Retrospective review of medical records, 1973-89. SUBJECTS: 17 patients with affective psychiatric disorders who were treated with lithium (n = 6) or with tricyclic antidepressant, or neuroleptic, drugs (n = 11) all of whom were operated on for hyperparathyroidism. MAIN OUTCOME MEASURE: Duration of lithium therapy and parathyroid histology. RESULTS: Parathyroid hyperplasia was present in 5 patients who had taken lithium during a median period of 13 years. A parathyroid adenoma was found in one patient treated with lithium for three years. Ten of the 11 patients who had been treated with tricyclic antidepressant, or neuroleptic drugs had a parathyroid adenoma and the remaining one had an adenoma as an underlying cause of hyperparathyroidism. CONCLUSION: Hyperparathyroidism in patients who have undergone long term treatment with lithium is associated with parathyroid hyperplasia. This indicates that lithium may exert a chronic stimulus that results in secondary hyperparathyroidism.

Adenoma

Proliferative myositis and fasciitis. A light and electron microscopic, cytologic, DNA-cytometric and immunohistochemical study.

Two cases of proliferative myositis, four cases of proliferative fasciitis and one mixed form of proliferative myositis and fasciitis have been analyzed in terms of cell differentiation and DNA content. Light microscopically, the lesions were characterized by a mixture of proliferating spindle-shaped cells and uni-, bi- or occasionally multinucleated ganglion cell-like cells. The spindle cells showed ultrastructural features and immunohistochemical properties, including an immunoreactivity for smooth muscle-specific actin, indicative of a myofibroblastic differentiation. The ganglion cell-like cells displayed some resemblance to active osteoblasts ultrastructurally and differed immunohistochemically from the spindle cells by being non-immunoreactive for smooth muscle-specific actin. None of the two cell types showed immunoreactivity for desmin, myoglobin or factor VIII RAG. It is suggested that the two cell types represent different lines of cell differentiation. The cytologic features in smears, as seen in two cases of proliferative fasciitis and one case of proliferative myositis, are considered to be characteristic of these lesions and to permit the diagnosis to be made by fine-needle aspiration. In two of the cases, the lesion was diagnosed only cytologically and thereafter disappeared spontaneously within a month. Cytometric DNA measurements, using two different image analysis systems on Feulgen-stained sections and smears, revealed a "diploid" spindle-shaped cell population with a variable proportion of cells with scattered DNA values. The ganglion cell-like cells differed from the spindle cells by having a broad DNA peak in the diploid region and additional peaks in the tetraploid region, as well as a higher proportion of cells with scattered DNA values compared with those of the spindle-shaped cells. The results of the quantitative DNA analysis are well in keeping with the benign and proliferative nature of these lesions. However, with the technique used here, quantitative DNA analysis, does not distinguish these pseudosarcomatous fibrous lesions from diploid and tetraploid soft tissue sarcomas.

Actins

Stimulation of CRP secretion in HepG2 cells: cooperative effect of dexamethasone and interleukin 6.

This report described the capability of the human. human acute phase reactant, C-reactive protein (CRP). Its secretion is stimulated by interleukin 6 (IL-6) in a dose-dependent fashion and can further be positively modulated by dexamethasone. The way in which this glucocorticoid influences the CRP response depends on its time of application. Incubation of HepG2 cells simultaneously with IL-6 and dexamethasone increases the magnitude of CRP release significantly above that seen with IL-6 alone. After preincubation with dexamethasone, the kinetics of CRP release, induced by IL-6, are increased and approach that observed in the case of alpha 1-acid glycoprotein (alpha 1-AGP) without dexamethasone pretreatment. Conditions for optimal secretion of CRP were determined.

C-Reactive Protein

Effect of sulfur mustard on murine lymphocytes.

The effect on spleen cells of a single in vivo treatment with sulfur mustard was analyzed in mice 1 week after intoxication. A marked decrease in the number of total spleen cells was observed in mice receiving high doses of sulfur mustard. Flow cytometric analysis indicated that B-lymphocytes were relatively more affected than T-lymphocytes by this toxic compound. However, the function of remaining B-cells, measured by thymidine incorporation and immunoglobulin secretion in the presence of lipopolysaccharide, was not significantly impaired. In addition, sulfur mustard did not depress T-lymphocyte function since their proliferation in response to concanavalin A or to an anti-CD3 antibody was not affected by the treatment. These results suggest that whereas some observations reported in patients can be found in a murine model, additional in vitro studies with human lymphocytes could more adequately provide further information on sulfur-mustard-induced alterations of the immune system.

Animals

The value of the intracoronary electrogram for the early detection of myocardial ischaemia during coronary angioplasty.

The clinical value of intracoronary electrography for the detection of myocardia ischaemia was assessed during coronary angioplasty and compared to a standard technique of surface ECG monitoring. In 73 patients undergoing single lesion angioplasty, an intracoronary electrogram and four representative surface ECG leads were obtained. During angioplasty of the left anterior descending artery leads, I, V3, V5, V6 were recorded. For the circumflex artery leads I, aVL, aVF, V6, and for the right coronary artery leads II, III, aVF, V6 were monitored. Eight patients were excluded due to transient intraventricular conduction disturbances during balloon inflation; 65 patients remained for further analysis. Out of a total of 154 balloon inflations (35 in the circumflex, 71 in the left anterior descending and 48 in the right coronary artery), the percentage that produced a greater than or equal to 1 mm ST segment elevation, the time to the appearance of a greater than or equal to 1 mm ST segment elevation and the maximal ST segment elevation were recorded. During inflations in the circumflex artery, the respective values of these three parameters were 20%, 22.6 +/- 11.5 s and 0.37 +/- 0.80 mm in V6, the most sensitive surface lead, versus 70% (P less than 0.001), 14.4 +/- 9.6 s (P less than 0.01) and 5.82 +/- 6.35 mm (P less than 0.0001) on the intracoronary electrogram.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary

Histological and histochemical study of paraoxon myopathy in the rat.

Time and dose dependency of paraoxon-induced myopathy in rats was studied in relation to esterase inhibition and clinical symptoms. High-dose poisoning resulted in a major cholinergic crisis with concomitant acetylcholinesterase inhibition in the first few hours with rapid restoration thereafter. Dose-dependent segmental muscle fiber necrosis occurred in clusters around the end-plates and was more frequent in diaphragms as compared to gastrocnemius muscles. However, in low-dose poisoned rats without major cholinergic symptoms or end-plate cholinesterase inhibition, necrotic fibers were also present. This indicates that not only end-plate cholinesterase inhibition but also neural or neuronal factors might be responsible for acetylcholine overflow and muscle fiber degeneration.

Animals

Effects of chlorpromazine on PMN-mediated activities in vivo and in vitro.

Polymorphonuclear neutrophils (PMN) play a central role in the acute inflammatory response and functions associated with phagocytosis and bacterial killing, including lysosomal enzyme release and superoxide anion (O2-) generation, are also implicated in tissue injury. We have studied the modulation by chlorpromazine (CPZ) on the effects of lipopolisaccharide (LPS) in vivo in mice. Pretreatment with CPZ (4 mg/kg) and, to lesser extent, promethazine, inhibited LPS-induced hypoferraemia and lethality in mice. We have also observed that CPZ (1-15 microns) inhibited lactoferrin release by PMN in vitro, suggesting that this effect could be responsible for the inhibition of hypoferraemia. We have also evaluated the effect of CPZ on other PMN functions implicated in tissue damage and inflammation, chemotaxis and O2- production. CPZ inhibited both activities, although it had chemokinetic activity per se. These data indicate that CPZ is a modular of PMN functions in vivo and in vitro and this effect could be directly implicated in the protective action of CPZ against endotoxic shock.

Animals

A cell culture, chromosomal and quantitative DNA analysis of a metastatic epithelioid sarcoma. Deletion 1p, a possible primary chromosomal abnormality in epithelioid sarcoma.

The chromosomal banding pattern and the in vitro growth characteristics of a metastatic epithelioid sarcoma are described. The cultured tumor cells retained growth characteristics as well as ultrastructural and immunohistochemical properties similar to the cells of the primary tumor. Cytogenetic analysis revealed a modal range in the diploid-hypodiploid region, a finding which was corroborated by quantitative DNA determinations of both the primary tumor and a lymph node metastasis. Fourteen different marker chromosomes were identified. The most frequent clonal rearrangement was a 1p-marker resulting from a short arm terminal deletion, i.e., del (1) (p21-22). A similar 1p- marker has previously been observed in an established epithelioid sarcoma cell line. The finding of an apparently identical 1p-marker in two of two analyzed epithelioid sarcomas suggests that this rearrangement may be a primary cytogenetic abnormality in epithelioid sarcoma. An elevated ras p21 expression was demonstrated using immunohistochemical methods. The possible involvement of the N-ras gene and/or a tumor suppressor in the 1p deletion is considered.

Chromosome Aberrations

The neutrophil-activating proteins interleukin 8 and beta-thromboglobulin: in vitro and in vivo comparison of NH2-terminally processed forms.

Isolation of the human neutrophil activating protein (NAP) interleukin 8 (IL8) from leukocytes has revealed that it is structurally related to beta-thromboglobulin (beta TG) from platelets. Both these proteins occur as natural mixtures of multiple forms, differing from each other by unequal truncation at the NH2 terminus. In this study we have compared IL8 and beta TG forms for in vitro and in vivo neutrophil activation. In contrast to IL8, none of the beta TG forms were found to exert granulocyte chemotactic activity in vitro, as measured in the agarose assay. However, fractions rich in the most extensively processed forms of beta TG (e.g. NAP-2) as well as pure NAP-2 did induce lactoferrin release from granulocytes, whereas fractions containing only the longer forms (e.g. connective tissue-activating peptide III) were inactive. In order to observe this in vitro effect, about 10-fold less IL8 (10 nM) than NAP-2 was required. In the presence of a vasodilator substance low doses (2-20 pmol) of IL8 and the shorter forms of beta TG caused granulocyte accumulation and plasma leakage in rabbit skin whereas the longer forms of beta TG again failed to do so. Finally, granulocytosis induction following i.v. injection was found to occur with NAP-2. At the maximal dose tested (250 pmol), this in vivo effect of NAP-2 was less pronounced than that of IL8. In the case of IL8, NH2-terminal processing did not seem to affect granulocyte stimulatory activity. It should be noted, however, that the extent of processing of IL8 is less than that occurring with beta TG. It can be concluded that the platelet factor beta TG, structurally related to the monokine IL8, can also play a role in neutrophil activation during inflammatory reactions.

Amino Acid Sequence

Interferon therapy in multiple myeloma.

A woman with multiple myeloma relapsed after 6 years of satisfactory tumor control with melphalan therapy. When progression then occurred, she was given exogenous human leukocyte interferon, 3 x 10(6) reference units twice daily i.m., as the sole therapy. Side-effects of the interferon therapy consisted of fever reactions and thrombocytopenia. One month after the initiation of interferon therapy there was 1) improvement of general health with less pain and tiredness, 2) reduction of the M-component, IgG-lambda, in the serum, and 3) a reduced plasma cell concentration in the bone marrow. After 5 months of interferon therapy tumor progression occurred despite continuous interferon treatment. At the same time, the tumor cells were less sensitive to interferon in in vitro tests than prior to interferon therapy. It is suggested that interferon therapy should be given as initial treatment to a few patients with multiple myeloma in a phase I trial.

Aged