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Biomedical subjects

J Willems

Publications and source records attributed to J Willems.

At least 55 records · Page 3Linked to original sources

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↗

Three-point linkage analysis using multiple DNA polymorphic markers in families with X-linked nephrogenic diabetes insipidus.

The gene for X-linked nephrogenic diabetes insipidus (NDI), a disorder which, if untreated, causes severe dehydration, mental retardation, and possibly death in affected males, has been mapped recently to the Xq28 band through demonstration of linkage to the DX552 locus and other DNA markers (N. Knoers et al., 1987, Cytogenet. Cell Genet. 46:640; M. Kambouris et al., 1987, Cytogenet. Cell Genet. 46:636). Linkage studies in 11 families with NDI have enabled us to map the NDI gene between closely linked flanking markers in the Xq28 region and to obtain the following gene order: centromere-F9-DXS98-F8/CBD,CBP-DXS52/NDI-DXS134- telomere. These results have implications for presymptomatic and prenatal diagnosis of NDI and should also improve the prospects for identifying the fundamental gene defect underlying this disorder.

Chromosome Deletion↗

A synthetic peptide defines a serologic IgA response to a human papillomavirus-encoded nuclear antigen expressed in virus-carrying cervical neoplasia.

The growing awareness of the role of human papillomavirus (HPV) in cervical carcinoma has triggered a search for uncomplicated detection methods. To define a serologic response to HPV, we synthesized peptides based on sequences deduced from the genome of HPV type 16, the most common malignancy-associated type of HPV. One of these peptides reacted with IgA antibodies present in sera from 24 of 33 patients with cervical intraepithelial neoplasia or cervical carcinoma, whereas this peptide reacted with only 6 of 27 sera from individuals without cervical intraepithelial neoplasia. Immunoaffinity-purified human antipeptide IgA antibodies detected HPV-specific 58- and 48-kDa proteins in cervical carcinoma cell extracts and also detected a nuclear antigen in HPV-carrying cervical cancer cell lines and cervical intraepithelial neoplasia biopsied tissue. These antigens were also detected with mouse monoclonal and rabbit polyclonal antibodies to the same peptide. The results indicate that screening for infection with malignancy-associated types of HPV may be possible by simple synthetic peptide-based serology.

Antibodies, Neoplasm↗

Human granulocyte chemotactic peptide (IL-8) as a specific neutrophil degranulator: comparison with other monokines.

The influence of human monocyte-derived chemotactic peptide (GCP/IL-8) on degranulation of neutrophils was investigated in relation to that of other monokines. GCP/IL-8 promoted a dose-dependent release of lactoferrin from specific granules but had no effect on enzyme release from primary granules. From the other monokines that were tested, tumour necrosis factor alpha (TNF alpha) also induced degranulation, while IL-1 beta and IL-6 scored negatively. TNF alpha-induced lactoferrin release was enhanced by cytochalasin B pretreatment of the granulocytes, while GCP/IL-8-promoted degranulation was not. In contrast to GCP, TNF alpha also caused the release of LDH, suggesting a non-specific cell destruction. These observations further support the view that, unlike the other monokines, GCP/IL-8 is a true and specific granulocyte activator.

Biological Factors↗

[Cutaneous burns caused by Yperite. Apropos of 2 new cases].

Based on two of their own cases, the authors review the lesions produced by Yperite. This chemical agent produces cutaneous burns which are quite characteristic; histological study of biopsies carried out on cutaneous lesions was used to define the effects on the epidermis and dermis. The treatment of patients, with this rare condition, remains symptomatic.

Adult↗