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Biomedical subjects

A Lehmann

Publications and source records attributed to A Lehmann.

At least 73 records · Page 4Linked to original sources
PubMed1996

[Role of plastic surgery in the treatment of breast cancer].

The surgical treatment of breast cancer has changed dramatically since the last twenty years. Radical and super-radical mastectomy are almost no longer indicated except in certain cases of local recurrences. Breast saving procedures are the best indication for small tumors. And the psychological impact of the different treatments including radiotherapy and chemotherapy is considered as an important issue. Therefore, plastic surgeons are more and more frequently called upon to restore the breast appearance using some technique of breast reconstruction or to improve the bad results of a conservative treatment. Moreover, a good knowledge of the plastic surgery techniques allows a better exploration of the breast and large resections in case of fibrocystic diseases with extensive foci of microcalcifications. Such extensive explorations of the breast are more frequently indicated with the development of screening campaigns. When the mastectomy remains the best indication, it is mandatory to propose an immediate breast reconstruction. Insertion of a silicone implant is discussed in several countries, especially in France, although more and more studies are showing the inocuity of such material. A long experience at the Gustave-Roussy Institute of such material used for breast reconstruction showed us the inocuity of long term silicone exposure in patients treated for breast cancer. The conservative surgery should remove the tumor with a free margin of 1 to 2 or even 3 cm and the defect left is sometimes large enough to justify some local glandular mammoplasty in order to prevent from final mammary distorsion or local visible defect. Partial reconstructions could sometimes require more sophisticated techniques including musculo-cutaneous flaps or prosthesis implantation. Finally the integration of the plastic surgery in the surgical protocols of breast cancer treatment, requires a close collaboration between the plastic and the cancer teams. In certain cases, a special surgical training provides the surgeon with a double competence in oncology and in plastic surgery. With such breast surgeon competent both in oncology and plastic surgery, a patient can ask for an aesthetic operation without missing a complete cancer screening as well as she can be treated for a cancer with the best chance to obtain the best cosmetic result.

Breast Neoplasms↗
PubMed1996

Impaired jun-NH2-terminal kinase activation by ultraviolet irradiation in fibroblasts of patients with Cockayne syndrome complementation group B.

c-jun-NH2 kinases (JNK) are among the UV-activated protein kinases that play an important role in cellular stress response via the phosphorylation of c-jun, ATF2, and p53. Activation of JNK by UV irradiation requires cooperation between membrane and nuclear components, including DNA lesions per se. The role of DNA lesions in JNK activation led us to explore the inducibility of these kinases in cells of repair-deficient patients. Analyses of primary fibroblast cell lines from patients with Cockayne Syndrome of complementation group B (CS-B) revealed poor JNK activation after UV irradiation in four of five cases when compared with three repair-proficient, normal human fibroblast cell lines. Impaired ability to activate JNK persisted at various time points and with different doses of UV irradiation and coincided with failure of in vitro damaged DNA to activate these kinases. In contrast to UV irradiation, other forms of stress, such as H2O2 or heat shock were capable of inducing JNK activation in CS-B cells. Interestingly, when UV irradiation was administered after osmotic shock, it led to JNK activation in CS-B cells, indicating that alternate signal transduction pathways that are activated in response to other forms of stress can potentiate JNK activation by UV irradiation. Unlike CS-B cells, those of other repair-deficient cells, including xeroderma pigmentosum of different complementation groups, revealed proper activation of JNK by UV irradiation. Together, our findings point to deficiency of JNK activation by UV irradiation in CS-B cells, a phenomenon which may be associated with impaired CS-B, the mutant repair gene in these patients.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1995

Neurotoxicity of cysteine: interaction with glutamate.

L-Cysteine produces excitotoxic brain damage but its chemical structure differs from that of other excitotoxins. Although it is an NMDAmimetic, its mode of action is complex and may encompass antiexcitotoxic components. The purpose of the present study was to investigate whether cysteine kills neurons by potentiating the effects of glutamate and/or by releasing glutamate. In primary cultures of cortical neurons, 24 h of exposure to glutamate caused a concentration-dependent, dizocilpine-sensitive cell death as measured by release of lactate dehydrogenase. Cysteine was also toxic but higher concentrations were required. In addition, N-acetylcysteine produced mild toxicity at 1 mM. There was no general potentiation between either glutamate and cysteine or glutamate and N-acetylcysteine although some combinations acted synergistically. In no case did the thiols inhibit glutamate toxicity. The interaction between glutamate and cysteine toxicity was also assessed in the immature rat arcuate nucleus in vivo. When given at a dose (0.5 mg/g) that did not cause any toxicity per se, cysteine enhanced the toxicity of glutamate (0.3-0.8 mg/g). Cortical microdialysis was carried out in anesthetized rats (8-10 days old) administered a toxic dose of cysteine (1 mg/g). The levels of taurine were elevated 15-fold, phosphoethanolamine 3-fold and alanine 2-fold. Despite the observation that glutamine decreased markedly and rapidly, there was only a delayed doubling of glutamate concentrations. It is therefore unlikely that cysteine induces neurotoxicity by releasing glutamate. Taken together, the results suggest that there is a synergistic effect between cysteine and glutamate. Speculatively, this potentiation may be produced by reduction by cysteine of the redox site of the glutamate-activated NMDA receptor-ionophore complex.

Animals↗
PubMed1995

Defects in the DNA repair and transcription gene ERCC2 in the cancer-prone disorder xeroderma pigmentosum group D.

Xeroderma pigmentosum (XP) is a sun-sensitive, cancer-prone genetic disorder characterized by a defect in nucleotide excision repair. The human nucleotide excision repair and transcription gene ERCC2 is able to restore survival to normal levels after exposure to UV light in XP complementation group D cells. No enhancement of UV survival is seen in groups C, E, F, or G. XP-CS-2 cells are complemented by ERCC2, confirming the reassignment to group D of this combined XP/Cockayne's syndrome patient. Nucleotide sequence analysis of the ERCC2 cDNA from five XP group D cell strains [XP6BE(SV40), XP17PV, XP102LO, A31-27 (a HeLa/XP102LO hybrid), and XP-CS-2] revealed mutations predominantly affecting previously identified functional domains. The mutations include base substitutions resulting in amino acid substitutions, deletions due to splicing alterations, and defects in expression. XP6BE(SV40), XP17PV, XP102LO, and A31-27 all have one allele with an Arg683 to Trp substitution within the putative nuclear location signal. The genetic disorder trichothiodystrophy (which is not cancer-prone) can also result from mutations in the ERCC2 gene, some of which are the same as those found in XP-D. The various clinical presentations can be correlated with the particular mutations found in the ERCC2 locus.

Adult↗
PubMed1994

In vivo acidosis reduces extracellular concentrations of taurine and glutamate in the rat hippocampus.

Microdialysis-perfusion of the urethane-anesthetized rat hippocampus was performed to assess the effects of acidosis on extracellular amino acids. Perfusion with Krebs-Ringer bicarbonate buffer at pH 6.9 produced a selective decrease in taurine. A further reduction of pH to 6.4 induced diminished glutamate levels. The Cl-/HCO3- exchange inhibitor 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS) did not affect interstitial taurine during perfusion, but there was a rebound increase in taurine levels upon withdrawal of the agent. In contrast, glutamate concentrations were elevated during DIDS administration, and decreased upon reperfusion with standard buffer. The reduction of extracellular taurine and glutamate concentrations caused by low pH was inhibited by DIDS. The results suggest that taurine and glutamate uptake and/or release in vivo is pH-dependent, and that the effects of acidosis possibly are mediated by the Cl-/HCO3- antiporter. The decrease in extracellular glutamate brought about by low pH may have pathophysiologic implications in conditions associated with disturbed pH homeostasis such as cerebral ischemia and spreading depression.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

[Anesthesia in carotid surgery].

Carotid endarterectomy has become a standard surgical procedure in the therapy of cerebrovascular insufficiency. An important consideration in this form of therapy is to maintain a low perioperative morbidity and mortality. In planning the procedure the two most frequent complications deserve special consideration. Thromboembolism is the major cause of new neurological deficits and prevention should be emphasized as therapeutic interventions are of limited value. The cardiovascular status needs special attention, since the long-term prognosis is predominantly influenced by concomitant coronary artery disease. Regional anaesthesia provides good cardiovascular stability and the chance to monitor neurological changes in an awake patient. Patient discomfort and limited control of vital functions are obviated by general anaesthesia raising the challenge of maintaining cardiovascular stability and establishing adequate cerebral monitoring. Both electroencephalography and somatosensory evoked potentials monitor cerebral function continuously and enable detection of cerebral ischaemia secondary to inadequate blood flow. Another continuous technique is transcranial Doppler sonography; this, however, does not monitor brain function and its role in carotid surgery is still under investigation. Carotid stump pressure or cerebral blood flow measurements provide intermittent data and should therefore only be used as an adjunct. The goal to find an approach that minimizes the risk for the individual patient can only be attained by close cooperation between anaesthesiologists and surgeons.

Anesthesia, General↗
PubMed1994

Can breast reconstruction with gel-filled silicone implants increase the risk of death and second primary cancer in patients treated by mastectomy for breast cancer?

An increased risk of cancer and autoimmune disease associated with gel-filled silicone implants has been suggested recently, but these possible detrimental effects have not been adequately studied in patients with breast cancer. In order to evaluate these effects, we have studied 146 patients with breast cancer treated by mastectomy at the Gustave Roussy Cancer Institute between 1965 and 1983 and who received a gel-filled silicone implant for immediate or delayed breast reconstruction between 1976 and 1984. These patients were compared with 146 matched controls with breast cancer who were treated in the same center by mastectomy without breast reconstruction and were matched for age at diagnosis (within 10 years), year of diagnosis (within 3 years), stage, histologic type of the tumor, histopathologic grade, and nodal status. The relative risks of death, relapse, and second primary cancer were estimated by means of the Cox proportional hazards model stratified on age at diagnosis. The risks of distant metastasis and death due to breast cancer were significantly lower in the breast reconstruction group than in the control group. The risks of local recurrence, second breast cancer, and second primary cancer in another site than the breast were not significantly different between the two groups of patients. Our results do not support the hypothesis of a detrimental effect of gel-filled silicone implants either in the course of breast cancer or in the risk of death due to other diseases.

Breast Neoplasms↗
PubMed1993

Cysteine sulphinate and cysteate: mediators of cysteine toxicity in the neonatal rat brain?

Excitotoxic amino acids contain two acidic groups, but cysteine represents an exception to this rule. The hypothesis that cysteine toxicity is mediated by the oxidized and diacidic metabolites cysteine sulphinate and/or cysteate was tested in the present study. The issue was approached in three different ways. Firstly, the distribution of brain injury after subcutaneous administration of cysteine (1 mg/g) to 4-day-old rats was compared with that caused by cysteine sulphinate (3 mg/g). Secondly, the effects of excitatory amino acid receptor antagonists on cysteine and cysteine sulphinate toxicity were investigated. Thirdly, the cerebral concentrations of cysteine sulphinate were determined after cysteine administration and compared with those obtained after cysteine sulphinate injection. The cerebral cortex was the region most vulnerable to cysteine toxicity, followed by the hippocampus (especially the medial subicular neurons), amygdala, caudoputamen, cerebellum and septum. Pronounced extravasation of red blood cells was observed in lesioned areas. One day after cysteine administration, the injury was infarction-like and sharply demarcated. Cysteine sulphinate-induced damage resembled cysteine-induced lesions in some respects: the anterior cingulate and retrosplenial cortices, as well as medial subicular cells, were quite vulnerable. However, the differences prevailed. Cysteine sulphinate, but not cysteine, killed neurons of the superficial part of the tectum, the medial habenula, the ventromedial hypothalamus and the arcuate nucleus. Further, while cysteine toxicity was prominent in deep cortical layers, cysteine sulphinate preferentially damaged superficial cortical neurons. Cysteine toxicity was abolished by pretreatment with MK-801, a selective NMDA antagonist, but not by 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline, a selective AMPA receptor blocker. In contrast, the considerably smaller lesion seen after cysteine sulphinate administration was only partially prevented by MK-801. Large (19-fold) increases in cortical cysteine sulphinate concentration were noted after injection of a toxic dose of cysteine. This corresponds to 90 nmol cysteine sulphinate/g protein. The cysteate concentration was not increased above the detection limit. Injection of a toxic dose of cysteine sulphinate elevated cysteine sulphinate concentration in the frontomedial cortex (a region consistently injured by cysteine sulphinate) almost three orders of magnitude more than that observed after cysteine administration. Taken together, these results strongly suggest that neither cysteine sulphinate nor cysteate alone mediate cysteine toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMed1993

Neuronal-glial exchange of taurine during hypo-osmotic stress: a combined immunocytochemical and biochemical analysis in rat cerebellar cortex.

Rat cerebellar Purkinje cells show a high level of taurine-like immunoreactivity. Light-microscopic immunocytochemistry indicated that the level of taurine in these cells was substantially decreased in animals that had survived for 4 h after an intraperitoneal injection of distilled water. This treatment resulted in a 15-20% reduction in plasma osmolality. The changes in the Purkinje cells were accompanied by an increased immunolabeling of neighboring glial cells (Golgi epithelial cells). The changes in both cell types were reversed in animals whose plasma osmolality had been normalized by injections of hypertonic saline 4 h after the water loading. Adjacent sections incubated with a GABA antiserum did not exhibit any overt changes in response to the hypo-osmotic stress. Quantitative electron-microscopic analysis of ultrathin sections subjected to postembedding immunogold cytochemistry indicated that the Purkinje cells had lost 50-60% of their taurine contents after water loading and that the loss affected all intracellular compartments, including mitochondria and cytoplasmic matrix. The loss of taurine immunoreactivity from Purkinje cells was accompanied by an estimated 70-80% increase in the contents of immunoreactive taurine in adjacent glial cells. Biochemical recordings of tissue amino acids in a parallel series of animals revealed a 12% reduction in cerebellar taurine contents 4 h after water loading (value corrected for changes in specific gravity). This reduction had progressed to 32% after 8 h and was only partly prevented by normalization of plasma osmolality. The tissue levels of GABA and several other amino acids showed a decrease similar to that of taurine, while glutamine displayed a considerable increase after water loading. Our findings indicate that acute reductions in plasma osmolality cause a flux of taurine from Purkinje cells to glia, and that this flux is reversed upon normalization of plasma osmolality. These changes are superimposed on a decrease in the biochemically recorded tissue level of taurine. Unlike the cellular redistribution, this decrease was not reversible within the time frame of the present study, and it was not specific for taurine. Cellular redistribution of taurine may represent a rapid adjustment to osmotic perturbations in vivo. In addition, it may reflect a higher priority for neuronal compared with glial volume regulation.

Amino Acids↗