Isoniazid intoxication. Light and electron microscopic findings in muscle and sural nerve biopsies

This study indicates the cellular and ultrastructural changes of the thigh muscle and sural nerve biopsies of a patient intoxicated as a result of isoniazid intake for tuberculosis treatment. The observation of the relative degradation of myelination and fibre type II groups was apparent. The regular concentric layers of the myelin sheath were destroyed. There was a consistent increase in irregular vacuolization and membranous structures in the axon and the cytoplasm of the Schwan cells. It is concluded that poisoning cannot be attributed solely to the axonal degradation but also to the direct toxic effect of the drug.     

The lymphomas: molecular pathways and novel therapeutic targets

In recent years, several molecular mechanisms involved in promoting cancer cell survival and growth have been identified. These discoveries helped in designing and testing novel drugs that target specific cellular pathways. In this review, we focus on new molecular targets that are currently being explored for the treatment of non-Hodgkin's lymphoma and Hodgkin's lymphoma.     

Protein expression profiling of endometriosis: validation of 2-mm tissue microarrays

Tissue microarrays (TMAs) are useful tools for studying protein expression in endometriosis. Tissue microarray analyses of immunohistochemical profiles of estrogen receptor-alpha and P receptor corroborate previously published results from the use of conventional immunohistochemistry, thus validating TMA use in endometriosis.     

Mechanical effect of posterior wire or half-pin configuration on stabilization utilizing a model of circular external fixation of the foot

BACKGROUND: Numerous studies have addressed biomechanical characteristics of circular external fixation of long bones. The objective of the present study was to evaluate stabilization of a simulated foot model using external fixation with either calcaneal tensioned stopper wires or half-pins. METHODS: Fixation configurations of the calcaneus included two parallel wires, two wires crossing at either 30 degrees or 45 degrees, a 4-mm- and 5-mm-diameter single half-pin, or two half-pins inserted at a cross-angle of either 45 degrees or 90 degrees. All frames were tested in axial compression, anteroposterior (AP) bending, and mediolateral (ML) bending. RESULTS: An increase in wire cross-angle improved the axial and AP bending stabilization but had no influence on ML bending. Utilization of a single calcaneal half-pin instead of two cross-wires resulted in a considerable reduction in ML bending stabilization. Frame configurations with two half-pins substantially improved axial and ML bending stabilization. Due to the medial location of the metatarsal wire stopper, an increase in half-pin cross-angle significantly improved ML bending stiffness under lateral foot loading. Under the medial foot loading, however, the half-pin cross-angle had no effect on ML bending stabilization. Replacement of cross-wires with two half-pins significantly improved the AP bending stiffness only when the half-pin cross-angle was reduced to 45 degrees. In all modes of two half-pin frame loading, the half-pin diameter had a substantial effect on foot stabilization. CONCLUSIONS: Although the wire cross-angle, half-pin cross-angle, and half-pin diameter affect the stability of foot circular external fixation, the influence of these mechanical parameters on foot stabilization is dependent on the mode and location of loading. CLINICAL RELEVANCE: The results of the present mechanical testing can be utilized as a useful guideline for the optimization of circular external fixation of the foot.     

Brown tumor of the femur associated with double parathyroid adenomas

Severe parathyroid bone disease is a rare clinical presentation of primary hyperparathyroidism. Double parathyroid adenomas are even more rare cause of primary hyperparathyroidism. The authors present a case of double parathyroid adenomas in a 48-year-old man, who presented with painful left lower limb swelling, which was slowly growing in size in the last 20 years. Magnetic resonance imaging revealed a cystic bony lesion and coincidentally, a urinary bladder calculus. Biopsy of the mass revealed giant cell lesion. Laboratory investigations showed hypercalcemia and hypophosphatemia with elevated parathyroid hormone level. A computerized tomography scan of the neck delineated an adenoma of the left superior parathyroid gland, which was surgically removed. The left inferior parathyroid was also enlarged and was removed. Histological diagnosis confirmed double parathyroid adenomas. The rarity and the interesting clinical presentation of such association are discussed.     

Ethical issues in non-heart-beating donation

A shortage of organ donors and the large number of patients desperately waiting for kidney transplant have led to the search for new sources of transplantable organs. The waiting list has grown at an alarming rate resulting in increased waiting times and deaths. The introduction of non heart beating (NHB) donation programmes generates a lot of ethical issues. How should death of a patient be defined in the case of NHB donation? Is there a strict separation of responsibilities of the medical teams in the different phases of the procedure (patient treatment and actual donation)? How should consent be obtained? Is sufficient respect and care given to the patient and his family? How is the viability of the organs assessed and how should the organs be allocated? We believe that it is very important to debate these issues and to try to outline an ethical framework for NHB donation that can enjoy the widest possible community support.     

The Edpm5 locus prevents the 'angiogenic switch' in an estrogen-induced rat pituitary tumor

Edpm5 is one member of a group of quantitative trait loci that are responsible for the difference in susceptibility to estrogen-induced prolactinoma between the Fischer 344 (F344) and Brown Norway (BN) strains. Upon chronic estrogen treatment F344 rats develop large, hemorrhagic and invasive pituitary tumors, which exhibit both tumor angiogenesis and neoplasia. In contrast, BN rats do not develop a tumor despite an estrogen-induced increase in lactotroph density. To investigate the role of Edpm5 in the development of these tumors, we have generated a novel congenic rat strain F344.BN-Edpm5BN by introgressing the segment of rat chromosome bearing Edpm5 from BN into the F344 strain background. Phenotypic differences between F344 and F344.BN-Edpm5BN must be due to a gene(s) within the chromosomal interval encompassing Edpm5. Through use of these strains, we find that Edpm5 specifically regulates the switch to angiogenic phenotype, independent of neoplasia. The F344.BN-Edpm5BN rats developed tumors, which exhibited significant growth, 7-fold greater mass than the pituitary of untreated rats, and neoplasia indistinguishable from that of the F344 strain. However, the F344.BN-Edpm5BN rat tumor had a non-angiogenic phenotype. After chronic estrogen treatment, there was no increase in microvessel count over untreated controls in F344.BN-Edpm5BN tumors, whereas F344 rat tumors showed a significant increase (P < 0.0005). The ultrastructural morphology of the pituitary blood vessels also did not show significant angiogenesis associated changes in F344.BN-Edpm5BN rat pituitary tumors. In contrast the parental strain F344 had pronounced angiogenic activity. The F344.BN-Edpm5BN strain also fails to express VEGF at the high levels seen in the F344 rat pituitary after estrogen treatment. Hence at least one gene that has a large impact, directly or indirectly, on the switch to angiogenic phenotype must reside within the chromosomal interval that is the Edpm5 quantitative trait locus.     

Can we predict 22q11 status of fetuses with tetralogy of Fallot?

OBJECTIVE: To determine if chromosome 22q11 deletion status can be predicted in fetuses with tetralogy of Fallot as regards additional phenotypic anomalies. METHODS: One hundred and fifty-one consecutive fetuses with tetralogy of Fallot without or with pulmonary atresia were screened for 22q11 deletion. Additional echographic features [increased nuchal translucency (NT), intrauterine growth retardation (IUGR), polyhydramnios, extracardiac malformations, pulmonary arteries abnormalities] were noted. RESULTS: Twenty-five fetuses had a 22q11 deletion (16.6%). Increased NT, polyhydramnios and IUGR were more frequent in fetuses with 22q11 deletion as well as pulmonary arterial abnormalities. When these different features were present in the same fetus with tetralogy of Fallot, 22q11 deletion can be predicted with a sensitivity of 88%. CONCLUSION: Simple echographic features can help to predict 22q11 status in fetuses with tetralogy of Fallot. This may improve the efficiency of prenatal screening for this defect.