Application of multiplex ligation-dependent probe analysis to define a small deletion encompassing PMP22 exons 4 and 5 in hereditary neuropathy with liability to pressure palsies

Hereditary neuropathy with liability to pressure palsies arises as a result of defects at the chromosome 17p11.2-12 locus and in 84% of cases a 1.5 Mb deletion containing the PMP22 gene is detected by analysis that utilises polymorphic (CA)_n repeat markers which flank this gene. We report the clinical and electrophysiological findings observed in a kindred with three members affected by HNPP due to a deletion containing exons 4 and 5 of the PMP22 gene. This small deletion cannot be detected using standard analysis with polymorphic (CA)_n repeat markers and a definitive diagnosis was made by multiplex ligation-dependent probe analysis of PMP22 exons 1A-5. MLPA can be readily utilised as a routine diagnostic laboratory test to detect the common HNPP 1.5 Mb deletion, as well as the reciprocal 1.5 Mb insertion observed in CMT1A, but has the advantage over other diagnostic techniques of being able to define single exon deletions.     

Descending projections to the inferior colliculus from the posterior thalamus and the auditory cortex in rat,cat, and monkey

Projections from the posterior thalamus and medial geniculate body were labeled retrogradely with wheat germ agglutinin conjugated to horseradish peroxidase injected into the rat, cat, and squirrel monkey inferior colliculus. Neurons were found ipsilaterally in the (1) medial division of the medial geniculate body, (2) central gray, (3) posterior limitans nucleus, and the (4) reticular part of the substantia nigra. Bilateral projections involved the (5) peripeduncular/suprapeduncular nucleus, (6) subparafascicular and posterior intralaminar nuclei, (7) nucleus of the brachium of the inferior colliculus, (8) lateral tegmental/lateral mesencephalic areas, and (9) deep layers of the superior colliculus. The medial geniculate projection was concentrated in the caudal one-third of the thalamus; in contrast, the labeling in the subparafascicular nucleus, substantia nigra, and central gray continued much further rostrally. Robust anterograde labeling corresponded to known patterns of tectothalamic projection. Biotinylated dextran amine deposits in the rat inferior colliculus revealed that (1) many thalamotectal cells were elongated multipolar neurons with long, sparsely branched dendrites, resembling neurons in the posterior intralaminar system, and that other labeled cells were more typical of thalamic relay neurons; (2) some cells have reciprocal projections. Similar results were seen in the cat and squirrel monkey. The widespread origins of descending thalamic influences on the inferior colliculus may represent a phylogenetically ancient feedback system onto the acoustic tectum, one that predates the corticocollicular system and modulates nonauditory centers and brainstem autonomic nuclei. Besides their role in normal hearing such pathways may influence behaviors ranging from the startle reflex to the genesis of sound-induced seizures.     

Tracheo-oesophageal fistula. A rare complication of percutaneous tracheostomy

Percutaneous tracheostomy is more and more used in the intensive care units. However, it's not devoid of risks. We report the case of a patient who developed a tracheo-esophageal fistula discovered after removal of the cannula 23 days after tracheotomy. During the procedure, difficulties occurred during the insertion of the cannula. This case report reminds the importance of a peroperative continuous endoscopic guidance and the need of a rigorous learning.     

Follow-up care of breast cancer survivors

Breast cancer survivors may have several medical and psychosocial concerns in follow-up care. Women with a history of breast cancer should be followed for local-regional recurrence or metastatic disease, as well as for the development of a second primary breast cancer in the contralateral breast. Regular follow-up visits can foster an ongoing patient-clinician relationship both to ensure adequate surveillance and so that symptoms of recurrence or complications of therapy will be reported by the patient and addressed promptly. There are multiple possible long-term complications that may arise following breast cancer treatment, many of which may be ameliorated with various therapies. Clinicians can also provide guidance and counseling as well as psychosocial support to patients regarding medical and psychosocial decisions that may be affected by their personal history of breast cancer.     

Cost-Effectiveness of Switching to Exemestane after 2 to 3 Years of Therapy with Tamoxifen in Postmenopausal Women with Early-Stage Breast Cancer

OBJECTIVES: Data from the Intergroup Exemestane Study (IES) suggest that switching to the aromatase inhibitor, exemestane, after 2 to 3 years of tamoxifen therapy prolongs disease-free survival versus continuing on tamoxifen therapy. We sought to evaluate the cost-effectiveness of this management strategy. METHODS: A Markov model was developed to predict patients' transitions across various health states based on treatment strategy (continuing tamoxifen vs. switching to exemestane), breast cancer status (no recurrence, local or distant recurrence, contralateral breast cancer), and other related health events (osteoporosis, endometrial cancer, death). Rates of disease-related events (recurrence and contralateral breast cancer) were estimated using data from the IES. Survival and lifetime medical-care costs by type of disease-related event were estimated using SEER-Medicare data. The model was used to estimate direct costs (in 2004 US dollars), life expectancy, quality-adjusted life-years (QALYs), and incremental cost-effectiveness. RESULTS: Switching to exemestane versus continuing tamoxifen therapy was associated with increased disease-free survival (181 vs. 172 months), QALYs (12.21 vs. 11.89), and net discounted lifetime costs of cancer care ($12,124 vs. $7724 per patient). The incremental cost-effectiveness ratio of exemestane was $20,100 per QALY gained (95% confidence interval: $12,100, $59,000). Sensitivity analyses showed that results were robust to plausible variations in recurrence rates, costs, and utilities. CONCLUSIONS: Switching postmenopausal early-stage breast cancer patients to exemestane after 2 to 3 years of tamoxifen appears to be a cost-effective treatment strategy versus completing a 5-year course of tamoxifen.     

Is axillary lymph node dissection indicated for early-stage breast cancer? A decision analysis.

PURPOSE: Axillary lymph node dissection (ALND) has been a standard procedure in the management of breast cancer. In a patient with a clinically negative axilla, ALND is performed primarily for staging purposes, to guide adjuvant treatment. Recently, the routine use of ALND has been questioned because the results of the procedure may not change the choice of adjuvant systemic therapy and/or the survival benefit of a change in adjuvant therapy would be small. We constructed a decision model to quantify the benefits of ALND for patients eligible for breast-conserving therapy. METHODS: Patients were grouped by age, tumor size, and estrogen receptor (ER) status. The model uses the Oxford overviews and three combined Cancer and Leukemia Group B studies. We assumed that patients who did not undergo ALND received axillary radiation therapy and that the two procedures are equally effective. All chemotherapy combinations were assumed to be equally efficacious. RESULTS: The largest benefits from ALND are seen in ER-positive women with small primary tumors who might not be candidates for adjuvant chemotherapy if their lymph nodes test negative. Virtually no benefit results in ER-negative women, almost all of whom would receive adjuvant chemotherapy. When adjusted for quality of life (QOL), ALND may have an overall negative impact. In general, the benefits of ALND increase with the expected severity of adjuvant therapy on QOL CONCLUSION: Our model quantifies the benefits of ALND and assists decision making by patients and physicians. The results suggest that the routine use of ALND in breast cancer patients should be reassessed and may not be necessary in many patients.     

Maternal citrulline supplementation enhances placental function and fetal growth in a rat model of IUGR: involvement of insulin-like growth factor 2 and angiogenic factors

Objective: To determine the effects of maternal citrulline supplementation on fetal growth and placental efficiency in a rat model of intrauterine growth restriction (IUGR) induced by maternal protein restriction.

Methods: Pregnant Sprague–Dawley rats were randomly assigned to three groups: NP (receiving a control 20% protein diet), LP (a 4% protein diet), or LP-CIT (an LP diet along with L-citrulline, 2?g/kg/d in drinking water). On the 15th and 21st day of gestation (GD15 and GD21, respectively), dams underwent a C-section, by which fetuses and placentas were extracted. The expression of genes involved in placental growth and angiogenesis was studied by quantitative RT-PCR.

Results: Maternal citrulline supplementation increased fetal weight at GD21, and fetal weight/placental weight ratio, an index of placental efficiency, from mid gestation (p?Igf2-P0, a placenta-specific variant of insulin-like growth factor 2 (Igf2) gene, and Vegf and Flt-1, involved in angiogenic pathways, was enhanced in the LP-CIT group (versus NP, p?p?p?Igf2-P0, Vegf, and Flt-1, respectively).

Conclusions: In a model of IUGR induced by protein deprivation, citrulline enhances fetal growth, placental efficiency, and the expression of genes involved in angiogenesis. The relevance of such effect in human pregnancies complicated by IUGR warrants further study.     

The pyramidal neurons in layer III of cat primary auditory cortex (AI)

The neuronal architecture of pyramidal cells in layer III of the primary auditory cortex (AI) of adult cats was examined as a prelude to connectional and fine structural studies; in a further paper, the results of parallel studies of non-pyramidal layer III cells are presented. Layer III is about 400 micron thick, comprises about one-quarter of the thickness of AI, and lies some 400-800 micron deep to the pial surface. It is distinguished in Nissl, fiber, and Golgi preparations from layers II and IV, and also on connectional grounds, since its neurons are one of the principal inputs to the contralateral AI. Layer III may be divided into two roughly equal tiers on the basis of its neuronal and cytoarchitecture. Layer IIIa is populated by small cells with oval somata and many tiny pyramidal cells; the fiber architecture is dominated by radial bundles of medium-sized axons interspersed among columns of apical dendrites arising from deeper-lying pyramidal cells. In layer IIIb medium-sized and large pyramidal cells are more numerous, and the fiber architecture has a different, much denser texture, including extensive lateral components which invade layer IV, and large contingents of descending, probably corticofugal, axons. Five kinds of pyramidal neurons occur in Golgi preparations. Most numerous are the small, medium-sized, and large pyramidal cells; the two types of star pyramidal neurons are less common. The small pyramidal cell has a limited dendritic field and rather delicate dendrites; all but the apical one usually end in layer III. The medium-sized pyramidal cell is the most common neurons, and its rich basilar dendritic arbors are conspicuous, with their many dendritic appendages, in the layer III neuropil; their distal dendrites spread into layer IV. The largest pyramidal cells lie mainly in layer IIIb, and their lateral dendrites often mark the layer IIIb-IVa border. The apical dendrites of medium-sized and large pyramidal cells often extend to layer Ib, where they branch obliquely. The axons of these cells branch laterally after descending through layer III and toward the white matter. Often secondary or tertiary branches reascend to layer IV and more superficially; there is considerable stereotypy in this branching pattern. These numerous secondary branches contribute heavily to the layer IIIb-IVa lateral fiber plexus. The fourth variety of pyramidal cell has a round soma and a stellate dendritic field whose distal branches extend from layer V to layer I, but whose axon is chiefly in layer III. Finally, a star pyramidal cell with long lateral basilar arbors but rather smooth dendrites completes the picture.(ABSTRACT TRUNCATED AT 400 WORDS)     

Physiopathologie de la prééclampsie

Preeclampsia is agestational complication that classically appears from the start of the second trimester and which is specific to humans.