Clinical relevance of parasternal uptake in sentinel node procedure for breast cancer

BACKGROUND AND OBJECTIVES: Preoperative lymphoscintigraphy contributes highly to the accuracy of the sentinel node procedure. Besides routing towards the axilla, in a number of patients additional parasternal focal accumulation may be observed. So far the clinical consequences of this parasternal uptake remains unclarified, i.e., whether any internal mammary lymph node uptake should be surgically biopsied. An analysis of all sentinel node procedures with parasternal uptake was performed. METHODS: Sixty-nine patients with scintigraphic parasternal uptake and with a minimal follow-up of 24 months, were selected from a prospective database. Tumor characteristics, treatment strategies, and recurrences of these patients were analyzed and subsequently matched against the present day indications for adjuvant treatment. RESULTS: During follow-up (median 41 months) only four (6%) patients developed systemic disease. Initially, three of these patients did not receive adjuvant chemotherapy. Two are alive without evidence of disease after treatment of these recurrences. Currently these patients would, initially, all have been eligible for chemotherapy based on tumor characteristics and age according to international guidelines. CONCLUSIONS: For the indication of adjuvant treatment, the status of the internal mammary lymph nodes was not relevant in our patients. Parasternal uptake is not an indication to extend the surgical procedure.     

Incipient CADASIL

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene. Knowledge of disease expression in young adult NOTCH3 mutation carriers (MCs) is limited. OBJECTIVE: To characterize clinical, neuropsychological, and radiological status in NOTCH3 MCs younger than 35 years. DESIGN: Clinical characterization and blinded survey comparing MCs with non-MCs. SETTING: Referral center. PARTICIPANTS: Individuals younger than 35 years who were at a 50% risk of a NOTCH3 mutation, from our CADASIL database. Thirteen individuals, from 8 families, met the criteria. METHODS: Comprehensive clinical, genetic, neuropsychological, and radiological investigations. Magnetic resonance images were scored according to a standardized white matter hyperintensities rating scale. RESULTS: Six individuals, from 5 families, were MCs. Clinical symptoms consisted of migraine (with aura), stroke, and stroke-like episodes. We did not find evidence for psychiatric disturbances, functional disability, or cognitive dysfunction, compared with non-MCs. Radiologically, a characteristic magnetic resonance imaging lesion pattern emerged for all MCs. This comprised white matter hyperintensities in the anterior temporal lobes, the frontal lobes, and the periventricular frontal caps. CONCLUSIONS: Migraine (with aura) and stroke can present in NOTCH3 MCs younger than 35 years; however, more importantly, physical function and cognition are intact. Possible subtle cognitive dysfunction needs to be assessed in a larger study. White matter hyperintensities on magnetic resonance imaging are characteristic, and are consistently visualized from the age of 21 years and onward. Awareness of the clinical and radiological features of CADASIL in those younger than 35 years should increase early diagnosis and allow for customized counseling of young adults from families with CADASIL.     

Porous polymethylmethacrylate as bone substitute in the craniofacial area

In craniofacial surgery, alloplastic materials are used for correcting bony defects. Porous polymethylmethacrylate (PMMA) is a biocompatible and nondegradable bone cement. Porous PMMA is formed by the classic bone cement formulation of methylmethacrylate liquid and PMMA powder in which an aqueous biodegradable carboxymethylcellulose gel is dispersed to create pores in the cement when cured. Pores give bone the opportunity to grow in, resulting in a better fixation of the prostheses. We evaluated the long-term results (n = 14), up to 20 years, of augmentations and defect fillings in the craniofacial area, with special interest in possible side effects and bone ingrowth. The evaluation consisted of a questionnaire, a physical examination, and a computed tomography (CT) scan. There were no side effects that could be ascribed to the porous PMMA. Twelve CT scans showed bone ingrowth into the prostheses, proving the validity behind the concept of porous PMMA.     

Left-right differences in Eustachian tube function in children with ventilation tubes

OBJECTIVE: To study the intraindividual variation in Eustachian tube (ET) function in children with ventilation tubes. METHODS: The forced response test, the pressure equilibration test and the sniff test were performed on both ears of 148 children. The results of both ears were compared. RESULTS: No systematic differences were found between the left and the right ears. However, the intraindividual variation was very pronounced. The variation in passive ET function within children was of similar magnitude as the variation in passive ET function between children. Twenty-eight percent of the children had different active ET function in both ears and 15% had an opposite result in each ear with respect to the sniff test. CONCLUSIONS: This study shows that ET function is much more a characteristic of the individual ear than of the individual child. These findings also question the validity of trials on ET function or middle ear disease that use the opposite ear as a control (split level design).     

LPS-induced expression of a novel chemokine receptor (L-CCR) in mouse glial cells in vitro and in vivo

There is increasing evidence that chemokines, specialized regulators of the peripheral immune system, are also involved in the physiology and pathology of the CNS. It is known that glial cells (astrocytes and microglia) express various chemokine receptors like CCR1, -3, -5, and CXCR4. We have investigated the possible expression of the known CC chemokine receptors (CCR1-8 and D6) in murine glial cells. In addition, we examined possible glial expression of the orphan CC chemokine receptor L-CCR that has been identified previously in murine macrophages. We report here expression of L-CCR mRNA in murine astrocytes and microglia. Furthermore, L-CCR mRNA expression was strongly induced after application of bacterial lipopolysaccharide (LPS), both in vitro and in vivo. Functional studies and binding experiments using biotinylated monocyte chemoattractant protein (MCP)-1 (CCL2) indicate that CCL2 could be a candidate chemokine ligand for glial L-CCR. Based on the data presented, it is suggested that L-CCR is a functional glial chemokine receptor that is important in neuroimmunology.     

Constitutive EGFR signaling confers a motile phenotype to neural stem cells

The epidermal growth factor receptor (EGFR) has been shown to play an important role in brain development, including stem and precursor cell survival, proliferation, differentiation, and migration. To further examine the temporal and spatial requirements of erbB signals in uncommitted neural stem cells (NSCs), we expressed the ligand-independent EGF receptor, EGFRvIII, in C17.2 NSCs. These NSCs are known to migrate and to evince a tropic response to neurodegenerative environments in vivo but for which an underlying mechanism remains unclear. We show that enhanced erbB signaling via constitutive kinase activity of EGFRvIII in NSCs sustains an immature phenotype and enhances NSC migration.