Modified anterior intercostal artery perforator flap (AICAP) for autologous breast volume restoration after explantation.

Explantation of breast implants has become increasingly common. This study aimed to analyze breast auto-augmentation following implant explantation (using a laterally designed anterior intercostal artery perforator [AICAP] flap) in patients who did not need new implants and required volume preservation. Twenty-four patients (48 breasts) aged 31-67 years (mean, 52.4 years) with body mass index (BMI) between 24.43 and 29.34 (mean, 27.32) kg/m2 underwent this procedure. All patients had implant-related problems, such as recurrent capsular contracture (n=11), seroma (n=2), animation deformity (n=3), rupture-induced bleeding (n=5), and breast implant disease (n=3). Sizes of implants removed ranged from 215 to 355 ml. The mean flap size was 23.9 cm × 7.5 cm, and the average flap thickness was 2.3 cm (range, 2.0-3.2 cm). Flap survival was clinically examined postoperatively by ultrasonography. Pre- and postoperative final breast volumes were compared by direct patient observation and independent photograph observation by three plastic surgeons according to a 4-point scale (bad=1, regular=2, good=3, and excellent=4) and the brassiere size. All flaps were completely viable after harvesting. No postoperative signs of fat necrosis were observed, and independent plastic surgeon evaluation revealed good and excellent results in all cases. Patient satisfaction evaluated by BREAST-Q data was >90%. This new design, AICAP flap (with a lateral thoracic extension), can be safely used for breast volume restitution after breast implant explantation with high patient satisfaction. This flap exhibited reasonable potential of providing additional volume in patients who undergo implant explantation and require the preservation of similar volume.

Acquired MET expression confers resistance to EGFR inhibition in a mouse model of glioblastoma multiforme.

Glioblastoma multiforme (GBM) is an aggressive brain tumor for which there is no cure. Overexpression of wild-type epidermal growth factor receptor (EGFR) and loss of the tumor suppressor genes Ink4a/Arf and PTEN are salient features of this deadly cancer. Surprisingly, targeted inhibition of EGFR has been clinically disappointing, demonstrating an innate ability for GBM to develop resistance. Efforts at modeling GBM in mice using wild-type EGFR have proven unsuccessful to date, hampering endeavors at understanding molecular mechanisms of therapeutic resistance. Here, we describe a unique genetically engineered mouse model of EGFR-driven gliomagenesis that uses a somatic conditional overexpression and chronic activation of wild-type EGFR in cooperation with deletions in the Ink4a/Arf and PTEN genes in adult brains. Using this model, we establish that chronic activation of wild-type EGFR with a ligand is necessary for generating tumors with histopathological and molecular characteristics of GBMs. We show that these GBMs are resistant to EGFR kinase inhibition and we define this resistance molecularly. Inhibition of EGFR kinase activity using tyrosine kinase inhibitors in GBM tumor cells generates a cytostatic response characterized by a cell cycle arrest, which is accompanied by a substantial change in global gene expression levels. We demonstrate that an important component of this pattern is the transcriptional activation of the MET receptor tyrosine kinase and that pharmacological inhibition of MET overcomes the resistance to EGFR inhibition in these cells. These findings provide important new insights into mechanisms of resistance to EGFR inhibition and suggest that inhibition of multiple targets will be necessary to provide therapeutic benefit for GBM patients.

[Acute intermittent porphyria in 2 Moroccan families. Clinical and biological study]. / La porphyrie aiguë intermittente chez deux familles marocaines. Etude clinique et biologique.

Three patients from Moroccan kindreds with acute intermittent porphyria (AIP) are described. The propositus of family A originating from Mrirt, Morocco, is living in Embrun, France. This 26 year-old woman who experienced an acute attack with visceral manifestations presented an elevated urinary level of 5-ALA and PBG, and a half-normal activity in porphobilinogen deaminase (PBG-D) in red blood cells (RBC). The family's survey was carried out by measuring the PBG-D activity in RBC (normal values = 125 +/- 40 U). Three of the 16 subjects tested, beside the propositus, were found to be asymptomatic carriers (PBG-D < 70 U). The two patients of family B, originating from Tetouan in the Rif area, were living in Bastia, Corsica. The two brothers, respectively 37 and 39 years old, had a long history (6 years) of neuropsychiatric manifestations before the AIP diagnosis was evidenced by elevated urinary level of 5-ALA and PBG, and showed a partial deficiency, approximately, 50%, of PBG-D activity in RBC. The youngest patient also presented a peripheral neuropathy and recently died after surgery from an unknown reason at the age of 45.

Exacerbation of panic disorder during propranolol therapy.

Two patients experienced new onset or worsening of panic disorder during treatment with propranolol for tachycardia or palpitations associated with a diagnosis of mitral valve prolapse. Both patients had a family history of panic disorder; one also had a family history of mitral valve prolapse and depression. As antidepressant drugs can treat both depression and panic disorder, it would not be inconsistent that propranolol might exacerbate either disorder. Other possible interpretations of these two cases are discussed.