siRNA screening identifies differences in the Fanconi anemia pathway in BALB/c-Trp53+/- with susceptibility versus C57BL/6-Trp53+/- mice with resistance to mammary tumors.

BALB/c mice heterozygous for Trp53 develop a high proportion of spontaneous mammary tumors, a phenotype distinct from other mouse strains. BALB/c-Trp53+/- female mice, thus, resemble the hereditary Li-Fraumeni syndrome (LFS) characterized by early-onset of breast cancer, even though LFS involves TP53 mutations, which may involve not only loss- but also gain-of-function. Previous analysis of tumors in BALB/c-Trp53+/- females showed frequent loss of heterozygosity involving the wild-type allele of Trp53 and displayed characteristics indicative of mitotic recombination. Critical involvement of DNA double-strand break (DSB) repair dysfunction, particularly of homologous recombination (HR), was also noticed in the etiology of human breast cancer. To better define functional alterations in BALB/c-Trp53+/- mice, we applied a fluorescence-based DSB repair assay on mouse embryonic fibroblasts (MEFs) from BALB/c-Trp53+/- versus C57BL/6J-Trp53+/- mice. This approach revealed deregulation of HR but not non-homologous end-joining (NHEJ) in BALB/c-Trp53+/-, which was further confirmed for mammary epithelial cells. Screening of a small interfering RNA-library targeting DSB repair, recombination, replication and signaling genes, identified 25 genes causing differences between homologous DSB repair in the two strains upon silencing. Interactome analysis of the hits revealed clustering of replication-related and fanconi anemia (FA)/breast cancer susceptibility (BRCA) genes. Further dissection of the functional change in BALB/c-Trp53+/- by immunofluorescence microscopy of nuclear 53BP1, Replication protein A (RPA) and Rad51 foci uncovered differences in crosslink and replication-associated repair. Chromosome breakage, G2 arrest and biochemical analyses indicated a FA pathway defect downstream of FancD2 associated with reduced levels of BRCA2. Consistent with polygenic models for BRCA, mammary carcinogenesis in BALB/c-Trp53+/- mice may, therefore, be promoted by a BRCA modifier allele in the FA pathway in the context of partial p53 loss-of-function.

The precise midline forehead flap as a musculocutaneous flap.

The forerunners of the midline forehead flap date back to ancient India. The flap, as modified in this presentation, is often the treatment of choice for reconstructing significant full-thickness defects of the nose. The flap described is designed as a musculocutaneous flap incorporating skin, subcutaneous tissue, muscle, and aponeurosis. The enhanced vascularity of this flap allows precise thinning and tailoring at the distal end. A stepwise description of flap design is outlined.

Steps for a safer method of osteotomies in rhinoplasty.

Knowledge of osteotomy technique is essential to rhinoplasty. Using cadaver specimens, in addition to clinical observation, a safer method of osteotomy was acquired. Discussion of anatomy with reference to medial and lateral osteotomy follows. Several safety tips for each type of osteotomy are given.

The relationship of lateral osteotomies in rhinoplasty to the lacrimal drainage system.

Damage to the lacrimal drainage system is a potentially complicating factor in rhinoplasty utilizing lateral osteotomies. The authors present data from osteotomies performed on a series of fresh cadavers. Following completion of the osteotomies, the lacrimal sac and nasal lacrimal ducts were identified and cannulated. Soft tissue was dissected to demonstrate the osteotomy site. The specimen was inspected to delineate involvement (if any) of the lacrimal duct or sac. The proximity of the osteotomy site to the lacrimal drainage apparatus components was measured in each specimen. Various parameters were observed, including the effect of curved vs. straight osteotomies, guarded vs. unguarded osteotomies, and the effect of various widths of osteotomies. Likewise, the degree of risk to the lacrimal system was evaluated, and the technique of the novice and resident surgeon was compared to that of the experienced rhinoplastic surgeon. A low, curved osteotomy, performed with a sharp osteotome without subperiosteal tunnels, provides the safest maneuver. Lateral osteotomies, properly performed, prove to be an unusual cause of lacrimal drainage dysfunction.

Fascial pulley: cross-commissure lip reanimation for inferior division facial nerve paralysis.

The risks of causing further harm to the facial nerve are greater in surgery for partial facial paralysis. We present a new active and passive reconstruction technique for paralysis of the buccal-mandibular divisions of the facial nerve. Our fascial pulley technique of reanimation and suspension of the oral commissure produces no further injury to the facial nerve and the eyelids. In addition, it adds a better technique to the armamentarium of the reconstructive surgeon dealing with partial lower facial nerve paralyses.