Evolving concepts in ventral hernia repair and physical therapy: prehabilitation, rehabilitation, and analogies to tendon reconstruction.

PURPOSE: The abdominal wall and musculoskeletal tendons share many anatomic, physiologic, and functional characteristics. This review aims to highlight these similar characteristics and to present a rationale why the treatment principles of successful musculoskeletal tendon reconstruction, including principles of surgical technique and physical therapy, can be used in the treatment of complex abdominal wall reconstruction or ventral hernia repair. METHODS: The MEDLINE/PubMed database was used to identify published literature relevant to the purpose of this review. CONCLUSIONS: There are several anatomical and functional similarities between the linea alba and musculoskeletal tendons. Because of this reason, many of the surgical principles for musculoskeletal tendon repair and ventral hernia repair overlap. Distribution of tension is the main driving principle for both procedures. Suture material and configuration are chosen to maximize tension distribution among the tissue edges, as seen in the standard of care multistrand repairs for musculoskeletal tendons, as well as in the small bites for laparotomy technique described in the STITCH trial. Physical therapy is also one of the mainstays of tendon repair, but surprisingly, is not routine in ventral hernia repair. The evidence surrounding physical therapy prehabilitation and rehabilitation protocols in other disciplines is significant. This review challenges the fact that these protocols are not routinely implemented for ventral hernia repair, and presents the rationale and feasibility for the routine practice of physical therapy in ventral hernia repair.

Osteocutaneous defects of the clavicle: two case reports, analysis of the literature, and a novel management algorithm.

Osteocutaneous defects of the clavicle follow surgical management of chronic infections, tumors, and trauma. There are several reconstructive options, but it is unknown whether the bone needs to be reconstructed, which flaps are the best for reconstruction, nor why certain flaps favored over other options for a given scenario. Factors such as wound etiology, defect size, patient demographics, and co-morbidities guide therapy. The management of osteocutaneous defects of the clavicle is herein reviewed. Two clinical cases are presented, literature discussing clavicle form and function, disease pathogenesis, and reconstructive approaches are analyzed, and a resultant algorithm proposed.

[Femur reconstruction using combined autologous fibula transfer and humeral allograft]. / Femurrekonstruktion mit kombiniertem autologem Fibulatransfer und Humerus-Allograft.

Wide resection far into the femoral metaphysis may be required to treat malignant bone tumors in the pediatric and adolescent patient population. Biological reconstruction using a free, vascularized fibular graft is a well-established surgical technique. A short remaining femoral medullary canal and a relatively small fibula diameter can make fixation of the vascularized bone transfer difficult. Stable fixation and short fusion times, however, can be achieved with the use of an additional humeral allograft and plate osteosynthesis.

Fetal rat amniotic fluid: transforming growth factor beta and fibroblast collagen lattice contraction.

BACKGROUND: In several mammalian animal models, early-gestational-age fetal wounds heal without scar, but wounds of late gestational age heal with scar. This change in wound healing phenotype can be a result of both intrinsic (i.e., cellular characteristics) and extrinsic (i.e., environmental) factors. Our question was: Does amniotic fluid (AF) influence the change from scarless to scar-forming repair in the rat? METHODS: Rat AF was investigated for its modulation of fibroblast-populated collagen lattice (FPCL) contraction and morphological changes of adult fibroblasts. AF was also assayed for transforming growth factor beta (TGF-beta) levels. Adult rat dermal fibroblasts in monolayer and incorporated into FPCLs were incubated with AF additions from gestational age 14, 16, 18, and 21 days at 10% (v/v). RESULTS: Day 14 AF significantly stimulated FPCL contraction, but AF of 16, 18, and 21 days inhibited FPCL contraction. Fluorescence histology identified microtubules and microfilaments in AF treated adult rat dermal fibroblasts. The staining pattern of microtubules in Day 14 AF-treated fibroblasts showed denser structures at the cell center. Cells incubated with Day 16 or 18 AF showed fine peripheral microtubules. A mink lung epithelial cell bioassay was used to analyze concentrations of TGF-beta in AF. TGF-beta levels were greatly elevated in Day 14 AF, but were relatively low in Day 16, 18 and 21 AF. The inhibitor of FPCL contraction from AF of Days 16, 18, and 21 was not identified. CONCLUSION: It is proposed that the robust expression of TGF-beta or cytoskeletal changes induced by Day 14 AF contributes to enhanced FPCL contraction.

Discoidin domain receptors and their ligand, collagen, are temporally regulated in fetal rat fibroblasts in vitro.

The biochemical regulation of collagen deposition during adult cutaneous wound repair is poorly understood. Likewise, how collagen is perceived and modulated in fetal scarless healing remains unknown. Recently, discoidin domain receptors-1 and 2 (DDR1 and DDR2) with tyrosine kinase activity have been identified as novel receptors for collagen. In light of these findings, it was speculated that the production of collagen receptors DDR1 and DDR2 by fetal fibroblasts may be temporally regulated to correlate with the ontogeny of embryonic scar formation. More specifically, because DDRs directly bind collagen and transmit the signals intracellularly, it was hypothesized that they may play an important role in fetal scarless healing by ultimately regulating and modulating collagen production and organization. As part of a fundamental assessment to elucidate the role of DDRs in scarless fetal wound repair, the endogenous expression of DDR1, DDR2, collagen I, and total collagen, as a function of fetal Sprague-Dawley rat skin fibroblasts of different gestational ages, representing scar-free (E16.5) periods was determined. Using explanted dermal fibroblasts of gestational days E13.5, E16.5, E18.5, and E21.5 (term gestation = 21.5 days) fetuses (n = 92), [3H]proline incorporation assay and Northern and Western blotting analysis were performed to compare the expressions of these molecules with scar-free and scar-forming stages of embryonic development. These results revealed a pattern of increasing collagen production with increasing gestational ages, whereas DDR1 expression decreased with increasing gestational age. This observation suggests that elevated levels of DDR1 may play an important role in scarless tissue regeneration by early gestation fetal fibroblasts. In contrast, DDR2 was expressed by fetal rat fibroblasts at a similar level throughout gestation. These data demonstrate for the first time the temporal expression of collagen and DDR tyrosine kinases in fetal rat fibroblasts as a function of gestational ages. Overall, these data suggest that differential temporal expression of the above-mentioned molecules during fetal skin development may play an important role in the ontogeny of scar formation. Future studies will involve the characterization of the biomolecular functions of these receptor kinases during fetal wound repair.

Cellular signaling by tyrosine phosphorylation in keloid and normal human dermal fibroblasts.

Keloids represent a dysregulated response to cutaneous wounding that results in disfiguring scars. Unique to humans, keloids are characterized by an accumulation of extracellular matrix components. The underlying molecular mechanisms of keloid pathogenesis, however, remain largely uncharacterized. Similarly, cellular signaling mechanisms, which may indicate inherent differences in the way keloid fibroblasts and normal human dermal fibroblasts interact with extracellular matrix or other cells, have not been investigated. As part of a fundamental assessment of cellular response to injury in keloid fibroblasts, phosphorylation studies were performed using three different keloid (n = 3) and normal human dermal (n = 3) fibroblast cell lines. These studies were undertaken to elucidate whether keloid and normal human dermal fibroblasts exhibit different tyrosine kinase activity. Initially, distinct tyrosine phosphorylation patterns of keloid and normal human dermal fibroblasts were demonstrated. Next, the phosphorylation patterns were correlated with known molecules that may be important to keloid pathogenesis. On the basis of molecular weight, it was hypothesized that the highly phosphorylated bands seen in keloid fibroblasts represented epidermal growth factor receptor (EGFR); discoidin domain receptor 1 (DDR1); and Shc, an adaptor protein known to bind many tyrosine kinases, including EGFR and DDR1. Individual immunoblotting using EGFR, DDR1, and Shc antibodies revealed greater expression in keloid fibroblasts compared with normal human dermal fibroblasts. These data substantiate for the first time the finding of greater phosphorylation by the above-mentioned molecules, which may be important in keloid pathogenesis.

Differential expression of receptor tyrosine kinases and Shc in fetal and adult rat fibroblasts: toward defining scarless versus scarring fibroblast phenotypes.

The remarkable ability of the fetus to heal early gestation skin wounds without scarring remains poorly understood. Taking advantage of recent advances in signal transduction, the tyrosine phosphorylation patterns of fetal rat fibroblasts, representing the scarless cutaneous repair phenotype, and adult rat fibroblasts, representing scarforming phenotype, were examined whether there were inherent differences in cellular signaling. Specifically, correlation of the phosphorylation patterns with the expression levels of the signaling molecules that transmit information from the plasma membrane receptor to the nucleus was sought. By using three different cell lines of explanted fibroblasts from gestational day 13 fetal rat skin (n = 24) and 1-month-old postnatal adult rat skin (n = 3), immunoblotting was performed to compare tyrosine phosphorylation patterns. The results revealed five major protein bands of interest in fetal rat fibroblasts, but not in the adult rat fibroblasts. These phosphorylated protein bands are of interest because of their possible role in wound repair and may have the potential to regulate cellular responses to the extracellular matrix and their secondary signaling molecules. It was hypothesized that these bands represented receptor tyrosine kinases, epidermal growth factor receptor, and discoidin domain receptor 1, and their downstream adaptor protein Shc that binds receptor tyrosine kinases to transduce signals intracellularly. Furthermore, elevated expression of platelet-derived growth factor receptor-beta in adult compared with fetal fibroblasts was demonstrated, suggesting that decreased expression of certain growth factors may also be important for the scarless phenomenon to occur.

Phosphatase activity and lead resistance in Citrobacter freundii and Staphylococcus aureus.

It has been previously reported that strains of Citrobacter freundii and of Staphylococcus aureus accumulated lead as Pb-phosphate when grown on media supplemented with high levels of lead salts. Phosphatase activity, which has been postulated to be involved in lead accumulation, was unrelated to lead resistance, resistant and sensitive cells displaying similar levels and patterns of enzyme activity.

Germ cell loss in the XXY male mouse: altered X-chromosome dosage affects prenatal development.

Male mammals with two X chromosomes are sterile due to the demise of virtually all germ cells; however, the underlying reasons for the germ cell loss remain unclear. The use of a breeding scheme for the production of XXY male mice has allowed us to experimentally address the question of when and why germ cells die in the XXY testis and whether the defect is due to the presence of an additional X chromosome in the soma, the germ cells themselves, or both. Our studies demonstrate that altered X-chromosome dosage acts to impair germ cell development in the testis at a much earlier stage than suggested by previous studies of XX sex-reversed males or XX/XY chimeras. Specifically, we noted significantly reduced germ cell numbers in the XXY testis during the period of germ cell proliferation in the early stages of testis differentiation. Although the somatic development of the XXY testis is morphologically and temporally normal, our studies indicate that germ cell demise reflects a defect in somatic/germ cell communication, since, in an in vitro system, the proliferative potential of fetal germ cells from XXY males is indistinguishable from that of normal males.

Lead resistance and sensitivity in Staphylococcus aureus.

Five lead-resistant strains of Staphylococcus aureus were isolated. Plasmid-free lead-sensitive variants were obtained from the three plasmid-bearing strains. Lead-resistant strains tolerated an approximately 600 x higher Pb(NO3)2 concentration than lead-sensitive strains. Both types of strains initially bound lead, but only the resistant strains accumulated the metal as an intracellular lead-phosphate.

Degradation of meta-trifluoromethylbenzoate by sequential microbial and photochemical treatments.

m- and p-trifluoromethyl (TFM)-benzoates are incompletely degraded by aerobic bacteria that catabolize alkylbenzoates; biodegradation ceases after ring-fission with the accumulation of a trifluoromethyl muconate semialdehyde (2-hydroxy-6-oxo-7,7,7-trifluorohepta-2,4-dienoate, TFHOD) which is resistant to biochemical attack. A bacterium (Strain V-1), isolated from sea-water, grew aerobically on benzoate or m-toluate. Cells grown on benzoate or m-toluate oxidized both compounds at similar relative rates. Catabolism involved benzoate 1,2-dioxygenase (decarboxylating) and meta-cleavage to yield muconate semialdehydes. Cells grown on benzoate metabolized m-TFM-benzoate to TFHOD. The ring-fission products from m-toluate and TFHOD were degraded by sunlight, and equimolar fluoride was released from TFHOD. Sequential biochemical and photochemical treatment allowed the destruction of m-TFM-benzoate beyond the biochemically recalcitrant intermediate TFHOD.

Dramatic favorable responses of children with learning disabilities or dyslexia and attention deficit disorder to antimotion sickness medications: four case reports.

Responses of four learning disabled children who showed dramatic improvements to one or more antimotion-sickness-antihistamines and -stimulants are described qualitatively. These cases were selected from a prior quantitative study in which three antihistamines (meclizine, cyclizine, dimenhydrinate) and three stimulants (pemoline, methylphenidate, dextroamphetamine) were tested in variable combinations (using a specific clinical method) for favorable responses by 100 children characterized by diagnostic evidence of learning disabilities and cerebellar-vestibular dysfunctioning. Pending validation in double-blind controlled studies, these qualitative results suggest that the "cerebellar-vestibular (CV) stabilizing" antimotion-sickness medications, Piracetam included, and their combinations may be shown to be therapeutically useful in treating children with learning disabilities or dyslexia and attention deficit disorder.

The diagnostic value of cerebellar-vestibular tests in detecting learning disabilities, dyslexia, and attention deficit disorder.

Neurological and optokinetic measures of cerebellar-vestibular (CV) dysfunctioning were shown to be of significant diagnostic value in differentiating between learning disabled subjects and controls matched for chronological age, sex, handedness, IQ, and background (ns = 35). Although traditionally used electronystagmographic positional and caloric parameters were not similarly discriminating, quantitative measures of vertical nystagmus in various eyes-closed positions appeared to have diagnostic potential and were related significantly to such CV-determined neurological signs as positive monopedal Romberg. As a substantial majority of learning disabled (82.9%) evidenced ADD-like symptoms and since learning disabled subsamples with and without Attention Deficit Disorder (ADD) shared similar coexisting symptoms and CV signs, it appeared probable that learning disabilities and ADD were reflections of the same underlying CV determinants.

Abnormal optokinetic and perceptual span parameters in cerebellar-vestibular dysfunction and related anxiety disorders.

As prior studies indicated abnormal cerebellar-vestibular-based sensorimotor mechanisms and neurological and ENG diagnostic parameters in anxiety disorders and because ocular fixation and sequential scanning are cerebellar-vestibular-modulated, it appeared reasonable to measure these and related ocular functions in matched samples of anxiety-disordered and control subjects. In this study, the optokinetically-determined fixation, sequential scanning, and perceptual span capacities obtained by means of a newly revised blurring-speed method were significantly lower or impaired in 70 anxiety-disordered patients vs 70 controls. Such data supported further the hypothesis that there may be cerebellar-vestibular predispositions to anxiety disorders and the optokinetically-based tracking method may prove useful in separating a diverse array of CV-determined or related anxiety symptoms from those of other origins. However, independent validation as well as additional studies of anxiety disorders using larger samples vs random or "normal" controls are required before conclusions are justified.

The cerebellar-vestibular predisposition to anxiety disorders.

To test for a cerebellar-vestibular (CV) predisposition to anxiety disorder, 402 consecutively referred subjects with varying anxiety symptoms were separated into eight DSM-III--R diagnostic categories and evaluated for CV dysfunction, using neurological and electronystagmographic (ENG) examinations. Of the total sample, 94% evidenced CV-dysfunction on the basis of two or more abnormal neurological or ENG parameters per subject. All DSM-III--R diagnostic anxiety-disorder categories contained a high percentage of abnormal neurological and ENG parameters, regardless of the size of the subsample. Moreover, each DSM-III--R subsample of anxiety disorders contained additional coexisting symptoms of anxiety sufficient to overlap with and form the basis for diagnosis of most other DSM-III--R anxiety-disorder categories. Such findings suggested that anxiety disorders, regardless of surface descriptions and DSM-III--R category, have a common denominator with varying symptom-shaping mechanisms and that this denominator is significantly CV-based. Although the above findings do not justify cause and effect convictions, they have provided crucial insights leading to (1) a proposed functional classification based on underlying determining mechanisms rather than on descriptions of symptoms, (2) a possible relationship between anxiety and learning disorders, and (3) a new method of treating these disorders by means of CV-stabilizing medications in conjunction with traditional approaches. Needless to say, independent and controlled studies, including comparisons with "normal" persons, are required for both validation and elucidation of those specific determining vs compensatory mechanisms and related diagnostic parameters crucial for symptom formation.

Abnormal optokinetic and perceptual span parameters in cerebellar-vestibular dysfunction and learning disabilities or dyslexia.

To measure the ocular fixation and sequential scanning dysfunction assumed responsible for the visual reading symptoms which characterize dyslexia or learning disabilities, an optokinetically based tracking method was devised. This method quantitatively demonstrated significantly reduced fixation, tracking, and perceptual or visual-span scores as well as "movement illusions" for 70 cerebellar-vestibular dysfunctioning persons with learning disabilities vs 70 controls. Such data tended to validate the hypothesis that cerebellar-vestibular-determined fixation and tracking mechanisms predispose dyslexic or learning disabled individuals to visual reading disorders. Moreover, a newly revised method is presented which may prove useful in rapidly screening and diagnosing cerebellar-vestibular-determined reading and learning disorders from those of other origins. Additional independent studies using significantly larger samples and asymptomatic or "normal" controls are required for further validation and development of the method.

A cerebellar-vestibular explanation for fears/phobias: hypothesis and study.

To clarify and test the cerebellar-vestibular (CV) basis of fears/phobias, responses of 4000 learning disabled children, adolescents, and adults with neurological and electronystagmographic (ENG) evidence of CV-dysfunction were analyzed for anxiety-related symptoms. Of this sample, 64.6% indicated fears/phobias; females were significantly more predisposed; mixed-handedness was significantly related to fears of heights and reduced vestibular response or asymmetric vestibular functioning. Also, adults had a higher incidence of the specific fears/phobias characterizing agoraphobia than children and adolescents. Analysis of factors reported as triggering the fears/phobias led to (1) a classification and theory of fears/phobias, obsessions/compulsions, and related anxiety symptoms based on realistic or traumatic, neurotic, and CV- or other CNS-based mechanisms rather than on DSM-III--R surface descriptions; (2) an understanding of the relationships between mitral valve prolapse, agoraphobia and panic episodes, as well as depression; and (3) new insights into differential diagnosis and selective treatment.

Nucleotide sequence of a chromosomal mercury resistance determinant from a Bacillus sp. with broad-spectrum mercury resistance.

A 13.5-kilobase HindIII fragment, bearing an intact mercury resistance (mer) operon, was isolated from chromosomal DNA of broad-spectrum mercury-resistant Bacillus sp. strain RC607 by using as a probe a clone containing the mercury reductase (merA) gene. The new clone, pYW33, expressed broad-spectrum mercury resistance both in Escherichia coli and in Bacillus subtilis, but only in B. subtilis was the mercuric reductase activity inducible. Sequencing of a 1.8-kilobase mercury hypersensitivity-producing fragment revealed four open reading frames (ORFs). ORF1 may code for a regulatory protein (MerR). ORF2 and ORF4 were associated with cellular transport function and the hypersensitivity phenotype. DNA fragments encompassing the merA and the merB genes were sequenced. The predicted Bacillus sp. strain RC607 MerA (mercuric reductase) and MerB (organomercurial lyase) were similar to those predicted from Staphylococcus aureus plasmid pI258 (67 and 73% amino acid identities, respectively); however, only 40% of the amino acid residues of RC607 MerA were identical to those of the mercuric reductase from gram-negative bacteria. A 69-kilodalton polypeptide was isolated and identified as the merA gene product by examination of its amino-terminal sequence.