Microbiomes as sources of emergent host phenotypes.

Microbial communities associated with animals exert powerful influences on host physiology, regulating metabolism and immune function, as well as complex host behaviors. The importance of host-microbiome interactions for maintaining homeostasis and promoting health raises evolutionarily complicated questions about how animals and their microbiomes have coevolved, and how these relationships affect the ways that animals interact with their environment. Here, we review the literature on the contributions of host factors to microbial community structure and corresponding influences of microbiomes on emergent host phenotypes. We focus in particular on animal behaviors as a basis for understanding potential roles for the microbiome in shaping host neurobiology.

Epidermal growth factor receptor distribution in burn wounds. Implications for growth factor-mediated repair.

Epidermal growth factor (EGF) along with several related peptide growth factors has been shown both in vivo and in vitro to accelerate events associated with epidermal wound repair. EGF and transforming growth factor alpha act by binding to a common EGF receptor tyrosine kinase thereby initiating a series of events which ultimately regulate cell proliferation. This study examined the immunohistochemical localization of EGF receptor (EGF-R) in burn wound margins, adjacent proliferating epithelium, and closely associated sweat ducts, sebaceous glands, and hair follicles. Tissue specimens removed during surgical debridement were obtained from full and partial thickness burn wounds in 32 patients with total body surface area burns ranging from 2 to 88%. In the early postburn period (days 2-4), prominent staining for EGF-R was found in undifferentiated, marginal keratinocytes, adjacent proliferating, hypertrophic epithelium, and both marginal and nonmarginal hair follicles, sweat ducts, and sebaceous glands. During the late postburn period (days 5-16), EGF-R was depleted along leading epithelial margins; however, immunoreactive EGF-R remained intensely positive in the hypertrophic epithelium and all skin appendages. Increased detection of immunoreactive EGF-R and the presence of [125I]EGF binding in the hypertrophic epithelium correlated positively with proliferating cell nuclear antigen distributions. Thus, the presence of EGF-R in the appropriate keratinocyte populations suggests a functional role for this receptor during wound repair. Dynamic modulation in EGF receptor distribution during the temporal sequence of repair provides further evidence that an EGF/transforming growth factor alpha/EGF-R-mediated pathway is activated during human wound repair.

Protection from pathogenic SIV challenge using multigenic DNA vaccines.

To assess DNA immunization as a strategy for protecting against HIV infection in humans, we utilized SIVmne infection of Macaca fascicularis as a vaccine challenge model with moderate pathogenic potential. We compared the efficacy of DNA immunization alone and in combination with subunit protein boosts. All of the structural and regulatory genes of SIVmne clone 8 were cloned into mammalian expression vectors under the control of the CMV IE-1 promoter. Eight M. fascicularis were immunized twice with 3 mg of plasmid DNA divided between two sites; intramuscular and intradermal. Four primed macaques received a further two DNA immunizations at weeks 16-36, while the second group of four were boosted with 250 microg recombinant gp160 plus 250 microg recombinant Gag-Pol particles formulated in MF-59 adjuvant. Half of the controls received four immunizations of vector DNA; half received two vector DNA and two adjuvant immunizations. As expected, humoral immune responses were stronger in the macaques receiving subunit boosts, but responses were sustained in both groups. Significant neutralizing antibody titers to SIVmne were detected in one of the subunit-boosted animals and in none of the DNA-only animals prior to challenge. T-cell proliferative responses to gp160 and to Gag were detected in all immunized animals after three immunizations, and these responses increased after four immunizations. Cytokine profiles in PHA-stimulated PBMC taken on the day of challenge showed trends toward Thl responses in 2/4 macaques in the DNA vaccinated group and in 1/4 of the DNA plus subunit vaccinated macaques; Th2 responses in 3/4 DNA plus subunit-immunized macaques; and Th0 responses in 4/4 controls. In bulk CTL culture, SIV specific lysis was low or undetectable, even after four immunizations. However, stable SIV Gag-Pol- and env-specific T-cell clones (CD3+ CD8+) were isolated after only two DNA immunizations, and Gag-Pol- and Nef-specific CTL lines were isolated on the day of challenge. All animals were challenged at week 38 with SIVmne uncloned stock by the intrarectal route. Based on antibody anamnestic responses (western, ELISA, and neutralizing antibodies) and virus detection methods (co-culture of PBMC and LNMC, nested set PCR- of DNA from PBMC and LNMC, and plasma QC-PCR), there were major differences between the groups in the challenge outcome. Surprisingly, sustained low virus loads were observed only in the DNA group, suggesting that four immunizations with DNA only elicited more effective immune responses than two DNA primes combined with two protein boosts. Multigenic DNA vaccines such as these, bearing all structural and regulatory genes, show significant promise and may be a safe alternative to live-attenuated vaccines.

Single-stage reconstruction of mandibular and soft tissue defects using a free osteocutaneous groin flap.

Microvascular reconstruction of the mandible and soft tissues using the composite groin flap is ideal in selected patients. No other available bone so closely approximates the mandible in both thickness and curvature as does the iliac crest. The soft tissues are available for reconstruction and may allow the surgeon to avoid a second flap, except in cases where both lining and cover are needed. The deep circumflex artery is of generous size, usually 2 to 2.5 mm in diameter, allowing greater reliability in the microvascular anastomoses. The flap has a fairly long vascular predicle, 6 to 8 cm. The ability of this flap to withstand irradiation and infection because of its blood supply permits early institution of postoperative radiotherapy and prevents bone loss due to small intraoral wound dehisicence or total flap loss. Although the donor site requires extensive dissection, it can be closed primarily, eliminating the need for skin grafts or other flaps. As further experience is gained with this flap, both the functional and cosmetic results should be improved. In patients undergoing resection of the remaining portion of the mandible, the symphysis or the anterior portion of the mandible, a procedure of this type should be done primarily to prevent deformity and to minimize disability for the patient.

Pectoralis major musculocutaneous flap: a new flap in head and neck reconstruction.

The pectoralis major musculocutaneous flap described by Ariyan has great potential in single stage reconstructions of the head and neck. The advantages of the flap are greater length, improved vascularity, bulk, and one-stage reconstruction of oropharyngeal defects. The flap was used successfully in eight patients to reconstruct large defects in the head and neck area. Experience to date indicates that this flap has greater versatility than the deltopectoral flap in one-stage head and neck reconstructions.

Interleukin-1 receptor antagonist as an adjunct in the treatment of Haemophilus influenzae otitis media in the chinchilla.

OBJECTIVES: This purpose of this study was to investigate the effect of blockade of the inflammatory cytokine pathway on experimentally induced otitis media in the chinchilla model. STUDY DESIGN: Pilot, randomized placebo-controlled trial. METHODS: Ampicillin-sensitive Haemophilus influenzae otitis media was induced in 45 adult chinchillas. The animals were randomly assigned to the following treatment groups: 1) transbullar injections (TBI) of interleukin-1 receptor antagonist (IL-1ra) and intramuscular ampicillin, 2) TBI of saline and intramuscular ampicillin, 3) TBI of IL-1ra and intramuscular sa-1 line or 4) TBI of saline and intramuscular saline. Blinded investigators measured resolution of otitis media by otomicroscopy, tympanogram, and culture results. RESULTS: Comparisons were made between the treatment groups to assess the ability of IL-1ra to assist with resolution of otitis media using exact two-group binomial tests with the StatXact statistical program. The group with TBI of IL-1ra and intramuscular ampicillin as a treatment demonstrated trends suggesting more rapid resolution of positive cultures and more rapid and complete return to normal results on tympanograms and otomicroscopic findings compared with the group treated with TBI of saline and intramuscular ampicillin. These trends did not achieve statistical significance with the relatively small sample sizes used in this pilot study. CONCLUSIONS: This investigation provides further evidence that the inflammatory cytokine cascade plays a significant role in the pathophysiology of otitis media and that modulation of this inflammatory pathway may provide novel and efficacious treatments for otitis media Further studies with larger groups of animals are warranted to determine whether the trends identified in this pilot study are reproducible and achieve statistical significance.

Radiation dermatitis.

Even in this era of modern radiotherapy, injuries associated with the medical and industrial use of radiation devices will continue to pose a difficult problem for the reconstructive surgeon. It must be borne in mind that the single most serious hazard to surgery in irradiated tissue is the lodgement of bacteria in tissue rendered avascular by the radiation and the secondary necrosis from the infection itself. The basic principles of wound management must be augmented by thorough knowledge of the use of well-vascularized muscle and musculocutaneous flap to provide adequate, blood-rich, soft-tissue coverage.

Intraoral cancer of the minor salivary glands.

Intraoral minor salivary gland carcinomas are relatively uncommon. The glands are concentrated in the mucosa of the mouth but occur over a wide area in the head and neck region. Little is known about the etiologic factors responsible for these tumors. Histologically, most salivary gland tumors are similar to those occurring in the parotid gland, but are more likely to be malignant. The most common presentations is an asymptomatic submucosal mass on the palate in a patient in the fifth or sixth decade, although it can occur in any age group. Neck node metastases occur in about one fourth of these patients. Surgical resection is the treatment of choice; irradiation may be a useful adjunctive method of palliation. Multiple recurrences over a long period of time are the rule, with 5 year survival for all malignant lesions being 44.5 per cent. The survival decreases another 10 per cent for each succeeding 5-year period of follow-up.

Cutaneous melanoma of the head and neck.

Melanoma of the head and neck, if diagnosed early and treated with aggressive appropriate surgical therapy, is potentially curable in up to 80 to 90 per cent of the cases. The use of microscopic staging by level of invasion and thickness of the tumor is helpful in determining the appropriate surgical procedure for the individual patient and is of prognostic significance. If possible, prophylactic incontinuity regional node dissection should be performed for melanomas of the head and neck that have invaded to Level III or deeper, especially those that are greater than 1.5 mm in thickness. The histological status of the regional nodes is beneficial both therapeutically and prognostically, in that patients who have negative nodes have a better prognosis than those with microscopically positive nodes. Also, these patients with microscopically positive nodes have a much better survival than those with macroscopically positive nodes. Melanoma of the head and neck should be treated very aggressively with wide excision of the primary tumor in order to prevent local recurrence and further spread of the disease. Since surgical treatment is the only effective curative measure for melanoma, all localized tumor in the region of the primary and solitary distant metastasis should be removed if possible. The adjunctive use of chemotherapy and immunotherapy when regional nodes are involved with melanoma is being studied and may be of some benefit. The combinations of surgical therapy, chemotherapy, immunotherapy, and radiotherapy offers the patient with advanced disease significant palliation, sometimes for prolonged periods. The treatment of head and neck melanoma is best summarized by the statement in the December 4, 1965 of The Lancet.-.29 "The surgeon who first operates on a malignant melanoma has a great responsibility. Prompt and competent action will give the patient a chance of survival better than in most other forms of cancer. The only additional operative surgical skill required is the ability to cut and apply split skin grafts. If he lacks confidence therein, let the surgeon refer the case at once and certainly before he has ruined, by niggling interference, the patient's chance of survival."

Five-year history of the American Society of Plastic and Reconstructive Surgeons, 1974--1978.

This report was intended to summarize the significant happenings in the American Society of Plastic and Reconstructive Surgeons, and its affiliates, from the end of the annual meeting in 1973 to the end of the 1978 annual meeting. It was decided to not include our sister organizations--the American Association of Plastic Surgeons, the American Society for Aesthetic Plastic Surgery, the American Society of Maxillofacial Surgeons--because their historians publish periodic reports about their activities. I am sure that the future reports of historians will record with pride the continued growth and development of plastic surgery, because the future of our specialty has never seemed brighter.

Effects of topical applications of epidermal growth factor on wound healing. Experimental study on rabbit ears.

In wounds in rabbit ears, the application every 12 hours of an ointment containing epidermal growth factor appears to produce faster and better healing. The resulting epithelium is thicker and more cellular than in the untreated ear wounds, and more fibroblasts appeared sooner during the healing process. Less wound contracture occurred in the EFG-treated wounds, and wound maturation occurred earlier. The healed wounds that had been treated with EGF more closely resembled the surrounding normal tissue, producing less local deformity than in the controls. It is too early to know whether this will have clinical application, but other experiments are under way to further investigate the effects of EGF on wound healing.

Adriamycin extravasation.

Adriamycin extravasation creates a severe tissue necrosis which is unusual, because it may not appear until several weeks later, and may continue to worsen for several months. As soon as the progressive nature of the tissue necrosis is established, we recommend that an early wide excision be performed in an attempt to remove the necrotic area and the surrounding tissues containing the extravasated drugs--before it has had an opportunity to diffuse even further. Adequate debridement requires removal of any adjacent tissue that is indurated, reddened, edematous, or pale. Skin grafts take poorly if there are small amounts of Adriamycin left in the tissue of the recipient site. Synergistic effects with radiotherapy, and continued systemic Adriamycin therapy, can aggravate or recall necrosis. The administration of more dilute solutions of Adriamycin may decrease the hazard of extravasation necrosis.

Xeroradiography for non-metallic foreign bodies.

Xeroradiography can demonstrate many non-metallic foreign bodies that do not show by conventional radiography techniques. Two examples are shown.

Classification of oblique facial clefts with microphthalmia.

We believe the Tessier classification system facilitates the description of complicated facial clefts, and we describe its use in 4 cases--all of whom had variations of a Tessier-3 cleft. Microphthalmia is associated with the Tessier-3 cleft. Computerized axial tomography may be helpful in differentiating an extreme microphthalmia from a true anophthalmia, and in detecting bony clefts not seen on roentgenographic studies. Facial tomograms show that abnormalities of the medial wall of the orbit in the Tessier-3 cleft vary from actual clefts to widening of the ethmoid. In our experience (with 4 patients) mental retardation does not necessarily occur in patients with the Tessier-3 cleft and extreme microphthalmia. Abnormalities of the nasolacrimal apparatus may be the most constant finding in patients with the Tessier-3 cleft. Children with the Tessier-3 cleft should be identified early for purposes of determining the proper treatment and valid genetic counseling.

Esthesioneuroblastoma. Case report.

We present a case of esthesioneuroblastoma, and we emphasize the importance of considering this tumor in the differential diagnosis of primary intranasal carcinomas. Although the tumor is uncommon, we feel that many cases have been misdiagnosed histologically. The typical history in these patients is one of intermittent recurring epistaxis or nasal destruction and frequently, at the time of the initial examination, the tumor has reached a considerable size with evidence of local invasion.

Observations on the myth of "informed consent".

A series of 100 patients in a general plastic surgery population were interviewed by standard format to determine their retention rate of preoperative information given to them. An overall recall, or retention rate, of 35 percent was found.

Loss of silicone implants after subcutaneous mastectomy and reconstruction.

We studied 89 patients who had immediate or delayed placement of implants after subcutaneous mastectomies. The complications of infection, necrosis of the skin or areola, and extrusion of the prosthesis occurred in 28 percent of these patients, and the incidence was the same after immediate or delayed placement. Only one of the 45 patients who received prophylactic antibodies preoperatively developed an infection after insertion of the prosthesis. The late complications in some of these patients indicate the need for long-term follow-up.

Fluorescein test for prediction of flap viability during breast reconstructions.

The fluorescein test is a useful ancillary procedure for predicting the viability of breast flaps in reconstructive procedures after subcutaneous mastectomy or radial mastectomy.

Resection of a massive arteriovenous malformation of the head and neck.

We report a patient with a massive arteriovenous malformation of the head and neck treated by surgical extirpation of the lesion. Arteriography, hypotensive hypothermic anesthesia, and the intraoperative use of the Doppler flowmeter were most helpful in this case.