Exploring the acceptability of controlled human infection with SARSCoV2-a public consultation.

Rapid development of an effective vaccine for SARSCoV2 is a global priority. A controlled human infection model (CHIM) would accelerate the efficacy assessment of candidate vaccines. This strategy would require deliberate exposure of volunteers to SARSCoV2 with no currently available treatment and a small but definite risk of serious illness or death. This raises complex questions about the social and ethical acceptability of risk to individuals, given the potential benefit to the wider population, and as such, a study cannot be done without public involvement. We conducted a structured public consultation with 57 individuals aged 20-40 years to understand public attitudes to a CHIM, and pre-requisites for enrolment. The overall response to this strategy was positive, and many would volunteer altruistically. Carefully controlled infection is viewed as safer than natural exposure to wild virus. The prolonged social isolation required for the proposed CHIM is considered an obstacle but not insurmountable, with reasonable compensation and supportive care. Given the significant level of public interest, a CHIM should be done as open science with regular, controlled dissemination of information into the public domain. Importantly, there was a strong view that the final decision whether to conduct a CHIM should be in the hands of qualified and experienced clinician-scientists and the authorities.

Doxorubicin-induced impairment of wound healing in rats.

The mortality rate induced by 3 doses of iv doxorubicin was evaluated in F344 rats, and a dose of 8 mg doxorubicin/kg body weight was the maximum dose tolerated with an acceptable mortality rate. Rats treated with 8 mg doxorubicin/kg prior to or on the day of wounding demonstrated decreased wound breaking strength in incisional wounds at all intervals after wounding. Decreased amounts of collagen and DNA and less cellularity were noted in wound chambers from rats treated in the same manner. In both the incisional wound and wound chamber models, rats treated with doxorubicin 7 days after wounding showed a less dramatic healing impairment. No difference in collagen types was noted between chambers from the doxorubicin-treated and untreated rats. Doxorubicin also produced a significant reduction in platelet and white blood cell counts 1 week after it was administered. The data indicate that doxorubicin impedes healing by decreasing wound cellularity and collagen synthesis.

Preoperative or postoperative doxorubicin hydrochloride (adriamycin): which is better for wound healing?

The purpose of this study was to determine if any interval between preoperative or postoperative administration of doxorubicin hydrochloride (Adriamycin) and wounding would limit the impairment in healing induced by Adriamycin. The question was evaluated in 7 cm incisional wounds on the dorsal midline of rats. Preoperative Adriamycin was administered 42, 28, 21, 14, and 7 days before wounding, and wound breaking strengths (WBS) of the incisional wounds were measured 7, 18, and 28 days after wounding. Postoperative Adriamycin was administered 0, 7, 14, 21, and 28 days after wounding, and WBS were measured 7, 14, 28, 35, and 42 days after wounding. A similar and significant degree of impairment was induced in healing by all preoperative Adriamycin regimens evaluated. Postoperative Adriamycin administered up to 21 days after wounding induced a healing deficit that manifested 1 to 2 weeks after Adriamycin administration. Adriamycin administered 28 days after surgery induced no demonstrable impairment in WBS. In addition, Adriamycin never decreased the WBS of a wound after a certain degree of strength had been obtained. These results lead us to warn against the use of preoperative Adriamycin and support the use of postoperative Adriamycin administered 28 days after a surgical procedure.

Fibronectin in the tendon-synovial complex: quantitation in vivo and in vitro by ELISA and relative mRNA levels by polymerase chain reaction and northern blot.

An enzyme-linked immunosorbent assay was used to quantitate fibronectin (Fn) levels in the outer synovia (epitenon) and internal fibrous portion (endotenon) of chicken flexor tendon and sheath. Primary cell cultures from these tissues and their secretions also were assayed for Fn levels. The polymerase chain reaction (PCR) was used to determine relative steady-state levels of Fn mRNA in primary cultures of synovial and internal fibroblasts from chicken tendon, and Northern blot analysis was performed to verify relative levels of the Fn message. The epitenon contained 3.8-fold more Fn than did the endotenon, and the sheath synovium contained 21-fold more Fn than did the internal fibrous portion of sheath. Cells cultured from the epitenon produced 9.3 and 13-fold more cell-associated and secreted Fn, respectively, than did cultured endotenon fibroblasts. Sheath synovial cells produced 17 and 3.2-fold more cell-associated and secreted Fn, respectively, than did sheath internal fibroblasts. Levels of Fn mRNA, as measured by PCR and Northern blot, were 1.6 and 1.8-fold greater, respectively, in tendon synovial cells compared with tendon internal fibroblasts. The biologic reason for increased Fn in tendon synovium is not known. We theorize that Fn may stabilize tendon synovium to shear stress and may play a role in the modulation of synovial rheology in the normal tendon. In the injured tendon, Fn may be involved in the organization of collagen deposition or may act through association with growth factors to aid healing.

Insulin-like growth factor-I is expressed by avian flexor tendon cells.

Cells in normal tendon are in a resting G0 state, performing maintenance functions. However, traumatic injury introduces growth factors such as platelet-derived growth factor and insulin-like growth factor from blood as well as activates endogenous growth factors. These factors stimulate migration and proliferation of tendon cells at the wound area. Tendon cells require growth-promoting factors to transit the cell cycle. To evaluate the contribution of endogenous growth factors in tendon, extracts of the epitenon and internal compartment of avian flexor tendon as well as medium of cultured cells from the epitenon (tendon surface cells) and internal tendon (tendon internal fibroblasts) were collected to assess their ability to stimulate DNA synthesis. Acid-ethanol extracts of tissues and medium were chromatographed on a P-30 molecular sieve column and assayed for mitogenic activity by quantitating [3H]thymidine incorporation into tendon cell DNA. The extract from the internal tendon compartment was more stimulatory for DNA synthesis than that from the epitenon, particularly when tested on tendon internal fibroblasts. However, conditioned medium fractions from surface epitenon cells stimulated DNA synthesis to a high degree on both tendon surface cells and tendon internal fibroblasts. Conditioned medium from tendon internal fibroblasts was also stimulatory. An anti-insulin-like growth factor-I antibody ablated most of the mitogenic activity present in both tissues and conditioned medium. The levels of acid-extractable insulin-like growth factor-I in tendon were determined by competitive radioimmunoassay as 1.48+/-0.05 ng/g tissue for the epitenon and 3.83+/-0.03 ng/g tissue for the internal compartment. Results of Western immunoblots of conditioned medium revealed insulin-like growth factor-I at the 7.5 kDa position. Cultured tendon surface cells and tendon internal fibroblasts as well as cells in intact flexor tendon expressed insulin-like growth factor-I mRNA detected by reverse transcriptase-polymerase chain reaction. In situ hybridization histochemistry positively identified insulin-like growth factor-I mRNA in tendons from 52-day-old chickens. Platelet-derived growth factor was not detected at the protein or message levels. Furthermore, tendon surface cells and tendon internal fibroblasts both expressed receptors for insulin-like growth factor-I detected by flow cytometry. These data suggest that tendon cells express insulin-like growth factor-I mRNA and synthesize insulin-like growth factor-I in both the epitenon and the internal compartment of tendon, which is present in an inactive form, most likely bound to insulin-like growth factor-binding proteins.

Deformity correction and long-term survival in an infant with iniencephaly. Case report.

The authors describe the case of a male infant who was diagnosed prenatally as having iniencephaly. Since birth, the child has grown, thrived, and undergone two successful operations to correct his cervical deformity. This case demonstrates that the iniencephaly defect is not uniformly fatal and that neurosurgical intervention may offer significant improvement in the cervical deformity.

PDGF-BB, IGF-I and mechanical load stimulate DNA synthesis in avian tendon fibroblasts in vitro.

Resident cells in the surface epitenon and internal compartment of flexor tendons are subjected to cyclic mechanical load as muscle contracts to move limbs or digits. Tendons are largely tensile load bearing tissues and are highly matrix intensive with nondividing cells providing maintenance functions. However, when an injury occurs, tendon cells are stimulated to divide by activated endogenous growth factors and those from platelets and plasma. We hypothesize that tendon cells detect mechanical load signals but do not interpret such signals as mitogenic unless an active growth factor is present. We have used an in vitro mechanical load model, application of cyclic strain to cells cultured on flexible bottomed culture plates, to test the hypothesis that tendon cells require platelet-derived growth factor (PDGF-BB) and insulin-like growth factor-I (IGF-I) in addition to mechanical load to stimulate DNA synthesis. In addition, we demonstrate that in avian tendon cells, load and growth factors stimulate phosphorylation of tyrosine residues in multiple proteins, including pp60src, a protein kinase that phosphorylates receptor protein tyrosine kinases. A lack of mitogenic responsiveness to mechanical load alone by tendon cells may be a characteristic of a regulatory pathway that modulates cell division.

Physiology of the acute wound.

The human response to injury involves the coordinated interplay of a variety of physiologic processes that result in a healed wound. In a highly reproducible manner, hemostasis is achieved, inflammation is induced, mesenchymal cells migrate into the wounded area and proliferate, revascularization occurs, epithelial continuity is re-established, collagen and other matrix components are synthesized, wound contraction occurs, and the wound remodels itself. These various functions involved in the healing process are all orchestrated by cytokines and other mediators of cellular function.

Plastic surgery research.

Several areas of plastic surgery research, both in and out of the basic science laboratory, have been highlighted. Progress is being made in our ability to produce biologic structures to replace destroyed or damaged ones in vitro, our ability to manipulate the genetic structure of cells, and our ability to define and potentially manipulate the wound healing process in normal and abnormal healing states. More is also being learned about the biology of nerve repair, the physiologic response to silicone implants, and the mechanism of reperfusion injury. Virtual surgery may become a major part of the planning, performance, and teaching of surgical procedures in the future. Outcomes need to be better defined to prove the value of what plastic surgeons do to increasingly skeptical third parties, and progress is being made in this area as well. These areas represent only a few aspects of what is new in plastic surgery research, but they at least provide a window into the field and demonstrate the increasing sophistication of work being done in all areas. This work, as well as work in other areas, will undoubtedly affect clinical practices in the near future.

Comparison of the Furlow double-opposing Z-palatoplasty with the Wardill-Kilner procedure for isolated clefts of the soft palate.

This retrospective investigation compared the operative experience speech results of 21 patients who underwent a Furlow double-opposing Z-palatoplasty with those of 10 patients who underwent a modified Wardill-Kilner procedure. The modification consisted of not incising the nasal mucosa. All patients presented with an isolated cleft of the soft palate and were operated on by a single surgeon. The choice of operative technique was based solely on the fact that the surgeon developed an increasing preference for the Furlow procedure over time. The mean age at surgery was 1.3 and 1.5 years for the Furlow group and the Wardill-Kilner group, respectively. The average postoperative follow-up was 2.5 and 3.1 years, respectively. The mean operative times and hospital stay were the same for both groups. Postoperative speech assessments involved equal-appearing interval scale ratings of hypernasality and nasal emission, as well as pressure-flow testing and perceptual judgments of overall velopharyngeal adequacy. Analysis failed to reveal any statistically or clinically significant differences between the two groups.

Burns and injuries resulting from the use of gel candles.

Scented gel candles are common decorative household items composed of gelled mineral oil, fragrances, and dye. Like traditional wax candles, they have an open flame. Because of defective design, there have been several burns and injuries caused by these products. Here we report our experience with a scald burn from a gel candle and describe 34 additional injuries attributed to gel candles previously unreported in the medical literature.

Treatment of urethral stricture disease by internal urethrotomy followed by intermittent 'low-friction' self-catheterization: preliminary communication.

The aim of this study was to determine whether the natural course of urethral stricture disease could be modified following urethrotomy by teaching patients intermittent self-catheterization. Preliminary results in 42 patients show that postoperative urine flow rates can be maintained if this method of 'low-friction' catheterization is adopted. The technique has been well received by an elderly group of patients and can be recommended for wider use.

Development of a 20-item food frequency questionnaire to assess a 'prudent' dietary pattern among young women in Southampton.

OBJECTIVE: To develop a short food frequency questionnaire (FFQ) that can be used among young women in Southampton to assess compliance with a prudent dietary pattern characterized by high consumption of wholemeal bread, fruit and vegetables, and low consumption of sugar, white bread, and red and processed meat. METHODS: Diet was assessed using a 100-item interviewer-administered FFQ in 6129 non-pregnant women aged 20-34 years. In total, 94 of these women were re-interviewed 2 years later using the same FFQ. Subsequently, diet was assessed in 378 women attending SureStart Children's Centres in the Nutrition and Well-being Study (NWS) using a 20-item FFQ. The 20 foods included were those that characterized the prudent dietary pattern. RESULTS: The 20-item prudent diet score was highly correlated with the full 100-item score (r=0.94) in the Southampton Women's Survey (SWS). Both scores were correlated with red blood cell folate (r=0.28 for the 100-item score and r=0.25 for the 20-item score). Among the women re-interviewed after 2 years, the change in prudent diet score was correlated with change in red cell folate for both the 20-item (r(S)=0.31) and 100-item scores (r(S)=0.32). In the NWS a strong association between the 20-item prudent diet score and educational attainment (r=0.41) was observed, similar to that seen in the SWS (r=0.47). CONCLUSIONS: The prudent diet pattern describes a robust axis of variation in diet. A 20-item FFQ based on the foods that characterize the prudent diet pattern has clear advantages in terms of time and resources, and is a helpful tool to characterize the diets of young women in Southampton.