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.

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.

Constraints on food choices of women in the UK with lower educational attainment.

OBJECTIVE: Women of lower educational attainment have less balanced and varied diets than women of higher educational attainment. The diets of women are vital to the long-term health of their offspring. The present study aimed to identify factors that influence the food choices of women with lower educational attainment and how women could be helped to improve those choices. DESIGN: We conducted eight focus group discussions with women of lower educational attainment to identify these factors. We contrasted the results of these discussions with those from three focus group discussions with women of higher educational attainment. SETTING: Southampton, UK. SUBJECTS: Forty-two white Caucasian women of lower educational attainment and fourteen of higher educational attainment aged 18 to 44 years. RESULTS: The dominant theme in discussions with women of lower educational attainment was their sense that they lacked control over food choices for themselves and their families. Partners and children exerted a high degree of control over which foods were bought and prepared. Women's perceptions of the cost of healthy food, the need to avoid waste, being trapped at home surrounded by opportunities to snack, and having limited skill and experience with food, all contributed to their sense they lacked control over their own and their family's food choices. CONCLUSIONS: An intervention to improve the food choices of women with lower educational attainment needs to increase their sense of control over their diet and the foods they buy. This might include increasing their skills in food preparation.

Trimethoprim versus gentamicin for the prevention of bacteriuria following transrectal biopsy of the prostate--do patients need additional anaerobic cover?

OBJECTIVES: To study the incidence of aerobic and anaerobic bacteriuria in patients undergoing transrectal ultrasound-guided biopsies of the prostate. A comparative assessment of efficacy of trimethoprim with gentamicin for the prevention of bacteriuria following the transrectal biopsy of the prostate. To assess the need for additional prophylaxis against anaerobes for patients undergoing transrectal biopsies of the prostate gland. PATIENTS AND METHODS: In a pilot study during 1995-1997, all the patients undergoing transrectal ultrasound-guided biopsy of the prostate were randomised to receive either trimethoprim or gentamicin prophylaxis prior to the procedure. Midstream urine (MSU) samples were taken just prior to biopsy and 72 h later. A patient questionnaire to determine the symptoms of urinary tract infection (UTI) accompanied the 72-hour MSU request form. Urine samples were cultured aerobically, using a semiquantitative technique if dipstick analysis revealed the presence of blood, pus cell or nitrite. In addition to the routine aerobic culture, post-biopsy samples were also cultured for anaerobes by direct and enrichment methods. Bacteriuria was defined as a pure or mixed growth of 10(5) colony-forming units/ml. Fisher's test of exact probability was used for statistical analysis. RESULTS: 115 patients were available for final analysis. 53 had received gentamicin and 62 trimethoprim. Four patients had pre-existing bacteriuria (3.5%), 3 in the trimethoprim group and 1 in the gentamicin group. Post-operative bacteriuria developed in 5 patients given gentamicin (9.4%) and 1 given trimethoprim (1.6%). This difference was not statistically significant (p = 0.085). Post-procedure bacteriuria was asymptomatic in all but 1 case. Anaerobes were detected in only 5 MSUs (4.3%) post-biopsy. CONCLUSION: Though there was no statistical significant difference in the rates of bacteriuria following administration of trimethoprim and gentamicin, data appear to favour trimethoprim prophylaxis. Further studies are warranted. Transrectal biopsy of the prostate is associated with a low incidence of anaerobic UTI. In view of the very low incidence of anaerobic bacteriuria, routine antibacterial prophylaxis against anaerobes does not appear to be justified.

Digital constriction bands in pseudoainhum: morphological radiographic, and histological analysis.

Pseudoainhum is a rare condition of unknown etiology that produces digital constricting rings, most commonly on the small fingers. A thorough discussion of pseudoainhum in the plastic surgical literature is apparently lacking at this time. The authors describe the gross morphology, radiographic and laboratory features, and surgical pathology of the disease, and provide well-defined guidelines for its treatment.

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.

Composite grafting and hyperbaric oxygen therapy in pediatric nasal tip reconstruction after avulsive dog-bite injury.

It is estimated that more than four million people are bitten by dogs in the United States each year. The majority of such injuries are minor, and their treatment does not usually require surgical consultation. However, the authors report a case in which a Rottweiler inflicted a mutilating nasal tip/alar rim avulsion on a 5-year-old boy. They report their experience with immediate reconstruction of the nasal defect using a large ipsilateral auricular cartilage composite graft (crus helix). Adjunctive hyperbaric oxygen therapy (without sedation or anesthesia) was used to maximize the stimulus for graft revascularization. Reconstructive goals were achieved while avoiding the need for a central facial donor site defect.

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.

Does endoscopic laser ablation of the prostate stand the test of time? Five-year results from a multicentre randomized controlled trial of endoscopic laser ablation against transurethral resection of the prostate.

OBJECTIVE: To determine the long-term objective and subjective outcome of patients with benign prostatic enlargement (BPE) treated by endoscopic laser ablation of the prostate (ELAP), as part of a multicentre randomized controlled trial of ELAP against TURP. PATIENTS AND METHODS: Initially, 151 patients with BPE were randomized to undergo either ELAP or TURP, starting in March 1992. ELAP was performed using the Urolasetrade mark fibre (Bard, Covington, GA, USA) in conjunction with a Nd:YAG laser source. All patients who had originally participated in the study were approached 5 years later to obtain a urological history, American Urological Association (AUA) symptom score and two measurements of urinary flow rate, with an ultrasonographic assessment of the postvoid residual urine volume (PVR). RESULTS: The mean duration of follow-up was 61 months; 109 patients were traced, comprising 69 who were alive and well, and had undergone no further bladder outlet surgery, 26 who had required revision surgery, 12 who were dead or terminally ill and three who had dementia. Both ELAP and TURP produced sustained improvements in mean AUA score, maximum flow rate and PVR, with respective values at 5 years of 6.3, 17.8 mL/s and 76 mL, and 6.5, 20.0 mL/s and 55 mL. Eighteen of 47 ELAP patients (38%) and eight of 51 (16%) TURP patients underwent revision surgery within the follow-up. CONCLUSION: ELAP and TURP produced similar subjective and objective outcomes at 5 years. The re-operation rate after ELAP was more than double that after TURP and suggests that ELAP should not be used routinely in the management of men with BPE.

IL-10 and GM-CSF expression and the presence of antigen-presenting cells in chronic venous ulcers.

BACKGROUND: White cell trapping and activation occurs in the legs of patients having chronic venous insufficiency (CVI), and it is thought that this process may be important in the development of CVI ulcers. This study has compared the tissue distribution of proinflammatory (GM-CSF) and anti-inflammatory cytokines (IL-10) and inflammatory cell markers (CD68, HLA-DR) between CVI ulcers, other chronic and acute wounds, and autologous nonwounded skin to determine whether cell-mediated immunity (CMI) is impaired in CVI ulcers. METHODS: Wound and donor site tissue was obtained from 10 patients with CVI ulcers and 10 patients with other chronic and acute wounds. Serial Formalin-fixed sections were processed by standard hematoxylin and eosin staining or by indirect immunoperoxidase histochemical staining. RESULTS: HLA-DR-positive antigen-presenting cells (APC), including CD68-positive macrophages and dermal dendritic cells, were found with greater frequency in CVI ulcers than in other chronic or acute wounds (P = 0.0015) or in the autologous CVI donor site tissue (P = 0.006). CVI ulcers also demonstrated increased IL-10 staining of the entire epidermis compared to non-CVI wounds (P = 0.0019) or autologous donor site tissue (P = 0.004), whereas there was no significant change in the presence of the counteracting cytokine, GM-CSF. CONCLUSIONS: These findings suggest that although the cellular components of CMI are present in CVI ulcers, their function may be impaired by the increased level of IL-10. Future studies will examine whether IL-10-mediated suppression of CMI and/or inhibition of GM-CSF-stimulated keratinocyte proliferation may contribute to the chronic nature of CVI ulcers.

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.

Improved axon diameter and myelin sheath thickness in facial nerve cable grafts wrapped in temporoparietal fascial flaps.

Injury to the facial nerve in the temporal bone presents a challenge to the recovery of nerve function, in that the fallopian canal in which it lies is poorly vascularized. This study was designed to determine if wrapping an intratemporal facial nerve defect repaired with a cable graft with a well-vascularized temporoparietal fascial (TPF) flap would improve facial nerve regeneration. To evaluate this question, a defect was created in the intratemporal left facial nerve of 10 rabbits. All nerves were repaired using cable grafts. In 5 animals, the nerve graft was wrapped with temporoparietal fascia, whereas in the other 5 rabbits it was not. Three additional animals underwent exposure only. The contralateral nerve served as a control in all animals. Quantitative analysis of the nerve graft 12 weeks after repair revealed greater recovery of original fiber diameter and myelin sheath thickness in TPF flap-wrapped repairs. Histological evidence of improved neural regeneration and functional nerve recovery was also seen in the repairs where the TPF flap was utilized. Nerve conduction and electromyographic studies of the cable-grafted nerve at 6 and 12 weeks were equivocal, however.

Biochemical assessment of cellular damage after adipocyte harvest.

Free fat transplantation for soft tissue augmentation yields variable results, which may be related to the technique of fat harvest. To compare the viability of adipocytes harvested by liposuction (sal) or by excision (exc), fat harvested by both techniques from seven lipectomy patients was analyzed by glycerol-3-phosphate dehydrogenase (G3PDH) enzyme assay. Leakage of this lipogenic enzyme through the plasma membrane is a potential indicator of fat cell damage. Preliminary experiments showed this assay to be sensitive and specific for adipocyte G3PDH activity. Treatment of fat tissue with collagenase H resulted in complete release of the component fat cells for analysis with less loss of G3PDH activity, compared to other collagenase preparations. Each sample was digested and separated into three compartments: mature adipocytes-floating layer (F), acellular supernatant (S), and stromal pellet (P). Samples from each compartment were assayed for G3PDH activity, normalized to DNA content, and represented as a percentage of the whole (F + S + P). Within the subgroups, the fat cell fraction of the liposuction samples (Fsal) showed statistically more activity than the excised samples (Fexc) by paired Student's t test (P = 0.004). The supernatant (representing leaked G3PDH) and pellet fractions of excised samples revealed more G3PDH activity than the same fractions from liposuctioned tissue; the former (Sexc) to a significant degree (P = 0.036). Using this assay, the results indicate that liposuction fat harvest does not result in increased fat cell damage compared to fat harvested by excision.

A randomized controlled trial of transurethral microwave thermotherapy.

OBJECTIVE: To establish the short term clinical and urodynamic effect of transurethral microwave thermotherapy (TUMT) in men with symptomatic uncomplicated benign prostatic hyperplasia (BPH) using a randomized controlled trial comparing the treatment with both 'placebo-like' and untreated control groups. PATIENTS AND METHODS: The study comprised 120 symptomatic patients with BPH who were candidates for transurethral resection and TUMT. They were randomized to one of three groups: group 1 underwent a standard TUMT, group 2 underwent a simulated treatment identical to group 1 but with no emission of microwaves and group 3 received no treatment. The treatment of the first two groups was 'double-blind' and the heat experienced by the patients during treatment was simulated in both. Patients were assessed on entry to the study and 6 months after treatment using an identical protocol to measure the American Urological Association (AUA) symptom score, maximum urinary flow rate (Qmax), post-void residual urine volume (PVR), minimum urethral opening pressure (Pmuo) and maximum detrusor pressure (Pdet max). RESULTS: In the untreated group there were no clinically or statistically significant changes in the median AUA symptom score, Qmax, PVR, Pmuo and Pdet max. In group 1 the AUA score changed significantly, from 19 to 9.5, but the Qmax, PVR, Pmuo and Pdet max did not. In group 2, the AUA score also changed significantly, from 17.5 to 9.5, but Qmax, PVR, Pmuo and Pdet max did not. CONCLUSION: The untreated control group showed no clinically relevant deterioration or improvement. The standard and simulated TUMT groups showed little clinically relevant improvement in 'objective' variables, while the clinically significant symptom improvement was of a similar magnitude in both groups.

Transurethral microwave thermotherapy (Prostatron version 2.5) compared with transurethral resection of the prostate for the treatment of benign prostatic hyperplasia: a randomized, controlled, parallel study.

OBJECTIVE: To compare transurethral microwave thermotherapy (TUMT) with urethral cooling in a high-energy protocol (Prostatron version 2.5), with transurethral resection of the prostate (TURP) for the treatment of symptomatic, uncomplicated, urodynamically obstructive benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Patients with moderate to severe symptomatic, uncomplicated BPH, unequivocally obstructed as assessed from the Abrams-Griffith nomogram, who were technically suitable for either form of treatment, were randomized into two groups of 30 patients each to undergo either TUMT or TURP. Five efficacy variables, i.e. the American Urological Association (AUA) symptom score, maximum flow rate (Qmax), post-void residual urine volume (PVR), voiding pressure at maximal flow (Pdet max) and prostatic volume determined by ultrasonography (PV) were measured initially and 6 months after treatment using a defined protocol. Complications were recorded during and up to 6 months after the treatment. As the variables were independent, the data were analysed using a paired t-test for each to assess the treatment effect for each group. RESULTS: After TURP, all the variables improved significantly; after TUMT, the symptoms improved both clinically and statistically (P < 0.001), with the mean AUA symptom score decreasing from 18.4 to 5.2. However, none of the objective variables improved after TUMT. The energy delivered under software control correlated poorly with prostatic volume (r = 0.322). TUMT had considerably lower morbidity than TURP, but failure of ejaculation occurred in four of 18 sexually active men after TUMT. CONCLUSIONS: Despite considerable improvement in their symptoms, TUMT using the Prostatron and Prostasoft v2.5 did not alleviate obstruction in patients with BPH. Patients treated using TUMT controlled by this software should be informed of the possibility of ejaculatory dysfunction.

Treatment of earlobe keloids with surgery plus adjuvant intralesional verapamil and pressure earrings.

Treatment for keloids remains less than ideal. Previous discouraging results prompted a change in the author's standard treatment for keloids to surgery plus adjuvant intralesional verapamil and pressure earrings. Intralesional verapamil (2.5 mg per milliliter) was administered 7 to 14 days after keloid removal and again approximately 1 month after removal when possible. Between 0.5 ml and 2.0 ml was administered each time, depending on the size of the keloid. Patients were instructed to wear pressure earrings essentially continuously for a minimum of 6 months after excision. Thirty-five African American patients with 45 earlobe keloids were treated with this regimen. Information regarding recurrence was obtained by follow-up, mail, or phone call from 31 patients (89%) with 40 keloids (89%). Minimum follow-up for inclusion was 6 months and average follow-up was 28 months. Twenty-two keloids (55%) in 16 patients (52%) were cured by this treatment modality. There were no significant differences in recurrence rates related to sex, age, keloid size, length of time the keloid was present, how long the ears had been pierced, and how many verapamil injections were received. There was a trend toward an increased recurrence rate for previously treated keloids. Though not optimal, this regimen is superior to some previously evaluated regimens.

Increased proliferation in keloid fibroblasts wounded in vitro.

A keloid is a pathological overgrowth of scar expanding beyond the boundaries of the initiating skin wound. Ultimately, this expansive scar is a result of excess collagen synthesized by fibroblasts within the wound. The processes that lead to this collagen excess remain unknown. An in vitro wound model was developed to test the hypothesis that fibroblasts isolated from keloid tissue and wounded in vitro might proliferate more rapidly that similarly wounded normal dermal fibroblasts. Keloid fibroblasts (KF) and normal human dermal fibroblasts (NDF) were grown to confluence and quiescence in flexible-bottomed culture plates. Wounds were created in a standardized fashion using a specially designed jig. The jig utilized a 25 gauge needle to reproducibly ablate 16-20% of cells from confluent cell sheets. Wounded and nonwounded cells were labeled with 3H-thymidine at 24, 48, 72 and 96 hr postwounding to measure DNA synthesis. Wounded KF and NDF demonstrated increased 3H-thymidine incorporation compared to nonwounded control cultures, and wounded KF demonstrated significantly higher levels of 3H-thymidine incorporation than wounded NDF both 24 and 48 hr after wounding. A similar trend was seen in cell counts. The wounded KF also showed a statistically greater labeling index quantitated by autoradiography than did wounded NDF. The increased commitment to DNA synthesis in response to wounding in vitro in keloid fibroblasts correlates with pathology seen in vivo. Keloid fibroblasts may have a lower inherent threshold for S phase entry than do normal fibroblasts contributing to the increased proliferation of keloid fibroblasts in response to wounding in vitro.

Pit viper bites: rational management in locales in which copperheads and cottonmouths predominate.

The management of pitviper bites remains controversial. In order to better assess the efficacy of different treatment modalities, charts of 107 patients hospitalized for pitviper bites at University of North Carolina Hospitals between 1952 and 1992 were retrospectively reviewed. The series included 68 copperhead bites (64%), 8 cottonmouth bites (7%), 3 rattlesnake bites (3%), and 28 bites (26%) in which the snake could not be identified. First aid measures taken prior to hospitalization included cryotherapy (21%), incision and suction (22%), tight or loose tourniquets (32%), and moist heat (2%). After hospitalization, 29 patients (27%) underwent wound excision and 4 patients (4%) required fasciotomy. Antivenin was administered to 34 patients (32%) and 9 patients (26%) developed serum sickness. No patients died as a result of a bite injury and 84 patients (79%) recovered uneventfully. Complications of the injuries included coagulopathies (4%), infections (13%), tissue loss (12%), and permanent physical deformities (8%). No first aid measure significantly affected the outcome, although there was a trend toward increased complication rates in bites with moderate (grade II) or greater envenomation if cryotherapy or tourniquets were utilized. Wound excision after hospitalization was associated with a decreased complication rate in these significantly envenomated bites. Antivenin utilization did not improve outcome and there was a significantly higher incidence of tissue loss associated with its use. Therefore, no first aid measures are recommended for pitviper bites due to copperheads and cottonmouths except immobilization and elevation. Excision is efficacious for patients seen within 1 to 2 hours of bite injury. The risk of complications and questionable efficacy of antivenin outweigh any potential benefit for these patients. Data from the current series were insufficient to make definitive recommendations regarding rattlesnake bites.