Assessing potential legal responses to medical ghostwriting: effectiveness and constitutionality.

Pharmaceutical companies are extensively involved in shaping medical knowledge to market their products to physicians and consumers. Specialized planning is undertaken to produce scientific articles driven by commercial interests. Rather than the listed authors, hidden analysts and publication management firms hired by pharmaceutical companies are often responsible for the content of scientific articles. Such ghostwriting practices raise serious concerns regarding the integrity of knowledge and thus demand urgent attention. This paper analyses the strategies of legal regulation on medical ghostwriting and their comparative advantages and disadvantages. Many of regulatory proposals suffer from a lack of effectiveness, whereas others are subject to constitutional concerns. The analysis in this paper offers insights into framing adequate regulation; it supports the strategy for reforming the structure of information production while calling for cautiousness in shaping its regulatory outline. In addition, this paper contributes to the analysis of First Amendment jurisprudence, suggesting that the judiciary should allow a certain amount of leeway for political branches to develop effective regulation.

Angiogenin Attenuates Scar Formation in Burn Patients by Reducing Fibroblast Proliferation and Transforming Growth Factor ß1 Secretion.

BACKGROUND: Deep burn wounds have a high tendency to form hypertrophic scars. Previously, we found that angiogenin promoted neovascularization during deep burn wound healing. However, the association between angiogenin and scar formation is unclear. METHODS: We obtained human burn scar tissues from patients who underwent scar surgery and examined the role of angiogenin in scar tissues and determined its effects in scar fibroblasts and on transforming growth factor ß1 (TGF-ß1) secretion. RESULTS: Our results showed an inverse correlation between angiogenin expression and scar severity. Next, we examined the effects of angiogenin in scar fibroblasts. We found that angiogenin was persistently expressed in human scar fibroblasts and that angiogenin expression significantly increased with time in the culture medium of scar fibroblasts. Treatment of scar fibroblasts with recombinant angiogenin significantly decreased their proliferation and TGF-ß1 secretion. Moreover, angiogenin inhibited TGF-ß1-mediated Smad2 signaling pathway. CONCLUSION: Our data suggest a negative role of angiogenin in fibroblast proliferation via TGF-ß1-mediated Smad2 signaling pathway.

Predominance of CD14+ Cells in Burn Blister Fluids.

BACKGROUND: Burn blister fluid contains several angiogenic factors to promote wound neovascularization. In our previous study, we found that deep partial-thickness burn (DPTB) wounds showed higher expression levels of angiogenin to enhance vascularization compared with superficial partial-thickness burn wounds. Neovascularization is a complex process that involves an interaction between circulating angiogenic cells and mediators. We hypothesized that in addition to angiogenic factors burn blisters may contain specific cell types. The aim of the present study was to characterize the specific cells present in burn blisters. METHODS: Twenty-four burn blister fluid samples were obtained with informed consent from patients with superficial partial-thickness burn (n = 16) or DPTB (n = 8) wounds. Blister cells were isolated from individual intact blisters and characterized with flow cytometry analysis using CD14, CD34, vascular endothelial growth factor receptor 2, and CD133 markers. CD14 and CD34 blister cells were also isolated using a magnetic-activated cell sorting system to examine their potential for endothelial differentiation. Angiogenin levels in the burn blister fluids were evaluated with enzyme-linked immunosorbent assay. RESULTS: CD14 cells were the most highly represented cell type in the burn fluids of both groups, although a significantly greater percentage of CD14 cells were observed in DPTB fluids. CD14 blister cells had a higher potency to differentiate into functional endothelial cells as compared with CD34 cells. The proportion of CD14 cells gradually increased after burn injury. In contrast to CD14 cells, angiogenin showed the highest expression levels at day 1 postburn. With regard to burn wound neovascularization, angiogenin expression was partially correlated with CD14 blister cells in the burn fluids. CONCLUSIONS: We provide the first report on the characterization of blister cells in burn fluids. Our data suggest that CD14 blister cells may play a role in burn wound neovascularization. Measurement of CD14 blister cells serves as a possible tool for assessing burn wound status.

Validation of a Taiwanese Version of the Burn-Specific Health Scale-Brief.

The purposes of this study were to translate the brief version of the Burn-Specific Health Scale (BSHS-B) into traditional Chinese (Taiwanese) and to evaluate its psychometric properties to measure quality of life of burn patients in Taiwan. The BSHS-B-Taiwanese was translated and reviewed by an expert committee. Patients were invited to participate in this study while they visited the outpatient burn clinic. One hundred and eight burn patients participated in this study by filling out the BSHS-B-Taiwanese and SF-36 Taiwanese version. Forty-one of 108 patients completed a retest on the BSHS-B-Taiwanese. A ceiling effect was found for psychosocial functioning and all domains of the BSHS-B-Taiwanese. Internal consistency shown by Cronbach's alpha was all above 0.70 except for the interpersonal relationships domain. Of these, Cronbach's alpha ≥0.9 was found in the work, heat sensitivity, and body image domains. Test-retest reliabilities ranged from 0.74 to 0.93 except for the simple activity domain. As for the criterion validity, most of the BSHS-B-Taiwanese version was shown to have fair to moderate correlations with the SF-36-Taiwanese in corresponding domains. The discriminant validity of the BSHS-B-Taiwanese was demonstrated by significant score differences in several domains between subgroups of different severity regarding length of hospital stay and TBSA. Our finding suggests that the BSHS-Taiwanese is generally reliable and valid. A shorter version of BSHS-B-Taiwanese together with a generic instrument, such as SF-36, can be used to measure the quality of life of burn patients in Taiwan.

Angiogenin expression in burn blister fluid: implications for its role in burn wound neovascularization.

Deep partial thickness burn (DPTB) wound fluids have a greater propensity for establishing neovascularization than did superficial partial thickness burn (SPTB) wound fluids in our previous study. To investigate the factors responsible for this activity, cytokine array and enzyme-linked immunosorbent assay were used to perform an expression analysis of angiogenic factors in burn fluid. Although present in approximately equal amounts in both SPTB and DPTB blister fluids from burn patients, angiogenin does appear to be involved in the ability of DPTB blister fluid to promote neovascularization in vitro and in vivo. Angiogenin alone was sufficient to induce endothelial differentiation of circulating angiogenic cells (CAC) without vascular endothelial growth factor A involvement. In addition, angiogenin was positively associated with CAC differentiation in the burn blister fluid. Blocking the effect of angiogenin in burn blister fluids resulted in a significant reduction of endothelial cell proliferation, CAC differentiation, and new blood vessels formation in vivo. Moreover, immunohistochemistry revealed that high angiogenin expression colocalizes with high vascularity in human burn wounds at day 7, further supporting our hypothesis that angiogenin is involved in burn wound neovascularization.

Analysis of factors influencing limb amputation in high-voltage electrically injured patients.

BACKGROUND: Limb amputation is considered one of the most devastating consequences of electrical injury. Any factors that correlate with the degree of muscle damage can be used to predict the necessity of limb amputation. The aim of this study was to determine the factors that can be used to predict limb amputation in high-voltage electrically injured patients. METHODS: Eighty-two high-voltage electrically injured patients were admitted to our hospital during a 17-year period. A retrospective analysis of the possible related risk factors between amputation and non-amputation patients was performed. RESULTS: A total of 68 patients were enrolled for analysis. Thirteen patients underwent limb amputations. Multivariate analysis of the risk factors between amputation and non-amputation groups showed statistical significance for day 1 creatine kinase-isoenzyme MB (CK-MB) level. A serum CK-MB level above 80 ng/ml predicted high risk of limb amputation with high specificity (84%) and sensitivity (77%). Only one patient with a remarkable decrease of creatine kinase (CK) and CK-MB levels after fasciotomy avoided a major limb amputation. CONCLUSION: Our results suggest that CK-MB level is an independent factor for prediction of limb amputation. We suggest that the addition of CK-MB evaluation to clinical symptoms screening may be a valuable method to early detection of muscle damage.

Development of a telecare system based on ZigBee mesh network for monitoring blood pressure of patients with hemodialysis in health care centers.

In Taiwan, the number of the patients needing dialysis increases rapidly in recent years. Because there is risk in every hemodialysis session, monitoring physiological status, such as blood pressure measurement every 30 min to 1 h is needed during about 4 h hemodialysis process. Therefore, an assisted measurement on blood pressure is needful in dialysis care centers. Telecare system (TCS) is regarded as one of important technique in the medical care. In this study, we utilized ZigBee wireless technique to establish a mesh network for monitoring blood pressure automatically and data storage in medical record system for display and further analysis. Moreover, while the blood pressure exceeds the normal range, the system could send a warning signal to remind, or inform the relatives and clinicians in health care center through the personal handy-phone system (PHS) immediately. The proposed system provides an assisted device for monitoring patients' blood pressure during hemodialysis process and saving medical manpower.

Deep partial thickness burn blister fluid promotes neovascularization in the early stage of burn wound healing.

The effect of burn blister fluid in neovascularization during burn wound healing is unknown. Burn blister fluid, containing a large amount of chemokines, is thought to play a role in the early stage of neovascularization. This process includes angiogenesis and vasculogenesis. Because of different healing time of burn wounds, we hypothesized that neovascularization in superficial partial thickness burn (SPTB) and deep partial thickness burn (DPTB) wounds were different. The neovasculogenic effects of two different burn blister fluids were also different. We found Day 7 DPTB wounds had a significant increase in blood vessels compared with SPTB wounds by immunohistochemistry. DPTB blister fluid significantly promoted neovascularization via increasing endothelial cell proliferation, and migration and differentiation of circulating angiogenic cells relative to SPTB blister fluids. In the animal study, DPTB blister fluids markedly promoted new blood vessel formation compared with those from SPTB blister fluids using in vivo Matrigel plug assay. These results suggest that DPTB wounds require more new vessel formation than SPTB. Furthermore, the measurement of angiogenic activities in burn blister fluids serves as a possible tool for assessing burn wound status.

Factors related to return to work and job modification after a hand burn.

Occupational therapy aims to help patients resume their occupations. Therefore, we must know their work status after our intervention. We collected demographic and burn-related data from patient charts and analyzed it to determine the work status of former patients with burned hands and what influenced their returning to work. From 284 former patients with burns, we screened 159 with burned hands, 108 of whom were interviewed through the telephone about their work status. We used logistic regression analysis to analyze factors for having work, returning to work, the length of time required to return to work, and job modifications. We found that 1) having preburn employment increased the likelihood of having postburn employment; 2) being the primary wage earner in a family increased the likelihood of having work and of a return to work postburn; 3) a longer stay in the hospital, and burn injuries on both hands and trunk increased the time required to return to work; and 4) being older and having a smaller percentage of total body burn area decreased the likelihood of returning to a job modified because of a burn injury. Returning to work was affected not only by burn-related factors but also by general demographic and employment factors. We urge occupational therapy departments to include a return-to-work program in their routine services to improve the chances of patients with hand burns to return to work. We strongly recommend that a multicenter prospective study of hand-burn injuries should be performed.

Effectiveness of web space pressure inserts for postburn dorsal slant.

Postburn web space scar, if not appropriately treated, can result in the progressive loss of the web space or the increase in angle of the dorsal slant of the web space or both, which will not only lead to cosmetic and hygiene problems, but also to functional limitations. The purpose of this study was to determine the effectiveness of web space pressure inserts for postburn dorsal slants. An individualized custom-made web space pressure insert was fitted into each web space. Inserts were worn underneath the pressure glove to create additional pressure on each web space and to inhibit distal migration of the scar to avoid the increase in the angle of the dorsal slant of the web space. Twenty-four survivors with 36 burned hands, who had been treated in the burn clinic of National Cheng Kung University Hospital, were recruited for this study. When skin wounds were closed, the participants received custom-made web space pressure inserts. The dorsal slant of each web space was measured by a conventional goniometer every time the participants visited the burn clinic. The initial and final measurements were used to compare the change in the angle of the dorsal slant of the web space. Paired t-tests were computed to determine the effectiveness of pressure inserts. The final dorsal slant angle of each web space was also compared with the unburned value by independent t-test. After 234.6 +/- 177.0 days of intervention, the mean dorsal slants of 36 dorsal burn hands' four web spaces were all significantly reduced (P < .001). The most important finding was that the angle of the first dorsal slant could be improved to normal. A custom-made web space pressure insert could be used to improve postburn dorsal slant.

Necrotizing fasciitis in patients with liver cirrhosis: predominance of monomicrobial Gram-negative bacillary infections.

Necrotizing fasciitis (NF), a rare but severe infection, usually occurs in individuals with underlying chronic illness, but its clinical presentation among cirrhotic patients is infrequently discussed. Forty-two cirrhotic patients with 47 episodes of NF between 1995 and 2006 were analyzed. Their mean age was 55.6 years, with male preponderance (34 patients, 81%). Lower extremities were mainly involved (70%). Of 42 episodes with identified pathogens, 41 (97%) were monomicrobial infections and were caused mainly by Gram-negative rods (GNBs) (32, 76%), including Vibrio (15, 36%), Klebsiella (9, 21%), and Aeromonas spp. (6, 14%). As compared with NF caused by Gram-positive cocci (GPCs), NF caused by GNBs tended to have concurrent bacteremia (81% versus 50%, P=0.09) and initially presented with septic shock (75% versus 30%, P=0.02). However, the in-hospital mortality rate was similar for NF caused by GNBs and GPCs (34% versus 30%, P=1.00). In multivariate analyses, higher sepsis-related organ failure assessment scores (>8) and Child-Pugh class C at initial presentation were independently associated with poor prognoses.

Acute stroke in the burn patient.

A 3-year-old boy was brought to our hospital with 62% TBSA burn injury by boiled water. He received modern burn therapy, including early débridment and skin grafts. The patient discharged 70 days after being burned. Unfortunately, he sustained an acute right-sided hemiparesis 7 days after discharge. Magnetic resonance imaging revealed left middle cerebral artery territory infarction, and a magnetic resonance angiogram showed nonvisualization of left distal intra-cranial carotid artery and proximal middle cerebral artery. Thickened walls of these arteries indicated acute dissection. The patient received a follow-up magnetic resonance angiogram study 10 years later to check cerebral vascular lesions that may not have been apparent on the original image studies. It showed only persistently thickened left distal intra-cranial carotid artery and middle cerebral artery walls, indicative of old dissection. Therefore, carotid artery dissection must be considered as one cause of acute stroke in pediatric burn patient, even in the recovery phase of burn injury.

Stenotrophomonas maltophilia bacteremia in burn patients.

Stenotrophomonas maltophilia has been increasingly reported as a nosocomial opportunistic pathogen in debilitated patients, including burn patients. There is, however, only one published report in English that discusses S. maltophilia bacteremia in burns. We performed a retrospective chart review and statistical analysis of the incidence, the duration of hospital stays before a diagnosis of bacteremia, antimicrobial susceptibility, prognosis, and mortality risk factors in burn patients. From January 1996 to December 2004, 14 episodes of S. maltophilia bacteremia in 13 of 666 patients admitted to the burn center at our hospital were identified. The patients, nine males and four females, ranged in age from 1 to 76 years (mean: 42.9+/-24.4 years). Eleven injuries were from flame burns and two were from scald burns. The mean total burned surface area (TBSA) was 47+/-30.2% and mean prognostic burn index (PBI) was 81.7+/-31.3. The average annual incidence was 2.3 episodes per 1000 admissions, and no outbreak cluster was noticed. The mean hospital stay before bacteremia was 19.8+/-11.9 days. Most isolates were susceptible to ticarcillin-clavulanate (87.5%) and moxalactam (85.7%). The overall mortality was 30.7% (4/13) and correlated significantly with TBSA (P<0.01) and PBI (P<0.05). The incidence of S. maltophilia bacteremia was higher in hospitalized burn patients than in hospitalized non-burn patients. Different antimicrobial susceptibility patterns may exist, especially in different geographic regions. Awareness of the possibility of infection by this opportunistic pathogen and commencement of adequate antibiotics treatment, especially after 3 weeks of intensive care, should be incorporated into the strategy of treatment in major burn patients.

Implementation of a burn scar assessment system by ultrasound techniques.

Tissue injury and its ensuing healing process cause scar formation. In addition to physical disability, the subsequent disfigurements from burns often bring negative psychological impacts on the survivors. Scar hypertrophy and contracture limit the joint motion and body function of the patient. With fast development of the current available technologies regarding the scar therapies, not only the process of wound healing has to be focused, but also the cosmetic and functional outcomes need to be emphasized. Therefore, proper evaluation and assessment of the healing process to nil scar status is highly recommended. However, the currently employed tools for scar evaluation are mostly subjective. For example, Vancouver General Hospital (VGH) scar index uses color, pigmentation, vascularity, pliability, and depth of the scar as dependent variables for scar evaluation. These parameters only estimate the superficial surface of the scar, but they can not evaluate the deeper tissue within dermis. Ultrasound is a safe, inexpensive, and multifunctional technique for probing tissue characteristics. In addition, its resolution is not inferior to other measurement techniques. Although 3D-ultrasound is available in clinical application, it's still not widely used in scar evaluation because of its high cost. In this study, we proposed a system for scar assessment using B-mode ultrasonic technique. By utilizing the reconstruction methods to search the scar border, many characteristic parameters, including depth, area and volume, can be estimated. The proposed method is useful in assisting the clinician to evaluate the treatment effect and to plan further therapeutic strategy more objectively. In this report, the quantitative assessment system was used to evaluate the scar of a seriously burned patient. In order to verify the reliability of systematic reconstruction method, we constructed a phantom to imitate the scar tissue. The results show that it can achieve more than 90% in accuracy.

Herpes simplex infection in a minor burn wound: a case report.

The etiology of herpetic lesions on burn wounds generally is believed to be a reactivation of previous infection or possible exposure to the pathogens under an immunocompromised status. However, this scenario rarely happens in a non-immunocompromised infant with low burned body surface area (<4% TBSA). We report a case of previously healthy 21-month-old boy who sustained minor scald burn injury involving only 4% TBSA that was complicated with herpes simplex type 1 viral infection. The infection presented with ulcerative burn wound and delayed wound healing. The Tzanck smear of vesicular fluid for the identification of multinucleated giant cells is helpful in making the decision for the early initiation of acyclovir. In this work, we describe a case of pediatric burn patient with herpetic infection and emphasize the need for careful and impartial examination of the child to improve the accuracy of diagnosis.

Metabolic fate of extrahepatic arginine in liver after burn injury.

Increased nitrogen loss in the form of urea is a hallmark of the metabolic aberrations that occur after burn injury. As the immediate precursor for urea production is arginine, we have conducted an investigation on the metabolic fate of arginine in the liver to shed light on the metabolic characteristics of this increased nitrogen loss. Livers from 25% total surface burn (n = 8) and sham burn rats (n = 8) were perfused in a recycling fashion with a medium containing amino acids and stable isotope labeled l-[(15) N(2)-guanidino, 5,5-(2)H(2)]arginine for 120 minutes. The rates of glucose and urea production and oxygen consumption were measured. The rate of unidirectional arginine transport and the intrahepatic metabolic fate of arginine in relation to urea cycle activity were quantified by tracing the disappearance rate of the arginine tracer from and the appearance rate of [(15)N(2)]urea in the perfusion medium. Perfused livers from burned rats showed higher rates of total urea production (mean +/- SE, 4.471 +/- 0.274 v 3.235 +/- 0.261 mumol. g dry liver(-1). min(-1); P <.01). This was accompanied by increased hepatic arginine transport (1.269 +/- 0.263 v 0.365 +/- 0.021 mumol. g dry liver(-1). min(-1)) and an increased portion of urea production from the transported extrahepatic arginine (12.9% +/- 2.9% v 3.5% +/- 0.4%, P <.05). The disposal of arginine via nonurea pathways was also increased (0.702 +/- 0.185 v 0.257 +/- 0.025 mumol/g dry weight(-1)/min(-1); P <.05). We propose that increased inward transport and utilization of extrahepatic arginine by the liver contributes to the accelerated urea production after burn injury and accounts, in part, for its conditional essentiality in the nutritional support of burn patients.