Severe infections in patients with lupus nephritis treated with immunosuppressants: A retrospective cohort study.

AIM: Lupus nephritis (LN) is associated with significant morbidity and mortality and hence usually treated aggressively with immunosuppressants. This predisposes LN patients to increased infections, yet few studies have evaluated LN patients for infective complications. We aimed to describe the epidemiology and identify risk factors for infections requiring hospitalization among patients with biopsy-proven LN. METHODS: This was a single-centre retrospective cohort study of patients with biopsy-proven LN between 1 January 2000 and 31 May 2009. Patients were excluded if they were <16 years old at time of biopsy, had previous kidney transplant or if pharmacotherapy data were incomplete. Hospitalizations for infections, bacteraemia and polymicrobial infections were recorded until patients' last visit or when they received immunosuppression for non-glomerulonephritis indications, such as solid organ transplant or chemotherapy. RESULTS: We studied 189 patients who had biopsy-proven lupus nephritis. Median age at diagnosis was 36.9 (IQR: 27.4, 47.5) years and 82% were female. Most patients received at least one immunosuppressant after LN diagnosis, including glucocorticosteroids in 94.2%. One hundred and four patients (60.3%) had at least one hospitalization for infection at 11 (1, 53) months from diagnosis. Bacteraemia occurred in 26 patients (13.8%) and 32 patients (16.9%) had polymicrobial infections. On multivariate analysis, LN relapse was associated with hospitalization for infection (OR 2.33 (1.18, 4.60), P = 0.01) and bacteraemia (OR 3.47 (1.05, 11.45), P = 0.04). Infection-related mortality occurred in 10 patients (5.3%). CONCLUSION: Serious infections are common among patients with LN and are associated with mortality.

[An Epidemiological Survey on Echinococcosis in Yushu Prefecture of Qinghai Province].

Objective: To investigate the prevalence of echinococcosis in Yushu Prefecture of Qinghai Province in 2012. Methods: Two to three towns were selected in each of Chengduo, Nangqian, Qu malai, Yushu, Zaduo and Zhiduo Counties from June to August in 2012. Ultrasound examination was conducted for residents aged over 1 year, and ELISA was performed to detect serum antibody against Echinococcus. Visceral dissection was performed to detect hydatid infection in rodents and livestock. ELISA was used to detect Echinococcus antigen in collected dog feces. Results: A total of 7 025 residents received ultrasound examination, of whom 319 showed hydatid cysts with a morbidity rate of 4.54%. ELISA showed a serum antibody positive rate of 16.38% （457/2 790）. The mobidity of hydatid disease was highest in Chengduo County （7.41%, 181/2 444）, and the rate of serum antibody was highest in Yushu County （23.18%, 127/548）. The morbidity and serum antibody in males were 3.91% （118/3 018） and 13.93% （172/1 235） respectively, and those in females were 5.02% （201/4 007） and 18.33% （285/1 555）. In terms of age distribution, the morbidity was relatively higher in residents of 60- （8.39%, 38/453） and 40- years （6.61%, 67/1 014）; and the rate of serum antibody was highest in residents over 70 years （33.93%, 19/56）. In terms of occupation, the morbidity was relatively higher in herdsmen （5.28%, 252/4 777）, Herdsmen-peasants （6.52%, 24/368）, and religious workers（3.37%, 11/326）, while the rate of serum antibody was relatively higher in children（24%, 6/25）, religious workers （18.79%, 31/165） and herdsmen（18.34%, 328/1 788）. In terms of education level, the morbidity and the rate of serum antibody were both highest in the uneducated（5.04%, 41/4 779; 18.34%, 359/1 958, respectively）. In terms of residential pattern, the morbidity and the rate of serum antibody were both highest in those who were settled in winter and nomadic in summer （8.25%, 227/2 753; 19.48%, 158/811, respectively）. There were significant differences in the morbidity and the rate of serum antibody in aspects of residential region, sex, age, occupation, education level and residential pattern (P<0.05 or P<0.01). In 872 rodents detected, the Echinococcus hydatid rate was 0.46% （4/872）, while in 809 cattle and sheep detected, the Echinococcus hydatid rate was 10.14% （82/809）. The fecal antigen positive rate in 838 samples of dog feces was 10.74%（90/838）. Conclusion: It shows a high morbidity of hydatid diesease and serum antibody positive rate in residents, a high Echinococcus hydatid rate in cattle and sheep, and a high fecal antigen positive rate in dogs in Yushu Prefecture.

Transient knockdown of tyrosine hydroxylase during development has persistent effects on behaviour in adult zebrafish (Danio rerio).

Abnormal dopamine (DA) signaling is often suggested as causative in schizophrenia. The other prominent hypothesis for this disorder, largely driven by epidemiological data, is that certain adverse events during the early stages of brain development increase an individual's risk of developing schizophrenia later in life. However, the clinical and preclinical literature consistently implicates behavioural, cognitive, and pharmacological abnormalities, implying that DA signaling is abnormal in the adult brain. How can we reconcile these two major hypotheses underlying much of the clinical and basic research into schizophrenia? In this study we have transiently knocked down tyrosine hydroxylase (TH, the rate limiting enzyme in DA synthesis) gene expression in the early stages of brain development in zebrafish using morpholinos. We show that by adulthood, TH and DA levels have returned to normal and basic DA-mediated behaviours, such as locomotion, are also normal. However, when they were exposed to a novel environment the levels of freezing and immediate positioning in deeper zones were significantly reduced in these adult fish. The neurochemistry underlying these behaviours is complex, and the exact mechanisms for these abnormal behaviours remains unknown. This study demonstrates that early transient alterations in DA ontogeny can produce persistent alterations in adult brain function and suggests that the zebrafish may be a promising model animal for future studies directed at clarifying the basic neurodevelopmental mechanisms behind complex psychiatric disease.

A denatured collagen microfiber scaffold seeded with human fibroblasts and keratinocytes for skin grafting.

Biomaterial scaffolds are categorized into artificial or natural polymers, or combinations of the two. Artificial polymers often undergo serum protein adsorption, elicit foreign body and encapsulation immune responses post-implantation. Large pore bovine electrospun collagen I was therefore screened as a candidate for human keratinocyte and fibroblast cell scaffolds. Human HaCaT keratinocyte and dermal fibroblasts were seeded on electrospun denatured collagen I microfiber (DCM) scaffolds and after 72 h Livedead(®) assays performed to determine adhesive cell, survival and scaffold penetration. Both keratinocytes and fibroblasts attached to and survived on DCM scaffolds, however only fibroblasts migrated over and into this biomaterial. HaCaT keratinocytes remained largely stationary on the scaffold surface in discrete islands of monolayered cells. For this reason, normal human epidermal keratinocyte (NHEK) scaffold interactions were assessed using scanning and transmission electron microscopy (EM) that demonstrated DCM scaffolds comprised networks of interlocking and protruding collagen fibers with a mean diameter of 2-5 µm, with a mean inter-fiber pore size of 6.7 µm (range 3-10 µm) and scaffold thickness 50-70 µm. After 72 h the keratinocytes and fibroblasts on DCM scaffolds had attached, flattened and spread over the entire scaffold with assembly of lamellapodia and focal adhesion (FA)-like junctions. Using transmission EM, NHEKs and HaCaT keratinocytes assembled desmosomes, lamellapodia and FA junctions, however, neither hemidesmosomes nor basal lamina were present. In long term (21 day) co-culture fibroblasts migrated throughout the scaffold and primary keratinocytes (and to a lesser extend HaCaTs) stratified on the scaffold surface forming a human skin equivalent (HSE). In vivo testing of these HSEs on immunocompetent (BalbC) and immunodeficient (SCID) excisionally wounded model mice demonstrated scaffold wound biocompatibility and ability to deliver human cells after scaffold biodegradation.

Fetuin-A promotes primary keratinocyte migration: independent of epidermal growth factor receptor signalling.

Previously, we reported that fetuin-A is a major component of ovine foetal skin and significantly enhances 'wound closure' in primary keratinocyte cultures. In this study, we found that in human newborn foreskin, a high level of fetuin-A protein is detected throughout the dermis. However, in adult skin a low level of fetuin-A is observed throughout the epidermal and dermal layers, except at regions surrounding hair follicles and at the epidermal-dermal junction where the level of fetuin-A is relatively high. Fetuin-A significantly induces actin-rich protrusions in human primary keratinocytes. Interestingly, blockade of epidermal growth factor (EGF) receptor signalling has a limited effect on fetuin-A promoted 'wound closure' on primary human keratinocytes, but significantly inhibits fetuin-A's effect on HaCaT cells. These results indicate that high levels of fetuin-A may partially contribute to less scar formation in newborn foreskin and that the effect of fetuin-A on primary keratinocyte migration is independent of EGF receptor signalling.

The optimal duration and delay of first aid treatment for deep partial thickness burn injuries.

Using our porcine model of deep dermal partial thickness burn injury, various durations (10min, 20min, 30min or 1h) and delays (immediate, 10min, 1h, 3h) of 15 degrees C running water first aid were applied to burns and compared to untreated controls. The subdermal temperatures were monitored during the treatment and wounds observed weekly for 6 weeks, for re-epithelialisation, wound surface area and cosmetic appearance. At 6 weeks after the burn, tissue biopsies were taken of the scar for histological analysis. Results showed that immediate application of cold running water for 20min duration is associated with an improvement in re-epithelialisation over the first 2 weeks post-burn and decreased scar tissue at 6 weeks. First aid application of cold water for as little as 10min duration or up to 1h delay still provides benefit.

Cyanoacrylate glue as an alternative mounting medium for resin-embedded semithin sections.

Commercially available generic Superglue (cyanoacrylate glue) can be used as an alternative mounting medium for stained resin-embedded semithin sections. It is colourless and contains a volatile, quick-setting solvent that produces permanent mounts of semithin sections for immediate inspection under the light microscope. Here, we compare the use of cyanoacrylate glue for mounting semithin sections with classical dibutyl phthalate xylene (DPX) in terms of practical usefulness, effectiveness and the quality of the final microscopic image.

Silver deposits in cutaneous burn scar tissue is a common phenomenon following application of a silver dressing.

BACKGROUND: Silver dressings have been widely and successfully used to prevent cutaneous wounds, including burns, chronic ulcers, dermatitis and other cutaneous conditions, from infection. However, in a few cases, skin discolouration or argyria-like appearances have been reported. This study investigated the level of silver in scar tissue post-burn injury following application of Acticoat, a silver dressing. METHODS: A porcine deep dermal partial thickness burn model was used. Burn wounds were treated with this silver dressing until completion of re-epithelialization, and silver levels were measured in a total of 160 scars and normal tissues. RESULTS: The mean level of silver in scar tissue covered with silver dressings was 136 microg/g, while the silver level in normal skin was less than 0.747 microg/g. A number of wounds had a slate-grey appearance, and dissection of the scars revealed brown-black pigment mostly in the middle and deep dermis within the scar. The level of silver and the severity of the slate-grey discolouration were correlated with the length of time of the silver dressing application. CONCLUSIONS: These results show that silver deposition in cutaneous scar tissue is a common phenomenon, and higher levels of silver deposits and severe skin discolouration are correlated with an increase in the duration of this silver dressing application.

The evaluation of a clinical scar scale for porcine burn scars.

This study describes the evaluation of a clinical scar scale for our porcine burn scars, which includes scar cosmetic outcome, colour, height and hair, supplemented with reference porcine scar photographs representing each scar outcome and scar colour scores. A total of 72 porcine burn scars at week 6 after burn were rated in vivo and/or on photographs. Good agreements were achieved for both intra-rater reliability (correlation is 0.86-0.98) and inter-rater reliability (ICC=80-85%). The results showed statistically significant correlations for each pair in this clinical scar scale (p<0.01), with the best correlation found between scar cosmetic outcome and scar colour. A multivariate principle components analysis revealed that this clinical scar assessment was highly correlated with scar histology, wound size, and re-epithelialisation data (p<0.001). More severe scars are clinically characterised by darker purple colouration, more elevation, no presence of hair, histologically by thicker scar tissue, thinner remaining normal dermis, are more likely to have worse contraction, and slower re-epithelialisation. This study demonstrates that our clinical scar scale is a reliable, independent and valuable tool for assessing porcine burn outcome and truthfully reflects scar appearance and function. To our knowledge, this is the first study demonstrating a high correlation between clinical scar assessment and scar histology, wound contraction and re-epithelialisation data on porcine burn scars. We believe that the successful use of porcine scar scales is invaluable for assessing potential human burn treatments.

Silver absorption on burns after the application of Acticoat: data from pediatric patients and a porcine burn model.

Silver dressings have been widely used to successfully prevent burn wound infection and sepsis. However, a few case studies have reported the functional abnormality and failure of vital organs, possibly caused by silver deposits. The aim of this study was to investigate the serum silver level in the pediatric burn population and also in several internal organs in a porcine burn model after the application of Acticoat. A total of 125 blood samples were collected from 46 pediatric burn patients. Thirty-six patients with a mean of 13.4% TBSA burns had a mean peak serum silver level of 114 microg/L, whereas 10 patients with a mean of 1.85% TBSA burns had an undetectable level of silver (<5.4 microg/L). Overall, serum silver levels were closely related to burn sizes. However, the highest serum silver was 735 microg/L in a 15-month-old toddler with 10% TBSA burns and the second highest was 367 microg/L in a 3-year old with 28% TBSA burns. In a porcine model with 2% TBSA burns, the mean peak silver level was 38 microg/L at 2 to 3 weeks after application of Acticoat and was then significantly reduced to an almost undetectable level at 6 weeks. Of a total of four pigs, silver was detected in all four livers (1.413 microg/g) and all four hearts (0.342 microg/g), three of four kidneys (1.113 microg/g), and two of four brains (0.402 microg/g). This result demonstrated that although variable, the level of serum silver was positively associated with the size of burns, and significant amounts of silver were deposited in internal organs in pigs with only 2% TBSA burns, after application of Acticoat.

Burn healing is dependent on burn site: a quantitative analysis from a porcine burn model.

This retrospective review examines healing in different sites on a porcine burn model; 24 pairs of burns on 18 pigs from other animal trials were selected for analysis. Each pair of burns was located on the either the cranial or the caudal part of the thoracic ribs region, on the same side of the animal. The burns were 40-50 cm(2) in size and of uniform deep-dermal partial thickness. Caudal burns healed significantly better than cranial burns, demonstrated by earlier closure of wounds, less scar formation and better cosmesis. To our knowledge, this is the first detailed study reporting that burn healing is affected by location on a porcine burn model. We recommend that similar symmetrical burns should be used for future comparative assessments of burn healing.

The efficacy of Aloe vera, tea tree oil and saliva as first aid treatment for partial thickness burn injuries.

Many alternative therapies are used as first aid treatment for burns, despite limited evidence supporting their use. In this study, Aloe vera, saliva and a tea tree oil impregnated dressing (Burnaid) were applied as first aid to a porcine deep dermal contact burn, compared to a control of nothing. After burn creation, the treatments were applied for 20 min and the wounds observed at weekly dressing changes for 6 weeks. Results showed that the alternative treatments did significantly decrease subdermal temperature within the skin during the treatment period. However, they did not decrease the microflora or improve re-epithelialisation, scar strength, scar depth or cosmetic appearance of the scar and cannot be recommended for the first aid treatment of partial thickness burns.

Cystic and alveolar echinococcosis: an epidemiological survey in a Tibetan population in southeast Qinghai, China.

An epidemiological investigation on echinococcosis was made in Jiuzhi County of Qinghai Province, western China. Ultrasonography and an indirect hemagglutination test revealed a morbidity of 8.0% (124/1,549) and a seroprevalence of 25.8% (287/1,113), respectively, in the Tibetan population. The morbidity in herdsmen (16.6%) and Buddhist priests (15%) was significantly higher than that in other occupation groups (3.2%), and it was higher in females (9.8%) than in males (6.2%). The ultrasound images showed a coexistence of cystic echinococcosis (CE) and alveolar echinococcosis (AE), occupying 69 and 31% of the cases, respectively. An Echinococcus Western blot assay was performed as a serological backup test for differentiating CE and AE. The assay revealed that serum samples from most cases with a positive AE image showed a specific antibody against antigen bands at 16/18 kDa. Autopsy proved that 9 out of 12 stray dogs were infected with Echinococcus granulosus (n = 8) and E. multilocularis (n = 1). Inspection at the abattoirs demonstrated a hydatid rate of 78.5% in yaks and 82.6% in sheep. The data indicate that Jiuzhi County is an important endemic area for both CE and AE, in both human and animal populations.

Conservative surgical debridement as a burn treatment: supporting evidence from a porcine burn model.

In thermal deep-dermal burns, surgical debridement is normally used in conjunction with skin grafting or skin substitutes and debridement alone as a burn treatment is not usually practiced. The current study addresses whether or not debridement alone would enhance burn wound healing on small deep-dermal-partial thickness burns. This was a prospective and blinded experimental trial using a porcine deep-dermal-partial thickness burn model. Four burns, approximately 50 cm(2) in size, were created on each of eight pigs. Two burns from each pig were immediately surgically debrided and the other two were not debrided as the internal control. Hydrate gel together with paraffin gauze were used to cover the burns for four pigs and silver dressings for the other four. Clinical assessment of wound healing was conducted over a 6-week period. Skin samples were collected at the end of the experiment and histopathological evaluation was performed. The results show thinner scar formation and lower scar height in the debrided compared with nondebrided wounds in the hydrate gel/paraffin gauze groups. There were no statistically significant differences in wound healing assessment between the debrided and nondebrided wounds dressed with silver dressings. This study provides supporting evidence that immediate debridement with an appropriate dressing and without skin grafting may promote wound healing, suggesting its potential benefit for clinical patients.

[An epidemiological survey on echinococcosis in Zhiduo County of Qinghai Province].

The survey was carried out in July, 2006 in Zhiduo County. The IHA and ELISA positive rate in human population was 4.5% (42/933) and 8.2% (76/931) respectively. Ultrasonography revealed a morbidity of 3.4% (33/979) with 3.2% Echinococcus granulosus and 0.2% of E. multilocularis respectively. Animal dissection showed an infection rate of 15.1% (14/93) in pikas with one infected by E. shiquicus proved by molecular biology. Coproantigen rate by ELISA was 62% (12/193) in dogs and 35.7% (5/14) in wolves. The results indicated that Zhiduo County is a mixed endemic area for echinococcosis.