Recombinant human granulocyte-macrophage colony-stimulating factor hydrogel promotes healing of deep partial thickness burn wounds

Objective

To assess the effects of recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF) hydrogel on the healing of deep partial thickness burn wounds.

Methods

Ninety three wounds of 65 burn patients who suffered from a deep partial thickness burn of <5% TBSA and could not heal over 3 weeks were included in this study. The patients were randomly assigned to use rhGM-CSF hydrogel (GC group, n = 32) or hydrogel without rhGM-CSF (control group, n = 33). rhGM-CSF hydrogel or hydrogel without rhGM-CSF was topically applied to the wounds, the dressing was changed once a day. Wound healing time and percentage, wound discharge, periwound inflammation, the positive wound swabs culture count, and adverse drug reactions were observed and compared between two groups.

Results

Healing time was 12.2 ± 5.0 days after the application of rhGM-CSF hydrogel. This was significantly shorter than that of control wounds (15.5 ± 4.7 days). Healing percentage at 14 days in the rhGM-CSF-treated wounds was 97.5 ± 7.7%, which was markedly higher than the control (85.9 ± 6.8%). At 3, 6, 12, 14 day, the GC group was significantly superior to the control group with respect to the score of periwound inflammation, wound purulence and discharge. The positive wound swabs culture count of the GC group on the 7th and 14th day post-treatment was 14 and 4, respectively, which was significantly lower than the control.

Conclusion

rhGM-CSF hydrogel promotes the healing process of deep partial thickness burns effectively. No adverse reaction of the drug was observed during the study.     

Early depth assessment of local burns by videomicroscopy: a novel proposed classification

Purpose

Videomicroscopy is very useful for burn depth assessment in an early phase; however, there is no practical classification that includes complicated anatomic, pathologic, and morphologic findings of burn wounds.The aim of this study was to propose a novel classification to assess burn depth in its early phase easily and reliably by videomicroscopy.

Methods

Forty-four patients with 56 intermediate-depth burn wounds were included. Burn depth was divided into each grade according to our proposed classification, which is composed of five categories based on dermal capillary integrity patterns. The intrarater and interrater reliabilities of the assessment by the second and third authors were evaluated by Cohen's unweighted κ-value.

Results

The results of the measurements according to the proposed classification showed an accuracy of 92.9%, sensitivity of 81.8%, and specificity of 100.0%.The intrarater reliability of the second and third authors showed substantial agreement (κ = 0.719 and 0.729, respectively). The interrater reliability of the sum of each observer's variable also showed substantial agreement (κ = 0.636).

Conclusion

This pattern analysis system is easy to use even for inexperienced personnel, and is reliable with high accuracy and specificity. Intrarater and interrater statistics also support its reliability and reproducibility.     

Outcomes of sprayed cultured epithelial autografts for full-thickness wounds: a single-centre experience

Introduction

The lack of autograft donor sites with major burns provides the impetus to develop innovative solutions due to the difficulty of wound closure. Autograft donor sites are particularly limited in patients with burns involving over 50% total body surface area (TBSA). The introduction of cultured epithelial cell autografts offers a potential solution to assist in wound closure. The objective of this study was the assessment of clinical results after sprayed application of the cultured epithelial autograft (CEA, Keraheal™, Seoul, Korea, MCTT) suspension onto the wounds of extensively burned patients.

Materials and methods

This retrospective clinical audit of major burn patients (n = 16) describes the use of CEA which was combined with 6:1 meshed expansion grafts in those with the burn over 40% TBSA in our hospital between the period of August 2007 and January 2010. The burn patients included 12 males and 4 females with a mean age 41.5 and a burn area of 51.3 ± 3.1% TBSA (30–70%; median: 50.5%) and a mean third burn area of 32.5 ± 3.0% TBSA (median 34.0%).

Results

The take rates were 37.6%, 68.0% and 90.0% on average at 2, 4 and 8 weeks after treatment with the suspension, respectively, and the transplantation of the cultured cells was applied to full-thickness burns, with the coverage of a skin area of 497.5 cm² per 1 ml of the cultured cells. For clinical follow-up, 12 patients were observed for 21.5 months on average, with a maximum follow-up period of 39 months. Six patients were excluded from the surveillance because two died during hospitalisation and the other four were impossible to trace.

Conclusion

The use of a sprayed cultured epithelial cell autograft (Keraheal™) in treating a full-thickness skin wound in severely burned patients results in favourable quality of scars and also good potential to save lives by providing epidermal cover.     

Occlusion of seminal vesicles increases sexual activity in a mouse model

Background

Little is known about the physiologic role of seminal vesicles beyond their fertility function. It has been suggested repeatedly that seminal vesicles have an impact on sexual activity. Although this has been investigated in various animal models, such a role has never been found.

Objective

To assess in a novel mouse model whether occlusion of seminal vesicles affects sexual activity.

Design, setting, and participants

Adult male CD1 mice (n = 77) were assigned randomly to the experimental groups: (1) seminal vesicle occlusion (SVO) (n = 24), (2) seminal vesicle resection (SVR) (n = 23), and (3) sham operation (SO) (n = 30). Adult females were brought into estrus by the Whitten effect. After recuperation, mouse pairs were observed during sessions of 3 h each. Sexual activity was analyzed separately by three observers blinded to the experimental conditions.

Intervention

SVO, SVR, and SO.

Outcome measurements and statistical analysis

The primary end point was percentage of sessions with intromission; secondary end points were number of intromissions and latency until first intromission. A logistic regression model and the Kruskal-Wallis test were used.

Results and limitations

A total of 141 sessions for a total of 423 h were analyzed. Intromission was scored in 20 of 42 sessions (48%) with SVO mice, a significantly higher rate than the 8 of 39 sessions (21%) with SVR mice (p = 0.001) and 18 of 60 sessions (30%) with SO mice (p = 0.004). Secondary end points were comparable in all three groups (p = 0.303 and 0.450, respectively).

Conclusions

Males with SVO were significantly more often sexually active than males undergoing SVR or SO. This suggests that occluded, and thus engorged, seminal vesicles increase sex drive in male mice. Since the potential clinical benefit might be highly relevant, further studies should confirm these promising results and investigate the potential application in men.     

NRAMP1 and hGPX1 gene polymorphism and response to bacillus Calmette-Guérin therapy for bladder cancer

Background

The natural resistance-associated macrophage protein 1 (NRAMP1) gene is associated with susceptibility to Mycobacterium tuberculosis in humans and to bacillus Calmette-Guérin (BCG) in mice. The detoxification enzyme, human glutathione peroxidase 1 (hGPX1), is associated with recurrence of bladder cancer (BCa).

Objective

To determine whether NRAMP1 and hGPX1 gene polymorphisms correlate with response to BCG immunotherapy for non–muscle-invasive BCa (NMIBC).

Design, setting, and participants

DNA was obtained from the peripheral blood of 99 NMIBC patients who were prospectively randomized to receive postresection intravesical BCG (81 mg [n = 50] or 27 mg [n = 19]) or BCG (27 mg) with interferon alpha (IFN-α; n = 30). The median follow-up time was 60 mo.

Intervention

Intravesical BCG or BCG–IFN-α.

Measurements

Restriction fragment length polymorphism (RFLP) analysis was performed to identify polymorphisms in the NRAMP1 promoter region (GT repeat number) and at position 543 (aspartate [D] and/or asparagine [N] expression) within the NRAMP1 protein (D543N) and position 198 (proline and/or leucine expression) within the hGPX1 protein (Pro198Leu). Data were analyzed using χ² analysis, multivariate analysis, and Kaplan-Meier curves.

Results and limitations

On univariate analysis, the NRAMP1 D543N G:G genotype had decreased cancer-specific survival (CSS; p = 0.036). The hGPX1 CT genotype (Pro-Leu) had decreased recurrence time (p = 0.03) after BCG therapy. On multivariate analysis, patients with the NRAMP1 D543N G:G genotype and allele 3 (GT)n polymorphism had decreased recurrence time (p = 0.014 and p = 0.03) after BCG therapy. The limitation of this study was its small sample size.

Conclusions

Polymorphisms of the NRAMP1 and hGPX1 genes may be associated with recurrence of BCa after BCG immunotherapy.     

Are Antisperm Antibodies Really Associated with Proven Chronic Inflammatory and Infectious Diseases of the Male Reproductive Tract?

Background

It is debated whether chronic urogenital inflammations and infections may trigger the formation of antisperm antibodies (ASA) in semen.

Objective

To evaluate the formation of ASA in defined chronic inflammatory and infectious diseases of the male reproductive tract (MRT).

Design, setting, and participants

Three hundred sixty-five patients retrospectively enrolled in a single center were categorized as having National Institutes of Health (NIH) category II chronic prostatitis (n = 38), NIH category IIIa chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) (n = 59), NIH category IIIb CP/CPPS (n = 213), chronic epididymitis (n = 34), and chronic urethritis (n = 21). Forty-five age-matched men served as controls.

Measurements

All subjects underwent microbiologic and cytologic analysis for common bacteria, yeasts, and mycoplasma using the four-glass test. Urine samples, ejaculates, and urethral swabs were analyzed with polymerase chain reaction (PCR) for Chlamydia trachomatis and Neisseria gonorrhea. Semen analysis followed World Health Organization (WHO) standards. ASA in seminal plasma were analyzed using the mixed agglutination reaction (MAR) test.

Results and limitations

The overall positive detection rate of clinically significant levels (≥50% of spermatozoa coated by ASA) of IgG and IgA antibodies was 1.8% and 0.8%, respectively, in the patient group. No clinically significant levels of ASA were detected in the control group, and no statistically significant difference was observed between controls and patients (IgG, p = 1.0; IgA, p = 1.0). No difference was found between the different inflammatory and infectious diseases and the control group in the detection rate of ASA, even when the cut-point value was lowered to ≥1% (IgG, p = 0.4; IgA, p = 0.3). Moreover, in one selected subgroup of patients (n = 26) with persistent increased inflammatory parameters (peroxidase-positive leukocytes [PPL] ≥1 × 10⁶/ml and elastase ≥230 ng/ml), no significant difference in the levels of ASA was observed compared with the controls (IgG, p = 0.1; IgA, p = 0.8).

Conclusion

There is no association between chronic inflammatory or infectious diseases of the MRT and the presence of ASA in semen.     

Effects of Once-Daily Tadalafil on Erectile Function in Men with Erectile Dysfunction and Signs and Symptoms of Benign Prostatic Hyperplasia

Background

Lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH; BPH-LUTS) may be associated with erectile dysfunction (ED).

Objective

To evaluate the effects of once-daily tadalafil on erectile function in men with ED and BPH-LUTS.

Design, setting, and participants

Post hoc analysis of a phase 2–3, multinational, randomized, double-blind, placebo-controlled, parallel-group study of men with ED and moderate-to-severe LUTS secondary to BPH who reported being sexually active. In contrast to typical ED trials, no sexual activity threshold was required to participate.

Interventions

Screening and 4-wk washout period for patients taking BPH and/or ED treatments; 4-wk placebo run-in period; then once-daily placebo or tadalafil 2.5, 5, 10, or 20 mg for 12 wk.

Measurements

International Index of Erectile Function–Erectile Function (IIEF-EF) domain score, International Prostate Symptom Score (IPSS), peak urinary flow rate (Q_max), and postvoid residual volume (PVR). Analyses were performed in men who reported being sexually active with a female partner and who expected to remain so throughout the study. IIEF-EF data are presented for the BPH/ED population overall and for subgroups stratified by baseline age group, body mass index, BPH-LUTS severity, prostate-specific antigen, prior α-blocker use, and prior ED therapy.

Results and limitations

Overall, 581 men were included (placebo, n = 115; tadalafil 2.5 mg, n = 113; tadalafil 5 mg, n = 117; tadalafil 10 mg, n = 120; tadalafil 20 mg, n = 116). IIEF-EF domain score improvements from baseline to end point with tadalafil were 5.4 (2.5 mg), 6.8 (5 mg), 7.9 (10 mg), and 8.2 (20 mg) versus 2.0 with placebo (least-squares means; all p values <0.001). IIEF-EF domain score improvements were observed with tadalafil for all subgroup analyses, with no significant differences between subgroup or subgroup-by-treatment interaction terms. IPSS improvements from baseline to end point were significantly greater for all tadalafil doses versus placebo (all p values <0.05). Changes in Q_max and PVR were small and not clinically meaningful.

Conclusions

These data support the use of once-daily tadalafil in men with ED and BPH-LUTS.

Trial registration

http://www.clinicaltrials.gov: NCT00384930.     

A Pollen Extract (Cernilton) in Patients with Inflammatory Chronic Prostatitis–Chronic Pelvic Pain Syndrome: A Multicentre, Randomised, Prospective, Double-Blind, Placebo-Controlled Phase 3 Study

Background

National Institutes of Health (NIH) category III prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent condition for which no standardised treatment exists.

Objectives

To assess the safety and efficacy of a standardised pollen extract in men with inflammatory CP/CPPS.

Design, setting, and participants

We conducted a multicentre, prospective, randomised, double-blind, placebo-controlled phase 3 study comparing the pollen extract (Cernilton) to placebo in men with CP/CPPS (NIH IIIA) attending urologic centres.

Intervention

Participants were randomised to receive oral capsules of the pollen extract (two capsules q8 h) or placebo for 12 wk.

Measurements

The primary endpoint of the study was symptomatic improvement in the pain domain of the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). Participants were evaluated using the NIH-CPSI individual domains and total score, the number of leukocytes in post–prostatic massage urine (VB3), the International Prostate Symptom Score (IPSS), and the sexuality domain of a life satisfaction questionnaire at baseline and after 6 and 12 wk.

Results and limitations

In the intention-to-treat analysis, 139 men were randomly allocated to the pollen extract (n = 70) or placebo (n = 69). The individual domains pain (p = 0.0086) and quality of life (QoL; p = 0.0250) as well as the total NIH-CPSI score (p = 0.0126) were significantly improved after 12 wk of treatment with pollen extract compared to placebo. Response, defined as a decrease of the NIH-CPSI total score by at least 25% or at least 6 points, was seen in the pollen extract versus placebo group in 70.6% and 50.0% (p = 0.0141), respectively. Adverse events were minor in all patients studied.

Conclusions

Compared to placebo, the pollen extract significantly improved total symptoms, pain, and QoL in patients with inflammatory CP/CPPS without severe side-effects.     

Extracorporeal shock waves improve angiogenesis after full thickness burn

Objective

Extensive wounds of burn patients remain a challenge due to wound infection and subsequent septicemia. We wondered whether extracorporeal shock wave application (ESWA) accelerates the healing process. The aim of the study was to analyze microcirculation, angiogenesis and leukocyte endothelium interaction after burns by using ESWA with two types of low intensity.

Methods

Full-thickness burns were inflicted to the ears of hairless mice (n = 51; area: 1.3 mm²). The mice were randomized into five groups: (A) low-energy shock waves after burn injury (0.04 mJ/mm²); (B) very low-energy shock waves after burn injury (0.015 mJ/mm²); (C) mice received burns but no ESWA (control group); (D) mice without burn were exposed to low-energy shock waves; (E) mice without burns and with no shock wave application. Intravital fluorescent microscopy was used to assess microcirculatory parameters, angiogenesis and leukocyte behavior. ESWA was performed on day 1, 3 and 7 (500 shoots, 1 Hz). Values were obtained straight after and on days 1, 3, 7 and 12 post burn.

Results

Group A showed accelerated angiogenesis (non-perfused area at day 12: 5.3% vs. 9.1% (group B) and 12.6% (group C), p = 0.005). Both shock wave groups showed improved blood flow after burn compared to group C. Shock waves significantly increased the number of rolling leukocytes compared to the non-ESWA-treated animals (group D: 210.8% vs. group E: 83.3%, p = 0.017 on day 7 and 172.3 vs. 90.9%, p = 0.01 on day 12).

Conclusion

Shock waves have a positive effect on several parameters of wound healing after burns, especially with regard to angiogenesis and leukocyte behaviour. In both ESWA groups, angiogenesis and blood flow outmatched the control group. Within the ESWA groups the higher intensity (0.04 mJ/mm²) showed better results than the lower intensity group. Moreover, shock waves increased the number of rolling and sticking leukocytes as a part of an improved metabolism.     

Methylated spirit burns: an ongoing problem

Objective

Despite many educational campaigns we still see burns caused by methylated spirit every year. We undertook a retrospective study to analyse the impact of this problem.

Methods

We retrospectively collected data of all patients with burns caused by methylated spirit over twelve years from 1996 to 2008. Our main endpoints were: incidence, age, mechanism of injury, total body surface area (TBSA) burned, burn depth, need for surgery and length of hospital stay.

Results

Ninety-seven patients with methylated spirit burns were included. During the study period there was no decrease in the number of patients annually admitted to the burn unit with methylated spirit burns. 28% of the patients (n = 27) were younger than eighteen years old, 15% (n = 15) were ten years old or younger. The most common cause of burns was carelessness in activities involving barbecues, campfires and fondues. Mean TBSA burned was 16% (SD 12.4). 70% (n = 68) had full thickness burns. 66% (n = 64) needed grafting. Mean length of hospital stay was 23 days (SD 24.7).

Conclusions

The use of methylated spirit is an ongoing problem, which continues to cause severe burns in adults and children. Therefore methylated spirit should be banned in households. We suggest sale only in specialised shops, clear labelling and mandatory warnings.     

Duloxetine for mild to moderate postprostatectomy incontinence: preliminary results of a randomised, placebo-controlled trial

Background

Duloxetine is effective in the management of stress urinary incontinence (SUI) in women but has been poorly evaluated in the treatment of SUI following radical prostatectomy (RP).

Objective

To establish the superiority of duloxetine over placebo in SUI after RP.

Design, setting, and participants

We conducted a prospective, randomised, placebo-controlled, double-blind, monocentric superiority trial. After a placebo run-in period of 2 wk, patients with SUI after RP were randomised to receive either 80 mg of duloxetine daily or matching placebo for 3 mo.

Measurements

The primary outcome measure was the relative variation in incontinence episodes frequency (IEF) at the end of study compared to baseline. Secondary outcomes included quality of life (QoL) measures (Incontinence Impact Questionnaire Short Form [IIQ-SF], Urogenital Distress Inventory Short Form [UDI-SF], Incontinence Quality of Life [I-QoL]), symptom scores (Urinary Symptom Profile [USP] questionnaire, International Consultation on Incontinence/World Health Organisation Short Form questionnaire [ICIQ-SF], the Beck Depression Inventory [BDI-II] questionnaire), 1-h pad test, and assessment of adverse events.

Results and limitations

Thirty-one patients were randomised to either the treatment (n = 16) or control group (n = 15). Reduction in IEF was significant with duloxetine compared to placebo (mean ± standard deviation [SD] variation: −52.2% ± 38.6 [range: −100 to +46] vs +19.0% ± 43.5 [range: −53 to +104]; mean difference: 71.2%; 95% confidence interval [CI] for the difference: 41.0–101.4; p < 0.0001). IIQ-SF total score, UDI-SF total score, SUI subscore of the USP questionnaire, and question 3 of the ICIQ-SF questionnaire showed improvement in the duloxetine group (p = 0.006, p = 0.02, p = 0.0004, and p = 0.003, respectively). Both treatments were well tolerated throughout the study period.

Conclusions

Duloxetine is effective in the treatment of incontinence symptoms and improves QoL in patients with SUI after RP.     

Amino-Terminal Pro-C-Type Natriuretic Peptide is Associated with the Presence, Severity, and Duration of Vasculogenic Erectile Dysfunction

Background

Endothelial dysfunction is a key event in the pathophysiology of erectile dysfunction (ED) and generalized vascular disease. C-type natriuretic peptide (CNP) is a paracrine molecule that effects endothelial integrity and vascular tone.

Objective

To determine the role of CNP in men with vasculogenic ED.

Design, setting, and participants

Fifty-two consecutive men (age: 57 ± 10 yr) with nonpsychogenic and nonhormonal ED for >6 mo and free of cardiovascular disease who were referred to the Cardiovascular Diseases and Sexual Health Unit of our Department for evaluation of ED were compared with 31 subjects with normal erectile function matched for age, body mass index, and traditional risk factors.

Measurements

Vasculogenic ED was diagnosed according to comprehensive history, physical examination, Sexual Health Inventory for Men (SHIM-5) scoring, hormonal testing, and penile color-Doppler ultrasound. Amino-terminal proCNP (NT-proCNP) was measured in plasma with enzyme-linked immunosorbent assay (ELISA).

Results and limitations

Compared to controls, ED patients had significantly lower NT-proCNP levels (0.21 ± 0.08 pmol/l in ED patients vs 0.34 ± 0.07 pmol/l in control subjects; p < 0.001). NT-proCNP levels were associated with erectile performance as expressed by SHIM-5 score (r = 0.57; p < 0.001), even after adjusting for confounders. There was also an inverse linear relationship between ED duration and NT-proCNP levels (p < 0.05). In patients with arteriogenic ED, there was a positive correlation of NT-proCNP levels with peak systolic velocity (PSV) (r = 0.51; p = 0.01).

Conclusions

CNP levels are associated with the presence, severity, and duration of ED. These findings provide further insight into the role of CNP in the pathophysiology of ED.     

Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial

Background

Tadalafil improved lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH; LUTS/BPH) in clinical studies but has not been evaluated together with an active control in an international clinical study.

Objective

Assess tadalafil or tamsulosin versus placebo for LUTS/BPH.

Design, setting, and participants

A randomised, double-blind, international, placebo-controlled, parallel-group study assessed men ≥45 yr of age with LUTS/BPH, International Prostate Symptom Score (IPSS) ≥13, and maximum urinary flow rate (Q_max) ≥4 to ≤15 ml/s. Following screening and washout, if needed, subjects completed a 4-wk placebo run-in before randomisation to placebo (n = 172), tadalafil 5 mg (n = 171), or tamsulosin 0.4 mg (n = 168) once daily for 12 wk.

Measurements

Outcomes were assessed using analysis of covariance (ANCOVA) or ranked analysis of variance (ANOVA) (continuous variables) and Cochran-Mantel-Haenszel test or Fisher exact test (categorical variables).

Results and limitations

IPSS significantly improved versus placebo through 12 wk with tadalafil (−2.1; p = 0.001; primary efficacy outcome) and tamsulosin (−1.5; p = 0.023) and as early as 1 wk (tadalafil and tamsulosin both −1.5; p < 0.01). BPH Impact Index significantly improved versus placebo at first assessment (week 4) with tadalafil (−0.8; p < 0.001) and tamsulosin (−0.9; p < 0.001) and through 12 wk (tadalafil −0.8, p = 0.003; tamsulosin −0.6, p = 0.026). The IPSS Quality-of-Life Index and the Treatment Satisfaction Scale–BPH improved significantly versus placebo with tadalafil (both p < 0.05) but not with tamsulosin (both p > 0.1). The International Index of Erectile Function–Erectile Function domain improved versus placebo with tadalafil (4.0; p < 0.001) but not tamsulosin (−0.4; p = 0.699). Q_max increased significantly versus placebo with both tadalafil (2.4 ml/s; p = 0.009) and tamsulosin (2.2 ml/s; p = 0.014). Adverse event profiles were consistent with previous reports. This study was limited in not being powered to directly compare tadalafil versus tamsulosin.

Conclusions

Monotherapy with tadalafil or tamsulosin resulted in significant and numerically similar improvements versus placebo in LUTS/BPH and Q_max. However, only tadalafil improved erectile dysfunction.

Trial registration

Clinicaltrials.gov ID NCT00970632     

Pulmonary microvascular hyperpermeability and expression of vascular endothelial growth factor in smoke inhalation- and pneumonia-induced acute lung injury

Introduction

Acute lung injury (ALI) and sepsis are major contributors to the morbidity and mortality of critically ill patients. The current study was designed further evaluate the mechanism of pulmonary vascular hyperpermeability in sheep with these injuries.

Methods

Sheep were randomized to a sham-injured control group (n = 6) or ALI/sepsis group (n = 7). The sheep in the ALI/sepsis group received inhalation injury followed by instillation of Pseudomonas aeruginosa into the lungs. These groups were monitored for 24 h. Additional sheep (n = 16) received the injury and lung tissue was harvested at different time points to measure lung wet/dry weight ratio, vascular endothelial growth factor (VEGF) mRNA and protein expression as well as 3-nitrotyrosine protein expression in lung homogenates.

Results

The injury induced severe deterioration in pulmonary gas exchange, increases in lung lymph flow and protein content, and lung water content (P < 0.01 each). These alterations were associated with elevated lung and plasma nitrite/nitrate concentrations, increased tracheal blood flow, and enhanced VEGF mRNA and protein expression in lung tissue as well as enhanced 3-nitrotyrosine protein expression (P < 0.05 each).

Conclusions

This study describes the time course of pulmonary microvascular hyperpermeability in a clinical relevant large animal model and may improve the experimental design of future studies.     

Prevention of recurrent urinary tract infections by intravesical administration of hyaluronic acid and chondroitin sulphate: a placebo-controlled randomised trial

Background

Urinary tract infection (UTI) is a prevalent condition in women during their lifetime with a high rate of recurrence within 3–6 mo.

Objectives

Our aim was to investigate the efficacy and tolerability of the intravesical administration of combined hyaluronic acid (HA) and chondroitin sulphate (CS) in female patients with a history of recurrent UTI.

Design, setting, and participants

We conducted a prospective, randomised, double-blind, placebo-controlled study comparing the intravesical instillation of HA-CS with placebo in women with recurrent UTI.

Intervention

Participants were randomised to receive 50 ml of sterile sodium HA 1.6% and CS 2.0% solution (IALURIL^®) weekly for 4 wk and then monthly for 5 mo.

Measurements

The primary end point of the study was defined as the mean number of UTI per patient per year. Participants were evaluated addressing UTI status/urinary symptoms and with a general health-related quality-of-life (QoL) questionnaire at baseline and after 3, 6, 9, and 12 mo.

Results and limitations

In the intention-to-treat analysis, 57 women were randomly allocated to HA-CS (n = 28) or placebo (n = 29). The UTI rate per patient per year at the end of the study (12 mo) (mean ± SD: −86.6% ± 47.6 vs −9.6% ± 24.6; mean difference: 77%; 95% confidence interval, 72.3–80.8; p = 0.0002) and the mean time to UTI recurrence (52.7 ± 33.4 vs 185.2 ± 78.7 d; p < 0.001) were significantly reduced after treatment with HA-CS compared with placebo. Overall urinary symptoms and QoL measured by questionnaires significantly improved compared with placebo (Pelvic Pain and Urgency/Frequency questionnaire symptom score: 14.53 ± 4.32 vs 9.88 ± 6.77; p = 0.004; SF-36 QoL score: 78.6 ± 6.44 vs 53.1 ± 4.72; p < 0.001). No serious adverse event was reported.

Conclusions

Compared with placebo, HA-CS intravesical instillations significantly reduced UTI rate without severe side effects while improving symptoms and QoL over a 12-mo period in patients with recurrent UTI.

Trial registration

ISRCTN 76354426.     

The use of Suprathel(®) in deep dermal burns: first results of a prospective study

Introduction

While autologous skin grafting has been the standard for coverage of full-thickness areas, several options for deep-partial-thickness defects exist. With regard to economising donor sites, we compared a copolymer based on dl-lactid acid (Suprathel^®) as temporary wound dressing with autologous skin, and analysed time to healing and scar quality in matched areas of deep-partial-thickness burn.

Methods

We recruited 18 patients with a median age of 45 years (range: 25–83 years), for this prospective, non-blinded controlled non-inferiority study, suffering from deep-partial-thickness burns from November 2009 to July 2010. After early tangential excision, matched deep-partial-thickness areas were covered with 1:1.5 meshed autologous skin grafts and the copolymer for direct intra-individual comparison. Scars were evaluated by means of the Vancouver Scar Scale (VSS), the Patient and Observer Scar Assessment Scale (POSAS) and suction cutometry (MPA 580, Courage and Khazaka Electronic GmbH, Cologne, Germany) on days 30 and 90, postoperatively.

Results

Fifteen days after surgery, complete wound closure was present in 44.4% (8/18) of all areas covered with copolymer and 88.9% (16/18) in the split-thickness skin graft (STSG) area (p = 0.008). Evaluation of the total VSS, POSAS and cutometry satisfied the criterion of non-inferiority for Suprathel^® on day 30. Ninety days after surgery, only the Observer Scar Scale showed that Suprathel is non-inferior to STSG, albeit the mean total VSS and Patient Scar Scale were better in Suprathel^® areas.

Conclusion

Suprathel^® represents a solid, reliable epidermal skin substitute with longer healing times in comparison to skin grafts but comparable results concerning early scar formation. Suprathel^® can serve as a tool in treatment portfolio for adult patients suffering from deep dermal burns. Especially in patients with extensive burns, Suprathel^® can be used to cover the deep dermal burn wounds to save STSGs and its donor sites for the coverage of full-thickness burned areas.     

Effect of ephedrine on the intubation conditions using rocuronium versus succinylcholine

Objective

The goal of this study was to determine if ephedrine could improve intubating conditions when it is administered before the muscle relaxant (rocuronium and succinylcholine).

Patients and methods

In this prospective randomized double-blind study, 80 patients ASA I- II, scheduled for elective surgery, were allocated randomly to receive: succinylcholine 1 mg/kg + ephedrine 70 μg/kg (Group I, n = 20); rocuronium 0.6 mg/kg + ephedrine 70 μg/kg (Group II, n = 20); succinylcholine 1 mg/kg + 0.9% saline (Group III, n = 20); rocuronium 0.6 mg/kg + 0.9% saline (Group IV, n = 20). Induction of anaesthesia started with administration of the first syringe containing either ephedrine or saline, then 30 s later propofol 2.5 mg/kg and fentanyl 3 μg/kg, were administered followed by the contents of the second syringe containing either rocuronium or succinylcholine. Thirty seconds after injection of the muscle relaxant, another blinded staff anaesthetist performed intubation of the patient. Intubating conditions were evaluated according to criteria's of the conference of Copenhagen. Heart rate, systolic blood pressure and diastolic were also noted. Kruskall-Wallis test for non-parametric variable and Student t test for quantitative variables were used for statistical analysis.

Results

There was no significant difference between the groups concerning age, sex, BMI and ASA status. Pretreatment by ephedrine improved significantly (p < 0.0001) intubating conditions after succinylcholine and rocuronium.

Conclusion

Use of ephedrine 30 seconds before induction with propofol, fentanyl followed by rocuronium or succinylcholine provides faster good conditions of intubation.     

Stress proteins and cytokines are urinary biomarkers for diagnosis and staging of bladder cancer

Background

Cancer often involves inflammatory processes. We hypothesized that immune mediators in urine may serve as biomarkers for bladder cancer (BCa).

Objective

To investigate whether BCa might be marked by urinary levels of heat shock proteins (HSPs; HSP60, HSP70, or HSP90) or cytokines (interferon [IFN]-γ, tumor necrosis factor [TNF]-α, tumor growth factor [TGF]-β, interleukin [IL]-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, or IL-13).

Design, setting, and participants

This was a case–control study with a discovery and validation phase. We examined urine from 106 consecutive patients: healthy controls (n = 18); hematuria with no evidence of BCa (n = 20); non–muscle-invasive BCa (n = 50); and muscle-invasive BCa (n = 18). The concentrations of HSPs and cytokines were assessed by enzyme-linked immunosorbent assay. In the validation phase, independent urine samples from 40 patients were analyzed (controls [n = 19] and BCa [n = 21]).

Measurements

We used the area under the curve (AUC) of a receiver operating characteristic analysis to determine the ability of HSPs and cytokines to mark BCa and applied a multivariate logistic regression to create a formula able to diagnose BCa. The formula was applied to the validation set without recalculation, and positive and negative predictive values were calculated.

Results and limitations

Urinary concentrations of IL-8, IL-10, and IL-13 were significantly elevated in BCa; IL-13 was the most prominent marker (AUC: 0.93; 95% confidence interval [CI], 0.85–0.99). The multivariate regression analysis highlighted HSP60 (odds ratio [OR]: 1.206; 95% CI, 1.041–1.397, p = 0.003) and IL-13 (OR: 1.020; 95% CI: 1.007–1.033, p = 0.012).The validation assay was performed using HSP60 and IL-13. The overall positive predictive value was 74% (95% CI, 64–84%); and the negative predictive value was 76% (95% CI, 66–86%). Since we examined a small number of patients, the results need to be confirmed in a larger cohort.

Conclusions

These results suggest that it might be possible to develop a urinary biomarker for BCa and raise the possibility that expression of anti-inflammatory cytokines and HSPs might allow BCa to evade immune surveillance.     

Perioperative efficacy of laparoscopic partial nephrectomy for tumors larger than 4 cm

Background

Laparoscopic partial nephrectomy (LPN) is typically reserved for kidney tumors ≤4 cm in size. The use of LPN in patients with larger tumors (>4 cm) has not been systematically evaluated.

Objective

To examine technical feasibility and perioperative safety and efficacy of LPN for clinical stage pT1b–T2 tumors >4 cm.

Design, setting, and participants

This is a retrospective review of data from an Institutional Review Board–approved, prospectively maintained database of 425 LPN procedures over a 6-yr period (September 1999 through December 2005). Patients were grouped according to tumor size: control group1: <2 cm (n = 89; 21% of patients); control group 2: 2–4 cm (n = 278; 65% of patients); and study group 3: >4 cm (n = 58; 14% of patients).

Intervention

Retroperitoneal and transperitoneal LPN.

Measurements

Serum creatinine levels, estimated glomerular filtration rates.

Results and limitations

For groups 1, 2, and 3, mean tumor size was 1.5 cm, 2.9 cm, and 6 cm in diameter, respectively (p < 0.001). Study group 3 patients more often had an American Society of Anesthesiologists score ≥3 (p < 0.05), central tumors (p < 0.001), pelvicalyceal repair (p = 0.004), and heminephrectomy (p < 0.001). Total operative time, estimated blood loss, and duration of hospital stay were equivalent. Mean warm ischemia time was 30 min, 32 min, and 38 min in groups 1, 2, and 3, respectively (p = 0.007). Tumor size >4 cm did not increase significant risk for positive tumor margins, intraoperative complications, or postoperative genitourinary complications. In each group preoperative stage ≥3 chronic kidney disease (CKD) was present in 31%, 35%, and 44% of patients in groups 1, 2, and 3, respectively (p = 0.15); postoperatively, stage 3–5 CKD incidence increased to 52%, 52%, and 63% in groups 1, 2, and 3, respectively (p = 0.20). Patients with tumor size >4 cm and preoperative stage 3–5 CKD had an 8-fold increase in risk for CKD stage progression. Limitations of the study include retrospective analysis and a relatively low number of patients in group 3.

Conclusions

Given laparoscopic expertise and appropriate patient selection, LPN is feasible and efficacious for kidney tumors >4 cm. Indications for LPN should be expanded to include patients with amenable tumors >4 cm in order to maximally preserve kidney function in these patients.     

Are parents in the UK equipped to provide adequate burns first aid?

Aim

Simple first aid following a burn injury has been shown to improve outcome. With this in mind, a prospective study was conducted to evaluate the knowledge of burns first aid amongst parents in South Yorkshire, United Kingdom. This information was used to identify which aspects of burn first aid need to be highlighted in an education campaign and who the target audience should be. A simple mnemonic is suggested to assist parental education on the topic.

Methods

Parents attending outpatient clinics at Sheffield Children's Hospital were interviewed and asked about the first aid they would provide for a child with a large scald. Removal of hot clothes and jewellery; application of cold water for 10–20 min; obtaining medical advice; and covering the burn with a plastic film or clean cloth were all considered to be ideal responses. Variations in responses in relation to the age and ethnicity of the parent were noted.

Results

One hundred and eighty eight parents were included in the questionnaire. Of these, 81% (n = 152) were white British and 20% (n = 36) were from other ethnic groups. Only 10% (n = 18) of all respondent would give all the ideal first aid steps. Less than 40% (n = 73) of parents questioned would remove hot clothes and jewellery. There was no significant difference in responses between ethnic groups when assessing knowledge of the need to remove hot soaked clothing. Although 73% (n = 137) of parents would run the burn under cool water, only 35% (n = 66) would cool the burn for an adequate length of time. White British parents were significantly more likely to run cool water over the burn, and to continue this for the recommended 10–20 min. Whilst 88% (n = 165) of parents would seek medical attention, this was significantly less in parents under 20 years old. Finally, 92% (n = 173) of parents would protect the wound with appropriate dressings, but of note, 26% (n = 9) of parents from minority ethnic groups would potentially impair burn healing by using inappropriate dressings and topical agents including butter, milk, cooking oil and toothpaste.

Conclusions

The questionnaire findings highlighted the need for improved parental awareness of burns first aid. This was across all ethnic groups and ages questioned. In particular, knowledge of appropriate cooling times and the use of inappropriate dressings were highlighted as areas for concern. Ideal burns first aid measures were summarised with the mnemonic STOP–Strip clothes, turn on the tap for 10 min, organise help, put on plastic film. This mnemonic is to be used in a pilot educational campaign in the Sheffield area, with possible expansion nationwide.