The degree of joint range of motion limitations after burn injuries during recovery.

INTRODUCTION: The aim of this study was to determine the degree of ROM limitations of extremities, joints and planes of motion after burns and its prevalence over time. METHOD: The database of a longitudinal multicenter cohort study in the Netherlands (2011-2012) was used. From patients with acute burns involving the neck, shoulder, elbow, wrist, hip, knee and ankle joints that had surgery, ROM of 17 planes of motion was assessed by goniometry at 3, 6 weeks, 3-6-9 and 12 months after burns and at discharge. RESULTS: At 12 months after injury, 12 out of 17 planes of motion demonstrated persistent joint limitations. The five unlimited planes of motion were all of the lower extremity. The most severely limited joints at 12 months were the neck, ankle, wrist and shoulder. The lower extremity was more severely limited in the early phase of recovery whereas at 12 months the upper extremity was more severely limited. CONCLUSION: The degree of ROM limitations and prevalence varied over time between extremities, joints and planes of motion. This study showed which joints and planes of motion should be watched specifically concerning the development of scar contracture.

Successful intergeneric transfer of a major apple scab resistance gene (Rvi6) from apple to pear and precise comparison of the downstream molecular mechanisms of this resistance in both species.

BACKGROUND: Scab is the most important fungal disease of apple and pear. Apple (Malus x domestica Borkh.) and European pear (Pyrus communis L.) are genetically related but they are hosts of two different fungal species: Venturia inaequalis for apple and V. pyrina for European pear. The apple/V. inaequalis pathosystem is quite well known, whereas knowledge about the pear/V. pyrina pathosystem is still limited. The aim of our study was to analyse the mode of action of a major resistance gene of apple (Rvi6) in transgenic apple and pear plants interacting with the two scab species (V. inaequalis and V. pyrina), in order to determine the degree of functional transferability between the two pathosystems. RESULTS: Transgenic pear clones constitutively expressing the Rvi6 gene from apple were compared to a scab transgenic apple clone carrying the same construct. After inoculation in greenhouse with V. pyrina, strong defense reactions and very limited sporulation were observed on all transgenic pear clones tested. Microscopic observations revealed frequent aborted conidiophores in the Rvi6 transgenic pear / V. pyrina interaction. The macro- and microscopic observations were very comparable to the Rvi6 apple / V. inaequalis interaction. However, this resistance in pear proved variable according to the strain of V. pyrina, and one of the strains tested overcame the resistance of most of the transgenic pear clones. Comparative transcriptomic analyses of apple and pear resistant interactions with V. inaequalis and V. pyrina, respectively, revealed different cascades of molecular mechanisms downstream of the pathogen recognition by Rvi6 in the two species. Signal transduction was triggered in both species with calcium (and G-proteins in pear) and interconnected hormonal signaling (jasmonic acid in pear, auxins in apple and brassinosteroids in both species), without involvement of salicylic acid. This led to the induction of defense responses such as a remodeling of primary and secondary cell wall, lipids biosynthesis (galactolipids in apple and cutin and cuticular waxes in pear), systemic acquired resistance signal generation (in apple) or perception in distal tissues (in pear), and the biosynthesis of phenylpropanoids (flavonoids in apple but also lignin in pear). CONCLUSION: This study is the first example of a successful intergeneric transfer of a resistance gene among Rosaceae, with a resistance gene functioning towards another species of pathogen.

The prevalence and development of burn scar contractures: A prospective multicenter cohort study.

OBJECTIVE: The objective of this study was to identify the prevalence and development of after burn joint limitation by scar contracture. METHODS: In 2011-2012, consecutive patients were enrolled in this prospective multi center cohort study. Eligible were all patients admitted to the 2 participating Dutch Burn Centers with acute burns across or adjacent to the neck, shoulder, elbow, wrist, hip, knee and ankle. Passive range of motion was measured in week 3 and subsequently every 3 weeks until discharge, on discharge from the hospital and during follow-up at the outpatient clinic at 3-6-9-12 months after burn. RESULTS: Limited range of motion of non-operated burned joints (N = 195) was restored back to normal within 6-9 months. From the operated burned joints (N = 353), 58.6% demonstrated a limited range of motion at 3-6 weeks declining to 20.9% at 12 months. The upper part of the body was affected more often by scar contracture than the lower part. At 12 months, the shoulder was limited most often (51.3%) and the hip least often (0%). Reconstructive surgery was performed in 13.3% of the operated burned joints. CONCLUSIONS: Persistent joint limitations at 12 months were exclusively present in joints that needed skin grafting for rapid wound closure. The upper part of the body was more prone to contracture formation than the lower part, from which the shoulder was most often involved. More than half of the limited range of motion seen in the acute phase, resolved in the long term. The need for reconstructive surgery was less than expected.

[Perioral treatment options in cosmetic facial surgery]. / Periorale behandelingsmogelijkheden in de cosmetische aangezichtschirurgie.

The perioral region is unique and important in the face, both from a functional and an aesthetic point of view. There is a strong relationship between the perioral soft tissues, such as the lips and the corners of the mouth, and the underlying dentition and the jaws. Perioral ageing phenomena, such as depressed corners of the mouth, volume loss and wrinkles, can be improved, however, to a limited extent with intraoral treatment. These ageing phenomena can usually be treated more effectively with several extraoral treatment modalities that also enhance perioral aesthetics. The perioral cosmetic treatment options can be divided into various lifting procedures and volumising techniques. Considering that the dentist has to deal regularly with patients with perioral aesthetic wishes and also functional problems, it is important that one has knowledge of the different perioral treatment options, for both cosmetic and functional options.

Methods for the Quantification of Resistance of Apple Genotypes to European Fruit Tree Canker Caused by Neonectria ditissima.

European fruit tree canker, caused by Neonectria ditissima, is an important disease of pome fruit worldwide. Apple cultivars differ in their levels of susceptibility to N. ditissima. In order to design an effective plant resistance test, we examined the effectiveness of two resistance parameters: infection frequency and lesion growth. Both parameters were evaluated in parallel tests using 10 apple cultivars in three experimental years, applying seminatural infection of leaf scars (infection frequency) or inoculation of artificial wounds (lesion growth). We compared six parameters for lesion growth, of which a new parameter, lesion growth rate (LGR), appeared to be the best with respect to reproducibility and statistical significance. LGR is defined as the slope of the regression of lesion size versus time. The slope was estimated for each lesion, employing a common start date and a lesion-specific end date determined by the girdling of the lesion. The two parameters (infection frequency and LGR) were examined in separate experiments and in three successive years, and provided complementary information and resulted in reproducible conclusions on the relative resistance levels to N. ditissima of the tested cultivars. The presented methods can be used to develop strategies for the control of European fruit tree canker (e.g., in the breeding of new apple cultivars with high levels of resistance to N. ditissima).

[Blepharoplasty in aesthetic facial surgery]. / Ooglidcorrecties in de cosmetische aangezichtschirurgie.

Blepharoplasty is the most commonly performed procedure in aesthetic facial surgery. The upper eyelid is part of the same aesthetic subunit as the eyebrow and the lower eyelid is part of the same aesthetic subunit as the cheek. In upper eyelid blepharoplasty the excess skin and possibly also a portion of the sphincter is removed. A low-hanging eyebrow is preferably corrected by lifting the brow instead of over excising the redundant eyelid skin. Blepharoplasty of the lower eyelid is generally carried out by a very limited excision of the skin and the orbicularis oculi muscle in order to prevent lower lid retraction (ectropion). Rejuvenation in the lower lid region is also achieved by fat resection or redistribution, by means of which the double convex contour deformity is reduced. Blepharoplasty is generally performed under local anaesthesia and complications are rare. Patient satisfaction is generally high.

A review on static splinting therapy to prevent burn scar contracture: do clinical and experimental data warrant its clinical application?

BACKGROUND: Static splinting therapy is widely considered an essential part in burn rehabilitation to prevent scar contractures in the early phase of wound healing. However, scar contractures are still a common complication. In this article we review the information concerning the incidence of scar contracture, the effectiveness of static splinting therapy in preventing scar contractures, and specifically focus on the - possible - working mechanism of static-splinting, i.e. mechanical load, at the cellular and molecular level of the healing burn wound. METHOD: A literature search was done including Pubmed, Cochrane library, CINAHL and PEDRO. RESULTS: Incidence of scar contracture in patients with burns varied from 5% to 40%. No strong evidence for the effectiveness of static splinting therapy in preventing scar contracture was found, whereas in vitro and animal studies demonstrated that mechanical tension will stimulate the myofibroblast activity, resulting in the synthesis of new extracellular matrix and the maintenance of their contractile activity. CONCLUSION: The effect of mechanical tension on the wound healing process suggests that static splinting therapy may counteract its own purpose. This review stresses the need for randomised controlled clinical trials to establish if static splinting to prevent contractures is a well-considered intervention or just wishful thinking.

Anthocyanin production as a potential visual selection marker during plant transformation.

A mutant allele of the transcription factor gene MYB10 from apple induces anthocyanin production throughout the plant. This gene, including its upstream promoter, gene coding region and terminator sequence, was introduced into apple, strawberry and potato plants to determine whether it could be used as a visible selectable marker for plant transformation as an alternative to chemically selectable markers, such as kanamycin resistance. After transformation, red coloured calli, red shoots and red well-growing plants were scored. Red and green shoots were harvested from apple explants and examined for the presence of the MYB10 gene by PCR analysis. Red shoots of apple explants always contained the MYB10 gene but not all MYB10 containing shoots were red. Strawberry plants transformed with the MYB10 gene showed anthocyanin accumulation in leaves and roots. No visible accumulation of anthocyanin could be observed in potato plants grown in vitro, even the ones carrying the MYB10 gene. However, acid methanol extracts of potato shoots or roots carrying the MYB10 gene contained up to four times higher anthocyanin content than control plants. Therefore anthocyanin production as result of the apple MYB10 gene can be used as a selectable marker for apple, strawberry and potato transformation, replacing kanamycin resistance.

Regional differences in cardiovascular risk factor profile cannot fully explain differences in cardiovascular morbidity in the Netherlands: a comparison of two urban areas.

BACKGROUND: Our objective was to investigate whether a region in the south of the Netherlands (Heerlen/Kerkrade) had a high burden of cardiovascular disease in comparison with a nearby region (Maastricht) and the average Dutch population, respectively. We also wanted to determine if there are interregional differences in cardiovascular risk factor profile. DESIGN: Cross-sectional study. METHODS: Data from a nationwide registry (CBS) were used to analyse cardiovascular mortality in the two regions and the average in the Netherlands. Data from a primary care morbidity registration network (RNH) were used to compare cardiovascular morbidity and cardiovascular risk factors in both regions. A standardisation procedure was carried out for age and sex. Data were analysed using logistic regression analyses. RESULTS: The overall cardiovascular mortality rate was higher in the Heerlen/Kerkrade region (7.8 per thousand) compared with Maastricht (6.1 per thousand, OR=1.3, 95% CI 1.2-1.5) and the average in the Netherlands (5.7 per thousand). Similarly, most cardiovascular morbidity rates for Heerlen/Kerkrade were more elevated compared with the RNH overall and with Maastricht. Prevalence rates of risk factors such as diabetes mellitus (7.2%, OR=1.5, 95% CI 1.3-1.7) and overweight (10.8%, OR= 2.0, 95% CI 1.8-2.2) were significantly higher in the Heerlen/Kerkrade region compared with Maastricht. There were no differences with regard to hypertension (15.2%, OR=1.0, 95% CI 0.9-1.1). CONCLUSION: Heerlen/Kerkrade is indeed a region with a high burden of cardiovascular disease. Differences in morbidity between Heerlen/Kerkrade and Maastricht cannot be fully explained by differences in cardiovascular risk factor profile.

Genomic cloning and linkage mapping of the Mal d 1 (PR-10) gene family in apple (Malus domestica).

Fresh apples can cause birch pollen-related food allergy in northern and central European populations, primarily because of the presence of Mal d 1, the major apple allergen that is cross-reactive to the homologous and sensitizing allergen Bet v 1 from birch. Apple cultivars differ significantly in their allergenicity. Knowledge of the genetic basis of these differences would direct breeding for hypoallergenic cultivars. The PCR genomic cloning and sequencing were performed on two cultivars, Prima and Fiesta, which resulted in 37 different Mal d 1 gDNA sequences. Based on the mapping of sequence-specific molecular markers, these sequences appeared to represent 18 Mal d 1 genes. Sixteen genes were located in two clusters, one cluster with seven genes on linkage group (LG) 13, and the other cluster with nine genes on the homoeologous LG 16. One gene was mapped on LG 6, and one remained unmapped. According to sequence identity, these 18 genes could be subdivided into four subfamilies. Subfamilies I-III had an intron of different size that was subfamily and gene-specific. Subfamily IV consisted of 11 intronless genes. The deduced amino acid sequence identity varied from 65% to 81% among subfamilies, from 82% to 100% among genes within a subfamily, and from 97.5% to 100% among alleles of one gene. This study provides a better understanding of the genetics of Mal d 1 and the basis for further research on the occurrence of allelic diversity among cultivars in relation to allergenicity and their biological functions.

Resistance gene analogues identified through the NBS-profiling method map close to major genes and QTL for disease resistance in apple.

We used a new method called nucleotide-binding site (NBS) profiling to identify and map resistance gene analogues (RGAs) in apple. This method simultaneously allows the amplification and the mapping of genetic markers anchored in the conserved NBS-encoding domain of plant disease resistance genes. Ninety-four individuals belonging to an F1 progeny derived from a cross between the apple cultivars 'Discovery' and 'TN10-8' were studied. Two degenerate primers designed from the highly conserved P-loop motif within the NBS domain were used together with adapter primers. Forty-three markers generated with NBS profiling could be mapped in this progeny. After sequencing, 23 markers were identified as RGAs, based on their homologies with known resistance genes or NBS/leucine-rich-repeat-like genes. Markers were mapped on 10 of the 17 linkage groups of the apple genetic map used. Most of these markers were organized in clusters. Twenty-five markers mapped close to major genes or quantitative trait loci for resistance to scab and mildew previously identified in different apple progenies. Several markers could become efficient tools for marker-assisted selection once converted into breeder-friendly markers. This study demonstrates the efficiency of the NBS-profiling method for generating RGA markers for resistance loci in apple.

The effect of glutamate infusion on cardiac performance is independent of changes in metabolism in patients undergoing routine coronary artery bypass surgery.

In a double-blind randomized placebo-controlled study, the effects of intravenous glutamate infusion on myocardial haemodynamics and metabolism were studied in 22 patients undergoing routine coronary artery bypass graft (CABG) surgery. Immediately after aortic cross-clamp release, an intravenous infusion of a solution of glutamate (125 mmol x l(-1)) at a rate of 1.5 ml x h(-1) x kg(-1) was given over 1 h to 11 patients (G group). The other 11 patients received a placebo infusion (0.9% NaCl) (P group). Haemodynamic functions and rates of exchange of glucose, non-esterified fatty acids and lactic acid over the heart were measured before sternotomy (T1), 40 min after cross-clamp release (T2) and 4 h after cross-clamp release (T3). At T2, decreases were seen in comparison with T1 in systemic vascular resistance index, and increases were seen in cardiac index and coronary sinus flow. All of these changes were greater in the G group than in the P group (P<0.05). Myocardial glutamate consumption increased 2-fold after glutamate administration. No significant changes were observed in the myocardial utilization of glucose, lactate or non-esterified fatty acids between the P and the G groups at T1, T2 or T3. These data show that an intravenous glutamate infusion after routine CABG surgery significantly improved cardiac haemodynamic performance without direct effects on cardiac substrate metabolism. This suggests that a reduction of the afterload via a peripheral vasodilatory effect is the main mechanism leading to the observed changes in haemodynamics. Earlier claims that patients with post-operative cardiac failure show metabolic benefits from the glutamate infusion do not seem to apply to patients undergoing routine CABG surgery.

Combined evidence from multiple outcomes in a clinical trial.

Clinical investigators are encouraged to apply recently developed statistical methodology. For each patient in a trial, favorable and unfavorable results from multiple outcomes may be summarized in a suitable summary measure. This summary measure may be used in a two-sample t-test to decide which treatment is best. An example illustrates how the evidence from the main outcome criteria may be combined. The required study size depends on the mean treatment effect on the outcomes in the summary measure. When separate outcomes are considered, there is a multiple comparisons problem, for which Hochberg offered a simple solution. Evaluation of a single-summary measure may require a larger or a smaller study size than evaluation of separate outcomes, depending on whether treatment effects are about the same or very different.

Diagnosing sensory abnormalities with either normal values or values from contralateral skin: comparison of two approaches in complex regional pain syndrome I.

BACKGROUND: To diagnose sensory abnormalities, patient values can be compared with values of the general population (absolute approach) or to values measured at contralateral homologous skin (relative approach). The current study gives normal values for both approaches and compares the advantages of each method by applying the technique to patients with complex regional pain syndrome type I (CRPS I). METHODS: In 50 healthy control subjects, sensory and pain thresholds were measured for pressure, warmth, and cold on both wrists and both feet. In 53 patients with unilateral CRPS I (33 hand, 20 foot), the same assessments were conducted twice, at an interval of 1 month. RESULTS: In control subjects, contralateral homologous sides have approximately the same sensitivity, supporting the validity of the relative approach in patients. Hypoesthesia and allodynia can be diagnosed by either the absolute or relative approach, whereas hyperesthesia and hypoalgesia can only be identified with the relative approach. The two approaches obtain different results in 20% of cases. Age, gender, and subject criteria may influence the absolute but not the relative approach. Both approaches are comparable with regard to reproducibility. Frequency distributions of sensory abnormalities in chronic CRPS I are presented. The most frequent diagnoses were cold allodynia and mechanical hypoesthesia and allodynia. CONCLUSIONS: To divide sensory characteristics into a binary classification of "normal" and "abnormal," the relative approach is the best choice, with the exception of cases in which the contralateral homologous side is absent or affected by disease. The authors recommend the relative approach for both research and clinical purposes.

Kupffer cell depletion by CI2MDP-liposomes alters hepatic cytokine expression and delays liver regeneration after partial hepatectomy.

BACKGROUND: Although Kupffer cells (KCs) are capable of producing important growth-stimulating cytokines, their role in liver regeneration following partial hepatectomy (PH) remains poorly understood. METHODS: In the present study liver regeneration was studied after KC-depletion by intravenous administration of liposome-encapsulated dichloromethylene-diphosphonate (C12MDP), a method known to physically eliminate KCs. Furthermore, splenectomy was performed one week prior to PH to exclude the effect of C12MDP-liposomes on macrophage populations in the spleen. RESULTS: KC-depletion was confirmed in cryostat liver sections stained with the monoclonal antibody ED2, a marker for resident tissue macrophages. Forty-eight hours after PH, the cumulative hepatocyte DNA synthesis, as determined in liver sections by the hepatocyte bromodeoxyuridine labeling index, was significantly decreased in KC-depleted rats when compared to control-rats. The weight of the remnant liver, expressed as a percentage of the initial liver weight, was significantly less at 96 h after PH in KC-depleted rats. KC-depletion abolished the hepatic interleukin-6 (IL-6) and interleukin-10 (IL-10) mRNA synthesis and decreased hepatic expression of tumor necrosis factor-alpha (TNF-alpha), hepatocyte growth factor (HGF) and transforming growth factor-beta1(TGF-beta1) mRNA after PH, as was assessed by reverse-transcriptase polymerase chain reaction (RT-PCR). Moreover, at 4 h after PH the systemic release of IL-6 was significantly decreased in KC-depleted rats. CONCLUSION: We conclude that KCs are important for hepatocyte regeneration after PH. Delayed liver regeneration in KC-depleted rats can be explained, at least in part, by an imbalanced hepatic cytokine expression, thereby suppressing important growth-stimulating cytokines.

Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin.

OBJECTIVE: To investigate the effectiveness of aspirin and coumarin in preventing thromboembolism in patients with non-rheumatic atrial fibrillation in general practice. DESIGN: Randomised controlled trial. PARTICIPANTS: 729 patients aged >/=60 years with atrial fibrillation, recruited in general practice, who had no established indication for coumarin. Mean age was 75 years and mean follow up 2. 7 years. SETTING: Primary care in the Netherlands. INTERVENTIONS: Patients eligible for standard intensity coumarin (international normalised ratio 2.5-3.5) were randomly assigned to standard anticoagulation, very low intensity coumarin (international normalised ratio 1.1-1.6), or aspirin (150 mg/day) (stratum 1). Patients ineligible for standard anticoagulation were randomly assigned to low anticoagulation or aspirin (stratum 2). MAIN OUTCOME MEASURES: Stroke, systemic embolism, major haemorrhage, and vascular death. RESULTS: 108 primary events occurred (annual event rate 5.5%), including 13 major haemorrhages (0.7% a year). The hazard ratio was 0.91 (0.61 to 1.36) for low anticoagulation versus aspirin and 0.78 (0.34 to 1.81) for standard anticoagulation versus aspirin. Non-vascular death was less common in the low anticoagulation group than in the aspirin group (0.41, 0.20 to 0.82). There was no significant difference between the treatment groups in bleeding incidence. High systolic and low diastolic blood pressure and age were independent prognostic factors. CONCLUSION: In a general practice population (without established indications for coumarin) neither low nor standard intensity anticoagulation is better than aspirin in preventing primary outcome events. Aspirin may therefore be the first choice in patients with atrial fibrillation in general practice.