Axial and rotational alignment of lower limb in a Caucasian aged non-arthritic cohort.

BACKGROUND: The alignment of human lower limb has been an area of ongoing study for decades. The purpose of this study was to analyze the axial and rotational alignment from hip to ankle in a Caucasian aged non-arthritic cohort. METHODS: A non-arthritic cohort of aged patients was retrospectively analyzed by computer tomography. Anatomical-mechanical angle of femur (AMA), femur inclination (FI), femoral anteversion (FA), posterior condylar angle (PCA), proximal tibial torsion (TEAs-PTC and TEAs-PTT) and tibial fibular torsion (PTC-TFA) were measured. RESULTS: The median age of the patients was 76 years (range 67 to 91 years). Regarding axial alignment, the AMA was 5 (2.94; 6.80). No significance differences were reported by side and age. AMA was significantly lower in men. The FI was 125.3 (120.0; 134.8) with no differences in terms of side, age or gender. Regarding torsion alignment, the median values of FA, PTC-TFA and TEAs-PTT were, respectively, 16.8, 28.5 and - 1.4. No differences were reported by age. Right tibia was externally rotated by 1.5 degrees as compared to the left side (P 0.035). CONCLUSION: The broad variability of the parameters analyzed highlights the necessity for a more anatomical and individualized approach during surgery of lower limb. The present study offers the fundament to understand and treat lower limb deformities. Hence, these data can constitute the normal reference values useful to investigate lower limb malalignment. Moreover, it helps to assess the possible changes of axial and rotational alignment in idiopathic OA of lower limb. LEVEL OF EVIDENCE III: Retrospective cohort study.

Synovial and serum levels of NGF in osteoarthritis and rheumatic diseases: a systematic review.

NGF has raised interest as a target molecule in the treatment of OA, after the clinical evidences that antagonization of NGF axis provides symptoms relief in OA. Thus, we conducted a systematic review of the literature to investigate the evidence of NGF being overexpressed during OA. We conducted a database search on Medline using keywords including NGF, serum, synovial fluid, AND osteoarthritis or arthritis. We included study conducted on human, with serum or synovial specimens and an OA cohort. Nine studies met the inclusion criteria. Serum levels ranged from non-detectable to 153.5±28.6 pg/ml. Synovial fluid levels ranged from non-detectable to nearly 210±82 pg/ml. One study supported the evidence of an increased level of NGF in SF and serum of OA patients. The concentration of NGF reported in these studies is controversial and evidence of overexpression of NGF is low.

The metabolic effects of quinolones and steroids on human ligament cells: an in vitro study.

The toxic effects of fluoroquinolones and steroid on tendon cells have been well established, but their role on human ligamentocytes remain unclear. We have investigated the effects of ciprofloxacin and methylprednisolone on human anterior cruciate ligamentocytes after 7 and 14 days of culture. We evaluated cell viability, Annexin V-FITC/PI assay, senescence-associated ß-galactosidase staining, and collagen type I detection. Regarding quinolones administration, we observed that ligament cells treated with ciprofloxacin have characterized by a significantly decrease of cell viability and collagen type I expression and an increase of apoptotic cells. In cells treated with high dose of steroid we observed a significantly decrease of cell viability and collagen type I expression and the presence of senescent cells. Therefore, ciprofloxacin and methylprednisolone might have cytotoxic effects on ligamentocytes by two distinct mechanisms. Quinolones seem to induce cell apoptosis, while steroids might be able to induce cellular senescence. Hence their use should be avoided in athletes and in orthopedic surgery.

Effects of NGF and BDNF on chondrocytes: a microarray analysis.

Osteoarthritis (OA) represents an inflammation-driven injury of articular tissues, progressively leading to structural and functional joint impairment. The main symptom of OA is pain. Although it has been well established that OA represents a whole joint disease, the source of pain remains to be clarified. Nowadays, it has been well established that neurotrophines expression is evident in joints affected by OA. In addition, elevated NGF levels are found in the synovial fluid of patients with inflammatory or degenerative rheumatic diseases, including OA, rheumatoid arthritis and spondylarthritis. Growing evidences indicate that blocking NGF signaling using an anti NGF agent (i.e. tanezumab) provides effective pain relief. This study analyzed the effects of NGF and BDNF on cultured human chondrocytes by evaluating and their effects on chondrogenesis, chondrocyte differentiation and cartilage degeneration through a microarray analysis. The whole transcriptome analysis performed in this study highlighted how NGF and BDNF could be able to induce a proinflammatory response in human chondrocytes. Moreover, NGF and BDNF treatments seems to be able to induce the activation of several genes involved in the OA pathogenesis as IL17AR, HLA-DRB1, GDF-15, NR1D1, MCF2L and TGF-Beta.

An improved cleaning system to reduce microbial contamination of poultry transport crates in the United Kingdom.

AIM: Following previous research on improving the cleaning of crates used to transport broiler chickens from the farm to the abattoir, a demonstration project was undertaken to investigate improvements in crate washing on a commercial scale. METHODS AND RESULTS: The soak tank of a conventional crate washing system was replaced with a high-performance washer fitted with high-volume, high-pressure nozzles. The wash water could be heated, and a greatly improved filtration system ensured that the nozzles did not lose performance or become blocked. Visual cleanliness scores and microbial counts were determined for naturally contaminated crates which had been randomly assigned to different cleaning protocols. CONCLUSIONS: When a combination of mechanical energy, heat and chemicals (i.e. detergent and disinfectant) was used, the results showed significant improvements to crate cleaning. Reductions of up to 3·6 and 3·8 log10 CFU per crate base were achieved for Campylobacter and Enterobacteriaceae, respectively, along with a marked improvement in visual cleanliness. SIGNIFICANCE AND IMPACT OF THE STUDY: Broiler transport crates may become heavily contaminated with faeces and this may contribute to the spread of disease between farms. The results of this trial may be of use in reducing the spread of zoonotic pathogens in the poultry meat supply chain.

Disease progression in blepharospasm: a 5-year longitudinal study.

BACKGROUND AND PURPOSE: The clinical manifestation of dystonic spasms in blepharospasm (BSP) patients may be heterogeneous. Whether the varying phenomenology of eyelid spasms becomes manifest sequentially during the course of the disease or aggregates in separate clusters according to different disease courses is still unclear. For this purpose, the clinical features in BSP patients were evaluated longitudinally over a 5-year period and also the blink reflex recovery cycle was tested in a subgroup of BSP patients. METHODS: Sixty BSP patients were videotaped at time 0 and after approximately 5 years of follow-up. Two experts in movement disorders, who were blinded to the video order, reviewed the videotapes and scored the severity of BSP using the Blepharospasm Severity Rating Scale. Changes in the R2 recovery index were also evaluated in 18 patients twice, i.e. upon enrolment and at the follow-up. RESULTS: The severity of BSP worsened significantly over the 5-year follow-up period owing to the appearance or the increased duration and frequency of prolonged spasms. It was also found that the blink reflex recovery cycle worsened at follow-up in comparison with the baseline. CONCLUSIONS: This study shows that the disease progression of BSP is characterized by the appearance or worsening of prolonged spasms. Prolonged spasms are accompanied by changes in the excitability of brainstem interneurons. Aging-related effects may exacerbate the pathophysiological mechanisms underlying spasms.

Characterization of human costal cartilage: is it an adapt tissue as graft for articular cartilage repair?

Several techniques and different biological or artificial tissues have been proposed as graft to restore articular defects. However, among the numerous and heterogeneous procedures proposed over time, the current literature findings are not conclusive. The aim of the current study is to evaluate if human costal cartilage can be suitable as graft for restoring articular cartilage defects. Knee articular cartilage and costal cartilage samples were obtained respectively from patients that underwent anterior cruciate ligament reconstruction (samples from notch plasty) or knee joint replacement and ear reconstruction or rhinoplasty through rib graft. The samples were stained with hematoxylin eosin, safranine-O, Gomori paraldehyde-fuchsin and Von Kossa for light microscopy. Immunohistochemistry was performed using anti-collagen I, II, IV and anti-SOX9 antibodies. Furthermore, samples were analyzed by transmission electron microcopy (TEM). In both cartilage, the cells are arranged in quite similar layers and the matrix show the same hyaline appearance: presence of type II collagen and solphated glycosaminoglycans, and absence of type I collagen and SOX-9. The bigger difference between the two hyaline tissues is the presence of perichondrium that surrounds all the specimens of costal cartilage. It consists of two separate layers where the inner one seems to get thinner with aging. The results show that rib cartilage seems to be an adapt tissue as graft for articular cartilage repair from a histological point of view. However, to date its therapeutic potential remains to be clearly defined by animal and clinical studies.

Spread of dystonia in patients with idiopathic adult-onset laryngeal dystonia.

BACKGROUND AND PURPOSE: Adult-onset laryngeal dystonia (LD) can be isolated or can be associated with dystonia in other body parts. Combined forms can be segmental at the onset or can result from dystonia spread to or from the larynx. The aim of this study was to identify the main clinical and demographic features of adult-onset idiopathic LD in an Italian population with special focus on dystonia spread. METHODS: Data were obtained from the Italian Dystonia Registry (IDR) produced by 37 Italian institutions. Clinical and demographic data of 71 patients with idiopathic adult-onset LD were extracted from a pool of 1131 subjects included in the IDR. RESULTS: Fifty of 71 patients presented a laryngeal focal onset; the remaining subjects had onset in other body regions and later laryngeal spread. The two groups did not show significant differences of demographic features. 32% of patients with laryngeal onset reported spread to contiguous body regions afterwards and in most cases (12 of 16 subjects) dystonia started to spread within 1 year from the onset. LD patients who remained focal and those who had dystonia spread did not show other differences. CONCLUSIONS: Data from IDR show that dystonic patients with focal laryngeal onset will present spread in almost one-third of cases. Spread from the larynx occurs early and is directed to contiguous body regions showing similarities with clinical progression of blepharospasm. This study gives a new accurate description of LD phenomenology that may contribute to improving the comprehension of dystonia pathophysiology.

Nerve growth factor administration on cultured human ligamentocytes: an in vitro pilot study.

Nerve growth factor (NGF) is involved in several joint pathologies. It has been demonstrated that its concentration increases in synovial fluid and tissue from arthritis. However, its role in joint homeostasis and pathophysiology still remain to be clarified. This study analyzed the effect of 200 ng/ml on cultured human ligamentocytes by evaluating cell proliferation, cell phenotype and gene expression. The MTT test excluded an influence on cell viability at 7 and 14 days. Regarding cell phenotype, we observed that NGF might promote the synthesis of COL1A1. On the other hand, real time PCR showed that NGF did not influence gene expression of COL3A1, FGF-BETA, IGF1, MMP2, MMP3, MMP9 and MMP13. However, COL1A1 gene was significantly upregulated in treated cell at 14 days. Our results suggest that NGF may have an anabolic effect on ligament. Additional investigations are necessary to determine how NGF may influence ligamentocytes..

Malnutrition is prevalent in patients with cardiorenal syndrome and negatively influences clinical outcome.

Cardiorenal syndrome (CRS) describes the concurrent failure of cardiac and renal function, each influencing the other. Malnutrition and cachexia frequently develop in patients with heart failure or kidney failure. However, no information is currently available on the prevalence of malnutrition in CRS patients. We studied CRS patients admitted to an internal medicine ward during a 5-month period and evaluated their clinical characteristics and nutritional status. Malnutrition risk was assessed by using the validated screening tool NRS-2002 whilst body composition was assessed by bioimpedance analysis and muscle function was measured by handgrip (HG) strength. Cardiac mass was also recorded. Length of stay, hospital readmission and 6-month mortality were registered. During the study period, 22 CRS patients were studied. Twenty patients were diagnosed with either CRS type 1 or CRS type 5. In CRS patients, fat-free mass showed a trend toward representing a protective factor for 6-month mortality (OR=0.904; p=0.06). Also, fat-free mass correlated with HG strength and cardiac ejection fraction. Malnutrition risk was diagnosed in 45% of the patients, whereas 8 patients met the definition of cachexia. Even without statistical significance, CRS patients with malnutrition had lower BMI (Body Mass Index) (p=0.038) and fat-free mass (p= n.s.). However, CRS malnutrition was associated to higher 6-month mortality (p= 0.05), and appears to negatively influence the outcome in CRS (OR= 9; p= 0.06). Our results show that malnutrition is prevalent in CRS patients and influences the clinical outcome. The assessment of nutritional status, and particularly body composition, should be implemented in daily practice of patients with CRS.

Correction to: The Italian Dystonia Registry: rationale, design and preliminary findings.

In the original article, Gina Ferrazzano was affiliated to Department of Neurology and Psychiatry, Neuromed Institute IRCCS, Sapienza University of Rome, Pozzilli, Italy.The corrected affiliation should be: Neuromed Institute IRCCS, Pozzilli, IS, Italy.

Relationship between pain and motor and non-motor symptoms in Parkinson's disease.

BACKGROUND AND PURPOSE: Although female gender, depressive symptoms and medical conditions predisposing to pain are more common in patients with Parkinson's disease (PD) with pain, no study has yet explored the relationship between pain and other non-motor symptoms (NMS). METHODS: A total of 321 consecutive patients with PD [190 men/131 women aged 68.3 (SD 9.2) years] attending four Italian movement disorder clinics were studied. Demographic/clinical data were obtained by a standardized interview and the NMS scale. The association of pain with motor and NMS was assessed by multivariable logistic regression models. RESULTS: At the time of the study, 180 patients with PD (56%) reported chronic pain that, in most cases, was described as being muscular or arthralgic pain. Pain preceded the onset of motor signs in 36/180 patients. In the main-effect model, factors independently associated with pain were female sex [odds ratio (OR), 2.1; P = 0.01], medical conditions predisposing to pain (OR, 2.9; P < 0.001), Hoehn-Yahr staging (OR, 1.9; P = 0.04), motor complications (OR, 4.7; P = 0.04) and NMS belonging to the sleep/fatigue (OR, 1.6; P = 0.04) and mood/cognition (OR, 1.6; P = 0.03) domains. Most explanatory variables in the multivariable analysis were similarly distributed in patients in whom pain may have been related to PD or to a cause other than PD. CONCLUSIONS: We confirm that pain in PD is more frequent in women and in subjects with medical conditions predisposing to painful symptoms. Moreover, this strengthens the association between pain and motor severity measures and NMS domains, particularly sleep and mood disturbances.

The effect of anti-IgE therapy in knee osteoarthritis: a pilot observational study.

Osteoarthritis is a whole-joint disease and its pathogenesis remains poorly understood. Recent evidence proposed the importance of the innate immune system as trigger of synovium inflammation following the degeneration of cartilage. Moreover, synovial mast cells (MCs) might be correlated with pain and disability reported by patients. Anti IgE therapy represents a new class of MCs stabilizing agent, licensed for people with asthma and chronic urticaria. Therefore, we studied if the stabilizing effect of anti IgE would improve the pain and disability in patients affected by knee osteoarthritis and atopic disease. This pilot study provides the first evidence that anti IgE treatment induces a short-term clinical improvement supporting the role of MCs in osteoarthritis.

Altered diurnal cardiac sympathovagal balance correlates with nutritional status indexes in systemic sclerosis patients.

Autonomic nervous system is involved in body weight regulation. Gastrointestinal manifestations of systemic sclerosis (SSc) can influence patients’ nutritional status and facilitate the development of protein–energy malnutrition. The aim of the study is to assess the nutritional status of SSc patients and to explore its possible correlation with autonomic dysfunction using heart rate variability (HRV). We enrolled 19 SSc subjects and 19 healthy subjects as controls. Body mass index (BMI) and body surface area (BSA) were collected and recorded in all patients. HRV was measured and the domains of low frequencies (LF, index of the sympathetic modulation) and high frequencies (HF, index of the parasympathetic modulation) were recorded. As assessed by the LF/HF RATIO, sympathovagal balance is altered in SSc patients because of increased sympathetic modulation and reduced parasympathetic activity. BMI positively correlates with LF (r=0.57; p less than 0.01) and LF/HF RATIO during daytime (r= 0.46; p less than 0.05). Similarly, BSA positively correlates with LF (r= 0.51; p less than 0.05), LF day time (r= 0.53; p less than 0.05) and LF/HF RATIO night time (r=-0.51; p less than 0.05). In SSc patients the autonomic dysfunction is characterized by increased sympathetic modulation. We observed a correlation between autonomic dysfunction and nutritional status in SSc patients.

The Italian Dystonia Registry: rationale, design and preliminary findings.

The Italian Dystonia Registry is a multicenter data collection system that will prospectively assess the phenomenology and natural history of adult-onset dystonia and will serve as a basis for future etiological, pathophysiological and therapeutic studies. In the first 6 months of activity, 20 movement disorders Italian centres have adhered to the registry and 664 patients have been recruited. Baseline historical information from this cohort provides the first general overview of adult-onset dystonia in Italy. The cohort was characterized by a lower education level than the Italian population, and most patients were employed as artisans, builders, farmers, or unskilled workers. The clinical features of our sample confirmed the peculiar characteristics of adult-onset dystonia, i.e. gender preference, peak age at onset in the sixth decade, predominance of cervical dystonia and blepharospasm over the other focal dystonias, and a tendency to spread to adjacent body parts, The sample also confirmed the association between eye symptoms and blepharospasm, whereas no clear association emerged between extracranial injury and dystonia in a body site. Adult-onset dystonia patients and the Italian population shared similar burden of arterial hypertension, type 2 diabetes, coronary heart disease, dyslipidemia, and hypothyroidism, while hyperthyroidism was more frequent in the dystonia population. Geographic stratification of the study population yielded no major difference in the most clinical and phenomenological features of dystonia. Analysis of baseline information from recruited patients indicates that the Italian Dystonia Registry may be a useful tool to capture the real world clinical practice of physicians that visit dystonia patients.

Rest tremor in idiopathic adult-onset dystonia.

BACKGROUND: Tremor in dystonia has been described as a postural or kinetic abnormality. In recent series, however, patients with idiopathic adult-onset dystonia also displayed rest tremor. METHODS: The frequency and distribution of rest tremor were studied in a cohort of 173 consecutive Italian patients affected by various forms of idiopathic adult-onset dystonia attending our movement disorder clinic over 8 months. RESULTS: Examination revealed tremor in 59/173 patients (34%): 12 patients had head tremor, 34 patients had arm tremor, whilst 13 patients presented tremor in both sites. Head tremor was postural in all patients, whereas arm tremor was postural/kinetic in 28 patients, only at rest in one and both postural/kinetic and at rest in 18 patients. Patients with tremor were more likely to have segmental/multifocal dystonia. Patients who had rest tremor (either alone or associated with action tremor) had a higher age at dystonia onset and a greater frequency of dystonic arm involvement than patients with action tremor alone or without tremor. CONCLUSIONS: Both action and rest tremor are part of the tremor spectrum of adult-onset dystonia and are more frequently encountered in segmental/multifocal dystonia. The higher age at dystonia onset and the greater frequency of arm dystonia in patients with rest tremor may have pathophysiological implications and may account, at least in part, for the previous lack of identification of rest tremor as one possible type of tremor present in dystonia.

Smoking in Patients with Parkinson's Disease: preliminary striatal DaT-SPECT findings.

OBJECTIVE: To assess whether cigarette smoking interferes with dopaminergic transmission in current- and never-smoking patients with Parkinson's disease. MATERIALS AND METHODS: Striatal [123I]FP-CIT single photon emission computed tomography was performed in 67 patients with Parkinson's disease (35 women and 32 men aging 60.8 ± 10.1 years and staging 1.76 ± 0.5 on the Hoehn and Yahr scale). At study time, there were 13 current-smokers and 54 never-smokers. RESULTS: Current-smokers showed a significantly lower putamen/occipital [123I]FP-CIT ratio and a non-significant trend to a lower caudate/occipital [123I]FP-CIT ratio uptake. Current-smokers were also characterized by a lower off UPDRS-III motor score. A logistic regression analysis adjusted for age, sex, disease duration, Hoehn and Yahr staging, and medication indicated a significant lower [123I]FP-CIT uptake not only in the putamen (odds ratio, 0.1; 95% confidence interval, 0.01 to 0.65; P = 0.02) but also in the caudate (odds ratio, 0.2; 95% confidence interval, 0.04 to 0.71; P = 0.015) as well as a lower UPDRS-III motor score (odds ratio, 0.9; 95% confidence interval, 0.81 to 0.99; P = 0.04) in current-smokers. CONCLUSIONS: The lower [123I]FP-CIT uptake together with the lower UPDRS-III motor score observed in our current-smokers patients with Parkinson's disease (even taking into account variables that are probably expression of dopaminergic neuron decline and treatment) would support an effect of smoking on dopaminergic synaptic mechanisms.