Femoroacetabular impingement: biomechanical and dynamic considerations.

Femoroacetabular impingement (F.A.I.) is a pathologic process caused by an abnormal shape of the acetabulum, of the femoral head, or both. F.A.I., often referred to as idiopathic, may be secondary to slipped capital femoral epiphysis, congenital hypoplasia of the femur, Legg-Calvé Perthes disease, post-traumatic mal-union and protrusio acetabuli. From 2009 to 2012 we studied 21 patients (14 males), with a mean age of 52 (33 y - 75 y), affected by idiopathic F.A.I. Every patient underwent pelvic and hip joint X-rays and CT scan with 3D reconstructions, in order to evaluate the morphology of the pelvis and the hip joint and the torsion of the lower limbs (Femoroacetabular ante-retroversion). Our results show an average femoral ante-version angle of 12,4° (15°-20° physiological range) in patients affected by CAM impingement and an average acetabular ante-version angle of 13,5° (15°-20° physiological range) for those with PINCER impingement. These values, in patients affected by F.A.I., are probably related to morphologic and biomechanical features that may lead to the onset of idiopathic femoroacetabular impingement. In the literature, other studies partially support our findings, suggesting a more critical approach to a patient with idiopathic F.A.I. extending evaluations to nearby articulations.

Spina bifida occulta. Foot deformities, enuresis and vertebral cleft: clinical picture and neurophysiological assessment.

AIM: The aim of the study was to investigate the relationship between the clinical evidence of foot deformities in spina bifida occulta and the associated neurophysio-logical damage. METHODS: The authors studied 47 patients with foot deformities (37 flat foot, 10 pes cavus) and vertebral cleft, variably associated with enuresis, midline cutaneous lesions, and further orthopaedic deformities. An electrophysiological evaluation was performed in an attempt to investigate the peripheral nervous system in greater detail, including conventional motor and sensory nerve conduction, F-wave recording and electromyogram (EMG) testing. RESULTS: The peroneal nerve F wave latency was longer in patients with pes cavus than in those with flat foot (P<0.04). Conversely, the posterior tibial nerve F-wave latency was longer in patients with flat foot than in those with pes cavus (P<0.02). Needle EMG showed large amplitude motor unit potentials during voluntary recruitment in all patients, suggesting a neurogenic origin of these EMG changes. Neurophysiological study makes it possible to distinguish between myogenic and lower motor neuron involvement. The existence of some degree of spinal cord dysraphism may be pathophysiologically associated with foot deformities. CONCLUSION: Children with foot deformities and clinical evidence of occult spinal dysraphism should have a neuro-physiological assessment in order to obtain an early diagnosis and avoid ineffective foot surgery.

Interferential and horizontal therapies in chronic low back pain due to multiple vertebral fractures: a randomized, double blind, clinical study.

UNLABELLED: Chronic low back pain due to multiple vertebral fractures is of difficult management. Electrical nerve stimulation is frequently used, but its efficacy has never been properly evaluated. In a randomized placebo-controlled clinical trial, we have shown that both interferential currents and horizontal therapy are more effective than placebo for functional. INTRODUCTION: Multiple vertebral fractures almost invariably ensue in chronic low back pain that remains of difficult management. Electrical nerve stimulation is frequently used but its efficacy has never been properly evaluated. METHODS: One hundred and fifteen women with chronic back pain due to previous multiple vertebral osteoporotic fractures (CBPMF) were randomly assigned to either interferential currents (IFT), horizontal therapy (HT) or sham HT administered for 30 minutes daily for 5 days per week for two weeks together with a standard exercise program. Efficacy assessment was obtained at baseline and at week 2, 6 and 14 and included a functional questionnaire (Backill), the standard visual analog scale (VAS) and the mean analgesic consumption. RESULTS: At week 2 a significant and similar improvement in both the VAS and Backill score was observed in the three groups. The two scores continued to improve in the two active groups with changes significantly (p < 0.001) greater than those observed in control patients at week 6 and 14. The use of analgesic medications improved only in the HT group. CONCLUSION: This randomized double-blind controlled study provides the first evidence that IFT and HT therapy are significantly effective in alleviating both pain and disability in patients with CBPMF.

Interferential and horizontal therapies in chronic low back pain: a randomized, double blind, clinical study.

OBJECTIVE: Chronic Low Back Pain (CLBP) is one of the most frequent medical problems. Electrical nerve stimulation is frequently used but its efficacy remains controversial. METHODS: Twenty-six men and 94 women with CLBP associated with either degenerative disk disease or previous multiple vertebral osteoporotic fractures were randomly assigned to either interferential currents (IFT), horizontal therapy (HT) or sham HT administered for 10, 40 and 40 minutes, respectively, daily for 5 days per week for two weeks together with a standard flexion-extension stretching exercise program, Blind efficacy assessment were obtained at baseline and at week 2, 6 and 14 and included a functional questionnaire (Backill), the standard visual analog scale (VAS) and the mean analgesic consumption. RESULTS: At week 2 a significant and similar improvement in both the VAS and Backill score was observed in all three groups. The Backill score continued to improve only in the two active groups with changes significantly greater than those observed in control patients at week 14. The pain VAS score returned to baseline values at week 6 and 14 in the control group while in the IFT and HT groups it continued to improve (p< 0.01 vs controls). The use of analgesic medications significantly improved at week 14 versus pretreatment assessment and over control patients only in the HT group. CONCLUSION: This randomized double-blind controlled study provides the first evidence that IFT and HT therapy are significantly effective in alleviating both pain and disability in patients with CLBP. The placebo effect is remarkable at the beginning of the treatment but it tends to vanish within a couple of weeks.

Chitotriosidase gene expression in Kupffer cells from patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) is a clinicopathological condition characterised by a necroinflammatory disorder with fatty infiltration of the hepatocytes. The molecular mechanisms involved in the anomalous behaviour of liver cells have only partially been determined. Human chitotriosidase (Chit) is a chitinolytic enzyme mainly produced by activated macrophages. The aim of this study was to investigate the expression of the chitinase-like gene in Kupffer cells, to determine how chitotriosidase may be implicated in the progression from uncomplicated steatosis to steatohepatitis with progressive fibrosis. METHODS: 75 subjects were studied: 40 with NASH, 20 with simple steatosis, and 15 normal controls. Kupffer cells obtained from liver biopsies were used to detect CHIT expression, superoxide anion (O2-), lipid peroxidation, and tumour necrosis factor alpha (TNFalpha) and ferritin levels. RESULTS: CHIT expression differed markedly in livers from normal controls and in those from patients with simple steatosis or non-alcoholic steatohepatitis. A significant correlation between mRNA CHIT and O2-, lipid peroxidation, TNFalpha, and ferritin levels was observed in both NASH and simple steatosis. CONCLUSIONS: Human Kupffer cells in NASH patients overproduce chitotriosidase. At the highest levels of production, this enzyme may play a role in increasing the risk for a poor outcome in steatohepatitis.

Plasma membrane localization of palmitoylated tubulin.

PC12 pheochromocytoma cells incorporate [(3)H]palmitic acid into tubulin in a time- and cell-density-dependent manner. The plasma membrane-enriched fraction contains most of the radioactivity of the membrane pellet. While palmitoylated tubulin is found in both the cytoplasm and particulate fraction, the bulk of [(3)H]palmitic acid bound to tubulin is present in the crude membrane pellet and the tubulin extracted from the plasma membrane is more heavily palmitoylated than that extracted from endoplasmic reticulum. Detergent-extracted tubulin from plasma membrane is, to a large extent, polymerization competent; a substantial fraction, increasing as a function of labeling time, is not hydroxylamine-labile. The requirement for detergent extraction, the accompanying changes in tubulin properties and the present findings of preferential incorporation of labeled tubulin into plasma membranes, make it clear that direct incorporation of tubulin into the plasma membrane can occur.

Autopalmitoylation of tubulin.

Pure rat brain tubulin is readily palmitoylated in vitro using [3H]palmitoyl CoA but no added enzymes. A maximum of approximately six palmitic acids are added per dimer in 2-3 h at 36-37 degrees C under native conditions. Both alpha and beta tubulin are labeled, and 63-73% of the label was hydroxylamine-labile, presumed thioesters. Labeling increases with increasing pH and temperature, and with low concentrations of guanidine HCl or KCl (but not with urea) to a maximum of approximately 13 palmitates/dimer. High SDS and guanidine HCl concentrations are inhibitory. At no time could all 20 cysteine residues of the dimer be palmitoylated. Polymerization to microtubules, or use of tubulin S, markedly decreases the accessibility of the palmitoylation sites. Palmitoylation increases the electrophoretic mobility of a portion of alpha tubulin toward the beta band. Palmitoylated tubulin binds a colchicine analogue normally, but during three warm/cold polymerization/depolymerization cycles there is a progressive loss of palmitoylated tubulin, indicating decreased polymerization competence. We postulate that local electrostatic factors are major regulators of reactivity of tubulin cysteine residues toward palmitoyl CoA, and that the negative charges surrounding a number of the cysteines are sensitive to negative charges on palmitoyl CoA.

Nerve conduction changes during lower limb lengthening. Somatosensory evoked potentials (SEPs) and F-wave results.

The effect of lower limb lengthening on nerve conduction was investigated in 5 achondroplastic subjects who underwent callotasis on a "cross-over" basis. Somatosensory evoked potentials (SEPs) and F waves from the posterior tibial nerve (PTN) were studied preoperatively and then after removal of the axial fixators. SEPs at the end of lengthening showed that both the latency of the plexus potential (P9) and, albeit to a lesser extent, the interpeak time between the plexus and the spinal cord (N15) potentials were significantly increased. The central conduction time (N15-P33) and the amplitude of the scalp responses were not modified. The latencies of the F waves were much longer at the end of bone distraction than in basal conditions. The increases in both PTN SEPs and F-wave latencies are consistent with a slowing of conduction The extent of these latency shifts correlated closely with the degree of limb lengthening. We calculated that, on average, each cm of lengthening could produce 0.21 msec and 0.22 msec delays respectively, suggesting a similar effect of the stretching on both sensory and motor fibers. Our findings indicated that the damage could be widely distributed along the whole length of the nerve, affecting both the peripheral (trunk) and proximal (plexus and root) segments. The electrophysiological changes were not associated with any persistent clinical complaint.

Lower-limb lengthening in short stature. An electrophysiological and clinical assessment of peripheral nerve function.

We assessed peripheral nerve function during and after lower-limb lengthening by callotasis in 14 patients with short stature, using motor conduction studies. Four patients with short stature of varying aetiology showed unilateral and one showed bilateral weakness of foot dorsiflexion. Both clinical and electrophysiological abnormalities consistent with involvement of the peroneal nerve were observed early after starting tibial callotasis. There was some progressive electrophysiological improvement despite continued bone distraction, but two patients with Turner's syndrome had incomplete recovery. A greater percentage increase in tibial length did not correspond to a higher rate of peroneal nerve palsy. The function of the posterior leg muscles and the conduction velocity of the posterior tibial nerve were normal throughout the monitoring period. The F-wave response showed a longer latency at the end of the bone distraction than in basal conditions; this is probably related to the slowing of conduction throughout the entire length of the nerve.

Palmitoylation of tubulin.

Tubulin is a very water soluble protein, yet a significant portion is firmly associated with cell membranes. Because recent work has shown that palmitoylation is a dynamic process that can alter the targeting of proteins to membranes, we tested whether or not tubulin could be palmitoylated to account for its membrane location. Tubulin acylation was measured by incorporation of [3H]palmitate into PC12 cells in culture. We found palmitoylated tubulin in both cell pellet and cytosol with a higher concentration in the former. EGF-stimulated PC12 cells incorporated the same amount of palmitate per unit protein but the proportion in the membrane fraction was enhanced. More palmitate of the pellet was found in alpha than beta tubulin; EGF stimulation primarily increased palmitate in beta tubulin. In addition we found that palmitic acid was present both as thioesters and as oxyesters. We suggest that palmitoylation may contribute to the membrane localization of tubulin and can be regulated by growth factors.

Achalasia. A possible late cause of postpolio dysphagia.

The aim of this paper is to describe a patient with severe postpolio problems who developed achalasia. A 66-year-old patient came to our observation for severe dysphagia. He had suffered from paralytic poliomyelitis at the age of 7 months and had severe residual deficits. At the age of 62 he presented with sudden pain localized in the distribution of the C4 and C5 dermatomes and an inability to abduct the left arm. At the time, he experienced only occasional and mild dysphagia; his esophagus was not dilated and emptied normally. Over the following months his muscular function improved, but dysphagia worsened. We found a megaesophagus with a sigmoid appearance and the manometric features of achalasia. Pneumatic dilatation produced good resolution of dysphagia. A year later manometry showed the reappearance of peristalsis after all wet swallows. In patients with postpolio dysphagia, the possible presence of achalasia must be considered.

Glucose may induce cell death through a free radical-mediated mechanism.

It has been reported that glucose may autooxidize generating free radicals which have been hypothesized to induce important cellular abnormalities. To investigate the cell damage induced by glucose-dependent oxidative stress, the FRTL5 cell strain was incubated in 10 or 20 mM glucose, either alone or in the presence of buthionine-sulfoximine, a transition state inhibitor that blocks glutathione synthesis. We found indeed that buthionine-sulfoximine greatly inhibited glutathione production and increased malondialdehyde (a marker of oxidative cell damage) levels, especially in 20mM glucose. We also found that, when glutathione production was inhibited, 10mM glucose induced apoptosis and 20 mM glucose induced necrosis. These data show that the glucose-dependent cell damage is a function of glutathione production. They also show that such glucose-dependent free radical production may be critical for determining cell damage, even for small variations as the ones we tested (from 10 to 20 mM glucose).

Markers of T lymphocyte activation in HLA-B8, DR3 positive individuals.

Many autoimmune diseases are associated in Caucasians with HLA-B8 and/or HLA-DR3 antigens. There is evidence that bearers of these antigens may display significant changes in immune parameters when compared to individuals not having these antigens. Recently, increased numbers of blood activated T lymphocytes have been reported in the majority of these diseases. The increase in activated blood T lymphocytes is paradoxically characterized by an in vitro impairment of T cell activation. Particularly, an inadequate production of interleukins has been observed. We have studied blood levels of activated T cells in HLA-typed, healthy subjects. The results show that the percentage of activated T cells, as recognized by monoclonal antibodies anti-CD25, anti-Ia and anti-MLR3, was more frequent in HLA-B8, DR3 positive individuals. On the other hand, in the 24 h, PHA stimulated cultures IL-2, IFN-gamma and the percentage of T cells CD25 positive were decreased. Thus, there was an apparent discrepancy between the increase of blood activated T cells and the in vitro impaired T cell activation. Since there is evidence that HLA-B8, DR3 positive subjects are genetically low responders, a possible reason for the discrepancy might be their relative inability to remove antigenic stimuli from the body. In this case, the increased number of activated blood T cells may reflect a cellular activation caused by persistent antigenic stimulation.

Interleukin 2 and soluble interleukin 2-receptor secretion defect in vitro in newly diagnosed type I diabetic patients.

In this study, we investigated whether an interleukin 2 (IL-2) secretion defect by peripheral blood mononuclear cells (PBMCs) after in vitro stimulation with phytohemagglutinin (PHA-M) occurs in either newly diagnosed or long-standing type I (insulin-dependent) diabetic patients and whether it is accompanied by a dysregulation of soluble IL-2-receptor (IL-2RS) production. PBMC cultures (2.5 x 10(6) cells), unstimulated or stimulated with PHA-M (25 micrograms/ml), from 20 type I diabetic patients (10 with time since onset less than 3 mo and 10 with long-term diabetes of less than 3 yr) and 10 control subjects were studied for the production of IL-2 and IL-2RS in their respective supernatants. No difference was found in IL-2 production in unstimulated cultures of type I patients compared with control subjects, although a significant decrease from PHA-M-stimulated cultures were seen (newly diagnosed, 1.7 +/- 0.3 ng/2.5 x 10(6) cells; long-standing, 2.2 +/- 0.3 ng/2.5 x 10(6) cells; P less than .001 and P less than .05, respectively) compared with control subjects (3.6 +/- 0.4 ng/2.5 x 10(6) cells). In regard to the production of IL-2RS, no difference exists for unstimulated cultures, whereas, after PHA-M stimulation, both newly diagnosed and long-term-diabetic patients showed a decrease in the IL-2RS levels (318 +/- 50 and 331 +/- 62 U/2.5 x 10(6) cells; P less than .02 and P less than .05, respectively) compared with normal subjects (463 +/- 34.2 U/2.5 x 10(6) cells). Thymus-activated cell phenotypes confirmed the T-lymphocyte activation after a 48-h culture period.(ABSTRACT TRUNCATED AT 250 WORDS)

Dissociated production of interleukin-2 and immune gamma-interferon by phytohaemoagglutinin stimulated peripheral mononuclear cells in type 1 (insulin-dependent) diabetes.

In order to analyze the first steps of T cell activation in type 1 diabetes we studied in vitro IL-2 and gamma-IFN production by peripheral blood mononuclear cells after 24 h PHA stimulation. There was a significant decrease in IL-2 production by mononuclear cells of the diabetic patients with respect to the controls. No significant difference was observed between the diabetic patients and the healthy subjects as regards gamma-IFN production. These observations may be interesting in relation to the pathogenetic mechanisms involved in type 1 diabetes. In particular, normal gamma-IFN production may indicate integrity of the natural killer circuit.

[Rehabilitative approach in osteoarticular pathology in the elderly]. / L'approccio riabilitativo nella patologia osteoarticolare dell'anziano.

Acute and chronic osteoarticular pathology is quickly reviewed. After a review of the most important orthopaedic operations, the most significant types of physical therapy that are most suitable for individual cases are described in detail. Finally it is pointed out that physical exercise is the most natural way to stimulated new bone growth and that medical gymnastics is important for the elderly and using menopause.

Voluntary regularization method of the respiratory act applied to chronic obstructive pulmonary disease.

Respiration is a vital, complex function, fundamentally automatic that can be modulated by will. The aim of the original method submitted is the progressive rehabilitation of the patient to strain, by a gradual reduction of respiratory frequency at the progressive increase in expiration phases and the execution of a growing effort in strict relation to the execution of the method itself. The patient learns to beat out the rhythm of his respiration based upon the strokes of the metronome, calibrated at 60 strokes a minute. The most evident documentation of the efficacy of our method of voluntary regularization of the respiratory act is in the evaluation of the effort capacity of each patient, before and after the method. The data are referred to the distance covered by cyclette, in standard conditions. The examined clinical parametres comprehend: cardiac frequency, respiratory frequency, maximal pause and arterial pressure. The laboratory parametres examined include the value of the arterial astrup: pH, pCO2, HCO3-, total CO2, pO2, excess basis. The scarcity of clinical survey examined during our research does not permit the formulation of any conclusive considerations, which would lead to a critical revision of the whole field of the physiology of respiration. For this reason, it is more prudent to establish the modifications of various parametres collected, until a more certain and wider confirmation is available.