Identification of mutations in AP4S1/SPG52 through next generation sequencing in three families.

BACKGROUND AND PURPOSE: The term hereditary spastic paraplegia (HSP) covers a spectrum of genetically heterogeneous disorders in which lower limb spasticity is the common clinical feature. Many patients with childhood-onset HSP are mistakenly diagnosed with cerebral palsy (CP). METHODS: A group of as yet molecularly undiagnosed HSP patients were analyzed using SpastoPlex, a customized target re-sequencing panel able to investigate the coding regions of 72 genes linked to HSP, spastic ataxias or related motor diseases. RESULTS: Our investigations identified loss-of-function mutations in AP4S1/SPG52 in four children (three families) who had previously received a diagnosis of diplegic/quadriplegic CP. The patients presented spastic paraparesis, mild facial dysmorphisms, moderate-to-severe intellectual disability and severe speech delay. Two patients manifested febrile seizures and childhood-onset focal seizures. In all the patients, brain magnetic resonance imaging (MRI) showed a peculiar hypoplastic posterior corpus callosum, often associated with ventriculomegaly, white matter loss and cerebral atrophy. CONCLUSION: Adaptor protein 4 (AP-4) deficiency disorders should be suspected in children with spastic paraparesis, cognitive deficit and absent speech accompanied by suggestive MRI features. Seizures might be amongst the clinical manifestations of the syndrome.

Large deletion mutation of SPAST in a multi-generation family from Sardinia.

BACKGROUND AND PURPOSE: The hereditary spastic paraplegias (HSP) are characterized by progressive spasticity of the lower limbs, mostly inherited as an autosomal dominant trait. Analyses of large HSP pedigrees could help to better characterize the phenotype due to a single causative mutation. Patients in a seven-generation kindred carrying a large deletion in SPAST/SPG4 are described. METHODS: Individuals originating from Sardinia were clinically and genetically studied. RESULTS: Sixty-seven subjects carried a heterozygous deletion encompassing exons 2-17 of SPAST. Fifty patients (53.2 ± 15.4 years) presented a pure form of spastic paraparesis characterized by mild impairment and slow progression. Most patients showed spasticity, increased tendon reflexes in the lower limbs and Babinski sign, whilst weakness was rarely detected and urinary disturbances occasionally reported. Amongst the 17 asymptomatic carriers of the mutation, minimal neurological signs were detected in 11 cases. CONCLUSIONS: A focus on spasticity, increased tendon reflexes and Babinski sign, more than on weakness, could help clinicians to promote early diagnosis in asymptomatic carriers of SPAST deletions.

Three-dimensional changes of the upper airway in patients with obstructive sleep apnea syndrome after a non-adjustable oral appliance treatment.

The diagnosis, the therapy and the monitoring of the obstructive sleep apnea syndrome (OSAS) are to be considered as critical factors in order to prevent severe systemic complications that can be caused by this pathological condition. This work presents three cases of adult patients affected by OSAS, undergoing therapy with oral appliances (OAs), meant to remove the pharyngeal obstruction caused by mandibular retrusion and tongue collapse in nocturnal supine position. The aim of this work was to evaluate the effect of the OAs both through the comparison of the polysomnographic analysis, in the presence and absence of the appliance in situ, and also through the volumetric measurements of the pharingeal airway thanks to the cone beam computed tomography.

Oral manifestation of cleido cranial displasia.

Cleidocranial dysplasia (CCD) is a congenital hereditary condition caused by a dominant autosomal mutation. The orthodontic management of CCD patients is often complicated by the manifestations associated with the condition. The aim of this study was to evaluate the oral manifestations of patients suffering from CCD. The subjects underwent a thorough clinical evaluation that examined both hard and soft tissue. The subjects also underwent an X-ray examination in order to isolate possible anomalies in the stomach region related to the condition. Case 1 presented with a bilateral cross-bite, retention of deciduous teeth, presence of supernumerary teeth and agenesis. Case 2 presented with bilateral cross-bite, retention of deciduous teeth, and the presence of supernumerary teeth. The individuals in this study represent a broad range of typical CCD manifestations and confirm the close correlation between the mutation at CBFA1 level and the presence or oral-dental alterations. An early diagnosis of CCD is essential and based on clinical manifestations, x-ray evidence and genetic tests. Diagnosing the condition can be difficult in cases where there are no evident morphological signs; however, in most cases, an alteration in the rhythm of deciduous tooth loss is immediately apparent, making a closer collaboration between dentists and geneticists fundamental in achieving early diagnosis. As stated above, the timing of the treatment is crucial in establishing a correct course of treatment that involves extractions, orthodontic surgery and the use of prosthetics.

Effectiveness of chlorhexidine on dental plaque: a new technique.

AIM: Regular home care by the patient in addition to professional removal of subgingival plaque is generally very effective in controlling most inflammatory periodontal diseases. The purpose of this study is to evaluate the effectiveness in removing plaque, a new tool for oral hygiene, suitable for any type of population, associating it to the patient's motivation in the early stages of a session of occupational hygiene. METHODS: The experiment involved a total of 120 patients. In the initial stages of the professional oral hygiene treatment, there were the values for the percentage of plaque index in all 120 subjects, after application of the agent detector plate, containing erythrosin, in liquid solution. Subsequently, the same operator, used for about two minutes with a woven gauze roller movement toward apico-coronal (Digital Brush, Mycerium, SpA, Avegno, Ge) on all teeth. Soon after it was re-applied the same detector that has enabled us to evaluate the plaque index, after using the digital brush. A statistical analysis has been carried out. RESULTS: Results show a statistically significant decrease of the averages of plaque index before and after treatment. At the end of the study the 120 patients showed an average index of plaque equal to 74.2, which after the use of the Digital Brush was reduced to 44.3. CONCLUSION: The research has shown a very simple and effective treatment's procedure, therefore it should be widely employed in oral hygiene practice.

The importance of lung recruitability: A novel ultrasound pattern to guide lung recruitment in neonates.

BACKGROUND: Lung Ultrasound (LUS)-guided Lung Recruitment Maneuver (LRM) has been shown to possibly reduce ventilator-induced lung injury in preterm infants. However, to avoid potential hemodynamic and pulmonary side effects, the indication to perform the maneuver needs to be supported by early signs of lung recruitability. Recently, a new LUS pattern (S-pattern), obtained during the reopening of collapsed parenchyma, has been described. This study aims to evaluate if this novel LUS pattern is associated with a higher clinical impact of the LUS-guided LRMs. METHODS: All the LUS-guided rescue LRMs performed on infants with oxygen saturation/fraction of inspired oxygen (S/F) ratio below 200, were included in this cohort study. The primary outcome was to determine if the presence of the S-pattern is associated with the success of LUS-guided recruitment, in terms of the difference between the final and initial S/F ratio (Delta S/F). RESULTS: We reported twenty-two LUS-guided recruitments, performed in nine patients with a median gestational age of 34 weeks, interquartile range (IQR) 28-35 weeks. The S-pattern could be obtained in 14 recruitments (64%) and appeared early during the procedure, after a median of 2 cmH2O (IQR 1-3) pressure increase. The presence of the S-pattern was significantly associated with the effectiveness of the maneuver as opposed to the cases in which the S-pattern could not be obtained (Delta S/F 110 +/- 47 vs 44 +/- 39, p = 0.01). CONCLUSIONS: Our results suggest that the presence of the S-pattern may be an early sign of lung recruitability, predicting LUS-guided recruitment appropriateness and efficacy.

Morphological characteristics of primary enamel surfaces versus permanent enamel surfaces: SEM digital analysis.

AIM: The morphology of permanent and primary enamel surface merits further analysis. The objective of this study was to illustrate a method of SEM digital image processing able to quantify and discriminate between the morphological characteristics of primary and permanent tooth enamel. METHODS: Sixteen extracted teeth, 8 primary teeth and 8 permanent teeth, kept in saline solution, were analysed. The teeth were observed under SEM. The SEM images were analysed by means of digitally processed algorithms. The two algorithms used were: Local standard deviation to measure surface roughness with the roughness index (RI); Hough's theorem to identify linear structures with the linear structure index (LSI). RESULTS: The SEM images of primary teeth enamel show smooth enamel with little areas of irregularity. No linear structures are apparent. The SEM images of permanent enamel show a not perfectly smooth surface; there are furrows and irregularities of variable depth and width. CONCLUSION: In the clinical practice a number of different situations require the removal of a thin layer of enamel. Only a good morphological knowledge of both permanent and primary tooth enamel gives the opportunity to identify and exploit the effects of rotary tools on enamel, thus allowing for a correct finishing technique.

Veterinary-focused assessment with sonography for trauma-airway, breathing, circulation, disability and exposure: a prospective observational study in 64 canine trauma patients.

OBJECTIVE: To describe the technique and findings of the 'veterinary focused assessment with sonography for trauma-airway, breathing, circulation, disability and exposure' protocol in dogs suffering from trauma. MATERIALS AND METHODS: Prospective observational study on a new point-of-care ultrasound protocol on 64 dogs suffering from trauma and comparison of findings with radiology. RESULTS: Comparison of the results of this new ultrasound protocol for trauma patients with radiography findings for pneumothorax, pleural effusion, alveolar-interstitial syndrome and abdominal effusion revealed positive agreement of 89, 83, 100 and 87% and negative agreement of 76, 83, 76 and 92%, respectively. Novel findings of the 'veterinary focused assessment with sonography for trauma-airway, breathing, circulation, disability and exposure' exam, which were not previously reported for dogs undergoing focused assessment with sonography for trauma, included alveolar-interstitial syndrome (suggestive of pulmonary contusions), diaphragmatic hernia, retroperitoneal effusion and tracheal injury. Our new technique may also help identify increased intracranial pressure via changes in optic nerve sheath diameter and haemodynamic instability through the evaluation of the caudal vena cava and cardiac function. CLINICAL SIGNIFICANCE: The described ultrasound examination protocol can be rapidly performed on dogs suffering from trauma during resuscitation and it may detect injuries previously undetectable using other veterinary point-of-care ultrasound protocols.

Decreased fluid volume to reduce organ damage: a new approach to burn shock resuscitation? A preliminary study.

OBJECTIVE: To evaluate the impact of decreased fluid resuscitation on multiple-organ dysfunction after severe burns. This approach was referred to as "permissive hypovolaemia". METHODS: Two cohorts of patients with burns>20% BSA without associated injuries and admitted to ICU within 6 h from the thermal injury were compared. Patients were matched for both age and burn severity. The multiple-organ dysfunction score (MODS) by Marshall was calculated for 10 days after ICU admission. Permissive hypovolaemia was administered by a haemodynamic-oriented approach throughout the first 24-h period. Haemodynamic variables, arterial blood lactates and net fluid balance were obtained throughout the first 48 h. RESULTS: Twenty-four patients were enrolled: twelve of them received the Parkland Formula while twelve were resuscitated according to the permissive hypovolaemic approach. Permissive hypovolaemia allowed for less volume infusion (3.2+/-0.7 ml/kg/% burn versus 4.6+/-0.3 ml/kg/% burn; P<0.001), a reduced positive fluid balance (+7.5+/-5.4 l/day versus +12+/-4.7 l/day; P<0.05) and significantly lesser MODS Score values (P=0.003) than the Parkland Formula. Both haemodynamic variables and arterial blood lactate levels were comparable between the patient cohorts throughout the resuscitation period. CONCLUSIONS: Permissive hypovolaemia seems safe and well tolerated by burn patients. Moreover, it seems effective in reducing multiple-organ dysfunction as induced by oedema fluid accumulation and inadequate O2 tissue utilization.

[Chronic myelomonocytic leukemia in adults. Apropos of 3 personal cases]. / La leucemia mielomonocitica cronica dell'adulto. A proposito di tre osservazioni personali

Three cases of chronic myelomonocytic leukaemia are discussed and compared with the most recent data of the literature. The cytomorphological and cytochemical aspects of the disease as well as the therapy are discussed.

[Generalized hemorrhagic diathesis and anemia of sudden onset caused by rhabdomyolysis diagnosed as acute leukosis]. / Diatesi emorragica generalizzata e anemizzazione di spiccata entità da grave rabdomiolisi diagnosticata leucosi acuta.

A case of severe acute rhabdomyolysis (RML) is reported which was caused by marked hypokalemia associated with long-lasting diarrhea. Since the patient not only had severe muscular symptoms but also intense hemorrhagic diathesis and anemia, the first diagnosis on admission was acute leukemia. Due to the increasing occurrence of acute RML associated with different clinical conditions, including hematologic disorders, the hematologist should keep in mind the possibility of RML, both as a primitive disorder or complication, and require CPK and myoglobin assay routinely.

[Lymphomatoid granulomatosis. Lymphoma of a particular type which is very difficult to diagnose]. / Granulomatosi linfomatoide. Linfoma di tipo particolare di assai difficile diagnosi.

This paper reports two cases of lymphomatoid granulomatosis. Since at presentation the disease is generally characterized by lung involvement without any typical clinical manifestation and/or laboratory finding, it is generally diagnosed as interstitial lung disorder or neoplasm of the lung. The pathological feature of lymphomatoid granulomatosis is an angiocentric and angioinvasive polymorphic cellular infiltrate with necrotic areas, affecting primarily the lungs. Until recently this disorder was mainly known to pneumologists. Recent studies, however, have clearly shown that lymphomatoid granulomatosis is a particular lymphoproliferative disease which may progress to frank lymphoma in a proportion of cases. Therefore, lymphomatoid granulomatosis should be included within the neoplastic hematological disorders. Unfortunately, hematologists are not yet familiar enough with this disorder, whose diagnosis is very difficult in the majority of cases.

Bridging Over the Troubled Heterogeneity of SPG-Related Pathologies: Mechanisms Unite What Genetics Divide.

The hereditary spastic paraplegias (HSP) are characterized by spastic gait with weakness in the legs and additional neurological or extra-neurological signs in "complicated" forms. The past two decades have witnessed major advances in our understanding of their molecular bases with the identification of a plethora of loci and the cloning of several SPG genes. Combined genetic and clinical information has permitted a modern, molecularly-driven classification and an improved diagnosis, with several new data on the possible disease mechanisms. Further heterogeneity will rapidly emerge with the diffusion of next-generation sequencing platforms and, under the shadow of common themes in the pathogenesis, new therapeutic options will likely emerge for a great number of patients.

Lung ultrasound in the ICU: from diagnostic instrument to respiratory monitoring tool.

Imaging has greatly contributed to the understanding of lung disease in the critically ill and currently serves as a tool to diagnose lung pathology, monitor its course, and guide clinical management. Lung ultrasound is a real-time imaging modality that is simple, non-invasive, potentially ubiquitous, and free of ionizing radiation. Its increasing popularity and supporting research data substantiate its role as an emerging technique for bedside chest imaging in critical care. Furthermore, the International Consensus Conference on Lung ultrasound (ICC-LUS) promoted by the World Interactive Network Focused on Critical UltraSound (WINFOCUS) recently standardized the nomenclature and technique for lung ultrasound, and provided recommendations supporting its use in clinical practice. While the utility of lung ultrasound in the emergency setting is unquestioned, its potential role in the more complex and resource-rich intensive care environment is still under investigation. The purpose of this paper was to describe current and potential uses of lung ultrasound in the specific setting of adult intensive care, with an emphasis on respiratory monitoring, and to provide a framework for the practical application of this tool at the bedside.