Label-free imaging and identification of typical cells of acute myeloid leukaemia and myelodysplastic syndrome by Raman microspectroscopy.

In clinical practice, the diagnosis and classification of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) start from the manual examination of stained smears of bone marrow (BM) and peripheral blood (PB) by using an optical microscope. This step is subjective and scarcely reproducible. Therefore, the development of subjective and potentially automatable methods for the recognition of typical AML/MDS cells is necessary. Here we have used Raman spectroscopy for distinguishing myeloblasts, promyelocytes, abnormal promyelocytes and erhytroblasts, which have to be counted for a correct diagnosis and morphological classification of AML and MDS. BM samples from patients affected by four different AML subtypes, mostly characterized by the presence of the four subpopulations selected for this study, were analyzed. First, each cell was scanned by acquiring 4096 spectra, thus obtaining Raman images which demonstrate an accurate description of morphological features characteristic of each subpopulation. Raman imaging coupled with hierarchical cluster analysis permitted the automatic discrimination and localization of the nucleus, the cytoplasm, myeloperoxidase containing granules and haemoglobin. Second, the averaged Raman fingerprint of each cell was analysed by multivariate analysis (principal component analysis and linear discriminant analysis) in order to study the typical vibrational features of each subpopulation and also for the automatic recognition of cells. The leave-one-out cross validation of a Raman-based classification model demonstrated the correct classification of myeloblasts, promyelocytes (normal/abnormal) and erhytroblasts with an accuracy of 100%. Normal and abnormal promyelocytes were distinguished with 95% accuracy. The overall classification accuracy considering the four subpopulations was 98%. This proof-of-concept study shows that Raman micro-spectroscopy could be a valid approach for developing label-free, objective and automatic methods for the morphological classification and counting of cells from AML/MDS patients, in substitution of the manual examination of BM and PB stained smears.

Extensive rhabdomyoma of the head and neck region: a case report and a literature review.

Rhabdomyomas are rare mesenchymal benign tumors of striated muscle origin that can be classified into cardiac and extracardiac types. Cardiac rhabdomyomas are considered as hamartomatous lesion because of their association with phacomatosis. Extracardiac type is further classified into adult, fetal and genital form, depending on the individual tumor's degree of differentiation. Adult head and neck rhabdomyomas are rare pathologies of adult patients, with a male predominance. The occurrence of multifocality is a rare manifestation of this uncommon lesion. Presenting symptoms are related to the location and dimension of the tumors and they include upper airway obstruction, Eustachian tube dysfunction, dysphagia and mucosal and neck mass. Because of their high rate of recurrence, radical resection is the treatment of choice of this kind of tumors. In this article is reported a rare and particularly large case of head and neck adult rhabdomyoma, presenting with an history of sleep apnea and night-time stridor.

Dual regulation of Myc by Abl.

The tyrosine kinase c-Abl (or Abl) and the prolyl-isomerase Pin1 cooperatively activate the transcription factor p73 by enhancing recruitment of the acetyltransferase p300. As the transcription factor c-Myc (or Myc) is a known target of Pin1 and p300, we hypothesized that it might be regulated in a similar manner. Consistent with this hypothesis, overexpression of Pin1 augmented the interaction of Myc with p300 and transcriptional activity. The action of Abl, however, was more complex than predicted. On one hand, Abl indirectly enhanced phosphorylation of Myc on Ser 62 and Thr 58, its association with Pin1 and p300 and its acetylation by p300. These effects of Abl were exerted through phosphorylation of substrate(s) other than Myc itself. On the other hand, Abl interacted with the C-terminal domain of Myc and phosphorylated up to five tyrosine residues in its N-terminus, the principal of which was Y74. Indirect immunofluorescence or immunohistochemical staining suggested that the Y74-phosphorylated form of Myc (Myc-pY74) localized to the cytoplasm and coexisted either with active Abl in a subset of mammary carcinomas or with Bcr-Abl in chronic myeloid leukemia. In all instances, Myc-pY74 constituted a minor fraction of the cellular Myc protein. Thus, our data unravel two potential effects of Abl on Myc: first, Abl signaling can indirectly augment acetylation of Myc by p300, and most likely also its transcriptional activity in the nucleus; second, Abl can directly phosphorylate Myc on tyrosine: the resulting form of Myc appears to be cytoplasmic, and its presence correlates with Abl activation in cancer.

Effectiveness of maxillo-mandibular advancement in obstructive sleep apnea patients with and without skeletal anomalies.

This study evaluates the effectiveness of maxillo-mandibular advancement (MMA) in patients with obstructive sleep apnea syndrome (OSAS), even those without skeletal anomalies, indicating the possibility of extending this procedure to more patients. Two groups with different skeletal patterns were studied pre- and post-surgery. Group 1 (11 patients) had severe or moderate OSAS and maxillo-mandibular hypoplasia and/or mandibular deformities (SNA angle 78 degrees or less or SNA angle>78 degrees but with SNB<65 degrees and severe skeletal class II malocclusion). Group 2 (11 patients) had severe or moderate OSAS without maxillo-mandibular hypoplasia or deformity (SNA angle>80 degrees , dental class I occlusion). Analysis comprised: apnea hypopnea index (AHI), posterior airway space (PAS), SNA and SNB angles, Epworth sleepiness scale (ESS), body mass index (BMI), and a subjective standardized questionnaire about aesthetic appearance. All patients had increased PAS width and complete remission of objective and subjective OSAS symptoms evaluated by AHI and ESS. Results in both groups are comparable. Data were analysed using t-test; p<0.005 was statistically significant. All patients were satisfied with the functional and aesthetic results. MMA is effective in patients with severe or moderate OSAS, even in those without skeletal and/or occlusal anomalies and can be considered in more patients.

Voluminous frontoethmoidal mucocele with epidural involvement. Surgical treatment by coronal approach.

The case is described of mucocele of the right frontoethmoidal sinus with bilateral maxillary sinusitis and a large polyp in the right nasal cavity. The mucocele had determined erosion of the anterior and posterior walls of the frontal sinus and superomedial wall of the orbit. The patient was operated upon by a surgical team comprising ENT and maxillofacial specialists. Right maxillary sinusotomy (Caldwell-Luc procedure) was performed, and an osteoplastic flap was prepared, repositioned in the canine fossa and fixed with a titanium plate. Debris was removed from the left osteomeatal complex during endoscopy. To reach the mucocele, an external surgical approach was used, through a bitemporal coronal cutaneous incision, according to Unterberger. This approach was used in order to gain better access to the area of the lesion and in order to make reconstruction easier, with a view to achieving good functional results without untoward scarring. The scalp was detached down to the root of the nose to allow optimal visualisation of the anterior area of erosion determined by the mucocele, and, after excision and removal of the latter from the bony walls, of the posterior bony breach and underlying dura mater. Another bony breach involved the medial and superior walls of the orbit. The nasofrontal canal was obliterated with bone fragments and Tissucol; the posterior breach, with Surgical and Tissucol. The orbit wall was repaired with high-density porous polyethylene sheeting; the frontal sinus was filled with fat. The anterior wall of the frontal sinus was repaired with two split of calvarial bone grafts harvested from the parietal bone and fixed with a titanium microplate. The morphological outcome of reconstruction was satisfactory, with no recurrences, as confirmed at post-operative follow-up, including computed tomography scan, at 5 months. Ocular motility and patency of the tear drainage system were also normal. No diplopia, or inflammation occurred.

Central dopaminergic function in anorexia and bulimia nervosa: a psychoneuroendocrine approach.

Data on central dopamine (DA) function in patients with Anorexia Nervosa (AN) and Bulimia Nervosa (BN) are contradictory. To tentatively clarify the brain secretory state of the amine and its relationship with the nutritional impairments and/or the psychopathological aspects of the two disorders, we measured the responses of growth hormone (GH) to acute stimulation with apomorphine (APO), a selective D-1 and D-2 receptor agonist, in 16 AN patients, 8 restricted (AN-R) and 8 bingeing-purging (AN-BP), in 7 BN patients and in 8 healthy controls (CTR). Interference of impairment of the somatotropic axis in the GH response to APO stimulation was excluded by measuring the GH and insulin-like growth factor-1 (IGF-1) basal levels and GH responses to growth hormone-releasing hormone (GHRH) stimulation. Psychological aspects of patients and controls were investigated by the rating scales Eating Disorder Inventory (E.D.I.), Bulimic Investigation Test Edinburgh (B.I.T.E)., and Yale-Brown Cornell Eating Disorder Scale (YBC-ED). Basal GH levels were significantly higher and those of IGF-1 lower in AN-R than in AN-BP, BN and CTR subjects. GH responses to GHRH stimulation were significantly higher in AN-R than in AN-BP and BN patients and in CTR. GH responses to APO stimulation were significantly lower in AN-R and AN-BP than in BN and CTR subjects, suggesting that at the hypothalamic level there is a subsensitivity of postsynaptic D-2 receptors and possibly a presynaptic DA hypersecretion. The altered GH responses to APO stimulation did not correlate with the Body Mass Index, while they correlated negatively with E.D.I. scores.

Transformation of beta-amyloid (A beta) (1-42) tyrosine to L-dopa as the result of in vitro hydroxyl radical attack.

A form of beta-amyloid peptide A beta ending at amino acid 42 (A beta42) is the major component of senile amyloid plaques in Alzheimer's Disease (AD). The A beta-peptide earliest modifications are extremely important since they constitute the key events in the progression towards further changes finally leading to fibril formation and to A beta deposits which constitute the core pathological change in AD. Chemical and conformational early modifications of the beta-amyloid peptide are critical steps in AD pathogenesis and have been widely investigated. We now show that a Fenton-type OH-generating system is capable of generating L-Dopa (3,4-dihydroxyphenylalanine) in the tyrosine residue of A beta-peptide via aromatic ring hydroxylation, as the result of hydroxyl radical attack on proteins. Since L-Dopa is not a constituent of mammalian proteins and peptides, the formation of L-Dopa in A beta in vitro constitutes a possible important modification caused by hydroxyl radical attack. These results lay the groundwork for further studies on modification and damage associated with the degenerative disorder in AD where oxidative stress and inflammation are known to occur.

In vitro peroxidase oxidation induces stable dimers of beta-amyloid (1-42) through dityrosine bridge formation.

beta-amyloid (A beta) is a normal soluble peptide found in the cerebrospinal fluid (CSF) and other biological fluids. A beta fibrils are associated with Alzheimer's disease (AD) senile plaques. We have used purified soluble A beta (1-42) and A beta (12-28) peptides in order to determine the oxidative modification induced in these peptides by exposure to peroxidase and hydrogen peroxide. We have demonstrated that under these in vitro conditions, dimeric forms of A beta (1-42) can be detected by high-resolution polyacrylamide SDS-PAGE electrophoresis. Further experiments performed by reverse-phase high performance liquid chromatography (RP-HPLC), and monitored by fluorescence detection, showed that the dimeric A beta (1-42) forms induced by the peroxidase reaction are the outcomes of dityrosine bridge formation. This cross-link results from the enzyme catalyzed oxidation. During this reaction, phenolic coupling of tyrosine residues of two A beta (1-42) peptides occurs. No detectable peroxidative modifications were observed with the A beta (12-28) peptide which lacks a tyrosine residue. Since oxidative stress is thought to be associated with AD, the experimental model described here can help in understanding the early events leading to chemical, structural and conformational modifications before the conversion of sA beta to amyloid fibrils and eventually the formation of senile plaques in AD.

Simultaneous rhinoplasty and maxillomandibular osteotomies: Indications and contraindications.

Functional and esthetic correction of a dentofacial deformity may require not only maxillary or mandibular osteotomies but also a rhinoplasty. Rigid internal fixation makes it possible to perform rhinoplasty and maxillary osteotomies simultaneously. Nevertheless, to plan rhinoplasty correctly it is of paramount importance to predict changes of the nose that will follow osteotomy of the maxilla. The authors present their experience concerning the surgical technique, advantages, and disadvantages of rhinoplasty in combination with orthognathic surgery.

Predictive value of obsessive-compulsive personality disorder in antiobsessional pharmacological treatment.

Previous reports have stressed the implication of Personality Disorders as predictors of a poorer treatment outcome in Obsessive-Compulsive Disorder (OCD). The aim of this study was to see whether or not Obsessive-Compulsive Personality Disorder in Obsessive-Compulsive Disorder may be predictive for a poorer outcome to antiobsessive pro-serotonergic pharmacological treatment. For this purpose, 30 OCD patients were divided into two groups according to the presence or absence of Obsessive-Compulsive Personality Disorder. Ten-week standardized treatments with oral SRI drugs were given to look for different outcomes between the two groups in Obsessive-Compulsive symptom severity. At the end of the study we found that the presence of Obsessive-Compulsive Personality Disorder, along with the total number of Personality Disorders, did predict poorer response to pharmacological treatment in OCD.

Modified intraoral maxillo-malar osteotomy: long-term results in 16 consecutive cases.

The authors report their experience with sixteen consecutive cases of maxillo-malar osteotomy via an intraoral approach. Some technical expedients and modifications to the original technique are described here. This procedure was associated in all cases with bilateral sagittal splitting of the mandible and in two cases with vertical reduction of the chin. Results from this series confirm the reliability of this technique and the stability of functional and aesthetic results.

[Warthin tumor of the palate: an unusual location]. / Il tumore di Warthin del palato: un'insolita localizzazione.

UNLABELLED: Warthin's tumor (papillary cystadenoma lymphomatosum) primarily involves the parotid gland, whereas localization in the palate has been reported by a few authors. A new case of true Warthin's tumor arising from the hard palate is here presented and histogenesis and differential diagnosis are briefly discussed. CASE REPORT: A 50 year-old woman who was referred to us because of the presence of multiple contiguous bluish cyst-like lesions involving both sides of the hard palate mucosa. The lesion was removed with a wide excision involving almost all the soft tissues of the hard palate. Histologic diagnosis (E.E stain) was: papillary cystadenoma lymphomatosum. DISCUSSION AND CONCLUSION: The histogenesis of Warthin's tumor is still controversial. The most widely accepted theory is that the tumor represents a neoplastic proliferation of salivary gland ducts entrapped in pre-existing lymph nodes. In fact, immunohistochemical analysis and cell-surface markers studies have shown that the lymphoid component is predominantly formed by T-lymphocytes, with a relatively small number of polyclonal B-lymphocytes. On the contrary, other authors found opposite relationship between T and B lymphocytes. These findings supported the concept that lymphoid tissue in Warthin's tumor represented a reactive cellular infiltrate in a pattern similar to that seen in reactive lymph nodes. Similar results have been found in this report; moreover, the hard palate does not usually contain lymphatic tissue. This could support the idea that the lymphoid tissue associated with this case is reactive and a direct origin from the ductal epithelium with secondary lymphocytic infiltration is more likely to occur in this area.

Deranged platelet calcium homeostasis in diabetic patients with end-stage renal failure. A possible link to increased cardiovascular mortality?

OBJECTIVE: Platelet hyperfunction is a typical feature of the prothrombotic state that frequently complicates the natural history of diabetes. In uremia, a bleeding diathesis is present, which principally involves the primary phase of hemostasis. Thus, in patients with uremia of diabetic origin, the infrequent coexistence of two opposite alterations of hemostasis takes place. In patients with uremia, an increased incidence of cardiovascular events and related mortality is observed. This phenomenon is greatly amplified in uremia of diabetic origin. Calcium homeostasis is a critical aspect of platelet function, which has recently become available in human diseases. The aim of this study was to evaluate calcium homeostasis in platelets from patients with uremia of diabetic and nondiabetic origin. RESEARCH DESIGN AND METHODS: We evaluated, by means of Fura 2, the intracellular concentration of ionized calcium ([Ca2+]i) in platelets from 18 patients with uremia of diabetic origin, 12 patients with uremia of nondiabetic origin and 16 healthy control subjects [Ca2+]i was evaluated in resting conditions and after stimulation with 0.05, 0.1, 0.5 U/ml thrombin. RESULTS: Platelets from uremic patients with diabetes had higher resting [Ca2+]i than both control subjects (P = 0.01) and uremic patients without diabetes (P = 0.001). Similarly, after stimulation with thrombin, the absolute increase of [Ca2+]i was higher (P < 0.05) in platelets from uremic patients with diabetes compared with both control subjects and uremic patients without diabetes. The relative increase of [Ca2+]i was higher (P < 0.05) than normal in platelets from uremic patients after weak or intermediate strength thrombin. No correlation were present between [Ca2+]i values and other clinical and laboratory variables potentially associated with platelet hyperfunction. CONCLUSIONS: Diabetes and uremia in combination further deteriorate the abnormal platelet calcium homeostasis observed in uremia.

Endosseous implants for prosthetic rehabilitation in bone grafted alveolar clefts.

The authors report their experience in the surgical and prosthetic rehabilitation of three patients affected by sequelae of cleft lip and palate, with residual alveolar cleft and absence of maxillary anterior teeth. The patients were treated by means of late secondary bone grafting of the alveolar cleft, followed by the insertion of endosseous titanium plasma-sprayed implants (IMZ). After a further healing period (6-12 months) fixed dental prostheses were constructed. Preliminary results from this series have shown how dental prostheses supported by endosseous implants in grafted alveolar clefts are a very reliable possibility in dental rehabilitation of this malformation.

Laboratory response of patients with panic and obsessive-compulsive disorders to 35% CO2 challenges.

OBJECTIVE: The DSM-III-R anxiety disorders section includes both panic disorder and obsessive-compulsive disorder. To evaluate the relationship between these two disorders, subject responses to inhalation of a 35% CO2 and 65% O2 mixture were assessed. METHODS: Twenty-three patients with panic disorder, 23 with obsessive-compulsive disorder, 12 with both obsessive-compulsive and panic disorder, and 23 healthy comparison subjects were given a single vital capacity inhalation of 35% CO2 and 65% O2 or a placebo mixture of compressed air. A double-blind, random, crossover design was used. RESULTS: Patients with panic disorder and patients with both panic disorder and obsessive-compulsive disorder showed similar strong anxiogenic reactions to 35% CO2; while patients with obsessive-compulsive disorder alone did not differ from comparison subjects. CONCLUSIONS: These results confirm that obsessive-compulsive disorder and panic disorder are two distinct syndromes and that patients with these disorders have different sensitivity to CO2 inhalation.

Platelet calcium homeostasis is abnormal in patients with severe arteriosclerosis.

To evaluate platelet calcium homeostasis in a typical thrombosis-prone clinical condition, 14 patients with severe arteriosclerosis and 11 healthy control subjects were studied. Platelet intracellular free calcium concentration ([Ca2+]i) was evaluated by means of the fluorescent probe fura 2 under resting conditions and after challenge with 0.05, 0.1, and 0.5 U/mL thrombin (final concentrations). Three different concentrations of extracellular ionized calcium ([Ca2+]e) were used: 1 mmol/L, 1 mumol/L, and < 1 nmol/L. Resting platelet [Ca2+]i was significantly higher (P < .001) in patients than in control subjects. After addition of 0.05 U/mL thrombin, the relative increase of [Ca2+]i was lower in patients than in control subjects in each of the three [Ca2+]e conditions (P = .05 at 1 mmol/L, P = .02 at 1 mumol/L, and P = .04 at < 1 nmol/L). After addition of 0.1 U/mL thrombin, the relative increase of [Ca2+]i was lower in patients than in control subjects under two [Ca2+]e conditions, 1 mumol/L and < 1 nmol/L (P = .04 and P = .03 respectively). With 0.5 U/mL thrombin, a trend toward lower values in patients than in control subjects was observed, reaching statistical significance (P = .03) only at < 1 nmol/L [Ca2+]e. These results suggest that calcium homeostasis is abnormal in platelets from patients with severe arteriosclerosis and probably reflects a chronic activation.

Sinus lift and endosseous implants--preliminary surgical and prosthetic results.

The authors present their experience in 43 cases of maxillary sinus augmentation with autologous bone and hydroxylapatite granules via a lateral maxillary approach. During the same operation or after six months, according to width and height of the residual alveolar ridge, hydroxylapatite coated titanium endosteal implants (IMZ) were inserted in the maxilla; after an additional healing period of 6 months, dental prostheses were applied; the mean follow-up was 14.5 months (range: 12-24 months). Out of 124 implants inserted in the grafted sinuses, 8 failed, with a 93.5% success rate, whereas of 38 implants inserted in the grafted sinuses, 8 failed, with a 93.5% success rate, whereas of 38 implants inserted in the anterior maxilla, 2 (5.3%) failed. The results from this preliminary report indicate that composite bone grafting of the maxillary sinus is a very reliable technique that provides the bony structure for correct placement of endosseous implants.

[Neurilemmoma (schwannoma) of the oral cavity. A report of 2 clinical cases]. / Il neurilemmoma (schwannoma) del cavo orale. Presentazione di 2 casi clinici.

Neurilemmoma (schwannoma) is a benign, encapsulated perineural tumor of neuroectodermal derivation that originates from the Schwann cells of the neural sheath of motor and sensitive peripheral nerves; the etiology is still unknown. The tumor is normally solitary, smooth-surfaced, slow growing and generally asymptomatic. It may develop at any age and there is no gender predilection. Head and neck are one of the most frequent localizations, but intraoral development is quite uncommon. In this area the mobile portion of the tongue, and in a decreasing order, the palate, the cheek mucosa, the lip and gingiva are the most frequent locations. Although it origins from the nervous tissue, only in 50% of the cases a direct relation with a nerve is demonstrated. The term schwannoma has been attributed in the past either for neurofibroma and neurilemmoma. Their histogenesis remain anyway a controversial argument. Some authors think that both tumors originate from Schwann cells and perineural connective cells. Others think that the first one originate from perineural cells, while the latter from Schwann cells. Diagnosis is confirmed by microscopic examination. Neurilemmoma shows two different components: Antoni type A and Antoni type B tissue. The first one consists of Schwann cells arranged in compact, twisted bundles, associated with delicate reticulin fibres and spindle-shaped nuclei aligned in parallel rows forming a typical palisading pattern. Between the rows there are fine cytoplasmatic fibrils with acellular, eosinophilic masses called Verocay bodies. The second one is formed by irregularly arranged masses of elongated cells and fibers similar in appearance to neurofibroma, with areas of cystic degeneration and edema.(ABSTRACT TRUNCATED AT 250 WORDS)