A possible novel objective intraoperative measurement of maxillary bone density.

AIM: Implant survival and success rates are strictly related to the density of the bone they are placed in. Bone density, in fact, affects both implant primary stability and implant micromovements after implant positioning. Current bone density classifications rely on subjective, scarcely reproducible evaluations. A novel implant micro motor featuring a bone density measurement probe has been recently introduced. The objective of this study was to test such bone density measurement system for its capability of distinguishing different bone density areas in the upper and in the lower jaw. METHODS: 1254 implant placement sites had their bone density measured during standard implant placement at a single clinical facility. After data collection bone density distribution was statistically analyzed in order to test the hypothesis of a non-homogeneous distribution in four different predefined anatomical maxillary zones, namely pre-antral (between teeth from 14 to 24) and sub-antral (more distally) in the upper maxilla and interforaminal (between and including teeth from 34 to 44) and retroforaminal (more distally) zone. RESULTS: Measured bone density values, organized according the named four anatomical zones, produced a statistically significant inhomogeneous pattern (P<0.001). Density distribution was consistent with data from literature, but not always corresponding with the one achieved by applying the well known Misch classification. CONCLUSION: The measuring system we tested allowed to distinguish different and clinically significant anatomical zones according to their different bone density, and can represent a fundamental diagnostic tool to plan the proper implant placement steps.

The use of cortical heterologous sheets for sinus lift bone grafting: a modification of Tulasne's technique with 7-year follow-up.

In this article, the authors describe their experience with using cortical deantigenated equine bone sheets in sinus lift grafting procedures performed on 23 patients. The technique employed resembles that described by Tulasne but avoids the need for using harvested calvaria bone and introduces some additional operating variants. The use of heterologous cortical bone sheets effectively managed even large lacerations of the Schneiderian membrane and allowed for immediate stabilization of the heterologous bone granules. Average histomorphometric values for bone cores collected six months after grafting, at the time of implant placement, were: newly formed bone tissue, residual bone substitute, medullary spaces. At seven year follow-up, clinical and radiographic examination indicated that the use of the bone sheets preserved the regenerated bone volume. In conclusion, the use of heterologous cortical bone sheets in association with granular bone graft material enabled long-term stabilization of the graft material and effective management of intra-surgical complications.

Breast metastasis from clear cell renal cell carcinoma.

In Western countries, breast cancer is the most common cancer in women, whereas metastases to the breast from extramammary malignancies are extremely rare. We present the case of a 60-year-old woman, who underwent surgery in 2007 for clear cell renal cell carcinoma and who 4 years later presented with a breast metastasis from clear cell renal cell carcinoma.

Treatment of a bone defect consequent to the removal of a periapical cyst with equine bone and equine membranes: clinical and histological outcome.

AIM: While deproteinized bovine bone and bovine membranes have been well studied and can yield good results when used to treat bone defects and peri-implant dehiscences, enzymatically deantigenated equine bone and equine membranes have emerged as possible alternative biomaterials. The objective of this study was the clinical and histological assessment of such materials: equine bone granules, an equine collagen membrane and an equine pericardium membrane. METHODS: Enzymatically deantigenated equine bone and an equine collagen membrane were used to restore a bone defect caused by the removal of a bone cyst in the upper anterior maxilla. After 4.5 months, an implant was placed and a bone core sample was obtained from the grafted site. Implants threads, though, were exposed. This defect was grafted with a mixture of autogenous and equine bone and covered with an equine pericardium membrane. RESULTS: Four months after implant placement the peri-implant bone levels were maintained. A prosthesis was delivered three months later providing functional and esthetic rehabilitation. Also four-year follow-up controls showed implant success. Histological analysis of the bone core revealed that the graft material had undergone remodelling, and a fair amount of newly formed vital bone was present at the time of sample collection. CONCLUSION: The deantigenated equine bone is biocompatible and undergoes osteoclastic remodelling. Both the equine collagen and pericardium membrane acted as effective barriers for guided bone regeneration.

A randomized, double-blind, placebo-controlled study of benfluorex in HIV-infected patients with insulin resistance or impaired glucose tolerance.

PURPOSE: We previously reported a beneficial effect of benfluorex (BFL) on oral glucose tolerance test (OGTT) and visceral fat mass in an open-label study conducted in 60 HIV-infected patients. The objective of this study was to assess whether administration of BFL compared to placebo (PBO) improves insulin resistance (IR) in HIV+ patients with HAART- induced lipodystrophy. METHOD: 22 HIV-infected patients with IR or impaired glucose tolerance were double-blind randomly assigned to receive BFL 3 tablets/day or PBO for 24 weeks. Efficacy assessments included OGTT, abdominal computed tomography, and the measurement of fasting lipids. RESULTS: Change of median insulin AUC was -53.0 microIU/mL (IQR, -126.0 to -12.7) in the BFL group vs. +33.6 microIU/mL (IQR, 7.0 to 115.6) (p = .01) in PBO group. Weight decreased significantly in the BFL group (-2 kg +/- 2.6; IQR, -6.8 to 2.0) compared to the PBO group (0.8 kg +/- 1.7; IQR, -2.0 to 0.5) (p = .02). No significant changes in visceral or subcutaneous fat mass and plasma lipid level were observed between the two groups. CONCLUSION: Added to antiretroviral therapy, a 6-month therapy with BFL improved insulin sensitivity but is not sufficient to reduce significantly visceral fat mass.

[Severe cystitis and perivesical collection posterior to Mitomycin C immediate instillation in a patient with inadverted bladder perforation]. / Cistitis severa y colección perivesical posterior a instilación inmediata de Mitomicina C en paciente con perforación vesical inadvertida.

We present the clinical case of a 40 years male patient who, after a TURBt for non-muscle invasive recurrence with inadverted vesical perforation and Mitomycin C immediate instillation, come in his fourth postoperative day to the emergency room with severe irritative urinary symptomatology. An ultrasound was indicated, documenting a perivesical collection. The management was conservative with vesical drilling for 10 days and a puncture/drainage was necessary to solve it.

High cervical neurenteric cyst; acute post-traumatic rupture and respiratory failure: a case report.

The neuroenteric cyst is a rare developmental lesion originating from incomplete formation of the primitive neuroenteric canal. We report on the difficult management of an acute post-traumatic rupture of a cervical neuroenteric cyst. A 35-year-old male patient came to our observation after a spinal injury incurred during a football match. The patient immediately demonstrated tetraplegia and respiratory failure and was operated on. After two weeks the patient died of cardiopulmonary failure. High cervical neurenteric cysts, even those representing benign lesions, can produce dramatic results after a spinal injury.

Primary intradural extramedullary ependymoma: imaging findings and review of the literature. A case report.

We describe a 32-year-old woman who presented with progressive dorsal back pain. Neither sensory nor motor deficit was reported. Magnetic resonance imaging (MRI) of the dorsal spine revealed a primary intradural extramedullary lesion with severe spinal cord compression. No other lesion was found in the central nervous system. During surgery an intradural extramedullary tumor was found without medullary infiltration and a total removal was achieved under microscopic guidance. The histological diagnosis revealed a benign extramedullary ependymoma. The patient recovery completely after surgery and at a follow-up of 24 months MRI showed no evidence of tumor recurrence. Ependymoma should be taken in account in the differential diagnosis on intradural extramedullary tumours.

Regulation of autophagy by the inositol trisphosphate receptor.

The reduction of intracellular 1,4,5-inositol trisphosphate (IP(3)) levels stimulates autophagy, whereas the enhancement of IP(3) levels inhibits autophagy induced by nutrient depletion. Here, we show that knockdown of the IP(3) receptor (IP(3)R) with small interfering RNAs and pharmacological IP(3)R blockade is a strong stimulus for the induction of autophagy. The IP(3)R is known to reside in the membranes of the endoplasmic reticulum (ER) as well as within ER-mitochondrial contact sites, and IP(3)R blockade triggered the autophagy of both ER and mitochondria, as exactly observed in starvation-induced autophagy. ER stressors such as tunicamycin and thapsigargin also induced autophagy of ER and, to less extent, of mitochondria. Autophagy triggered by starvation or IP(3)R blockade was inhibited by Bcl-2 and Bcl-X(L) specifically targeted to ER but not Bcl-2 or Bcl-X(L) proteins targeted to mitochondria. In contrast, ER stress-induced autophagy was not inhibited by Bcl-2 and Bcl-X(L). Autophagy promoted by IP(3)R inhibition could not be attributed to a modulation of steady-state Ca(2+) levels in the ER or in the cytosol, yet involved the obligate contribution of Beclin-1, autophagy-related gene (Atg)5, Atg10, Atg12 and hVps34. Altogether, these results strongly suggest that IP(3)R exerts a major role in the physiological control of autophagy.

A case of intraroot cauda equina cavernous angioma: clinical considerations.

STUDY DESIGN: Case report and literature review. OBJECTIVE: Intradural-extramedullary cavernoma is a rare condition with only 23 cases reported in the literature. Most cases described adhere to spinal root or spinal cord. We report an example of this rare entity located within the sheets of one cauda equina nerve root. SETTING: Rome, Italy. METHODS: The authors report clinical, radiological, surgical, and pathological features of intraroot cavernoma with a literature review. RESULTS: Patient was operated. One year after surgery, he was healthy. CONCLUSION: Lumbar intradural cavernous angioma may present with sciatalgia, low-back pain, neurological deficit, or, more rarely with subarachnoid hemorrhage or hydrocephalus. They are treated successfully with surgical resection but preoperative status is a predicting factor for outcome. Sometimes the sacrifice of the spinal root is inevitable because, as in present case, the cavernous angioma is included in the nerve root. These lesions are rare and benign lesions. It is important for neurosurgeons to be aware of the existence of this entity to avoid preoperative misdiagnosis with tumor.

Post-radiation intramedullary malignant peripheral nerve sheath tumor.

We report the intramedullary growth of a malignant peripheral nerve sheath tumour (MPNST). A 50year-old man developed a severe tetraparesis over a 4-month period. Following irradiation of a chronic tonsillitis during his childhood, the patient had later experienced a number of post-radiation diseases, including a laryngeal cancer that required permanent tracheotomy. Before admission, a magnetic resonance imaging (MRI) study had disclosed a C4-C5 intramedullary lesion. On admission to our Department, the patient had a nearly complete tetraparesis. At surgery, the lesion was exposed through a posterior midline myelotomy. A friable neoplasm, with no clear plane of cleavage, was found. The tumour was subtotally resected. Histological examination, which intraoperatively had not yielded a specific diagnosis, eventually revealed a MPNST, grade intermediate, with ultrastructural and immunohistochemical features consistent with a schwannian differentiation. No postoperative radiotherapy was undertaken. The patient died 9 months later from pneumonial complications. MPNSTs may develop within the spinal cord similarly to their benign schwannian counterpart. The reported sequence of events might support a possible relation between irradiation of the spinal cord and induction, followed by malignant transformation, of intramedullary schwannosis. This unique case must be added to the growing list of radiation-induced spinal cord tumours.

Cranklike conformational transitions in polyethylene.

Molecular dynamics simulations of a variety of polymeric systems provide the evidence for two different kinds of conformational transitions: independent single bond transitions and cranklike transitions (or correlated bond transitions). While single bond transitions can be rationalized according to standard theories of activated processes controlled by the saddle point crossing, a more complex description is required for the other type of transitions. In a recent work devoted to the analysis of the simplified chain model with three rotors [B. Nigro and G. J. Moro, J. Phys. Chem. B 106, 7365 (2002)], a theory has been proposed for cranklike transitions represented as a kinetic process between equilibrium states differing by two torsional angles (i.e., two bond transitions). Moreover their rate coefficients were estimated on the basis of a local expansion about the bifurcation of the separatrices departing from the potential function maximum. In the present work the same theory is applied to a model for long alkyl chains in solution, in order to rationalize the behavior of cranklike transitions in polyethylene and to recognize the molecular features controlling them. We obtain probabilities of occurrence of cranklike transitions in substantial agreement with simulation results. Furthermore, the theory is capable of explaining the dependence of the rate on the separation between the two reactive bonds, as well as the dependence on the conformational state of the starting configuration. In particular, selection rules for next-to-nearest neighbor transitions are recovered from the shape of the separatrices and the location of the corresponding bifurcations.

Benfluorex as a therapeutic option for insulin resistance in HIV lipodystrophy syndrome.

BACKGROUND: HIV lipodystrophy syndrome, characterized by a significant excess of visceral adiposity and a reduced subcutaneous fat mass in association with insulin resistance and dyslipidemia, still affects the majority of antiretroviral-treated HIV-infected patients. The therapeutic management of this syndrome has not yet been well established. Benfluorex is known to decrease insulin resistance with no side effects on lactate levels in HIV-negative patients. METHOD: We conducted an open-label study of benfluorex (150 mg, 2-3 times a day) that was prescribed for 60 HIV-infected patients who were diagnosed with glucose metabolism abnormalities by oral glucose tolerance test (OGTT); 47 of these patients had visceral fat accumulation measured by computed tomography (VAT). Median follow-up was 12 months (interquartile range [IQR] = 6-12 months). The great majority of patients (90%) were treated with at least triple therapy (in 70% the therapy included at least one PI), with a nonsignificant change over the study period. RESULTS: Added to antiretroviral therapy, benfluorex improved OGTT in 47/60 cases, including total normalization in 34/60 without lactate concentration modification. A trend toward a decrease in VAT distribution was observed (p =.06). No significant difference was observed in subcutaneous fat distribution, although an increase in subcutaneous thigh adipose tissue was observed in 17/47 (36.2%) cases and 6 patients (12.7%) presented both subcutaneous fat increase and VAT decrease.

Human pituitary tumours express the bHLH transcription factors NeuroD1 and ASH1.

Among the transcription factors involved in pituitary ontogenesis and physiology, basic helix-loop-helix (bHLH) have been poorly studied. Members of bHLH family include NeuroD1 and ASH1, both involved in neuroendocrine differentiation. We evaluated their mRNA expression patterns, by semi-quantitative RT-PCR analysis (sq-RT-PCR) and/or Northern blot, in a series of 33 pituitary adenomas (PA), anterior pituitaries, and pituitary cell lines. Immunohistochemistry for NeuroD1 was also performed in 25 PA. Low levels of NeuroD1 were observed in normal pituitaries and in the somatomammotroph cell lines GH3/GH4C1, contrasting with high levels in corticotroph AtT20 cells. NeuroD1 mRNA was widely expressed in PA (82%), with measurable levels found especially in those derived from Pit-1 independent lineages, i.e. corticotroph (5/5) and clinically non-secreting (CNS) adenomas (9/11). According to sq-RT-PCR analysis, overexpression of NeuroD1 compared to normal pituitaries was frequent. Variable nuclear NeuroD1 immunopositivity was also present in about 70% of studied cases. ASH1 mRNA was widely detected in normal pituitaries, in all tumour cell lines and in most PA (84%), with measurable levels in corticotroph (5/5) and CNS (9/11) adenomas, and in a significant subset of PA derived from Pit-1 dependent lineages (9/16). We conclude that: a) NeuroD1 is differentially expressed in PA and its possible ontogenetic and/or pathogenetic implications in non-corticotroph PA are discussed; b) ASH1 is a neuroendocrine marker whose expression is largely conserved in normal and neoplastic pituitary cells.

A critical reappraisal of MIB-1 labelling index significance in a large series of pituitary tumours: secreting versus non-secreting adenomas.

Pituitary tumours are usually benign neoplasia, but may have a locally aggressive or malignant evolution. This study aimed to identify factors which mostly influence their proliferative activity, in order to clarify its value for clinical and research purposes. The proliferative index was determined in a prospective series of 132 pituitary tumours as the percentage of monoclonal antibody MIB-1-immunopositive cells and referred to as the MIB-1 labelling index (LI). Its distribution was analysed according to both univariate and multivariate models. A life-threatening pituitary tumour is presented separately. The mean LI was 1.24+/-1.59%, with significant differences between clinically secreting (CS) and clinically non-secreting (CNS) adenomas. In CS adenomas (n=65), LI was highly variable and markedly influenced by pre-operative pharmacological treatment (0.80+/-1.03 vs 2.06+/-2.39% in treated vs untreated cases, P=0.009); it decreased with patient's age (P=0.025, r=0.28) and increased with tumour volume and invasiveness. The influence of pre-operative treatment and macroscopic features on LI in this group was confirmed by multivariate analysis. In CNS adenomas (n=67), LI distribution was less variable than in CS adenomas (P<0.0001), it was age-independent and correlations with tumour volume, invasiveness or recurrence did not reach significance. In a rapidly growing parasellar tumour, the mean LI was 24% at first surgery and exceeded 50% at second surgery performed 4 months later. LI should be interpreted according to hormone secretion and pre-operative treatment. Unusually high LI values deserve particular attention.

Hodgkin's disease: prognostic role of gallium scintigraphy after chemotherapy.

Evaluation of the response to therapy is important for optimal selection of treatment strategy in patients with Hodgkin's disease (HD). Refractory disease requires intensive high-dose chemotherapy, whereas unnecessary treatment should be avoided in patients in complete remission. The purpose of this study was to evaluate the contribution of gallium-67 scintigraphy in predicting the clinical outcome in patients with HD and mediastinal involvement on the basis of scan results at the end of chemotherapy. Seventy-four patients with HD and mediastinal involvement were retrospectively investigated with 67Ga scintigraphy 72 h after injection of 220 MBq 67Ga citrate (planar and single-photon emission tomographic studies) following the completion of chemotherapy. At the same time, they all underwent computed tomography (CT). Patients were followed up for an average of 63 months (range 28-124 months). The disease status was newly diagnosed disease in 64 of the patients and relapse in 10. Systemic symptoms were absent (A) in 34 cases and present (B) in 40 cases. Forty-one patients had stage I or II disease and 33 patients had stage III or IV disease. Twenty-two patients had bulky disease on initial diagnosis. At the end of chemotherapy, all 74 patients showed regression of the mass by more than 50% (50%-100%) on CT. Patients were divided into two groups according to the positivity or negativity of the gallium scan after chemotherapy: 61 patients had negative and 13 patients had positive gallium scans. In the gallium-negative group, 19.7% of the patients relapsed and 91.8% were alive at the end of the follow-up. Relapse occurred in 20% of the patients with residual mass and in 19.6% of the patients without residual mass. In the gallium-positive group, 84.6% of the patients had recurrent disease and 61.5% were alive after intensive chemotherapy. There was a statistically significant difference in overall survival between patients with positive and patients with negative gallium results (P=0.0034). Disease-free survival differed significantly between patients with positive and patients with negative gallium scans at the end of chemotherapy (P<0.0001). The relative risk of death was 5.2 and the relative risk of relapse was 11.3 for patients with positive gallium scans, in comparison to those with negative gallium scans. The positive and negative predictive values for predicting relapse were 85% and 87%, respectively. It is concluded that even if gallium scan is performed at the end of chemotherapy, it can predict outcome. Alternative therapy may be required on the basis of gallium scan results obtained after treatment.

Two familial giant pituitary adenomas associated with overweight: clinical, morphological and genetic features.

OBJECTIVE: Pituitary adenomas are usually sporadic, although rare familial cases have been described. Here we report two first degree female cousins with giant pituitary adenoma and overweight. Both presented with secondary amenorrhoea, occasional headache and weight gain. MATERIALS AND METHODS: In both patients clinical, morphological and genetic studies were performed. Both patients underwent surgery and post-operative medical therapy with somatostatin analogues and dopamine agonist, followed by a conventional radiotherapy course. RESULTS: Clinical examination at presentation revealed an acromegaloid habitus only in the second patient. Basal and dynamic hormonal evaluation showed high serum GH and serum IGF-I values, higher in the second than in the first patient, and a mild hyperprolactinaemia only in the first patient. On optical and electron microscopy, both tumours were oncocytic adenomas, immunopositive for GH in the first patient and GH/prolactin in the second. The genetic analysis for germ-line mutations of the multiple endocrine neoplasia type 1 gene was negative. Two years after radiotherapy a remarkable shrinkage of both tumours was observed, whereas the overweight worsened in both patients, accompanied by high plasma leptin values. CONCLUSION: To our knowledge, this is the first report of familial pituitary adenomas including one case of a clinically silent GH-secreting adenoma. In addition, it provides further evidence that familial pituitary tumours can occur as a multiple endocrine neoplasia type 1 unrelated disease.

Radiation injury involving the internal carotid artery. Report of two cases.

Radiation therapy is an uncommon cause of stenosis and occlusions of the cervical internal carotid artery (ICA). We describe two cases of cerebral ischemia due to ICA stenosis in patients irradiated for malignant tumors (lymphoma and breast cancer). The first patient, a 32-year-old man, presented with an episode of cerebral ischemia. Six years previously he had received irradiation therapy for a left laterocervical mass histologically diagnosed at biopsy as a Hodgkin's lymphoma. Cerebral angiography on entry revealed bilateral occlusion of the cervical ICA, with a 2-cm stump at the origin of the left ICA. Despite anti-platelet aggregation therapy the ischemic attacks persisted, necessitating a stumpectomy. After vascular-repair surgery the patient had no further ischemic symptoms. The second patient, a 42-year-old woman, began to experience the sudden onset of pain in the right arm and left hemiparesis five years after surgery plus irradiation (4500 rad) for breast cancer, and three years after excision of a single cerebral metastasis. Cerebral angiography obtained on admission showed occlusion of the right ICA and right subclavian arteries, both lesions necessitating thrombectomy. After surgery the right radial pulse immediately re-appeared and the hemiparesis regressed. In both patients, 2-year follow-up assessment by Doppler ultrasonography and magnetic resonance angiography (MRA) confirmed that the operated arteries remained patent. These two unusual cases underline the potential risk of irradiation-induced ischemic cerebrovascular symptoms, suggesting that patients who have received radiation therapy to the neck and mediastinum who survive for more than 5 years should undergo regular non-invasive imaging of neck vessels (Doppler ultrasonography and MRA).

p16 (INK4a, MTS-1) gene polymorphism and methylation status in human pituitary tumours.

OBJECTIVE: The p16 gene, which encodes a physiological inhibitor of the cyclin D-CDK4 complex, is now considered as an important tumour-suppressor gene in a variety of tumours. A marked reduction of its expression has been reported to occur without significant genetic alterations in human pituitary adenomas, although rare point mutations of uncertain functional significance have been described. On the other hand, p16 gene silencing due to hypermethylation has been reported in several human primary tumours. The aim of this study was to further investigate the pathogenetic events leading to p16 gene inactivation in pituitary tumours. DESIGN: To screen a european series of human pituitary tumours for p16 gene alterations and possible gene hypermethylation. PATIENTS: A representative series of 31 human pituitary tumours-30 macroadenomas, including a MEN-1 non-secreting pituitary adenoma and a non-MEN-1 familial giant GH-secreting adenoma, and one FSH-secreting pituitary carcinoma-was studied. METHODS: Polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) analysis was used to screen for p16 gene alterations in all cases. Direct sequencing of PCR-products was obtained by the di-deoxynucleotide method where suspected abnormalities of the PCR-SSCP analysis were observed. In 24 samples, a methylation-specific PCR assay (MSP-PCR) was used to determine p16 gene methylation status. RESULTS: Two sporadic cases of pituitary adenomas had a similar single A to G base substitution leading to an heterozygous Ala140Thr p16 polymorphism, which has not previously been described in such tumours, but is known to be functionally silent. No other p16 abnormality could be suspected from PCR-SSCP analysis in this series. In contrast, the presence of methylated-specific PCR products was observed in 20/24 cases (83.3%). CONCLUSIONS: This study confirms that p16 gene mutations are not involved in the pathogenesis of human pituitary tumours, although polymorphisms can be demonstrated, depending on the population considered. In contrast, the high incidence of hypermethylation of the p16 gene suggests that such an alteration occurs early in pituitary tumours, and may play a role in pituitary tumorigenesis.