Effect of Cabergoline on weight and glucose metabolism in patients with acromegaly.

PURPOSE: Cabergoline (CAB) has shown to have benefic effects on the metabolism in different clinical settings but its metabolic role in acromegaly disease has not been studied yet. Aim of our study was to evaluate the impact of CAB on glucose metabolism and weight in patients with acromegaly. METHODS: All patients with acromegaly undergoing continuous treatment with CAB for at least 6 months were retrospectively screened. Exclusion criteria were discontinuation of CAB for more than one month, change of antidiabetic or other therapy for acromegaly, concomitant untreated hormonal deficiency, initiation of pregnancy and/or breastfeeding. All patients were evaluated in terms of biochemical disease control, glucose metabolism and weight at baseline (T0) and after the introduction of CAB therapy at 6 (T6) and 12 months (T12). RESULTS: Twenty-six patients (15 females and 11 males) were evaluated at T0 and T6 and 19 patients (12 females and 7 males) were also evaluated at T12. Insulin-like growth factor I (IGF-I) and prolactin (PRL) levels were significantly lower at T6 and T12 compared to baseline (p < 0.001 for IGF-I, p < 0.05 for PRL) even if no further differences were observed between T12 and T6. Considering the entire cohort, no differences were appreciated regarding the metabolic parameters but a significant reduction in weight and body mass index (BMI) was observed at both T6 (p = 0.009 for weight, p = 0.021 for BMI) and T12 (p = 0.014 for weight, p = 0.017 for BMI) compared to baseline. CONCLUSION: Our results confirm the efficacy of CAB in providing a significant improvement in the biochemical disease control but do not demonstrate a marked benefit on glucose metabolism of acromegaly patients. In such patients, CAB appears to have a rapid effect on weight and BMI, with significant changes noticeable as early as 6 months and persisting for at least 12 months.

Built-in tensile strain dependence on the lateral size of monolayer MoS2 synthesized by liquid precursor chemical vapor deposition.

Strain engineering is an efficient tool to tune and tailor the electrical and optical properties of 2D materials. The built-in strain can be tuned during the synthesis process of a two-dimensional semiconductor, such as molybdenum disulfide, by employing different growth substrates with peculiar thermal properties. In this work, we demonstrate that the built-in strain of MoS2 monolayers, grown on a SiO2/Si substrate by liquid precursor chemical vapor deposition, is mainly dependent on the size of the monolayer. In fact, we identify a critical size equal to 20 µm, from which the built-in strain increases drastically. The built-in strain is the maximum for a 60 µm sized monolayer, leading to 1.2% tensile strain with a partial release of strain close to the monolayer triangular vertexes due to the formation of nanocracks. These findings also imply that the standard method for evaluation of the number of layers based on the Raman mode separation can become unreliable for highly strained monolayers with a lateral size above 20 µm.

Neuroendocrine response to diclofenac in healthy subjects: a pilot study.

PURPOSE: The precise effects of non-steroidal anti-inflammatory drugs on the neuroendocrine hydro-electrolytic regulation are not precisely understood. The aim of this pilot study was to evaluate, in healthy subjects, the neuroendocrine response of the antidiuretic system to intravenous diclofenac infusion. METHODS: For this single-blinded, cross-over study, we recruited 12 healthy subjects (50% women). Test sessions were divided into three observation times (pre-test; test; 48 h post-test), which were repeated equally on two different occasions, with the administration of diclofenac (75 mg in saline solution 0.9% 100 cc) on 1 day, or placebo (saline solution 0.9% 100 cc) on another day. The night before the test the subjects were asked to collect a salivary cortisol and cortisone sample, which was repeated on the night of the procedure session. Serial urine and blood samples were collected on the test day (for osmolality, electrolytes, ACTH, cortisol, copeptin, MR-proADM, MR-proANP; the last three represent more stable and analytically reliable molecules than their respective active peptides). Moreover, the subjects were evaluated with the bioimpedance vector analysis (BIVA) before and after the test. Forty-eight hours after the end of the procedure urine sodium, urine potassium, urine osmolality, serum sodium and copeptin were revaluated together with BIVA. RESULTS: No significant changes in circulating hormone levels were observed; anyway, 48 h after diclofenac, BIVA showed a significant water retention (p < 0.00001), especially in extracellular fluid (ECF) (16.47 ± 1.65 vs 15.67 ± 1.84, p < 0.001). Salivary cortisol and cortisone tended to increase only the night after placebo administration (p = 0.054 cortisol; p = 0.021 cortisone). CONCLUSION: Diclofenac resulted in an increased ECF at 48 h, but this phenomenon seems to be associated with a greater renal sensibility to the action of vasopressin rather than with an increase in its secretion. Moreover, a partial inhibitory effect on cortisol secretion can be hypothesized.

Minimal residual disease and outcome characteristics in infant KMT2A-germline acute lymphoblastic leukaemia treated on the Interfant-06 protocol.

BACKGROUND: The outcome of infants with KMT2A-germline acute lymphoblastic leukaemia (ALL) is superior to that of infants with KMT2A-rearranged ALL but has been inferior to non-infant ALL patients. Here, we describe the outcome and prognostic factors for 167 infants with KMT2A-germline ALL enrolled in the Interfant-06 study. METHODS: Univariate analysis on prognostic factors (age, white blood cell count at diagnosis, prednisolone response and CD10 expression) was performed on KMT2A-germline infants in complete remission at the end of induction (EOI; n = 163). Bone marrow minimal residual disease (MRD) was measured in 73 patients by real-time quantitative polymerase chain reaction at various time points (EOI, n = 68; end of consolidation, n = 56; and before OCTADAD, n = 57). MRD results were classified as negative, intermediate (<5∗10-4), and high (≥5∗10-4). RESULTS: The 6-year event-free and overall survival was 73.9% (standard error [SE] = 3.6) and 87.2% (SE = 2.7). Relapses occurred early, within 36 months from diagnosis in 28 of 31 (90%) infants. Treatment-related mortality was 3.6%. Age <6 months was a favourable prognostic factor with a 6-year disease-free survival (DFS) of 91% (SE = 9.0) compared with 71.7% (SE = 4.2) in infants >6 months of age (P = 0.04). Patients with high EOI MRD ≥5 × 10-4 had a worse outcome (6-year DFS 61.4% [SE = 12.4], n = 16), compared with patients with undetectable EOI MRD (6-year DFS 87.9% [SE = 6.6], n = 28) or intermediate EOI MRD <5 × 10-4 (6-year DFS 76.4% [SE = 11.3], n = 24; P = 0.02). CONCLUSION: We conclude that young age at diagnosis and low EOI MRD seem favourable prognostic factors in infants with KMT2A-germline ALL and should be considered for risk stratification in future clinical trials.

Graphene oxide prepared by graphene nanoplatelets and reduced by laser treatment.

The Hummers' method for graphite oxide (GO) preparation has been applied to graphite nanoplatelets, in order to achieve higher reaction yield and faster kinetics. Aqueous GO solutions have been used to produce uniform GO films on a polyethylene terephthalate substrate, generating graphene patterns in a controlled way (widths of a few tens of microns). The reduction of GO deposited on the polymeric substrate has been performed by using a Nd:YVO4 continuous-wave frequency-duplicated laser. Spectroscopic and diffractometric characterizations (FT-IR, visible-NIR, Raman, XPS, and XRD) have shown that the reduction process induced by the laser annealing technique is mainly due to dehydration of the GO layers. It has been obtained by means of a suitable laser optical apparatus, a controlled reduction of GO without damaging the substrate, and precise writing of micro-tracks that can be used as electrically and thermally conductive patterns.

[Medical surveillance in the confectionary industry]. / Aspetti sanitari nell'industria dolciaria.

In the confectionery industry in addition to traditional and usual risks to every productive activity there are particular risks related with the use of aromas, arabic gum and other chemicals that can cause in workers exposed diseases affecting the skin and the respiratory system. Even if the literature does not show significant casuistry, but only anecdotal, risks control related to the substances above mentioned is essential, through a careful medical surveillance and a constant activity of information and training on work phases at risk outlined above together with the content of the health protocol.

Epstein Barr virus in relation to apoptosis markers and patients' outcome in pediatric B-cell non-Hodgkin lymphoma.

In this study, we investigated Epstein Barr virus (EBV) presence, associated to proliferation and apoptosis proteins in pediatric B-cell Non-Hodgkin lymphoma (B-NHL). EBERs, Ki67, active caspase 3, Bax and Bcl2 were analyzed on B-NHL tissue from 40 patients. Forty percent showed EBV expression, significantly higher among patients ⩽10years (P=0.027), and associated with immunosuppression (P=0.020), but not associated apotosis markers. However, EBV was associated with a worse event-free survival (P=0.016), particularly under immunosuppression. Even though EBV did not seem to alter apoptotic pathways, it exhibited survival disadvantage and could be an important cofactor in B-cell lymphomagenesis in younger children.

Vulvar plasmablastic lymphoma in a HIV-positive child: a novel extraoral localisation.

Plasmablastic lymphoma (PBL) has been characterised by the World Health Organization as a new entity. This report describes an unusual case of PBL in a 3-year-old HIV-infected patient showing a cutaneous vulvar lesion with 9 months of evolution and prolapsed vulvovaginal mucosa. Histopathological examination of a biopsy sample showed diffuse submucosal infiltration by large cells with a cohesive growth pattern, and round and vesicular nuclei with fine chromatin centrally or eccentrically placed with one or more prominent nucleoli. Immunohistochemical staining in neoplastic cells was positive for multiple melanoma oncogene (MUM1), CD138, CD45 and epithelial membrane antigen (EMA). The diagnosis was PBL, stage III. Epstein-Barr virus (EBV) expression was positive by EBV encoded RNAs in situ hybridisation. This is believed to be the third case of paediatric HIV-associated PBL reported in the literature, and the first with vulvar localisation, which is a new anatomical location for this entity.

Autologus parietal grafts in preprosthethic surgery.

Edentulous patients usually request implant supported/fixed rehabilitation. Ridge resorption after teeth loss usually affect three-dimensional implant position. Vertical and/or horizontal bone augmentation procedures are often the only choice the clinician has to deliver prosthetic guided restoration. Gold standard for augmentation procedures such as sinus lift, onlay or inlay grafts, is still autologous bone. The patient in this report underwent a pre-prosthetic reconstruction of the jaws with parietal bone, followed by fixtures insertion and fixed prosthetic rehabilitation. This clinical report aims to underline the importance of multidisciplinary treatment to optimize the results of the rehabilitation.

A prospective study of antibodies to beta2-glycoprotein I and prothrombin, and risk of thrombosis.

Antiphospholipid syndrome (APS) is a clinical autoimmune disorder characterized by thrombosis/pregnancy morbidity associated with the persistence of lupus anticoagulant (LA) and/or anticardiolipin (aCL) antibodies. We assessed the contribution of antibodies to beta2-glycoprotein I (anti-beta2GPI) and prothrombin (anti-PT) to the thrombotic risk in a cohort of 194 consecutive patients with persistent LA and/or aCL. Median follow-up was 45 months. A total of 39 patients (20.1%) had one documented episode of thrombosis during follow-up. Eleven of these patients had no previous thrombosis before enrollment in the study and 28 had recurrences of thrombosis. There were 21 venous and 18 arterial thrombotic events and the overall incidence of thrombosis was 5.6% per patient-year. After multivariate analysis, the male sex (P = 0.025), a previous thrombosis (P < 0.01), the presence of anti-beta2GPI (P = 0.001), and the presence of anti-PT (P = 0.03) remained as independent risk factors for recurrent thrombosis. Only IgG anti-beta2GPI and anti-PT were associated with an increased risk of thrombosis (P < 0.01 and P = 0.005). Patients testing positive for anti-beta2GPI had a higher rate of thrombosis than did antiphospholipid patients without anti-beta2GPI (8.0% vs. 3.1% per patient-year). Similarly, a higher rate of thrombosis was found in patients with positive anti-PT compared with patients without anti-PT (8.6% vs. 3.5% per patient-year). Considering only the group of 142 LA positive patients, the highest incidence of thrombosis was found in LA patients positive for both anti-beta2GPI and anti-PT (8.4% per patient-year). In conclusion, the presence of IgG anti-beta2GPI and anti-PT in patients with LA and/or aCL and mainly in those with LA predicts a higher risk of thromboembolic events.

Infection through sprays in medical devices for dentistry. A controllable epidemiological impact.

The risk of infections via dental sprays has been confirmed once again by the detection, inside dental unit waterlines, of bacterial and viral contaminations, both from water supplies and from the oral cavity of patients. Conventional means of prevention, flushing of the ducts before any dental treatment and anti-retraction devices intended to avoid contamination originating from the patient, evaluated in laboratory and clinical conditions, have been shown to be ineffective in controlling the risk. Tests carried out in vitro, with circuit models, and with the dental unit in service, have confirmed the efficacy of a method to disinfect the waterlines with a disinfecting solution based on TAED and Peroxidant, which in aqueous solution develop peracetic ions (Autosteril method). Zero bacterial count, zero viral charge and a complete biofilm demolition were achieved both in lab conditions and in service units. After hygienic treatment, the same disinfection method, once installed on old units that had been in service for years and without any hygienic device, allowed us to restore and to maintain the microbiological quality of the irrigant also in dental units of old design, and significantly reduced biofilm formation inside the waterlines. Therefore, on the basis of scientific findings, a microbiologic monitoring protocol is proposed in order to verify the hygienic conditions of units which are in service.

The challenge of severe acute respiratory syndrome (SARS) in dentistry.

Severe Acute Respiratory Syndrome (SARS) is caused by a newly identified coronavirus, called SARS-associated coronavirus (SARS-CoV) that appears to be transmitted primarily through droplets of saliva. This is the reason why the most important international organizations recommend that the dentists adopt a unique preventive approach to the problem: SARS patients should not be treated in the dental office. This is possible only if a suspected case of SARS is correctly and promptly identified. But a correct identification is made difficult by several factors, such as the incubation period, a possibly asymptomatic onset of the illness, the still low specificity and sensitivity of laboratory and instrumental tests. A case or suspected case of SARS may thus unwillingly be treated at the dental office. It is therefore necessary to adopt protective measures for the dental personnel and to implement and enforce infection control measures in order to eliminate the risk of viral contamination. Nonetheless, these procedures do not ensure a complete elimination of SARS-CoV contamination risk since a major risk is represented by blood-borne infection, which is originated by the mouth of patients, and the contamination of dental units water lines (DUWLs) is most difficult to control. Blood-borne contamination may be achieved only by adopting a high level, between-patients disinfection protocol of the DUWLs based on the use of chemical agents with biocidal activity against spores, viruses, bacteria and fungi (Autosteril method). In conclusion a fully effective control of the cross-infection risk will be obtained only by adopting a correct, integrated use of different infection control procedures.

[Allogeneic hematopoietic transplantation with stem cells extracted from peripheral blood]. / Trasplante hematopoyético alogénico con células progenitoras extraidas de la sangre periférica.

Fifty three patients (pts) received an allogeneic hematopoietic transplant using peripheral blood progenitor cells (PBPC). Diagnosis were acute myeloid leukemia (AML) in 16 pts, acute lymphoblastic leukemia (ALL) in 15, chronic myeloid leukemia (CML) in first chronic phase in 12, aplastic anemia in 4, myelodysplasia in 3 and Hodgkin's disease, major thalasemia and Hunter's syndrome in one each. Mean age was 20 years-old (2-55), 28 males and 25 females. Conditioning regimens were total body irradiation with 1200 cGy and cyclophosphamide 120 mg/kg in 38 pts, busulfan 16 mg/kg and cyclophosphamide 120 mg/kg in 10 pts, total lymphoid irradiation and cyclophosphamide in 3, 2 pts received other chemotherapy based conditionings. PBPC were infused unmanipulated through a central catheter. Graft versus host disease (GVHD) prophylaxis was cyclosporin and short course methotrexate. Donors were 6/6 HLA compatible siblings in 52 cases and 5/6 match in one case. PBPC mobilization was done with G-CSF at a dose of 10 micrograms/kg/day subcutaneously for four days, pheresis started on day 5. Bone marrow harvest was also done in the first thirty cases. Mean cellularities for CD34, CD3, CD4, CD8, CD56, CD19 (cel x 10(6)/kg) were 4.12; 4.59; 2.57; 1.9; 0.55 and 0.68, respectively. Mean recovery of neutrophils > 500/microL was obtained on day +11 and platelets > 20,000/microL on day +13. Patients were hospitalized for a mean period of 26 days (range 18-39) and days with parenteral antibiotics were 12.2 (5-45). Two pts had venoocclusive disease of the liver. Transplant related mortality was 15%. Acute graft versus host disease (GVHD) was observed in 43.4% of pts, only 5 pts had acute GVHD III or IV. Mean time for aGVHD diagnosis was +23 (8-76). Forty three pts were evaluable for chronic GVHD with a mean follow-up of 18 months (4-39). Chronic GVHD was observed in 26.4% by day +240, only 2 pts developed severe cGVHD. The present experience demonstrates an acceptable incidence for cGVHD; however, taking into account recent reports showing an increase of this complication, it seems reasonable not to perform this procedure for non-malignant diseases in which graft versus malignancy effect is not to be expected.

Glanzmann thrombasthenia in children from Argentina.

PURPOSE: Glanzmann thrombasthenia is a well-defined inherited disorder of platelet function characterized by a decrease or absence of functional platelet glycoprotein (GP) GPIIbIIIa. The diagnosis must be considered in patients presenting with mucocutaneous bleeding, purpura, a normal platelet count, abnormal platelet aggregation, and a prolonged bleeding time. In most of the patients, the presence of small amounts of either GPIIb or GPIIIa was detected in their platelets. These observations could provide a basis for determining the clinical and laboratory heterogeneity of the disease. PATIENTS AND METHODS: We studied 10 patients of seven unrelated families with the usual methods and an immunoalkaline phosphatase technique (APAAP) to analyze the biosynthesis of GP in megakaryocytes. RESULTS: The results allowed us to classify six patients as GT type I, three as type II, and one as a variant. CONCLUSION: The nature and severity of the bleeding manifestations, in our patients, were not predictible by the laboratory findings. These confirm the clinical and laboratory heterogeneity of the disease.

Incomplete hemolytic-uremic syndrome in Argentinean children with bloody diarrhea.

Argentina has an exceptionally high frequency of hemolytic-uremic syndrome (HUS). We sought to define prospectively the role of verocytotoxins (Shiga-like toxins [SLTs]) in 254 Argentinean children with grossly bloody diarrhea during spring and summer. Free fecal SLTs (I/II) and/or DNA probe-positive isolates were found in 99 (39%) of the children. During the follow-up period, HUS developed in 6 patients (4 with evidence of recent SLT infection based on stool studies); another 14 patients had some, but not all, of the abnormalities seen in typical HUS. The development of HUS or incomplete HUS in these children was significantly associated with recent SLT-Escherichia coli infection (p = 0.024). The high incidence of SLT-associated bloody diarrhea in Argentina explains, at least partially, the unusually high frequency of HUS. Our data indicate that incomplete forms of HUS may be common in patients with SLT-associated bloody diarrhea.

Bleeding time in normal children.

PURPOSE: Because there is little information on bleeding times (BTs) in children we initiated the following study. MATERIALS AND METHODS: Normal children undergoing elective surgery and adult volunteers had their bleeding times measured with a disposable device (Simplate) with a vertical incision in the forearm. Results in children (four age groups) and adults, male and female, were compared. RESULTS: The mean time in children was 270 s with a 95th percentile of 420 s compared with a mean time in adults of 320 s and a 95th percentile of 480 s (p = 0.001). Although the values in the various age groups and sexes were different, only sex had a statistically different value in adults. CONCLUSIONS: The following reference values should be used for children: 0-4 years, 4 +/- 1 min; boys > 4 years, 5 +/- 1 min; girls > 4 years, 5.5 +/- 1 min. We conclude that results obtained in children are significantly shorter than those obtained in normal adult subjects.

[The CO2 laser and endodontic surgery: an epicritical evaluation]. / Laser CO2 e chirurgia endodontica: valutazione epicritica.

The authors analyse the use of laser CO2 in endodontic surgery. They describe the laser biological effects on teeth, comprehending immediate structural changes (coagulation, carbonization, volatilization, fusion of dental tissue), and side effects (sterilization, modification of biomechanical properties and biostimulation). A surgical technique joining traditional aspects and laser radiation, restoring the apical shape to the anatomical origin is described. The employment of the laser in a defocalized way allows the sterilization of the apical region even in zones normally not reachable by the usual instruments. These devices are connected with laser irradiation and could improve the clinical results either improving bone restoration on raising dental tissue resistance to acidity. The authors emphasize that, whereas the clinical follow-up is in fact similar to the results obtained in a previous traditionally treated control group an accurate surgical technique will be the real important aspect to reach the recovery and the laser irradiation can help in it.