A case of severe allergic eosinophilic asthma with nasal polyposis in a patient affected by Birt-Hogg-Dubé syndrome successfully treated with benralizumab.

SUMMARY: Birt-Hogg-Dubé (BHD) syndrome is a rare genetic pathology characterized by cutaneous fibrofolliculomas, pulmonary cysts and kidney tumours. Severe asthma is the most serious form of asthma that does not respond to standard treatments. We present the case of a 68 years-old male patient who had frequent respiratory tract infections, shortness of breath and decline in lung function, nasal polyposis and hypertrophy of the nasal turbinates, for this reason was treated as a severe asthmatic patient for several years with ICS + LABA and high doses of OCS. When we tried to reduce OCS the patient had worsening of the symptoms, we requested a HRTC scan that showed presence of several cysts spread ubiquitously. The patient had a family history of pneumothorax, for this reason we requested a genetic test that resulted in a heterozygous point mutation on exon 12 (c.1429 C > T) of FLCN gene. Despite the diagnosis of BHD syndrome, the patient's clinical condition kept on suggesting an underlying severe asthma and the blood tests we requested pointed out a high percentage of eosinophils, for this reason we opted for the administration of benralizumab that resulted in an excellent asthma control and increased quality of life.

Tumefactive Primary Central Nervous System Vasculitis: Dynamic Susceptibility Contrast Perfusion-Weighted Magnetic Resonance Imaging Findings With Histological Correlation.

Purpose: Primary central nervous system vasculitis (PCNSV) is a rare inflammatory disease affecting the central nervous system. In some cases, it presents with large, solitary lesion with extensive mass effect that mimic intracranial neoplasms. This condition results in a diagnostic confusion for neuroradiologists because the differentiation is almost impossible on conventional MRI sequences. The aim of this study is to reveal the significance of dynamic susceptibility contrast (DSC) perfusion-weighted imaging in differentiating of tumefactive PCNSV (t-PCNSV) lesions from intracranial neoplasms such as glio-blastomas and metastasis. Methods: In this retrospective study, DSC of 8 patients with biopsy-proven t-PCNSV has been compared with DSC obtained in 10 patients with glioblastoma, 10 patients with metastasis, who underwent surgery and histopathological confirmation. The ratio of relative cerebral blood volume (rrCBV) was calculated by rCBV (lesion) / rCBV (controlateral normal-appearing white matter) in the gadolinium-enhancing solid areas. Results: The mean rrCBV was 0.86±0.7 (range: 0.76-0.98) in the patients with t-PCNSV, 5,16±0.79 in patients with glioblastoma (range: 3.9-6.3), and 4.27±0.73 (range: 2.8-5.3) in patients with metastases. Conclusion: DSC-PWI seems to be useful in the diagnostic work-up of t-PCSNVs. A low rrCBV, i.e. a rCBV similar or lower to that of the contralateral normal white matter, seems to be consistent with the possibility of t-PCSNV.

Outstation for x-ray powder diffraction at the Italian beamline at the European synchrotron.

LISA [Linea Italiana per la Spettroscopia di Assorbimento X, Italian beamline for X-ray Absorption Spectroscopy (XAS)] is the Italian CRG (Collaborating Research Group) beamline at the ESRF (European Synchrotron Radiation Facility) dedicated to XAS [d'Acapito et al., J. Synchrotron Radiat. 26, 551-558 (2019)]. In this work, a methodical test of the LISA beamline in performing diffraction measurements is carried out. Synchrotron x-ray diffraction measurements would complement absorption spectroscopy techniques with the long-range characterization of the material under investigation, while XAS provides the short-range element selective information.

Continuous subcutaneous insulin infusion is more effective than multiple daily insulin injections in preventing albumin excretion rate increase in Type 1 diabetic patients.

AIMS: To compare the effect of continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) on albumin excretion rate (AER) in Type 1 diabetic patients. METHODS: In a 3-year multicentre retrospective observational study, 110 Type 1 diabetic patients treated with CSII were compared with 110 patients treated with MDI matched at baseline for age, sex, diabetes duration and HbA(1c). At entry, 90 patients in each group had normal AER and 20 persistent microalbuminuria. AER, estimated glomerular filtration rate (eGFR), HbA(1c,) lipids and blood pressure were assessed. RESULTS: HbA(1c) was lower in the CSII than in the MDI group (8.1 +/- 0.9 vs. 8.4 +/- 1.3%; P < 0.005 after 3 years). Blood pressure and eGFR were similar during the study. AER [median (95% confidence interval)], similar at baseline [6.0 microg/min (9, 21) in the CSII group vs. 4.4 (8, 16) in the MDI group, NS] was significantly lower in the patients treated with CSII both at year 2 and at year 3 of follow-up [4.7 microg/min (6, 12) vs. 6.4 (13, 29), P < 0.002]. This difference was observed even when normo- and microalbuminuric patients were analysed separately. Nine patients progressed to microalbuminuria in the MDI group and only one in the CSII group. Nine patients regressed to normoalbuminuria in the CSII group, whereas only two regressed to normoalbuminuria in the MDI group. CONCLUSIONS: Despite a small benefit in terms of improved glycaemic control, CSII therapy may be useful in decreasing the progressive increase in AER in Type 1 diabetic patients.

In Type 1 diabetic patients with good glycaemic control, blood glucose variability is lower during continuous subcutaneous insulin infusion than during multiple daily injections with insulin glargine.

AIMS: The superiority of continuous subcutaneous insulin infusion (CSII) over multiple daily injections (MDI) with glargine is uncertain. In this randomized cross-over study, we compared CSII and MDI with glargine in patients with Type 1 diabetes well controlled with CSII. The primary end-point was glucose variability. METHODS: Thirty-nine patients [38.1 +/- 9.3 years old (mean +/- sd), diabetes duration 16.6 +/- 8.2 years, glycated haemoglobin (HbA(1c)) 7.6 +/- 0.8%], already on CSII for at least 6 months, were randomly assigned to CSII with lispro or MDI with lispro and glargine. After 4 months they were switched to the alternative treatment. During the last month of each treatment blood glucose variability was analysed using glucose standard deviation, mean amplitude of glycaemic excursions (MAGE), lability index and average daily risk range (ADRR). As secondary end-points we analysed blood glucose profile, HbA(1c), number of episodes of hypo- and hyperglycaemia, lipid profile, free fatty acids (FFA), growth hormone and treatment satisfaction. RESULTS: During CSII, glucose variability was 5-12% lower than during MDI with glargine. The difference was significant only before breakfast considering glucose standard deviation (P = 0.011), significant overall using MAGE (P = 0.016) and lability index (P = 0.005) and not significant using ADRR. Although HbA(1c) was similar during both treatments, during CSII blood glucose levels were significantly lower, hyperglycaemic episodes were fewer, daily insulin dose was less, FFA were lower and treatment satisfaction was greater than during MDI with glargine. The frequency of hypoglycaemic episodes was similar during both treatments. CONCLUSIONS: During CSII, glucose variability is lower, glycaemic control better and treatment satisfaction higher than during MDI with glargine.

D-glucose induces microtubular changes in C1300 neuroblastoma cell line through the incorporation of 3-nitro-L-tyrosine into tubulin.

The microtubular network of neurons is involved in several functions such as formation and tropism of cellular processes, cell division and intracellular transport. A lot of evidences testify that the microtubular network of neurons can be impaired by oxidative stress. A condition of oxidative stress is often possible when D-glucose overloads its metabolic pathway, resulting in an increase in reactive oxygen species and subsequent neurological disorders. The aim of this work was to check in undifferentiated mouse neuroblastoma cells (C1300) the possible oxidative effects of D-glucose on microtubules. Using a concentration of 110mM D-glucose, cell morphology, growth rate, viability and catalase activity were seriously altered. Noteworthy, an increase in 3-nitro-L-tyrosine and a downregulation of tubulins was found in D-glucose-exposed cells, whereas another cytoskeletal proteins, namely actin, did not show any changes. In conclusion, microtubular network can be impaired by D-glucose through specific nitrosative effects, suggesting a possible mechanism at the basis of hyperglycemia-induced neuronal damage.

Testosterone induces neuroprotection from oxidative stress. Effects on catalase activity and 3-nitro-L-tyrosine incorporation into alpha-tubulin in a mouse neuroblastoma cell line.

3-nitro-L-tyrosine is formed by nitric oxide following different pathways such as NADPH oxidase, xanthine oxidase or glutamate NMDA receptor activation and is involved in the pathology of different neurological disorders. Unlike estradiol, a neuroprotective role of androgens against oxidative cell injury has not been fully investigated. This work targets the possible effects of testosterone on neuroblastoma cells exposed to 3-nitro-L-tyrosine. C1300 mouse undifferentiated neuroblastoma cells exposed to 3-nitro-L-tyrosine were cultured in the presence of testosterone. Morphological examination, proliferation and nuclear viability assays were performed. The expression of tyrosinated alpha-tubulin and incorporation of 3-nitro-L-tyrosine into protein were also estimated. Cells exposed to 3-nitro-L-tyrosine showed globular shape, reduced cytoplasmic processes and growth inhibition in comparison with controls. When testosterone was added to the medium, these changes were not evident. In addition, testosterone induced an upregulation of tyrosinated alpha-tubulin, a marker of neuronal plasticity, and a decrease in 3-nitro-L-tyrosine incorporation into tubulin. Our results suggest that testosterone exposure can diminish 3-nitro-L-tyrosine toxic effects on the morphology and growth rate of neuroblastoma cells. The upregulation of tyrosinated alpha-tubulin in testosterone-exposed cells would be consistent with concurrent plasticity events. Failure in alpha-tubulin nitration detected in cells exposed to both 3-nitro-L-tyrosine and testosterone, may support the idea that testosterone interferes with 3-nitro-L-tyrosine protein incorporation. Moreover, testosterone-induced neuroprotection likely entails a linkage with the androgen receptor as is suggested by the flutamide-induced inhibition of the hormone activity. Finally, the neuroprotective effects of testosterone in neuroblastoma cells could deal with the cellular antioxidant defence system, as shown by testosterone-induced increase in catalase activity.

Survey on the use of insulin pumps in Italy: comparison between pediatric and adult age groups (IMITA study).

AIMS: The aim of the study was to evaluate and compare continuous subcutaneous insulin infusion (CSII) use in pediatric and adult age groups. METHODS: Data were collected with a questionnaire sent by e-mail to CSII-experienced Diabetes Centers. The questionnaire assessed: (1) number of CSII-treated patients; (2) patient demographic data and characteristics; (3) structure and organization of Diabetes Centers providing CSII therapy; (4) pump characteristics (conventional pump, sensor-augmented pump); and (5) CSII dropouts. RESULTS: A total of 217 out of 1093 Italian centers participated: 51 pediatric (23.5 %) and 166 (76.5 %) adult centers (AP). Compared to a survey performed in 2005, there was a significant increase in the number of pediatric units when compared to adult units (112 vs 37 %, respectively, p < 0.05). Pediatric age is characterized by a greater concern for quality of life and injections, and a higher dropout rate (10.6 vs 8.9 %) mainly related to pump wearability and site reactions. A complete diabetes-care team is associated with a superior use of technology (fewer dropouts, increased CGM and advanced bolus use) which is, however, still used in a small percentage of patients. CONCLUSIONS: In Italy, the number of CSII-treated pediatric patients (PP) is growing more significantly when compared to adults. Only 60 % of all patients are using advanced functions and 20 % are using CGMs continuously. This confirms the great interest in diabetes technology that is growing in pediatric diabetologists. However, much improvement is warranted in the organization and specialized training of pediatric, adult and transitional facilities.

Morphology, Morphometry and Spatial Distribution of Secondary Osteons in Equine Femur.

A high number of differences exist in bone histological features depending on the species, breed, age and bone. Moreover, osteon distribution may vary in the different sides of a bone as a consequence of different biomechanical strains. The aim of this work was to study the distribution and morphology of osteons in different sides of the equine femoral diaphysis with the attempt to correlate them to the main strains operating on them. The following parameters of secondary osteons and Haversian canals were measured in the transverse sections of diaphyses: perimeter, area, minimum and maximum diameter, eccentricity and osteon population density. A typical Haversian tissue was observed with elliptic secondary osteons consisting in about 10 well-defined lamellae surrounding a circular Haversian canal. Quantitative analysis displays a different population density of secondary osteons depending on the side. The caudal and medial sides, where compression strains are higher, have more secondary osteons in comparison with the cranial and lateral sides, where tension strains are prevalent. These data suggest that secondary osteon population density may depend on the predominant strains. Even the elliptical shape of secondary osteons may be related to biomechanical strains, as their major axes are oriented cranio-caudally parallel to prevalent strains.

Aluminum promotes neuronal plasticity events in a mouse neuroblastoma cell line.

The effects of aluminum(III) on microtubular meshwork have been investigated using cultured murine neuroblastoma cells grown in a medium containing aluminum lactate at defined metal concentrations (10-20 microM). A role of aluminum(III) in promoting neuronal plasticity events is suggested. These events including sprouting and neurite outgrowth are associated with an increased tyrosine-tubulin (Tyr-Tub) expression, which can be due to the enhanced needs of recently formed, highly dynamic microtubules typical of neuronal plasticity. After 48 and 72 h aluminum exposure, an upregulation of Tyr-Tub expression is detected and this is concentration-dependent. A high amount of Tyr-Tub is observed also in non-treated cells, although later than in aluminum-exposed cells. Thus, it is possible that aluminum(III) accelerates neuronal plasticity events, for which Tyr-Tub is confirmed to be a useful marker.

Pure ductal carcinoma in situ and in situ component of ductal invasive carcinoma of the breast. A preliminary morphometric study.

Nuclear pleomorphism is a fundamental feature in evaluating the aggressiveness of ductal carcinoma in situ (DCIS) of the breast. In this study, pure DCIS and the in situ component (IS-comp) of invasive duct carcinoma (IDC) are compared in order to verify if these are two different entities or the same process observed at different times during its evolution. Five cases of pure DCIS and nine of IDC with extensive in situ component were selected. They were moderately and poorly differentiated. 30 nuclei for each DCIS, and 30 nuclei for both the in situ and invasive component of each IDC were studied; thus, a total of 720 nuclei were submitted to the SAM (Shape Analytical Morphometry) analysis, which enables a numerical expression not only of dimensions (area, perimeter, diameter) but also of nuclear contour irregularities and nuclear shape distortions. Univariate statistical comparisons were carried out between the nuclei of: (1) DCIS and in situ component of invasive duct carcinoma, (2) DCIS and the invasive component of infiltrating carcinoma and (3) between the in situ and invasive component of infiltrating carcinoma. Multivariate analysis was utilized to compare nuclei of DCIS with the in situ component of IDC. The in situ features of each tumor were also evaluated with the mitotic index (MI). Nuclei of pure DCIS resulted significantly larger (p < 0.001) and with a more regular shape (p < 0.001) than those of the in situ component of IDC. No differences were observed between the nuclei of the in situ and the invasive component of infiltrating carcinomas. Multivariate statistical analysis discriminated 77% of nuclei of in situ proliferation when both G2 and G3 tumors were considered, and 80% when only G3 tumors were considered. In conclusions morphological differences exist between pure DCIS and the in situ component of IDC, which may be an expression of their biological behavior; moreover, these morphological differences seem to have a better discriminating power within the same histological grade.

[Remarks on a case of Fitz-Hugh-Curtis syndrome]. / Osservazioni su un caso di sindrome di Fitz-Hugh Curtis.

A case of Fitz-Hugh Curtis syndrome caused by chlamydia is described in which the perihepatic and abdominal swelling also extended to the right perirenal tissue. The case was diagnosed on the basis of the clinical picture, the behaviour of anti-chlamydia serum antibodies, abdominal echography and laparoscopy. The infection was quickly cured by the administration of tetracycline.

[Phallin syndrome. Reports on 28 cases]. / Sindrome fallinica. Osservazione su 28 casi.

28 cases of phallinic syndrome have been studied: 24 out of them were from amanita phalloides poisoning and 4 from amanita verna poisoning. After a lag phase lasting from 7 to 30 hours, symptomatology characterized by starting gastroenteric troubles as vomit, diarrhea, abdominal cramps, meteorism and pain following abdomen palpation. In one case the syndrome started with parasympathicomimetic crisis, probabily due to ingested amanita containing muscarinic type poison. Subsequent evolution of clinical picture included signs of hepatic and renal involvement. As far as laboratory diagnosis is concerned, high levels of serum aminotransferases were found and, less frequently, hyperbilirubinmia and high BUN levels occurred. In severe cases, in addition, lowered values for plasma prothrombine, fibrinogen and cholinesterase were found. Low therapeutic effect followed rehydration, equilibration of electrolytic unbalance and administration of thioctic acid, coagulants and so on. As a matter of fact 3 out or 28 patients, treated only with such therapy, died. On the contrary good therapeutic effect followed to peritoneal dialysis, in two cases coupled to exchange transfusion: 10 patients were treated in such a way and no one died but all of them quickly recovered. Forced diuresis also appeared greatly useful and practical in therapeutic treatment of phallinic syndrome: results compared favourably with those obtained by means of peritoneal dialysis. As a matter of fact 15 patients, 5 of them having ingested a great amount of amanita phalloides, were treated with forced diuresis and no one of them died. Finally, the need is stressed for a very quick therapeutic intervention (exchange transfusion; plasmapheresis; peritoneal dialysis; forced diuresis, and so on) in order to lower the plasma concentration of the toxins responsible for the phallinic syndrome. Only in such a way diffusion of toxins from blood to tissues is avoided.

[The diagnosis of chronic pyelonephritis in internal medicine]. / La diagnosi di pielonefrite cronica in medicina interna.

All those clinical, laboratory, radiological and radioisotopic elements of importance in the diagnosis of chronic pyelonephritis in internal medicine have been examined. Anamnestic indications of chronic pyelonephritis include previous infections episodes of the urinary ways, pain in the lumbar and suprapubic region and micturition disturbances. Less significant are objective findings such as pain at percussion of the lumber region, hypertension and possible signs of renal insufficiency. Important diagnostically among laboratory examinations are leucocyturia higher than 1,000.000 in 24 hours, a findings of leucocyte cylinders, bacteriuria higher than 100.000 per cc of urine and the observation of immunoantibodies covering bacteria isolated from the urine. X-ray and radioisotopic examinations are recognised as having considerable diagnostic usefulness. None of the clinical, laboratory, X-ray or radioisotopic findings is, however, strictly specific. Confirmation of a diagnostic suspicion is only possible when scrupulous accumulation of the most typical subjective and objective findings regarding the disease is accompanied by the positivity of diagnostic tests. The results of these tests must in all cases be assessed critically in the context of the clinical picture for, taken singly, they have no decisive value.

Tyrosinated alpha-tubulin changes following epileptogenic and non-epileptogenic lesions in rat brain cortex.

The expression of the tyrosinated isoform of alpha-tubulin was monitored in rat frontal cortex, in order to investigate the neuronal plasticity changes occurring either in a mirror focus or in a deafferented area. A mirror focus was triggered by epidural implantation of a cobalt gelatin disk in the contralateral left somatosensory area (group one). A deafferented area was obtained by surgical removal of the left frontal cortex (group two). All animals including controls underwent EcoG recordings immediately before killing (45, 60, 90 days post surgery). The right frontal cortex was removed from all the animals and processed with Western blot method. EcoG recordings revealed a paroxysmal activity in epileptic rats, whereas in rats with frontal deafferentation and controls, EcoG activity was normal. A significant increase in tyrosinated alpha-tubulin expression was detected both in the mirror focus (group one) and the "non-epileptic" deafferented frontal cortex (group two) in comparison with controls (group three). The transcallosal deafferentation, which is involved in both epileptogenic and non-epileptogenic lesions, is supposed to play a role in the mechanism responsible for the plasticity responses recorded in the cortical areas studied.

[Use of omega-3 in diabetic patients]. / Impiego degli omega-3 nel paziente diabetico.

The use of omega-3 fatty acids for diabetic patients is based on well confirmed observations concerning the presence of cardiovascular risk factors in these patients. Changes of lipid metabolism, reduced erythrocyte deformability, increased platelet aggregation, and high blood pressure often found in subjects with diabetes mellitus are all favourably influenced by the administration of eicosapentanoic and docosahexanoic acid. In non insulin dependent subjects, these fatty acids may bring about a rapid reversible deterioration of blood glucose balance while in insulin dependent patients there is no relevant interference. Therefore, omega-3 administration would appear advisable in insulin dependent diabetics with increased cardiovascular risk factors.

[The complex relation of pregnancy and diabetes mellitus]. / I complessi rapporti tra gravidanza e diabete.

A glucose metabolism impairment occurs in about 2-3% of all pregnancies. Two different groups of women are involved: diabetic women who become pregnant and healthy women developing gestational diabetes or glucose intolerance during pregnancy. Due to therapeutic improvements and new techniques of fetal monitoring, maternal and perinatal mortality now approaches that of normal pregnancies. On the contrary, congenital anomalies are still four times more frequent. A good control of the mother metabolism is necessary to reduce complications in fetal development, especially during the first six weeks, a crucial period for the early cell division. Fetal monitoring is very important not only to control the normality of the growth and the well-being of the fetus, but also for early identification of possible anomalies.