Retrogasserian radiofrequency thermocoagulation: A repeatable treatment in trigeminal neuralgia unresponsive to drug therapy.

BACKGROUND: Trigeminal neuralgia present an incidence rates ranging between 5.9 and 12.6 per 100.000 persons; although not frequent, it is a pathology often characterized by intense pain, an extremely significant reduction in quality of life and medical therapy is not always effective or tolerated. In these cases, the patient can undergo interventional treatments including radiofrequency thermocoagulation. There are still doubts regarding the effectiveness over time, the injury parameters and the repeatability of the procedure. MATERIALS AND METHODS: We analyze patients with trigeminal pain undergo retrogasserian radiofrequency in a single center over a period of 8 years. The procedure was performed with the following parameters: Lesion time 60 sec, lesion temperature 70°C for first thermolesion 72°C for subsequent thermolesions. Duration of benefit, number of repetitions of the maneuver, and incidence of adverse events were assessed. RESULTS: Totally, 122 patients with essential trigeminal neuralgia and 20 patients with trigeminal neuralgia secondary to multiple sclerosis were analyzed; almost all patients (96.5%) showed a significant reduction in pain after one or more procedures over time; 96.5 of the patients showed excellent pain relief after 1 (40%) or more procedures (60%). The average time between one procedure and the next was 26 months. CONCLUSION: The use of time and temperature parameters chosen shows excellent efficacy, in line with the literature, with very low incidence of adverse events. The pain-free time between one procedure and the next does not seem to be a significant prognostic criterion which may or may not indicate the repetition of the procedure.

Chronobiology of acute pancreatitis in a single Italian centre.

OBJECTIVE: Seasonal variation may occur in many different diseases hence influencing awareness in clinical practice. This study aimed to establish seasonal variations of acute pancreatitis by using a validated chronobiological analysis. PATIENTS AND METHODS: All cases of acute pancreatitis consecutively observed in fifteen years, i.e., from January 2003 to December 2017, at St. Anna University Hospital of Ferrara, Italy, were included in this study. Accurate statistical and logistic regression analyses were applied to our database. RESULTS: A total number of 1883 consecutive cases of acute pancreatitis were observed. A significant peak was identified in the summer period (p=0.014). Patient stratification, according to age, showed that elderly people had an increased incidence of acute pancreatitis in autumn and summer (being the biliary stone disease the main cause, p=0.011) vs. other seasons (p=0.003). Mortality occurred more prominently in males vs. females, although the latter gender was more prone to acute pancreatitis (p=0.017). CONCLUSIONS: In a single centre of Northern East of Italy, we demonstrated that acute pancreatitis had a clear seasonal variation with a prominent incidence during summer. Various associated factors could contribute to this chronobiological pattern, including gender, age, and biliary stone disease.

PML is required for telomere stability in non-neoplastic human cells.

Telomeres interact with numerous proteins, including components of the shelterin complex, whose alteration, similarly to proliferation-induced telomere shortening, initiates cellular senescence. In tumors, telomere length is maintained by Telomerase activity or by the Alternative Lengthening of Telomeres mechanism, whose hallmark is the telomeric localization of the promyelocytic leukemia (PML) protein. Whether PML contributes to telomeres maintenance in normal cells is unknown. We show that in normal human fibroblasts the PML protein associates with few telomeres, preferentially when they are damaged. Proliferation-induced telomere attrition or their damage due to alteration of the shelterin complex enhances the telomeric localization of PML, which is increased in human T-lymphocytes derived from patients genetically deficient in telomerase. In normal fibroblasts, PML depletion induces telomere damage, nuclear and chromosomal abnormalities, and senescence. Expression of the leukemia protein PML/RARα in hematopoietic progenitors displaces PML from telomeres and induces telomere shortening in the bone marrow of pre-leukemic mice. Our work provides a novel view of the physiologic function of PML, which participates in telomeres surveillance in normal cells. Our data further imply that a diminished PML function may contribute to cell senescence, genomic instability, and tumorigenesis.

Identification and characterization of a high-affinity choline uptake system of Brucella abortus.

Phosphatidylcholine (PC), a common phospholipid of the eukaryotic cell membrane, is present in the cell envelope of the intracellular pathogen Brucella abortus, the etiological agent of bovine brucellosis. In this pathogen, the biosynthesis of PC proceeds mainly through the phosphatidylcholine synthase pathway; hence, it relies on the presence of choline in the milieu. These observations imply that B. abortus encodes an as-yet-unknown choline uptake system. Taking advantage of the requirement of choline uptake for PC synthesis, we devised a method that allowed us to identify a homologue of ChoX, the high-affinity periplasmic binding protein of the ABC transporter ChoXWV. Disruption of the choX gene completely abrogated PC synthesis at low choline concentrations in the medium, thus indicating that it is a high-affinity transporter needed for PC synthesis via the PC synthase (PCS) pathway. However, the synthesis of PC was restored when the mutant was incubated in media with higher choline concentrations, suggesting the presence of an alternative low-affinity choline uptake activity. By means of a fluorescence-based equilibrium-binding assay and using the kinetics of radiolabeled choline uptake, we show that ChoX binds choline with an extremely high affinity, and we also demonstrate that its activity is inhibited by increasing choline concentrations. Cell infection assays indicate that ChoX activity is required during the first phase of B. abortus intracellular traffic, suggesting that choline concentrations in the early and intermediate Brucella-containing vacuoles are limited. Altogether, these results suggest that choline transport and PC synthesis are strictly regulated in B. abortus.

Mortality and causes of death in Italian persons with haemophilia, 1990-2007.

Although a number of studies have analysed so far the causes of death and the life expectancy in haemophilic populations, no investigations have been conducted among Italian haemophilia centres. Thus, the aim of this study was to investigate mortality, causes of deaths, life expectancy and co-morbidities in Italian persons with haemophilia (PWH). Data pertaining to a total of 443 PWH who died between 1980 and 2007 were retrospectively collected in the 30 centres who are members of the Italian Association of Haemophilia Centres that chose to participate. The mortality rate ratio standardized to the male Italian population (SMR) was reduced during the periods 1990-1999 and 2000-2007 such that during the latter, death rate overlapped that of the general population (SMR 1990-1999: 1.98 95% CI 1.54-2.51; SMR 2000-2007: 1.08 95% CI 0.83-1.40). Similarly, life expectancy in the whole haemophilic population increased in the same period (71.2 years in 2000-2007 vs. 64.0 in 1990-1999), approaching that of the general male population. While human immunodeficiency virus infection was the main cause of death (45%), 13% of deaths were caused by hepatitis C-associated complications. The results of this retrospective study show that in Italian PWH improvements in the quality of treatment and global medical care provided by specialized haemophilia centres resulted in a significantly increased life expectancy.

Effect of tidal volume and respiratory rate on the power of breathing calculation.

BACKGROUND: The power of breathing (PoB) is used to estimate the mechanical workload of the respiratory system. Aim of this study was to investigate the effect of different tidal volume-respiratory rate combinations on the PoB when the elastic load is constant. In order to assure strict control of the experimental conditions, the PoB was calculated on an airway pressure-volume curve in mechanically ventilated patients. METHODS: Ten patients received three different tidal volume-respiratory rate combinations while minute ventilation was constant. Respiratory mechanics, PoB and its elastic and resistive components were calculated. Alternative methods to estimate the elastic workload were assessed: elastic work of breathing per litre per minute, elastic workload index (the square root of elastic work of breathing multiplied by respiratory rate) and elastic double product of the respiratory system (the elastic pressure multiplied by respiratory rate). RESULTS: Despite constant elastance and minute ventilation, the elastic PoB showed an increment greater than 200% from the lower to the greater tidal volume, accounting for approximately 80% of the whole PoB increment. On the contrary, elastic work of breathing per litre per minute, elastic workload index and elastic double product did not change. CONCLUSION: Changes in breathing pattern markedly affect the PoB despite constant mechanical load. Other indexes could assess the elastic workload without tidal volume dependence. Power of breathing use should be avoided to compare different mechanical loads or efficiencies of the respiratory muscles when tidal volume is variable.

Effect of breathing pattern on the pressure-time product calculation.

BACKGROUND: The pressure-time product (PTP) is often used to compare conditions with different breathing patterns. Being the pressure-time product calculated with pressures changes over a minute, mechanical load and inspiration time per minute should be its main determinants. The aim of this study was to investigate if the method of PTP computation is affected by the breathing pattern when mechanical load and inspiratory time per minute are constant. METHODS: Respiratory mechanics and the PTP developed by the ventilator were calculated in 10 mechanically ventilated patients at three different respiratory rate/tidal volume combinations, provided that minute ventilation and inspiratory time per minute were constant. RESULTS: The static elastance did not change at different tidal volumes. Despite the constant elastic load over a minute, the elastic PTP showed an increment greater than 200% from the higher to the lower respiratory rate, responsible for approximately 80% of the whole PTP increment. On the contrary a 'corrected' elastic PTP (calculated using the square root of the elastic pressure-time area), the elastic double product of the respiratory system and the mean elastic pressure per minute, did not significantly change. CONCLUSIONS: Changes in breathing pattern markedly affected the PTP independently by the mechanical load and the inspiratory time per minute. In these conditions it could not correctly estimate the metabolic cost of breathing. The use of a 'corrected' PTP, the mean inspiratory pressure per minute or the double product of the respiratory system, could overcome this limitation.

Oligofructose does not affect the development of type 1 diabetes mellitus induced by dietary proteins in the diabetes-prone BB rat model.

BACKGROUND: Prevention of Type 1 diabetes mellitus (T1DM), a major childhood chronic disease with rapidly increasing incidence, is an urgent topic of research. We investigated whether 5% oligofructose (OF) as compared to 5% cellulose had a protective effect against diet-induced T1DM in the diabetes-prone BioBreeding (BB) rat model. METHODS: Groups of BB rats were fed the experimental diets from weaning. The diets were a cereal-based rodent diet (diabetogenic, positive control) and semi-synthetic rodent diets containing hydrolysed casein (non-diabetogenic, negative control), soy or whey as the sole protein source and 5% cellulose as fibre source. In additional groups fed soy and whey protein, the fibre source was 5% OF. T1DM incidence up to the age of 160 days was recorded applying biochemical and morphological criteria. Physiological effects of fibre were assessed through the analysis of biochemical parameters in plasma and of the protein/DNA ratio in intestinal mucosa. RESULTS: T1DM incidence was diet-dependent. Cereal-, soy- and whey-based diets were significantly more diabetogenic than the hydrolysed casein-based diet. Five per cent OF did not affect the incidence of T1DM induced by either soy or whey proteins as compared to cellulose, nor induce any of the biological effects attributed to a fermentable fibre. CONCLUSIONS: In the BB rat model, 5% OF in the diet did not have any protective effects against diet-induced T1DM. The present data do not suggest dietary OF as a promising approach for the dietary prevention of T1DM.

Relationships between age, mammographic features and pathological tumour characteristics in non-palpable breast cancer.

Non-palpable breast cancers are often in situ or smaller and have less nodal and distant metastases than palpable lesions. They represent a heterogeneous group of tumours, which may have different prognostic behaviour. We analysed a retrospective series of 982 non-palpable breast cancers assessed histologically at the National Cancer Institute of Milan from 1985 to 1995, following pre-operative mammography-guided localization. The association between mammographic data (parenchymal pattern and findings), patient age and tumour histology was investigated by review of clinical records and statistical modelling. We also investigated the association between the presence or absence of microcalcification as a mammographic finding and pathological tumour characteristics (tumour size, axillary nodes status and grading) or receptor status for oestrogen (ER) and progesterone (PgR). In situ disease or invasive tumour with an intraductal component, whether extensive or not, were commoner in young women and mammography more frequently showed a dense parenchymal pattern and microcalcifications in these cases. In older women (55 years or more), a fatty breast pattern, nodular opacities with or without microcalcifications, and invasive tumours of the ductal, lobular, mixed or other types were closely related. When the relationships between mammographic findings, pathological tumour characteristics and receptor status were investigated for invasive cancers, there was an association between the presence of microcalcifications and less favourable tumour characteristics.

CD4(+) T cell clones producing both interferon-gamma and interleukin-10 predominate in bronchoalveolar lavages of active pulmonary tuberculosis patients.

The pattern of cytokine production in T cell clones derived from bronchoalveolar lavages (BAL) of active pulmonary tuberculosis (TB) patients was analyzed in clones obtained by limiting dilution procedures which expand with high efficiency either total T lymphocytes, independently of their antigen-recognition specificity, or Mycobacterium tuberculosis-specific T cells. BAL-derived clones, representative of CD4(+) cells from five patients with active TB, produced significantly higher amounts of IFN-gamma than BAL-derived CD4(+) clones from three inactive TB donors or four controls (with unrelated, noninfectious pathology). Average IL-4 and IL-10 production did not differ significantly in the three groups. Although these data suggest a predominant Th1 response to M. tuberculosis infection in the lungs, the majority of BAL-derived CD4(+) clones produced both IFN-gamma and IL-10 and the percentage of clones with this pattern of cytokine production was significantly higher in clones derived from BAL of active TB patients than from controls. Only rare clones derived from peripheral blood (PB)-derived CD45RO(+) CD4(+) T cells of both patients (nine cases) and controls (four cases) produced both IFN-gamma and IL-10; instead, the IL-10-producing clones derived from PB T cells most often also produced IL-4, displaying a typical Th2 phenotype. Higher average amounts of IFN-gamma and IL-10 were produced by BAL-derived CD8(+) clones of four active TB patients than of four controls, although the frequency of CD8(+) clones producing both IFN-gamma and IL-10 was lower than that of CD4(+) clones. The M. tuberculosis-specific BAL-derived T cell clones from three active TB patients were almost exclusively CD4(+) and produced consistently high levels of IFN-gamma often in association with IL-10, but very rarely with IL-4. Unlike the BAL-derived clones, the M. tuberculosis-specific clones derived from PB CD45RO(+) CD4(+) T cells of three different active TB patients and two healthy donors showed large individual variability in cytokine production as well as in the proportion of CD4(+), CD8(+), or TCR gamma/delta(+) clones. These results indicate the predominance of CD4(+) T cells producing both the proinflammatory cytokine IFN-gamma and the anti-inflammatory cytokine IL-10 in BAL of patients with active TB.

[Non-invasive lymphatic staging of lung neoplasms: comparative study with computerized tomography and endoscopic ultrasonography]. / La stadiazione linfonodale non invasiva delle neoplasie polmonari: studio comparato tomografia computerizzata-ecoendoscopia.

INTRODUCTION: A prospective comparative study with pathology was performed at the National Cancer Institute, Milan, to assess the clinical value of Computed Tomography (CT) and endoscopic ultrasound (EUS) for nodal staging in lung cancer. MATERIAL AND METHODS: In three years, 71 patients with histological diagnosis of non-small-cell lung cancer were operated on. They underwent CT and EUS examinations to identify mediastinal lymphadenopathies after major nodal involvement had been excluded by chest X-ray. Diagnostic staging was completed in two weeks prior to treatment. Patients received complete tumor removal and radical lymphadenectomy (55 patients), invasive staging with node resection and sampling (11 patients), or mediastinoscopy (5 patients). Blinded interpretation of CT alone, EUS alone, and CT and EUS together were performed, with systematic correlation of imaging findings and pathological results. RESULTS: The frequency of mediastinal involvement was 42.2%. A total of 329 nodal stations were dissected or sampled and 755 lymph nodes were examined at histology. On a per-station basis, CT had greater sensitivity (74%) than EUS (56%), but EUS was more specific (83.4% vs 92.7%). The accuracy rates of the two techniques were similar (CT 81%, EUS 83%). A site by site analysis showed highest sensitivity (100%) in the lower right paratracheal nodes for CT, and in the superior left paratracheal and subcarinal nodes for EUS. When the EUS and CT images were studied together by specialists on a per-station basis, sensitivity, specificity, and accuracy increased to 85%. CONCLUSIONS: Endoscopic ultrasound should be part of the routine preoperative diagnostic approach to non-small-cell lung cancer, because of its high specificity. Results can be improved when EUS and CT are combined, which suggests that these imaging modalities should be used together in selected patients for the noninvasive staging of non-small-cell lung cancer to identify local lymphatic spread.

Superoxide anion in human semen related to seminal parameters and clinical aspects.

OBJECTIVE: To study the possible presence of extracellular superoxide anion (O2-) in untreated semen of normal and pathological subjects and to determine the possible relationship between superoxide anion levels, number of seminal leukocytes (WBCs) and seminal parameters. PATIENTS: Semen samples were analyzed from fertile normospermic subjects (n = 20) and patients (n = 132) attending the Outpatient Department of the 5th Medical Clinic. MAIN OUTCOME MEASURE: We evaluated superoxide anion levels by monitoring the reduction of cytochrome c. RESULTS: O2- was detected in 55.0% of fertile normospermic subjects. Both the percentage of subjects in whom O2- was detected and the mean values +/- SD of O2- were significantly higher in the male partners of infertile couples, in subjects with varicocele, and in subjects with positive sperm culture than normospermic subjects. No variations were seen in vasectomized subjects or in patients with past cryptorchidism. A high correlation was observed between O2- levels and WBCs (rs = 0.58), nonrapid, immotile sperm (rs = 0.64), percentage decrease of motility within a specified time frame (2 to 6 hours) (rs = 0.73), and sperm abnormalities (rs = 0.49). CONCLUSIONS: Superoxide anion in untreated semen is produced by WBCs and atypical and nonrapid, immotile sperm. A significant increase of superoxide anion was detected in the male partners of infertile couples and in some selected andrological conditions. The toxic effect of superoxide anion on sperm cells is dependent on the time of exposure and superoxide anion concentration.