Quality of Cure in Depth of Commercially Available Bulk-fill Composites: A Layer-by-layer Mechanical and Biological Evaluation.

Despite their popularity, the use of bulk-fill composites remains controversial, both in terms of their properties and their in-depth development. The objectives of the present work were (1) to provide a more comprehensive evaluation of the quality of cure in depth of commercially available bulk-fill composites by combining various key mechanical and biological characterization methods, (2) to evaluate the inter-material differences when optimally cured, and (3) to evaluate the efficiency of an antioxidant-N-acetyl-cysteine (NAC)-to restrain the adverse effects of the leached components on cell viability. Nine bulk-fill composites (including flowable and high-viscosity materials) were investigated and compared to two conventional resin-based composites, one flowable and one high-viscosity restorative material. The materials were injected or packed into Teflon molds of various configurations, up to 6 mm material thickness. They were then light-cured from the top for 20 seconds with Bluephase G2 (Ivoclar Vivadent, irradiance = 1050 mW/cm2). The following physico-mechanical properties were measured for the upper (0-2 mm), intermediate (2-4 mm), and lower (4-6 mm) layers: degree of conversion using Raman Spectrometry (DC, in %), microhardness using a Vickers micro-indenter before (VHN dry) and after 24 hours of storage in ethanol (VHN EtOH), and flexural strength (in MPa) and flexural modulus (in GPa) using a three-point bend test. Each composite layer and an uncured layer were also stored for one week in a standard cell growth medium to generate conditioned media. Human dental pulp cells were then cultured for 24 hours with the latter and cell viability was measured using an MTS assay. A similar experiment was repeated with conditioned media produced in contact with uncured composites, with and without the addition of 4 mM NAC. The data were subjected to a Shapiro-Wilk test, then one-way ANOVA or Kruskal-Wallis test, followed either by Tukey's test (inter-material comparison) or by Dunnett's or Dunn's test (comparison between layers relative to the upper one). The level of statistical significance was set at 0.05. Some materials (EverX, X-traF, VenusBF, X-traB) did not show any significant differences (p>0.05) for any of the properties considered between the intermediate layers compared to the upper one (considered as reference). Others displayed significant differences, at least for some properties, highlighting the value of combining various key mechanical and biological characterization methods when investigating the quality of cure in depth. Significant inter-material differences (p<0.05) were observed when comparing the properties of their upper layer, considered as "optimally" polymerized. Hence, one needs to consider the absolute property values, not only their relative evolution concerning layer thickness. Finally, the use of NAC appeared as beneficial to reduce the risk of harmful effects to dental pulp cells, especially in case of excessive thickness use, and may therefore be of potential interest as an additive to composites in the future.

Gemcitabine, ifosfamide and paclitaxel in advanced/metastatic non-small cell lung cancer patients: a phase II study.

UNLABELLED: Although platinum-based two-drug combinations represent the elective therapeutic approach for advanced/metastatic NSCLC, there is still interest in exploring the efficacy and tolerability of platinum-free combinations including third generation agents in selected NSCLC population. Based on the satisfying activity of gemcitabine (G), ifosfamide (I) and paclitaxel (T) as single agents in NSCLC, we have designed a phase II study to explore an alternative approach to platinum-containing regimens using a combination of these three drugs. To investigate the activity/toxicity of T 175 mg/m2 on day 1, I 3 g/m2 on day 1 (with Mesna uroprotection) and G 1,000 mg/m2 on day 1-8, every 3 weeks in the treatment of advanced/metastatic NSCLC, 46 patients (38 male, 8 female) with NSCLC were enrolled: mean age 58 (range 33-70); Stage IIIB/IV=15/31; ECOG PS 0-1/2=31/15; HISTOLOGY: adenocarcinoma=20, squamous=14, large cell=3, NSCLC=8, adenosquamous=1. A total of 221 cycles have been administered (median number 4.8 for patients). In intent-to-treat analysis, partial response was achieved in 17 patients (36.95%), stable disease and progressive disease was detected in 16 (34.78%) and 10 (21.73%) patients, respectively. Time to progression was 30.9 weeks; median survival time was 42.7 weeks; the survival rates at 12 and 18 months were 34.79 and 15.21%, respectively. No toxic deaths occurred. No patients experienced grade 4 neutropenia and thrombocytopenia. Neutropenia grade 3 occurred in 10 patients (21.7%); Anemia grade 3 in 1 (2.1%); Thrombocytopenia grade 2 in two patients (4.3%) and grade 3 in one (2.1%). Peripheral neuropathy grade 1 occurred in ten (21.7%) and grade 2 in two patients (4.3%). Additional non-haematological toxicities were mild nausea, emesis and fatigue. GIT is well tolerated and active regimen in both advanced and metastatic NSCLC. These data suggest future investigations for GIT schedule as a possible alternative to platinum-based regimens in selected advanced/metastatic NSCLC patients where survival, tolerability and quality of life are the primary goals.

Natural killer cells in Bal and peripheral blood of patients with idiopathic pulmonary fibrosis (IPF).

Idiopathic Pulmonary Fibrosis/ Usual Interstitial Pneumonia (IPF/UIP) represents the most important interstitial pneumonia. ATh2 cytokine pathway predominance, favoring collagen deposition, associated to a deficit in (IFN- gamma) network, seems to be involved in the pathogenesis of this disease. Nonetheless, few data are available about the potentially involved cells. Natural killer cells (NK), are one of the most important subsets implicated in the IFN-gamma network. The aim of this study was to assess NK cells, both in BAL and peripheral blood of 11 patients suffering from IPF (group A) with respect to 11 patients with other interstitial pneumonia (Group B). Our results did not show any statistically significant difference in NK percentage in BAL between group A and B. On the contrary, patients with IPF showed a higher percentage of NK cells (t = 2.41; p < 0.05) and absolute number of cells (t = 2.32; p < 0.05) in peripheral blood, as well as a strong positive correlation between circulating and BAL NK cells (r = 0.69; p < 0.05). This finding shows, for the first time, a relationship between peripheral and lung resident cell environments in humans suggesting a possible systemic involvement in the natural history of IPF.

Analgesic action of methylphenidate on parkinsonian sensory symptoms. Mechanisms and pathophysiological implications.

Intravenous administration of methylphenidate hydrochloride, a central stimulant, was unexpectedly found to exert a potent analgesic effect on primary sensory symptoms in a group of patients with Parkinson's disease. This effect, which has now been studied in a short-term, double-blind, placebo-controlled experiment, subsequently disappeared if patients were pretreated with a beta-blocker or with a serotonin antagonist. Cerebrospinal fluid monoamine metabolites were determined in some of these patients, and the 5-hydroxyindoleacetic acid level was found to be significantly lower than in parkinsonian patients without pain and in normal volunteers. Given the mechanism of action of methylphenidate on the central nervous system, the adrenergic and serotoninergic mediation of its analgesic effect, and the demonstration of impaired central serotonin metabolism in the patient group, it is concluded that not only central dopaminergic deficiency but also altered noradrenergic and serotoninergic transmission in the spinal cord are quite likely to play a role in the pathophysiology of pain in Parkinson's disease.

Further observations on carbamazepine plasma levels in epileptic patients. Relationships with therapeutic and side effects.

Plasma levels of carbamazepine, phenytoin and phenobarbital were monitored weekly over a period of 9 weeks in 20 epileptic patients unresponsive to treatment. No attempts were made to modify phenytoin and/or phenobarbital plasma levels; emphasis was on achieving carbamazepine plasma levels of 4 to 10 mug per milliliter. A remarkable drop in seizure frequency was attained within 2 to 3 weeks of monitoring, with carbamazepine plasma and concentrations within the desired range. Children disposed of the drug faster than adults. No effects of phenytoin and phenobarbital on carbamazepine plasma levels could be observed, while phenobarbital on carbamazepine plasma levels fluctuated remarkably without any relationship to carbamazepine levels. Transient leukopenia was present in most of the patients, while a significant reversible drop in red blood cells was observed in eight patients. The data reported confirm that with a careful monitoring of drug plasma levels, carbamazepine may exert a definite passive effect on seizure frequency in epileptic patients poorly responsive to therapy.

A syndrome resembling limbic encephalitis, associated with bronchial carcinoma, but without neuropathological abnormality: a case report.

A patient, suffering from an oat-cell bronchial carcinoma, presented with complex partial seizures, complete loss of recent memory, mild disorientation and confabulation. There was no complaint of anxiety. The rest of the neurological examination and four computed tomographic scans of the head were normal. Repeated EEG recordings were abnormal. Antiepileptic and antipsychotic treatment led to full remission within 10 days. Post-mortem examination of the brain revealed no pathological changes.

Isolated hypophyseal tuberculoma: case report.

A 45-year-old woman, lifelong resident in Turin presented an isolated tuberculous granuloma of the hypophysis with no other systemic localizations. Diagnosis could be established only by biopsy. With antituberculous therapy the intracellular tumor regressed but not the endocrine disorders.

[Neurotoxic action of muzolimine at high doses in uremic patients. Observation of a group of 29 subjects]. / Azione neurotossica della muzolimina ad alte dosi in pazienti uremici. Osservazione su un gruppo di 29 soggetti.

We report the results of a study on 29 patients affected by renal chronic insufficiency and treated with high doses of muzolimine. From our data it results that to the muzolimine is probable due a neurological syndrome very similar to combined sclerosis. Up today, it is not possible to know how and where the muzolimine develops its neurotoxic effect.

[Preliminary open multicenter study on the anti-tremorigenic effectiveness of bornaprine (Sormodren)]. / Studio preliminare multicentrico "in aperto" sulla efficacia antitremorigena del bornaprine (Sormodren).

Out of 1500 patients suffering from tremor of diverse origin, reliable data on 521 were selected for analysis. The drug was given for over two months (mean daily dose 8 mg) and effectively reduced all kinds of tremor by an average 50%. The only side-effects occurring with any frequency were dryness of the mouth and constipation. The data collected show bornaprine to have a beneficial effect on all types of tremor.

[Correlated study of visual evoked potentials-polyneuropathy in diabetic patients without retinopathy]. / Studio correlato potenziali evocati visivi-polineuropatia in pazienti diabetici non retinopatici.

The functional study of visual pathways by means of pattern reversals VEPs (visual evoked potentials) was used as a noninvasive method in the study of diabetic patients, but the correlations between alterations in VEPs and the involvement of peripheral nervous system were not explored. Among 35 diabetic patients not suffering from retinopathy, we tested early deteriorations in visual pathways by means of pattern reversals VEPs and we considered similarities between these alterations, clinical metabolic parameters of the disease and clinical and paraclinical aspects of polyneuropathy (PNP). Four of these patients were insulin-dependent and 31 non-insulin-dependent, all with normal electroretinography and fluorangiography. Monitoring control of diabetes was performed by measuring hemoglobin HbA1. The control group was composed of 35 healthy subjects with normal neurologic and ophthalmologic examinations and normal visual acuity. In all subjects we tested four peripheral nerve conduction velocities (PNCV) (sensory and motor conduction of median nerve, motor conduction of peroneal nerve, anthidromic sensory conduction of sural nerve) diabetic patients were distributed in two groups according to the presence (group A, 15 patients) or absence (group B, 20 patients) of polyneuropathy. Pattern reversals PEVs were recorded after mono and binocular stimulation; screen was 25 x 18 cm with black and white check board pattern, check size 1.1 cm. Subject-to-stimulus distance was 1 m, corresponded to a visual angle of 38 degrees. Active electrode were located in Oz, O1 and O2, reference electrode in Fz.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hypokalemic myopathy caused by fluoroprednisolone in a nasal spray. Observations 2 cases]. / Miopatia ipokaliemica da fluoroprednisolone in spray nasale. Osservazioni su due casi.

Reference is made to the picture observed in two patients with flaccid tetraparesis, severe hypopotassaemia, and myoglobinuric muscle necrosis (hypokalaemic myopathy). Recent onset of hypertension was a feature of both cases. Initially, however, no reason could be assigned for this, nor for the massive loss of potassium. Numerous investigations in the first case (and relatively quick verification in the second) incriminated a steroid, 9-alpha-fluoroprednisolone acetate, in a nasal spray. This has often been reported as the cause of an iatrogenic syndrome due to excess of mineral corticoids, with hypertension, hypokalaemia and alkalosis, suppression of plasma renin activity, and reduction of blood and urinary aldosterone, all of which were observed in these two patients. Withdrawal of the drug and treatment with potassium chloride led to relatively rapid normalisation of the serum electrolytes. Recovery of muscle strength took place after about 20 days, almost at the same time as the normalisation of muscle enzymes. Hypertension, on the other hand, regressed slowly. The nexus between chronic use of the spray and the occurrence of hypokalaemic muscle necrosis is examined in detail. Stress is laid on the importance of specific investigation of the prior use of intranasal steroids in the differentiation of muscle disturbances due to potassium depletion.

Risk factors for tuberculosis infection and disease.

We conducted a prospective study among patients with newly diagnosed pulmonary tuberculosis and their close contacts to identify clinical and socio-economic risk factors for tuberculosis infection and disease. Ninety patients and 277 contacts were enrolled. The prevalence of infection was 45% [95% confidence interval (CI): 39-51%] among contacts. Factors like age, gender, race, delay of diagnosis and treatment, presence of cavitation in chest radiograph, cough, unwillingness to cover the mouth, volume of air shared by close contacts and patients were investigated. Inclusion of all these factors in a multivariate logistic regression model showed that only delay in diagnosis is significantly associated to the increase of prevalence (p < 0.0002), documenting that delay in diagnosis of the case is a crucial factor for tuberculosis infection and/or disease.

[The action of different coagulants to remove Cryptosporidium during the process of water treatment]. / Acción de distintos coagulantes para la eliminación de Cryptosporidium spp. en el proceso de potabilización del agua.

Cryptosporidium is one of the microorganisms of main concern from the point of view of Public Health, being a priority problem for water treatment plants and water regulatory institutions. Due to its small size and resistance to chlorination, Cryptosporidium removal during the process of drinking water treatment is a hard task. The effectiveness of different coagulants commonly used in the process of removal of oocysts was analyzed. The technique used was the Jar Test. It was found that: 1) coagulants with the addition of polimeric coadjuvants produce over 2 logs of oocyst removal; 2) a low value in turbidity does not necessarily mean optimal parasite removal, and 3) the addition of polyelectrolites to ferric chloride diminishes variability, both in final turbidity and Cryptosporidium removal.

[Cryptosporidium and water]. / Cryptosporidium y agua.

During the last years, cryptosporidiosis has been recognized as an important cause of diarrheal disease. According to different references, water has been an important vehicle responsible for the transmission in many epidemic outbreaks. The high number of oocysts eliminated by human and animal hosts, as well as low infectious dose and its resistance to desinfectants are some factors which contribute to the infectious risk. It has been also pointed that bacteriologically acceptable water may contain parasites. In order to minimize such risks, it is desirable to protect the water supplies and to use multiple barriers (coagulation, sedimentation and filtration) in drinking water treatment. The aim of this work is to provide information about the different aspects conditioning the presence of Cryptosporidium in drinking water.

[Cryptosporidium y Giardia in surface water]. / Cryptosporidium y Giardia en aguas superficiales.

The aim of this work was to determine Giardia and Cryptosporidium levels in surface water used either as recreational or drinking water source, and to estimate the relationship with bacteriological and physicochemical parameters determining water quality. This study was carried out during 22 months, in Santa Fe and Santo Tomé cities (Santa Fe Province, Argentina). Cryptosporidium from 100% of the recreational samples (44-2404 oocysts/100 l) and from 92% of water sources (< 20-539 oocysts/100 l) was detected, while Giardia was found in lower concentrations and frequencies: 72% (< 20-670 cysts/100 l) and 31% (< 20-65 cysts/100 l), respectively. Statistically significant relationships were found between these parasites and organic matter, turbidity and bacteriological indicators of contamination (Escherichia coli, streptococci, Enterococcus spp, Pseudomonas aeruginosa). These relationships, however, vary according to the sampling place, the source and levels of contamination.

Mood changes associated with "end-of-dose deterioration" in Parkinson's disease: a controlled study.

Fluctuations of mood and psychic activation were assessed in relation to "mobile" and "immobile" periods in 18 patients with Parkinson's disease presenting typical "end-of-dose deterioration". Twelve subjects with chronic but active rheumatoid arthritis presenting increased physical disability due to severe morning joint stiffness with a repetitive pattern of mobile and immobile periods acted as controls. The overall degree of disability and its fluctuations were close enough in the two groups for fair comparison of changes in affective behaviour. Temporary immobility was accompanied by adverse changes of mood and activation, which were significantly more marked in the Parkinson's disease group than in the controls, though to a lesser extent in those Parkinson's disease patients rated depressed even in their mobile periods. The possible correlation between mood changes and fluctuations of central dopaminergic function in the Parkinson's disease patients is discussed.

[The influence of noise on the human central nervous system (author's transl)]. / Die Wirkung von Strassenlärm auf das Zentralnervensystem des Menschen

We studied the effects of the road noise on the central nervous system in a group of 40 normal adult subjects. The neurophysiological research included the following parameters: acoustic and visual evoked cortical potentials, percentage of EEG desynchronization, contingent negative variation (CNV) and sleep-EEG. The results showed in every subject a reduction of the amplitude of the acoustic evoked potential recorded during the road noise as against to that one we recorded during normal silence. This fact, also in contrast to the stability of the visual evoked potential during the road noise and the normal silence, permitted to verify the existence of a neuronal occlusion phenomenon interesting the evocative acoustic stimulus when the noise is provided at the same time. The study of the EEG desynchronization during the road noise compared to that one during the normal silence did not give any statistically difference. The study of the CNV gave analogous results. Only if we complete the research with the study of the base-personality of every subject by the Rorschachtest, we found significant differences among the neurphysiological parameters as the EEG desynchronization and the CNV during the normal silence and the noise in relation to the different levels of anxiety and endotensivity of every subject.

Brain stem auditory evoked potentials and blink reflexes in quiescent multiple sclerosis.

Brain stem auditory evoked potentials (BAEP) and blink reflexes (BR) were studied in 25 patients with multiple sclerosis (MS), the diagnosis being definite according to McAlpine's criteria, in the quiescent phase, without signs of brain stem involvement. BAEP abnormalities were found in 64% of the cases and BR abnormalities in 60%. A good correlation between the two tests was found in most patients. The abnormalities consisted of delayed latencies and/or high intraindividual variability in shape and latency of BAEP and BR components. It seems that demyelination of brain stem pathways results not only in conduction slowing but also in more serious dysfunction of the generators of the evoked components.

Bornaprine vs placebo in Parkinson disease: double-blind controlled cross-over trial in 30 patients.

The study covers 30 patients with idiopathic Parkinson disease, 13 men and 17 women, aged between 50 and 70, on stabilized L-Dopa and/or bromocriptine, which failed to ensure adequate control of the symptoms, especially tremor. To this regimen was added Bornaprine/placebo in randomized sequence. The patients were tested according to the Webster Rating Scale before, during and after each stage of the treatment. Statistical analysis of the results showed the superiority of Bornaprine over the placebo in reducing tremor (p less than 0.01) and, to a lesser degree, some other parkinsonian symptoms. No noteworthy side effects were found apart from dryness of the mouth, which was more frequent with Bornaprine.