Multi-center study on overall clinical complexity of patients with prolonged disorders of consciousness of different etiologies.

Aim: to assess overall clinical complexity of patients with acquired disorders of consciousness (DoC) in vegetative state/unresponsive wakefulness syndrome (VS/UWS) vs. minimally conscious state- MCS) and in different etiologies..Design: Multi-center cross-sectional observational study.Setting: 23 intensive neurorehabilitation units.Subjects: 264 patients with DoC in the post-acute phase: VS/UWS = 141, and MCS = 123 due to vascular (n = 125), traumatic (n = 83) or anoxic (n = 56) brain injury.Main Measures: Coma Recovery Scale-Revised, and Disability Rating Scale (DRS); presence of medical devices (e.g., for eating or breathing); occurrence and severity of medical complications.Results: patients in DoC, and particularly those in VS/UWS, showed severe overall clinical complexity. Anoxic patients had higher overall clinical complexity, lower level of responsiveness/consciousness, higher functional disability, and higher needs of medical devices. Vascular patients had worse premorbid clinical comorbidities. The two etiologies showed a comparable rate of MC, higher than that observed in traumatic etiology.Conclusion: overall clinical complexity is significantly higher in VS/UWS than in MCS, and in non-traumatic vs. traumatic etiology. These findings could explain the worse clinical evolution reported in anoxic and vascular etiologies and in VS/UWS patients and contribute to plan patient-tailored care and rehabilitation programmes.

Demographical and clinical indices for long-term evolution of patients in vegetative or in minimally conscious state.

Objective. To evaluate the prognostic value of demographical, anamnestic, and clinical findings on long-term outcome (up to 36 months) in individuals with severe brain injury in vegetative state (VS) or in minimally conscious state (MCS).Participants. Patients (N = 216) in VS (N = 159) or in MCS (N = 57) consecutively admitted to a neurorehabilitation unit within 1-3 months after severe anoxic (n = 71), vascular (n = 96), or traumatic (n = 49) brain injury.Main outcome. Mortality and improvements in clinical diagnosis at 12, 24, and 36 months after brain injury. Multivariable logistic regression analyses were performed to verify independent relationships of variables collected at study entry with outcome measures.Results. In patients in VS, at the 12-month follow-up, higher level of responsiveness assessed by the Coma Recovery Scale-Revised (CRS-R) total scores at study entry predicted a higher likelihood of both survival and clinical improvement, whereas younger age predicted survival only. At 24 months, female sex and higher CRS-R total scores tended to be associated with clinical improvements. In patients in MCS, younger age and female predicted consciousness recovery at 12 months.Conclusions. Several patients' features easy to collect in rehabilitation setting might help clinicians in prognostication of long-term mortality and clinical evolution of VS and MCS.

Study of ethane level in exhaled breath in patients with age-related macular degeneration: preliminary study.

PURPOSE: A variety of factors have been implicated in the pathogenesis of age-related macular degeneration (ARMD), and oxidative stress plays an important role in the onset and progression of the disease. Breath ethane is now considered a specific and non-invasive test for determining and monitoring the trend of lipid peroxidation and free radical-induced damage in vivo. This test provides an index of the patients' overall oxidative stress level. We evaluated the breath ethane concentration in exhaled air in patients with advanced ARMD. METHODS: In this study, we enrolled 13 patients with advanced ARMD and a control group, and a breath analysis was carried out by gas chromatography. RESULTS: The mean ethane level in the ARMD patients was 0.82 ± 0.93 nmol/l (range: 0.01-2.7 nmol/l) and the mean ethane value in the control group was 0.12 ± 0.02 nmol/l (range: 0.08-0.16 nmol/l). The difference between the values of the 2 groups was statistically significant (p < 0.005). Receiver operating characteristic analysis showed an elevated area under the curve (0.831; 95% CI: 0.634-0.948), with a significance level of p < 0.0014 (area = 0.5). CONCLUSIONS: These preliminary results seem to indicate that breath ethane levels are higher in most patients with ARMD. The breath ethane test could thus be a useful method for evaluating the level of oxidative stress in patients with ARMD. To our knowledge, there are no data on this type of analysis applied to ARMD.

Spontaneous regression of congenital cutaneous hemangiomas in a calf.

Congenital vascular tumors of the skin have been described in people and a few animals, but unlike infantile hemangiomas in children, spontaneous regression has not been described in animals. A 2-day-old male Belgian Blue cross calf was presented for multiple congenital cutaneous masses that were soft, alopecic, and hyperemic; the calf had no other apparent abnormalities. Two weeks later, one mass had regressed. Surgical excision of one of the remaining masses was performed; histopathologic and immunohistochemical findings were considered diagnostic for epithelioid hemangioma. Eight months following initial presentation, all the masses had regressed spontaneously. This constitutes the first account in the veterinary literature of spontaneous regression in a congenital vascular tumor.

Histone deacetylase inhibitors induce thyroid cancer-specific apoptosis through proteasome-dependent inhibition of TRAIL degradation.

Anaplastic thyroid carcinoma (ATC) is considered one of the most aggressive malignancies, having a poor prognosis and being refractory to conventional chemotherapy and radiotherapy. Alteration in histone deacetylase (HDAC) activity has been reported in cancer, thus encouraging the development of HDAC inhibitors, whose antitumor action has been shown in both solid and hematological malignancies. However, the molecular basis for their tumor selectivity is unknown. To find an innovative therapy for the treatment of ATCs, we studied the effects of deacetylase inhibitors on thyroid tumorigenesis models. We show that HDACs 1 and 2 are overexpressed in ATCs compared with normal cells or benign tumors and that HDAC inhibitors induce apoptosis selectively in the fully transformed thyroid cells. Our results indicate that these phenomena are mediated by a novel action of HDAC inhibitors that reduces tumor necrosis factor-related apoptosis-inducing ligand protein degradation by affecting the ubiquitin-dependent pathway. Indeed, the combined treatment with HDAC and proteasome inhibitors results in synergistic apoptosis. These results strongly encourage the preclinical application of the combination deacetylase-proteasome inhibitors for the treatment of ATC.

Genetic differentiation of wild and cultivated populations: diversity of Coffea canephora Pierre in Uganda.

Coffea canephora Pierre ex Frohener is a perennial plant originated from Africa. Two main groups, Guinean and Congolese, have already been identified within this species. They correspond to main refugia in western and central Africa. In this paper we present the analysis of a region that has not yet been studied, Uganda. Two wild, one feral (once cultivated but abandoned for many years), and two cultivated populations of C. canephora from Uganda were evaluated using 24 microsatellite markers. Basic diversity, dissimilarity and genetic distances between individuals, genetic differentiation between populations, and structure within populations were analysed. Expected heterozygosity was high for wild compartments (0.48 to 0.54) and for cultivated and feral ones (0.57 to 0.59), with the number of private alleles ranging from 12 for cultivated genotypes to 37 for a wild compartment. The Ugandan samples show significant population structuring. We compared the Ugandan populations with a representative sample of known genetic diversity groups within the species using 18 markers. Coffea canephora of Ugandan origin was found to be genetically different from previously identified diversity groups, implying that it forms another diversity group within the species. Given its large distribution and extremely recent domestication, C. canephora can be used to understand the effect of refugia colonization on genetic diversity.

[Historical Archives of Italian Nephrology. The gout as a paradigmatic example of the ancient humoral theory of diseases]. / Archivi storici della Nefrologia Italiana. La gotta come paradigma e superamento dell'antica teoria umorale delle malattie.

Gout is one of the oldest known diseases. The term derives from the Latin "gutta", which means "a drop" This word expresses and describes, as no other term can, a method of interpreting the pathologies that have been with us for more than 2000 yrs. The theory of humoral disturbance goes back to the time of Hippocrates. This paper is a historical review of gout, with particular attention given to the interpretation of the origins of clinical, articular and renal involvement allowing us paradigmatically to sum up all the stages in the evolution of the etiopathogenetic and nosographic concepts of medicine through the ages.

N-acetyl-beta-D-glucosaminidase activity in urine of dental personnel.

BACKGROUND: Dental personnel is exposed to several potential nephrotoxic agents. Urinary N-acetyl-beta-d-glucosaminidase (U-NAG) activity has emerged as a sensitive marker of early nephrotoxicity. METHODS: U-NAG was evaluated, by fluorimetric assay, in urine from 30 healthy subjects and 30 dental personnels. RESULTS: The median value of U-NAG activity (133.5 U/mmol urinary creatinine (U-Cr) in urines of dental personnel was not statistically different (P>0.05) from activity (100.7 U/mmol U-Cr) of control urines. CONCLUSIONS: The results suggest that, for dental personnel, exposure to potential nephrotoxic agents is not usually high enough to increase U-NAG activity.

Changes in plasma level of human leukocyte elastase during leukocytosis from physical effort.

Physical exercise is known to induce immunological changes, mainly leukocytosis and neutrophil activation. However, it is not known to what extent the leukocytosis, observed after exertion, is associated with an increase in plasma neutrophil elastase, an early marker of inflammatory response and neutrophil degranulation. In the present study changes in circulating leukocyte and neutrophil counts and human neutrophil elastase plasma levels were evaluated in volley-ball players before and after 2 h and 12 h prolonged training, during a competition season. For comparison, the same parameters were evaluated in untrained subjects before and after a jogging session. Basal white blood cell WBC, polymorpho nuclear PMN, and human polymorpho nuclear-elastase PMN-ELA values were within the normal healthy reference range and no significant differences were found between the two groups studied. Venous blood samples of nine volley-ball players showed a statistically significant increase in blood WBCs after 2 h exercise. This effect was paralleled by a statistically significant increase in PMN-ELA concentration compared to the values observed in the same individuals at rest. The exercise did not significantly change the basal correlation parameters between PMN level and PMN-ELA concentration. More pronounced WBC, PMN, and PMN-ELA increases were observed in the seven inactive subjects after 2 h jogging. There was no linear correlation between increased PMN counts and increased PMN-ELA concentrations in untrained subjects after exercise. The results show that not only the leukocyte count but also PMN-ELA plasma levels can be higher after physical effort. This has a practical significance as regards differential diagnosis demonstrating that determination of these two laboratory parameters can give abnormally high values even in the absence of an existing inflammatory process. Besides, lack of correlation between PMN count and PMN-ELA plasma levels in the untrained group suggest a state in which activation of the neutrophils is not connected with their number in peripheral blood.

Neutrophil peripheral count and human leukocyte elastase during chronic lithium carbonate therapy.

Plasma levels of human polymorphonuclear elastase (PMN-E) are considered a marker of granulocyte activation and can potentially complement the peripheral neutrophil count in laboratory and pathophysiological settings. Neutrophilic leukocytosis is a well known effect of lithium therapy, but there is no information about the concomitant behaviour of PMN-E in these patients. The aim of this study was to evaluate both polymorphonuclear leukocyte count and plasma PMN-E levels in depression patients undergoing chronic lithium therapy. Absolute and differential leukocyte count in venous peripheral blood was determined by an automated method, and PMN-E evaluated by enzyme immunoassay. 39 patients (11 males, 28 females; mean age 43. +/- 6.02) with depression disorders were studied, during lithium carbonate therapy. Neutrophilia (neutrophil count > 7.500x10(9) cells per liter) was found in 7 (18%) patients and an increase in plasma PMN-E levels (PMN-E > 56 microg per liter ) in 6 (15%). No correlations were found between neutrophil count, plasma concentration of PMN-E, plasma level of lithium and duration of therapy. The results show that in these patients, not only the PMN count but also elastase levels can exceed the normal range. The absence of correlation between these two parameters suggests that the state of PMN activation is not linked to their number in peripheral blood.

Effect of lansoprazole on human leukocyte function.

Recent findings on the capacity of omeprazole to influence various leukocyte functions, in vitro, raises the question on the potential use of protonic pump inhibitors, commonly used in the treatment of acid-secretion-related disorders, as immunomodulators. The aim of this study was to evaluate the in vitro effect of lansoprazole on human natural killer (NK) cell cytotoxix activity, chemotaxis and superoxide anion (O2*-) generation exerted by polymorphonucleated cells (PMNs). NK cytotoxicity activity was assessed by a 51Cr release assay, PMN chemotaxis was determined by an under agarose method and O2*- generation was analyzed on the basis of reduced cytochrome C. Incubation times with lansoprazole was 30 min for PMNs and 1-4.5 hours for NK cells, respectively. Lansoprazole induced significant dose dependent inhibition of NK cell activity and PMN functions at concentrations ranging from 100 to 1,000 microM. This study demonstrate that lansoprazole, like omeprazole, inhibits several leukocyte functions, in vitro, then suggesting that protonic pump inhibitors are able to provoke these effects, at least at certain doses.

[Leukocytic procoagulant activity and chemotherapeutic drugs: the comparative effects of cisplatin and carboplatin on lympho-/monocytic procoagulant activity in vitro]. / Attività procoagulante leucocitaria e farmaci chemioterapici: effetti comparativi del cisplatino e del carboplatino sull'attività procoagulante linfo/monocitaria in vitro.

It is well known that a number of chemotherapeutic agents are able to induce procoagulating activity not only in neoplastic cells but also in normal, monocyte/macrophage cells, and some of them, including cisplatin, even increase procoagulating activity of the factor already expressed, providing a further example of the possible co-participation of chemotherapy in the onset of thrombotic complications in cancer patients. Carboplatin is an analogue of cisplatin but differs strikingly in terms of its collateral effects, in particular being less oto- and nephrotoxic. To the authors' knowledge there are no data regarding the possible effect of carboplatin on lympho/monocyte procoagulating activity. This study shows that not only platin but also carboplatin is able to increment the levels of lympho/monocyte procoagulating activity in vitro, with a dose-dependent effect, and to synergize with bacterial endotoxin in increasing this leukocyte activity, although the synergic effect is significantly greater in the case of carboplatin. The importance of these findings at a practical and clinical and clinical level still remains to be defined, in particular in the light of the different pharmacokinetic behaviour of these two chemotherapeutic agents and in the context of those neoplastic diseases for which cisplatin and carboplatin treatment is most frequently used.

[Leukocyte procoagulant activity and chemotherapeutic agents: comparison between the effects of adriamycin and epiadriamycin on the procoagulant lympho/monocytic activity in vitro]. / Attività procoagulante leucocitaria e farmaci chemioterapici: comparazione tra gli effetti dell'adriamicina e dell'epiadriamicina sull'attività procoagulante linfo/monocitaria "in vitro".

It is well known that a number of antineoplastic agents are able to induce procoagulant cellular activity and tissue factor not only in neoplastic cells but also in normal, monocyte/macrophage cells, and some of them, including adriamycin, even increase procoagulating activity of the factor already expressed, providing a further example of the possible co-participation of chemotherapy in the onset of thrombotic complication in cancer patient. Epirubicin is an analogue of adriamycin but differs strikingly in terms of its collateral effect, in particular being less cardiotoxic. To the authors' knowledge there are no data regarding the possible effect of epirubicin on lympho/monocyte procoagulant activity. This study shows that not only adriamycin but also epirubicin is able to increment the level of lympho/monocyte procoagulant activity "in vitro", with a dose-dependent effect, and to synergize with bacterial endotoxin in increasing this leukocyte activity, although the effect is significantly greater in the case of adriamycin. The importance of these findings at practical and clinical level remains to be defined, in particular in the length of the different pharmacokinetic behavior of these two chemotherapeutic agents and in the context of those neoplastic diseases for which adriamycin and Epirubicin treatment is most frequently used.

[Reduced ex vivo production of superoxide anion by polymorphonuclear leukocytes during therapy with omeprazole. A pharmacological effect?]. / Ridotta produzione "ex vivo" di anione superossido da parte dei leucociti polimorfonucleati durante terapia con omeprazolo. Un effetto farmacologico?

Among available drugs, omeprazole is the one that cures gastric acid secretion-related pathologies, including reflux oesophagitis which responds poorly to H2-receptor antagonists, most rapidly and efficaciously. This marked therapeutic action is thought to reflect the drug's capacity to adequately control parietal hydrochloric acid secretion. Our data suggest an omeprazole effect on human neutrophil function too. Neutrophils are more or less a constant, and often conspicuous anatomo-pathological component of the phlogistic processes associated with gastric acid secretion. A direct or indirect effect exerted by omeprazole on leukocyte function would be of great scientific-biological and therapeutic interest. Furthermore, it would contribute to marking the drug superior in terms of more rapid relief of the symptoms and range of therapeutic action.

In-vitro effects of teicoplanin, teicoplanin derivative MDL 62211 and vancomycin on human polymorphonuclear cell function.

The in-vitro effects on human neutrophil (PMN) functions of three structurally related glycopeptide antibiotics, vancomycin, teicoplanin and the teicoplanin derivative MDL 62211 were investigated. Teicoplanin and MDL 62211 significantly inhibited adherence, chemotaxis, phagocytosis and killing of Candida albicans by PMN's at a concentration of 500 mg/l, whereas PMN viability was only affected at drug concentrations of 2000 mg/l. Vancomycin interfered with PMN adherence and phagocytosis only at a concentration of 2000 mg/l without affecting PMN viability. Chemotaxis and killing of C. albicans were also not affected by this concentration. Teicoplanin and the teicoplanin-derivative MDL 62211 was found to have adverse effects on selected indices of PMN function in vitro only at concentrations higher than those employed in therapy, while vancomycin interfered only at very high concentrations.