Preliminary profiling of blood transcriptome in a rat model of hemorrhagic shock.

Hemorrhagic shock is a leading cause of morbidity and mortality worldwide. Significant blood loss may lead to decreased blood pressure and inadequate tissue perfusion with resultant organ failure and death, even after replacement of lost blood volume. One reason for this high acuity is that the fundamental mechanisms of shock are poorly understood. Proteomic and metabolomic approaches have been used to investigate the molecular events occurring in hemorrhagic shock but, to our knowledge, a systematic analysis of the transcriptomic profile is missing. Therefore, a pilot analysis using paired-end RNA sequencing was used to identify changes that occur in the blood transcriptome of rats subjected to hemorrhagic shock after blood reinfusion. Hemorrhagic shock was induced using a Wigger's shock model. The transcriptome of whole blood from shocked animals shows modulation of genes related to inflammation and immune response (Tlr13, Il1b, Ccl6, Lgals3), antioxidant functions (Mt2A, Mt1), tissue injury and repair pathways (Gpnmb, Trim72) and lipid mediators (Alox5ap, Ltb4r, Ptger2) compared with control animals. These findings are congruent with results obtained in hemorrhagic shock analysis by other authors using metabolomics and proteomics. The analysis of blood transcriptome may be a valuable tool to understand the biological changes occurring in hemorrhagic shock and a promising approach for the identification of novel biomarkers and therapeutic targets. Impact statement This study provides the first pilot analysis of the changes occurring in transcriptome expression of whole blood in hemorrhagic shock (HS) rats. We showed that the analysis of blood transcriptome is a useful approach to investigate pathways and functional alterations in this disease condition. This pilot study encourages the possible application of transcriptome analysis in the clinical setting, for the molecular profiling of whole blood in HS patients.

Transcriptomic analyses and leukocyte telomere length measurement in subjects exposed to severe recent stressful life events.

Stressful life events occurring in adulthood have been found able to affect mood and behavior, thus increasing the vulnerability for several stress-related psychiatric disorders. However, although there is plenty of clinical data supporting an association between stressful life events in adulthood and an enhanced vulnerability for psychopathology, the underlying molecular mechanisms are still poorly investigated. Thus, in this study we performed peripheral/whole-genome transcriptomic analyses in blood samples obtained from 53 adult subjects characterized for recent stressful life events occurred within the previous 6 months. Transcriptomic data were analyzed using Partek Genomics Suite; pathway and network analyses were performed using Ingenuity Pathway Analysis and GeneMANIA Software. We found 207 genes significantly differentially expressed in adult subjects who reported recent stressful life experiences (n=21) compared with those without such experiences (n=32). Moreover, the same subjects exposed to such stressful experiences showed a reduction in leukocyte telomere length. A correlation analyses between telomere length and transcriptomic data indicated an association between the exposures to recent stressful life events and the modulation of several pathways, mainly involved in immune-inflammatory-related processes and oxidative stress, such as natural killer cell signaling, interleukin-1 (IL-1) signaling, MIF regulation of innate immunity and IL-6 signaling. Our data suggest an association between exposures to recent stressful life events in adulthood and alterations in the immune, inflammatory and oxidative stress pathways, which could be also involved in the negative effect of stressful life events on leukocyte telomere length. The modulation of these mechanisms may underlie the clinical association between the exposure to recent Stressful life events in adulthood and an enhanced vulnerability to develop psychiatric diseases in adulthood.

The -665 C>T polymorphism in the eNOS gene predicts cardiovascular mortality and morbidity in white Europeans.

We recently identified rs3918226 as a hypertension susceptibility locus (-665 C>T), TT homozygosity being associated with higher hypertension risk. T compared with C allele transfected cells had lower endothelial nitric oxide synthase (eNOS) expression. In the family-based Flemish Study on Environment, Genes and Health Outcomes (50.9% women; mean age 40.3 years), we investigated whether 32 TT homozygotes had worse outcomes than 2787 C allele carriers. Over 15 years (median), total and cardiovascular mortality and cardiovascular and coronary events amounted to 269 (9.5%), 98 (3.5%), 247 (8.8%) and 120 (4.3%), respectively. While accounting for family clusters, the hazard ratios associated with TT homozygosity were 4.11 (P=0.0052) for cardiovascular mortality (4 deaths), 2.75 (P=0.0067) for cardiovascular events (7 endpoints) and 3.10 (P=0.022) for coronary events (4 endpoints). With adjustment for cardiovascular risk factors, these hazard ratios were 6.01 (P=0.0003), 2.64 (P=0.0091) and 2.89 (P=0.010), respectively. Analyses unadjusted for blood pressure and antihypertensive treatment produced consistent results. For all fatal plus nonfatal cardiovascular events, the positive predictive value, attributable risk and population-attributable risk associated with TT homozygosity were 21.9, 61.5 and 2.0%, respectively. In conclusion, TT homozygosity at the position -665 in the eNOS promoter predicts adverse outcomes, independent of blood pressure and other risk factors.

Unusual presentation of large B cell lymphoma: a case report and review of literature.

Diffuse large B cell lymphoma (DLBCL) is the largest subtype of non-Hodgkin's lymphomas (NHLs) and is characterized by relatively frequent extranodal presentation. In these cases, the most common extranodal localizations are stomach, CNS, bone, testis and liver. Simultaneous detection of multiple extranodal involvement at presentation is quite uncommon, with the majority of these cases characterized by gastric or intestinal disease localization. Retrospective analysis concerning multifocal extranodal NHLs never pointed out disease features such as those described here. We report a patient with an unusual presentation of DLBCL, characterized by adrenal and renal involvement, associated with symptoms and signs of the cold agglutinin disease and a hypercoagulable state. Subsequently, computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning disclosed a rapidly extensive spread to nodes and bones. Cytofluorimetric analysis of a renal specimen showed medium-to-large lympho-monocytoid elements positive for CD20 with monoclonal expression of immunoglobulin kappa light chain. Histopathological examination confirmed a renal CD20 positive DLBCL localization.

Duodenal ulcers preceding cervical tuberculous lymphadenitis.

Lymphadenitis is the most common presentation of extra pulmonary tuberculosis, whereas gastrointestinal localization, particularly duodenal involvement, is rare. We report a case of extra pulmonary tuberculosis with association between cervical lymphadenitis and duodenitis with multiple ulcers, not responsive to treatment with protonic pump inhibitors, in a human immunodeficiency virus-seronegative adult woman of Eritrean origin. Clinical patterns of duodenal TB, diagnostic difficulties and aetiopathogenesis are discussed according to the literature. In this case report it is suggested that tuberculous infection must be considered when duodenal ulcers fail to respond to proton pump inhibitors, especially when the patient comes from an endemic area.

Onset of allergy and asthma symptoms in extra-European immigrants to Milan, Italy: possible role of environmental factors.

BACKGROUND: Allergy and asthma are typical disorders of the affluent societies. Migrants from developing to industrialized countries seem to be at increased risk of allergy and asthma development. OBJECTIVE: To evaluate time of onset, spectrum of sensitization and clinical features in a population of extra-European immigrants to Milan, Italy, complaining of allergy and asthma symptoms. METHODS: Data regarding 243 extra-European immigrants checked at an allergy clinic from 1994 to 2000 were collected retrospectively. The demographic data were compared with those of the extra-European immigrants living in Milan at the end of 1999. RESULTS: The patients were complaining of asthma (63.7%), rhinoconjunctivitis (56.7%), rhinitis alone (21%) or urticaria (3%). One hundred and eighty-seven out of 222 patients (84.3%) declared they were healthy before migrating and allergy/asthma symptoms started to appear after their arrival in Italy, namely after an average period of 4 years and 7 months. The proportion of male patients was lower than the proportion of men in the extra-European immigrant population (48% vs. 55%), suggesting that in adult immigrants allergy and asthma are more common in women than in men. Furthermore, there was an over-representation of Central-South Americans attending the clinic, which seemed to be due to a genetic predisposition to allergy/asthma development. When data were analysed for single countries, a trend towards an increased risk of allergy and asthma was found in immigrants from all Central-South American countries. A skin test positivity for at least one inhalant allergen was found in 196 out of 232 patients (81%), and the spectrum of allergic sensitization was similar to that of the Italian population living in the North of Italy. CONCLUSION: Most extra-European immigrants declared that they were healthy at home and that allergy and asthma symptoms had appeared after immigration to Milan; lifestyle and environmental factors in a western industrialized city seem indeed to facilitate allergy/asthma onset in immigrants from developing countries. Allergy/asthma risk seems to be different in different ethnic groups.

[A thioridazine-dihydroergotoxine combination in the treatment of senile pruritus]. / Associazione tioridazina-diidroergotossina nel trattamento del prurito senile.

Senile itching, a peculiar clinical situation consisting of a cutaneous senile involution associated with a relevant neurogenic component, still keeps being a difficult therapeutic problem. For the purpose, a clinical trial, carried out with a combination of thioridazine and dihydroergotoxine on 19 patients carriers of the affection, could show a relevant decrease in all parameters assessed, ie itching, muscle tension and skin temperature measured by biofeedback. The combination also showed a good tolerance.

[Peripheral stenosing-occlusive arteriopathies. Doppler echographic and digital angiographic evaluation]. / Arteriopatie steno-occlusive periferiche. Valutazione ecografica Doppler e angiografia digitale.

The value of Doppler ultrasound examination and digital intravenous angiography was comparatively evaluated in 207 patients with peripheral vascular disease submitted to both techniques. Owing to the fact that in some patients more than one vascular district was examined, the overall number of evaluations was 232 Doppler ultrasounds and 233 digital angiographies. Doppler ultrasound revealed a normal picture in 18/232 cases, steno-occlusive disease in 186/232 cases and various pathological conditions in the remaining 18 cases. With digital angiography, normal vascularity was observed in 33/233 patients, while steno-occlusive disease was present in 164/233 and vascular anatomical abnormalities, like kinking, were found in 20 cases. Doppler/angiographical correlation was fairly good, being complete in 83/207 patients and substantial (i.e.: the same diagnosis but different degree of pathological involvement) in 79 additional cases: the overall diagnostic agreement between Doppler and angiography was 162/207 cases (78%). False negative Doppler results were 29/207, while the false positive Doppler examinations were 16/207. The most common causes of diagnostic errors are evaluated and discussed, both for Doppler ultrasound and for digital angiography. Arterial kinking and vascular abnormalities are recognized as an obvious cause of wrong Doppler diagnoses which can be easily discovered by the angiographic picture. The usefulness of performing both techniques in combination is demonstrated and stressed.

[Digital angiography of the pudendal arteries in erectile impotence]. / L'angiografia digitale delle arterie pudende nello studio della impotenza erettile.

Digital angiography of pudendal and penile arteries was performed on 32 consecutive patients with erectile failure of suspected vascular origin. Intra-arterial injection of contrast medium via selective catheterization of the hypogastric arteries was used in 6 cases. In 27 cases, one of which already submitted to arterial catheterism, the intravenous route was employed for contrast administration, using a single, large volume, high speed bolus. In one case, digital angiography was diagnostically unreliable due to patient's motion and to blurring artifacts. Among the remaining cases, 9/31 (29%) showed a normal angiographic picture, while 22/31 (71%) possessed stenotic-obstructive lesions of different severity. The pictures obtained after intravenous contrast administration were diagnostically equivalent to those obtained with arterial catheterism: in addition, intravenous route allowed the simultaneous representation of the arterial network of both sides and the overall examination resulted less invasive and quicker. In 22/32 patients (69%), functional determinations of erectile capability and of penile blood flow were performed for comparison. Nocturnal penile tumescence (12 cases diagnostically useful) was well correlated with the angiographic picture. Penile blood flow measurements with the Doppler technique (21 cases) seemed on the contrary to be less sensitive than digital angiography.

A comparison of IHA and ELISA tests in the detection of antibodies to entamoeba histolytica.

In this report we have evaluated the sensitivity and specificity of IHA and ELISA for the detection of anti-amebic antibodies in the serum samples of 147 patients with poor mental and hygienic status hospitalized in mental institutions. Our data have demonstrated a positive agreement between ELISA and IHA on positive sera. The major drawback of IHA is the occurrence of false negative results, 13/82 sera negative in IHA (less than 1/128) are positive in the ELISA. Furthermore, the ELISA is useful for serological diagnosis of amebiasis in the laboratories of low endemic areas.