Incidence, clinical features and management of acute allergic reactions: the experience of a single, Italian Emergency Department.

OBJECTIVES: Few data on the incidence, aetiology, clinical features and management of patients with acute allergic reactions presenting to the Emergency Department are currently available. The aim of the study was to report the annual experience of a single Italian adult Emergency Department about anaphylaxis. PATIENTS AND METHODS: This is a retrospective, case-based study of adult patients attending the Emergency Department in Alessandria, Italy, during the years 2009-2010. We evaluated the medical records of patients satisfying diagnostic codes involving acute allergic reactions. Incidence, demographic data, causative agents, clinical features, management and outcome were reported. RESULTS: 390 patients with acute allergic reactions were evaluated during the year, corresponding to 0.7% of all Emergency Department visits. Causative agents were recognized in 55.1% of patients and more commonly included drugs (26.9%), insects (14.8%) and foods (8.9%). Cutaneous features were the single most common clinical presentation although two or more clinical features were frequently reported (17.7%). Anaphylaxis was diagnosed in 4.6% of patients. After therapy and a period of monitoring, 92.8% of patients were discharged directly from the Emergency Department, 7.0% were admitted and one patient died, corresponding to a fatality rate of 0.2%. CONCLUSIONS: Acute allergic reactions are common diseases referring to our Emergency Department. In the half of cases a precipitant agent was identified and cutaneous and/or mucosal changes were often the first feature. Most patients were definitely treated and discharged but about 7.0% of patients required hospitalisation. Observation Unit and Intermediate Care Unit were essential for clinical management of these patients.

Spinal anesthesia plus ketamine-midazolam sedation for pediatric orthopedic surgery in a developing country.

INTRODUCTION: Spinal anesthesia produces a profound and uniformly distributed sensory block with rapid onset and muscle relaxation, and results in complete control of cardiovascular and stress responses. Ketamine is an anesthetic agent that is widely used for pediatric sedations in settings where safety and efficacy of the agents are mandatory because of limited healthcare resources. The authors report on their experience in a refugee hospital located in Bol-la (Saharawi, Algeria). METHODS: Spinal anesthesia was performed for orthopedic surgery procedures in children. Before the spinal puncture, the patients were sedated with intramuscular ketamine followed by intravenous ketamine and midazolam. Boluses of midazolam were also administered throughout the surgery to keep the patients sedated; spinal anesthesia was performed with levobupivacaine 0.25 mg/kg. RESULTS: There were no intraoperative adverse events; vital signs were within the normal pediatric ranges during the procedures and there was no need to switch to general anesthesia. In the postoperative period, no symptoms of dural puncture headache or postoperative delirium or nightmares were reported. CONCLUSION: Based on the authors' experience, the combination of spinal anesthesia and sedation with midazolam and ketamine was found to be a safe approach for children undergoing orthopedic surgery in a low resources setting.

Role of immune-derived diffusible mediators in AIDS-associated neurological disorders.

Neurologic abnormalities are common in HIV-1 infected patients and often represent the dominant clinical manifestation of pediatric AIDS. Although the neurological dysfunction has been directly related to CNS invasion by HIV-1, the pathogenesis of neurologic disorders remains unclear. This review will first discuss the spectrum of potential interactions between HIV-1 and neural (neuronal and glial) cells, in the face of experimental data. Next, we will focus on the role of immune-derived cytokines and other soluble compounds which have been proposed to act as neurotoxic mediators and appear to play a role in the pathogenesis of AIDS-associated neurodegeneration.

Decreased T cell apoptosis and T cell recovery during highly active antiretroviral therapy (HAART).

T cell apoptosis represents a common mechanism of T cell depletion in HIV-1-infected individuals reflecting maturational and functional T cell abnormalities either directly or indirectly induced by the virus. In the present study, the effects of highly active antiretroviral therapy (HAART) on the spontaneous apoptosis of distinct T cell subsets were investigated during a 6-month follow-up in a cohort of HIV-1-infected individuals with CD4(+) cell counts between 100 and 500 cells/microliter and plasma HIV-1 RNA levels >/=10, 000 copies/ml. We determined that the rapid and sustained increase of both naive (CD45RA(+)CD62L(+)) and memory (CD45R0(+) and CD45RA(+)/CD62L(-)) CD4(+) and, to as lesser extent, CD8(+) T cells in peripheral blood was associated with a significant decrease of apoptotic CD4(+) and CD8(+) as well as CD3(+)CD4(-)CD8(-) T cells. Among CD4(+) lymphocytes, at enrollment, the highest frequency of apoptotic cells was observed within the memory compartment, as defined by CD45R0 expression. During HAART, however, the frequency of CD4(+)CD45R0(+) apoptotic T cells progressively decreased in association with a significant downregulation of surface activation markers that indicated decreased levels of systemic immune stimulation. These results indicate that effective viral suppression can contribute to progressive normalization of maturational and functional T cell abnormalities responsible for the high levels of T cell apoptosis in HIV-1-infected individuals. This, in turn, may contribute to a reduced rate of T cell loss and immune reconstitution during HAART.

Immune-derived cytokines in the nervous system: epigenetic instructive signals or neuropathogenic mediators?

The investigation of the effects of inflammatory cytokines (IC) on the growth and differentiation of neural cells has provided new insights on the role of such soluble mediators in nervous system development and/or plastic remodeling as well as in the pathogenesis of inflammatory neurodegenerative disorders, which are characterized by chronic IC dysregulation in the central nervous system (CNS). Thus, the study of the interaction between CNS and immune-derived soluble signals in physiological or pathological conditions is of increasing interest. This review first discusses experimental evidence supporting the instructive/permissive role of immune-derived cytokines on CNS development and plasticity. Next, we focus on human neurological disease states such as multiple sclerosis and the neurodegeneration associated to the acquired immune deficiency syndrome in which different inflammatory cytokines have been proposed as potential neuropathogenic mediators.

Inflammatory cytokines and HIV-1-associated neurodegeneration: oncostatin-M produced by mononuclear cells from HIV-1-infected individuals induces apoptosis of primary neurons.

Neurologic abnormalities are common in HIV-1-infected patients and often represent the dominant clinical manifestation of pediatric AIDS. The neurological dysfunction has been directly related to CNS invasion by HIV-1 that is principally, if not exclusively, supported by blood-derived monocytes/macrophages and lymphocytes. By using primary long term cultures of human fetal sensory neurons as well as sympathetic precursors-like neuronal cells, we determined that blood-derived mononuclear cells from HIV-1-infected individuals spontaneously release soluble mediators that can potently inhibit the growth and survival of developing neurons as well as the viability of postmitotic neuronal cells by inducing apoptotic cell death. Analysis of the cytokines produced by lymphomonocytic cells, HIV-1 infected or activated, indicated that oncostatin M (oncM) is a major mediator of these effects. Since low TGF-beta1 concentrations were capable of enhancing oncM-mediated neuronal alterations, our data indicate that by acting in concert with other cytokines, oncM may induce neuronal demise in both the developing and the mature brain. Thus, this cytokine may contribute to the setting of the neuronal cell damage observed in HIV-1-infected individuals.

Early detection of locally recurrent rectal cancer by endosonography.

After curative surgery for rectal cancer, the goal of an aggressive surveillance programme is the detection of local recurrence (LR) at an early and potentially curable stage 62 patients (mean age 66.2 years) operated on for rectal cancer were prospectively enrolled in a follow-up study including endorectal ultrasound (EUS), serial CEA levels, digital examination, colonoscopy and pelvic CT. A total of 192 sonographic scans were performed, with a mean of three (range 2-7) for each patient. LR occurred in 11 patients; in all cases this was suggested by EUS. In two patients (18%) other techniques had failed to detect recurrent disease, which was identified solely by EUS. These two were treated radically and the remainder received radiotherapy or other palliative management. Five patients are alive at, on average, 18 months after LR (range 4-26 months). These include both cases treated with salvage surgery and who remain disease free. EUS is a valuable tool in the detection of locally recurrent rectal cancer.

Pelvic recurrence following resection of rectal cancer: a multivariate predictive model.

Local recurrence of rectal cancer (LR) after "curative" surgery is a major clinical problem, with a low resectability rate and a dismal prognosis. Prediction of LR might permit more targeted postoperative surveillance with earlier diagnosis of recurrent disease and might help in selecting the patients to be assigned to the most suitable adjuvant treatment protocol. To evaluate if a simple multivariate model could predict the LR and survival probability in the single case, we retrospectively evaluated 118 consecutive patients (63 males, 55 females; mean age 62 +/- 12 years) operated on for rectal cancer and followed up for a minimum of 4 years (range 51-111 months). Local recurrence rate was 28%, with a 6% of local + distant failure. Age and sex of patients, type of surgery, location of tumour in the rectum, size, morphology and grading of the tumour were all unrelated to the event under investigation. At Cox regression, the Dukes' stage and the postoperative radiotherapy were the only independent prognostic factors for LR (p < 0.001). The multivariate model was able to correctly reclassify the patients and predict local recurrence in 86.2% of the cases. Prevention of LR by adequate surgery and adjuvant therapy as well as its early detection offer the best prospect of improving the results of surgery for rectal cancer.

Enzymatic basis for the lack of oxamniquine activity in Schistosoma haematobium infections.

The notion that oxamniquine is active against Schistosoma mansoni but inactive against S. haematobium was confirmed using in vitro cultures of adult worms. Since oxamniquine and hycanthone have been shown to become effective upon activation by a schistosome enzyme, enzymatic tests were carried out to detect possible differences between the enzyme of S. mansoni and that of S. haematobium. It was found that the S. mansoni enzyme could activate hycanthone and, to a lesser extent, oxamniquine. The S. haematobium enzyme, on the other hand, was capable of activating hycanthone but virtually incapable of activating oxamniquine. It is concluded that the different activity of oxamniquine in the two species is due to differences in the drug-activating enzyme.

[Surgery for familial polyposis of the colon. A functional follow-up]. / Chirurgia per poliposi familiare del colon. Follow-up funzionale.

Functional assessment of pelvic pouch procedures for FAP is not different from that of UC and consists of clinical, manometric and radiologic investigations. Ileo-rectal anastomosis and pelvic pouch operation are equally effective for the disease, but function is still questionable after restorative proctocolectomy. Based on a personal series of 43 patients, relevant technical aspects influencing functional results are discussed and guidelines for a correct follow-up of these patients are presented.

Transanal excision and postoperative radiation therapy in selected patients with cancer of the low rectum.

Preliminary results of 24 patients (15 males, 9 females; age range 30-81 years) with localized low rectal cancer treated with transanal excision and postoperative radiation therapy are reported. Preoperative endosonographic staging was T1 (10), T2a (12) and T2b (2). All had negative resection margins, except one patient who underwent salvage major resection (no tumor found in the specimen). The mean follow-up was 33 months (range 29-61 months). Twenty patients (83.3%) are alive with no sign of local or distant failure. Two patients (9%) developed a local recurrence and were both salvaged with major surgery. Operative and radiotherapy-related morbidity was minor, with diarrhoea and perianal discomfort occurring in most patients following irradiation. Long-term sphincter function was satisfactory in 90% of cases. Rectal endosonography provided a reliable preoperative staging of T (100% correlation with histology) and, indirectly, N parameter, appearing as the key investigation in selecting candidates for conservative treatment. Postoperative radiotherapy might also be proposed after excision of T1 cancers as it produced few side effects and has the potential to control any residual disease. Additional experience is needed to determine long-term results of this combined radiosurgical approach.

External anal sphincter defects: correlation between pre-operative anal endosonography and intraoperative findings.

In order to correlate operative findings with external anal sphincter (EAS) defects identified on anal endosonography (AES), 30 faecally incontinent patients undergoing overlapping sphincteroplasty or total pelvic floor repair were investigated by AES before and after surgery. Endosonic findings were correlated with the appearance of EAS at operation. 21 out of 22 defects seen at surgery had been pre-operatively detected by AES (one false negative). Post-operatively the sphincteroplasty was clearly evident on AES. In three cases of failure it showed an extensive hypoechoic area and these patients underwent dynamic graciloplasty. Endosonography is the method of choice for pre-operative imaging of EAS, having an established role in identifying sphincter defects and correlating well with intraoperative findings. Post-operatively, it has the potential to identify breakdown of the previous repair, allowing prompt surgical intervention. Endosonography is helpful in planning the best type of operation following sphincter injury and is useful in auditing the results of surgery.

Regression of cardiac hypertrophy: morphometric and biochemical studies in rat heart after swimming training.

There is currently little information about the morphological changes of the myocardium accompanying the reversal of cardiac hypertrophy. In this study the hypothesis was tested that myocardial alterations induced by exercise will regress within a short interval after the end of training. Rat hearts were examined using morphometric and biochemical methods at the end of a 9-week period of endurance training and also 7, 10 and 14 days after its termination. At the end of the training period the heart weight had increased by 65% but the weight ratio of the right and left ventricular wall remained unchanged. A decline in the DNA content by 27% as well as a decrease in the volume density of the interstitial space by 14% and in the number of interstitial cell nuclei by 32% against controls, are explained by a 30% increase in the width of myofibres. The capillary density was reduced by 22% but the volume density of capillaries remained nearly constant as a result of widening of the capillary diameter by 27%. The surface density of capillaries was diminished by 10%. Ultrastructurally an increase in the ratio of mitochondrial to myofibrillar volume density was observed in the myocytes of hypertrophied hearts as compared to controls (0.54 and 0.63, respectively). Fourteen days after termination of training, 80% of the increment in heart weight had regressed. At this time the width of the myofibres and the volume density of the interstitial space had nearly normalized, while the capillary to fibre ratio had significantly increased. The ratio of mitochondrial and myofibrillar volume density became nearly normal, and a confluence of intermyofibrillar mitochondria resulted in significantly longer organelles. The increased DNA content 10 days after the training, as compared to controls, is attributable to the genesis of non-myocardial cells during the hypertrophic growth and their persistence during regression. The study has shown that cardiac hypertrophy induced by physical training nearly completely regresses within 14 days after termination of conditioning. The increased capillary to fibre ratio indicates neoformation of transversely oriented capillary branches in hypertrophy which particularly becomes apparent in two-dimensional estimation in the regression period. In comparison with myofibres, regression of capillaries seems to be delayed. The decline of heart weight and a significantly diminished RNA content during the regression of hypertrophy suggest that reduced synthesis is responsible for the decrease in heart weight.

Regression of aflatoxin B1-induced hepatocellular carcinomas by reduced glutathione.

Reduced glutathione administered to rats bearing aflatoxin B1-induced liver tumors caused regression of tumor growth and resulted in survival of the animals. since glutathione is a harmless natural product, it merits further investigation as a potential antitumor drug for humans.

[Early morphological changes during the development of cardiac hypertrophy (author's transl)]. / Frühe morphologische Veränderungen bei der Entwicklung der Herz-Hypertrophie.

The development of a cardiac hypertrophy depends on modulation of two parameters, such as the amount of increased work load imposed on the heart and the rapidity with which the work load is applied. A gradual development of cardiac hypertrophy is usually observed in humans; at variance, the induction of cardiac hypertrophy is quite a rapid process in animal experiments. The enlargement of cardiac muscle cells during hypertrophy is due not only to an increased synthesis of contractile proteins but also to an accumulation of other cell constituents parallelly involved in the hypertrophy process. The mechanism whereby new sarcomeres are formed during cardiac hypertrophy is not yet completely clarified. Once the stimulus producing overload is removed, cardiac hypertrophy can regress completely. The possible role of biological regulators in inducing cardiac hypertrophy was also discussed.

Aurintricarboxylic acid (ATA) and DNA synthesis. I. Inhibition of DNA synthesis by ATA in Go cells stimulated to proliferate.

Aurintricarboxylic acid (ATA) at a concentration which produces 40% inhibition of protein synthesis, inhibits completely isoproterenol-stimulated DNA synthesis in mouse parotid glands. The drug was found to interfere with some essential changes occurring during the prereplicative phase of IPR-stimulated DNA synthesis. It inhibits the increase in ribosonal protein synthesis that takes place by 2 h after stimulation. The peak of ribosonal RNA that occurs 8 h after isoproterenol was also abolished by ATA. Since the drug completely inhibits isoproterenol-stimulated DNA synthesis, these results suggest that the control of ribosome production may be involved in cell growth activation. In view of the finding that ATA first inerferes with the binding of adenylate-rich RNA to polysomes, it was suggested that the drug may act by preferentially inhibiting that fraction of protein synthesis dependent on the newly transcribed messenger RNA.

Aurintricarboxylic acid (ATA) and DNA synthesis. II. Effect of ATA on structure and function of the crypts of the small intestine.

ATA affects only slightly DNA synthesis of continuously replicating cells. A single injection of the drug reduces the incorporation of (3H)-thymidine into DNA of crypt cells to only 62% of the control. The effect on DNA synthesis is preceded by a slight inhibition of protein synthesis, and by a partial decrease in the number of dividing cells. On the contrary, the incorporation of (3H)-uridine into RNA was enhanced. Electron microscopic studies revealed no cytologic abnormalities in ATA-treated animals. In view of the fact that ATA at the same concentration inhibits DNA synthesis of growth stimulated cells to 100% (Novi, 1976), it was suggested that the drug may become an useful tool in inducing a preferential inhibition of growth stimulation.