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L Anselmi

Publications and source records attributed to L Anselmi.

At least 19 recordsLinked to original sources

Role of carbon monoxide in electrically induced non-adrenergic, non-cholinergic relaxations in the guinea-pig isolated whole trachea.

BACKGROUND AND PURPOSE: Nitric oxide (NO) and vasoactive intestinal peptide (VIP) are considered transmitters of non-adrenergic, non-cholinergic (NANC) relaxations in guinea-pig trachea, whereas the role of carbon monoxide (CO) is unknown. This study was designed to assess the participation of CO, and to investigate the localization of haem oxygenase-2 (HO-2), the CO-producing enzyme, in tracheal neurons. EXPERIMENTAL APPROACH: NANC responses to electrical field stimulation (EFS) at 3 and 10 Hz were evaluated in epithelium-free whole tracheal segments as intraluminal pressure changes. Drugs used were: L-nitroarginine methyl ester (L-NAME, 100 microM) to inhibit NO synthase (NOS), alpha-chymotrypsin (2 U ml(-1)) to inactivate VIP, zinc protoporphyrin-IX (ZnPP-IX, 10 microM) to inhibit HO-2, and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM), a soluble guanylyl cyclase inhibitor. For immunohistochemistry, tissues were exposed to antibodies to PGP 9.5, a general neuronal marker, HO-2 and NOS, and processed with an indirect immunofluorescence method. KEY RESULTS: alpha-Chymotrypsin did not affect NANC relaxations. ODQ inhibited NANC responses by about 60%, a value similar to that obtained by combining L-NAME and ZnPP-IX. The combination of ODQ, L-NAME and ZnPP-IX reduced the responses by 90%. Subpopulations of HO-2 positive neurons containing NOS were detected in tracheal sections. CONCLUSIONS AND IMPLICATIONS: In the guinea-pig trachea, NANC inhibitory responses at 3 and 10 Hz use NO and CO as main transmitters. Their participation is revealed following inhibition of NOS, HO-2 and soluble guanylyl cyclase. The involvement of CO as a relaxing transmitter paves the way for novel therapeutic approaches in the treatment of airway obstruction.

Animals↗

Metastatic breast cancer: an updating.

This article reports on recent advances on metastatic breast cancer. Detection, prognostic factors, predictors of response to therapy and therapy, with particular regard to targeted therapies, were examined. DETECTION: Unlike current guidelines that yet do not routinely recommend intensive clinical-instrumental post-operative follow-up of breast cancer patients, relatively large data collected in the last decades have shown that an intensive post-operative follow-up with 'dynamic evaluation' of a suitable tumour marker panel precedes a few months as average the clinical and/or instrumental sign of a pending relapse in most relapsed patients and largely limits the use of the common instrumental examinations. PROGNOSIS AND THERAPY PREDICTORS: Disease-free interval (DFI) 24 months and disease confined to bony skeleton are prognostic factors more often correlated with relatively poor or prolonged survival, respectively. Estrogen receptor (ER) expression in primary tumour and at the relapse correlates strongly with response to salvage hormone therapy and data from large trials showed that 38-59% of ER and/or PR+ post-menopausal patients had clinical benefit from first line tamoxifen or aromatase inhibitors. An inverse correlation of ER with epidermal growth factor receptor (EGFR) has been found. The co-expression of HER-2/neu and/or elevated serum HER-2/neu protein level were associated with a low rate and shorter duration of response of ER+ patients to first line hormone therapy. Accordingly, ER-EGFR- compared with ER-EGFR+ tumours are usually more responsive to endocrine therapy. High class III beta-tubulin expression or fall in insulin-like growth factor binding protein-3 (IGFBP-3) from baseline levels have been found to significantly predict resistance to chemotherapeutic agents. THERAPY: Liposomes as carrier of doxorubicin (Caelix, Evacet, Myocet) is one approach to decrease the anthracycline-related cardiac toxicity. Weekly paclitaxel or docetaxel and oral formulation of vinorelbine and 5-fluorouracil (5-FU) (capecitabine) provide new effective and well tolerated options that reach greater dose intensity and cumulative dose than with the conventional schedules. As to the so called 'tailored' or targeted therapies, the more potent and highly selective third generation of aromatase inhibitors (letrozole, anastrozole, exemestane) targeting ER+ tumours by estrogen deprivation, challenge tamoxifen as current standard first line therapy in postmenopausals. One pilot study showed that stimulation of cellular immunity by the addition of beta-interferon-interleukin-2 sequence in patients on clinical benefit on first line tamoxifen significantly prolonged median overall survival (OS) and duration of response compared to that observed in similar patients only treated with tamoxifen. Trastuzumab, a humanised monoclonal antibody to extracellular domain of HER-2, plus conventional chemotherapy has become a standard of care for women with overexpressing HER-2 tumours. Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor (VEGF) that in refractory metastatic breast cancer doubled the response rate of capecitabine although it did not affect survival. Finally, the so called 'oligometastatic' and a few stage IV diseases are conditions amenable to be rendered with no evidence of disease (NED) after local surgery and/or radiation. In both, as well as in complete responders to chemotherapy, minimal residual disease (m.r.d.) likely continues to be present. Recent data suggest that 'biological' therapy (immunomodulators and/or retinoids with or without hormone therapy), might be suitable to be successfully tested in these patients as maintenance treatment given soon after local intervention or chemotherapy.

Angiogenesis Inhibitors↗

Identification of galanin receptor 1 on excitatory motor neurons in the guinea pig ileum.

Exogenously administered galanin inhibits cholinergic transmission to the longitudinal muscle and reduces peristaltic efficiency in the guinea pig ileum with a mechanism partially mediated by galanin receptor 1 (GAL-R1). We investigated the effect of exogenous galanin 1-16, which has high affinity for GAL-R1, on the ascending excitatory reflex of the circular muscle elicited by radial distension in isolated segments of guinea pig ileum. We used a three-compartment bath that allows dissecting the ascending pathway into the oral (site of excitatory motor neurons), intermediate (site of ascending interneurons) and caudal compartment (site of intrinsic primary afferent neurons). Galanin 1-16 (0.3-3 micromol L(-1)) applied to the oral compartment inhibited in a concentration-dependent manner the ascending excitatory reflex elicited by the wall distension in the caudal compartment. This effect was antagonized by the GAL-R1 antagonist, RWJ-57408 (1 and 10 micromol L(-1)). By contrast, galanin 1-16 was ineffective when added to the intermediate or caudal compartment up to 3 micromol L(-1). GAL-R1 immunoreactive neurons did not contain neuron-specific nuclear protein, a marker for intrinsic primary afferent neurons. These findings indicate that GAL-R1s are present on motor neurons responsible for the ascending excitatory reflex, but not on ascending interneurons and intrinsic primary afferent neurons.

Animals↗

Oral low-dose cyclophosphamide in metastatic hormone refractory prostate cancer (MHRPC).

The chemotherapeutic approach to hormone-refractory metastatic prostate cancer (MHRPC) for a long time included only estramustine. Then, attempts have been made with other various agents as cyclophosphamide, vinblastine, etoposide, taxanes and carboplatinum. Although the new drugs and combinations have increased the response rate of MHRPC, they have had no impact on the natural history of MHRPC, which is about 1 year as median time of survival. After an occasional observation of prolonged response in a patient with MHRPC treated with a very well tolerated oral low-dose of cyclophosphamide, from February 1996 to October 2002, seven more patients with MHRPC and progressive disease were consecutively recruited. Response to treatment was evaluated by conventional radiological procedures and/or serial serum PSA measurements. The decline of PSA value was considered to assess the response consistent with the response guidelines from the prostate specific antigen-working group. All eight studied patients continuously received oral low dose cyclophosphamide until progression or the occurrence of significant toxicity. So far three patients (37.5%) progressed (PD), two (25%) showed PR and the three remaining SD. Response rate was 25%, and clinical benefit occurred in 62.5% of the studied patients. In the five patients with clinical benefit on cyclophosphamide median duration of clinical benefit, PR and SD were 9, 24+ and 8 months, respectively. In these five patients median overall survival times from cyclophosphamide and from the first regimen of chemotherapy were 17 and 33+ months respectively, while in the three patients with PD they were 4 and 13 months. The same interval times in patients with > or =50% decline of serum PSA were 29 and 50.5 months, while in those with <50% decline of the same marker, they were 13 and 32 months, respectively. Grade 2 or 3 neutropenia were observed in all the studied patients. In four (50%) of them pulmonary and urinary infections that were easily cured by the common antibiotics occurred. These data suggest that the metronomic use of cyclophosphamide, given alone, has similar or higher activity with lower toxicity than when administered with other active drugs. So it can be an useful option before or after the use of other single or combined potentially active chemotherapeutic agents.

Administration, Oral↗

Role of galanin receptor 1 in peristaltic activity in the guinea pig ileum.

Galanin effects are mediated by distinct receptors, galanin receptor 1 (GAL-R1), GAL-R2 and GAL-R3. Here, we analyzed 1) the role of GAL-R1 in cholinergic transmission and peristalsis in the guinea-pig ileum using longitudinal muscle-myenteric plexus preparations and intact segments of the ileum in organ bath, and 2) the distribution of GAL-R1 immunoreactivity in the myenteric plexus with immunohistochemistry and confocal microscopy. Galanin inhibited electrically stimulated contractions of longitudinal muscle-myenteric plexus preparations with a biphasic curve. Desensitization with 1 microM galanin suppressed the high potency phase of the curve, whereas the GAL-R1 antagonist, RWJ-57408 (1 microM), inhibited the low potency phase. Galanin (3 microM) reduced the longitudinal muscle contraction and the peak pressure, and decreased the compliance of the circular muscle. All these effects were antagonized by RWJ-57408 (1 or 10 microM). RWJ-57408 (10 microM) per se did not affect peristalsis parameters in normal conditions, nor when peristalsis efficiency was reduced by partial nicotinic transmission blockade with hexamethonium. In the myenteric plexus, GAL-R1 immunoreactivity was localized to neurons and to fibers projecting within the plexus and to the muscle. GAL-R1 was expressed mostly by cholinergic neurons and by some neurons containing vasoactive intestinal polypeptide or nitric oxide synthase. This study indicates that galanin inhibits cholinergic transmission to the longitudinal muscle via two separate receptors; GAL-R1 mediates the low potency phase. The reduced peristalsis efficiency could be explained by inhibition of the cholinergic drive, whereas the decreased compliance is probably due to inhibition of descending neurons and/or to the activation of an excitatory muscular receptor. Endogenous galanin does not appear to affect neuronal pathways subserving peristalsis in physiologic conditions via GAL-R1.

Acetylcholine↗

Role of galanin receptor 1 in gastric motility in rat.

Galanin actions are mediated by distinct galanin receptors (GAL-R), GAL-R1, -R2 and -R3. We investigated the role of GAL-R1 in gastric motility and the expression of GAL-R1 in the rat stomach. In vivo, in urethane-anaesthetized rats, galanin (equipotent for all GAL-Rs) induced a short inhibition of gastric motility, followed by increase in tonic and phasic gastric motility; the latter was significantly reduced by the GAL-R1 antagonist, RWJ-57408. Galanin 1-16 (high affinity for GAL-R1 and -R2) induced a long-lasting decrease of intragastric pressure, which was not modified by RWJ-57408. In vitro, galanin and galanin 1-16 induced increase of intragastric pressure that was not affected by RWJ-57408. Tetrodotoxin (TTX) did not suppress the galanin excitatory effect, whereas the effect of galanin 1-16 on gastric contraction was increased by TTX- or N-nitro-L-arginine, an inhibitor of nitric oxide synthase. GAL-R1 immunoreactivity was localized to cholinergic and tachykinergic neurons and to neurons immunoreactive for nitric oxide synthase or vasoactive intestinal polypeptide. This study suggests that an extrinsic GAL-R1 pathway mediates the galanin excitatory action, whereas an extrinsic, non GAL-R1 pathway is likely to mediate the galanin inhibitory effect in vivo. GAL-R1 intrinsic neurons do not appear to play a major role in the control of gastric motility.

Animals↗

5-HT4 receptors contribute to the motor stimulating effect of levosulpiride in the guinea-pig gastrointestinal tract.

BACKGROUND: The dopamine D2 receptor antagonist levosulpiride is a substituted benzamide derivative, whose gastrokinetic properties are exploited clinically for the management of functional dyspepsia. However, for other benzamide derivatives, such as cisapride and mosapride, agonism towards serotonin 5-HT4 receptors is considered the main mechanism leading to gastrointestinal prokinesia. AIMS: To assess whether levosulpiride is able to activate 5-HT4 receptors in the guinea-pig isolated gastrointestinal tract. MATERIALS AND METHODS: Circular muscle strips from gastric antrum, and colonic longitudinal muscle strips were used to detect electrically stimulated neurogenic contractions. The effect of levosulpiride was assessed in the absence and presence of GR125487, a selective 5-HT4 receptor antagonist. Furthermore, potential interaction of levosulpiride with 5-HT3 receptors and tissue cholinesterases was assessed in unstimulated ileal longitudinal muscle-myenteric plexus preparations. RESULTS: Antral and colonic strip contractions were cholinergic/tachykinergic in nature. Micromolar concentrations of levosulpiride potentiated submaximal responses, through a mechanism competitively antagonized by GR125487 (pKB=9.4). In LMMPs, levosulpiride slightly affected contractions caused by the 5-HT, receptor agonist 2-methyl-5-HT, and had no effect on contractions to exogenous acetylcholine. CONCLUSIONS: Our results indicate that levosulpiride acts as a moderate agonist at the 5-HT4 receptor. This property, together with antagonism at D2 receptors, may contribute to its gastrointestinal prokinetic effect.

Animals↗

Review of the implications of dietary tryptophan intake in patients with irritable bowel syndrome and psychiatric disorders.

In this review, we address the possible role of the essential amino acid L-tryptophan or its metabolic derivative 5-hydroxytryptophan in the modulation of serotonin (5-hydroxytryptamine) synthesis and thereby in affecting the pathophysiology of central and peripheral nervous system disorders, including depression and irritable bowel syndrome. L-Tryptophan may represent a link between apparently disparate functional disorders and is of interest for general gastroenterologists, neurogastroenterologists, and neurologists. On the basis of estimates showing that approximately 20% of patients with functional bowel disorders seeking care in referral centres have psychiatric comorbidity, we attempt to provide a conceptual framework for defining the possible role of L-tryptophan in this population.

5-Hydroxytryptophan↗

Long-term monitoring of cell-mediated immunity in disease-free breast cancer patients: a preliminary retrospective study.

In 102 N- and 44 N+ disease-free breast cancer patients, lymphocytic populations and skin reaction of delayed hypersensitivity (SRDH) were monitored up to 266 months after mastectomy to find out whether they were similar or different from control values. In two selected groups of 34 N- and 11 N+ breast cancer patients, the whole 10 year follow-up was divided into three subintervals, each of them lasting 40 months and the time course of lymphocytic populations was evaluated. In the 102 N- patients, mean CD4+, CD8+, CD3+ values were lower (P < 0.01, P < 0.001, P < 0.01, respectively) while CD4+/CD8+ ratio was higher (P < 0.05) than in controls. Fifteen N- breast cancer patients (16%) were anergic compared to 30(32%) of controls (P < 0.05). In the 34 selected N- breast cancer patients soon after mastectomy the mean value of CD4+, CD8+, CD3+ T subpopulations was lower (P < 0.01, P < 0.001, P < 0.01, respectively) than in controls. Successively their mean value increased so that in the last subinterval they were not or were only slightly lower (P n.s., P < 0.05, P < 0.05, respectively) than in controls. In the 44 N+ patients, mean CD4+, CD8+, CD3+ values were lower (P < 0.001, v < 0.05, P < 0.01, respectively) and CD19+ lymphocytes higher (P < 0.001) than in controls. Five N+ breast cancer patients (13%) were anergic compared to 32% of controls (P < 0.05). In the 11 selected N+ breast cancer patients soon after mastectomy, the mean value of CD4+, CD8+ T subpopulations and CD16+56+ cells was significantly lower (P < 0.001, P < 0.001, P < 0.01, respectively) than in controls. Successively their mean value constantly increased so that in the last subinterval, no or slight (P n.s., P < 0.05, P n.s., respectively) significant difference compared to controls occurred. The mean CD4+/CD8+ ratio value of N- patients was significantly higher than in controls. However in the last subinterval, the significance was lower than in the first one (P < 0.05 and P < 0.01, respectively). In the N+ patients, the mean value of CD4+/CD8+ ratio was constant, although not significantly, lower than in controls; however it progressively increased from the first to the last subinterval. Therefore the significance of the difference of the mean CD4+/CD8+ ratio between N- and N+ patients strongly decreased from the first to the last subinterval (P < 0.001 and P < 0.05, respectively). These data indicate that in breast cancer patients, following mastectomy, a significant activation of memory and CD4+ T cells and long-term decrease of the circulating immunocompetent CD4+, CD8+ and CD16+56+ cells occurs. The prolonged disease-free interval observed in the 34 N- and 11 N+ breast cancer patients can be correlated with the restoration of the normal state of cell-mediated immunity.

Adult↗

The role of tumour markers in improving the accuracy of conventional chest X-ray and liver echography in the post-operative detection of thoracic and liver metastases from breast cancer.

The aim of this retrospective study was to assess the value of a serum tumour marker panel in selecting from among the patients with equivocal chest X-ray (CXR) or liver echography (LE) those with thoracic or liver metastases respectively. Between January 1984 and December 1999, 467 (341 non-relapsed and 126 metastatic) breast cancer patients were followed-up postoperatively. Among the 126 metastatic patients 36 showed thoracic (19 patients) or liver (17 patients) metastases, alone or in conjunction with other organs as the first evidence of distant spread. We focused on this series of 377 patients including 341 non-relapsed plus 36 with liver or thoracic metastases. The patients were followed-up after mastectomy with serial determinations of a panel of CEA-TPA-CA15.3 tumour markers, bone scintigraphy, CXR and LE. Up to December 1999, equivocal CXR occurred in 23 (6.1%) patients of whom 11 (47.8%) developed thoracic metastases; 14 (3.7%) patients showed an equivocal LE of whom 5 developed liver metastases. In the 37 patients with equivocal CXR or equivocal LE prolonged clinical and imaging follow-up over 41 +/- 36 months (mean +/- SD, range 3-163) was used to ascertain the presence or absence of thoracic or liver metastases. In the 23 patients with equivocal CXR the negative and positive predictive values of the tumour marker panel to predict thoracic metastases were 92% and 100% respectively. In the 14 patients with equivocal LE the negative and positive predictive values of the tumour marker panel for prediction of liver metastases were 90% and 100% respectively. This study shows that in breast cancer patients the CEA-TPA-CA15.3 tumour marker panel has a high value for selecting those patients at high risk of developing clinically evident pulmonary or liver metastases from amongst those subjects with equivocal CXR or equivocal LE.

Adult↗

A multistep therapy with subcutaneous low dose recombinant interleukin-2, 5-fluorouracil and leucovorin prolongs the response of metastatic colorectal cancer patients: a pilot study.

Data from 12 metastatic colorectal cancer patients who were submitted to a pilot study with a multistep subcutaneous (sc) low dose recombinant interleukin-2 (rIL-2), 5-fluorouracil (5-FU) and leucovorin (LV) administration were compared with those from 13 historical controls who were comparable for the major prognostic indices. All 12 patients in the pilot study were subjected initially to six to eight courses of 5-FU-LV by endovenous (ev) bolus consistent with the Machover schedule alternating with 6 weeks of rIL-2 cycles. At the progression of metastatic disease, the patients were given 500 mg/m2 per day of 5-FU by continuous infusion (ci) for 5 days every 4 weeks and in case of further progression, 2,600 mg/m2 of 5-FU by 24-h ci once a week for 6 weeks. The control patients were treated with 5-FU-LV by the Machover schedule until progression and then observed. As yet, two patients in the pilot study and three control patients are currently alive. In the pilot study, the patients' response rate (CR + PR) and overall response rate (CR + PR + SD) were much higher than in the controls (50 vs 23% and 92 vs 54%, respectively). Time duration of response and survival from primary surgery were more prolonged in the pilot study than in the historical control, although not significantly (10.5 vs 6 and 41.5 vs 29 months, respectively). Time from starting therapy to progression and survival from relapse were significantly in favour of the pilot study (11.5 vs 4 and 31 vs 13.5 months; P < 0.01 and P < 0.05 unpaired t-test, respectively). Low dose s.c. rIL-2 cycles were well tolerated and no interruption occurred. In the pilot study sporadic grade 3 toxicity (diarrhoea or leucopenia) was responsible for the reduction of 5-FU doses to 80% of the previous infusion, but no treatment was postponed. In conclusion, these preliminary data suggest the opportunity to initiate large prospective randomized trials using a multistep therapy with rIL-2, 5-FU ci at conventional and at high dose in metastatic colorectal cancer.

Aged↗

Prolonged survival by 'early' salvage treatment of breast cancer patients: a retrospective 6-year study.

Between 1977 and 1993, 384 breast cancer patients were followed up post-operatively every 4 or 6 months with a serum tumour marker panel (CEA-TPA-CA15-3) and the usual imaging techniques. Twenty-eight patients were treated 13.5 +/- 10 months (mean +/- s.d.) before the clinical and/or radiological occurrence of distant metastases that were suspected because of an increase in the tumour markers (patients treated 'early'). Their outcome was compared with that of 22 similar patients who were treated only after a definite radiological diagnosis was achieved (patients treated 'not early'). The median survivals from mastectomy and salvage treatment were also compared for the two groups. The groups were similar for all the major prognostic factors (menopause, staging, hormone dependency). In the group treated 'early', the lead time from the tumour marker increase to the clinical and radiological signs of metastases was significantly longer than that of the group not treated 'early' (13.5 +/- 10 vs 3.4 +/- 2.8 months respectively; P < 0.001 by unpaired t-test). For patients treated 'early', the survival curves up to 30 months after salvage treatment and up to 72 months after mastectomy showed greater survival than those for the patients treated later (42.9% vs 13.6% and 42.9% vs 22.7% respectively; P = 0.04 in both instances). These data suggest that treatment triggered by rising tumour markers before clinical and/or radiological appearance of distant metastases can be useful in prolonging both the asymptomatic interval and the duration of response of some relapsed patients. Randomized prospective trials must be encouraged to confirm these data and to better evaluate the effect on the disease-free survival (DFS) and overall survival (OS) of 'early' salvage treatment protocols.

Adult↗

Immunological and side effects of low sc recombinant interleukin-2 dose in addition to conventional treatment in relapsed breast and colorectal cancer patients.

Thirteen relapsed cancer patients, four of them operated for colorectal and the nine remaining for breast cancer, were cyclically given low subcutaneous (sc) recombinant interleukin-2 (rIL-2) doses in addition to chemo- or hormone therapy. Cycle intervals were 2 or 6 weeks in length, and the number of cycles ranged from one to 14 and from one to six respectively. Tolerance assessed by clinical and laboratory data, eosinophils, lymphocytes (total number), T subpopulations, B lymphocytes and NK cells were the evaluated parameters. One (7.6%) of the 13 studied patients interrupted the first low dose sc rIL-2 cycle due to a hypersensitive reaction. This case showed relapse from breast cancer. During further cycles, three patients (25%), one operated on for colorectal and two others for breast cancer of the 12 remaining cases who completed all rIL-2 cycles showed an increase in glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), gamma-gt, and creatininemia without any clinical symptoms. A slight influenza-like syndrome and 10-20 mmHg decrease in blood pressure sporadically occurred in all patients under rIL-2 therapy. In both cancer types, a significant (P < 0.05 - P < 0.001) increase in lymphocytes, eosinophils. T4 and T3 subpopulations but not in T8 subpopulations and NK cells occurred at the end of the rIL-2 cycles. In 11 of the 13 patients responsive to conventional therapy, a highly significant increase (P < 0.001) in all parameters apart from B lymphocytes and T4/T8 ratio was observed, while in three cases which were no longer responsive and in another case which had never been responsive to conventional therapy, a slightly significant increase in eosinophils only occurred (P < 0.05). Three colorectal cancer patients showed a partial response and the last a complete response to conventional therapy. In these four patients, time to progression during rIL-2 cycles ranged from 2.5-5 months and the duration of response ranged from 8-19 months. In seven of the eight breast cancer patients who completed all rIL-2 cycles, the response ranged from 3-51+ months and in the last case, which was not responsive to conventional therapy, the disease progressed in spite of the addition of rIL-2. These data suggest that: a) rIL-2 is likely to constitute a well-tolerated and suitable home therapy even when cyclically given for a prolonged period; b) following rIL-2 administration, eosinophils and lymphocytes increase in addition to the T subpopulations.

Adult↗

Nitrous oxide is a potent cerebrovasodilator in humans when added to isoflurane. A transcranial Doppler study.

Nitrous oxide during neurosurgical procedures is almost always given in combination with either volatile or intravenous anesthetics. The modifying influence of such interventions has been studied clinically and in experimental settings; the reported findings, however, are inconsistent. The present study compares the cerebrovascular effects of MAC equivalent concentrations of isoflurane alone and isoflurane plus nitrous oxide. Twenty lumbar laminectomy patients randomized either to receive isoflurane or isoflurane plus nitrous oxide were investigated over a dose range from 0.5 to 1.5 MAC. A transcranial Doppler (TCD) ultrasonography device was used to measure cerebral blood flow velocity (CBFV) in the right middle cerebral artery (MCA) as an index of anesthetic-induced alterations in cerebral blood flow (CBF). A small but marginally significant decrease in CBFV at 1 MAC and no change at 1.5 MAC occurred in the isoflurane anesthetized patients. In contrast, a small but significant increase in CBFV at 1 MAC and a very significant increase at 1.5 MAC occurred in the isoflurane plus nitrous oxide anesthetized patients. Nitrous oxide added to an isoflurane anesthetic regimen is concluded to be a potent vasodilator. In addition, the vasodilating effects of nitrous oxide were not uniform; they progressively increased with an increasing isoflurane concentration.

Adult↗

Teaching fibreoptic intubation in anaesthetised patients.

One hundred ASA grade 1 and 2 patients requiring orotracheal intubation for various general surgical procedures were randomly assigned to receive either expert rigid laryngoscopic or novice fibreoptic orotracheal intubation under total intravenous anaesthesia. Five anaesthesia residents in the 4th year, with no prior experience in fibreoptic laryngoscopy, participated in a fibreoptic training course, viewing two instructional videos and practising on the intubation manikin. Each resident intubated 20 patients in a randomised fashion either as an expert laryngoscopist or as a fibreoptic novice. The time (SEM) to achieve successful intubation was statistically different for fibreoptic and rigid intubation (77.2 (5.1) s vs 17.7 (1.6) s, p < 0.01). The time to achieve successful rigid laryngoscopic intubation remained constant over the ten intubations, whereas time required for fibreoptic intubation decreases significantly (p < 0.01). The learning objectives (fibreoptic intubation times in 60 s or less and with 90% or greater success rate on the first intubation attempt) were met by all residents. The haemodynamic profile was similar for fibreoptically intubated and conventionally intubated patients and there was no difference between the first two or the last two fibreoptic or rigid intubations. The study was designed to detect a difference of 10% in means (assuming alpha = 0.05 and beta < or = 0.2). The incidence of postoperative sore throat, dysphagia or hoarseness was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Intrinsic endometriosis of the ureter. Clinical case].

Endometriosis is defined as the presence of endometrial tissue outside the cavity of the uterus. The urinary tract is rarely affected, only 1 to 11%. Bladder is the most frequent urinary localization while the ureteral involvement is rare. We report a case of intrinsic ureteral endometriosis in a woman with left hydronephrosis, lumbar pain and septic fever. Instrumental and laboratory investigations can hardly lead to a reliable diagnosis of ureteral endometriosis. A final diagnosis is feasible only by histologic examination, which obviously implies surgery.

Adult↗

[A case of acute voluntary poisoning with flecainide in a suicide attempt].

A case of acute poisoning caused by an overdose of flecainide (1.5 gr. per os), taken in order to commit suicide, is described here. With a plasmatic concentration of 5000 ng/ml the drug induced a soporose condition, shallow breathing with phases of apnea and intermittent muscular clonuses, a clinical picture of shock with a idioventricular rhythm at a rate of 40/min. and widening of the QRS (400 msec.). The infusion of orciprenaline and 5% glucose solution induced an increase in the ventricular frequency and the normalization of the circulatory condition. Twenty hours after ingestion sinus rhythm was restored. Highest therapeutic level of flecainide was reached 48 hours after ingestion. The stimulation threshold during the acute phase was 1.8 mA and came down 1.3 mA after wash-out. The outcome was favourable.

Adult↗