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Biomedical subjects

A Spinelli

Publications and source records attributed to A Spinelli.

At least 73 records · Page 4Linked to original sources

Control of breathing in patients with myasthenia gravis.

Control of breathing has seldom been investigated in patients with myasthenia gravis (MG). We evaluated lung volumes and respiratory muscle strength by measuring maximal inspiratory (MIP) and expiratory (MEP) pressures in 12 patients with moderate generalized (IIb) MG before and after an orally administered therapeutic dose (120 mg) of Mestinon, and in 11 age- and sex-matched normal subjects. Breathing pattern, mouth occlusion pressure (P0.1), and surface electromyographic activity of the diaphragm (EMGd) and intercostal (EMGint) muscles were evaluated during both room-air breathing and hypercapnic rebreathing. Before Mestinon, patients exhibited a slight decrease in VC, and normal TLC and FEV1/VC ratio. Compared with the normal control group, patients also exhibited respiratory muscle weakness (marked decrease in MIP and MEP; p less than 0.001 for both), and more rapid and shallower breathing (RSB): lower tidal volume (VT), inspiratory time (TI), expiratory time (TE), and greater respiratory frequency (f); mean inspiratory flow (VT/TI) and P0.1 were slightly supernormal, whereas both EMGd and EMGint were significantly higher in patients. During hypercapnic rebreathing, ventilation (VE) (p less than 0.001), VT (p less than 0.001), VT/TI, (p less than 0.003), P0.1 (p less than 0.003), and EMGd (p less than 0.001) response slopes to increasing PCO2 were found to be lower, whereas EMGint response slope was normal. At 60 mm Hg of PCO2 in the two groups the difference in terms of breathing pattern, P0.1, and EMGd were similar to that observed during room-air breathing. After Mestinon, VC (p less than 0.005), MIP (p less than 0.02), and MEP (p less than 0.01) significantly increased, whereas spontaneous breathing remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Delayed-action disopyramide in the treatment of hyperkinetic ventricular arrhythmia. A randomized clinical comparative study vs immediate-action disopyramide].

The authors report the results of an open randomized study to compare the efficacy of oral slow-release and immediate-release disopyramide, in the treatment of patients with chronic stable ventricular arrhythmias, evaluated with two Holter recordings. Twelve patients, selected after positive acute intravenous test, had been randomly assigned to slow-release (500 mg/day) and immediate-release (400 mg/day) disopyramide. Ten days later, a Holter recording was performed and then all patients were treated with slow-release disopyramide (500 mg/day); After one month drug efficacy has been evaluated by Holter recording. Total ectopic beats and arrhythmic Lown modified score were the end points. Immediate-release disopyramide significantly reduced both total beats and arrhythmic score; the slow-release formulation did not modify total beats and reduced the arrhythmic score, but only at the first Holter control. One month later there was no significant difference in arrhythmic score either. Low plasma drug levels could explain these results in some patients.

Aged↗

The effects of the Chernobyl explosion on induced abortion in Italy.

Four regression models have been fitted to data of the monthly number of induced abortions in Italy between January 1984 and April 1986, in order to predict the number which would have occurred in the 5 months following the Chernobyl explosion. In model I the average number of abortions per day in each month was the dependent variable and calendar months, a linear time trend and previous month's value were the independent variables. Model II included a quadratic time trend term in addition to the independent variables used in model I. Models III and IV were like models I and II except that the dependent variable was the average number of abortions per working day in each month and the effect of the previous month's value was omitted. The 4 models all implied that an excess number of abortions were performed in the 5 months following the Chernobyl accident. The mean daily excess was estimated to be 28 and 52 per day for models I and II and the mean excess per working day was estimated to be 20 and 30 by models III and IV, respectively. Clearly the estimated magnitude of the excess depends on whether the quadratic time trend is included among the explanatory variables, but these results imply that the excess is unlikely to be merely due to chance.

Abortion, Induced↗

Treatment of metastatic colorectal cancer by means of specific monoclonal antibodies conjugated with iodine-131: a phase II study.

Eighteen consecutive patients with advanced and/or metastatic colorectal carcinoma have been treated with intraperitoneal administration of radiolabelled (iodine-131) monoclonal antibodies raised against different antigens associated to these kinds of tumours: anti-CEA FO23C5, anti-CEA BW494/32, anti-TAG B72.3, AUA1. The doses of isotope ranged between 21 and 150 mCi (777-5550 MBq) which delivered a radiation dose to the target tumour from 768 to 4628 cGy. Thirteen patients were previously treated with conventional regimens which consisted of chemotherapy (5-fluoracil with or without other anti-neoplastic drugs) both in adjuvant or palliative setting. Three patients are considered non-evaluable owing to concomitant chemotherapy in 2 and lack of objective parameters in 1. Out of 15 evaluable patients 2 achieved complete remission and 2 partial remission with a response rate of 26.6%. Three stable and 8 with progressive disease have also been registered. The toxicity was negligible consisting of hematologic WHO grade 1 in 7 patients, grade 2 in 1 patient and grade 3 in 1 patient, as well as hepatic WHO grade 1 in 8 and grade 2 in 2 patients. The authors conclude that this innovative way of treatment for advanced colorectal carcinoma seems to offer promising therapy; from these data, therefore, a new trial is justified employing radiolabelled MoAbs in well selected patients with metastatic or locally advanced colorectal carcinoma.

Adenocarcinoma↗

Control of breathing in patients with chronic pulmonary obstructive disease: response to bamiphylline.

In two groups (A and B) of patients with severe chronic obstructive pulmonary disease (COPD), matched for age and routine pulmonary function testing, we evaluated inspiratory muscle strength (MIP), breathing pattern, mouth occlusion pressure (P0.1), inspiratory neural drive, assessed in terms of electromyographic activity of both diaphragm (EMGd) and intercostal (EMGint) muscles, and P0.1/EMGd ratio, an index of inspiratory neuromuscular coupling. Group A (8 patients) was studied before and after a 7-day period of a new oral xanthine derivative (bamiphylline, 1.2 g daily), and group B (7 patients) was given a placebo. Under control conditions, compared with an age-matched normal control group, groups A and B both exhibited a decrease in MIP, more rapid (increase in respiratory frequency RF) and shallower (decrease in tidal volume; VT) breathing (RSB), a marked increase in both EMGd and EMGint and a lower P0.1/EMGd ratio. With bamiphylline FEV1 and PaO2 significantly increased, while a substantial increase in MIP was found in 5 out of the 8 patients. VT and inspiratory time (Ti) also significantly increased, and RF decreased. Both EMGd and EMGint significantly decreased, whereas P0.1/EMGd exhibited a substantial increase in 5 out of the 8 patients. Conversely, no significant changes were observed in group B during the study period. From these data we conclude that in patients with COPD, clinical manifestations, probably associated with inspiratory muscle overloading (decrease in muscle strength, RSB, increase in respiratory neural drive, and derangement in neuromuscular coupling) may benefit from a short-term treatment with bamiphylline.

Aged↗

[Syncope due to sinus arrest secondary to marked vagal hypertonus. The role of permanent atrial stimulation in revealing associated atrioventricular node involvement].

The authors report a case of a 42-year-old man, with relapsing syncope, related to sinus arrest, documented by Holter recording. The clinical investigation, the electrophysiological study with autonomic blockade included, have proved normal and then an AAI pacemaker has been implanted. Some weeks later, the patient reported a lipothymic episode; a Holter recording showed a second degree AV block, with normal pacemaker function. A DDD pacemaker has been implanted and in the next ten months the patient felt well. The sinus arrest physiopathology, the role of the autonomic nervous system and the correct electrostimulation mode have been discussed.

Adult↗

General anaesthesia, a risk factor for complication following induced abortion?

Of the 10,000 abortions performed at the Regional hospital at Modena in Italy between 1982 and 1986, 199 (2%) led to early complications. Investigation of the relationship between the risk of haemorrhage, injury, other complications and all complications and eight explanatory variables revealed that the adjusted odds ratio associated with the use of general anaesthetic compared with local anaesthetic was 4.6 (95% CI, 2.2-9.5) for haemorrhage, 1.3 (95% CI, 0.78-2.2) for injury, 1.6 (95% CI, 1.0-2.6) for other complications and 1.8 (95% CI, 1.4-2.5) for all complications. It is speculated that if the relationship between use of general anaesthetic and risk of complication is causal there could be about 40% fewer cases of complications and 75% fewer cases of haemorrhage following induced abortion if local anaesthesia were used rather than general anaesthesia.

Abortion, Induced↗

Inspiratory muscle strength and respiratory drive in patients with rheumatoid arthritis.

In 15 patients with rheumatoid arthritis (RA) and in 12 age- and sex-matched normal subjects, we evaluated inspiratory muscle strength and respiratory control system. Inspiratory muscle strength was assessed by measuring maximal inspiratory pressure (MIP). Respiratory drive was assessed by evaluating surface electromyographic activity of the diaphragm (EMGd) during both room-air breathing and hypercapnic rebreathing. Compared to the predicted value (mean +/- 1.65 SD), MIP was significantly reduced in nine patients (60%). All told, we noticed a significant inverse relationship in the patients between MIP and duration of steroid therapy (p less than 0.01). During room-air breathing, both EMGd and mouth occlusion pressure (P0.1), expressed both in actual values and as percentage of MIP, were significantly greater in patients than in the normal control group (p less than 0.001 for both). Both EMGd and P0.1 (%MIP) response slopes to CO2 were significantly greater in patients than in the normal control group (p less than 0.01 and p less than 0.001, respectively) and significantly related to the functional stage of disease. During quiet breathing and for a PETCO2 of 60 mm Hg, both EMGd (p less than 0.01 and p less than 0.05, respectively) and P0.1 (%MIP) (p less than 0.01 and p = 0.001, respectively) were inversely related to MIP. These results indicate that RA patients may exhibit inspiratory muscle weakness and increased respiratory drive. Steroid myopathy and rheumatoid myositis could explain the reduction in MIP, whereas neural afferents arising from respiratory muscle, lung, or joint receptors could be involved in the observed increase in neural drive.

Arthritis, Rheumatoid↗

Changes in ventilatory muscle function with negative pressure ventilation in patients with severe COPD.

Patients with severe COPD may be in a state of ventilatory muscle (VM) fatigue. In these patients, rapid and shallow breathing has been hypothesized to be a compensatory mechanism that prevents more severe fatigue from taking place. To test these hypotheses, we studied the effects of VM resting in a group of patients with severe COPD. Eleven clinically stable patients with COPD and chronic hypercapnia were studied. Six of them (group A) had a seven-day period of negative pressure-assisted ventilation (NPV), and five (group B) with similar functional characteristics served as a control group. Compared with a normal age-matched control group, both A and B groups exhibited significantly lower tidal volume (VT), inspiratory time (TI), total time of the respiratory cycle (Ttot) and Ti/Ttot ratio, decrease in muscle strength, and greater electromyographic activity of diaphragm (EMGd) and parasternal muscles, but similar ventilation and VT/TI. After the study period, group A exhibited significant increase in VT, Ti, and TI/Ttot (p less than 0.05), and decrease in PaCO2 (p less than 0.05), EMGd, and EMGint (p less than 0.05 for both), and a slight but significant increase in maximal inspiratory pressure (MIP) (p less than 0.05). These data suggest that NPV rests VM, increases their strength, and reduces hypercapnia in patients with severe COPD.

Aged↗

Neural respiratory drive and neuromuscular coupling in patients with chronic obstructive pulmonary disease (COPD).

In 15 spontaneously breathing patients with chronic obstructive pulmonary disease (COPD) divided into two groups, one with normocapnia (A) and one with chronic hypercapnia (B), we evaluated the maximal voluntary inspiratory muscle strength (MIP), the pattern of breathing, the mouth occlusion pressure (Po.1), the neural respiratory drive (NRD), assessed by surface electromyographic (EMG) activity of the diaphragm (EMGd) and EMG activity of intercostal muscles (EMGint), and the chest wall neuromuscular coupling, assessed in terms of Po.1/EMGd ratio. Compared with an age-matched normal control group, both A and B groups exhibited lower MIP, significantly greater EMGd and EMGint, and lower Po.1/EMGd ratio. However, a similar pattern, along with a rapid and shallow breathing, differentiated group B from group A. In group B we found a significant direct relationship between Po.1/EMGd ratio and MIP, and an inverse relationship between PaCO2 and Po.1/EMGd ratio. These data seem to indicate the following: (1) EMG is a more precise method than Po.1 in assessing the magnitude of the NRD; (2) NRD is increased in these patients; and (3) clinical manifestations probably associated with inspiratory muscle fatigue (marked decrease in muscle strength, rapid and shallow breathing, and alveolar hypoventilation) may be accompanied by a greater NRD and a more marked derangement in chest wall neuromuscular coupling in COPD.

Aged↗

Cellular basis of allograft rejection in vivo. V. Examination of the mechanisms responsible for the differing efficacy of monoclonal antibody to CD4+ T cell subsets in low- and high-responder rat strains.

MRC OX35, an anti-CD4 mAb, was used to treat high responder Wistar Furth (W/F) (RT1u) and low responder DA (RT1a) rats which had been grafted with directly vascularized hearts from PVG (RT1c) rats across a full MHC plus non-MHC incompatibility. Four doses of mAb at 7 mg/kg given in the first 2 wk postgrafting induced indefinite graft survival (greater than 150 days) in DA hosts, but only delayed rejection to 18 to 42 days in W/F as compared to rejection times of 6 to 8 days in untreated rats. The extension of MRC OX35 treatment to 6 wk in W/F rats induced indefinite graft survival in three of six rats. During treatment MRC OX35 therapy only partially depleted CD4+ cells, and all circulating CD4+ cells were coated with MRC OX35. The capacity of naive CD4+ and CD8+ cells from W/F and DA to be activated to PVG alloantigen was compared both in vitro in an MLC assay and in vivo by an adoptive transfer assay of their capacity to restore rejection of PVG heart grafts in irradiated syngeneic hosts. CD4+ cells from both W/F and DA proliferated in MLC and restored graft rejection. W/F CD8+ cells both proliferated in MLC and restored rejection, but DA CD8+ cells neither proliferated nor reconstituted rejection. Examination of lymphocytes from MRC OX35 treated hosts with long-surviving grafts showed that they were neither depleted of CD4+ T cells nor did they lack the capacity to proliferate to PVG Ag in MLC, this response being similar to that to third-party Ag or by naive lymphocytes. Compared to first-set rejection, PVG skin graft rejection was delayed 2 to 3 days in W/F and 10 to 12 days in DA rats with long-surviving grafts after MRC OX35 therapy, whereas they rejected third-party skin grafts in first-set tempo. These studies show that differences in graft survival in anti-CD4 treated low and high responder strains may be due to the inherent capacity of CD8+ cells to be activated to effect rejection independent of CD4+ cells in W/F but not in DA. In those hosts that accept grafts, there is no evidence of clonal deletion, but there appears to be a form of unresponsiveness akin to that induced in adult rats by other immunosuppressive therapies that protects the graft from rejection.

Animals↗

Mechanisms maintaining antibody-induced enhancement of allografts. II. Mediation of specific suppression by short lived CD4+ T cells.

In DA rats grafted with PVG hearts, the injection of 1 ml of Wistar-Furth x DA)F1 anti-PVG serum on the day of grafting prevents rejection and induces a state of specific unresponsiveness. An adoptive transfer assay was used to test the capacity of T cell subsets, taken from rats given enhancing serum, to either restore rejection or to transfer unresponsiveness to syngeneic hosts irradiated with 9 Gy and grafted with donor (PVG) or third party (Wistar-Furth) hearts. W3/25+ (CD4+) cells from these animals retained some capacity to restore rejection until 50 days posttransplant, after which they invariably failed to restore PVG graft rejection but retained the capacity to effect Wistar-Furth rejection. At this time CD4+ cells were also capable of inhibiting naive but not specifically sensitized CD4+ cells capacity to restore PVG graft rejection in irradiated hosts. The development of CD4+ suppressor cells was concurrent with the appearance of clinically evident unresponsiveness in the host. MRC Ox8+ (CD8+) cells from enhanced rats when mixed with naive CD4+ cells delayed rejection in adoptive recipients but did not reestablish unresponsiveness. Paradoxically, the CD4+ cells that transfer unresponsiveness to the adoptive host proliferate such as normal cells in MLC to both donor and third party alloantigen. Unfractionated cells, CD4+ or CD8+ cells did not proliferate to relevant idiotype in vitro. The CD4+ cells after 3 days in culture, with either alloantigen or idiotype-bearing stimulator cells, lost their capacity to suppress in the adoptive transfer assay. The maintenance of specific unresponsiveness was thus shown to be due to a CD4+ suppressor T cell whose function was lost in culture, and therefore could not be detected in MLC or idiotype assays.

Adjuvants, Immunologic↗

Control of breathing in patients with short-term primary hypothyroidism.

In 8 patients (3 men and 5 women) with short-term primary hypothyroidism before and during replacement therapy, and in an age-matched control group (9 men and 7 women), we assessed maximal inspiratory muscle force (Pimax) and the ventilatory control system at neural (EMG), muscular (P0.1), and ventilatory (VE and Vt/Ti) levels. While hypothyroid, patients exhibited a significantly lower Pimax. During a CO2 rebreathing test, hypothyroid patients exhibited similar diaphragmatic electromyographic (EMGd) and ventilatory (VE) response slopes to increasing end-tidal CO2 tension (delta EMGd/delta Pet CO2 and delta VE/delta PetCO2), but significantly less delta P0.1/delta PetCO2 (p less than 0.05) and delta(Vt/Ti)/delta PetCO2 (p less than 0.05) response slopes. During replacement therapy with L-triiodothyronine (L-T3), Pimax (p less than 0.05), delta P0.1/delta PetCO2, and delta(Vt/Ti)/delta PetCO2 response slopes were found to be significantly increased (p less than 0.05 for both) while neither EMGd nor VE response changed significantly. We concluded that short-term hypothyroidism does not seem to be associated with blunted neural inspiratory output (EMGd), the respiratory control system seems to be affected mostly at a peripheral (muscular) level, and L-T3 increases both force (P0.1 and Pimax) and velocity (Vt/Ti) of inspiratory muscle contraction.

Adult↗

Locoregional immunotherapy of human ovarian cancer: preliminary results.

Ten patients with advanced ovarian carcinoma (5 in FIGO stage III and 5 in stage IV), following the failure of repeated chemotherapy courses, were submitted to i.p. radioimmunotherapy (RIT). Several antibodies (HMFG1, HMFG2, H17E2, B72.3) were employed. The antibody choice was made on the basis both of immunohistochemistry and immunoscintigraphy results. The mean dose administered in each single course was 17 mg, 3 patients underwent two treatments and 2 patients were injected three times. The isotope employed was 131I (mean dose 92 mCi). The early or late untoward effects were negligible. All patients developed anti-mouse antibodies (HAMA) which reduced, during the further RIT, the MoAbs' effective half-life. The estimated radiation dose delivered to the tumour ranged from 2910 to 11,000 cGy. Both wholebody and liver radiation burden resulted in tolerable limits while the thyroid irradiation was high. In 3 patients the RIT result was ineffective; in 2 cases a temporary ascitis staunch was obtained. In 2 cases the tumour growth was slower than expected and in 3 patients instrumental evidence of partial tumour reduction, still lasting after 4-11 months, was observed.

Antibodies, Monoclonal↗

Neural respiratory drive and neuromuscular coupling during CO2 rebreathing in patients with chronic interstitial lung disease.

In 12 patients with CILD and 18 age-matched normal subjects we assessed the ventilatory control system at three levels: (a) neural, as assessed by EMGd (XP/Ti) and EMGint muscles via surface electrodes; (b) muscular, as assessed by mouth occlusion pressure (P0.1); and (c) ventilatory, as assessed by both ventilation (VE) and the related parameters, tidal volume (VT) and respiratory frequency (f). Compared with a normal control group, patients exhibited a significant decrease in lung volumes and in MIP; VT and inspiratory time (Ti) were significantly lower, while VT/Ti, P0.1, and both EMGd and EMGint were significantly greater in patients. During a CO2 rebreathing test, patients exhibited significantly greater EMGd, EMGint, and P0.1 responses to increasing PETCO2 than the control group. VE response slopes were similar in the two groups. For a given EMGd response slope (delta XP/Ti/delta PETCO2), the average P0.1 response slope (delta P0.1/delta PETCO2) was found to be significantly lower in patients than in the normal control group. Compared with normal subjects, CILD patients have a normal or increased neural component of respiratory activity and relatively low neuromuscular coupling (delta P0.1/delta XP/Ti). The decreased neuromuscular coupling could be explained in these patients by a reduced inspiratory muscle strength.

Aged↗