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Biomedical subjects

M Malerba

Publications and source records attributed to M Malerba.

At least 55 records · Page 3Linked to original sources

[Respiratory effects of antihypertensive agents acting on alpha adrenergic receptors].

There are several factors involved in the bronchial muscle tone regulation, such as biochemical, nervous and humoral mechanisms. In general, in chronic obstructive bronchopneumopathy there is a reduction in air flow, due to different physiopathologic factors which, alone or combined, produce these disorders. In particular, according to suggestive hypotheses, it seems that asthma is due to a partial or complete block of beta-receptors with a prevalence of alpha-receptors and subsequent bronchial hypertonicity and hyperactivity, while in patients with allergic asthma a deficiency of beta-2-adrenergic system and an hyperresponsiveness of alpha-adrenergic and/or cholinergic system have been suggested. In relation to this part, alpha-1 antagonist drugs demonstrated to have a bronchodilator effect, thanks to their mechanism of action. Examples of this class of drugs are prazosin, indoramin, and an analogous of prazosin, doxazosin, which has a high antagonist and selective action for post-synaptic alpha-1 adrenergic receptors and a longer half-life. Several and recent observations show that these drugs do not interfere with the respiratory function principal parameters, both in healthy and in asthmatic or chronic bronchopathy subjects, but produce an appreciable improvement of these parameters. Presynaptic alpha-2-adrenergic receptors agonist drugs would mainly act by inhibiting the central nervous system, with a subsequent lower stimulation of post-synaptic alpha-1-adrenergic receptors. Examples of this class of drugs are clonidine, rilmenidine and guanabenz (but, in this case, the effects on the respiratory function are more controversial).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

Acute ventilatory and gas-exchange effects of a new beta-2 agonist, broxaterol, in asthmatics.

The ventilatory and gas-exchange effects of broxaterol, a new selective beta 2-adrenoceptor agonist, were investigated in ten asthmatics following intravenous administration of a single dose of 200 mcg. Broxaterol elicited a prompt and marked bronchodilating effect (increase in forced expiratory volume in one second and specific conductance), maintained at least up to the sixtieth minute. Minute ventilation and the mean expiratory flow did not increase significantly, the pattern of breathing showing a reduction of expiratory time, without modification of inspiratory time. On the other hand, occlusion pressure did not show any significant rise at all times of observation. Furthermore, the partial arterial oxygen and carbon dioxide pressures and alveolar-arterial difference in oxygen and physiological dead space remained unchanged, when measured at 20 min. The results demonstrated that broxaterol was an effective bronchodilating agent, also when rapidly injected, causing a prompt relief of bronchospasm. With respect to other beta 2-adrenoceptor agonists, this compound did not appear to increase minute ventilation or to induce an impairment of ventilation/perfusion ratio, at least after 20 min, when the bronchodilation was still evident. Finally, no side-effects or alterations of heart rate or blood pressure were reported.

Adrenergic beta-Agonists↗

[9 cases of early gastric cancer disclosed on chronic ulcer with or without complications].

The authors report their experience on 9 cases of early gastric cancer developed on a peptic ulcer border. They outline the paradoxical providence of the complications (hemorrhage and perforation) leading to cancer recognition as a focus in the benign ulcer. Therapeutic management of the occasionally discovered cancer on the peptic ulcer border is also discussed.

Aged↗

Antihypertensive efficacy and tolerability of captopril in the elderly: comparison with hydrochlorothiazide and placebo in a multicentre, double-blind study.

In this study we compared the antihypertensive efficacy and tolerability of captopril at 25 mg twice daily, hydrochlorothiazide (HCTZ), 12.5 mg twice daily and placebo in a multicentre, double-blind, randomized study that included 152 essential hypertensive patients (77 males, 75 females, 87 WHO stage I, 65 WHO stage II, aged 69 +/- 4 years, mean +/- s.d.). Supine and standing blood pressure were similarly reduced by captopril and HCTZ (P less than 0.01 for both compared with placebo). The heart rate did not change. Captopril (25-30 mg twice daily) and HCTZ (12.5 mg twice daily), alone or in combination, maintained their antihypertensive effect during a 24-week single-blind follow-up study. During the follow-up, diastolic blood pressure remained less than 100 mmHg in seven essential hypertensives on placebo, in 45 on captopril and in 25 on HCTZ. Side effects were observed in seven essential hypertensives during placebo (treatment withdrawn in two), in eight during HCTZ and in three during captopril. Serum potassium was reduced (P less than 0.05) and uric acid was increased (P less than 0.01) only during HCTZ. We conclude that captopril and HCTZ have similar antihypertensive efficacy in the elderly; however, captopril appears to be better tolerated.

Aged↗

Renal noradrenergic and dopaminergic activity in patients with borderline essential hypertension.

An opposite modulatory influence of renal noradrenergic and dopaminergic activities on sodium excretion has been suggested. In this study urinary noradrenaline (UNA) and dopamine (UDA) excretion were evaluated in patients with borderline essential hypertension (BH; n = 9) and in patients with established essential hypertension (EH; n = 11) as well as in normal subjects (NT, n = 8), during normal sodium and potassium intake. Measurements were performed on fractionated urine collections on two separate days: on the first day under basal conditions and on the second day after saline infusion (SAL), 2L/2h, i.v. In BH, basal UNA and UDA were higher with respect to NT and EH. The difference was significant (p less than 0.05) in urine collected between 8 and 14 h. In all three groups, SAL induced a significant decrease in UNA and a significant increase in UDA; the decrease in UNA after SAL was significantly lower in EH in respect to BH and NT. In conclusion, the increased UDA in BH may represent a compensatory mechanism to a defect in sodium excretion, possibly due to elevated renal and/or systemic noradrenergic activity; the normal response to volume and salt loading suggests that the physiological modulation of sympathetic tone is still preserved in BH.

Adult↗

Structured versus long-chain triglycerides: a safety, tolerance, and efficacy randomized study in colorectal surgical patients.

BACKGROUND: After trauma or surgery, researchers have suggested that medium-chain triglycerides have metabolic advantages, although they are toxic in large doses. To try to reduce this potential toxicity, structured lipids, which provide a higher oxidation rate, faster clearance from blood, improved nitrogen balance, and less accumulation in the reticuloendothelial system, could be used. Therefore, we evaluated, through a blind randomized study, the safety, tolerance, and efficacy of structured triglycerides, compared with long-chain triglycerides (LCT), in patients undergoing colorectal surgery. METHODS: Nineteen patients were randomized to receive long-chain or structured triglycerides as a lipid source. They received the same amount of calories (27.2/kg/d), glucose (4 g/kg/d), protein (0.2 g/kg/d), and lipids (11.2 kcal/kg/d). Patients were evaluated during and after the treatment for clinical and laboratory variables, daily and cumulative nitrogen balance, urinary excretion of 3-methyl-histidine, and urinary 3-methylhistidine/creatinine ratio. RESULTS: No adverse effect that required the interruption of the treatment was observed. Triglyceride levels and clinical and laboratory variables were similar in the two groups. A predominantly positive nitrogen balance was observed from day 2 until day 5 in the LCT group and from day 1 until day 4 in the structured triglycerides group. The cumulative nitrogen balance (in grams) for days 1 to 3 was 9.7+/-5.2 in the experimental group and 4.4+/-11.8 in the control group (p = .2). For days 1 to 5 it was 10.7+/-10.5 and 6.5+/-17.9 (p = .05), respectively. The excretion of 3-methylhistidine was higher in the control group but decreased in the following days and was similar to the experimental group on day 5. CONCLUSIONS: This study represents the first report in which structured triglycerides are administered in postoperative patients to evaluate safety, tolerance, and efficacy. It suggests that Fe73403 is safe, well tolerated, and efficacious in terms of nitrogen balance when compared with LCT emulsion.

Colitis, Ulcerative↗

Survival in early gastric cancer: multivariate analysis on 72 consecutive cases.

BACKGROUND/AIMS: Few reports from the Western hemisphere have investigated the impact of pathological features and surgical modalities on the prognosis of patients affected by early gastric cancer (EGC). In particular, the extent of lymphadenectomy (limited vs. extended) and the type of gastric resection (subtotal vs. total) remain controversial issues in the management of EGC. The aim of this study was to identify factors influencing prognosis in patients affected by EGC. METHODOLOGY: Hospital records and pathological specimens of 72 patients with EGC undergoing resective surgery during the period 1981-1995 were retrospectively reviewed. Patient status was determined by follow-up examination or by telephone contact. Univariate and multivariate analysis was used to calculate the 5-year survival probabilities with respect to the following variables: age (< or = 65, > 65), sex, depth of invasion (mucosal, submucosal) tumor location (upper, middle and lower third), gross appearance (type I, type II and type III), size (< or = 1.5 cm, > 1.5 cm), presence or absence of lymph node metastasis, histological type (intestinal, diffuse), extent of lymphadenectomy (limited or extended), and type of gastrectomy (total or distal subtotal). Survival was the outcome variable studied. RESULTS: Multivariate logistic regression analysis showed that age, nodal involvement and depth of invasion were independently associated with poor survival. CONCLUSIONS: Results showed a significant dominance of host- and tumor-related factors over the type of surgical procedure on prognosis of EGC patients.

Adult↗

[Severe alpha 1-antitrypsin deficiency: cross sectional clinical study].

The aim of this study was to investigate a group of severe alpha 1-antitrypsin deficient subjects. Of the 20 subjects detected, 7 were classified as Index Cases (discovered because they were symptomatic and had pulmonary emphysema or liver disease), while 13 were classified as Non-Index Cases (asymptomatic and discovered because they were relatives of Index Cases or because of the absence of alpha 1 band in serum electrophoresis). They underwent pulmonary function tests, determination of arterial blood gases, lung high resolution computed tomography and lung perfusion scan. All Index Cases were with the ZZ phenotype, indicating a major risk of developing related pulmonary emphysema or liver disease; most Index Cases (71%) were ex-smokers, while among the Non-Index Cases, 46% were smokers or ex-smokers, suggesting that smoking might be the main cofactor in the development of emphysema. Index Cases were older (statistical significance) and mostly male as compared with Non-Index Cases. A statistical significance was observed between the two groups for several lung function parameters (forced expiratory volume in one second, Tiffenau index, residual volume, diffusing capacity of the lung for carbon monoxide, arterial oxygen tension) as a result of a pathological impairment in Index Cases. This underdiagnosed condition merits more attention in order to prevent its complications and to get a better understanding about its diagnosis and management.

Adult↗

[Alpha 1-antitrypsin deficiency: the Brescia clinical study].

In a longitudinal clinical study, two hundred subjects have been evaluated in order to identify alpha 1-antitrypsin deficiency patients. According to their serum alpha 1-antitrypsin levels, they have been divided into three groups: 25 patients with severe deficiency (with both pathological alleles--ZZ, SZ or Z and rare deficiency allele--and, if clinically suggested, to be treated with augmentation therapy), 92 patients with intermediate deficiency (with one pathological allele, to be followed up in order to evaluate the risk to develop deficiency related disease) and 63 healthy subjects (normal alleles MM). They performed lung function test (including cardiopulmonary exercise test and methacholine bronchial challenge) chest X-ray and high resolution computed tomography, blood tests. Severe deficiency patients also performed perfusional lung scan to detect early disorders of blood flow, evaluation of arterial blood gases and liver echotomography. Expiratory flow limitation, the prevalence of vascular disease, the amount of urine elastin products and correlations between the amount of nitric oxide exhaled and bronchial hyperresponsiveness have been also investigated. The study showed that in Brescia county the deficiency is more common than expected and that evaluation of liver and vessels might be as useful as lung function tests. In addition, beneficial effect on local system has been observed. The longitudinal study might permit to detect early organ damage and to eliminate additive risk factors.

Adolescent↗

[A rare case of nerve-sheath sarcoma with rhabdomyoblastic differentiation (malignant triton tumor)].

Malignant peripheral nerve sheath tumors (MPNST) are spindle-cell sarcomas that appear in a setting of neurofibroma or schwannoma or are associated with peripheral nerves or demonstrate nerve sheath differentiation. Malignant triton tumor (MTT) is a subtype of MPNST that also contain tissue with skeletal muscle differentiation (embryonal, plemorphic and botryoid rhabdomyosarcoma). The estimated incidence of MPNSTs in patients with NF1 is 2-5% compared with 0.0001% in the general population and approximately 69% of the reported cases of MTT are associated with von Recklinghausen disease. In July 2002 a 37-year old man was readmitted to the Department of Oncologic Surgery of the S. Camillo-Forlanini Hospital in Rome for both a right-sided retroperitoneal paravertebral not palpable mass, incidentally detected at a follow-up MRI, and a left-sided popliteal mass, discovered at clinical evaluation. Seventeen months before, when the patient underwent surgery at the same Department for both a left-sided paravertebral inferior mediastinal neurofibroma and a right-sided axillary neurofibroma, diagnosis of von Recklinghausen disease (NF1) was made, according to the criteria established by the NIH Consensus Development. Conference on Neurofibromatosis of 1987. A xifopubic laparotomy was performed: the tumor appeared to be localized, well-capsulated and strictly associated to the lumbar and sacral nervous radicles (L4, L5, S1) without evidence of invasion. The tumor was completely resected with sparing of the psoas muscle and the lumbar plexus through a subperineural dissection technique. No intra-operative pathologic examination was performed. Postoperative pathologic findings showed evidence for a trition tumor. The popliteal mass was resected too and resulted to be a neurofibroma just like the tumors resected 17 months before when diagnosis of von Recklinghausen disease was made. The patient was disease free 6 months after initial surgery. Sarcoma arising in anatomic site other than extremity and superficial trunk are often more difficult to control because of anatomic constraints, delayed disease presentation, proximity to neurovascular and osseous structures and toxicity for normal adjacent tissues that limits the use of adequate radiation doses. Indeed, the anatomic site is an important prognostic factor in STS and the prognosis for retroperitoneal tumors is considerably worse than for extremity tumors. Reported local recurrence rates for retroperitoneal sarcomas range from 40% to 80% and, in marked contrast to extremity STS, most of patients can and do die from local recurrence in the absence of metastasis. In contrast to the benefit most patients with high grade soft tissue sarcomas of the extremities receive from adjuvant radiation and chemotherapy, these modalities have been of little value for retroperitoneal tumors. To overcome the problem of dose limitation, intraoperative electron beam radiotherapy (IORT) in combination with ERBT has been proposed. IORT plus ERBT was found to improve local control of disease in recent clinical trials. Current chemotherapy for retroperitoneal sarcomas is ineffective. Local adjuvant therapy such as intraperitoneal chemotherapy or experimental immunotherapy seems to be attractive in theory, but needs further investigations through prospective randomized multicentric trials. In conclusion, to date aggressive surgical management remains the most effective modality for selected primary and recurrent retroperitoneal soft tissue sarcomas including MPNSTs and the subtype MTT. Patients with incomplete resection and other risk factors such as younger age and high grade tumors may be suitable candidates for investigational adjuvant therapy.

Adult↗

[Surgical resection of gastrointestinal stromal tumor after treatment with imatinib: clinical case].

The stromal tumor is the most common mesenchymal tumor of the gastrointestinal tract. Surgical resection is the first-line therapy for operable lesions, however for inoperable imatinib is an effective therapy. In this setting a patient has been operated after a remarkable response to imatinib, used as both neoadjuvant and adjuvant. This approach led to a disease-free condition without toxicity and complications.

Adult↗

[Pharmacologic control of breathing].

Recent advances in respiratory neuropharmacology and neurophysiology have allowed the assessment of the effects of different drugs on the control of the ventilation both qualitatively (alterations of ventilatory pattern) and quantitatively (size and duration of the ventilatory and haemogasometric alterations). In the control mechanism of ventilation, the pharmacological intervention can act both on the respiratory input (basal metabolism, peripheral chemo-receptors, pulmonary receptors, bulbar neurons, cortical nervous system) and on the respiratory output (respiratory muscles). Based on personal experience in this field and the recent literature, the Authors briefly discuss the seat and the mechanism of action of the drugs with stimulating effect (respiratory analeptics, almitrines, progesterone, acetazolamide, salicylates, protriptyline, theophylline) and depressing effect (narcotics and narcotic-antagonists, anaesthetics, barbiturates and benzodiazepines) on the ventilation, as well as the role of the neurotransmitters and modulators. The clinical (positive and negative) effects of these drugs, particularly related to the patients with chronic lung disease, are also illustrated.

Central Nervous System Stimulants↗