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Biomedical subjects

L Santoro

Publications and source records attributed to L Santoro.

At least 19 recordsLinked to original sources

Amiodarone-induced experimental acute neuropathy in rats.

Amiodarone was injected endoneurially at increasing doses into the exposed tibial nerve of rats to study its electrophysiologic and pathologic effects on peripheral nerve fibers. Forty-five male Wistar rats were used, and each of the following concentrations was injected into 15 nerves: 25 micrograms/mL, 50 micrograms/mL, and 100 micrograms/mL. Microinjection of a 25 micrograms/mL concentration of amiodarone resulted in a subacute, incomplete conduction block evident at day 3 postinjection. This conduction block remained stable until day 10 and recovery was complete at day 35. Microinjection of a 50 micrograms/mL concentration of amiodarone produced a faster evolving conduction block, and significant axon degeneration (approximately 40% of fibers). Injection of a 100 micrograms/mL concentration resulted in severe acute motor axon degeneration followed by complete but delayed regeneration. Results of morphological studies closely correlated with electrophysiological findings. Amiodarone thus seems to have a direct toxic effect on axons at high concentrations in the peripheral nerve, and we suggest that different pathological changes described in human amiodarone neuropathy could be related to different concentrations of the drug in the nerve, perhaps due to variability of blood-nerve barrier efficacy.

Amiodarone

Is early onset cerebellar ataxia with retained tendon reflexes identifiable by electrophysiologic and histologic profile? A comparison with Friedreich's ataxia.

An electrophysiologic and histologic study was performed on 18 patients affected by early onset cerebellar ataxia with retained tendon reflexes (EOCA). Sensory and motor conduction velocity (SCV, MCV) was measured along peripheral nerves in all patients, somatosensory (SSEP) and brainstem auditory evoked potentials (BAEP) were recorded in 13; cortical stimulation (CS) in 12, and sural nerve biopsy in 4 patients were also performed. The results as a whole allow a division of EOCA patients into 2 groups: with (7 patients) and without (11 patients) peripheral neuropathy. Among EOCA patients with neuropathy a differential diagnosis with Friedreich's disease patients was not possible according to BAEPs and CS, while SSEPs could differentiate 2 out 5 patients in whom they were performed.

Adolescent

Body mass and acute myocardial infarction. GISSI-EFRIM Investigators.

BACKGROUND: The relation between body mass index and acute myocardial infarction was analyzed using data from a multicentric case-control study conducted in Italy between September 1988 and June 1989 within the framework of the GISSI-2 trial. METHODS: Subjects were 916 patients with acute myocardial infarction and no history of cardiovascular disease and 1,106 controls hospitalized for acute conditions not related to known or suspected risk factors for ischaemic heart disease. RESULTS: Relative to the lowest quintile of the Quetelet Index (weight/height2) the estimated risks for subsequent quintiles were 1.2 (95% confidence intervals, (CI): 0.9 to 1.6), 1.7 (95% CI: 1.2 to 2.2), 1.8 (95% CI: 1.4 to 2.4), and 2.2 (95% CI: 1.7 to 3.0) when adjustment was made for age, sex, education, and smoking habits by means of logistic regression. The association was consistent across strata of sex, education, and smoking status, but not age. The estimated risk for subjects in the fifth quintile of the Quetelet Index relative to those in the first was 4.1 under 55 years of age, but only 1.7 between 55 and 64 years and 1.5 above age 65. CONCLUSION: The relation between body mass and myocardial infarction was explained, at least in part, by higher serum cholesterol levels and the prevalence of diabetes and hypertension among fatter subjects. This does not, however, totally eclipse a possible causal relation between body mass and risk of myocardial infarction, since these conditions are a consequence, rather than a confounder, of overweight.

Adult

Upper gastrointestinal tract motility in children with progressive muscular dystrophy.

Gastric emptying was evaluated in 15 children (mean age, 8.0 years) with progressive muscular dystrophy to detect early gastrointestinal smooth muscle involvement; 10 of the children also underwent esophageal manometry. Clinical evidence of skeletal muscle dysfunction was minimal in 14 of the 15 patients; 10 of them had no gastrointestinal symptoms. Gastric emptying studies were performed by using 500 muCi of technetium 99m-sulfur colloid bound to a scrambled egg, and scintigraphic measurements were made continuously for 60 to 90 minutes. Gastric emptying studies and manometric tracings were compared with those from 11 children (mean age, 8.4 years) without gastrointestinal or muscular disorders. Mean (+/- SD) percentage retention of gastric isotope was significantly greater in patients with muscular dystrophy than in control subjects. No differences were found between the two groups in distal esophageal motility or in upper and lower esophageal sphincter pressures or relaxation. Contraction amplitudes in the upper portion of the esophagus, however, were significantly lower in patients with myopathy than in control subjects. These data suggest that dysfunction of smooth muscle of the upper gastrointestinal tract is detectable in children with muscular dystrophy early in the course of the disease, even when gastrointestinal symptoms are absent and skeletal muscle symptoms are minimal.

Adolescent

Modulation of arterial smooth muscle cell growth by haemodynamic forces.

To define the correlation between flow dynamics and the proliferation of arterial smooth muscle cells (SMCs), bovine arterial SMC were subjected to increasing laminar flow shear stress in an in vitro system. Smooth muscle cells were seeded in a fibronectin-coated polystyrene cylinder at 5 x 10(5) cells/tube. The experimental groups were subjected to increasing shear stress (3, 6, 9 dyn cm-2) for a 24-h period. The control group was subjected to similar incubation conditions without flow. Shear stress reduced significantly (p less than 0.01) the 24-h incorporation of tritiated thymidine and cell proliferation. This effect was proportional to the level of shear stress and was still evident 24 h after flow cessation. Flow cytometry demonstrated a lower percentage of SMCs in S-phase with increasing shear stress. Extrapolation of these findings to the clinical setting might explain how unphysiological shear stress can predispose to the abnormal proliferation rate of SMCs and early plaque formation.

Animals

The relationship between electrophysiological findings, upper limb growth and histological features of median and ulnar nerves in man.

In 19 median and 10 ulnar nerves of 28 healthy young volunteers, the maximum orthodromic sensory conduction velocity was studied along one or two fingers (the third and/or the fifth), the palm, and the forearm. In five 20 to 32-yr-old males and in a newborn male, post-mortem samples of either the median or the ulnar nerve were obtained from the finger (either the third or the fifth), the palm, the wrist and the forearm in order to study the size distribution of external fibre and axon diameters, and the fibre internodal length. In 2374 infants, children and adolescents, the height, length of both the third and the fifth finger, length of the palm, and length of the forearm were measured. The results showed (i) a significantly slower conduction velocity along the fingers; (ii) a significantly shorter internodal length without remarkable fibre diameter changes in the same nerve segments; (iii) a significantly smaller elongation of these body parts; (iv) a significant correlation between these data. In conclusion, internodal length seems to play an important role in governing conduction velocity of myelinated peripheral nerve fibres.

Adolescent

Role of family history in patients with myocardial infarction. An Italian case-control study. GISSI-EFRIM Investigators.

BACKGROUND: A family history of heart disease has been reported to increase the risk of coronary heart disease. We examined the relation between family history of myocardial infarction (MI) and risk of acute MI to establish the independency of this association, the degree of risk in relation to the number and age of relatives affected, and the possible interaction between family history and other major risk factors for MI. METHODS AND RESULTS: In a case-control study conducted in Italy within the framework of the GISSI-2 Trial, 916 cases of newly diagnosed MI and 1,106 hospital controls were identified. Using a structured questionnaire, data were collected on the history of MI in first-degree relatives and the age at which the event occurred. Compared with subjects without family history of MI in first-degree relatives, the relative risk (RR) of MI was 2.0 (95% confidence interval, CI, 1.6-2.5) in those with one and 3.0 (95% CI, 2.0-4.4) in those with two or more relatives affected (chi 2(1) test for trend, 54.1; p less than 0.001). Such an increase was not substantially affected by allowance for recognized risk factors. The risk related to family history involving at least two relatives was higher for early MI (less than 55 years) (RR, 20.0; 95% CI, 3.3-121.2) compared with later MI (less than or equal to 65 years) (RR, 3.5; 95% CI, 1.8-6.6). When known risk factors were considered for their interaction with family history, the effect on RR was approximately multiplicative for several variables, including smoking, serum cholesterol, hypertension, and hyperlipidemia but not for diabetes and body mass index. Thus, the presence of both family history and smoking and cholesterol levels greater than or equal to 226 mg/dl led to an RR of 14 (95% CI, 3.7-50.0) and 8.3 (95% CI, 1.8-38.7), respectively. CONCLUSIONS: This study indicates that a family history of MI is an independent risk factor for MI, and that the number of relatives and the age at which they were affected is related to the strength of the association. There is a multiplicative effect on RR between family history and several major risk factors for MI.

Case-Control Studies

Nerve conduction and electromyography.

The advent of computer-based methodology in routine electromyography has much improved the analysis of motor unit (MU) decomposition, of interference pattern study, and of MU counting. Measuring minimum motor and sensory conduction velocities is becoming more accessible and is considered an essential procedure in assessing the condition of peripheral nerves. A series of studies has shown that nerve resistance and vulnerability can be modified by a steep temperature gradient, by ciguatera toxin, or by hyperventilation-induced changes in the electrical properties of the axonal membrane. The controversy as to the diagnostic procedures to use in cases of radiculopathy and carpal tunnel syndrome (CTS) shows no sign of abating. There is, however, general consensus that electrophysiologic procedures must play a key diagnostic role in these conditions. Lastly, several interesting articles have been published describing the use of electrophysiologic tests in motor neurone diseases. Moreover, some advances have been made in the diagnostic yield of single-fibre electromyography (SFEMG) with axonal microstimulation in myasthenia gravis and Eaton-Lambert myasthenic syndrome.

Animals

Analysis for transaminases in serum with an amperometric glutamate electrode.

We determined transaminases in human blood serum with an amperometric glutamate biosensor. The probe was a hydrogen peroxide sensor assembled with appropriate selective membranes to enhance the probe specificity and lifetime. Calibration curves of glutamate were linear in the range 1-1000 mumol/L, with a response time of < 1 min. This probe was subsequently applied to the measurement of activities of aspartate and alanine aminotransferases in human sera. Analytical recovery studies demonstrated the suitability of the glutamate sensor by measuring 91-99% of added glutamate, 92-106% of added aspartate aminotransferase, and 101-105% of added alanine aminotransferase. Transaminase activity measured in 80 sera correlated well with results obtained with a spectrophotometric procedure.

Alanine Transaminase

[Microcirculatory changes in mitral prolapse as an expression of a systemic change in the connective tissue].

Many authors hypothesize that mitral valve prolapse (MVP) can be, in most cases, only a clinical sign of a primitive and systemic disorder of the connective tissue, like in Marfan Syndrome (MS). In our previous works we supported the presence of morphological and functional alterations of the microcirculation in patients affected by MS. In order to characterize a possible common denominator between these pathologies we have studied the cutaneous microcirculation in a group of patients affected by MVP, divided into 2 groups: anatomic MVP (MVP) and MVP syndrome (MVPS). The morphologic parameters have been investigated by nailfold capillaroscopy while digital laser-Doppler was used to study skin flowmetry. The results have been compared with a control group. Capillaroscopic remarkers showed an architecturally disorganized microvasculature with aspects related to a reduced compactness of the microvasculature unit with a significatively higher score compared with controls (7.3 +/- 2.9 vs 3.6 +/- 1 p less than 0.0005). Laser-Doppler flowmetry showed a significatively reduced rest flow; ischemic test showed: spike time 48.9 +/- 36.9 vs 15.3 +/- 7.7 s (p less than 0.0005), hyperemic acme 6.6 +/- 2.7 vs 12.5 +/- 8.4 UP (p less than 0.002); % increase 32.1 +/- 20.2 vs 51.5 +/- 15.4 (p less than 0.002). Thermic test showed a significatively higher thermic acme 8.7 +/- 4.2 vs 12.6 +/- 9.11 UP (p less than 0.05). These results appeared to be correlated with stage pathology as it was observed a severe microvasculature disorders in MVPS. Therefore we suppose that a phenotypic continuum may exist between MS and MVP.

Adult

Production and characterization of two immunotoxins specific for M5b ANLL leukaemia.

We describe the production and functional characterization of 2 monocytic-cell-lineage-specific immunotoxins constructed with saporin emitoxin (SAP) from Saponaria officinalis. Interest in the production of these immunotoxins, of possible clinical relevance, has been raised by the availability of 2 MAbs of high specificity for circulating monocytes and M5b ANLL, thus envisaging their potential use in bone-marrow purging. SAP emitoxin was selected on the basis of the low cytotoxicity in unconjugated form, as opposed to highly specific cytotoxicity and favourable pharmacokinetical properties in the conjugated form. SPDP conjugation produced immunotoxins which retained serological specificity and protein-synthesis-inhibitory activity. The 2 immunotoxins did not interfere with bone-marrow progenitor-cell growth in a CFU-GM colony assay. On the contrary, they were capable of killing monocytic cells selectively, as demonstrated in phenotypical and functional assays. Thus these 2 novel immunotoxins appear to be promising reagents in purging autologous bone marrow prior to transplantation in patients suffering from monocytic leukaemia.

Antibodies, Monoclonal

Motor and somatosensory evoked potentials in hereditary spastic paraplegia.

Motor evoked potentials (MEPs) from the arms and legs to transcranial stimulation of the motor cortex and somatosensory evoked potentials (SSEPs) from stimulation of the nerves of the arms and legs, were recorded in 11 patients with hereditary spastic paraplegia. Electrophysiological abnormalities were found to be distributed differently among the systems examined; the longer the pathway, the higher the incidence and severity of impairment. MEPs from the leg were either absent or clearly reduced or prolonged in all patients. Eight patients showed abnormal cortical SSEPs on stimulation of the leg (absent or reduced responses in four, slowed central conduction velocity in seven), but only two of these patients had abnormal MEPs from the arm (absent responses). Cortical SSEPs on stimulation of the median nerve were reduced in two patients. Mean values of amplitude and central conduction velocity for MEPs and SSEPs from the leg were significantly different between patients and controls. Such differences were not found for either MEPs or SSEPs from the arm. This distribution of abnormalities, which suggests a differential involvement of the spinal pathways, parallels the reported pathological pattern in which degeneration of axons is more common and severe in the motor and sensory fibres supplying the leg.

Adolescent

Pyridoxine neuropathy. A four-year electrophysiological and clinical follow-up of a severe case.

In a 54-year-old male a severe sensory neuropathy was observed during treatment for pulmonary tuberculosis with isoniazid (400 mg/day) and pyridoxine (600 mg/day). Eight months after withdrawal from isoniazid the sensory symptomatology was still progressing, although muscle strength was never reduced. A sural nerve biopsy revealed marked loss of large myelinated fibres. Only when pyridoxine treatment was interrupted did a slow improvement begin. A clinical and electrophysiologic follow-up showed a very slow and still incomplete recovery after four years. The possibility of an unusual individual susceptibility to toxic effects of pyridoxine is considered.

Electrophysiology

Histological characteristics of the human testis after long-term treatment with cyproterone acetate.

Cyproterone acetate, an antiandrogen drug, is used to reduce mammalian fertility. Effects on the human testis are controversial. Findings in this study reveal that long-term treatment-7 months with 200 mg/day-leads to disappearance of the germinal cells and to Sertoli cells with either a normal or undifferentiated aspect as well as involution of the Leydig cell. Some pathogenetic hypotheses on the action of cyproterone acetate upon human spermatogenesis are discussed.

Cyproterone

[Local regional recurrences after radical mastectomy. Studies of 50 cases].

Resection of locoregional recurrences was performed after mastectomy in 50 cases in the period 1961-1974. An incidence of 2% to 35% is reported for such recurrences, which are due to a variety of factors. In the present series, attention was directed to age at mastectomy and at recurrence, size of primary tumour, presence of axillary metastases, and details of menarche, menopause and pregnancy. Mean age at mastectomy was 50 yr and at recurrence 53 yr. Tumour diameter ranged from 2 to 5 cm in 73% of cases. Lympho node metastases were present in 42%. In 80%, the recurrence was paracicatricial, in 13% parasternal, and in 7% axillary. Treatment consisted of resection, radiochemotherapy or endocrino-ablative management.

Adult