Biomedical subjects

F Tomasello

Publications and source records attributed to F Tomasello.

At least 73 records · Page 4Linked to original sources

PubMed1996

Time-related ultrastructural changes in an experimental model of whole brain irradiation.

To stimulate therapeutic irradiation, we exposed rats to conventional fractionation (200 +/- 4 cGy/d, 5 d/wk; total dose, 4000 cGy). The effects of this regimen were assessed by electron microscopic examinations of brain microvascular and parenchymal cells 15 and 90 days after irradiation. Studies of the transendothelial passage of horseradish peroxidase provided information about the functional status of the blood-brain barrier. At 15 days after irradiation, there was an increased vesicular transport of horseradish peroxidase across the intact endothelium without opening of the tight junctions, and without evidence of structural alterations of neuropil, neuronal bodies, and astrocytes. Ninety days after irradiation, well-defined ultrastructural alterations were observed, involving the microvasculature, the neuropil, the neuronal bodies, and astrocytes. The main ultrastructural feature of cortical microvessels was their collapsed aspect, associated with perivascular edema containing cell debris. Altered neurons and reactive activated astrocytes were also noticeable. These data suggest a possible association, not necessarily causal, between damage of the microvascular/glial unit of tissue injury and development of radiation-induced brain toxicity.

Animals↗

PubMed1995

Intraoperative monitoring of cerebral blood flow during ventricular shunting in hydrocephalic pediatric patients.

Several studies have demonstrated lowered cerebral blood flow (CBF) in patients with hydrocephalus and symptoms of raised intracranial pressure. Ventricular shunting in such cases permits a sudden increase in CBF. The pathophysiology of functional brain deficit secondary to hydrocephalus is little understood. Improvement of the patient's clinical status after drainage of CSF suggests that cerebral dysfunction is not necessarily due to permanent brain damage. In fact, it improves rapidly after ventricular taps. In view of this it would be helpful to monitor cerebral perfusion. The transcranial Doppler (TCD) ultrasonography technique allows real-time monitoring of the intracranial circulation and makes it possible to evaluate the physiopathological correlation between ventricular dilatation and CBF. Continuous monitoring of the middle cerebral artery (MCA) by TCD was performed in three hydrocephalic children (2 months, 14 months, and 8 years old) during a ventricular-peritoneal shunt operative procedure. A TC-2000S device provided by an IMP-F fixed probe was utilized. In all patients, when the lateral ventricle was shunted and the CSF could flow away, a clear and sudden increase of flow velocity above 30% was detected. The pulsatility index (PI) was also pathologically increased in all patients. A gradual normalization of this index was revealed after the shunting procedure. Our experience has to be considered preliminary, but nonetheless, it suggests a clear correlation between hydrocephalic disease and concomitant CBF alterations.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗

PubMed1995

L-acetylcarnitine as a new therapeutic approach for peripheral neuropathies with pain.

With ST200 as the commercial source of L-acetylcarnitine hydrochloride, 94 patients were enrolled in this study; 31 were assigned to placebo, 31 to ST200 at 0.5 g/die and 32 to ST200 at 1 g/die, the i.m. treatments being injected daily for 15 consecutive days. In general, concerning the efficacy assessment, the administration of ST200 at 1 g/die appeared to be better than ST200 at 0.5 g/die when compared with the placebo administration. Statistically significant differences were revealed by the comparison of ST200 at 1 g/die to placebo, for the following variables: a) total motility as rated at the end of the 15-day study and confirmed by intention-to-treat analysis, b) visual analogue scale for all the patients having observation at day 15, and c) the objective and subjective judgements on efficacy. Safety and tolerability were good over the entire course of the study.

Acetylcarnitine↗

PubMed1995

Experimental incomplete spinal cord injury: treatment with a combination of nimodipine and adrenaline.

The effect of combination of nimodopine and adrenaline treatment on the motility deficits following secondary spinal cord damage was studied. Morphometric axonal analyses were also done. Incomplete spinal compression was induced in albino New Zealand rabbits anesthetized with ketamine. Neurological deficit was assessed by Tarlov's scale. The animals were divided into different groups. In one group the animals were anesthetized and subjected to all procedures except spinal cord injury and pharmacological treatment. Each of the other groups were divided into 2 subgroups; the spinal cord compression was induced for 2 min in one subgroup and 5 min in other subgroup. The pharmacological treatment in different groups consisted of slow intravenous infusions of saline alone, combination of adrenaline and nimodipine, nimodipine alone and adrenaline alone. The evolution of the motor damage was evaluated by comparing scores obtained with Tarlov's scale 1, 24 and 48 hrs after the end of spinal cord compression. In all animals, spinal cord compression for 2 and 5 min induced a 5th degree motor deficit. Treatment with saline improved slightly the motor deficit. The improvement of motor deficit was much better when a combination of nimodipine and adrenaline was used. The animals treated with nimodipine alone showed a better recovery in comparison with the animals treated with saline alone.

Animals↗

PubMed1994

Behavioral deficits following experimental subarachnoid hemorrhage in the rat.

To characterize some of the short-term and long-term functional consequences of subarachnoid hemorrhage (SAH) in rats, we employed a battery of well-characterized tests for assessment of acute and chronic behavioral and neurologic performances. Three groups of 10 rats (blood injected, mock CSF injected and sham-operated controls) were studied. During the acute stage, simple nonpostural somatomotor reflexes (pinna and corneal reflexes), simple postural responses (paw flexion, tail flexion, and head support), startle response, and postural functions (righting reflex) did not differ significantly between the experimental groups. Assessments of body weight, beam walking ability, and beam balancing revealed significant disturbances in blood-injected rats. This work demonstrates that this single-hemorrhage rodent model of SAH is associated with the induction of enduring neurologic and behavioral deficits. Because of the significant interspecies difference, a direct extrapolation of our results to humans may not be appropriate. However, we suggest that the observed behavioral and neurologic changes may parallel those seen in humans after SAH. Results reported here further confirm the rat model of SAH as a viable laboratory instrument for the study of the pathophysiology of SAH and provide normative values for the evaluation of new treatment modalities.

Acute Disease↗

PubMed1994

Beneficial effects of interleukin-6 in neonatal mouse models of group B streptococcal disease.

Previous studies have shown that tumor necrosis factor alpha (TNF-alpha) plays a pathophysiologic role in sepsis induced in rat pups by group B streptococci (GBS). In this model, TNF-alpha is also partially responsible for the induction of interleukin-6 (IL-6). The present study was undertaken to investigate the role of IL-6 in neonatal BALB/c mice infected with type III GBS. The effect of anti-IL-6 monoclonal antibodies and recombinant IL-6 on lethality and TNF-alpha production was investigated. In mouse pups infected with GBS strain COH1, plasma IL-6 reached levels of 3,067 +/- 955 and 1,923 +/- 891 U/ml when measured at 22 and 48 h, respectively (P < 0.05 compared with uninfected controls). Pretreatment with 25 micrograms of anti-IL-6 antibodies totally prevented the increase in circulating IL-6 bioactivity at both 22 and 48 h after infection (P < 0.05). Treatment with anti-IL-6 also induced a moderate decrease in survival time of mice infected with lethal doses of strains COH1 and COH31, as evidenced by increased lethality (P < 0.05) at 24 to 48 h but not at 96 h. Mouse recombinant IL-6 (12,500 U) given 6 h before challenge with strains COH1 and COH31 consistently increased survival time, as evidenced by decreased (P < 0.05) lethality at 48 to 72 h but not at 96 h. The effects of IL-6 pretreatment were dose dependent, since no protection was observed with doses lower than 12,500 U. In addition, no effects on lethality were noted when IL-6 was given at the time of challenge or at later times. TNF-alpha elevations (P < 0.05 compared with uninfected controls) were measured at 12, 22, and 48 h after challenge with strain COH1 (68 +/- 28, 233 +/- 98, and 98 +/- 34 U, respectively). Pretreatment with IL-6 significantly (P < 0.05) decreased plasma TNF-alpha levels at 12 and 22 h, with 55 and 69% inhibitions, respectively. Anti-IL-6 had an opposite effect, as evidenced by a 145% increase (P < 0.05) in TNF-alpha levels at 48 h after challenge. Collectively, our data are compatible with the hypothesis that IL-6 is involved in negative feedback regulation of plasma TNF-alpha levels in experimental GBS sepsis. In this model, IL-6 pretreatment can increase survival time. Future studies will be needed to investigate the mechanisms underlying this effect.

Animals↗

PubMed1994

Anti-lipoteichoic acid antibodies enhance release of cytokines by monocytes sensitized with lipoteichoic acid.

Lipoteichoic acid (LTA) from gram-positive bacteria can stimulate monocytes to produce cytokines. To ascertain whether aggregation of LTA receptors can contribute to this effect, human monocytes were sensitized with LTA from Streptococcus pyogenes, washed, and treated with anti-LTA antibodies. The addition of anti-LTA antibodies or F(ab')2 fragments markedly enhanced the aggregation of LTA receptors, as evidenced by indirect immunofluorescence and the release of tumor necrosis factor alpha and interleukin-1 beta. These findings suggest that aggregation of LTA receptors of monocytes is required for triggering marked cytokine responses.

Animals↗

PubMed1994

Induction of tumor necrosis factor alpha by the group- and type-specific polysaccharides from type III group B streptococci.

Previous studies suggested that circulating tumor necrosis factor alpha (TNF-alpha) may have a pathophysiologic role in experimental neonatal sepsis induced by group B streptococci (GBS). This study was undertaken to investigate the ability of the type III and group-specific polysaccharides of GBS to induce TNF-alpha production and TNF-alpha-dependent lethality in neonatal rats. The cytokine was detected in plasma samples by the L929 cytotoxicity assay. Intracardiac injections of either polysaccharide induced dose-dependent, transient elevations in plasma TNF-alpha levels that returned to baseline values after 5 h. The group-specific antigen induced significantly higher mean peak TNF-alpha levels than the type III antigen (125 +/- 47 versus 44 +/- 15 U/ml with 70 mg/kg of body weight). Glycogen (70 mg/kg), used as a negative control, did not induce TNF-alpha. The lipopolysaccharide-neutralizing agent polymyxin B did not decrease TNF-alpha levels induced by either polysaccharide, ruling out contamination with endotoxin as a possible cause of TNF-alpha induction. Fifty percent lethal doses of the type III and group-specific antigens given as intracardiac injections were 105 and 16 mg/kg, respectively. Salmonella endotoxin, used as a positive control, had a 50% lethal dose of 0.1 mg/kg. The lethal activities of GBS polysaccharides, as well as endotoxin, were completely prevented by pretreatment of neonatal rats with the respective specific antibodies or anti-murine TNF-alpha serum. To assess the relative importance of the type-specific substance in TNF-alpha induction by whole bacteria, two unrelated GBS transposon mutants devoid of only the type-specific capsular polysaccharide (COH1-13 and COH31-15) were employed. Each of the heat-killed unencapsulated mutants was able to produce plasma TNF-alpha level elevations or TNF-alpha-dependent lethality but was significantly less efficient in these activities than the corresponding encapsulated wild-type strain. These data suggest that the presence of type-specific material on GBS is not necessary for the stimulation of TNF-alpha production. Type III capsular polysaccharide, however, can significantly increase the ability of GBS to induce TNF-alpha. Further studies will be needed to assess the importance of TNF-alpha induction by the group- and type-specific antigens in the pathophysiology of GBS disease.

Animals↗

PubMed1994

Spinal cord compression in homozygous beta-thalassemia intermedia.

Symptomatic spinal cord compression caused by an epidural mass of extramedullary hematopoietic tissue in patients with beta-thalassemia is a rare occurrence, that becomes exceptional in childhood and adolescence. The literature is not uniform about the optimal treatment of these patients and different modes of therapy have been proposed so far, including surgical excision or decompressing laminectomy followed by local irradiation and/or hypertransfusional regimens. We report the successful treatment of such a complication in an adolescent with homozygous beta-thalassemia by surgery followed by repeated blood transfusions aimed at maintaining hematocrit at normal levels.

Adolescent↗

PubMed1994

Peritumoral edema in meningiomas: microsurgical observations of different brain tumor interfaces related to computed tomography.

Although generally benign tumors, meningiomas may be associated with extensive peritumoral brain edema as seen on computed tomographic scans. Fifty-two patients with intracranial meningiomas were studied, and the hypodense areas on computed tomographic scans were related to the intraoperative microsurgical findings and to the sizes of the tumors. We have identified three kinds of tumor-brain interfaces characterized by different difficulties in microsurgical dissection: smooth type, transitional type, and invasive type. These different microsurgical interfaces seem to correlate very precisely with computed tomographic images of halo-like and finger-like hypodense areas, allowing prediction of the microsurgical effort to be made in the surgery of meningiomas. The size of the tumor seems to be important in our subjects in determining the amount of edema produced. Indeed, a positive correlation (P < 0.001) was found between the sizes of the tumors and the extent of peritumoral hypodensity. A positive correlation (P < 0.002) also has been found between grade of edema and cortical penetration. Cerebral cortex disruption was systematically observed by us in invasive-type meningiomas and in 3 of 21 cases (14.3%) in transitional-type meningiomas. No penetration was observed in smooth-type meningiomas.

Blood-Brain Barrier↗

PubMed1994

Progressive perturbations in cerebral energy metabolism after experimental whole-brain radiation in the therapeutic range.

Basic mechanisms underlying the tolerance and reaction of the central nervous system to ionizing radiation have not been fully elucidated in the literature. The authors employed the [14C]-2-deoxy-D-glucose autoradiography method to investigate the effect of whole-brain x-irradiation on local cerebral glucose utilization in the rat brain. The animals were exposed to conventional fractionation (200 +/- 4 cGy/day, 5 days/week for a total dose of 4000 cGy), and the effects of this regimen were assessed at 2 weeks and 3 months postirradiation. In rats evaluated 2 weeks after treatment, statistically significant decreases in cerebral metabolic activity were found in 13 of the 27 regions studied, compared to control animals. In rats studied 3 months after treatment, additional metabolic suppression and statistically significant decreases in cerebral metabolic activity were found in 11 of the 27 regions, compared to rats studied 2 weeks after treatment. A weighted-average rate for the brain as a whole was approximately 15% and approximately 25% below that of control animals 2 weeks and 3 months after exposure, respectively. Although the difference in species is significant enough so that direct extrapolation to humans may not be appropriate, the data reported here may have potential clinical implications for the evaluation of the risk-benefit ratio for radiotherapy. This model can be used reproducibly for further investigations, including evaluation of therapies that may reduce irradiation-induced brain injury.

Animals↗

PubMed1994

Combined systemic beta-interferon and thymostimulin administration for metastatic brain tumors. A brief report.

Interferon-beta (IFN-B) plus thymostimulin (Th) were administered for eight weeks, intravenously and by intramuscular route to eight patients with metastatic brain tumors. No patient had a complete response. One had a stable disease and seven a progressive disease during that time. The mechanisms of the action of IFN-B and Th, and the possible therapeutic value are discussed.

Aged↗

PubMed1994

Cerebellopontine angle lipoma. Case report.

A cerebellopontine angle (CPA) lipoma in a 17 year-old woman is reported. The patient was admitted for evaluation of episodic vertigo, preauricolar pain and progressive hearing loss on the right ear. Auditory brain stem evoked potentials revealed an interwave latency increase on the right ear. Computerized Tomography and Magnetic Resonance Imaging showed a low density lesion and high intensity signal, respectively, in the right CPA. Reports of surgically treated lipomas of the CPA are extremely rare. Our patient underwent a right lateral suboccipital craniotomy and a subtotal resection of the lesion. Histological examination revealed a richely vascularized lipomatous tissue traversed by nerve fibers. The surgical indication for such rare lesion is discussed.

Adolescent↗

PubMed1993

Intracranial pressure monitoring in children: comparison of external ventricular device with the fiberoptic system.

Several intracranial pressure monitoring devices have been developed in the past several years. We have recently adopted the Camino fiberoptic device that permits subdural, intraparenchymal, and intraventricular monitoring. In this report we compare experiences in monitoring a group of pediatric patients with severe craniocerebral trauma and coma, grouped according to severity of Glasgow Coma Scale score. Patient age ranged from 2 to 16 years. Twelve patients were monitored by a ventricular catheter and 37, treated more recently, by a Camino fiberoptic device. The study demonstrated that the fiberoptic device and the ventricular catheter have the same accuracy and reliability. The fiberoptic method correlates very closely with the ventriculostomy method, but the pressure values are always 3 +/- 2 mmHg lower than those obtained with the conventional pressure transducer system, especially in more critically ill patients. This new technique is also easier to implant, safer to use, has minimal drift, and is minimally invasive, which particularly speaks for its use in pediatric patients.

Adolescent↗

PubMed1993

Cytokine appearance and effects of anti-tumor necrosis factor alpha antibodies in a neonatal rat model of group B streptococcal infection.

Cytokines are suspected of playing an important role in the pathophysiology of septic shock. This study was undertaken to determine whether tumor necrosis factor alpha (TNF-alpha) induces the production of other cytokines and mediates mortality in a neonatal rat model of sepsis caused by group B streptococci (GBS). We have measured TNF-alpha, interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6), and gamma interferon (IFN-gamma) levels in neonatal rats infected with different strains (H738, 259, and 90) and doses (1 50% lethal dose [LD50] and 5 90% lethal doses [LD90]) of type III GBS. TNF-alpha and IL-6 were detected by the L929 cytotoxicity and the B9 proliferation assays, respectively, in serial plasma samples. IL-1 alpha and IFN-gamma were measured in spleen homogenates by enzyme-linked immunosorbent assay kits by using antibodies raised against the corresponding mouse cytokines. Plasma TNF-alpha levels significantly rose above baseline values within 12 h after intraperitoneal challenge with 5 LD90 of GBS strain H738, corresponding to 3 x 10(3) CFU. A mean peak TNF-alpha concentration of 232 +/- 124 U/ml was reached at 20 h. Peak IL-1 alpha and IL-6 levels of 766 +/- 404 U/g and 1,033 +/- 520 U/ml, respectively, were reached at 24 h after bacterial challenge. Maximal spleen concentrations of IFN-gamma (449 +/- 283 U/g) were measured at 36 h. Concentrations of TNF-alpha, but not other cytokines, remained significantly elevated at 72 h, a time when mortality approached 100%. Significant correlations were found between concentrations of each of the cytokines tested and the logs of CFU concentrations in the blood. In order to ascertain whether TNF-alpha influenced the production of other cytokines, rat pups received two injections of anti-murine TNF-alpha or normal rabbit serum at 2 h before and at 26 h after challenge with live GBS. Plasma TNF-alpha bioactivity was undetectable in anti-TNF-alpha-treated animals, while IL-6 and IFN-gamma, but not IL-1 alpha, levels were significantly reduced, compared with normal serum controls. Rat pups pretreated with anti-TNF-alpha serum and infected with 1 and 5 LD90 of strains H738 and 259 showed enhanced early (48 to 72 h) survival. However, by 96 h this protection was no longer apparent.

Analysis of Variance↗

PubMed1993

Intracisternal rt-PA during early surgery for aneurysmal subarachnoid hemorrhage: an Italian report.

A patient undergoing surgery within 24 hours of aneurysm rupture was administered recombinant tissue plasminogen activator (rt-PA) directly into the basal subarachnoid cisterns after aneurysm clipping. Preoperatively, the patient had diffuse thick subarachnoid blood clots on CT. The rt-PA was given as a single injection of 10 mg. Postoperatively the patient was evaluated by serial CT scans and daily transcranial Doppler (TCD) examinations. An almost complete clot clearance was demonstrated on CT scans carried out on day 2 and day 4 after surgery. TCD studies failed to show any acceleration of blood flow velocity indicative of vasospasm. The postoperative curse was uneventful, without any clinical indication of delayed ischemia and no evidence of progressive hydrocephalus. Considering the data of the literature, as well as our initial experience, it appears that intracisternal thrombolysis with rt-PA can be achieved with relative safety and is effective for large-volume subarachnoid blood collections removal and vasospasm prevention. Results from open trials recently published suggest that a substantial advance in the management of an important subgroup of patients with aneurysmal subarachnoid hemorrhage (SAH) may be in the offing. However, randomized, placebo-controlled trials are still needed to confirm that there is a well-definite clinical benefit from the use of rt-PA. These considerations now call for a nation-wide multicentric italian trial which should be also addressed to evaluate other dose regimens and modalities of application.

Combined Modality Therapy↗

PubMed1992

Specificity and protective activity of murine monoclonal antibodies directed against the capsular polysaccharide of type III group B streptococci.

We have obtained 41 monoclonal antibodies directed against type III group B streptococci by immunizing Balb/c mice with formalin-killed bacteria. All of these antibodies reacted with purified type-specific carbohydrate by enzyme-linked immunosorbent assay and immunoprecipitation tests. The epitope recognized by all of these antibodies was associated with terminal sialic acid residues, as indicated by abrogation of immune reactions by treatment of the type-specific carbohydrate with neuraminidase. Two purified monoclonal antibodies (the IgM P9D8 and the IgG3 P4F12) were further characterized for their protective activity in a neonatal rat model of infection. P9D8 and P4F12 antibodies were significantly protective when administered in a dose of 0.5 and 2.5 mg/kg, respectively, at the same time as 3 x 10(5) colony forming units of type III streptococci. Protection was still observed when the antibodies were given up to 9 h after challenge. No protection was afforded against infections with type Ia/c and II streptococci. Similarly, both antibodies effectively opsonized type III, but not Ia, Ib or II bacteria, in an in vitro assay. These and similar, previously described, monoclonal antibodies may be useful, possibly after "humanization" by genetic engineering, for the therapy of neonatal group B streptococcal infections.

Animals↗

PubMed1992

Quantitative study of blood-brain barrier permeability changes after experimental whole-brain radiation.

Basic mechanisms underlying the tolerance and reaction of the central nervous system to ionizing radiation are not known precisely. We investigated the possibility of a change in blood-brain barrier (BBB) function as a causative factor for early delayed whole-brain radiation-induced cerebral dysfunction. Rats were exposed to conventional fractionation (200 cGy/d, 5 d/wk; total dose, 4000 cGy). BBB changes were assessed by means of the quantitative 14C-alpha-aminoisobutyric acid technique and electron microscopy. Studies of the passage of horseradish peroxidase across the BBB permitted comparative quantitative isotopical and qualitative morphological data. Experiments were carried out 2 to 3 weeks after the completion of the radiation exposure. The transport of 14C-alpha-aminoisobutyric acid across the BBB increased significantly in cerebral cortex and cerebellar gray matter, averaging 1.3 to 1.5 times over the normal values. Electron microscopy disclosed an intense vesicular response of the cortical microvascular endothelium that occurred without the opening of the tight junctions and resulted in an intense transport of HRP across the intact endothelium. The present data indicate that moderate doses of whole-brain radiation induce well-defined changes in BBB function, which possibly are involved in the pathogenesis of radiation-induced cerebral dysfunction in humans.

Aminoisobutyric Acids↗