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Biomedical subjects

F Tomasello

Publications and source records attributed to F Tomasello.

At least 19 recordsLinked to original sources

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

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

Blood-brain barrier permeability changes after experimental subarachnoid hemorrhage.

Basic mechanisms underlying cerebrovascular permeability responses to subarachnoid hemorrhage (SAH) are still to be defined in detail. Previous investigations examining the occurrence of blood-brain barrier (BBB) breakdown after SAH in the experimental setting have yielded conflicting results. In a rat model of SAH, we assessed BBB changes by means of the quantitative [14C]-alpha-aminoisobutyric acid technique. Experiments were carried out on the second day post-SAH. In blood-injected rats [14C]-alpha-aminoisobutyric acid transport across the BBB increased significantly in cerebral cortices and cerebellar gray matter, averaging 1.3 to 1.5 times control values. The present data indicate that SAH induces well-defined changes in BBB function, possibly involved in the pathogenesis of post-SAH cerebral dysfunction in humans. Results reported here have also potential clinical implications for the management of aneurysm patients.

Aminoisobutyric Acids

Monitoring of brain tissue pressure with a fiberoptic device.

Continuous monitoring of brain tissue pressure can now be achieved with intracerebral placement of fiberoptic microtransducers. This study was undertaken to test the safety, accuracy, and reliability of this relatively new type of intracranial pressure (ICP) monitoring. Initially, the fiberoptic device was compared with a concurrently functioning intraventricular catheter in 18 patients. The results from the two methods corresponded closely over a wide range of pressures, and the correlation coefficient approached 1.0. Subsequently, this monitor was used for routine measurement of ICP in a series of almost 200 neurosurgical patients at risk of intracranial hypertension. The tracings showed good wave forms and consistent absolute values of ICP. No instances of hemorrhage, mechanical failure, or other complications were associated with this monitor, except one case of infection, which was not directly attributable to the device per se. When bilateral intraparenchymal pressures were recorded in patients with unilateral mass lesions, significant transitory pressure differentials between the ipsilateral and contralateral sides were documented. It is concluded that monitoring intraparenchymal pressure with the fiberoptic device offers safe and reliable ICP recordings for routine neurosurgical practice. In patients with unilateral masses, ICP should be measured in close proximity to the lesion.

Adolescent

Production of tumor necrosis factor-alpha and interleukin-6 in mice infected with group B streptococci.

Group B streptococci (GBS) are a leading cause of sepsis and meningitis in neonates. Since cytokines are thought to play an important role in septic shock, we have studied serum levels of tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) in BALB/c mice infected with type III GBS. TNF alpha and IL-6 were detected by the L929 cytotoxicity and the B9 proliferation assays, respectively, in serial serum samples obtained after infection. After i.p. challenge with an LD50, serum TNF alpha rose above baseline values as early as 3 hr, peaked at 7 hr, and returned to baseline values at 20 hr. IL-6 serum levels rose concomitantly with TNF alpha, peaking 8 hr after challenge. No serum TNF alpha activity was detected in the course of sublethal infections. However, a transient rise in TNF alpha levels was observed after i.v. inoculation of high numbers (greater than or equal to 1 x 10(8) of heat-killed GBS. When groups of mice were injected i.v. with a single dose of anti-TNF alpha rabbit serum 2 hr before challenge with an LD90 or LD30, no effect was noted in terms of survival, although the serum TNF alpha peak was completely abrogated. Serum TNF alpha does not seem to play an obligatory role in GBS-induced lethality of adult mice. However, further studies are needed to assess better the role of this cytokine in the pathogenesis of GBS sepsis.

Animals

[Prevention of postoperative complications in vertebro-spinal cord pathology].

In 352 patients, affected by vertebral-medullary pathology, we evaluated the role played by the prevention or by the treatment of postoperative complications. We also evaluated their influence on the clinical outcome and neurological recovery. In every case we recorded a scrupulous post-operative neurological monitoring of the eventual complications, on the basis of the type, gravity and duration. From our results it appears that the complications, mostly secondary to infectious diseases, have an influence on the clinical and neurological recovery. We highlight the importance of an adequate nutritive management to prevent the complications, specifically those secondary to infectious diseases and cutaneous lesions.

Adolescent

Endothelin: an endothelium-derived vasoactive peptide and its possible role in the pathogenesis of cerebral vasospasm.

The contractile response to endothelin has been examined in cerebral arteries from rats subjected to a prior subarachnoid haemorrhage (SAH) and compared with saline injected controls. Endothelin elicited strong concentration-dependent contraction of rat basilar artery segments. The response was slow in onset and long lasting. The endothelin-induced contraction was much stronger in the SAH compared to control animals. Our findings suggest a role of the peptide in the pathophysiology of cerebral vasospasm.

Animals

Epidural spinal meningioma. Role of magnetic resonance in differential diagnosis.

A rare case of an extradurally growing spinal meningioma in an elderly woman is reported. Neuro-imaging, particularly magnetic resonance (MR), allowed to recognize the lesion, which, otherwise, could raise problems of differential diagnosis with a spinal metastasis. An emergency operation, required by a sudden neurological deterioration, was decisive in recovery of neurological deficits. In a review of the literature, extradurally growing spinal meningiomas appear to occur with a higher frequency than it is thought. Therefore, they are to be suspected when dealing with extradural spinal lesions.

Aged

Effect of experimental subarachnoid hemorrhage on CSF eicosanoids in the rat.

A simple and inexpensive experimental model of subarachnoid hemorrhage (SAH) was developed in the rat. Based on accumulating data indicating the important role of arachidonic acid metabolites in the etiology of delayed cerebral vasospasm, we investigated changes induced by SAH on cerebrospinal fluid (CSF) levels of prostaglandin E2 (PGE2), F2 alpha (PGF2 alpha), and thromboxane B2 (TXB2). SAH was produced by the cisternal injection of blood via percutaneous suboccipital puncture. SAH rats (n = 200) were injected with 300 microliters of fresh autologous arterial blood; Control rats (n = 100) received the same volume of mock CSF. In 60 additional animals, no injections were made. To follow the changes induced by SAH on both the spectrum and time course of CSF eicosanoids, cisternal CSF samples were collected under basal conditions, 6, 12, and 36 after cisternal injection. PGE2, PGF2 alpha, and TXB2 were assayed in aliquots of CSF obtained by pooling samples from each experimental group. Eicosanoids were assayed using radioimmunoassay techniques. Arterial spasm was verified in parallel groups of SAH and control rats by comparison of the angiographic diameters of the basilar arteries (BA) and middle cerebral arteries (MCA) to that of the stapedial artery. CSF levels of all three eicosanoids were significantly higher in the SAH groups compared to both noninjected and mock-CSF injected control rats. These increases in concentrations of eicosanoids were accompanied by a decrease in the mean vascular diameter (77.5-82.0% of control) on day 2 following cisternal injection. We conclude that marked elevations of spasmogenic eicosanoids in the CSF are associated with experimental SAH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Early stabilization in severe cervical vertebral and spinal cord injuries].

In the cervical vertebral-myelic trauma a high incidence of bronchopulmonary, metabolic, thromboembolic complications and bedsores is present. The authors, in agreement with the most recent literature (Tator, 1987), affirm that adoption of the precocious stabilization, allowing an equally precocious mobilization, considerably reduces the above-said complications. Thirty patients with vertebral-myelic lesions needing operation for stabilization have been followed. Twenty-one of these, presented irreversible myelic damages and nine cases had partially or completely reversible damages. Only in five cases severe bronchopulmonary affections and bedsores occurred. Thrombo-embolic complications did not occur. The authors conclude that the precocious mobilization allowed by the stabilization realized in acute state, permits a drastic decrease in the complications typical of this kind of affections.

Cervical Vertebrae

Adherence of group B streptococci to adult and neonatal epithelial cells mediated by lipoteichoic acid.

We have investigated the role of lipoteichoic acid in mediating the adherence of different serotypes of group B streptococci to human adult and neonatal epithelial cells. Pretreatment of neonatal buccal and vaginal epithelial cells with lipoteichoic acid, but not with deacylated lipoteichoic acid, induced a marked inhibition in the adherence of all strains tested. Pretreatment of bacteria with substances known to bind lipoteichoic acid, such as monoclonal and polyclonal antipolyglycerophosphate antibodies and albumin, also resulted in adherence inhibition. Group B streptococci adhered in 6- to 10-fold-higher numbers to buccal epithelial cells from neonates older than 3 days than to those from neonates less than 1 day old. This increase in receptiveness for group B streptococci was paralleled by an increased ability of epithelial cells from older neonates to bind group B streptococcal lipoteichoic acid. These data suggest a role for the lipid portion of lipoteichoic acid in the adherence of different serotypes of group B streptococci to vaginal and neonatal epithelial cells.

Age Factors

Early partial reperfusion in a new rat model of focal cerebral ischaemia.

The influence of early partial reperfusion in a new rat model of focal cerebral ischaemia was investigated. Two groups, each of 30 adult male rats, were subjected to permanent occlusion of the right middle cerebral artery. The former, (group A) had an additional permanent occlusion of both common carotid arteries; the latter (group B) had a temporary carotid occlusion lasting for two hours. Mortality rate, evaluated within three days, was 70% in group A and 20% in group B. The mean size of cerebral infarcts was 63% in group A whereas it was 21% in group B. These data suggest that, in this animal model, early partial reperfusion is effective in reducing the mortality rate, and the size of the cerebral infarcts. Furthermore, this experimental model appears suitable for studies elucidating the role of reperfusion and/or other efforts in focal cerebral ischaemia.

Animals

Evaluation of a rapid method to exclude the presence of certain enteric pathogens in stool specimens.

A new commercial method intended to exclude the presence of Salmonella spp., Shigella spp., and Yersinia enterocolitica and to presumptively identify Salmonella isolates within 2 h after primary isolation from stool specimens was evaluated. This system is marketed in Europe as API Z and in the United States as Rapid SST. The strip consists of five pairs of cupules for the screening of five lactose-negative colonies. The first cupule of each pair detects the presence of five enzymatic activities, whereas the second serves to maintain the strain for additional testing if necessary. A total of 197 fresh isolates from stool specimens and 217 stock cultures of Salmonella spp., Shigella spp., and Yersinia enterocolitica were tested, with the API 20E system as a reference method. In the stool specimens, 77.3% of the bacteria could be excluded from further workup for the presence of these organisms within 2 h. Over 97% of the stock strains and each of three fresh Salmonella isolates tested produced a reaction pattern corresponding to a correct presumptive identification. This reaction pattern was not produced by any isolate other than the Salmonella isolates. The API Z system can be used as a screen for the presence of Salmonella and Shigella spp. and can provide an accurate presumptive identification of Salmonella isolates within 2 h after primary isolation.

Bacteria