PubMed Health⌕ Search

Biomedical subjects

G Giuliani

Publications and source records attributed to G Giuliani.

At least 19 recordsLinked to original sources
PubMed1999

131I radioconjugated antibodies for the locoregional radioimmunotherapy of high-grade malignant glioma--phase I and II study.

Locoregional radioimmunotherapy (LR-RIT) was administered to 111 patients (20 were recruited in a phase I and 91 in a phase II study) with malignant gliomas: 1 patient with oligodendroglioma, 7 patients with anaplastic oligodendroglioma, 2 with grade II astrocytoma, 10 with anaplastic astrocytoma and 91 with glioblastoma, amounting to 58 newly diagnosed and 53 recurrent tumours. The 131I-labelled monoclonal antibodies BC-2 and BC-4 were used in order to recognize stromal and intracellular glycoprotein tenascin, an antigen present particularly in glioblastoma. The patients were enrolled between February 1990 and December 1997 after conventional therapy. The radiopharmaceutical was injected directly into the tumour site. Sequential scintigraphies demonstrated a high and enduring uptake in the tumour. The mean irradiation dose in the tumour was 300 Gy per cycle. In the group of 74 phase II glioblastoma patients the clinical responses were as follows: 10 patients with stable disease (SD), 9 with partial responses (PR), 23 with no evidence of disease (NED) and 1 patient with complete response (CR). The median survival was 19 months. The response rate (CR + PR + NED) was 17.8% for those patients with bulky lesions, with a median survival of 17 months, but 66.6% for patients with small lesions, with a median survival of 25 months. Better outcomes were recorded in cases with less aggressive diseases: oligodendroglioma, anaplastic oligodendroglioma and anaplastic astrocytoma. We conclude that fractionated LR-RIT can be safely performed, with promising results especially in patients with minimal disease.

Adult↗
PubMed1999

Lactoferrin-lipid A-lipopolysaccharide interaction: inhibition by anti-human lactoferrin monoclonal antibody AGM 10.14.

Lactoferrin (LF) is a glycoprotein that exerts both bacteriostatic and bactericidal activities. The interaction of LF with lipopolysaccharide (LPS) of gram-negative bacteria seems to play a crucial role in the bactericidal effect. In this study, we evaluated, by means of an enzyme-linked immunosorbent assay, the binding of biotinylated LF to the S (smooth) and R (rough) (Ra, Rb, Rc, Rd1, Rd2, and Re) forms of LPS and different lipid A preparations. In addition, the effects of two monoclonal antibodies (AGM 10.14, an immunoglobulin G1 [IgG1] antibody, and AGM 2.29, an IgG2b antibody), directed against spatially distant epitopes of human LF, on the LF-lipid A or LF-LPS interaction were evaluated. The results showed that biotinylated LF specifically binds to solid-phase lipid A, as this interaction was prevented in a dose-dependent fashion by either soluble uncoupled LF or lipid A. The binding of LF to S-form LPS was markedly weaker than that to lipid A. Moreover, the rate of LF binding to R-form LPS was inversely related to core length. The results suggest that the polysaccharide O chain as well as oligosaccharide core structures may interfere with the LF-lipid A interaction. In addition, we found that soluble lipid A also inhibited LF binding to immobilized LPS, demonstrating that, in the whole LPS structure, the lipid A region contains the major determinant recognized by LF. AGM 10.14 inhibited LF binding to lipid A and LPS in a dose-dependent fashion, indicating that this monoclonal antibody recognizes an epitope involved in the binding of LF to lipid A or some epitope in its close vicinity. In contrast, AGM 2.29, even in a molar excess, did not prevent the binding of LF to lipid A or LPS. Therefore, AGM 10.14 may represent a useful tool for neutralizing selectively the binding of LF to lipid A. In addition, the use of such a monoclonal antibody could allow better elucidation of the consequences of the LF-lipid A interaction.

Animals↗
PubMed1998

Cisternography in combination with single photon emission tomography for the detection of the leakage site in patients with cerebrospinal fluid rhinorrhea: preliminary report.

The site of leakage in a patients with rhinorrhea of various origin may be difficult to identify. The aim of our paper is to evaluate the contribution of cisternography in combination with single photon emission tomography (SPECT) to identify the fistulous track. From 1/1/1992 to 30/11/1997 we studied 20 patients with rhinorrhea posing a challenging diagnostic problem as to identification of the leakage site. Two mls of Indium DTPA (In 111) were injected into the subarachnoid space by the lumbar route. The tracer was followed by planar scintigraphy until it reached the cranial base and subsequently the SPECT acquisition started. A fistula was demonstrated in all of our cases including patients with no active leakage at the time of examination, patients with no bone defects on thin sliced CT scanning or patients with a normal MRI. At surgery the fistulous track was confirmed in all but two cases when a bilateral fistula was operatively identified only on one side. In conclusion whenever a CT scanning fails to demonstrate significant bone defects and MRI does not localize a fistulous track, SPECT cisternography via the lumbar route proved in our experience to be a reliable examination for a precise diagnosis.

Adolescent↗
PubMed1998

The German experience in reference pricing.

Price regulation schemes function both as a means for public authorities to contain costs, and as an economic tool to support the national pharmaceutical industry. This twofold contradictory aim of public intervention in pharmaceutical demand and supply makes such pricing schemes difficult to apply. This article concerns the reference price scheme which concerns setting a price cap for each active ingredient, or group of active ingredients considered equivalent according to some feature (e.g. therapeutic effects and chemical structure). In 1989, the reference price scheme for reimbursable drugs was introduced in Germany to reduce pharmaceutical expenditure, which had been steadily increasing in the past. The study investigates the economic effects of introducing reference prices in Germany in order to assess whether this system has been effective in containing public pharmaceutical expenditure. We conclude that the reference price scheme is an effective tool for price control, but cost containment requires further measures.

Analgesics, Non-Narcotic↗
PubMed1998

Importance of a reliable admission Glasgow Coma Scale score for determining the need for evacuation of posttraumatic subdural hematomas: a prospective study of 65 patients.

BACKGROUND: Patients who have an acute subdural hematoma with a thickness of 10 mm or less and with a shift of the midline structures of 5 mm or less often can be treated nonoperatively. We wonder whether the knowledge of the clinical status both in the prehospital determination and on admission to the neurosurgical center can predict the need for evacuation of subdural hematomas as well as the computed tomographic (CT) parameters. METHODS: From January 1, 1994, to May 31, 1996, 65 comatose patients harboring an acute subdural hematoma of 5 mm or more and not brain dead were admitted to our intensive care unit. Of the 65 patients, 15 patients were initially managed conservatively according to a protocol based on clinical, CT, and intracranial pressure parameters. During the study period, the use of long-lasting paralytic agents has been eliminated to allow detection of clinical deterioration in the Glasgow Coma Scale (GCS) score from the prehospital determination to the hospital admission assessment. RESULTS: Of the 15 patients initially managed conservatively, two were subsequently operated on because of evolving parenchymal hematomas. When comparing demographic, clinical, and CT parameters between the surgical group of patients and the patients initially conservatively treated, hematoma thickness (mean, 17.1 mm vs. 7.5 mm, p < 0.0001) and shift of the midline structures (mean, 12.8 mm vs. 4.7 mm, p < 0.008) were predictive of the need for surgery. A statistically significant change in the GCS score between prehospital determination and admission assessment was shown in the surgical group of patients (mean GCS score, 8.4 vs. 6.7, p < 0.01), and it was not present (mean GCS score, 7.3 vs. 7.2) in the patients initially conservatively treated. Functional outcomes were present in 23 cases (35.4%); functional outcomes in the initially conservatively treated patients were reached by 10 patients (66.7%). CONCLUSIONS: Nonoperative management for selected cases of acute subdural hematomas is at least as safe as surgical management. GCS scoring at the scene and in the emergency room combined with early and subsequent CT scanning is crucial when making the decision for nonoperative management. This strategy requires that administration of long-lasting sedatives and paralytic medications be avoided before the patient arrives at the neurosurgical center.

Acute Disease↗
PubMed1997

Local application of radiolabeled monoclonal antibodies in the treatment of high grade malignant gliomas: a six-year clinical experience.

BACKGROUND: Infusion of radiolabeled monoclonal antibodies (MAbs) directly into a tumor or into the site of disease after surgery concentrates a high quantity of antibody and radioisotope in the neoplastic tissue. The strong irradiation delivered by this method can result in control of high grade malignant gliomas. METHODS: Antitenascin MAbs BC-2 and BC-4 labeled with 131I (mean dose, 1998 MBq) were injected into 105 patients with malignant glioma by means of an in-dwelling catheter. Multiple courses (up to six) were given. The patients underwent MAb treatment after their tumors were minimized by surgery, radiotherapy, and, in recurrent lesions, a second operation. Data is presented in this article for 62 evaluable patients with high grade malignant gliomas (58 glioblastomas and 4 anaplastic astrocytomas), of which 31 were newly diagnosed tumors and 31 were recurrent lesions. In 40 cases the disease was minimal at the time of MAb injection, and in 22 cases a macroscopic remnant was present. RESULTS: There were very few adverse effects, all of which were minor. The treatment yielded a significant extension of patients' median survival (23 months) and of the disease free time to relapse (12 months). Favorable objective responses were recorded as follows: 9 partial responses, 3 complete responses, and 20 with no evidence of disease. A response rate of 51.6% was calculated for all assessable patients. The most important factor in obtaining beneficial outcomes was limited extension of the neoplasm at the time of therapy. CONCLUSIONS: In selected patients, locoregional radioimmunotherapy can be included in a multimodal strategy to control high grade malignant gliomas and produce favorable results.

Adult↗
PubMed1997

Melatonin effects on inhibition of thirst and fever induced by lipopolysaccharide in rat.

In 24 h water deprived rats we have evaluated the effects of melatonin on the inhibition of thirst and on fever induced by Escherichia coli lipopolysaccharide. Intraperitoneal (i.p) injection of lipopolysaccharide (0.32, 0.64 and 0.96 mg/kg) alone induced, a dose-dependent and significant inhibition of water intake as well as fever. In addition, lipopolysaccharide at the same concentrations increased urinary prostaglandins and serum cytokines levels. On the contrary, lipopolysaccharide treatment had no effects on cerebral brain nitric oxide synthase activity. All lipopolysaccharide effects were reverted by a prior, concomitant and subsequent i.p. treatment with melatonin (2, 4 and 6 mg/kg), whereas they were still present when melatonin was injected in combination with the melatonin receptor antagonist luzindole (15, 30 and 60 mg/kg, i.p.). We suggest that melatonin could exert its dipsogenic effects through a reduction of the free radical nitric oxide (NO.) whereas it may reduce body temperature by preventing an excessive formation of prostaglandins and cytokines.

Animals↗
PubMed1997

In vitro production of tumor necrosis factor-alpha, interleukin-6 and interleukin-8 from normal human peripheral blood mononuclear cells stimulated by Rhodococcus equi.

The capability of heat-killed Rhodococcus equi organisms to induce in vitro release of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8 from normal human mononuclear cells as well as the secretion kinetics of these inflammatory cytokines over a 48 h period were evaluated. Results show that normal human mononuclear cells are efficiently triggered to secrete TNF-alpha, IL-6 and IL-8 following R. equi stimulation according to a different kinetics. In particular, release of IL-B was already maximally expressed after 2 h of stimulation, while TNF-alpha amounts progressively increased in a time-dependent fashion. Finally, IL-6 secretion reached peak levels as soon as 18 h of incubation. Taken together, these data point out that monocyte-derived cytokines may play an important role in the immunological control of R. equi infection in immunocompetent people.

Cells, Cultured↗
PubMed1997

Pathogenetic role of phagocytic abnormalities in human virus immunodeficiency infection: possible therapeutical approaches. A review.

Polymorphonuclear cells (PMN) and monocytes/macrophages (M/M) represent the first defence line against invading microorganisms. Both phagocytic cell functions are precociously compromised in human immunodeficiency virus (HIV)-infected subjects, thus leading to infectious and neurological complications in the late stages of disease. Among intracellular pathogens, emerging bacteria such as Bartonella henselae and Rhodococcus equi can cause peculiar clinical pictures, i.e. the bacillary parenchimal angiomatosis and a classical pyogranulomatous broncopneumonia, respectively. On the other hand, overproduction of proinflammatory cytokines (CKs) and, in particular, tumor necrosis factor-alpha under HIV or lipopolysaccharide stimulation may cause neural damage in terms of demyelination and subsequent development of acquired immunodeficiency syndrome (AIDS) dementia complex. Some therapeutical attempts have been made with colony stimulating factors in order to increase the number and potentiate the function of PMN and M/M. On the other hand, the use of drugs able to reduce exaggerated release of CKs by M/M is suggested in AIDS patients in order to prevent a further aggravation of the clinical condition.

HIV Infections↗
PubMed1997

Role of lipopolysaccharide and related cytokines in Helicobacter pylori infection.

Helicobacter pylori is a gram-negative bacterium which accounts for the development of chronic gastritis and peptic ulcer in man. In this review, emphasis has been laid on the role of lipopolysaccharide (LPS) of the H. pylori cellular wall in the pathogenesis of gastroduodenal disease. H. pylori LPS exhibits a reduced endotoxic potency in terms of pyrogenicity, lethality, toxicity, mitogenicity, cytokine (CK) release and chromogenic limulus amebocyte lysate assay. This low biological activity of the LPS could be ascribed to the underacylation and underphosphorylation pattern of the lipid A backbone. However, also LPS core structures seem to contribute to the biological activity of the molecule. Despite this low immunological potential, an array of proinflammatory CKs are produced both in vitro and in vivo following stimulation of mucosal cells with H. pylori organisms. It is likely that LPS plays a major role in triggering interleukin (IL)-8, IL-1 and tumor necrosis factor-alpha production from both epithelial cells and macrophages. Finally, the lower immune response elicited by H. pylori LPS in comparison with other enterobacterial LPS may represent an escape mechanism from the host immunosurveillance exerted by this bacterium, thus allowing its survival and persistence in the gastric niche.

Animals↗
PubMed1997

Management of complex craniofacial traumas.

We report our experience in the treatment of cranio-facial traumas. The collaboration between neurosurgeons and maxillofacial surgeons is highlighted as well as the importance of the combined approaches, the use of Rigid Internal Fixations and bone grafting techniques in the immediate treatment of complex craniofacial fractures.

Bone Transplantation↗
PubMed1996

Effect of Helicobacter pylori lipopolysaccharide (LPS) and LPS derivatives on the production of tissue factor and plasminogen activator inhibitor type 2 by human blood mononuclear cells.

Different Helicobacter pylori lipopolysaccharides (LPSs) and LPS-derivatives were studied for their ability to induce the production of procoagulant activity (PCA) and plasminogen activator inhibitor type 2 (PAI-2) by human blood mononuclear leukocytes. Smooth (S)- and rough (R)-form LPSs caused a similar increase in cell-associated PCA (tissue factor) and PAI-2 antigen release. Both effects were potentiated by fetal bovine serum via a CD14-mediated mechanism. The potency of H. pylori LPSs was approximately 1000-fold lower than that of Salmonella typhimurium LPSs. When H. pylori LPS derivatives (dephosphorylated R-LPS, S-lipid A, and R-lipid A) were used, PCA and PAI-2 production were markedly reduced. R-lipid A was approximately 4-fold less efficient than S-lipid A. These findings suggest that the induction of monocyte tissue factor and PAI-2 by H. pylori LPS is influenced by the lipid A structure and modulated by the core oligosaccharide and that phosphate groups present in both regions may play an important role.

Helicobacter Infections↗
PubMed1996

Percutaneous dilational tracheostomy after anterior cervical spine fixation.

After spinal cord injury, quadriplegic patients generally require tracheostomy for ventilatory support and airway clearance. Early tracheostomy has several advantages over translaryngeal intubation, but in patients who undergo anterior surgical fixation of the spine, it is often delayed until after recovery of the surgical wound. We report the case of a quadriplegic patient who underwent a successful percutaneous dilational tracheostomy with the Ciaglia technique after surgical fixation of the spine. The percutaneous dilational technique minimizes the injury to the adjacent structures of the neck and the risk of stomal infection. Therefore, it should be considered the technique of choice when an early tracheostomy is indicated for quadriplegic patients who have undergone anterior surgical fixation of the cervical spine.

Adult↗
PubMed1995

Attenuated-dose idarubicin in acute myeloid leukaemia of the elderly: pharmacokinetic study and clinical results.

AML in the elderly is characterized by intrinsic biological features implying an enhanced chemoresistance. Intensive chemotherapy should be the treatment of choice, but the standard doses could induce unacceptable rates of aplastic deaths. We evaluated the efficacy of an induction protocol with attenuated-dose idarubicin (IDA) 8 mg/m2 for 3 d plus cytarabine and etoposide in 26 AML patients aged > 60. 18 patients (69%) achieved CR, five (19%) were non-responders and three (12%) died during induction. To compare the pharmacokinetics of IDA between elderly and young patients, we assayed daily the serum level of the drug and of its metabolite (idarubicinol, IDAol) in a group of eight elderly patients who received a dose of 8 mg/m2 (group A) and in a group of nine younger AML patients treated with 12 mg/m2 (group B). The apparent terminal half-life of IDAol was significantly longer in the elderly than in the younger patients (mean half-life 59.7 h versus 41.4 h, P < 0.05). The values of the area under the serum concentration curve of IDAol indicated that the two patient groups received a very similar exposure to the drug despite the different doses. In conclusion, this protocol, based on attenuated doses of IDA, compares well with the results obtained previously in similar age-matched patient series.

Adult↗
PubMed1995

Evolving brain lesions in the first 12 hours after head injury: analysis of 37 comatose patients.

From January 1, 1990, to April 30, 1994, 412 patients were admitted to our intensive care unit in coma after head injuries. Our study group consisted of 37 patients who were retrospectively identified as harboring lesions or developing new lesions within a 12-hour period from the time of admission. We defined the evolution of a lesion as an increase or decrease in the size of an already present hematoma or as the appearance of a totally new lesion. There were 25 male and 12 female patients (mean age, 34.9 yr), and the cause of trauma was road traffic accidents in 32 patients. Nine patients presented with shock, and six had evidence of abnormal coagulation at admission. Patients were divided into two different groups. In Group 1, 15 patients harbored lesions that evolved toward reabsorption. In Group 2, 22 patients harbored hematomas that evolved toward lesions requiring surgical removal. Fifteen of these patients had initial diagnoses of diffuse injury that evolved in this manner, whereas the remaining seven patients had already been operated upon and had developed second, noncontiguous, surgical lesions. Patients with lesions that required surgical evacuation had their computed tomographic (CT) scans obtained earlier and had a higher incidence of clinical deterioration. There was a significant difference in the evolution of the different lesions (P < 0.001), with subdural hematomas being more prone to reabsorption and intracerebral and extradural hematomas being more likely to increase in size or to appear as new lesions. Second CT scans were obtained because of clinical deterioration in 10 patients and because of increase in intracranial pressure in 5 patients. Scheduled CT scans were obtained in 13 patients, whereas in the remaining 9 patients, the diagnosis emerged from a combination of scheduled CT scans and intracranial pressure monitoring. There was a trend toward a poorer result among the patients with clinical deterioration, which, however, was not significant. A significant proportion of post-traumatic patients, particularly those who are unconscious, harbor early evolving intracranial lesions. When the first CT scan is performed within 3 hours after injury, a CT scan should be repeated within 12 hours.

Adolescent↗