[Integrated local management regarding patients suffering from the initial stage of chronic renal failure: NephroCare group pilot experience]. / La gestione integrata sul territorio del paziente con insufficienza renale cronica iniziale: l'esperienza pilota del gruppo NephroCare.

BACKGROUND: Early diagnosis of the initial stage of chronic renal failure (CRF) is a highly important factor for reducing morbidity and mortality in patients suffering from this pathology. It delays their undergoing hemodialysis (HD) treatment and prevents its complications. This is a well known problem, and the wrong approach causes the so-called late referral phenomenon. Undoubtedly general practitioners (GPs), can, first, identify at an early stage, patients suffering from this syndrome, as they are the first point of contact for patients at risk (for example, diabetic and hypertensive patients). Furthermore, patients very often turn to their GP for various reasons, even those who are 'apparently in good conditions of health'. This study aimed to implement, through NephroCare and the Cooperatives of General Practitioners, 'Progetto Leonardo' and 'Cumae', the evidence that local cooperation between GPs and nephrologists can be effective. METHODS: In a localized geographical area (Pozzuoli, Bacoli-Monte di Procida), NephroCare organized meetings with GPs, and doctors belonging to the cooperatives, aimed at creating interaction and discussion concerning the etiology and pathogenesis of kidney diseases that lead to CRF, its complications, prevention and management. Screening of 46277 patients, with a 2-yr follow-up was carried out to identify the two categories at risk, diabetics and hypertensives with creatinine (Cr) >1.5 mg/dL. RESULTS: The screening identified among 7403 hypertensives and 2501 diabetics two groups of, respectively, 274 and 192 patients with Cr >1.5 mg/dL. All patients screened were invited to talk to a nephrologist, who shared, together with the GP, the decision concerning diagnosis and care. CONCLUSION: The outcomes of the project highlighted the importance of cooperation between GPs and nephrologists to implement the integrated management of patients, increasingly elderly, suffering from CRF. This was achieved because the nephrologists belonged to the same regional area as the patients and were thoroughly dedicated to the project. In times of reduced economic resources, a possible correct approach is facing the 'late referral' problem and, consequently, easier and better management of patient care and cost rationalization can be solved by the intervention of nephrologists working in local clinics. In the future, this will always guarantee continuous care for patients suffering from this pathology.

Complications following anterior cervical spine surgery for disc diseases: an analysis of ten years experience.

The purpose of this study is to define, analyse and discuss the incidence and severity of the complications associated with anterior cervical spine surgery for degenerative disc diseases. The results and the management of complications of anterior spine surgery are discussed in relation to numerous previous published reports: precise knowledge of all potential accidents and pitfalls related to the surgical approaches and of their aetiology may contribute to preventing failures. The most common complication was a recurrent laryngeal nerve injury that developed in 7.9% of the cases. Dysphagia occurred in 5.6%, hoarseness in 5.2%, transient sore throat in 4.8%, worsening of pre-existing myelopathy in 3%, graft extrusion in 1.7%; root injury, haematoma, and wound infection developed in 0.87%. There was one case of oesophageal injury (0.43%) and there were no deaths related to the surgical approach. The rate of complications in our series has been reduced in the past years by 1) better patients selection: all of the patients in fact had previously received conservative treatment for at least four weeks; 2) more care in correct positioning of the patient during the operation; 3) meticolous removal of all harmful structures.

A cost-effectiveness analysis on different surgical strategies for intracranial aneurysms.

BACKGROUND: Economical studies on surgery of intracranial aneurysms have considered only the significant benefit of surgical approach on unruptured aneurysms and no studies have been performed comparing cost/benefit analysis of early vs delayed surgery. The present study was retrospectively performed in order to verify whether different treatment options in aneurysm surgery have a different cost/benefit ratio. METHODS: We have analysed a series of 137 patients which underwent surgery for intracranial aneurysms (21 unruptured aneurysms, 56 early surgery and 60 delayed surgery). In the analysis we assumed that each state of an operated patient has an assigned quality of life value and an associated medical cost. We expressed the outcome of each patient as the expected length of survival adjusted for quality, and referred to it as "quality-adjusted life years" (QALY). We considered for each patient the direct cost of Hospitalisation (obtained from DRG reimbursement), the Rehabilitation cost and the correction due to QALY adjusted for age and deficit. RESULTS: Significantly higher costs are reported in patients which present as major complication the hydrocephalus and which are treated with nimodipine; moreover, the costs for patients operated for unruptured aneurysms is significantly lower than that of patients which presented with SAH. Meanwhile, the average QALY adjusted for post-operative neurological deficit at three months follow-up is higher in patients operated for unruptured aneurysms than in patients operated after SAH. The cost-effectiveness of different treatment strategies did not significantly differ considering age and neurological deficit adjustment; thus, after SAH, the choice of early or delayed surgery may depend on clinical and logistic conditions related to the neurosurgical department and its organisation, because there is no significant economical advantage leading to recommend early versus delayed surgery. CONCLUSIONS: In conclusion the present data suggest that a decreased length of hospitalisation and a decreased cost for treatment of unruptured aneurysms should justify a more rigorous preventive screening with available non invasive neuroimaging techniques.

Antioxidant status and alpha1-antiproteinase activity in subarachnoid hemorrhage patients.

The antiproteasic activity of alpha1-antitrypsin (alpha1-AT) is reduced in cases of subarachnoid hemorrhage from ruptured intracranial aneurysm and particularly in patients currently smoking; alpha1-AT is very sensitive to oxidant agents. About 50% of physiological anti-oxidant systemic capacity is represented by Vitamin A, E and C. Plasmatic amounts of alpha1-AT, alpha1-AT Collagenase Inhibitory Capacity (CIC) and levels of vitamin A, vitamin E and vitamin C were analyzed in 39 patients, 26 women and 13 men, operated for intracranial aneurysm; 11 patients with unruptured intracranial aneurysm were considered as controls while 28 patients were included within 12 hours from subarachnoid hemorrhage (SAH). Plasmatic levels of vitamin A and vitamin E were significantly lower (p=0.038 and p=0.0158) in patients suffering SAH than in controls, while no statistically significant differences were found in mean plasmatic vitamin C levels. Level of alpha1-AT was not statistically different in controls and in patients with SAH; however, the activity of alpha1-AT, evaluated as CIC, is significantly reduced in patients with SAH (p=0.019). We have observed that systemic plasmatic levels of vitamins did not significantly differ in relation to smoking habit. Vitamin A and E represent an important defensive system against free radicals reactions. Particularly, vitamin E acts as an antioxidant by scavenging free-radicals. A reduced anti-oxidant status might be related to the higher sensibility of alpha1-AT to oxidative reactions and the activity of alpha1-AT is dependent on the antioxidant capacity of liposoluble vitamins. We can speculate that an acute systemic oxidative stress condition might influence the rupture of intracranial aneurysms.

Synaptosomal iron-dependent lipid peroxidation inhibition after subarachnoid hemorrhage by lazaroid in vivo treatment.

The production of oxygen-free radicals and their subsequent peroxidative action on membrane unsaturated fatty acids could be enhanced after subarachnoid hemorrhage (SAH). We have studied the effects of the in vivo pharmacological treatment with a lazaroid (U78517F) after experimental SAH, on lipid peroxidative patterns in cortical synaptosomal preparations. U78517F is a lipid-soluble antioxidant with a potent action to inhibit iron-dependent lipid peroxidation. Experimental SAH was induced in anesthetized rats by slow injection of 0.3 mL of autologous arterial blood into cisterna magna. The hemorrhagic animals were treated with 5 mg/kg iv of U78517F immediately after surgical operation. The animals were sacrificed 1 d after the hemorrhage and the thiobarbituric acid reactive material (TBAR) was assayed in basal conditions and after 1, 3, 5, 10, and 20 min of incubation at 37 degrees C with a pro-oxidant mixture on three different rat groups: sham-operated (0.3 mL of mock cerebrospinal fluid (CSF) into cisterna magna), hemorrhagic (0.3 mL of autologous arterial blood into cisterna magna), and hemorrhagic-treated. The hemorrhagic event did not influence the membrane lipoperoxidation levels in basal conditions, whereas peroxidative stimulation in vitro caused significant increases in hemorrhagic animals compared to the sham-operated, and in hemorrhagic-treated animals, the synaptosomal TBARs were similar to controls. The pharmacological treatment showed its effectiveness only following incubations with pro-oxidants; therefore, U78517F seems to be protective for membranes in case of severe lipid peroxidative stress.

Changes in non-synaptosomal and synaptosomal mitochondrial membrane-linked enzymatic activities after transient cerebral ischemia.

Non-synaptosomal and synaptosomal mitochondrial membrane-linked enzymatic activities, NADH-cytochrome c reductase rotenone insensitive (marker of the outer membrane) and cytochrome oxidase (marker of the inner membrane), were measured in rat brain hippocampus and striatum immediately after and 1, 4 and 7 days following the induction of complete transient ischemia (15 min) by the four vessel occlusion method. Furthermore citrate synthetase activity was measured with and without Triton X-100 in order to qualitatively evaluate the membrane permeability. Non-synaptosomal mitochondrial membranes showed reduction of both activities only in the late reperfusion phase: NADH-CCRRi decreased in striatal mitochondria after 4-7 days and only after 7 days in the hippocampus. COX activity decreased only in striatal mitochondria 7 days after ischemia. Non-synaptosomal mitochondrial membrane permeability did not show changes. Synaptosomal mitochondria showed a decrease of NADH-CCRRi only at 7 days of reperfusion both in hippocampus and striatum, while COX activity decreased only during ischemia and returned to normal levels in the following days in the two areas considered. In summary, free mitochondria showed insensitiveness to ischemia but they resulted damaged in the late reperfusion phase, while mitochondria from the synaptic terminal showed ischemic damage, partially restored during reperfusion. The striatal mitochondria showed a major susceptibility to ischemia/reperfusion damage, showing changes earlier than the hippocampal ones.

Effect of high-dose methylprednisolone and U74006F on eicosanoid synthesis after subarachnoid hemorrhage in rats.

Free radicals and lipid peroxidation of membrane fatty acids are thought to play a role in the pathogenesis of arterial vasospasm and the physiopathologic patterns of neuronal damage after subarachnoid hemorrhage. We have evaluated the effects of treatment with either high-dose methylprednisolone every 8 hours or a single dose of U74006F on the temporal profile of ex vivo synthesis of four selected eicosanoids in brain slices after experimental induction of subarachnoid hemorrhage in rats. Prostaglandins D2 and E2, prostacyclin and leukotriene C4 levels were determined by radioimmunoassay after 1-hour incubation of the brain slices. The synthesis of prostaglandin D2 and 6-ketoprostaglandin F1 alpha at 48 hours after subarachnoid hemorrhage was significantly higher when compared to sham-operated animals (p = 0.01); prostaglandin E2 release was significantly enhanced at 6 hours after subarachnoid hemorrhage (p = 0.01). The release of the lipoxygenase metabolite was significantly enhanced at 1, 6, and 48 hours after subarachnoid hemorrhage induction. Both treatment regimens significantly reduced the ex vivo synthesis of prostaglandin D2, prostaglandin E2, and leukotriene C4 at 1, 6, and 48 hours after subarachnoid hemorrhage, whereas the effects on 6-ketoprostaglandin F1 alpha synthesis differed in the two treatment groups. U74006F enhanced the synthesis of prostacyclin metabolite in the early phase after subarachnoid hemorrhage, and high-dose methylprednisolone reduced the increasing synthesis at 48 hours. A strict comparison between the two treatments was not possible because of the different modalities of administration. However, these data suggest that the antioxidant effect of single-dose treatment with U74006F influenced the early and delayed effects on enzymatic lipid peroxidation, whereas the effects of methylprednisolone administration every 8 hours were more significant in the delayed phase.

Single versus multiple drug therapy in the combined treatment of malignant gliomas. A multicenter study.

The best treatment of malignant gliomas has been considered to be surgery followed by irradiation and chemotherapy with nitrosourea compounds. Our controlled and randomized trial was designed in 1982 to analyze the effectiveness of multiple-drug versus single-drug therapy in patients bearing malignant gliomas. After 3 weeks from surgery and histopathological diagnosis 173 patients were randomly assigned to receive one of the three chemotherapy regimens: CCNU alone, CCNU plus VM-26 or CCNU plus VM-26 plus 5-FU. Radiotherapy was administered whole-brain (40-45 Gy) and coned-down focal (15-20 Gy) irradiation for a total of 60 Gy (1700 rets) in conjunction with the first course of chemotherapy. 150/173 patients are evaluable. Statistical analysis of results shows a better quality of life and survival for patients treated with polychemotherapy using a three drug combination than two drug or single drug therapy (13.8 vs 14.7 vs 18.2 months MST; P less than 0.01) but with a higher incidence of toxicity problems. An analysis of prognostic factors and their distribution in each arm of the protocol will be made in the near future.

An analysis of cerebrospinal fluid shunt infections in adults. A clinical experience of twelve years.

The authors analyze a group of 451 shunt operations where 317 patients had hydrocephalus and 23 cases were reported positive after cerebrospinal fluid (CSF) cultures. Staphylococcus was the most frequent bacterial organism found (57%). This retrospective study of 23 patients in whom infection developed following placement of an extrathecal shunt, although not a complete biometric evaluation, shows an incidence of infection of 5%. The authors also indicate the limitations in antibiotic treatment when three significant aspects of therapy are not considered fully: 1. sensitivity of the identified organism, 2. CSF levels of the drug that can be attained, and 3. the pharmacokinetic action of the drug in the CSF.

Chemotherapy plus immunotherapy for patients with primary and metastatic brain tumors.

The authors report two clinical trials concerning chemotherapy and immunotherapy combined in the treatment of primary and metastatic brain tumors. In the first study bacillus Calmette-Guerin (BCG) and in the second Levamisole (LMS) were utilized as immunostimulating agents. Chemotherapy was performed with BCNU or CCNU in association with surgery and/or radiotherapy. The immunological response was obtained but immunotherapy failed to demonstrate any significant effect on survival.

[Chemotherapy of malignant brain tumors in childhood]. / La chemioterapia dei tumori cerebrali maligni dell'infanzia.

The best conventional care for medulloblastoma and malignant ependymoma in children consists of surgery and radiotherapy. The preliminary observations of some authors suggested that chemotherapy could be useful in treating these tumors. The two major experiences in this field are those from SIOP and CCSG -RTOG trials which used chemotherapy as adjuvant to surgery and radiotherapy. In such studies chemotherapy appears to be effective mostly in high-risk patients. A study performed by Italian Child's Neurooncology Group ( ICNG ) confirms the preceding results.

[Steroid receptors in brain tumors]. / I recettori steroidei nei tumori cerebrali.

Recently the presence of steroid hormone receptors (SHR) have been reported in a series of nervous system human tumors, mainly in meningiomas. The possibility of characterizing brain tumors deserves attention because of the poor knowledge of endocrine-related behaviour of such tumors. The reliability of biochemical characterization of various receptor types should allow for better understanding of biological profile of primary and metastatic brain tumor, together with new avenues for combined modality treatment. In the future the highest priority might be assigned to the definition of the cut-off value of positivity for single receptors and to the receptor-endocrine modulation complex relationship for individual patients. A clear definition of the role of SHR in human brain tumors might improve our therapeutic potentials.

[Chemotherapy and immunotherapy of intracranial malignant gliomas]. / Chemioterapia ed immunoterapia dei gliomi maligni endocranici.

Although in recent years a great attempt has been made in brain tumor chemotherapy, this therapeutic approach appears to be conditioned by a large number of problems such as cell kinetics, tumor growth modalities, and drug delivery. Therefore only a small number of drugs (BCNU, CCNU, streptozotocin, and procarbazine) clearly demonstrate effectiveness against these tumors. Immunotherapy raises the same and other problems. In fact, if immune reaction is quite possible inside the brain, unfortunately current immunostimulant methods are unable to produce significant improvements.

[CCNU in the chemotherapy of tumours of the central nervous system (author's transl)]. / L'uso del CCNU nella chemioterapia dei tumori del sistema nervoso centrale.

This study concerns 59 patients with primary and metastatic tumors of the CNS. After surgery, each patients followed a therapeutic protocol requiring Radiotherapy (5500 Rads for 6 weeks) and antiblastic monochemotherapy with CCNU (130 MG/M2/D p.o. every 8 weeks). The results were evaluated according to Wilson's (1975) criteria of response to therapy. CCNU significantly improved the survival time in comparison to the data given for conventional treatment.