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Background: The senescence of the immune system is a complex phenomenon, characterized by impairment of several lymphocyte activities and generally considered a state of immune dysregulation. Aging is a condition associated with many social changes likely to induce psychological stress, which is often perceived as uncontrollable and can lead, in some cases, to clinically relevant depression. In the recent years a growing interest has been raised for the study of bidirectional interactions between the central nervous system and the immunological network (psychoneuroimmunology). Objective and Methods: We analyzed the possibility that chronic psychological distress and depression could worsen some immune functions in the aged. We postulate the neuroendocrine mechanisms of psychoimmune interaction, analyzing both the human and animal studies focused on aging. Results: The data from the literature reviewed suggest a significant impact of affective disorders on immune functions in the elderly subjects. This psychoimmune imbalance appears particularly important when the studies are carried out in otherwise healthy aged people. Conclusions: Here we reviewed the relationships between psychological stress and depression and immunological functions, with particular regard to those aspects pertinent to the aging process. The clinical relevance of these interactions remains to be elucidated, but the high frequency in the aged of autoimmune, infectious, and neoplastic diseases suggests to focus on the psychoneuroimmune interactions in the old age. We also propose some outlines for future studies concerning psychoneuroimmunology and aging.

The increased survival of patients in dialysis and the gradual increase in the age of uremic patients commencing chronic dialysis raises serious problems for the creation and maintenance of efficient vascular access. In cases in which it is extremely difficult to create arteriovenous fistulas (AVF) using existing upper limb veins, it is possible to resort to vascular grafts, lower limb AVF, central venous catheters or refer the patients for peritoneal dialysis if this method is technically possible. In order to evaluate the incidence of these phenomena in quantitative terms, the authors have made a retrospective analysis of patients undergoing vascular access surgery since the opening of the Dialysis Centre on 1/9/1973 to 30/9/1996. During this period (277 months) a total of 1,037 AVF implant operations were performed (in addition to 65 arteriovenous shunts in the earlier period and 28 permanent central venous catheters in the last 10 years). The survival of AVF grafts was lower than that in natural vessels in 384 patients without clinical risk. In diabetic subjects, those suffering from vascular pathologies, systemic diseases, or aged over 70, the survival of AVF was distinctly lower compared to the group without these risk factors. However, the higher risk group did not show any marked difference in survival between AVF in the patient's own veins and grafts. In only 4 out of 1,037 operations it was impossible to obtain vascular access in the upper limbs (2 patients were referred for peritoneal dialysis and AVF were executed in the thigh in 2 patients). In conclusion, the retrospective analysis of this series leads the authors to affirm that the rational use of natural vascular accesses normally allows a sufficient operating margin; however, in special cases suitable techniques (such as permanent central venous catheter or AVF in the thigh) can enable difficult situations to be resolved as an alternative to peritoneal dialysis.

Discoidal recombinant high density lipoproteins (rHDL) of apolipoprotein AI (apoAI) and palmitoyloleoylphosphatidylcholine (POPC), with or without cholesterol, were prepared by cholate dialysis. By gel filtration, rHDL containing 2–4 (Lp2, Lp3 and Lp4) apoAI molecules/particle were obtained. The ApoAI conformation in these rHDL was investigated by tryptophan fluorescence, denaturation with guanidine HCl, and immunoreactivity with two monoclonal antibodies recognizing epitopes in the N-terminal and central domains. Data show that apoAI conformation is highly dependent on particle size as well as on cholesterol. The ability of rHDL to interact with lipid bilayer was studied by measuring leakage induction on POPC and POPC/cholesterol vesicles loaded with terbium/dipicolinic acid. Among the cholesterol-free rHDL, the most efficient ones were the smallest Lp2. Leakage induction on POPC vesicles is dramatically decreased by the presence of cholesterol in Lp2 and Lp3. All the rHDL, but specially those containing cholesterol, induced more leakage on the POPC/cholesterol than on the POPC vesicles. These results suggest that in small cholesterol-poor particles, apoAI could have a conformation determining a high affinity for membranes, which could facilitate cholesterol efflux. After cholesterol enrichment, a conformational change in apoAI could decrease the affinity for membranes allowing the lipoprotein release.

Previous studies on DNA repair in ageing have demonstrated increased frequencies of single and double strand breaks in lymphocytes from elderly subjects and, as a consequence, decreased efficiency in DNA replication. We have investigated the relationship between cell proliferation and the nuclear expression of ku protein in a human population of 43 subjects of different ages. Ku is an heterodimeric protein composed of two subunits of 70 and 80 kDa, which is involved in the early steps of DNA damage recognition. In the present study, PBL from subjects of different ages were PHA-activated to evaluate the stimulation index and the production of Th1- and Th2-type cytokines. Moreover, nuclear extracts were obtained from activated lymphocytes to evaluate by a gel retardation assay the presence and the functional activity of the heterodimer ku 70/80. Our results indicate that ageing affects the mitotic responsiveness and cytokine production to a significant extent, but only marginally the expression of ku 70/80. These findings suggest that the age-related impairment in DNA repair mechanisms are only in part related to the reduced expression of ku protein able to recognize DNA damage.

Rifampin is a drug able to induce adverse reactions involving both the kidney and the hematological system. We observed a case, throughly studied and we deemed worth-while to report it, for some important features that were evident. Transient hemolytic anemia, recoverable acute renal failure, persistent increased titer of anti-platelet antibody lasting also after 3 weeks from the withdrawal of the drug and in spite of corticosteroid therapy, could be explained by the immune mechanisms that are, therefore, postulated.

To investigate patterns of monolateral and bilateral nephrolithiasis, we enrolled 196 patients with idiopathic calcium stone disease (ICaSD) and 36 with proven primary hyperparathyroidism (PHP). Monolateral disease occurred in 45 subjects with ICaSD and 3 with PHP. All had had three or more stone events. They were studied for a number of clinical and biochemical parameters. The expected prevalence of monolateral stone disease was calculated according to the binomial distribution of random events. Whereas the observed and expected prevalence of monolateral nephrolithiasis did not differ in PHP, the distribution did not follow a chance pattern in ICaSD, since monolateral disease was still frequent among patient with more than 6 episodes. To find out whether monolateral and bilateral ICaSD had distinct pathogenic mechanisms the two groups were compared for clinical and biochemical patterns: no differences emerged concerning metabolic derangements, urine saturation and diet-related biochemistries. Bilateral stone-formers had a higher recurrence rate, but a similar number of stone-operations or ESWL. In 81 of 151 bilateral idiopathic stone-formers in which we were able to assess the exact number of stone events in left and right kidney, the distribution of stones between kidneys did not differ from the binomial distribution. In conclusion, while PHP-associated nephrolithiasis presents predictable patterns, ICaSD comprises a subset in which the disease occurs monolaterally. These forms cannot be distinguished from bilateral forms with common clinical features or routine biochemistries.

With the increasing number of old people in all western countries and increasing life expectancy at birth, many seniors spend the last period of their life with various afflictions that may lead to cardiac arrest. Bystander cardiopulmonary resuscitation (CPR) increases survival rates. Octogenarians are the fastest growing segment of the population and despite empirical evidence that CPR is of questionable effectiveness in seniors with comorbidities, it is still the only treatment among life-sustaining ones. Cardiopulmonary resuscitation is frequently unsuccessful, but if survival is achieved, a fairly good quality of life can be expected. Various papers analyzed the effect of CPR in hospitalized patients or in cardiac arrest occurring at home or in public places, while less is known about events occurring in the emergency room (ER). We performed a retrospective analysis of cardiac arrest events occurred in ER within 54 months: we analyzed 415,001 records of ER visits (from 01/01/1999 to 30/06/2003) in San Giovanni Addolorata Hospital. Data were analyzed in terms of age and outcome. We identified 475 records with the outcome of death in ER or death on arrival. Out of them, we selected 290 medical records which had sufficient data to be analyzed. Of the 290 patients evaluated, 225 died in ER, 18 were deemed to die on arrival, and 47 survived the cardiac arrest and were admitted to intensive care unit (ICU). The overall mortality was 0.11%, while the incidence of the selected events was 0.072%. The mean age of the analyzed population was 71.3 years. The only possible diagnosis was often cardiac arrest, though most of the times we could specify and group the diagnosis even better. The analysis of the procedures showed that cardiac arrest treated by direct current (DC) shock was similarly distributed in different age groups, and no difference was detectable between the two groups. The mean age of the patients who underwent tracheal intubation (TI) was slightly but significantly lower in comparison with the group of non-intubated patients, thus showing a less aggressive resuscitator behavior in old people. Old people seem to have the same chance for surviving cardiac arrest as young people. Other factors like comorbidity can influence the outcome of a cardiac arrest in the elderly. The results of the present study demonstrate that age itself does not seem to be an independent, unfavorable prognostic factor for the outcome after CPR and that older people must be offered the same chance for surviving cardiac arrest as youngsters.

Wegener's granulomatosis (WG) is a rare small vessels necrotizing and granulomatous systemic vasculitis which usually affects the respiratory-tract and the kidneys. Diagnosis is often difficult, but has become easier with antineutrophil cytoplasmic antibodies (ANCA) detection that may justify a more aggressive biopsy policy also in the elderly. Classic treatment with steroids and oral cyclophosphamide (CY) has proven to be of benefit, but side-effects are severe and frequent and the search for less toxic therapeutic schemes should be encouraged. We treated with intravenous pulses of CY (1 g/m2 monthly for 6 months, every two months for the following 6 and quarterly for another year) 5 of 7 patients with WG recently admitted to our institution. We obtained a quick, complete response in 4 of these patients, with no side effects, nor relapses, after a mean follow-up of 17 months. The only patient who did not respond was identified soon after the beginning of the treatment because of a poor reduction of ESR and could be shifted to oral administration of CY successfully. From our still limited experience CY intravenous pulses have proven to be safe and effective enough to advice its use as the first-choice treatment for WG.

In recent years the relationships among immune, endocrine and nervous systems have been extensively studied, and grouped in a new research field: psychoneuro-immunoendocrinology. Since ancient times its has been known that, in humans, mood as well as environmental influences could affect health. In the late '70s, only, evidence of bi-directional pathways has been achieved, first in animal models and, later on, in humans. We reviewed current knowledge on neuroimmunomodulation, concerning the influence of stress and psychological status on immunity as well as neuroendocrine modulation by the immune system, reporting some data obtained from our studies. Particularly, having detected a relevant impairment concerning most of the parameters studied, we emphasized the effects of depressive disorders on immune function in the elderly.

Six patients (3 children and 3 adults) with the clinical and biochemical features of Bartter's syndrome are presented. Pediatric cases included a more severe form, in one patient, with physical and mental retardation, hypercalciuria and nephrocalcinosis, and a less severe one, including two patients, with milder clinical features, low calcium and high magnesium excretion and hypomagnesiemia. Adult patients were affected by either the mild congenital form (case n. 4) or the acquired variety (cases n.5 and 6). Tubular function was investigated in the 3 adults by assessing clearance measurements during maximal diuresis. There was a defective fractional distal solute reabsorption (FDR) ranging between 0.52 and 0.60. This was well below the results obtained in one patient with psychogenous vomiting (FDR 0.94) and comparable to those in two patients with interstitial nephropathies caused by vesico-ureteral reflux (FDR 0.63 and 0.67 respectively). We concluded that: 1) the etiopathogenetic spectrum of Bartter's syndrome corresponds to different clinical presentation (mild, heavy, congenital or acquired varieties), and alterations in mineral and electrolyte renal handling; 2) reduction in FDR is a feature neither essential nor exclusive of this syndrome.

The influence of acyl chain length, double bond number and position on the structural and dynamic properties of phosphatidylcholine bilayers in the liquid crystalline state was studied. The range and rate of the rotation of 1,6-diphenyl-1,3,5-hexatriene and a set of n-(9-anthroyloxy)stearates (n = 2, 7 and 12), which are located at different depths in the lipid bilayers, were measured using differential polarized phase fluorometry in multilamellar liposomes of several unsaturated synthetic phosphatidylcholines. For the anthroyloxystearate probes, two rotational modes, ‘in’ and ‘out’ of the plane of the anthroyl aromatic ring, were partially resolved by measuring at different excitation wavelengths. The data obtained here indicate that in lecithins containing the same acyl chain in sn-1 and sn-2, the introduction of double bonds towards the deep interior of the lipid bilayer decreases the order in the external region of the bilayer and the viscous resistance to the rotation of all the probes tested. On the contrary, double bonds located towards the external region of the bilayer increase order and viscous resistance to the rotation of probes located in the external region. Increasing acyl chain length has different effects depending on the probe and on the rotational mode considered. Measurements in mixed chain lecithins indicate that the influence of increasing unsaturation in sn-2 has different consequences depending on the acyl group that is present in sn-1. Similarly, increasing acyl chain length in sn-1 influences differently the bilayer properties depending on the fatty acid that is present in sn-2.

Lo scopo di questo lavoro è studiare varietà Riemanniane a curva omogenea il cui tensore di curvatura è della forma $aR_{s^{n}}+bK,\, a,b\epsilon\mathbb{R}$, dove K è semisimmetrico, i.e. K$\cdot$K=0, e di Einstein. Quando a > 0 si prova che la varietà deve avere curvatura sezionale costante, mentre il caso a < 0 rimane aperto. This paper is dealing with the problem of characterizing those curvature homogeneous Riemannian manifolds whose Riemannian curvature tensor is of the form $aR_{s^{n}}+bK,\, a,b\epsilon\mathbb{R}$, where K is semisymmetric, i.e. K$\cdot$K=0, and Einsteinian. When a > 0 it is shown that the manifold must be of constant sectional curvature, while the case a < 0 still remains open.

The risk of calcium stone formation in the course of primary hyperparathyroidism (PHPT) is known to arise from increases in excretion of promoters such as calcium1, phosphate2 and perhaps oxalate. In contrast, the role of inhibitors has so far received less attention and very little is known about citrate, which is a main inhibitor of calcium salt crystallization in urine. Therefore, we have studied patterns of citrate excretion and renal handling in patients with PHPT and calcium nephrolithiasis and their changes after successful parathyroidectomy (PTX).

Twenty eight patients with previously untreated oesophageal carcinoma without distant metastases were divided into two groups: Group A consisted of 18 pts. treated with conventional external radiotherapy only. Another group of 10 pts. (Group B) received treatment with external beam irradiation with further high dose rate intraluminal brachytherapy up to a dose of 4-12 Gy delivered in 2-3 sessions of 4 Gy (one session a week). All pts. were evaluated clinically, radiologically and endoscopically every 3 months. At the end of treatment there was a marked difference in relief of dysphagia (39% in Group A vs. 90% in Group B), local control (56.7% in Group A vs. 100% in Group B) and time to progression of dysphagia (20.8 weeks in Group A vs. 67.7 weeks in Group B). No marked difference was observed in overall survival. The complication rate was low in both groups and major complications were observed in pts. treated with external radiotherapy alone (two fistulas). The association of external beam and intraluminal radiotherapy can give a better local control of the disease, improving the quality of life.

Circulating immune complexes (CIC) have been detected in several autoimmune diseases, and studies have also suggested that CIC provide a useful tool as tumor markers. In order to identify differences or similarities in antigenic composition, CIC from 23 patients with gastrointestinal (GI) tumors, from 20 patients with stage III and IV melanoma and from 6 patients with inflammatory bowel disease (IBD) were studied. Serum from all GI, melanoma and IBD patients showed higher levels of CIC than controls. SDS/PAGE electrophoresis under reducing conditions revealed some differences between cancer and IBD patients as far as the CIC protein composition was concerned. In melanoma patients, two fast-migrating bands, in the regions of 71-74 and 30-49 kD, were found, consistent with previously isolated and characterized antigens described in the literature.

Sixty patients with Echinococcus granulosus infection of the liver, lungs, bone and/or soft tissues were treated for several months with oral mebendazole (50-60 mg kg-1 day-1), in divided doses after fat-rich meals, either without surgery (WS), post-surgery (PS) or pre- and post-surgery (PPS). Long-term follow-up, possible for 52 of the patients, showed that WS, PS and PPS patients have so far remained disease-free following treatment for (means +/- standard deviations) 65.5 +/- 37.7, 82.5 +/- 37.0 and 84.1 +/- 28.3 months, respectively. Ultrasound and computed tomography scans were similar in WS and PPS patients post-treatment. Blood eosinophil levels, which were sometimes elevated initially, returned to normal in all patients and this decrease indicated cyst degeneration before this was evident on the scans. Treatment of patients with cystic echinococcosis may no longer require surgery.

Coagulation disorders are frequently detected in patients affected by different tumours even though clinical symptoms occur in a very small percentage of such subjects. Coagulation processes are probably involved in the mechanism of metastatic spread. We assayed the plasma levels of thrombin-antithrombin III (TAT) complexes in a group of 276 patients with several tumours in different stages in order to achieve a better understanding of the complex interactions between coagulation disorders and either tumour growth or metastatic spread. High levels of TAT complexes were found in 51% of localized, 66.3% of metastatic and 58.3% of patients with no evidence of disease; a statistically significant difference was observed comparing metastatic cancer either with localized (p < 0.00015) or with free-of-disease (p < 0.004) groups. Gastrointestinal tract neoplasms showed higher levels of TAT complexes in the metastatic than in the localized group. No difference was seen between small-cell and non-small-cell lung-localized cancer. Our results confirm the frequent coexistence of cancer and subclinical blood coagulation disorders. The evidence of higher levels of TAT complexes in metastatic cancer than in the other groups could be related to the mechanisms involved in tumour spread.

The prognosis of esophageal adenocarcinoma is extremely poor. Despite recent improvements in diagnostic and therapeutic techniques, the 5-years survival rate remains below 10%. Management is primarily surgical or radiotherapeutical, although pre- or postoperative radiation or chemotherapy are often employed. Chemotherapy alone, however, has not demonstrated great therapeutic efficacy in the management of this neoplasm. As most patients with cancer of the lower esophagus have an advanced stage of the disease and a very poor prognosis, the main aim of treatment should be to improve the quality of life. Intracavitary radiation (high dose rate) is a well recognised method of treatment alone or in combination with external radiotherapy. Its simplicity, the convenience of short treatment time and radiation safety provided by the remote after loading system make this the ideal palliative treatment in esophageal cancer. Endoscopic techniques, like dilation and endoprosthesis placement, laser therapy or BI-CAP probe, provide good palliation for dysphagia, with a low morbidity rate. The paper describes a case of lower esophageal adenocarcinoma treated with combined external and intracavitary radiation and endoscopic palliative techniques. Good control of the disease was achieved and the patient is alive 26 months after treatment with a good quality of life.

The relationship between cancer and coagulation disorders is widely accepted. Such disorders can contribute to the metastatic spreading of the primary tumor. Aim of our study was to evaluate the alterations of thrombin-antithrombin III complex (TAT) measured by an ELISA plasma assay in a population of 78 patients suffering from various gastrointestinal tumors. We found high levels of TAT in 68.6% of the patients. Our data show that assay of TAT plasma levels may be a useful test in detecting early coagulation disorders in cancer patients.

We examine the interaction between curvature and growth properties of the fundamental group of compact Riemannian manifolds.

To investigate the presence of reduced bone mineral density (BMD) and to assess determinants of bone loss in rheumatoid arthritis, 45 female patients suffering from non-steroid treated rheumatoid arthritis were submitted to dual photon absorptiometry of the lumbar spine and to laboratory tests for calcium metabolism. The rheumatoid arthritis patients were divided into two groups according to anatomic grade and functional class; no abnormalities in calcium metabolism were detected whereas BMD was significantly lower in the third and fourth grade and in the third and fourth class patients (P less than 0.005 versus controls, versus grades I and II and versus classes 1 and 2). BMD was significantly correlated with age (P less than 0.001) and years postmenopausal (P less than 0.01), but not with duration of disease. By multiple linear regression we derived an equation predictive of BMD. Osteoporosis in rheumatoid arthritis is observed even in non-corticosteroid treated patients; articular lesions with subsequent reduction in physical activity appear to play an important role in axial bone loss in rheumatoid arthritis.

Circulating immune complexes (CIC) were previously reported to be higher in extended cancer rather than in localized one, by a few groups of investigators as well as by ourselves. The techniques employed were quite different in each study. We described a "direct" laser nephelometric assay. At the same time we determined the serum levels of 4 acute phase proteins (AFP)--alpha 2 macroglobulin, C reactive protein, haptoglobin, alpha 1 acid glycoprotein--by conventional light scattering method, in order to investigate on other possible "immune-modulating" factors. The possible correlations either with prognosis or clinical stage are looked for; the hypothetical behaviour of CIC as one of the serum "blocking factors" and of acute phase reactant as "immune modulating" proteins are discussed. The data concerning the techniques able to remove CIC from the blood stream of the cancer patients were also showed (plasmapheresis and immunoadsorption).

The aim of this volume is to offer a set of high quality contributions on recent advances in Differential Geometry and Topology, with some emphasis on their application in physics.A broad range of themes is covered, including convex sets, Kaehler manifolds and moment map, combinatorial Morse theory and 3-manifolds, knot theory and statistical mechanics.

Keeping calcium (Ca) balance in equilibrium is one of the main goals in dialysis patients, and the dialysis schedule by itself can affect mineral metabolism. The aim of this paper is to evaluate Ca and magnesium (Mg) balances on different Quf in patients on RDT. Twenty-one patients [7 on hemodialysis (HD), 14 on hemodiafiltration (HDF)] were studied. Ca and Mg balances were assessed by measuring Ca and Mg in whole dialysis fluid. One patients on HDF was observed for three dialysis sessions, on different Quf, and negative values were observed for Quf above 70 ml/min. Mg balance was always negative. We conclude that an accurate survey of Ca balance is mandatory in high-efficiency dialysis, when high fluxes may produce adverse effects on mineral metabolism.