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Two hundred and thirty-eight in-patients with signs and symptoms of acute purulent bronchitis or purulent exacerbation of chronic bronchitis at stage 1 and 2 of Anthonisen's classification were enrolled in 11 Centers and randomly assigned to one of the following 3 treatment groups: group A, cefodizime 1 g i.m. qD; group B, cefodizime 1 g i.m. BID; group C, ceftriaxone 1 g i.m. qD. Bacteriological results after treatment were satisfactory in 64 patients (91.4%) of group A, 64 (92.8%) of group B and 74 (94.9%) of group C. Global clinical results after treatment showed satisfactory efficacy in 57 patients (79.2%) of group A, 59 (85.5%) of group B and 63 (80.8%) of group C. There was no statistically significant difference in improvement in single symptoms, global bacteriological or clinical results between the 3 groups. Mild adverse events occurred in only 3 patients (one per group).

Doppler spectra were recorded at different cyclosporin A (CSA) levels (trough and peak) in 30 stable renal-transplanted outpatients: 15 with unimpaired renal function (plasma creatinine150 mumol/l) and 15 with renal impairment (plasma creatinine 150-350 mumol/l). Pulsatility (PI) and resistive indexes (RI) have been measured in the renal artery at the hilum and in the renal cortex. RI and PI were markedly increased (p0.0001) in the cortex at peak time while in the renal artery no significant changes were observed. These variations were statistically related with CSA blood levels (PI = p0.02; r = 0.54, RI = p0.05; r = 0.45). These effects were also found in the presence of renal damage. CSA dose-dependently reduces cortical blood flow, causing a persistent arteriolar vasoconstriction and a reduction in diastolic flow. This effect can be measured in man in a noninvasive and repeatable way using color Doppler sonograms.

A total of 124 patients with lower respiratory tract (44) or urinary tract infections (80) were enrolled in an open, multicenter study to evaluate the efficacy and tolerability of sulbactam/ampicillin, administered at the dosage of 3 g/die by intramuscular route. Pretreatment pathogens from patients with lower respiratory tract infections included: Streptococcus alpha-haemolyticus in 8 cases, Streptococcus beta-haemolyticus in 2 cases, Staphylococcus albus in 7 cases, Haemophilus influenzae in 7 cases, Staphylococcus aureus in 6 cases, Klebsiella oxytoca in 5 cases, Staphylococcus epidermidis in 3 cases, Streptococcus pneumoniae in 3 cases, Escherichia coli in 2 cases; in one subject (2.75%), no microorganisms were isolated. In vitro, 36 isolates (84%) were sensitive to SA and 7 (16%) were resistant. At the end of therapy, all the causative pathogens sensitive to sulbactam/ampicillin were eliminated. In patients with urinary tract infections, pretreatment pathogens were: E. coli in 40 cases, S. albus in 16 cases, Proteus mirabilis in 8 cases, Enterobacter agglomerans in 6 cases, Proteus vulgaris in 3 cases, Streptococcus faecalis in 3 cases, Streptococcus liquefaciens in 2 cases, Pseudomonas aeruginosa in 2 cases. In vitro, 64 isolates (80%) were sensitive to sulbactam/ampicillin and 16 (20%) were resistant. At the end of therapy, 63 out of the 64 pathogens sensitive to sulbactam/ampicillin were eliminated; in one case the therapy was interrupted due to adverse effect. Clinical efficacy: in subjects with lower respiratory tract infections, sulbactam/ampicillin cured 32 patients (72.72%) and ameliorated the clinical status of 8 patients (18.18%); efficacy rate: 90.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

Allergy to fresh fruits and vegetables is IgE-mediated. Its main clinical features are local, such as oral pruritus and swelling of lips and tongue but systemic symptoms such as urticaria, asthma, or anaphylactic shock may occur. Clinical associations with allergic rhinitis due to cross-reactive antigens of pollens and foods are frequent.

We recently succeeded in eradicating a Fusarium infection by treatment with liposomal amphotericin B (L-AmB). The patient, a 22-year-old man with acute lymphoblastic leukaemia (ALL), developed fever and diffuse cutaneous maculopapular necrotising nodules during post-chemotherapy neutropenia. Fusarium verticilloides was isolated from the skin, and hyphae were observed on direct microscopy. Despite increased WBC and amphotericin B (AmB) treatment (0.7 mg/kg/day for 11 days), he remained febrile and a chest X-ray revealed pulmonary lesions. Fusarium infection was confirmed by bronchial aspirate. AmB was increased to 1 mg/kg/day, and continued for 16 days (total dose 1630 mg). A slight improvement was observed at tomography, but nephrotoxicity developed. Treatment was changed to L-AmB (3 mg/kg/day). The patient received this drug for 20 days (total dose of 3850 mg) with complete regression of the pulmonary lesions. No adverse event occurred, and nephrotoxicity resolved. The patient was discharged from hospital cured of the Fusarium infection and in clinical and haematological remission. No relapse of fusariosis occurred, despite additional courses of intensive chemotherapy. Ambisome could represent an important advance in antifungal treatment since it allows aggressive treatment and eradication of mycoses refractory to conventional therapy while avoiding renal toxicity.

Important side-effects limit the use of cyclosporine A (CSA), the most insidious of which is nephrotoxicity, which manifests as a preglomerular arteriolar vasoconstriction causing a reduction in glomerular filtration rate (GFR) and renal plasma flow (RPF). This condition is initially purely functional, but with time can become anatomic and irreversible [4].

Important side-effects limit the use of cyclosporine A (CSA), the most insidious of which is nephrotoxicity, which manifests as a preglomerular arteriolar vasoconstriction causing a reduction in glomerular filtration rate (GFR) and renal plasma flow (RPF). This condition is initially purely functional, but with time can become anatomic and irreversible. In clinical practice we lack suitable methods for evaluating CSA vasoconstriction. Our present knowledge is based on indirect information obtained from repeated measurerments of plasma creatinine levels and from blood concentrations of the drug. Sometimes more complex and non-routine tests, such as the evaluation of GFR and RPF, or invasive methods, such as renal biopsy, are also employed. In this study we used the colour-Doppler technique to measure directly the vascular effects of CSA in patients with transplanted kidneys, evaluating changes in blood flow at the hilus and on the cortex of the kidney when the drug was at trough or peak levels.

The recombinant (r) cytokines interferon-gamma (rIFN-gamma), granulocyte/macrophage-colony stimulating factor (rGM-CSF) and tumor necrosis factor-alpha (rTNF-alpha) all activate neutrophils. The aim of this work was to determine the effect of these cytokines on neutrophil Fc-receptor (FcR)-mediated phagocytosis and membrane expression of FcR, particularly FcRII and FcRIII. A short treatment (greater than or equal to 15 min) of neutrophils with rGM-CSF and rTNF-alpha at concentrations greater than or equal to 62.5 U/ml significantly increased their ability to bind and phagocytize IgG-coated erythrocytes (EA). Both cytokines also showed more enhancing activity when suboptimally sensitized EA were used for binding and ingestion assays. A similar treatment of neutrophils with rIFN-gamma at doses up to 500 U/ml was ineffective. The effect of rGM-CSF and rTNF-alpha was blocked by a monoclonal anti-GM-CSF antibody and by a polyclonal anti-TNF-alpha antibody respectively, thus establishing that the cytokines were responsible for the activity of the recombinant preparations. The cytokine-induced enhancement of FcR-mediated phagocytosis did not correlate with an enhancement of FcRII membrane expression on treated neutrophils; rGM-CSF significantly increased FcRIII expression, but rTNF-alpha and rIFN-gamma were both ineffective in this respect. Since different roles of FcRII and FcRIII have been reported on ligand binding and ingestion, we also studied the effect of rGM-CSF and rTNF-alpha on the functional properties of these FcR, using specific monoclonal antibodies (mAbs). In the blocking experiments the pretreatment of neutrophils with rGM-CSF and rTNF-alpha did not modify the blocking properties of either anti-FcRII or anti-FcRIII mAbs, suggesting that cytokine-pretreatment does not affect the individual contribution of each type of FcR to ligand binding and internalization. Our data point to a new activity for both rGM-CSF and rTNF-alpha in augmenting FcR-mediated phagocytosis on neutrophils, but the mechanism of this enhancement remains to be elucidated.

The behaviour of some serological aspects of autoimmunity was studied in patients with inflammatory bowel disease (IBD) by determining the incidence and levels of serum IgM, IgG and IgA rheumatoid factors (RF) and of circulating immune-complexes (IC) in 67 patients suffering from ulcerative colitis (UC) and 53 from Crohn's disease (CD). Sera from 40 young healthy subjects were included as controls. RF were detected by an enzyme linked immuno-assay (ELISA) and IC by the CIC-conglutinin and the CIC-C1q assays. ELISA detected a higher incidence of IgM RF in both UC and CD groups than the routine agglutination tests, although the mean levels were non significantly higher than in controls. Mean IgG RF levels were significantly above normal in UC and CD patients, the latter showing a greater incidence of elevated values and higher mean levels. IgA RF were significantly elevated only in CD patients; mean values for the UC group were within the normal range. The CIC-conglutinin test did not detect a significant incidence or high mean levels of IC and the CIC-C1q assay turned up a sizeable number of positive samples only in the CD group. Although still only preliminary, these overall findings suggest that RF activity is somehow present in patients with IBD. The greater prevalence of IC in CD patients, together with the patterns of IgG and IgA RF support the concept that this disease possibly involves autoimmune phenomena more than ulcerative colitis.

The relationships between autoantibodies to soluble cellular antigens and clinical features in systemic lupus erythematosus (SLE) were investigated in a large clinical-serological study. The absence of these precipitins in serum was associated with a low prevalence of vasculitis and membranous nephropathy (MGN). Other significant findings were the associations between nRNP antibody and Raynaud's phenomenon and MGN, SSB antibody and sicca complex, PCNA antibody and a young age at onset, and Bu antibody and an old age at onset. However, the most impressive findings were in DA1-positive patients which showed a unique prevalence of photosensitive skin lesions, lymphoadenopathy and hepatosplenomegaly. The present study confirms the usefulness of antibodies to soluble cellular antigens in the classification of patients with SLE.

Foremost among the various mechanisms which have developed during the evolution of living creatures are those taking place during the inflammatory process, triggering defense mechanisms vs. chemical, physical and biological toxic agents. The present review aims at explaining some of the physiopathological mechanisms which play a role during inflammation.

Fifteen splenectomised and 15 normal subjects were studied, in absence of any intentional immunisation, for pokeweed mitogen induced synthesis of antipneumococcal capsular polysaccharide antibodies in vitro by peripheral blood mononuclear cells. Results showed that removal of the spleen had caused a persistent immune deficiency of circulating B cells capable of synthesising IgM antipneumococcal capsular polysaccharide. In vitro synthesis of polyclonal IgM and IgG by peripheral blood mononuclear cells of subjects without spleens was also depressed. These defects were due to an abnormality of the B cell compartment. These data are evidence of the major role of the spleen in the control and production of a consistent part of pokeweed mitogen responsive circulating B cells and add another facet to the complex immune dysfunction of splenectomised subjects. The findings, moreover, may help in understanding the susceptibility of splenectomised people to pneumococcal sepsis and the delayed and impaired antibody response to pneumococcal vaccine.

In 15 subjects immunized with two doses of purified adjuvant-free tetanus toxoid, the behaviour of specific IgE and hemoagglutinative antibodies was studied. In the majority of the subject the presence of specific IgE and hemoagglutinative antibodies was observed upon a control carried out 15 days after immunization. After reintroduction of antigen an increase both of specific IgE and hemoagglutinative antibodies was observed. No subject who had presented specific IgE in the serum after the first inoculation of tetanus toxoid showed local or general reaction after reintroduction.

Reference is made to a series of 620 cases of Raynaud's phenomenon observed at the University of Milan between 1951 and 1977. The following parameters are analysed: sex, age, aetiology (where known), incidence of involvement of the four limbs, presence or otherwise of a complete sign, percentage of trophic lesions, arteriographic picture, lab examinations performed. 534 thoracic sympathectomies were performed in 464 patients with Raynaud or Raynaud-like forms. The results are described.

Circulating immune-complexes (ICs) and complement system (C) were studied in sera from 10 patients with malignant skin melanoma. The presence of ICs was demonstrated in all of them by three distinct methods. Moreover, ICs were purified in all the patient sera. The fact that ICs were detected in each serum and that the results of the analysis obtained by the different methods were not overlapping is discussed. It is stressed that the differences among the intrinsic characteristic of each technique are responsible for these discrepancies. The C profile was altered if compared with normal values, but it was not strictly characteristic for an ICs disease. In the purified ICs C3, C4, IgM, IgC1, and IgG3 were demonstrated; C1q, C1s, IgA, IgG2, and IgG4 never. It is noteworthy that a rheumatoid activity was found in the purified material and that this activity was significantly correlated with serum immuno-conglutinins (IKs) titre.

From a clinical point of view Brouet’s classification of cryoglobulinemias, so widely accepted, has several limitations particularly because it cannot have a nosological meaning and also because of some technical aspects; in effect some cryoglobulins cannot be easily immunochemically classified: for example there are cryoglobulins consisting exclusively of polyclonal IgM or IgG [7]. But in order to discuss the problem of the classification of cryoglobulinemias we will present our case series; this collects also patients seen by Dr. M. Galli in the Clinic of Infectious Diseases of the University of Milan and by Dr. G. Monti in the Hospital of Saronno.

The presence of circulating soluble immune complexes and the level of complement were investigated in sera from 21 patients with beta-thalassaemia major, including both splenectomised and nonsplenectomised patients. A high level of immune complexes was found in half of these cases. Reduced complement levels were seen less frequently. There was no correlation between the presence of circulating immune complexes, decreased complement levels, and thpresence or absence of the spleen. The level of immune complexes increased with the age ofthe individual, i.e. with the duration of the disease.

We used an adaptation of an enzyme-linked immunoadsorbent assay (ELISA) to determine serum levels of IgM, IgG and IgA rheumatoid factors (RF) in 50 patients with classic or definite rheumatoid arthritis (RA) according to the ARA criteria, balanced for positive or negative-routine Latex-RF reaction. A control group of 50 young normal subjects and a reference group of 44 patients with other connective tissue diseases (OCTD) were also studied. We confirmed the high sensibility of the method, together with its good specificity and reproducibility. For the IgM RF a very significant correlation was found between ELISA results and Latex-RF titration (p less than 0.001). Many Latex-RF negative RA patients had high ELISA levels of IgM RF, suggesting that this assay reveals, at least in part, hidden or non-agglutinating IgM RF. Among the OCTD group only some SLE cases, mainly Latex-RF positive, had enhanced IgM RF on ELISA. Considered quantitatively, IgG RF did not play a significant diagnostic role for RA (p greater than 0.05), because they were also found, with widely dispersed values, in normal subjects, and because the mean increase in RA patients was relatively small. Interestingly, IgA RF were above the normal range in many RA patients, both Latex-RF positive or negative. The mean values differed significantly from those of controls (p less than 0.005), and a correlation was observed between IgA RF levels and IgA containing immune-complexes. Normal IgA RF values were observed in SLE patients, even if Latex-RF positive, suggesting that their increase in RA patients is not the mere expression of a polyclonal B cell activation.

Nasal challenge and intradermal injection with substance P (SP) were performed in five normal subjects and in five patients suffering from allergic rhinitis. No clinical symptoms, local histamine release, or modifications of nasal airway resistance were observed when SP was insufflated in the nose. Conversely, intradermal injection with SP caused a wheal and flare reaction in all the studied subjects. The different response to SP is likely to be due to the heterogeneity of human skin and nasal mucosa mast cells as far as sensitivity to histamine-releasing agents is concerned. Our findings indicate that SP has no relevant effect on human nasal mucosa, even if a synergetic action of SP with other allergic mediators cannot be excluded. The role of SP in the pathogenesis of allergic diseases in humans remains to be defined and deserves further study.

Persistent unexplained lymphadenopathy with intermittent fever, weight loss, night sweats and malaise was observed in the period from March 1983 to April 1984 in 66 intravenous drug addicts living in Milan. A high percent of these subjects showed cellular immunity alterations, with significant decrease of total lymphocyte count (p less than 0.001) and of OKT4+ cells (percent and absolute number) (p less than 0.001) OKT8+ cells were augmented in percent, but not in absolute count. OKT4/OKT8 cell ratio were inverted, with significant reduction versus the healthy controls (p less than 0.001). IgG mean concentrations were significantly higher than the normal (p less than 0.001). Anergy or hypoergy to recall skin testing were evidenced in 58/66 patients. Cases of persistent unexplained lymphadenopathy associated with abnormalities of cellular immunity are considered as a possible prodrom of AIDS and were frequently observed in high risk populations. The occurrence of this clinical syndrome in a urban area may be premonitory of further progression to the epidemic. It will be necessary to assess whether this clinical and immunological picture will result in some of these patients in full blown acquired immunodeficiency syndrome.

In 197 patients with perennial rhinitis, 49 patients (24.9%) were found to be allergic to perennial inhalant allergens, 37 patients (18.8%) allergic to seasonal allergens, 52 patients (26.4%) had food intolerance, 12 patients (6.6%) showed evidence of nasal infection, and in 46 patients (23.3%) etiology was undetermined.

Twenty patients with chronic urticaria exacerbated by aspirin or tartrazine were challenged with the offending substance after pre-treatment with either oral sodium cromoglycate or placebo in a double-blind, crossover study. The sequential vascular response test (SVR) described by Fisherman and Cohen 1-4 was used to assess response to challenge. Eighteen patients were protected by oral sodium cromoglycate and one by placebo, taking as a positive response an increase in the bleeding time of 100% or more over control values.

The behaviour of some immunologic parameters was studied in order to explain the presence or the lack of symptomatology in subjects with IgE specific to foods. In particular, we compared the levels of serum and salivary IgA and IgE antibody specific to apple in 33 patients allergic to birch and with anti-apple IgE, of whom 24 had oral allergy syndrome after eating apple and nine were apple tolerants. We found no differences in the IgE-related parameters such as levels of anti-apple IgE antibody in serum and secretions, mean size of apple skin prick test, and number of patients with a positive histamine release from peripheral basophils stimulated by apple. Similarly, we detected no statistically significant differences in serum and salivary total IgG and total anti-apple IgA antibody of the two groups. We could, however, observe a significantly higher anti-apple salivary IgA/anti-apple serum IgE and anti-apple salivary IgA/anti-apple serum IgA ratios and a significant correlation between the same parameters in tolerant patients when compared with the intolerants. These results seem to suggest that the presence of appropriate levels of secretory anti-apple IgA associated to anti-apple IgE might be one of the factors playing a key role in the prevention of clinical symptoms in atopic subjects.

Plasma and isolated cryoglobulins from ten patients with mixed cryoglobulinemia were studied for the presence of DNA using the diphenylamine reagent test. DNA-like material was detected in all the plasmas tested and it was also present in nine of the isolated cryoglobulins. IgM and IgG components of three cryoglobulins were purified by gel-filtration: anti-DNA activity was detected in IgG fraction (two cases), in IgM and IgG (one case); antigammaglobulin activity was always found in IgM fraction.

The case reported concerns a 19-year-old man who presented with clinical and laboratory findings compatible with the Wiscott-Aldrich Syndrome. Our patients is the eighth reported case of a long-term survivor with this syndrome. Immunologic studies revealed, in spite of a normal lymphocyte number, an impaired delayed hypersensitivity and a failure of response to mitogens and irradiated allogeneic cells. IgE and IgA levels were high while IgM levels were low. Studies of phagocytic cells showed normal phagocytosis, candidacidal activity, IgG receptors and phagocytic metabolic burst. However, the patient's neutrophils and monocytes responded poorly to chemoattractants and the serum generated less chemotactic activity than normal sera. Detailed studies revealed the presence in the patient's serum of 2 different inhibitors of chemotaxis: a cell-directed inhibitor and an inhibitor of chemotactic factors.

The distribution of T cell subsets has been studied by means of OKT monoclonal antibodies in 19 children with atopic dermatitis. In these patients a decreased percentage of circulating OKT4+ cells has been observed, while no difference has been found between atopic and normal subjects, regarding the percentages of circulating OKT8+ and OKT11+ cells. An increased OKT4+/OKT8+ ratio has been detected only in three children with a particularly severe and extensive atopic eczema.

This study was performed to evaluate mediator (histamine and leukotriene C4) release from cord blood and adult blood basophils, challenged with IgE-independent (calcium ionophore A23187) and IgE-mediated (anti-IgE) stimuli. IgE-independent mediator release was similar in adult blood and umbilical blood basophils. Conversely, the anti-IgE-induced histamine and immunoreactive leukotriene C4 (iLTC4) release was significantly reduced in cord blood basophils. Passive sensitization with an IgE-rich serum was followed by a significant increase in the number of eluted IgE molecules from cord blood basophils and by an increase in IgE-mediated histamine release. iLTC4 production was not affected by passive sensitization of umbilical blood basophils. The IgE-dependent mediator release from cord blood basophils was not correlated with the number of cell-bound IgE. In addition, histamine secretion and leukotriene C4 production from cord blood basophils seem to be independent events.

The action of the new non-steroidal anti-inflammatory drug (NSAID) pirprofen on different functions of human polymorphonuclear leukocytes (PMNs) has been studied. The chemotaxis of PMNs was found to be affected by pirprofen in a dose-dependent fashion; at a concentration of 2 micrograms/ml (10 times lower than the therapeutic blood levels) it significantly inhibited PMN locomotion toward two different chemoattractants. Moreover pirprofen inhibited the chemiluminescent response in a dose- and stimulus-dependent way. In fact the drug inhibited the chemiluminescence induced by the soluble stimuli FMLP or PMA, but it was ineffective when zymosan particles were used. The phagocytosis and adhesion functions of the PMNs were not modified by pirprofen at the concentrations tested. These experimental results suggest that a reduction of the accumulation and activation of inflammatory cells in tissues may represent another way, together with cyclooxygenase inhibition, by which pirprofen realizes its antiinflammatory activity in vivo.

We have studied the effects of the immunosuppressive agent Cyclosporin A (CsA) on the allogenic stimulation of human lymphocytes from 10 patients with progressive systemic sclerosis (PSS) and 10 healthy controls, when activated in vitro during 1ry and 2ry MLR. CsA markedly suppressed 1ry MLR in both PSS subjects and controls. In contrast to the marked suppression of 2ry MLR observed for most of the PSS subjects and all control subjects, lymphocytes from 3 out of 10 PSS patients had paradoxically amplified allogenic responses when primed in the presence of CsA. The possibility is discussed that in these patients the recruitment of suppressor-effector cells by CsA-resistant suppressor-inducer lymphocytes is impaired.

Twenty-four adult patients with adverse reactions to foods and food additives took part in a double-blind crossover study to compare the efficacy of oral sodium cromoglycate, 1600 mg daily, with placebo. Duration of treatment was eight weeks. There were statistically significant differences (p less than 0.01) in favor of active treatment as assessed by patients' diary card scores during the last week of treatment. Few side effects were observed. Oral sodium cromoglycate appears to be both effective and well tolerated in the treatment of food allergies, particularly when used in conjunction with a maintenance elimination diet.

A study of some complement functions was performed in two patients affected with hereditary angioneurotic edema (HAE) - mother and daughter - from a Southern Italy family (Apulia) and in three of their relatives. A decreased level of the C1 esterase plasma inhibitor was found in both the patients, who were treated with tranexamic acid with a slight, but definite improvement. However, the disease could not be traced beyond two generations in the pedigree and a couple of ascendants was found who were free from HAE both from the clinical standpoint and from that of the laboratory evaluation of complement functions. The possibility that HAE arose in the family through a mutational event is discussed.

A 23-year-old girl with clinical and laboratory findings characteristic of chronic granulomatous disease is described. The patient was admitted to hospital because of severe disseminated aspergillosis. Studies of neutrophils showed normal phagocytosis but impaired microbicidal killing and a failure of the respiratory burst activity as measured by NBT-reduction, superoxide generation, chemiluminescence and antibody-dependent cell mediated cytotoxicity. Patient's neutrophils had normal chemotactic responsiveness but a marked impairment in the level of serum chemotactic activity was observed. Neutrophils from the parents and 2 maternal aunts showed normal values for all the determinations. The lack of evidence for a carrier state in all the family members studied together with the inability to detect a mixed population of neutrophils in our patient are in contrast with the Lyon's hypothesis of X-chromosome inactivation. Our findings suggest an autosomal recessive inheritance in this female with chronic granulomatous disease.

We referred the data on association between M.S. patients and HLA complex in the different populations. Then we discussed the different aetiopathogenetic hypothesis that centre on the disease. We considered also viral and autoimmunity theory and the possibility that these two hypothesis don't wrangle but complete them.