Urokinase plasminogen activator and TGF-beta production in immunosuppressed patients with and without Pneumocystis carinii.
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Publications and source records attributed to P Serra.
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The Baker's cyst is a distension of the bursa subtendinea and is caused by noninfectious knee effusion secondary to arthrosis, meniscal tears, trauma, rheumatoid arthritis, gout, or any other form of sinovitis, like rheumatoid arthritis. An infected popliteal cyst is much less common; tuberculous arthritis is exceptional, in fact only four cases are described in literature. Herein we describe an additional tbc case of a 51 years old men, who has been initially treated with cytostatic and corticosteroid agents, for a suspected rheumatoid arthritis. The review of the literature suggests the importance of a correct approach to the diagnosis, based on the analysis and culture of the synovial fluid, because delays latency of effective antibiotic therapy can result in permanent joint damage that invalidate the patients.
For unknown reasons, autoimmune diseases such as type 1 diabetes develop after prolonged periods of inflammation of mononuclear cells in target tissues. Here we show that progression of pancreatic islet inflammation to overt diabetes in nonobese diabetic (NOD) mice is driven by the 'avidity maturation' of a prevailing, pancreatic beta-cell-specific T-lymphocyte population carrying the CD8 antigen. This T-lymphocyte population recognizes two related peptides (NRP and NRP-A7) in the context of H-2Kd class I molecules of the major histocompatibility complex (MHC). As pre-diabetic NOD mice age, their islet-associated CD8+ T lymphocytes contain increasing numbers of NRP-A7-reactive cells, and these cells bind NRP-A7/H-2Kd tetramers with increased specificity, increased avidity and longer half-lives. Repeated treatment of pre-diabetic NOD mice with soluble NRP-A7 peptide blunts the avidity maturation of the NRP-A7-reactive CD8+ T-cell population by selectively deleting those clonotypes expressing T-cell receptors with the highest affinity and lowest dissociation rates for peptide-MHC binding. This inhibits the local production of T cells that are cytotoxic to beta cells, and halts the progression from severe insulitis to diabetes. We conclude that avidity maturation of pathogenic T-cell populations may be the key event in the progression of benign inflammation to overt disease in autoimmunity.
To test the hypothesis that in chronic obstructive pulmonary disease (COPD) patients the ventilatory and metabolic requirements during cycling and walking exercise are different, paralleling the level of breathlessness, we studied nine patients with moderate to severe, stable COPD. Each subject underwent two exercise protocols: a 1-min incremental cycle ergometer exercise (C) and a "shuttle" walking test (W). Oxygen uptake (VO(2)), CO(2) output (VCO(2)), minute ventilation (VE), and heart rate (HR) were measured with a portable telemetric system. Venous blood lactates were monitored. Measurements of arterial blood gases and pH were obtained in seven patients. Physiological dead space-tidal volume ratio (VD/VT) was computed. At peak exercise, W vs. C VO(2), VE, and HR values were similar, whereas VCO(2) (848 +/- 69 vs. 1,225 +/- 45 ml/min; P < 0. 001) and lactate (1.5 +/- 0.2 vs. 4.1 +/- 0.2 meq/l; P < 0.001) were lower, DeltaVE/DeltaVCO(2) (35.7 +/- 1.7 vs. 25.9 +/- 1.3; P < 0. 001) and DeltaHR/DeltaVO(2) values (51 +/- 3 vs. 40 +/- 4; P < 0.05) were significantly higher. Analyses of arterial blood gases at peak exercise revealed higher VD/VT and lower arterial partial pressure of oxygen values for W compared with C. In COPD, reduced walking capacity is associated with an excessively high ventilatory demand. Decreased pulmonary gas exchange efficiency and arterial hypoxemia are likely to be responsible for the observed findings.
Deficiency of the seventh component of complement (C7D) is frequently associated with recurrent neisserial infections. We report in the present study the genetic basis for C7D in a Spanish family. We used exon-specific polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) analysis as a screening step for mutations, followed by direct sequencing of the target exon. The mutation in the proband was a homozygous G-to-T transversion at nucleotide 1957, the first nucleotide of the codon GAG for Glu-631, leading to a stop codon TAG (E631X). Our result provides further evidence that the molecular pathogenesis of C7D is heterogeneous.
PURPOSE: The aim of this study was to evaluate whether motor training could improve the straightening-up sequences in patients with Parkinson's disease and, consequently, could ease the capacity of the patients to change body's position. METHODS: Twenty out-patients with idiopathic Parkinson's disease (12 males, 8 females; mean age 72.9; H-Y, 1. 5-3) were enrolled in a rehabilitation programme which included exercises for the mobility of the trunk, of upper and lower limbs and of each segment of the spine, in order to improve the coordination of movement and to avoid postural disturbances. They received 1 hour of group treatment twice a week for a 5 week consecutive period. No changes were made in the pharmacological treatment received by each patient. The patients were evaluated at the beginning and at the end of the rehabilitation training. The statistical evaluation was made using the Wilcoxon test. RESULTS: Statistically significant differences were observed in all the motor parameters that were evaluated (supine to sitting and sitting to supine, supine rolling, standing from a chair). CONCLUSIONS: The observations demonstrate that physical training can be effective in improving motor performance related to changes in position which affects the simple daily activities of the patients.
Sera from sheep and goats in northern Somalia which are exported to countries of the Persian Gulf are systematically checked for brucellosis by local veterinary teams. The standard test used is rapid seroagglutination using the Rose Bengal test (RBT) and seropositive animals are not exported. In order to assess the reliability of the serological results, three randomised batches of samples (653 sera), corresponding to an equivalent number of shipments (October and December 1994 and March 1995) were counterchecked. Control RBTs were carried out by expatriate veterinarians working on behalf of international non-governmental organisations and by the Istituto Zooprofilattico Sperimentale of Padua, Italy, which also performed the complement fixation test (CFT). A fourth batch (n = 100), including a group of sera found positive by the local veterinary teams, was also checked. Agreement ranged from 96.3% to 98.5%.
OBJECTIVE: Exercise tolerance is often reduced in patients with systemic lupus erythematosus (SLE). Mechanisms have been proposed but the underlying causes have not yet been elucidated. The study of pulmonary gas exchange during exercise may be helpful in revealing circulatory, ventilatory, and metabolic abnormalities. We hypothesized that in SLE, exercise aerobic capacity would be reduced due to chronic inactivity and poor muscle energetics. METHODS: Thirteen women with SLE and low disease activity were studied; 5 age matched subjects served as controls. Clinical examination, chest radiography, electrocardiogram, and pulmonary function test were all normal. Subjects underwent 1 min incremental cycle ergometer exercise to exhaustion. Oxygen uptake (VO2), CO2 output (VCO2), minute ventilation (VE), heart rate (HR), and arterial O2 saturation were monitored. Anaerobic threshold (AT), VO2/HR, deltaVO2/deltaWatt, respiratory rate (RR), Ti/Ttot, VE/VCO2, and breathing reserve (BR) were computed. RESULTS: At rest, patients exhibited high VE, respiratory alkalosis, and a wide alveolar-arterial O2 gradient [(A - a)O2] during 50% O2 breathing. Other indexes of respiratory function were within the normal range. In the 6 patients with SLE where pulmonary artery systolic pressure at Doppler echocardiography was measurable, mean level was in the upper limits of normal. During exercise, maximal aerobic capacity was reduced in all patients (VO2 peak, 1098+/-74 vs. 2150+/-160 ml/min, p<0.01; AT, 36 +/-3 vs. 48+/-3% predicted VO2 max, p<0.05). Ventilation adjusted for the metabolic demand (VE/VCO2 at AT) was increased (31+/-1 vs. 24+/-1; p<0.05). A normal breathing pattern was observed during all tests. No patient stopped exercising because of ventilatory limitation (i.e., they had normal breathing reserve). CONCLUSION: Reduced muscle aerobic capacity is common in SLE and is most likely because of peripheral muscle deconditioning. Increased ventilatory demand, secondary to diffuse interstitial lung disease, is not a significant contributor to the reduction in exercise tolerance.
Recent findings have shown that systemic morphine increases extracellular dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), ascorbic acid (AA) and uric acid concentrations in the striatum of freely moving rats. The morphine-induced increase in DA oxidative metabolism is highly correlated with that of xanthine. In the present study, we evaluated the effects of subcutaneous (s.c.) naloxone (1 mg/kg) on morphine-induced changes in DA, DOPAC, HVA, 5-hydroxyindoleacetic acid (5-HIAA), AA, uric acid and glutamate in the striatum of freely moving rats using microdialysis. Dialysates were assayed by high performance liquid chromatography with electrochemical detection or (glutamate) ultraviolet detection. Morphine (5-20 mg/kg) given s.c. increased DA, DOPAC+HVA, 5-HIAA, AA and uric acid and decreased glutamate dialysate concentrations over a 3 h period after morphine. Morphine (1 mM), given intrastriatally, did not affect all the above parameters, with the exception of an early short-lasting decrease in AA concentration. Naloxone antagonised all morphine-induced changes with the exception of AA increase and glutamate decrease in dialysate concentrations. Systemic or intrastrial (0.2-2 mM) naloxone increased AA and decreased glutamate dialysate concentrations. When given intranigrally, morphine (1 mM) increased DOPAC+HVA, AA and uric acid and decreased glutamate dialysate concentrations over a 2 h period after morphine; DA and 5-HIAA concentrations were unaffected. These results suggest that: (i) morphine increases striatal DA release and 5-hydroxytryptamine oxidative metabolism by a micro-opioid receptor-mediated mechanism mainly at extranigrostriatal sites; (ii) morphine increases DA and xanthine oxidative metabolism and affects glutamate and AA release by a micro-opioid receptor mediated mechanism acting also at nigral sites; and (iii) a micro-opioid receptor-mediated mechanism tonically controls at striatal sites extracellular AA and glutamate concentrations.
Since there exist conflicting results with regard to the possible effect of aging on platelet [3H]-imipramine binding, taken as a peripheral marker of the serotonin (5-HT) transporter, we reinvestigated this matter by comparing the binding of the more selective ligand [3H]-paroxetine in 20 aged and 23 young subjects. The results showed that neither the maximum binding capacity nor the dissociation constant (Kd) were significantly different in the two groups. When the subjects were compared according to sex, the young females revealed a statistically significant lower Kd than the males, while the contrary was true for the aged females. The Kd was significantly and negatively correlated to age in males. In addition, a significant age x gender interaction was also observed. Therefore, the sex of a subject would seem to provoke significant age-related changes in the Kd of [3H]-paroxetine binding to platelet membranes. This might indicate modifications in the 5-HT transporter that could form the basis of a sex-related difference in vulnerability to disorders, such as depression, where a dysfunction at this level is hypothesized.
OBJECTIVES: To evaluate the relation between the exposure to specific pesticides in agricultural work and the risk of multiple myeloma (MM). METHODS: A case-control study was conducted in the province of Forlì, Italy. Forty-six cases of MM (20 females, 26 males; mean age 64 years, range 40 to 74) identified through the Romagna Cancer Registry in the years 1987-90, and 230 age- and gender-matched controls from the general population were interviewed in-person using a structured questionnaire focused on exposure to pesticides and other occupational and nonoccupational variables. RESULTS: Among nonoccupational factors, the education level and the altitude of the place of residence were related inversely to MM risk. First-degree familiarity for hematolymphopoietic neoplasias and previous herpes zoster diagnosis were associated positively with the disease. A nonsignificant increase in MM risk was observed among workers in agriculture as a whole (odds ratio [OR] = 1.31, 95 percent confidence interval [CI] = 0.62-2.74). An increased risk was associated specifically with the cultivation of apples and pears (OR = 1.75, CI = 1.05-2.91). As regards pesticide exposure, only the chlorinated insecticides were related to an increase in the risk of MM. CONCLUSIONS: This study suggests that agricultural work and exposure to pesticides have a role in the etiology of MM.
Gammadelta T lymphocytes respond to different bacterial antigens and transformed cells. The antigenic molecules responsible for this activity have been studied extensively in antigenic preparations from Mycobacterium. We describe here the in vitro effect of Pseudomonas aeruginosa on gammadelta T lymphocytes and the properties of the implicated compounds. We found a preferential gammadelta T-cell expansion when we used heat-treated P. aeruginosa preparations and a dose-dependent inhibition of proliferation of peripheral blood mononuclear cells (PBMC) when non-heat-treated antigens were studied. This expansion corresponded to a Vgamma9-positive subpopulation. In contrast to alphabeta T lymphocytes, the highest stimulatory activity was restricted to very small cytosolic compounds. This activity was protease resistant and phosphatase sensitive and always dependent on interleukin (IL)-2 or alphabeta T-cell activation. We concluded that the antigenic molecules from P. aeruginosa that activated gammadelta T lymphocytes were small, non-peptidic, phosphorylated compounds, similar to those previously described from Mycobacterium.
Palliative care and palliative medicine embrace the philosophy and the body of knowledge regarding the correct treatment of patients with terminal disease. Palliative treatments can be delivered intramurally (eg, in a hospice or palliative care unit) or at home (home care hospice). The optimal delivery pattern consists of the co-utilization of both care settings, to allow patients who need palliative, supportive, and terminal care to benefit from each setting. In obtaining the available resources, health service costs in Western countries have lately become exorbitant. Home care hospice is a system capable of defeating the challenge on two fronts: to meet the patients' needs and to fulfill this task through economically advantageous practices. Home care hospice is undoubtedly more cost-effective than conventional or generic home care, conventional care (hospitalization), and inpatient hospice care. Its advantage is more evident in the last 3 months of life, due to shorter hospitalization and nonutilization of high-technology interventions and high-cost drugs. The development of a range of palliative care programs integrating primary territorial care and specialized palliative services can constitute the ideal synthesis to respond to patients' needs in a threefold manner: firstly, the patient's right to qualified palliative and terminal care; secondly, the requirements of health services, and lastly, cost containment through a correct and tailored use of available resources.
BACKGROUND: Reduced muscle aerobic capacity in COPD patients has been demonstrated in several laboratories by phosphorus magnetic resonance spectroscopy and by analysis of oxygen uptake (VO2) kinetics. COPD patients are usually elderly, hypoxemic, poorly active with muscle atrophy, and often malnourished. Under these conditions there is usually reduction of O2 delivery to the tissues (bulk O2 flow), redistribution of fiber type within the muscle, capillary rarefaction, and decreased mitochondrial function, alterations all capable of reducing muscle aerobic capacity. In COPD, the effect of reduced body mass on muscle aerobic capacity has not been investigated (to our knowledge). METHODS: We studied 24 patients with stable COPD with moderate-to-severe airway obstruction (68+/-5 [SD] years; FEV1, 39+/-12% predicted; PaO2, 66+/-8 mm Hg; PaCO2, 41+/-3 mm Hg) with poor to normal nutritional status, as indicated by a low-normal percent of ideal body weight (IBW). Each subject first underwent 1-min maximal incremental cycle ergometer exercise for determination of VO2 peak and lactate threshold (LT). Subsequently, they performed a 10-min moderate (80% of LT-VO2) constant load exercise for determination of oxygen deficit (O2DEF) and mean response time VO2 (MRT). VO2, CO2 output (VCO2), and minute ventilation were measured breath by breath. RESULTS: Patients displayed low VO2 peak (1,094+/-47 [SE] mL/min), LT-VO2 (35+/-3% predicted O2 max), and higher MRT-VO2 (67+/-4 s). Univariate regression analysis showed that percent of IBW correlated with indexes of maximal and submaximal aerobic capacity: vs VO2 peak, R=0.53 (p<0.01); vs MRT R=-0.77 (p<0.001). Using stepwise regression analysis, MRT correlated (R2=-0.70) with percent of IBW (p<0.01) and with PaO2 (p<0.05). CONCLUSIONS: Reduced body mass has an independent negative effect on muscle aerobic capacity in COPD patients: this effect may explain the variability in exercise tolerance among patients with comparable ventilatory limitation.
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Seven cases of enterococcal endocarditis treated with teicoplanin (7-10 mg/kg/day for 28-105 days) alone (one case) or in combination with aminoglycosides (six cases) were reviewed. All patients were cured. Serum bactericidal activity titres after intravenous gentamicin (5 mg/kg every 24 h) and teicoplanin (10 mg/kg every 24 h) were measured on day 7 of treatment in four patients against five enterococcal isolates: mean titres were 1:54 (range 1:16-64) and 1:22 (1:8-32) at 0.5 and 24 h post-infusion, respectively. Time-kill studies showed synergy between teicoplanin and gentamicin against three isolates. We conclude that single daily-dose teicoplanin/gentamicin combined therapy may represent a rational alternative to standard penicillin/gentamicin therapy and a useful regimen for home treatment of selected cases of enterococcal endocarditis.
Systematic radon monitoring in the Gran Sasso Underground Laboratory was performed in order to determine the background radon contribution to the sophisticated experimental apparatus and to check health physics standards for the personnel. As expected, the radon concentrations were found to depend strongly on the ventilation in the three experimental halls. Considerable reductions in the radon concentrations were obtained in 1993, when fresh air was drawn into the laboratory through a pipe and exhaust air was routed into the highway tunnel.