Iron chelation in rheumatoid arthritis: clinical and laboratory evaluation.
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Biomedical subjects
Publications and source records attributed to L Altomonte.
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The AA. report a case of yellow nail syndrome associated with rheumatoid arthritis and monoclonal gammopathy (IgG-lambda). Because of the great variety of the diseases associated with this syndrome, the AA. suggest to control patients periodically to verify the probable appearance of other clinical manifestations.
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Juxtaarticular osteoporosis is a recognized clinical feature in both rheumatoid arthritis (RA) and psoriatic arthritis (PA), while generalised osteopenia seems to be characteristic of RA only. To assess differences in bone turnover in the two forms of disease, we measured serum osteocalcin levels and other parameters of bone metabolism in two groups of female, ambulant, age-matched patients suffering from active RA or active PA and never treated with steroid therapy. Serum osteocalcin levels were significantly higher in RA patients than in PA patients (13.05 +/- 1.27 ng/ml vs 4.83 +/- 0.88 ng/ml; p less than 0.001), with a significant positive correlation between osteocalcin and serum alkaline phosphatase in both groups. These data suggest that bone turnover is higher in active RA than in active PA. Juxtaarticular osteoporosis could be mediated by local disease mechanisms both in RA and in PA, while factors specifically related to active RA seem to determine a more generalized impairment of bone turnover.
Bone GLA protein (BGP) and other biochemical indices of bone turnover were measured in 42 female patients with rheumatoid arthritis (RA) and in a group of normal subjects matched for sex and age. Mean serum BGP concentrations were significantly higher in patients with active arthritis than in patients with mild activity (p less than 0.01) and controls (p less than 0.01). No significant difference was found in serum BGP levels and in other parameters of bone turnover when the patients were stratified according to functional class or duration of disease. There was a correlation between BGP and alkaline phosphatase levels only in RA patients with high activity of disease. Our data suggest an accelerated bone turnover in patients with active RA. We infer that in such patients the impairment of bone metabolism is a determinant of RA-associated osteopenia. Disease activity rather than functional impairment or duration of arthritis should be regarded as a factor in the bone loss of RA.
Nimesulide is a new non-steroidal anti-inflammatory drug which seems to be characterized by a low inhibitory action on prostaglandin synthesis and a high inhibitory action on oxygen free radicals production. The aim of this trial was to determine the effect of Nimesulide on degenerative joint disease and on non-articular rheumatism. One hundred and forty, 64 females and 76 males aged 51.9 +/- 1.2 years, affected with osteoarthritis or non-articular rheumatism (fibromyalgia, periarthritis, tendinitis, tenosynovitis, bursitis and enthesitis) were studied. Nimesulide was administered at a daily dosage of 200 mg. A significative improvement in the clinical parameters studied was observed in all the patients, but a more remarkable progress was noted in the group with non-articular rheumatism. The incidence of adverse reactions was irrelevant: 2 patients complained of epigastralgia that subsided reducing the daily dosage to 100 mg.
The authors report a case of a patient suffering from acute polyarthritis with a high rheumatoid factor titre, associated with a Klebsiella pneumonitis. A polyclonal B lymphocyte activation or a possible cross reaction between rheumatoid factor and an antigen related to Klebsiella may explain the elevated production of rheumatoid factor observed.
Clonidine, an imidazoline derivative, is an antihypertensive agent which reduces sympathetic tone by acting in the central nervous system to stimulate alpha-2 adrenoceptors. There is evidence that dopamine and norepinephrine modulate the secretion of GH. Stimulation of GH release is a well-known effect of clonidine in man. Obesity is characterized by an impairment of GH release in response to various stimuli. The aim of this work is to study GH release in response to alpha-2 adrenoceptors stimulation by clonidine in obesity. 12 volunteer obese subjects were studied. 10 normal weight subjects, sex and age matched, were controls. The GH responsiveness was tested with a single oral dose of clonidine (0.15 mg). Blood was sampled for GH radioimmunoassay at 0', 30', 60', 90', 120', 150', 180'. Serum GH basal levels were not significant different in obese subjects compared to controls. In obese subjects, no significant changes occurred in blood GH concentration after clonidine. In normal weight controls, instead, a significant increase of GH values was reached at 90' (P less than 0.05) and at 120' (P less than 0.05) after clonidine. The impairment of GH release after clonidine in obese subjects might be in a reduced serotonin release or in a failure of the hypothalamic-pituitary system to stimulate plasma GH caused by a diminished GH releasing factor stimulatory effect or by an excessive endorphin or somatostatin secretion in obesity.
Neutrophil chemiluminescence was determined in patients with active rheumatoid arthritis. Twelve patients were randomly assigned either to a diet high in polyunsaturated fatty acids supplemented with eicosapentaenoic and docosahexaenoic acids or to a diet high in saturated fatty acids. A correlation with clinical and laboratory parameters is also reported. No statistical difference was observed in neutrophil chemiluminescence and in clinical parameters in the group of patients treated with a diet high in saturated fatty acids. Fish oil ingestion resulted in subjective alleviation of active rheumatoid arthritis and reduction of neutrophil chemiluminescence. This study corroborates the hypothesis of an anti-inflammatory role for polyunsaturated fatty acids in patients with chronic inflammatory diseases.
A young woman presented with an aortic arch syndrome a few years after the onset of ankylosing spondylitis. Tissue typing showed HLA-B27. The possibility of an association between ankylosing spondylitis and Takayasu's arteritis is suggested.
Obesity is characterized by increased levels of insulin and by subnormal growth hormone (GH) release. Insulin/GH ratio is significantly higher in obese than in lean individuals. Fenfluramine, an anorectic drug, may have some effects on hypothalamic-pituitary function and on insulin secretion, possibly through a serotonergic stimulation. The aim of this work was to study the effects of fenfluramine on the insulin/GH ratio after arginine in obese subjects. Ten volunteer obese females were studied; 10 volunteer women were the normal weight controls. All subjects were given placebo and fenfluramine (60 mg p.o.) in a randomized order and after 120 min underwent arginine infusion (25 g i.v. for 30 min). Blood samples were taken every 30 min until 270 min for GH and insulin radioimmunoassay. In the obese group the GH response to arginine was significantly lower than in controls. Fenfluramine administration restored the subnormal GH response to arginine in obese subjects. Arginine infusion provoked a greater insulin secretion in obese subjects than in lean individuals. Fenfluramine administration diminished the insulin response to arginine. Fenfluramine did not modify the insulin/GH ratio in controls while it significantly lowered the insulin/GH ratio in obese subjects. Because insulin promotes fat and carbohydrate storage while GH stimulates lipolysis, the combination of high insulin and low GH concentrations may worsen the obese condition. A lower insulin/GH ratio can be useful in the treatment of obesity.
The present study was undertaken in order to establish the significance of glucagon in glucose intolerance in liver cirrhosis. The plasma glucose response to an oral glucose load (75 g) was determined in 10 control subjects and in 10 cirrhotic patients, after infusions of: glucagon (3 ng.kg-1.min-1) or saline (154 mmol/l); somatostatin (SRIH) (500 micrograms/h); and SRIH plus glucagon (3 ng.kg-1.min-1). Glucagon infusion did not impair glucose tolerance, neither in normal subjects nor in patients with cirrhosis. On the other hand, in both groups glucose tolerance was impaired by SRIH infusion, presumably owing to an absolute insulin deficiency. Both in normal subjects and in cirrhotic patients, SRIH plus glucagon infusion further impaired glucose tolerance, presumably as a result of excess glucagon and concomitant insulin deficiency. In conclusion, our data show that hyperglucagonemia is not an important factor in the development of the glucose intolerance in patients with hepatic cirrhosis.
Obese subjects show a subnormal growth hormone (GH) and prolactin (PRL) release in response to a variety of stimuli. Fenfluramine, an anorexiant drug used in obesity therapy, may have some effects on hypothalamic-pituitary function mediated by serotoninergic stimulation. The present investigation in obese subjects was carried out to study the effects of fenfluramine (60 mg orally) on GH and PRL secretion after intravenous arginine infusion. Ten volunteer obese females were studied and compared with 10 volunteer normal weight controls. In the obese group the GH response to arginine was significantly lower than in control group. Fenfluramine administration restored the subnormal GH response to arginine in obese subjects. The PRL response to arginine in obese women was subnormal. Fenfluramine administration restored the response of PRL to arginine infusion to normal. In conclusion, fenfluramine--under acute circumstances--enhances the hypothalamic-pituitary response to arginine in obese subjects. The decreased GH and PRL output in obese subjects is not due to an absolute hormonal deficiency and this effect of fenfluramine on GH secretion may--due to its lipolysis stimulation--be useful in obesity treatment.
In order to verify the immunostimulant effect of thymus humoral factors, a bovine thymic extract (TP 1-Thymostimulin) was given to 9 patients affected by primary immunodeficiency (mild deficit T/B combined) and to 8 patients affected by acquired immunodeficiency because of old age, lung neoplasm or with recurrent herpes simplex labialis. 6 patients affected by chronic hepatitis HBsAg+ and 1 patient affected by Behçet's syndrome were also studied. At the end of the study, after six months, all the patients with primary or acquired immunodeficiency showed a normalization of their immunological parameters and a clinical improvement. A clinical improvement was also observed in the patients affected by lung neoplasm. Instead, patients suffering from chronic active hepatitis HBsAg+ showed unsatisfactory results; the study did not reveal any clinical or immunological improvement in these cases. The patient affected by Behçet's syndrome showed a decreased recurrent uveitis.
The role of cAMP and prostaglandins as specific intracellular effectors of gastrin action at the level of the parietal cells has not been sufficiently clarified. For this reason we studied the responses of the parietal cells to stimulation with pentagastrin (6 micrograms/kg i.m.) during theophylline infusion (which causes an increase in the intracellular cAMP) and during acetylsalicylic acid infusion (which inhibits the prostaglandin synthesis) in 28 healthy volunteers. Both theophylline and acetylsalicylic acid provoked a significant increase of gastric acid secretion after pentagastrin. Our results suggest that: 1. an increase in intracellular cAMP may be the basis of the stimulatory effect of gastrin on gastric acid secretion 2. a decrease in the synthesis of prostaglandins may lead to a greater gastric acid response after pentagastrin.
The principal sites of gastrin production in man are localized at the level of the gastric antrum; both the oral glucose load and the protein meal stimulate the gastrin secretion. The aim of this study was to verify the gastrin response in patients with gastric resections presented with various stimuli. In the operated patients, the behavior of serum gastrin after a protein meal was different with respect to that observed in control subjects. After glucose, on the contrary, a very similar result was seen when compared to controls. The increase in serum gastrin of patients with Billroth II provides a further confirmation of an extragastric origin of gastrin.
The inhibitory effect of somatostatin (SRIF) on immunoreactive insulin release and on many other hormonal secretions has been widely studied in both animal and man. However, the mechanism by which SRIF acts on these functions remains poorly defined. Aim of this study is to determine the inhibitory effect of SRIF on insulin secretion induced by arginine after the administration of lysine acetylsalicylate (LAS) in a dose which inhibits the endogenous synthesis of prostaglandins. Ten healthy informed volunteer subjects were studied. Four studies were carried out in randomized order, each one separated by a three day interval. The first study was a test of arginine (25 g i.v. in 30 min). The second study was a test of arginine with SRIF infusion (150 micrograms bolus followed by 100 micrograms/h for 120 min). The third study was a test of arginine with an infusion of SRIF and LAS (66 mg/min for 120 min). The fourth study was a test of arginine with LAS infusion. Plasma insulin levels were determined by radioimmunoassay. After arginine administration the typical biphasic insulin response was observed with a precocious peak at 3 min and a late peak at 30 min. This response is not significantly modified under LAS infusion. With the infusion of SRIF at a dose of 100 micrograms/hr after arginine administration only a very modest insulin response was observed. The addition of LAS does not modify the inhibitory effect of SRIF on insulin secretion induced by arginine. This result demonstrates that the inhibitory action of SRIF on the secretion of insulin is not dependent upon the activation of the endocellular prostaglandin system.
Gastrin-like immunoreactive substances have been reported as occurring in both digestive tract tissues and nervous system, including the hypothalamus and the anterior and posterior pituitary. The carboxyterminal tetrapeptide shared by gastrin and cholecystokinin, which represents the bioactive site of both hormones, has been shown to be a secretagogue for insulin and glucagon and it might have a neurotrasmitter function. As small gastrin-like peptides may also play a role in the regulation of anterior pituitary hormones, the present study deals with the in vivo effect of pentagastrin on the release of growth hormone (GH) and prolactin (PRL). Six healthy volunteer males and six healthy volunteer females were studied. All females subjects were in the early follicular phase of the normal menstrual cycle and all subjects were not taking or had been taking any drug known to affect GH or PRL secretion. A continuous intravenous infusion of pentagastrin (1.5 micrograms/kg/h) was administered to all the subjects for a time of 3 hours. In males pentagastrin infusion resulted in a significant increase in GH concentration from basal values (P less than 0.01 at 60 min). In females pentagastrin infusion did not affect GH levels. PRL levels were not affected at all by intravenous pentagastrin infusion both in males and females. The exact understanding of pentagastrin action on GH release awaits further investigation. The different pattern between male and female subjects suggests a sexual hormone influence on the hypothalamic-pituitary sites of action of pentagastrin in vivo. Our data did not confirm a stimulatory effect of pentagastrin on PRL secretion in normal subjects.