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Biomedical subjects

G Ghirlanda

Publications and source records attributed to G Ghirlanda.

At least 73 records · Page 4Linked to original sources
PubMed1992

Hybrid artificial pancreas: islet transplantation inside membrane bioreactors.

The use of pancreatic islet transplantation in membrane bioreactors put in vascular circuits aims at resetting the glucose homeostasis in diabetic or pancreatectomized patients, avoiding immune host rejection. Our experience was carried out at following stages: porcine pancreas explantation and enzymatic separation of endocrine tissue from exocrine fraction by collagenase; evaluation of islet functionality (culture tests); in vitro tests of the islets-bioreactor system, to assess the metabolic response to the glucose; in vivo evaluation to assay the haemodynamic behaviour. The trials showed a good metabolic bioreactor functionality and a decreasing incidence of coagulative problems.

Animals↗
PubMed1992

[Lactic acidosis, hyperamylasemia, and phenformin].

Phenformin is still used in the therapy of non-insulin dependent diabetes in association with sulphonylureas. The controindications to the use of this drug often are not kept in due consideration. It is therefore often possible to observe cases of irreversible lactic acidosis with lethal outcome. In this paper, three cases of lactic acidosis from phenformin administration are reported. Some characteristics of this clinical picture are underscored: accompanying ketoacidosis, hyperamylasemia. On the basis of their observation, the Authors conclude that those diabetic patients who can be treated with diet alone or with diet and sulphonylureas must not be treated with phenformin. Metformin is then proposed as a more flexible and safer drug.

Acidosis, Lactic↗
PubMed1992

Nicotinamide treatment in subjects at high risk of developing IDDM improves insulin secretion.

Nicotinamide (NCT) has been shown to be effective in preventing the onset of type 1 diabetes mellitus (IDDM) in mice with non-obese diabetic (NOD) and beta cell damage, mediated by the diabetogenic agents including streptozotocin. NCT therapy in man has been shown to have a beneficial effect on the remission phase of IDDM, and its use is safe. In this open pilot trial we therefore studied the effect of oral NCT administration on insulin secretion rate and islet-cell antibody (ICA) titres in IDDM high risk subjects. NCT (25 mg/10 kg bw) was administered in 6/13 high risk patients identified by a family screening programme. Those subjects tested after eight months without treatment showed a decreasing secretion in comparison to onset baseline (56,1 +/- 37.8 versus 35,5 +/- 12.2), whereas the treated subjects showed an increasing insulin secretion after treatment (26 +/- 10 versus 50.2 +/- 26.6), in spite of ICA persistence. Statistical analysis shows an increased insulin secretion in the treated group versus the untreated group (chi 2 = 3.899, P = 0.048). No side-effects were observed. We conclude that NCT may repair beta-cell function in high risk subjects too if damage is not too severe; furthermore, the effect seems not to be mediated by an immune mechanism.

Adolescent↗
PubMed1992

Membrane bioreactors as hybrid artificial pancreas: experimental evaluation.

Results of cultured islet transplantation in the management of insulin-dependent diabetes are still unsatisfactory. The main problem preventing success is the swift and resolute host immune rejection. To obviate this we designed and experimented a model of bioartificial pancreas, made of polymeric hollow fibers, put into the blood circulation as an artero-venous bypass to immunoisolate endocrine tissue from leucocytes and immunoglobulins. We tested four different membrane bioreactors (BR1-4). BR1 and 2 had seven hollow fibers, the others more than 6,000 smaller fibers. In BR4 a connecting tube with a high-permeability membrane was inserted between the islet compartment and the bioreactor outlet to improve the ultrafiltration flow. In vitro, the islets inside the bioreactor perfused with glucose solutions (300 mg%) showed a rapid, high insulin secretory response, related to the glucose stimulation. The use of the outside connection allowed a twofold increase of insulin production.

Animals↗
PubMed1992

Effect of propionyl-L-carnitine in the treatment of diabetic angiopathy: controlled double blind trial versus placebo.

Diabetic angiopathy can be treated by medical or surgical means. In the initial stages of the disease (I and II according to Fontaine), pharmacological treatment aims at supplying ischaemic and therefore hypoxic regions with a sufficient quantity of energetic substrates for metabolic needs. A new method of treating peripheral vasculopathy was carried out in this study using propionyl-L-carnitine (PLC), a propionic ester of L-carnitine. The authors evaluated in a double-blind study the efficacy of chronic oral administration of PLC versus placebo. Twenty type II diabetic patients with peripheral angiopathy were enrolled in this study. They were divided into 2 groups of ten patients each. On termination of treatment, the ankle/arm pressure index, measured at rest, showed an improvement in the PLC treated group and a deterioration in the placebo group. The Windsor index, measured at 2, 5 and 10 min after exercise, showed a significant impairment in the PLC treated group with respect to the placebo group. The percent variation in walking distance, measured at various time intervals according to the protocol, showed a marked improvement in the PLC treated group. These results show that PLC significantly improves both walking distance autonomy and symptoms related to peripheral vasculopathy in diabetic patients. Like carnitine, PLC seems to act through a metabolic mechanism which results principally in preventing lactate formation in ischaemic tissue.

Administration, Oral↗
PubMed1991

Charge selectivity of proteinuria in type I diabetes explored by Ig subclass clearance.

To investigate the role of protein charge in early diabetic proteinuria, the clearance of proteins differing in charge and/or size (anionic and cationic Igs, albumin) was evaluated in 98 insulin-dependent (type I) diabetic patients selected as a representative sample of the 418 patients attending our clinics. Of the patients, 12.9% were microalbuminuric and 4.8% were macroalbuminuric. Anionic and total IgG clearances were significantly increased in 30.6 and 12.2% of patients and were correlated with duration of disease. Anionic IgG4 clearances were increased in patients (9.2%) with normal IgG excretion, suggesting that charge-selectivity impairment is responsible for protein loss. Anionic Ig clearances were also higher in some patients (14.3%) with normal albumin clearance, probably as a result of different glomerular filtration and/or tubular reabsorption. The anionic-cationic IgG clearance ratio tended to increase in parallel with albumin clearance, but once above macroalbuminuric levels, it tended to fall again, indicating the concomitant presence of size-selectivity loss. The anionic IgG clearance and the anionic-cationic IgG ratio, in addition to albumin excretion, may be valuable in assessing early kidney protein charge-selectivity impairment and better characterizing normoalbuminuric patients and those in the preclinical stage of diabetic nephropathy.

Adult↗
PubMed1991

Detection of inner retina dysfunction by steady-state focal electroretinogram pattern and flicker in early IDDM.

The effects of diabetes on the neural retina before the onset of clinically detectable retinopathy can be investigated with electrophysiological methods. Our aim was to detect early retinal dysfunctions in 60 patients with insulin-dependent diabetes mellitus (IDDM) and with a short duration of disease. We used the steady-state focal (9 degrees field size) electroretinogram (ERG) of the macula in response to luminance modulation of a uniform field (flicker ERG) or to counterphase-modulated sinusoidal gratings (pattern ERG). The harmonic analysis of flicker ERG and pattern ERG yielded three main components: a first and a second harmonic to flicker (1F and 2F, respectively) and a second harmonic to pattern (2P). The 1F is believed to be correlated to photoreceptor activity, whereas 2F and 2P represent different subsets of generators in the inner retina. Results of focal ERG in IDDM patients with no or early retinopathy were compared with age-matched control subjects. Mean 2F and 2P amplitudes were significantly reduced in IDDM patients compared with the control group (P = 0.0001 by analysis of variance). 2P but not 2F amplitude was significantly more reduced in patients with retinopathy than in those without retinopathy (P less than 0.05). 2F but not 2P phase abnormalities were observed in some patients. 2F and 2P alterations were slightly correlated with metabolic control (r = 0.22, P = 0.02) and disease duration (r = 0.28, P = 0.003). 1F was not significantly altered in IDDM patients. Our results suggest that early diabetes causes selective neurosensory deficits of inner retina layers, whereas the photoreceptors appear unaffected.

Adult↗
PubMed1991

Relationship between urinary neopterin excretion and islet cell antibodies in type 1 (insulin-dependent) diabetes.

Neopterin is specifically produced by interferon-activated macrophages, and it may be considered a marker of cellular immunity. In 40 newly diagnosed and 38 longer standing type 1 (insulin-dependent) diabetics the relationship between urinary neopterin levels and islet cell antibodies (ICA) was investigated. Raised urinary neopterin levels were found in 30 ICA positive (mean +/- SD: 729.8 +/- 602.1 mumol/mol creatinine, p = 0.0001) and 10 ICA negative (433.4 +/- 191.2 mumol/mol creatinine, p = 0.0005) diabetics at onset of disease compared with age-matched control subjects (118.1 +/- 33.2 mumol/mol creatinine). No significant difference in urinary neopterin levels was observed between diabetic groups. After the first stages of disease (greater than 5 months from onset), a significant difference (p = 0.0002) in urinary neopterin excretion was found between longer standing ICA positive patients and controls, but not between ICA negative diabetics and controls. In longer standing diabetics, neopterin levels were significantly higher in ICA positive patients than in ICA negative patients (544.6 +/- 341.3 versus 201.7 +/- 180 mumol/mol creatinine, p = 0.0002). No correlation between newly diagnosed or longer standing patients and HbA1c levels was found. Our results suggest that increased neopterin excretion in type 1 diabetes seems to be a sensitive indicator for the activation of cell-mediated immunity even when ICA are undetectable.

Adolescent↗
PubMed1991

Gastric emptying rate and hormonal response in type II diabetics.

Gastric emptying time was measured by ultrasonography in 18 NIDDM patients with and without autonomic neuropathy, evaluated by cardiovascular autonomic tests and in 10 controls before and after a physiologic test meal. Six neuropathic subjects showed gastrointestinal symptoms such as fullness and early satiety. Blood glucose, gastrin and pancreatic polypeptide were evaluated before and up to 200 min after the test meal. The gastric emptying rate was similar in controls (275 +/- 45 min) and in diabetic patients without (260 +/- 49 min) and with autonomic neuropathy (257 +/- 48 min) (p = ns), while diabetic symptomatics showed a significant reduction of gastric emptying rate (420 +/- 19.7 min) (p less than 0.001). Basal serum glucose concentration was similar in all diabetic patients (132 +/- 18 mg/dl, 166 +/- 52 mg/dl, 161 +/- 61 mg/dl, p = ns). A basal value of serum gastrin was similar in all groups while the test meal produced a rise with a peak at 40' significantly higher only in symptomatics (195 +/- 58 pg/ml vs control 107 +/- 88 pg/ml, diabetics without and with autonomic neuropathy: 98 +/- 12 pg/ml and 88 +/- 22 pg/ml respectively; p less than 0.01). Basal and stimulated PP values were similar in all groups. In conclusion ultrasonography is a simple, reliable method to evaluate gastric emptying rate without any interference in the mechanism of digestion and absorption of nutrients. The presence of non specific symptoms, such as nausea and gastric fullness, may indicate an early gastric involvement as supported by sonographic evidence of impaired emptying.

Adult↗
PubMed1990

Spatial frequency-selective losses with pattern electroretinogram in type 1 (insulin-dependent) diabetic patients without retinopathy.

Neurosensory abnormalities have been implicated in the first stages of diabetic retinopathy. The activity of retinal ganglion cells in 24 Type 1 (insulin-dependent) diabetic patients with short disease duration without retinopathy on fluorescein angiography was investigated by using a pattern electroretinogram in response to sinusoidal gratings of different spatial frequencies (0.6, 1.0, 1.4, 2.2 4.8 cycles/deg), counterphase modulated at 8 Hz. The pattern electroretinogram reflects, at least in part, the activity of subsets of generators (i.e. ganglion cells) which show spatial selectivity. Mean pattern electroretinogram amplitude was significantly reduced in patients at lower and intermediate, but not at higher spatial frequencies compared with 40 age-matched control subjects. At 1.4 cycles/deg the pattern electroretinogram amplitude was significantly correlated (r = 0.59) with age at onset (p = 0.002) and duration of disease (p = 0.002). Our results suggest that in Type 1 diabetic patients without retinopathy, there is an early sensory deficit of specific inner retina neurons which respond preferentially to gratings of medium and large size.

Diabetes Mellitus, Type 1↗
PubMed1990

Evidence for early impairment of macular function with pattern ERG in type I diabetic patients.

The electroretinogram (ERG) elicited by alternating gratings at constant mean luminance (pattern ERG) is a focal response reflecting the activity of the directly stimulated retinal area. In addition, pattern ERG is related, unlike the flash ERG, to ganglion cell activity. Therefore, this technique may be used to evaluate the integrity of inner retinal layers in the macular region. In this study, the steady-state pattern ERG, in response to alternating gratings (1.7 cycles/deg spatial frequency; 9 degrees field size) temporally modulated at 8 Hz, was recorded in 42 type I (insulin-dependent) diabetic patients with zero to four microaneurysms on fluorescein angiography and a duration of disease less than 11 yr. No patient had concomitant ocular or systemic complications. Mean pattern-ERG amplitude was significantly reduced in patients compared with age-matched control subjects (analysis of variance, F = 25.6, P less than 0.0001). Significant differences were observed between control and diabetic subjects without retinopathy (Scheffé F test, P less than 0.0001), between control and retinopathic subjects (Scheffé F test, P less than 0.0001), and between diabetic patients without retinopathy and those with early retinopathy (Scheffé F test, P less than 0.02). Pattern-ERG amplitude was inversely correlated with duration of diabetes (r = 0.22, P less than 0.05). Our results suggest a macular dysfunction in early diabetes resulting from metabolic and/or vascular injuries in the neurosensory retina.

Adolescent↗
PubMed1989

Steady-state pattern electroretinogram in insulin-dependent diabetics with no or minimal retinopathy.

Steady-state pattern electroretinogram (PERG) in response to sinusoidal gratings (1.7 c/deg spatial frequency; 9 x 9 deg field size) temporally modulated (sinusoidally) at 8 Hz were recorded in 40 insulin-dependent diabetics and 28 age-matched normal subjects. Visual acuity was greater than or equal to 20/20 in all 40 patients; 31 (62 eyes) showed no sign of retinopathy and nine (18 eyes) showed a few microaneurysms on fluorescein angiography. Insulin-dependent diabetics showed a significant reduction in the PERG mean amplitude as compared with age-matched control subjects (one-way analysis of variance: p less than 0.0001). Significant differences were observed between normals and diabetics without retinopathy (Scheffé test: p less than 0.0001), normals and diabetics with early retinopathy (Scheffé test: p less than 0.0001), no retinopathy and early retinopathy patients (Scheffé test: p less than 0.05). In diabetics without retinopathy multifactorial analysis of variance revealed a significant effect of age of onset of the disease (p less than 0.01) and an interaction effect between age of onset and duration (p less than 0.001) on PERG amplitude. These results suggest a possible use of the steady-state PERG to detect early macular dysfunction in insulin-dependent diabetics.

Adult↗
PubMed1989

Inhibition of basal insulin secretion induces insulin resistance in normal man: evidence for a tonic effect of insulin on carbohydrate metabolism.

Insulin resistance has been demonstrated both in insulin deficiency and insulin excess in man and in animals. This study was carried out in normal man to evaluate the role of insulinopenia in the pathogenesis of insulin resistance. Insulin suppression was obtained by 4 h somatostatin (SRIF) infusion. Insulin receptors on circulating monocytes were evaluated before and after SRIF infusion; an insulin tolerance test (ITT) was performed after SRIF, saline or SRIF and replacing basal insulin secretion. Insulin binding to circulating monocytes did not change after 4 h insulinopenia (2.19 +/- 0.30 vs. 2.35 +/- 0.80%), while insulin sensitivity appeared decreased after SRIF (KITT = 0.97 +/- 0.13) as compared with saline (KITT = 3.30 +/- 0.42), and this effect was prevented by insulin (KITT = 2.46 +/- 0.38). A relationship was detected between KITT and plasma insulin concentration before ITT (r = 0.85, p less than 0.01), suggesting that insulin deficiency is the main cause of the phenomenon observed. The present data suggest that basal insulin concentration plays an essential role in the control of insulin sensitivity. If insulin binding on monocytes mimics the behavior of major insulin target tissues, it is possible that the impaired insulin action after 4 h of insulin deficiency is related to a post binding effect.

Adult↗
PubMed1988

Effect of fenfluramine on insulin/growth hormone ratio in obese subjects.

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.

Adult↗
PubMed1988

Glucagon and glucose tolerance in liver cirrhosis.

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.

Adult↗
PubMed1988

Treatment of severe psoriasis with somatostatin: four years of experience.

Over a period of 4 years, 20 patients suffering from severe forms of psoriasis (erythrodermic, sub-erythrodermic, resistant generalized forms and/or forms associated with acute arthropathy) were treated with 96 h of continuous i.v. infusion of somatostatin (Stilamin, Serono) diluted in D5W at 250 micrograms/h. In addition to the usual blood chemistry parameters, circadian levels of growth hormone (GH) and epidermal growth factor (EGF) were measured before, during, and after therapy. Approximately 2-3 weeks after termination of therapy, erythrodermic and suberythrodermic symptoms had disappeared. In some patients, a few lesions of psoriasis vulgaris remained, although they were much less severe. Remission of acute arthropathy was impressive. Blood chemistry parameters were unchanged after therapy. Circadian levels of GH and EGF, normal before therapy, were significantly decreased after therapy. The infusion was well-tolerated. Infusion rates of greater than 250 micrograms/h caused only some complaints of abdominal pain, nausea, and vomiting. During the 4 years, erythrodermic symptoms reappeared only in seven patients, three of whom were also arthropathic. After 6-8 months, they underwent a second course of somatostatin therapy with good results. The other patients are still able to control their disease with tar-based products alone or with low-dose 8-methoxypsoralen + UVA (PUVA) or UV therapy. The arthropathic patients control their symptoms with periodic low-dose nonsteroidal antiinflammatory drug therapy.

Epidermal Growth Factor↗
PubMed1988

Negative correlation between ICA persistence and beta cell restoration after IDDM diagnosis.

We have studied 27 insulin-dependent diabetic patients since diagnosis for a period of six months; at diabetes onset and later on, ICA were found in 17 of them, whereas they were undetectable in 10 patients: age was remarkably homogeneous in the two groups. At diabetes onset, no significant differences were found in insulin requirement between ICA positive and ICA negative patients; however, six months after diagnosis, we observed that insulin requirement to keep metabolic control was significantly higher in ICA positive than in ICA negative subjects (0.515 +/- 0.2 U/Kg versus 0.22 +/- 0.15 U/Kg, p less than 0.001). Only one remission has been detected in ICA positive group (insulin requirement less than 0.25 U/Kg), while four ICA negative patients had complete remission and three had partial remission. ICA positive patients showed fasting C-peptide values higher than ICA negative (0.5 +/- 0.28 ng/ml versus 1.4 +/- 0.5 ng/m.; p less than 0.001, at rest; 1.1 +/- 0.6 ng/ml; versus 2.6 +/- 1.0 ng/ml, 6 minutes after stimulus; p less than 0.05). Our study suggests that presence and persistence of ICA may be considered an early and predictive marker for a worse beta cell function restoration resulting in a higher insulin requirement.

Adolescent↗