PubMed Health⌕ Search

Biomedical subjects

G Ghirlanda

Publications and source records attributed to G Ghirlanda.

At least 19 recordsLinked to original sources
PubMed1992

Lower limb arterio-venous shunts, autonomic neuropathy and diabetic foot.

We have quantitatively assessed the percentage of lower limb arterio-venous (a-v) shunting using a radioisotopic technique and correlated it with autonomic neuropathy evaluated by cardiovascular tests. We have studied three groups of diabetic patients: Group A, 12 non-neuropathic subjects without foot lesions; Group B, 12 neuropathic subjects without foot lesions; Group C, 12 neuropathic subjects with recurrent foot ulcers. Shunting was higher in Group C (10.4 +/- 2.7%) than in Group B (6.8 +/- 2.3%, P less than 0.01) and Group A (3.8 +/- 1.2%, P less than 0.001). Shunts in Group B were higher than in Group A (P less than 0.05). All the tests exploring autonomic function were more impaired in Groups B and C than in Group A, with no difference between Groups B and C. A direct correlation was found between a-v shunting and the following cardiovascular tests: postural hypotension (PH) (r = 0.41, P less than 0.02), sustained handgrip (SH) (r = 0.56, P less than 0.001), deep breathing (DB) (r = 0.40, P less than 0.005) and lying to standing (LS) (r = 0.44, P less than 0.01). A positive correlation was also found between a-v shunts and duration of the disease (r = 0.62, P less than 0.001). Arterio-venous shunting was found to be directly related to autonomic neuropathy even if the higher shunting found in the patients with foot ulcers was not related to a higher degree of autonomic involvement; in addition, this group of patients was characterized by having a more advanced sensory and motor neuropathy. In conclusion, autonomic neuropathy, through its influence on a-v shunts, may play a role in the pathogenesis of diabetic foot, but peripheral neuropathy probably plays a key role in conditioning the development of the overt clinical manifestations of diabetic foot.

Albuminuria↗
PubMed1992

The beta cell function in NIDDM patients with secondary failure: a three year follow-up of combined oral hypoglycemic and insulin therapy.

Eleven Type 2 (non-insulin-dependent) diabetic patients, islet cell autoantibodies negative, nonobese with secondary failure to oral hypoglycemic agents (OHA) [glyburide (7.5 mg/day) and phenformin (75 mg/day)] and HbA1c 10.2 +/- 0.6% were studied. Insulin receptors on circulating monocytes, glucose utilization at supraphysiological insulin concentrations, and plasma C-peptide after i.v. glucagon were evaluated before and after 2 months of combined therapy with OHA and insulin (Ultratard HM Novo). A significant improvement was demonstrated in HbA1c and glycemia after two months of treatment. Glucose MCR was increased after two months of treatment whilst basal C-peptide was decreased as well as receptor binding to monocytes. After three years of combined therapy, body weight, glycemia and HbA1c did not increase. After three years the C-peptide basal values were significantly increased with respect to values found after 2 months of therapy. These results demonstrate that insulin treatment may restore insulin sensitivity in NIDDM patients resistant to OHA treatment and that after three years there is no exhaustion of B-cell function.

Administration, Oral↗
PubMed1992

Nonselective loss of contrast sensitivity in visual system testing in early type I diabetes.

OBJECTIVE: Psychophysical methods in patients with diabetes mellitus reveal deficits of central or foveal vision. Our aim was to evaluate the contrast-sensitivity thresholds in 24 insulin-dependent (type I) diabetic patients with a short disease duration and without retinopathy, taking into account metabolic control. RESEARCH DESIGN AND METHODS: The control group consisted of age-matched nondiabetic subjects. None had visual or systemic symptoms. Contrast sensitivity measured at eight different spatial frequencies to sinusoidal bar patterns of 0.6-12.2 cycles/deg can detect functional defects in the spatially sensitive retinal ganglion cells or in higher visual pathways. We performed two different temporal types of contrast-sensitivity testing, dynamic (8 Hz) and static (0 Hz). RESULTS: Significant losses with dynamic contrast-sensitivity test at all but the highest spatial frequencies (i.e., 12.2 cycles/deg) were shown, whereas there was significant attenuation of contrast sensitivity at five spatial frequencies (1.0, 1.4, 2.2, 7.1, and 9.6 cycles/deg) in the static mode. Grating losses (less than 2SD of control means) of contrast sensitivity were found in 33.3% (dynamic) and in 72.9% (static) of eyes of diabetic patients. HbA1c values were positively correlated at variable spatial frequencies (1.0, 1.4, and 2.2 cycles/deg for dynamic test and 0.6, 1.0, 1.4, 2.2, 4.8, and 7.1 cycles/deg for static test). CONCLUSIONS: Our results suggest an early, generally nonselective neuronal damage of visual pathways that occurs before the onset of clinically detectable retinopathy. The visual deficit may be related directly to the effects of diabetes; repetitive minor hypoglycemic insults may contribute more than a marked hyperglycemic condition to the mechanisms underlying physiological changes along the optic nerve.

Adult↗
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↗
PubMed1979

Glucose, insulin and somatostatin infusion for the determination of insulin resistance in liver cirrhosis.

Twelve patients with liver cirrhosis and ten normal subjects were studied. Using a constant intravneous infusion of glucose, insulin and somatostatin over 2 1/2 hours we determined the stteady state plasma glucose level (SSPG) in order to measure insulin resistance. The results demonstrated that the cirrhotic patients were insulin resistant compared to normals and that plasma glucagon does not account for the insulin resistance in these patients.

Adult↗
PubMed1979

Early insulin and glucagon response to subsequent pulses of arginine, glucose, and tolbutamide in normal man.

To determine the dynamics of insulin and of glucagon secretion in response to several sequential stimuli administered shortly after an arginine pulse (5 g), 20 nonobese, apparently healthy volunteers were given arginine (5 g), glucose (5 g), and tolbutamide (1 g) by rapid intravenous injection. The early insulin and glucagon area 0-8 min was studied. At the intervals and with the dosages used in this study, different stimuli with and without prestimulation with arginine did not lead to changes in early secretion of insulin. There was no exhaustion of the pool of insulin released after multiple sequential pulses. These results suggest a pattern in which stimulation induces a rapid release of insulin and activates the interchange between the stored and labile insulin pool; the 8-min interval is sufficient for the rapid return of the two compartments to a state of equilibrium. Also for glucagon, subsequent different stimuli did not exhaust glucagon release; nevertheless, glucagon is immediately suppressed by a submaximal glucose pulse.

Adolescent↗
PubMed1979

GH secretion in open-angle glaucoma.

Open-angle glaucoma is frequently observed in patients with acromegaly suggesting that the somatotropic hormone might facilitate a condition of glaucoma. The open-angle glaucoma patients studied, displayed higher plasma human growth hormone (HGH) levels than control subjects 60 min (30.3 +/- 1.7 against 16.8 +/- 2.7 ng/ml; p less than 0.001) and 90 min (19.0 +/- 1.9 against 9.3 +/- 1.2 ng/ml; p less than 0.001) after intravenous administration of arginine (25 g in 30 min). The authors support the hypothesis that the increased plasma HGH level may interfere with the regulation of ocular pressure by modifying the flow of aqueous humor from the eyeball via changes in the sclero-corneal trabecular meshwork; these changes are also found in diabetic subjects. The interplay between HGH and changes of carbohydrate metabolism (frequently occurring in glaucomatous patients) may be at the root of the variations of intraocular pressure in open-angle glaucoma.

Arginine↗