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Biomedical subjects

G Galimberti

Publications and source records attributed to G Galimberti.

At least 19 recordsLinked to original sources
PubMed2005

Effectiveness of frequency-modulated electromagnetic neural stimulation in the treatment of painful diabetic neuropathy.

AIMS/HYPOTHESIS: The largely unsatisfactory results reported for the pharmacological treatment of diabetic neuropathy has spurred the search for alternative therapies. The aim of this study was to evaluate the efficacy of frequency-modulated electromagnetic neural stimulation (FREMS) as a novel treatment for painful diabetic neuropathy. METHODS: Patients (n=31) with painful neuropathy associated with decreased nerve conduction velocity (<40 m/s) and increased vibration perception threshold (>25 V) were enrolled in a randomised, double-blind, crossover study designed to compare the effects of FREMS with those of placebo. Each patient received two series of ten treatments of either FREMS or placebo in random sequence, with each series lasting no more than 3 weeks. The primary efficacy end point was the change in pain measured by a visual analogue scale (VAS). RESULTS: FREMS induced a significant reduction in daytime and night-time VAS pain score (all p<0.02). Furthermore, FREMS induced a significant increase in sensory tactile perception, as assessed by monofilament; a decrease in foot vibration perception threshold, as measured by a biothesiometer; and an increase in motor nerve conduction velocity (all p<0.01). No significant changes were observed after placebo. Comparison of measurements at the 4-month follow-up with those at baseline revealed that a significant benefit persisted for all measures that showed an improvement at the end of treatment, with an additional improvement in quality of life evaluated by the Short Form-36 questionnaire (all p<0.05). No significant side effects were recorded during the study. CONCLUSIONS/INTERPRETATION: FREMS is a safe and effective therapy for neuropathic pain in patients with diabetes and is able to modify some parameters of peripheral nerve function.

Cross-Over Studies↗
PubMed2001

Decreased platelet glutamate uptake in patients with amyotrophic lateral sclerosis.

Decreased glutamate uptake and a loss of the astrocytic glutamate transporter EAAT2 (GLT-1) have been shown in spinal cord and motor cortex of patients with ALS. Because platelets express the three major glutamate transporter subtypes, including GLT-1, and possess a high-affinity glutamate uptake, the authors investigated glutamate uptake in platelets from patients with ALS and controls. A 43% reduction of high-affinity glutamate uptake rate (p < 0.0001) was observed in patients with ALS compared with normal controls and chronic neurologic disorder patients, suggesting a systemic impairment of glutamate uptake in ALS.

Adult↗
PubMed1999

Characterization of the oriI and oriII origins of replication in phage-plasmid P4.

In the Escherichia coli phage-plasmid P4, two partially overlapping replicons with bipartite ori sites coexist. The essential components of the oriI replicon are the alpha and cnr genes and the ori1 and crr sites; the oriII replicon is composed of the alpha gene, with the internal ori2 site, and the crr region. The P4 alpha protein has primase and helicase activities and specifically binds type I iterons, present in ori1 and crr. Using a complementation test for plasmid replication, we demonstrated that the two replicons depend on both the primase and helicase activities of the alpha protein. Moreover, neither replicon requires the host DnaA, DnaG, and Rep functions. The bipartite origins of the two replicons share the crr site and differ for ori1 and ori2, respectively. By deletion mapping, we defined the minimal ori1 and ori2 regions sufficient for replication. The ori1 site was limited to a 123-bp region, which contains six type I iterons spaced regularly close to the helical periodicity, and a 35-bp AT-rich region. Deletion of one or more type I iterons inactivated oriI. Moreover, insertion of 6 or 10 bp within the ori1 region also abolished replication ability, suggesting that the relative arrangement of the iterons is relevant. The ori2 site was limited to a 36-bp P4 region that does not contain type I iterons. In vitro, the alpha protein did not bind ori2. Thus, the alpha protein appears to act differently at the two origins of replication.

Bacterial Proteins↗
PubMed1999

Haemodynamic changes during anaesthesia in knee-elbow position.

BACKGROUND: To evaluate hemodynamic alterations during surgical procedures performed in the knee-elbow position. METHODS DESIGN OF THE STUDY: prospective evaluation of the aortic blood flow (ABF) and other cardiovascular variables measured with a transesophageal Doppler (TED) in 2 groups of patients free of previous cardiovascular diseases undergoing lumbar discectomy. ENVIRONMENT: Operating theatre of a neurosurgical department. Beside TED, the standard monitoring included continuous ECG surveillance, capnometry, noninvasive measurement of blood pressure and pulsoxymetry. PATIENTS: Overall, 24 ASA 1 patients have been enrolled. In 12 patients (Group A) the intervention was performed without dobutamine. In the other 12 patients (Group B) dobutamine (2.5-3 micrograms/kg/min) was started from the beginning of the intervention; the two groups did not differ in terms of age, body size, duration of surgery or anesthetic technique used; hemodynamic measurements were obtained at the beginning of the intervention (T1), with the patients still supine, during the intervention in the knee-elbow position (T2) and finally at the end of the procedure (T3) being the patients still anesthetized but lying supine again. RESULTS: In both groups the ABF; the systolic volume and the ETCO2 significantly decreased in the knee-elbow position; concomitantly, peripheral vascular resistances increased. In Group B, the hemodynamic variables were significantly better than in the other group. CONCLUSIONS: In the patients enrolled, the perioperative administration of low-dose dobutamine was associated with better cardiovascular performance.

Adrenergic beta-Agonists↗
PubMed1997

A method for assessing catheter patency in implanted pumps for long-term intraperitoneal insulin delivery.

Catheter complications are a common problem during long-term insulin therapy with implanted pumps. The purpose of this study was to test the feasibility of imaging intraperitoneal catheters with technetium (Tc) 99m in implantable devices for insulin delivery. Testing physical stability of an insulin/Tc 99 mixture did not show formation of insulin aggregates during a period up to 48 h on a rotating wheel. Five hundred microCurie (equal to 18 MBq) of Tc 99m were injected in the flush port of a pump for intraperitoneal insulin delivery implanted in patients with type I (insulin dependent) diabetes mellitus, and gamma camera images were obtained for 30 min. In patent catheters the tracer rapidly imaged the whole length of the catheter while in occluded catheters the tracer remained in the flush port, imaging only the portion of the catheter before the occlusion. In patent catheters in which insulin absorption was impaired, the tracer rapidly imaged the whole length of the catheter, but its removal from the peritoneum was delayed. Tc 99m imaging of intraperitoneal catheters for insulin delivery can be used to assess catheter patency and impaired delivery into the peritoneal cavity.

Catheterization↗
PubMed1996

Treatment with modified heparins inhibits experimental metastasis formation and leads, in some animals, to long-term survival.

Two chemically modified heparins with low anticoagulant activity were studied in terms of their antimetastatic activity in the B16-BL6 melanoma model. The two heparins were a very low molecular weight heparin (VLMW-H) and a low molecular weight heparin with 100% succinylation of desulfated N groups (Succ100-LMW-H). Both heparins, VLMW-H more so than Succ100-LMW-H, were highly effective in decreasing the number of lung metastasis on day 21 when administered once subcutaneously 10 min before intravenous injection of melanoma cells or 2 times/week for 3 weeks. When the time of survival was measured, both heparins did not significantly prolong survival when administered once before injection of the tumor cells. When a repeated treatment schedule was adopted over 3 weeks, both heparins led to a slight, yet significant prolongation of survival. When the repeated treatment protocol was continued beyond 3 weeks, a highly significant prolongation of survival was observed with VLMW-H and there were some long-term survivors (20% for VLMW-H and 10% for Succ-LMW-H) that remained disease-free after discontinuation of therapy on day 90. The present results confirm and reinforce the concept that heparins with reduced anticoagulant activity may have interesting therapeutic applications in the prevention of tumor metastasis.

Animals↗
PubMed1995

Intraperitoneal insulin absorption after long-term intraperitoneal insulin therapy.

OBJECTIVE: To evaluate insulin absorption through the peritoneal membrane after long-term intraperitoneal insulin therapy using an implanted programmable device. RESEARCH DESIGN AND METHODS: Seven insulin-dependent diabetes mellitus (IDDM) patients implanted with a programmable pump were studied after 3 and 30 months of intraperitoneal insulin therapy. A 20-min square wave infusion of 15 IU of insulin was administered in the peritoneal space, and plasma glucose and plasma free insulin levels were monitored for 180 min. Hypoglycemia was prevented by intravenous glucose infusion. RESULTS: After 30 months of intraperitoneal insulin therapy, plasma free insulin profiles following the administration of insulin in the peritoneal space were similar to those observed at the beginning of this mode of therapy. CONCLUSIONS: In IDDM patients, intraperitoneal insulin absorption does not change after long-term intraperitoneal insulin therapy using an implanted device.

Adult↗
PubMed1994

Normalization of lipoprotein composition by intraperitoneal insulin in IDDM. Role of increased hepatic lipase activity.

OBJECTIVE: To characterize the effects of intraperitoneal insulin pump therapy on lipoprotein composition and lipolytic enzyme activity in patients with insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Ten IDDM patients were studied 3 times: when receiving conventional subcutaneous insulin therapy and at 3 and 9 months from the initiation of intraperitoneal insulin regimen. Ten nondiabetic subjects matched for age, sex, and body weight were studied as controls. Levels of cholesterol, triglycerides, apolipoprotein A-I (apoA-I) and B (apoB) were measured in total plasma and lipoprotein fractions (very-low-density lipoprotein [VLDL], intermediate-density lipoprotein [IDL], low-density lipoprotein [LDL], and high-density lipoprotein [HDL]: HDL2 and HDL3). Postheparin plasma lipoprotein lipase and hepatic lipase activities were determined by an immunochemical method. RESULTS: IDDM patients showed higher levels of HDL3 and lower levels of HDL2 particles during intraperitoneal insulin therapy in comparison with subcutaneous insulin therapy. Both cholesterol and apoA-I significantly increased in HDL3 and decreased in HDL2 during intraperitoneal treatment. Plasma total cholesterol significantly decreased in the diabetic patients at 3 months of intraperitoneal insulin therapy compared with both subcutaneous insulin regimen and control subjects. IDL triglyceride concentrations during intraperitoneal treatment were significantly lower than those seen with subcutaneous therapy. Furthermore, triglyceride:apoB ratio in VLDL and cholesterol:apoB ratio in LDL significantly decreased in IDDM patients treated by intraperitoneal insulin. A significant increase in the activity of hepatic lipase with intraperitoneal insulin therapy by 9 months compared with subcutaneous insulin therapy has been shown. CONCLUSIONS: The increased activity of hepatic lipase after intraperitoneal insulin administration in IDDM patients appears to be one of the main determinants of lipoprotein changes observed, resulting in the normalization of lipoprotein composition during this mode of therapy. The normal inverse relationship between VLDL triglycerides and HDL cholesterol, which was not present in IDDM patients with subcutaneous therapy, was restored with intraperitoneal insulin regimen.

Adult↗
PubMed1993

Influence of meal ingestion on insulin profiles following intraperitoneal delivery.

This study evaluated the effect of meal ingestion on intraperitoneal insulin absorption in type I diabetic patients with an implanted pump for long-term intraperitoneal insulin delivery. On four separate occasions, patients (n = 7) were administered 15 IU insulin as a 20-minute square-wave infusion using their implanted device; hypoglycemia was prevented by intravenous infusion of 10% dextrose at a variable rate. Two studies were performed during fasting conditions (n = 2 fasting tests) and two studies after the administration of an 800-kcal standard meal (n = 2 postprandial tests). An insulin peak of 630 +/- 545.4 pmol/L (mean +/- SD) in fasting tests and 696 +/- 420.5 pmol/L in postprandial tests was reached in the peripheral circulation after 45 +/- 11.7 and 45 +/- 14.7 minutes, respectively, with no significant difference between the two experimental conditions. Areas under the insulin curves were not significantly different in fasting and postprandial tests (51,500 +/- 34,278 v 50,916 +/- 20,558 pmol/L.min-1, respectively; NS). In type I diabetic patients receiving long-term intraperitoneal insulin therapy, the increase in splanchnic blood flow following ingestion of a standard meal does not accelerate the appearance of insulin in the peripheral circulation.

Adult↗
PubMed1993

Peritoneal and subcutaneous absorption of insulin in type I diabetic subjects.

We and others have shown that in type I diabetes, ip insulin delivery results in lower free insulin levels than sc delivery. The aim of this study was to compare the rate of appearance of insulin in the peripheral circulation during ip and sc insulin administration in type I diabetes, in steady state and nonsteady state. To do this, we determined free insulin levels during ip or sc infusion as well as the impulse response of the insulin system after iv injection of a 6-nmol bolus of insulin. Twelve hours after a constant basal insulin infusion (5.5 +/- 1.4 nmol/h) was started, five C-peptide-negative type I diabetic subjects showed a lower systemic rate of appearance of insulin (expressed as a percentage of the administered dose) with ip than sc administration (27 +/- 6% vs. 40 +/- 10%; P < 0.001). In nonsteady state, when the infusion rate was increased from basal to 15 nmol/h (0-150 min) and subsequently to 42 nmol/h (150-300 min), the percent increase in insulin's systemic rate of appearance was higher with ip than sc infusion (P < 0.05 from 60-150 min; P < 0.01 from 150-300 min), indicating faster absorption. Thus, we conclude that insulin is more rapidly absorbed from the peritoneal cavity than from sc tissue. However, with ip administration, a sizable amount of insulin, once absorbed, is extracted before reaching the peripheral circulation, most likely by the liver. This is indirect evidence that ip insulin delivery results in a portal-peripheral insulin gradient in humans.

Adult↗
PubMed1992

Intraduodenal absorption in the rabbit of a novel heparin salt.

The intraduodenal absorption of a new low-molecular-weight heparin (LMWH) diamine salt (ITF 1331) was compared with the parent compound ITF 1060 and with sodium LMWH, in anaesthetized rabbits. The administration of either salt, but not of sodium LMWH, resulted in a dose-related increase in plasma anti-Xa activity. In this respect ITF 1331 was slightly superior to ITF 1060, and in acute-toxicity studies the counterion itself (ITF 258) was less toxic than that in ITF 1060 (counterion No. 4). These data confirm that a tertiary diamine within the counterion is an important structural requirement for the bioavailability of heparin by the intraduodenal route, and suggest that ITF 1331 may represent an important advance in the search for an oral heparin.

Animals↗
PubMed1992

In vivo demonstration of insulin-receptor defect with 123I-labeled insulin and scintigraphic scanning in severe insulin resistance.

OBJECTIVE: Insulin-receptor function in humans is usually studied in vitro on readily available cells, e.g., erythrocytes and fibroblasts. Although these cells are not metabolically important targets for insulin action, information derived from them are often taken as representative of other tissues. The aim of this study was to investigate insulin receptors in vitro on erythrocytes and in vivo on one of the main insulin-target organs, the liver. RESEARCH DESIGN AND METHODS: A 16-yr-old girl affected by severe insulin resistance was identified. Insulin receptor binding was measured on the erythrocytes of the patient and of 6 nondiabetic volunteers. The biodistribution of 123I-labeled insulin was studied in vivo by scintigraphic scanning in the insulin-resistant patient and in 10 nondiabetic volunteers. RESULTS: Erythrocytes of this patient displayed a markedly reduced [125I]insulin binding. In vivo 123I-insulin biodistribution was characterized by lack of hormone uptake by the liver (4 vs. 21% of the injected dose in control subjects) contrasting with intense accumulation of radioactivity in the kidneys. CONCLUSIONS: Our studies show that defects of insulin binding can be directly demonstrated in vivo on liver receptors with a noninvasive technique with low radiotoxicity.

Adolescent↗
PubMed1990

Effects of intraperitoneal versus subcutaneous insulin administration on lipoprotein metabolism in type I diabetes.

In order to compare the effects of intraperitoneal (IP) versus subcutaneous (SC) insulin delivery on plasma lipoproteins, lipoprotein cholesterol, triglycerides, and very-low-density lipoprotein (VLDL) metabolism were compared in five type I diabetic patients while they were receiving continuous IP insulin (CIPII) or continuous subcutaneous insulin infusion (CSII). Each therapy regimen was of at least 1 month duration, and patients were treated in random order. Mean daily plasma insulin was lower on CIPII compared with CSII. CIPII was associated with lower VLDL triglycerides and VLDL apolipoprotein (apo) B, and higher high-density lipoprotein (HDL) and HDL3 cholesterol. The decreased VLDL on CIPII appeared to be the result of both decreased production and increased clearance of VLDL apo B. The results suggest that the more physiologic route of insulin therapy (CIPII) is associated with lipoprotein profiles of lower atherogenic potential.

Adult↗
PubMed1988

Glycerol-insulin raises circulating insulin antibodies in type I diabetic patients treated with permanently implanted devices.

The instability of insulin in the reservoirs of implantable insulin delivery devices has been a major obstacle in implementing this form of therapy. To overcome the problem of precipitation, a glycerol-insulin preparation has been used in large-scale long-term clinical trials. The aim of this study was to evaluate the stability of the glycerol-insulin solution and its effects on circulating insulin antibodies in eight type I diabetic patients who were implanted with an Infusaid pump (Infusaid Corporation, Norwood, MA) and followed for 1 year or more. Total insulin requirement did not change throughout the observation period. Plasma free insulin was higher during treatment with glycerol-insulin than with the standard insulin treatment (P less than .02). Insulin antibodies increased in all patients (P less than .05). High-performance liquid HPLC analysis of insulin samples from the pump reservoirs showed the generation of insulin modification products at a daily rate of 1.84%, reaching 40% to 50% of the total reservoir content 3 weeks after refilling; among these products, high molecular weight species accounted for about 15%. It is concluded that glycerol-insulin is not an adequate insulin preparation for use in implanted devices. Insulin deteriorated in the pump reservoirs, and insulin antibody concentration increased in the treated patients. It is believed that this antibody production is favored by circulating insulin fragments and polymers of insulin generated inside the pump reservoirs.

Adult↗