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P Compagnucci

Publications and source records attributed to P Compagnucci.

At least 19 recordsLinked to original sources
PubMed1999

Long-term intensive treatment of type 1 diabetes with the short-acting insulin analog lispro in variable combination with NPH insulin at mealtime.

OBJECTIVE: To establish whether the short-acting insulin analog lispro can be successfully implemented in long-term intensive insulin therapy in type 1 diabetes, and if so, what its effects are on glycemic control and frequency and awareness of hypoglycemia. RESEARCH DESIGN AND METHODS: We randomized 56 type 1 diabetic patients to treatment with either lispro (n = 28) or human regular insulin (Hum-R; n = 28) as mealtime insulin for 1 year (open design, parallel groups). Lispro was injected at mealtime and Hum-R was given 10-40 min before meals (bedtime NPH was continued on both occasions). With lispro, NPH was added at breakfast (approximately 70/30), lunch (approximately 60/40), and supper (approximately 80/20) (mixing percentage of lispro/NPH) to optimize premeal and bedtime blood glucose. RESULTS: Total daily insulin units were no different in the two treatment groups, but with lispro approximately 30% less short-acting insulin at meals and approximately 30% more NPH was needed versus Hum-R (P < 0.05). The bedtime NPH dosage was no different. With lispro + NPH, the mean daily blood glucose was lower than with Hum-R (8.0 +/- 0.1 vs. 8.8 +/- 0.1 mmol/l; P < 0.05), HbA1c was lower (6.34 +/- 0.10 vs. 6.71 +/- 0.11%, mean value over 1 year; P < 0.002), and hypoglycemia (blood glucose < or = 3.8 mmol/l) was less frequent (7.4 +/- 0.5 vs. 11.5 +/- 0.7 episodes/patient-month) and tended to occur more within 90 min after meals than in the postabsorptive state (P < 0.05 vs. Hum-R). After 1 year, plasma adrenaline and symptom responses to experimental, stepped hypoglycemia improved with lispro and were closer to the responses of 12 nondiabetic control subjects versus Hum-R both in terms of thresholds and magnitude (P < 0.05). CONCLUSIONS: We concluded that mealtime injection of lispro + NPH improves the 24-h blood glucose and the percentage HbA1c as compared with Hum-R. The improvement can be maintained long term. Intensive therapy with lispro + NPH results in less frequent hypoglycemia and better awareness and counterregulation of hypoglycemia.

Adult↗
PubMed1998

In vitro activity of five antifungal agents against clinical isolates of Saccharomyces cerevisiae.

We evaluated the in vitro activity of fluconazole, itraconazole, ketoconazole, 5-fluorocytosine and amphotericin B against 30 clinical isolates of Saccharomyces cerevisiae by a broth microdilution method, following the NCCLS recommendation. Testing was performed either in RPMI-1640 or yeast nitrogen base (YNB). YNB supported the growth of all isolates tested, while results in RPMI-1640 were not obtained for six isolates (20%). The MIC of all three azoles in YNB were one or two dilutions higher than those obtained in RPMI-1640 (P=0.0001 for fluconazole and itraconazole, P=0.03 for ketoconazole). Elevated MICs were observed for all three azoles, while all the isolates were susceptible to 5-fluorocytosine and amphotericin B. All MIC values were confirmed by spectrophotometric reading. Six strains of S. cerevisiae isolated from the faeces and consecutive blood cultures from an AIDS patient over a 7-month period were typed by electrophoretic karyotyping (EK). EK showed the maintenance of the same karyotype over time suggesting that the faecal isolate changed from a colonizing to infection-causing strain. The relative resistance of S. cerevisiae to azole drugs as well as its ability to cause widespread infections may promote the emergence of this species as a pathogen in immunosuppressed patients.

AIDS-Related Opportunistic Infections↗
PubMed1998

In-vitro interaction of terbinafine with amphotericin B, fluconazole and itraconazole against clinical isolates of Candida albicans.

A chequerboard titration broth microdilution method, performed according to the recommendations of the National Committee for Clinical Laboratory Standards, was applied to study the in-vitro interaction of terbinafine with amphotericin B, fluconazole and itraconazole against 30 strains of Candida albicans isolated from the oral cavities of AIDS patients. MICs were determined spectrophotometrically at 490 nm and read at either 24 h or 48 h. The end-point was defined as the drug concentration resulting in > or = 90% inhibition of growth relative to control growth. Synergy, defined as a fractional inhibitory concentration (FIC) index of < or = 0.50, was observed in 93% (28 of 30) of terbinafine-amphotericin B interactions, in 47% (14 of 30) of terbinafine-fluconazole interactions and in 43% (13 of 30) of terbinafine-itraconazole interactions; antagonism (FIC > 2.0) was not observed. Where synergy was not achieved, there was still a decrease, although not as dramatic, in the MIC of one or both drugs when used in combination. Reading the MICs on day 2 did not significantly affect the mode of interaction of terbinafine-triazoles, while for terbinafine-amphotericin B the proportion of synergic interactions dropped from 93% (28 of 30) to 30% (nine of 30; P = 0.0001). Antagonism was not observed for any drug combination even at 48 h. Minimum fungicidal concentrations (MFCs) of all drugs alone and in combination were determined against five isolates. Neither terbinafine nor the two triazoles showed fungicidal activity when tested alone or in combination. The fungicidal activity of amphotericin B was slightly enhanced when combined with terbinafine, there being a decrease of two-fold dilutions in the amphotericin B MFCs against all five isolates tested. Thus terbinafine enhances the activities of amphotericin B and triazoles against C. albicans in vitro. Clearly, clinical studies are warranted to elucidate further the potential utility of these combination therapies.

Amphotericin B↗
PubMed1998

Comparison of three methods for testing azole susceptibilities of Candida albicans strains isolated sequentially from oral cavities of AIDS patients.

Three susceptibility testing procedures were compared to determine fluconazole, itraconazole, and ketoconazole MICs against 47 Candida albicans strains isolated sequentially from the oral cavities of five AIDS patients undergoing azole therapy. They included the broth microdilution method (BM), performed according to the National Committee for Clinical Laboratory Standards' tentative standard, the agar dilution method (AD), and the Etest; the latter two tests were performed both in Casitone agar (AD-Cas and Etest-Cas) and in RPMI (AD-RPMI and Etest-RPMI). Twenty-four- and 48-h MICs obtained by AD and Etest were compared with 48-h MICs obtained by BM. The MICs of all the azoles determined by BM were usually lower than those obtained by the other methods, mainly due to different reading criteria. In order to assess the most appropriate way of evaluating the agreement of MICs obtained by different methods with those produced by the proposed reference method (BM), we used the mean differences calculated according to Bland and Altman's method. Comparison of fluconazole MICs obtained by BM and AD-Cas yielded a mean difference of 3, and the percentages of agreement within +/-2 dilutions were 98 and 100% at 24 and 48 h, respectively. For ketoconazole and itraconazole MICs, lower mean differences were noted, and agreement ranged from 96 to 100%. Agreement between the AD-RPMI and BM results was poor for all azoles, and an increase in MICs was always observed between the 1st- and 2nd-day readings. Similarly, Etest-Cas gave better agreement with BM than did Etest-RPMI for all the azoles. BM, AD-Cas, and Etest-Cas each demonstrated a progressive increase in fluconazole MICs against strains isolated sequentially from a given patient, in accordance with the decreased clinical response to fluconazole.

AIDS-Related Opportunistic Infections↗
PubMed1998

In vitro activity of terbinafine against clinical isolates of dermatophytes.

A broth macrodilution method following the recommendations established by the National Committee for Clinical Laboratory Standards was employed for testing terbinafine against 20 clinical isolates of dermatophytes belonging to seven species. The minimal inhibitory concentrations resulting in either 80% or 100% inhibition of growth, compared to growth in drug-free control tubes, ranged from </=0.03 to 0.25 g ml-1 and from </=0.03 to 2.0 g ml-1, respectively. Terbinafine was shown to be fungicidal at a concentration of </=1.0 microg ml-1 for 19 isolates. No differences in susceptibilities were found between strains isolated from HIV-positive and -negative individuals.

Antifungal Agents↗
PubMed1997

Genotypic identification of sequential Candida albicans isolates from AIDS patients by polymerase chain reaction techniques.

Random amplification of polymorphic DNA and inter-repeat polymerase chain reaction (IR-PCR) were compared with restriction fragment length polymorphism (RFLP) analysis as methods for DNA typing of Candida albicans. Forty-seven strains of Candida albicans isolated from the oral cavities of five AIDS patients undergoing fluconazole therapy were analyzed. There was an excellent correspondence between the DNA types obtained by both PCR-based techniques and by RFLP. With the exception of one patient who was infected with three DNA types of Candida albicans during a five-year observation period, the patients each harboured only one major strain, which became progressively less susceptible to fluconazole. Each DNA type was unique to a patient. The data suggest that these typing methods are suitable for investigating the epidemiology of oropharyngeal candidiasis in this patient group.

AIDS-Related Opportunistic Infections↗
PubMed1995

Effects of recent, short-term hyperglycemia on responses to hypoglycemia in humans. Relevance to the pathogenesis of hypoglycemia unawareness and hyperglycemia-induced insulin resistance.

A single episode of recent hypoglycemia increases, whereas long-term hyperglycemia decreases, the glycemic thresholds of responses of counterregulatory hormone and symptoms to subsequent hypoglycemia in humans. To assess whether short-term, antecedent hyperglycemia exerts effects opposite to those observed after acute hypoglycemia, seven normal, nondiabetic subjects and eight insulin-dependent diabetes mellitus (IDDM) patients were studied during hyperinsulinemic-hypoglycemic clamp (sequential, 90-min plateaus of plasma glucose [PG] of 4.3, 3.7, 3.0, and 2.4 mmol/l). Nondiabetic subjects were studied the morning after either 6-h clamped hyperglycemia (PG approximately 13.5 mmol/l) or euglycemia (PG approximately 5 mmol/l) between 1600 and 2200 the previous day (glucose and insulin infused on both occasions), as well as after nocturnal hyperglycemia (PG approximately 13.5 mmol/l) or euglycemia between 2300 and 0500. The IDDM patients were studied after 15 h of euglycemia or hyperglycemia (approximately 17 mmol/l) but identical hyperinsulinemia (approximately 225 pmol/l) between 1600 and 0700. Neither PG thresholds of counterregulatory hormone, symptoms, onset of cognitive dysfunction to hypoglycemia, nor maximal responses were affected by antecedent, short-term hyperglycemia in normal nondiabetic subjects and IDDM patients (NS). However, the rate of glucose infusion required to maintain hypoglycemic plateaus during hypoglycemia was lower after hyperglycemia (nondiabetic subjects 31.2 +/- 3.4 vs. 36.7 +/- 4 mumol.kg-1.min-1, IDDM patients 33 +/- 3.1 vs. 42.5 +/- 3.9 mumol.kg-1.min-1; P < 0.05) indicating greater insulin resistance induced by antecedent hyperglycemia. In conclusion, in contrast to acute hypoglycemia and long-term hyperglycemia, recent, short-term hyperglycemia does not affect physiological responses to hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A risk-benefit appraisal of acarbose in the management of non-insulin-dependent diabetes mellitus.

Acarbose is an alpha-glucosidase inhibitor proposed for the treatment of diabetic patients. It acts by competitively inhibiting the alpha-glucosidases in the intestinal brush border. The principal action of these enzymes is to convert nonabsorbable dietary starch and sucrose into absorbable monosaccharides (e.g. glucose). Enzyme inhibitors delay this conversion, slowing the formation and consequently the absorption of monosaccharides, and thus reducing the concentration of postprandial blood glucose. Both starch and sucrose are influenced, whereas lactose and glucose are not. Many studies in experimental animals, healthy volunteers and patients with non-insulin-dependent diabetes mellitus (NIDDM) have shown that acarbose decreases postprandial blood glucose, with a lesser reduction of fasting blood glucose, plasma triglycerides and postprandial insulin levels. In long term studies in NIDDM patients, acarbose significantly reduced glycosylated haemoglobin levels. Acarbose is only minimally absorbed from the gut and no systemic adverse effects have been demonstrated after long term administration. The drug allows undigested carbohydrates to pass into the large bowel where they are fermented causing flatulence, bloating and diarrhoea. These symptoms, which occur in approximately 30 to 60% of patients, tend to decrease with time and seem to be dose-dependent. They are minimised by starting therapy with low doses (such as 50mg 3 times daily) which may be effective in many patients. An increase in serum hepatic transaminases observed in earlier studies in the US, where doses of acarbose up to 900mg daily were used, has been not reported with the lower doses of the drug actually recommended [150 to 300mg (up to 600mg) daily]. In conclusion, acarbose may be useful in patients with NIDDM when diet alone is no longer able to maintain satisfactory blood glucose control. Furthermore, it may be a valid alternative to sulphonylurea or biguanide therapy when these drugs are contraindicated and insulin administration may be delayed. Acarbose seems also to be a useful adjunct to hypoglycaemic oral agents but its precise role in this field has not been fully clarified.

Acarbose↗
PubMed1993

[Oral glucose tolerance and HbA1c in the diagnosis of pregnancy in diabetes].

This study was undertaken in order to evaluate the plasma glucose response to oral glucose tolerance test (OGTT, 100 g) and the HbA1c values in pregnant women at different gestational ages. One-hundred twenty-nine OGTTs have been performed in 75 pregnancies. The results obtained show a decrease in glucose tolerance during pregnancy. Mean HbA1c value was significantly higher in women with gestational diabetes mellitus, but values of subjects with gestational diabetes and normal glucose tolerance overlapped widely. In conclusion, HbA1c is not a sensitive parameter in the diagnosis of gestational diabetes mellitus. Further studies are necessary to evaluate its specificity and prognostic significance.

Administration, Oral↗
PubMed1990

[Importance of CA-50 detection in malignant gynecologic tumors].

The role of Tumor Associated Antigens in the diagnosis of neoplasia is now actively investigated. The CA-50 antigen is known to be elevated in different types of gynecological neoplasia. In this study the CA-50 levels have been measured in 70 patients with ovarian, endometrial or cervical cancer. The data obtained show that the CA-50 levels, although elevated above normal in a high percentage of the patients studied, cannot be considered diagnostic for the presence of neoplasia.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1985

Improved column-chromatographic isolation of glycosylated hemoglobin S.

We investigated glycosylated hemoglobin S by means of chromatography on Bio-Rex 70. The selected elution conditions were similar to those described by Trivelli et al. (N Engl J Med 284: 353-357, 1971), except for modified ionic strength and accurate temperature control. This enabled us to isolate a minor hemoglobin fraction whose properties, as determined by chromatography, electrophoresis, and two-dimensional maps of its tryptic peptides, were typical of a hemoglobin S tetramer with blocked N-terminal residues of the beta subunits. The colorimetric test indicated this to be a glycosylated hemoglobin. This procedure is notably improved over previous chromatographic techniques for isolating glycosylated hemoglobin S. Moreover, it can be easily used in any laboratories where Trivelli's method is routinely in use.

Chromatography, Ion Exchange↗
PubMed1984

Mechanisms of glucagon secretion during insulin-induced hypoglycemia in man. Role of the beta cell and arterial hyperinsulinemia.

To elucidate the mechanisms controlling the response of glucagon to hypoglycemia, a vital component of the counterregulatory hormonal response, the role of intraislet insulin was studied in seven normal subjects and five subjects with insulin-dependent diabetes mellitus (IDDM) (of less than 15-mo duration). In the normal subjects, hypoglycemia (arterial plasma glucose [PG] 53 +/- 3 mg/dl) induced by an intravenous insulin infusion (30 mU/m2 X min for 1 h, free immunoreactive insulin [FIRI] 58 +/- 2 microU/ml) elicited a 100% fall in insulin secretion and an integrated rise in glucagon of 7.5 ng/ml per 120 min. When endogenous insulin secretion was suppressed by congruent to 50 or congruent to 85% by a hyperinsulinemic-euglycemic clamp (FIRI 63 +/- 1.5 or 147 +/- 0.3 microU/ml, respectively) before hypoglycemia, the alpha cell responses to hypoglycemia were identical to those of the control study. When the endogenous insulin secretion was stimulated by congruent to 100% (hyperinsulinemic-hyperglycemic clamp, FIRI 145 +/- 1.5 microU/ml, PG 132 +/- 2 mg/dl) before hypoglycemia, the alpha cell responses to the hypoglycemia were also superimposable on those of the control study. Finally, in C-peptide negative diabetic subjects made euglycemic by a continuous overnight intravenous insulin infusion, the alpha cell responses to hypoglycemia were comparable to those of normal subjects despite absent beta cell secretion, and were not affected by antecedent hyperinsulinemia (hyperinsulinemic-euglycemic clamp for 2 h, FIRI 61 +/- 2 microU/ml). These results indicate that the glucagon response to insulin-induced hypoglycemia is independent of the level of both endogenous intraislet and exogenous arterial insulin concentration in normal man, and that this response may be normal in the absence of endogenous insulin secretion, in contrast to earlier reports. Thus, loss of beta cell function is not responsible for alpha cell failure during insulin-induced hypoglycemia in IDDM.

Adult↗
PubMed1983

Carbohydrate metabolism in porphyria cutanea tarda.

A study on carbohydrate metabolism (glycaemia and insulinaemia curves during the oral and the intravenous glucose tolerance tests) in 20 porphyria cutanea tarda patients revealed diabetes mellitus in 2 and impaired glucose tolerance in 1 patient, but the carbohydrate tolerance did not differ greatly from that of matched controls. The porphyria cutanea tarda patients, instead, had a significantly exaggerated insulin response, which was more marked in patients with liver disorders. It is proposed that the hyperinsulinism is secondary to the liver damage.

Adult↗
PubMed1983

Abnormal glucose counterregulation in insulin-dependent diabetes mellitus. Interaction of anti-insulin antibodies and impaired glucagon and epinephrine secretion.

To evaluate the roles of counterregulatory hormones and insulin antibodies in the impairment of plasma glucose recovery from hypoglycemia in diabetes mellitus, and to assess the relationship between the glucagon response and duration of the disease, 21 insulin-dependent diabetic patients and 10 nondiabetic subjects were studied. The diabetics consisted of 5 patients with recent onset of diabetes (less than 1 mo); 11 with 2.6 +/- 0.3 (mean +/- SEM) yr duration of diabetes, 5 of whom had insulin antibodies; and 5 patients with long-term diabetes (21 +/- 3 yr), insulin antibodies, and autonomic neuropathy. During insulin-induced hypoglycemia (28 mU/m2 X min for 60 min) in patients with recent-onset diabetes, plasma free insulin, glucose, and counterregulatory hormone concentrations did not differ from those of nondiabetic subjects. In patients with insulin antibodies, the disappearance of insulin after insulin infusion was delayed, and both restitution of normoglycemia and plasma glucagon response were blunted compared with patients without antibodies. When glucagon was infused (80-130 ng/m2 X min) during hypoglycemia in diabetics with impaired glucagon responses in order to simulate normal glucagon responses, plasma glucose recovery was normalized in patients without antibodies but not in those with antibodies. In patients with long-standing diabetes, restitution of normoglycemia was further impaired and this was associated with an absent plasma glucagon response and a diminished plasma epinephrine response. Plasma glucagon responses to hypoglycemia were inversely correlated to the duration of diabetes (r = -0.943; P less than 0.0005). It is concluded that impaired A-cell secretion is the predominant mechanism for the delayed glucose recovery after hypoglycemia in diabetic patients without insulin antibodies and normal epinephrine responses. Slowed disappearance of insulin due to the presence of insulin antibodies further delays the restoration of normoglycemia. Patients with long-standing diabetes and autonomic neuropathy exhibit decreased epinephrine secretion, which leads to an additional retardation of glucose recovery. Since plasma glucagon and epinephrine responses to hypoglycemia were normal at the onset of diabetes but diminished in long-term diabetes, it appears that the impaired glucagon and epinephrine responses to hypoglycemia are acquired defects that develop subsequent to B-cell failure.

Adolescent↗
PubMed1983

The adrenergic contribution to glucose counterregulation in type I diabetes mellitus. Dependency on A-cell function and mediation through beta 2-adrenergic receptors.

In order to assess the adrenergic contribution to hypoglycemic glucose counterregulation in type I diabetes mellitus and to determine whether the adrenergic contribution is mediated through beta 1- or beta 2-adrenergic receptors, hypoglycemia was induced by an i.v. insulin infusion (30 mU/m2 x min) for 60 min in 11 insulin-dependent diabetic patients (IDDM), 5 with normal plasma glucagon responses and 6 with blunted responses, and also in 7 age-weight-matched nondiabetic subjects. Rates of plasma glucose decrease and postnadir increase, as well as plasma concentrations of free insulin and of counterregulatory hormones, were measured when insulin was infused alone, and when insulin was infused along with propranolol (a beta 1- and beta 2-adrenergic receptor antagonist) or metoprolol (a selective beta 1-antagonist). Postnadir plasma glucose recovery was decreased in IDDM with blunted plasma glucagon responses (21 +/- 0.8 mumol x L-1 x min-1, P less than 0.001), but was normal in patients with normal plasma glucagon responses (30 +/- 0.4 versus 33 +/- 0.5 mumol x L-1 x min-1 in nondiabetic subjects, P = NS). Postnadir plasma glucose recovery was not affected by either propranolol or metoprolol in normal subjects and in IDDM with normal glucagon responses. However, in IDDM with blunted plasma glucagon responses, postnadir plasma glucose recovery was further decreased by propranolol (14 +/- 0.6 mumol x L-1 x min-1, P less than 0.01), but was unaffected by metoprolol (22 +/- 0.9 mumol x L-1 x min-1, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗