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Biomedical subjects

A Doria

Publications and source records attributed to A Doria.

At least 91 records · Page 5Linked to original sources
PubMed1994

Angiotensin I-converting enzyme (ACE): estimation of DNA haplotypes in unrelated individuals using denaturing gradient gel blots.

The angiotensin I-converting enzyme (ACE) gene (17q23) is a candidate gene for essential hypertension and related diseases, but investigation of its role in human pathology is hampered by a lack of identified polymorphisms. Currently, a 287-bp insertion/deletion (I/D) RFLP in intron 16 represents the only one known. Additional polymorphisms for the ACE gene would make most families informative for linkage studies and would allow haplotypes to be assigned in association studies. To increase the information provided by the ACE gene, we used a sensitive screening technique, denaturing gradient gel electrophoresis (DGGE) blots, to identify polymorphisms and combined this with gene counting to identify haplotypes. Five independent polymorphisms, restriction fragment melting polymorphisms (RFMPs), were identified by four probes (encompassing half of the ACE cDNA) in digests produced by three restriction enzymes (DdeI, RsaI, and AluI). One RFMP has three alleles while the others have two alleles. In a sample of 67 unrelated control subjects, minor allele frequencies ranged from 0.12 to 0.49. A significant level of linkage disequilibrium was found for all pairs of markers. The four most informative RFMPs, taken in combination, define 24 potential haplotypes. Based on gene counting, 11 of the 24 are rare or nonexistent in this population, and the estimated heterozygosity of the remaining 13 haplotypes approaches 80%. Under these conditions for the ACE locus, phase-unknown genotypes could be assigned to haplotype pairs in unrelated subjects with reasonable certainty. Thus, using DGGE blot technique for identifying numerous DNA polymorphisms in a candidate locus, in combination with gene counting, one can often identify DNA haplotypes for both related and unrelated study subjects at a candidate locus. These markers in the ACE gene should be useful for clinical and epidemiologic studies of the role of ACE in human disease.

Alleles↗
PubMed1994

Antiphospholipid antibodies (aPL) in systemic lupus erythematosus. Are they specific tools for the diagnosis of aPL syndrome?

OBJECTIVE: Antiphospholipid antibody (aPL) specificity for aPL-related events was evaluated in systemic lupus erythematosus (SLE). METHODS: A study was carried out on 105 patients affected with SLE comparing the prevalence of lupus anticoagulant (LA) and IgG and IgM anticardiolipin antibodies (aCL) between patients with and without features of antiphospholipid syndrome (APS). Antiphospholipid antibody profile was subsequently evaluated in the aPL positive patients with and without aPL-related events, thus excluding the patients with complications of APS possibly due to factors other than aPL. RESULTS: LA showed a strong association with thrombosis and livedo reticularis, and IgG aCL with thrombosis and neurological disorders, while no clinical features were associated with IgM aCL. A considerable number of aPL positive patients with no aPL-related manifestations was also observed, suggesting the low specificity of aPL assays (54.4%). When studying the 60 aPL positive patients, LA was specific (91.3%) for the diagnosis of aPL-related thrombosis, whereas aCL were not specific, although IgG aCL mean levels were higher in patients with arterial thrombosis than in those without APS features. CONCLUSIONS: LA but not aCL positivity is a specific tool for the diagnosis of thrombotic complications due to aPL in SLE.

Adolescent↗
PubMed1994

Genetic predisposition to diabetic nephropathy. Evidence for a role of the angiotensin I--converting enzyme gene.

In search of genetic determinants of susceptibility to diabetic nephropathy, we examined the association between DNA sequence differences at the locus of angiotensin I-converting enzyme (ACE) and renal complications in 151 insulin-dependent diabetes mellitus (IDDM) patients with a diabetes duration of 16-21 years. This nested case-control study included 77 normoalbuminuric control subjects (albumin excretion rate < 30 micrograms/min) and 74 cases with evidence of nephropathy ranging from microalbuminuria to overt proteinuria. DNA from each of these patients was genotyped at the ACE locus by a three-allele restriction fragment-melting polymorphism (RFMP) (Dde I), which we described recently, and a two-allele insertion/deletion recognized as an Xba I restriction fragment-length polymorphism, which has been shown by other investigators to be associated with serum levels of ACE and with risk of myocardial infarction. The least common allele of the Dde I RFMP was significantly more frequent among cases with nephropathy than among normoalbuminuric control subjects (12.8 vs. 4.5%, P < 0.05). The deletion in the ACE gene was also more frequent in case than in control subjects (56.1 vs. 47.4%), but the difference was not statistically significant (P < 0.25) with this sample size. To determine the independence of these associations, the two polymorphisms were analyzed jointly to identify Xba I/Dde I haplotypes. As might be expected, carriers of the Xba I/Dde I '+ =' haplotype had a fourfold risk of developing diabetic nephropathy (odds ratio [OR] 4.0, 95% confidence interval [CI] 1.5-11.0). However, this did not explain all of the excess Xba I '+' allele among cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Giant cell arteritis of fallopian tube.

One case of giant cells arteritis involving tubaric arteries in a postmenopausal woman is described. The patient was 59 years old and presented with asthenia, anemia, fever, weight loss, an abdominal palpable mass and elevated erythrocyte sedimentation rate. Exploratory laparotomy revealed a large ovarian cyst of 14 cm in diameter. Extensive giant cell arteritis, Horton's type, of the small-sizes arteries was found unexpectedly in the fallopian tube of the patient who had had a prior ovariectomy. Giant cell arteritis of the female genital tract is a rare finding in elderly women and may occur as an isolated finding or as part of generalised arteritis.

Aged↗
PubMed1994

Therapy of lupus nephritis. A two-year prospective study.

The aim of our study was to compare the efficacy of 3 different therapeutic protocols in the treatment of patients with WHO class IV lupus nephritis and normal renal function. We carried out a randomized prospective trial. The treatment programs consisted of a standard therapy regimen alone (protocol A), plus plasmapheresis (protocol B) or pulse methylprednisolone (protocol C), followed by a slow (protocols A and B) or fast (protocol C) prednisone tapering schedule. Statistical analysis was performed, using univariate survival analysis according to Kaplan Meier and Breslow's test to compare survival curves. Eighteen patients entered the study: 6 protocol A, 5 protocol B and 7 protocol C. No patients developed renal insufficiency. Moreover, no statistical differences in the probability of inducing partial or complete disease remission and in reducing 24-hour urinary protein excretion to < or = 2 g per day were observed among the groups. Protocols A and B were more effective in comparison with protocol C in decreasing 24-hour urinary protein excretion to < or = 0.5 g and < or = 0.2 g per day. In conclusion, a slow prednisone tapering schedule is more effective in reducing 24-hour urinary protein excretion to < or = 0.5 and < or = 0.2 g per day as compared with a fast prednisone tapering schedule, even if it is preceded by methylprednisolone pulse therapy.

Adolescent↗
PubMed1993

Lipoprotein compositional abnormalities in type 1 (insulin-dependent) diabetic patients.

Patients with type 1 (insulin-dependent) diabetes mellitus in good metabolic control usually have normal plasma lipid levels yet they have an increased incidence of vascular complications. Abnormalities in the distribution and composition of lipoprotein subfractions might in part be responsible for the macroangiopathy seen in type 1 diabetes mellitus. The plasma lipids, lipoproteins and apolipoproteins were studied in 9 type 1 diabetic patients during conventional insulin therapy and in 14 healthy controls. Plasma lipoproteins were analysed by ultracentrifugation in a zonal rotor to evaluate their concentrations and flotation properties and for compositional analysis. In diabetic patients the mean glycosylated haemoglobin (HbA1c) was 9.44 +/- 1.02% and the plasma lipid concentrations were not significantly different from healthy controls. The very low density lipoprotein (VLDL) subclass cholesterol concentrations were no different in diabetic patients and control subjects, but the VLDL cholesterol/triglyceride ratio was significantly lower in diabetic patients than in control subjects (0.43 +/- 0.05 vs 0.85 +/- 0.14; p < 0.05). The flotation rate LDL2, the major component of low density lipoprotein (LDL) was lower in the diabetic patients compared with the control subjects. The cholesterol concentrations of intermediate density lipoprotein and LDL3, the minor component of LDL, were significantly higher (0.17 +/- 0.03 and 0.83 +/- 0.14 mmol/l respectively) in diabetic patients than in control subjects (0.05 +/- 0.02 and 0.24 +/- 0.08 mmol/l). The flotation properties and cholesterol concentrations of the high density lipoprotein (HDL) subclass, and the protein-lipid composition of LDL2, HDL2 and HDL3, were no different in diabetic patients and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Cyclosporin A in a pregnant patient affected with systemic lupus erythematosus.

Few data regarding the use of cyclosporin A (CyA) in pregnancy are available and those available refer mainly to transplant recipients and not to patients with connective tissue diseases. We report the case of a patient with systemic lupus erythematosus (SLE), taking CyA before, during and after her pregnancy at a dose of 4 mg/kg per day. CyA was effective in controlling SLE activity and no side effects were observed in mother or baby. The lack of teratogenicity in this case was in keeping with previous reports in experimental systems, animals and human transplant recipients. If our observation is confirmed by further studies, CyA might become useful in the treatment of pregnant patients with SLE.

Adult↗
PubMed1992

Antiphospholipid antibodies in mixed connective tissue disease.

We studied the prevalence and clinical significance of antiphospholipid antibodies (ab) in 28 patients affected with well-defined mixed connective tissue disease (MCTD). Forty-two patients affected with systemic lupus erythematosus (SLE) and 60 healthy subjects were also evaluated, as controls. In MCTD the prevalence of anticardiolipin (aCL) ab was: IgG high level 17.8% (p less than 0.01 versus healthy controls), IgG low level 7.1% and IgM high level 7.1%. No patients had low level of aCL IgM, lupus anticoagulant or false positive VDRL. The aCL profile was similar to that found in SLE patients, but in SLE all prevalences were higher than in MCTD. Furthermore, in MCTD patients the aCL ab were correlated with thrombocytopenia but not with recurrent thrombosis and/or abortions.

Adult↗
PubMed1992

Clustering of risk factors in hypertensive insulin-dependent diabetics with high sodium-lithium countertransport.

Diabetic nephropathy is more common in patients with a positive family history of hypertension and with elevated red blood cell sodium-lithium countertransport, a marker of risk for essential hypertension. To evaluate whether there is a relationship between this cation transport system and indicators of risk of renal and cardiovascular complications in diabetic patients before the development of clinical proteinuria, we studied 31 type 1 (insulin-dependent) diabetic patients with arterial hypertension, without clinical proteinuria and 12 normotensive normoalbuminuric diabetic patients. Sodium-lithium countertransport activity was significantly higher in hypertensive patients (0.43 +/- 0.03 mmol/l RBC x hr) than in normotensive patients (0.23 +/- 0.03; P less than 0.001). To better explore the nature of the association between this transport system and arterial hypertension, hypertensive patients were divided in two groups, with high (greater than 0.41 mmol/l RBC x hr) or normal (less than 0.41) sodium-lithium countertransport activity. The two groups of hypertensive diabetics were similar in age, sex, body mass index and blood pressure levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiporters↗
PubMed1992

Forearm ketone body metabolism in normal and in insulin-dependent diabetic patients.

In insulin deficiency, there is excessive arterial delivery of free fatty acid (FFA) to muscles where they are converted to acetoacetyl-CoA and acetyl-CoA. These intermediates may be metabolized further to acetoacetate and beta-hydroxybutyrate, which can be released into the venous circulation. When ketone body (KB) tracers are infused in vivo, they are diluted across muscle tissue. This dilution may be due to 1) KB newly formed within muscle (ketogenesis); 2) exchange of tracer between labeled and unlabeled acetyl-CoA and acetoacetyl-CoA, intermediates common to the metabolism of both FFA and KB (pseudoketogenesis). Thus this study assessed whether such label exchange could be detected across the human forearm and whether an increased delivery of FFA in insulin-sufficient controls provoked dilution of labeled KB tracer comparable to that observed in insulin-deficient diabetics. Five normal and five insulin-dependent diabetic (IDDM) subjects were infused with labeled [3,4-13C2]-acetoacetate. [13C]KB enrichments were lower in forearm vein than in the artery, and dilution of labeled KB was always higher than that which could be explained by arterial-venous differences of unlabeled KB. When arterial FFA concentrations in normals were raised (Intralipid+heparin) to values comparable to those of the diabetics, no additional increase in forearm arteriovenous dilution of labeled KB was observed. Neither in the basal state nor under conditions of increased plasma FFA were we able to detect venous appearance of KB labeled in the first and in the second carbon atoms, a necessary consequence of pseudoketogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Close relationship between microalbuminuria and insulin resistance in essential hypertension and non-insulin dependent diabetes mellitus.

The aim of this study was to investigate the relationships among insulin resistance and albumin excretion rate in 25 nondiabetic patients with essential hypertension and in 28 patients with non-insulin dependent diabetes mellitus (NIDDM). Two groups of healthy subjects matched for age, sex, and weight served as controls. Patients with essential hypertension were divided into two subgroups: without (H1) and with (H2) microalbuminuria. Diabetic patients were divided into four subgroups: those with normoalbuminuria without (NIDDM1) and with (NIDDM2) hypertension and those with microalbuminuria without (NIDDM3) and with (NIDDM4) hypertension. Whole-body glucose utilization during euglycemic hyperinsulinemic clamp (40 mU/m2/min insulin infusion) was calculated by tracer dilution techniques (6,6 2H2 glucose tracer continuous infusion) and was significantly lower in hypertensives with microalbuminuria than in those without (H2 versus H1 versus controls: 3.41 +/- 0.51 versus 6.52 +/- 0.62 versus 7.03 +/- 0.48 mg/kg/min; mean +/- SE). Whole-body glucose utilization in NIDDM patients--NIDDM4 versus NIDDM3 versus NIDDM2 versus NIDDM1 versus controls--was: 1.86 +/- 0.31 versus 2.21 +/- 0.39 versus 2.01 +/- 0.40 versus 5.98 +/- 0.77 versus 5.52 +/- 0.92 mg/kg/min (mean +/- SE). Whereas the first three subgroups did not differ among themselves, they had significantly lower glucose utilization than did the normotensive NIDDM1 patients without microalbuminuria and nondiabetic controls (P < 0.01). Hypertensives with microalbuminuria had higher Vmax of sodium-lithium countertransport (Na/Li CTT) in red blood cells than did both hypertensives without microalbuminuria and controls. It was also observed that NIDDM patients with microalbuminuria had higher Vmax of Na/Li CTT than did NIDDM patients without microalbuminuria and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1992

Molecular genetic approaches to the identification of genes involved in the development of nephropathy in insulin-dependent diabetes mellitus.

Genetic factors contribute significantly to the development of diabetic nephropathy in patients with insulin-dependent diabetes mellitus. This report discusses some models of diabetic nephropathy that incorporate genetic susceptibility and presents strategies for identifying the responsible genes. To identify variation at a locus, newly developed methods are discussed that employ denaturing gradient gel electrophoresis to study sequence differences in both polymerase chain reaction-amplified DNA fragments and genomic DNA. These techniques are illustrated with studies of the angiotensinogen gene and the insulin receptor gene. In preliminary data from a comparison between individuals with and without diabetic nephropathy, no DNA sequence difference in that part of the angiotensinogen gene that codes for angiotensin I was found. However, with a probe corresponding to exons 7 and 8 of the insulin receptor gene and denaturing gradient gel electrophoresis of Rsal digestions of genomic DNA, different distributions of a DNA polymorphism were found in patients with fast as compared with slowly progressing nephropathy. The interpretation of this finding and the need for further studies are discussed. In conclusion, the advent of methods of molecular genetics makes possible studies on genetic determinants of diabetic nephropathy. However, more clinical and epidemiologic data are needed to find out how many genes are involved and how they interact with exposure to diabetes. Foremost, DNA from families with two or more siblings with diabetic nephropathy must be collected to permit the necessary genetic studies.

Chromosome Mapping↗
PubMed1992

[Evaluation of cardiac involvement in systemic lupus erythematosus. Clinical and echographic study].

Thirty-five consecutive patients with systemic lupus erythematosus were enrolled in a prospective study. Investigations included a physical evaluation, tests for antinuclear antibodies and antiphospholipid antibodies, an electrocardiogram, a plain chest film, a 2D echocardiogram and a Doppler study. Clinical cardiac manifestations and alterations of the electrocardiogram were infrequent (17% and 11% of patients, respectively) and no patients had abnormal chest film findings. In contrast, echocardiographic abnormalities were common (82% of patients), although moderate in most instances. Pericardial involvement was found in 15 patients (42.8%); a pericardial effusion was seen in 9 of the 14 patients with inactive disease (p < 0.003), whereas thickening of the pericardium was visible in 4 patients with active disease and 2 of the 21 patients with inactive disease. Valve abnormalities were found in 17 patients (48.5%), but were not related to the presence of antiphospholipid antibodies; valve alterations included verrucous endocarditis in one case, valve thickening in one case, mitral prolapse in five cases, and mild or moderate regurgitation in 15 cases (aortic in 2 cases, mitral in 7 cases, pulmonary in 3 cases and tricuspid in 7 cases). Alterations in ventricular chamber size and kinetics were also fairly common, albeit of uncertain pathogenetic significance. These data confirm the value of 2D echocardiography for identifying and monitoring cardiac involvement in systemic lupus erythematosus, even in patients with no overt clinical manifestations.

Adult↗
PubMed1992

Japanese diagnostic criteria for mixed connective tissue disease in Caucasian patients.

Preliminary Japanese diagnostic criteria for the classification of mixed connective tissue disease (MCTD) were tested in a group of 32 Caucasian patients with this disease. Many clinical and laboratory similarities were found between Caucasian and Japanese patients. However, polyarthritis was more frequent in the Caucasians, while finger and hand swelling, DLCO reduction and muscle involvement were more frequent in the Japanese. In Caucasians the sensitivity of this criteria set was 87%, very similar to that found in the Japanese group (88%), and the specificity was 94%, higher than that of Japanese (87%). The difference resulted from the higher specificity of anti-nRNP antibody positivity in the Caucasian patients, probably due to the use of counterimmunoelectrophoresis in the detection of this antibody. The Japanese criteria seem more useful than others because they allow the use of techniques other than passive hemagglutination in detecting the anti-nRNP antibody. In our experience, such criteria also contribute to a better definition of MCTD in Caucasian patients.

Adult↗